Abstracts for the Cardiac Society of Australia and New Zealand Annual Scientific Meeting, Canberra, 4-7 August 2006

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Abstracts for the Cardiac Society of Australia and New Zealand Annual Scientific Meeting 4–7 August 2006 Canberra

1443-9506/04/$30.00 doi:10.1016/j.hlc.2006.05.003

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Ralph Reader Prize – Basic Science 1 Double Mutations in Hypertrophic Cardiomyopathy: Development of a Novel Mouse Model with a Severe Phenotype Tatiana Tsoutsman1,* , Emily Tu1 , Jessica Chung1 , Lien Lam1 , Jon Seidman2 , Christine Seidman2 , Christopher Semsarian1,3 , FCSANZ 1 Agnes

Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia; 2 Department of Genetics, Harvard Medical School, Boston, USA; 3 Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Background: Hypertrophic cardiomyopathy (HCM) is characterised by marked clinical heterogeneity. We have recently shown that 5% of HCM patients carry more than one disease-causing mutation in sarcomeric genes, resulting in a more malignant phenotype.1 This study sought to develop and investigate a double mutation mouse model of HCM. Methods: Two separate mouse models of sarcomererelated HCM were crossed to obtain offspring with a double mutation genotype. A cardiac-specific transgenic model overexpressing the Gly203Ser mutation in the troponin I gene (TnI-203) was crossed with mice harbouring the Arg403Gln mutation in the ␣ myosin heavy chain gene (MHC-403). Offspring [designated non-transgenic (NTG), TnI-203, MHC-403, and TnI-203/MHC-403] were characterised by survival rate, cardiac histopathology, RNA expression of hypertrophy markers and Western blotting. Results: Survival up to 10 days was normal in all four groups of littermates (NTG 24%, TnI-203 29%, MHC403 23%, TnI-203/MHC-403 24%; n = 189 pups, 26 litters). The TnI-203 and MHC-403 mice develop a mild form of HCM by age 20–30 weeks with normal lifespan. By age 14 days, the TnI-203/MHC403 double mutant mice developed a severe HCM phenotype characterised by significant myocyte disarray and interstitial cardiac fibrosis, marked elevation of ANF mRNA expression (TnI203/MHC-403 = 312 ± 105 versus NTG = 1.0 ± 0.2, TnI203 = 7.2 ± 2.3 MHC-403 = 2.8 ± 1.5; p = 0.0013) and BNP mRNA expression (TnI-203/MHC-403 = 15.0 ± 2.4 versus NTG = 1.00 ± 0.2, TnI-203 = 1.6 ± 0.4, MHC-403 = 1.6 ± 0.2; p < 0.0001). By day 21 (weaning age), mortality in the TnI203/MHC403 mice was over 98%, due to progressive heart failure. Conclusion: Mice carrying the double mutation TnI203/MHC-403 develop a severe HCM phenotype with premature death. This unique model mimics the clinical phenotype seen in human HCM families with double mutations, and provides an opportunity to further elucidate the underlying disease mechanisms in HCM.

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2 Right Ventricular Functional Response to Interventricular Septal (IVS) Damage and Mechanical Assist Using Left Ventricular Centrifugal Unloading or a Non-Blood Contacting Biventricular-Capable Direct Cardiac Compression (DCC) Device J. Mau1,* , S. Menzie1 , M. Ward2 , FCSANZ, Y. Huang1 , S. Hunyor1 1 Cardiac

Technology Centre, Kolling Institute, University of Sydney, NSW, Australia; 2 Department of Cardiology at Royal North Shore Hospital, Sydney, NSW, Australia Background: The role of IVS damage in causing RV failure during acute LV unloading is uncertain. DCC provides effective Uni- or -Biventricular support while avoiding inherent drawbacks of flow-through devices. This study examines RV function with and without septal damage during operation of these two device classes. Methods: Percutaneous Transluminal Septal Myocardial Ablation (PTSMA), with ethanol, induced IVS damage in 12 sheep while 12 others served as shams, 4w prior to hemodynamic assessment. LV unloading (50/75/100%) was used in half the animals with a Bio-Medicus pump. Non-surround DCC “patch” actuators attached to the LV and RV provided DCC assist in the remaining animals. Calibrated pulmonary and aortic probes provided steadystate flow values. RV ejection fraction (RVEF) and RV preload recruitable stroke work (RVPRSW) were derived from pressure/volume loops during caval occlusion and RV volume was derived from a 3-axis sonomicrometer ellipsoidal subtraction model.

Results: Response to assistance type and level is shown in the figure. BiV and UniV DCC improved RVEF/PRSW in both sham and PTSMA animals (* P < 0.05). RVPRSW in animals with PTSMA improved more during RVDCC († P < 0.05) and conferred protection during high level

(≥75%) LV unloading. In contrast, sham animals had a decrease in RV function (‡ P < 0.05). Conclusions: This study demonstrates that high-level LV unloading decreases RV function in the normal heart, whereas uni/biventricular DCC increases it. In situations where RV dysfunction is imminent and/or prophylactic biventricular assist device (BiVAD) support is deemed necessary, DCC-assist confers effective protection and/or RV assist. 3 DNAzymes Targeting the Transcription Factor Egr-1 Reduce Myocardial Infarct Size Following IschaemiaReperfusion R. Bhindi1,2,* , L. Khachigian1 , H.C. Lowe1,2 1 Centre

for Vascular Research, School of Medical Sciences, University of New South Wales; 2 Cardiology Department, Concord Repatriation General Hospital, NSW, Australia Background: The transcription factor Egr-1 is a crucial upstream activator in vascular pathophysiology. Any role Egr-1 plays in myocardial ischaemia-reperfusion (IR) injury is unknown. We hypothesised that Egr-1 has pathophysiologic importance in myocardial IR injury. Methods and results: In a rat cardiomyocyte model of IR injury, acute Egr-1 mRNA up-regulation was first observed. Effective suppression of Egr-1 up-regulation was then demonstrated with specific Egr-1 targeting oligodeoxynucleotide molecules or DNAzymes. Myocardial Egr-1 mRNA and protein up-regulation were next observed following myocardial IR injury in rats in vivo. After demonstrating myocardial uptake following intramyocardial injection of DNAzyme, 4 groups of rats underwent IR injury, receiving active DNAzyme, scrambled DNAzyme (SCR), vehicle solution (VEH) or no treatment. In the active DNAzyme-treated group, Egr-1 mRNA and protein up-regulation were selectively suppressed. Intracellular Adhesion Molecule-1 (ICAM-1) – known to be Egr-1-dependent and a mediator of leucocyte adhesion – was also selectively suppressed at both mRNA and protein level in the DNAzyme group, as was myocardial leucocyte infiltration, and other immunohistochemical indices of infarction. In these same animals infarct size (IS) was significantly reduced (mean IS ± S.D. = 19.2 ± 2.0%* (DNAzyme), 44.4 ± 2.6% (SCR), 38.1 ± 1.3 (VEH), 43.3 ± 1.3% (IR alone) * p < 0.05). Lastly, in pigs undergoing myocardial IR injury, intracoronary DNAzyme likewise resulted in selective suppression of Egr-1, ICAM-1 mRNA expression, improved left ventricular function and IS reduction (mean IS ± S.D. = 15.6 ± 4%* (DNAzyme), 28.1 ± 8.2% (SCR), 27.5 ± 6.0% (VEH), 26.4 ± 7.3% (IR alone) * p < 0.05). Conclusions: Egr-1 plays a key role in the pathogenesis of myocardial IR injury. Egr-1 targeting has important therapeutic potential.

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Ralph Reader Prize – Clinical Science 4 Conformational Activation of Neutrophil CD11b Without L-Selectin Shedding—A Novel Pro-Adhesive Neutrophil Phenotype Identified During Coronary Artery Bypass Surgery Y. Orr1,* , J.M. Taylor1 , P.G. Bannon3,4 , C. Geczy2 , L. Kritharides1,5 , FCSANZ 1 Center for Vascular Research; 2 Inflammatory Diseases Research Unit, School of Medical Sciences, The University of New South Wales, Anzac Parade, Kensington; 3 Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown; 4 The Baird Institute for Applied Heart and Lung Surgical Research, Newtown; 5 Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia

Background: The inflammatory response to coronary artery bypass surgery (CABG) is propagated by neutrophil-endothelial adhesion, an interaction mediated by neutrophil L-selectin and conformationally active CD11b/CD18 (Mac-1). We hypothesized that conformational activation of CD11b, identified by expression of an activation-specific neo-epitope (CBRM1/5) may be a more sensitive marker of neutrophil activation during CABG than total CD11b expression and that CD11b activation is not always associated with L-selectin shedding. Methods: Neutrophil CD11b/CD18, CBRM1/5 and Lselectin expression were studied in elective cardiac surgery patients (n = 16) before, during and after CABG using whole blood flow cytometry and soluble L-selectin levels were determined using ELISA. Results: A proportion of circulating neutrophils was identified as CBRM1/5+/L-selectin+ at baseline (6.28 ± 2.59%) which increased to 15.2 ± 4.2% during cardiac surgery (p = 0.001) and remained elevated post-operatively (11.5 ± 2.6%). In contrast total CD11b/CD18 expression increased transiently intra-operatively. Preservation of L-selectin on CBRM1/5+ neutrophils and decreased soluble L-selectin intra-operatively (665.2 ± 27.2 ng/ml at baseline versus 539.5 ± 32.0 ng/ml during CABG) excluded significant L-selectin shedding. Physiologically relevant inflammatory agonists (e.g. platelet activating factor, interleukin-8) generated expansion of the CBRM1/5+/L-selectin+ neutrophil subpopulation in vitro whereas unfractionated heparin markedly reduced detection of CBRM1/5+ neutrophils in vitro and in vivo (p < 0.05). Conclusions: CABG promotes formation of a potentially pro-adhesive circulating neutrophil phenotype exhibiting both conformationally active CD11b and preserved L-selectin expression. CD11b conformational activation is a more sensitive marker of neutrophil activation than total CD11b expression. We propose a novel anti-inflammatory role for systemic heparinisation in mitigating CD11b activation by masking recognition of activation-specific neoepitopes in vivo.

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5 Diastolic Stress Echocardiography: Hemodynamic Validation and Clinical Significance of Estimation of Ventricular Filling Pressure with Exercise M. Burgess* , C. Jenkins, J. Sharman, J. Meulet, G. Connors, P. Garrahy, T. Marwick, FCSANZ Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia The non-invasive Doppler index of left ventricular diastolic pressure (E/E ) approximates to invasive pressure at rest but there is limited validation of exercise E/E with invasive hemodynamic measurement, and its clinical implications are unclear. We validated E/E during exercise with simultaneously-measured (LVDP), investigated its association with exercise capacity and determined which patients to select for testing. Methods: E/E was measured at rest and during supine cycle ergometry in 37 patients undergoing left heart catheterization. In addition to correlation between invasive and estimated LVDP, the accuracy of different cut-offs to identify elevated LVDP during exercise (>15 mmHg) was determined. E/E was also measured at rest and immediately after maximal treadmill exercise in 232 patients to investigate the association between exercise E/E and exercise capacity (<8 METs). Results: In patients undergoing invasive measurement, 9 (24%) had elevation of LVDP only during exercise. There was a good correlation between E/E and LVDP at rest (r = 0.67) and during exercise (r = 0.59), and the regressions at rest and exercise corresponded closely. Receiver operator curve analysis indicated that a cut-off value of 13 for exercise E/E identified patients with an elevated LVDP during exercise. A post-exercise E/E >13 was specific (90%) for reduced exercise capacity. Resting E/E and exercise E were independent predictors of reduced exercise capacity. Even after classification of resting E/E , exercise E/E sub-classified groups with different levels of exercise capacity. Conclusions: E/E correlates with invasively measured LVDP during exercise. Exercise E/E can be used to reliably identify patients with elevated LVDP during exercise and reduced exercise capacity.

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6 High Levels of Subclinical Atherosclerosis and Cardiovascular Risk Factors in Rural South Indian Adults Clara Chow1,2,* , Brendan McQuillan5 , Krishnam Raju4 , Rama Raju3 , Bruce Neal1,2 , David Celermajer2,6 , FCSANZ 1 The

George Institute for International Health; 2 Royal Prince Alfred Hospital, Sydney, NSW, Australia; 3 Byrraju Foundation, Hyderabad, India; 4 CARE Hospital, Hyderabad, India; 5 University of Western Australia, Sir Charles Gardiner Hospital, Perth, Australia; 6 Department of Medicine, University of Sydney, Australia South Asian Indians in developed countries appear more susceptible to coronary disease than Caucasians, however the reasons for this are unclear. We therefore measured cardiovascular risk factors in 4535 adults from 20 rural Indian villages and assessed carotid intima-media thickness (IMT), as a measure of subclinical atherosclerosis, in 303 randomly selected participants. Results were compared to those from a population in Perth, WA (n = 1111). Carotid IMT levels were higher in rural Indians (mean 0.74, 95% CI 0.73–0.76) compared to urban Australians (0.69, 0.69–0.70; p < 0.001) (age and sex-adjusted). Risk factor levels were generally worse in Australians and adjustment for blood pressure, diabetes, total cholesterol and smoking did not attenuate observed IMT differences (0.75 versus 0.69 mm, p < 0.001). Total, LDL and HDL-cholesterol, blood pressure, waist-hip ratio and body mass index were all associated with carotid IMT. The association of total cholesterol and IMT was stronger in the Indian compared to the Australian populations (p = 0.009). Increasing HDL-cholesterol was protective in Australians but associated with increasing IMT in Indians (p < 0.001). Risk factor levels in the IMT subset were similar to those in the entire group surveyed (e.g. total cholesterol 4.7 mmol/L (4.7–4.8); LDL-cholesterol 3.0 (2.9–3.0); HDLcholesterol 1.2 (1.1–1.2); hypertension in 27%; smoking in 25% and diabetes in 13%). The higher level of subclinical atherosclerosis in rural Indians is of enormous public health concern and our data suggest that this may be a consequence of greater adverse effects of established cardiovascular risk factors, in addition to a possible adverse effect of HDL-cholesterol amongst South Indians.

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Affiliate Prize 7 Left Atrial Appendage Thrombus: Echocardiographic Parameters that Really Matter T. Mckay* , L. Thomas Department of Cardiology, Westmead Hospital, University of Sydney, NSW, Australia Atrial fibrillation (AF) is associated with left atrial appendage (LAA) thrombi. We examined echocardiographic parameters that were more likely to be associated with thrombus in the LAA. Methods: Forty-three AF patients with LAA thrombus on TOE were compared to 141 patients in AF without thrombus. LV mass and function, LA maximum volume (LAESV), LAA area, peak/mean velocities of LAA filling/emptying and spontaneous echo contrast (SEC) in the LA and RA were estimated. Results: The LAA area was increased in the thrombus group with a corresponding decrease in mean LAA emptying velocity. LA and RA SEC was increased and the odds ratio for a thrombus being present increased with the grade of SEC In a multiple regression model, the LAA mean emptying velocity and RA SEC were the only factors that correlated with thrombus. Table. Mean ± S.D. Thombus Group (n = 43) LAESV (ml) LVEF (%) LAA area (cm2 ) LAA peak filling vel (m/s) LAA mean emptying vel (m/s) *

80.2 42 4.7 0.37 0.43

± ± ± ± ±

20.6 13 1.9 0.15 0.17

AF Group (n = 141) 86.6 45 5.8 0.38 0.32

± ± ± ± ±

31.5 18 2* 0.16 0.14*

p < 0.05 compared to no thrombus group.

Conclusion: LAA thrombus is associated with reduced LAA function as estimated by the LAA size, LAA emptying velocity and LASEC. The presence of LAA thrombus should be carefully excluded in those with reduced LAA emptying velocity and RA SEC. 8 Side Effects of High Dose Dobutamine are Not Prevented by Normal Saline Infusion in Dobutamine Stress Echocardiography T. Hecker* , C.G. DePasquale, FCSANZ, R.B. Minson, H. Koutsounis, L. Brown, R. Perry, D. Chew, FCSANZ, M. Joseph, FCSANZ Cardiac Services, Flinders Medical Centre, SA, Australia High dose dobutamine used in dobutamine stress echocardiography (DSE) has haemodynamically based side effects due to a variable combination of ␤1 (inotropic) and ␤2 (vasodilator) effects. Of concern is the development

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of an “empty” ventricle syndrome associated with intacavitary or outflow tract obstruction and resultant symptomatic hypotension. This study was undertaken to determine whether the concurrent administration of normal saline (N/S) would decrease symptoms, limit the development of left ventricular outflow tract obstruction and hypotension by maintaining left ventricular volume. One hundred patients, mean age 66 years ±12, presenting for a DSE were randomised into two groups. One group (n = 50) received N/S at a rate of 800 ml/h during the test, the second group received dobutamine alone. Patients were instructed to report and quantify symptoms on a scale of one to ten. Echocardiographic measurements of end systolic volume (ESV) and left ventricular outflow tract (LVOT) gradients were taken pre-dobutamine and at peak dose. There was no difference in symptom scores (3.5 ± 5.1 (N/S) versus 3.0 ± 4.7, p = 0.6), change in systolic blood pressure (BP) (3.2 ± 33 (N/S) versus −0.89 ± 35, p = 0.6), maximum LVOT gradient at peak dose (20 ± 21 (N/S) versus 18 ± 24, p = 0.7), or ESV at peak (21 ± 19 (N/S) versus 18 ± 18, p = 0.4). Furthermore there was no difference in the number of patients (10/50 in both groups, 20%) who had a significant LVOT gradient, defined as >20 mmHg at peak dose. Despite the sound theoretical basis of N/S infusion to protect against empty ventricle syndrome during DSE this randomised trial does not demonstrate any symptomatic or haemodynamic benefit. 9 Controlled Trial of a Modular Guided Self-Choice Approach to Effective Secondary Prevention Following an Acute Coronary Syndrome (ACS) J. Redfern1,* , E. Ellis1 , T. Briffa2 , S.B. Freedman1,3 , FCSANZ 1 University

of Sydney NSW, Australia; 2 Curtin University WA, Australia; 3 Department of Cardiology Concord Hospital NSW, Australia Significant secondary prevention with cardiac rehabilitation is problematic given low participation rates, short exposure and lower baseline risk. The objective of this study was to test the effectiveness of a modular guided self-choice approach to secondary prevention over three months. Volunteer ACS survivors, not attending rehabilitation were randomly allocated to modular (n = 72) or conventional care (n = 72). Coronary risk factors, LIPID score and quality of life (SF36) were measured at baseline and three months. Modular and conventional groups were not significantly different in baseline level or prevalence for any risk factor. At three months, mean TC (4.1 ± 0.1 versus 4.6 ± 0.2 mmol/L, p = 0.04), LDL (2.1 ± 0.1 versus 2.4 ± 0.1 mmol/L, p = 0.02), SBP (133 ± 2.3 versus 144 ± 2.3 mmHg, p = 0.00), BMI (28 ± 0.7 versus 31 ± 0.6, p = 0.04) and LIPID score (3.6 ± 0.4 versus 5.2 ± 0.5, p = 0.04) were significantly lower for modular versus conventional care. At three months, there were fewer patients in modular care with TC ≥ 4 mmol/L (57% versus 75%), SBP ≥ 140 mmHg (33% versus 65%), physically inactive

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(25% versus 64%), overweight (29% versus 65%), smokers (8% versus 25%) and moderate-high LIPID risk scores (40% versus 57%) (p < 0.05 for all comparisons with conventional care). The modular group also had higher physicalfunctioning SF36 scores at follow-up. Compared to baseline values there was no difference in three month TC or LDL for conventional care, while significant reductions in TC (0.67 mmol/L, p < 0.01) and LDL (0.56 mmol/L, p < 0.01) occurred with modular care. Individualised modular secondary prevention for the large numbers of patients not accessing standard cardiac rehabilitation improves coronary risk profile compared to conventional care and may be an effective model for lowering recurrent cardiovascular events. 10 Ultimate Cost-Benefits of Altering the Natural History of Chronic Heart Failure Via Multidisciplinary, Home-Based Intervention: Ten-Year Follow-Up of Typically Old and Fragile Patients S. Inglis1 , J.D. Horowitz2 , FCSANZ, S. Stewart1,3 , FCSANZ 1 University of Queensland, Brisbane; 2 University of Adelaide, Adelaide; 3 University of South Australia, Adelaide, SA, Australia

Background: The medium-term benefits of nurse-led, multidisciplinary home-based interventions (HBI) in chronic heart failure (CHF) are well documented. Their cost-effectiveness over the longer-term, considering their ability to prolong survival, is unknown. Methods: The long-term effects of a nurse-led multidisciplinary HBI in an elderly CHF cohort discharged home from acute care randomly allocated to HBI (n = 149) or usual post-discharge care (UC; n = 148) were studied up to 10 years (minimum 7.5 years) following index admission. Mortality and hospitalisation data was collected, and the long-term cost-effectiveness of HBI calculated. Results: Median survival in the HBI cohort was almost twice that of UC (40 months versus 22 months, p < 0.001), with fewer deaths overall (HBI-77% versus 89%; adjusted RR 0.74, 95% CI 0.53–0.80; p < 0.001). HBI was associated with prolonged event-free survival (readmission or death) (median 4 versus 7 event-free months, p < 0.01). Given this prolonged survival, HBI patients accumulated more unplanned readmissions (560 versus 550), but took 7 years to overtake UC. However, the rate of readmission and hospital stay was significantly lower in the HBI group (2.04 ± 3.23 versus 3.66 ± 7.62 admissions p < 0.05; 14.8 ± 23.0 versus 28.4 ± 3.4 days/patient/year p < 0.05). HBI was associated with 120 more life-years per 100 patients treated compared to UC (405 versus 285 years) at a cost of $1729 per additional life-year gained when accounting for the cost of all hospital activity and HBI. Conclusion: In altering the natural history of CHF relative to UC (via prolonged survival and reduced frequency of recurrent hospitalisation), HBI is a remarkably cost and time-effective strategy over the longer-term.

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Basic Science – Electrophysiology 11 AV Junction Ablation and Pacing for AF—Long Term Outcome in a Randomised Comparison with Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial Kang-Teng Lim1 , MBBS, Michael Davis1 , FCSANZ, Anne Powell1 , FCSANZ, Andrei Catanchin1,* , Leonard Arnolda1 , Max Bulsara2 , Rukshen Weerasooriya1,2 , FCSANZ 1 Department

of Cardiology, Royal Perth Hospital; 2 University of Western Australia, Australia Background: The AIRCRAFT trial is one of the few prospective randomized trials comparing atrioventricular junction ablation and right ventricular (RV) apical pacing (AVJAP) with pharmacologic ventricular rate control (MED) in permanent AF. Methods/results: This study involves patients(pts) recruited in two of five centres accounting for the majority of the AIRCRAFT study cohort (63 of 81 pts), 4–7 years (mean 5.4 ± 0.9) after initial randomization. Forty-eight pts (25 males, mean age 74 ± 7.5 years), 23 randomized to AVJAP and 25 to MED were evaluated, 14 pts refused participation and 1 pt lost to follow-up. Deaths occurred in 10 MED and 5 AVJAP pts, with cardiac death in 2 MED and 1 AVJAP pts. The remaining 33 pts (15 MED, 18 AVJAP) were consented for re-evaluation. In the 15 AVJAP pts in whom LVEF was measured at both 12 months and mean 5.4 years, LVEF was lower (53.3% (12 months) versus 49% (5 years) p = 0.021). In the 11 MED pts in whom LVEF was measured at both 12 mths and 5.4 years, LVEF was also lower (63.7% (12 months), 58.8% (5.4 years), p < 0.01). The peak heart rate during activities of daily life was 108 ± 12 bpm (AVJAP) versus 132 ± 8 bpm (MED), p < 0.01). AVJAP pts had fewer symptoms of irregular heart beat (p < 0.001) on CAST quality of life questionnaires. Conclusion: Cardiac death rate, decline in LVEF and quality of life measures were similar at long-term follow-up of patients randomized to MED versus AVJAP despite inferior ventricular rate control and symptoms of irregular heartbeat with medical management. 12 Evaluation of Active Pacing Leads of Slim Profile P. Varghese* , C. Hiew, P. Diu, S. Adera, S. Mylabathula, J. Leitch, FCSANZ, M. Barlow John Hunter Hospital, Newcastle, NSW, Australia Aims: The FINELINE II STEROX EZ leads are unique steroid eluting active fixation leads with a lead body diameter of 1.7 and 1.6 mm helix, which can be implanted without active fixation tools. These leads are thinner, lighter and more flexible than other standard active fixation leads that use a retractable helix. Consequently, they may be less likely to cause perforation, but more prone to dislodge. The

pacing performance and complication rates of these leads were evaluated. Methods and results: Data from 88 patients who had 132 Fineline II leads implanted [73 atrial, 59 ventricular] by a single operator was analysed and compared to 57 standard steroid eluting active fixation leads [Med 5076 of 2 mm diameter], implanted by the same operator over the same period. Lead dislodgement rates of 1.5% [2/132] and 1.75% [1/57] occurred in the Fineline and control groups, respectively. No cases of cardiac perforation occurred in the Fineline group while one confirmed perforation [requiring lead repositioning later] and 2 probable perforations based on pericardial symptoms [but not requiring intervention] occurred in the other group. The sensing and pacing parameters at implant and follow-up [≥3 months] were comparable in the 2 groups. Conclusions: The Fineline leads performed similarly to a standard active lead in terms of pacing performance. Dislodgement rates were similar. However, risk of perforation was significantly less with the fine line leads. 13 The Effect of Beat-To-Beat Variations in Propagation on Cardiac Myocyte Local Cycle Duration Variability (LCDV) A.C. Boyd* , S.P. Thomas Department of Cardiology, Westmead Hospital, University of Sydney, NSW, Australia Temporal irregularity in electrical activation of myocardium may be due to variability at the source of activation. We hypothesized that beat-to-beat variations in propagation through a cellular network could also contribute to local cycle duration variability (LCDV). Method: Cultures of neonatal rat ventricular myocytes were plated on microelectrode arrays (MultiChannel Systems). The MEA consisted of a rectangular matrix of 60 electrodes, with an interelectrode distance of 500 ␮m. On day 4–5, cells were continuously stimulated with a bipolar electrode at cycle lengths of 500 ms, 400 ms, and 300 ms at a site remote from the array. The local activation time at each electrode was defined as the time of maximum negative voltage change (dV/dtmax ) of the unipolar signal. The S.D. of the cycle duration was used to express the LCDV for each electrode. Non-parametric Correlation analysis and repeated measures ANOVA were performed. Results: Eight preparations in total were analysed; 500 ms (n = 4), 400 ms (n = 8), 300 ms (n = 5) and all cycle lengths (n = 3). Pacing at 500 ms resulted in significantly lower S.D. than 400 ms (110 ± 70 ␮s versus 160 ± 100 ␮s; p = 0.007) and 300 ms (110 ± 70 ␮s versus 180 ± 110 ␮s; p < 0.000). Pacing at 400 ms resulted in lower S.D. than 300 ms, however this did not reach statistical significance (160 ± 100 ␮s versus 180 ± 110 ␮s; p = 0.8). There was a positive correlation between distance and S.D. (r = 0.15, p = 0.01). Conclusion: LCDV in a network of cardiac myocytes was affected by both beat rate and distance from the pacing source. Beat-to-beat variations in propagation contribute to LCDV. However, this effect is small.

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14 Atrial Electrical Remodelling Occurs Acutely in Response to Hypercapnia but not Hypoxemia—Implications for Promotion of Atrial Fibrillation I. Stevenson1,* , G. Edwards2 , S. Spence1 , P. Kistler1 , R. Hillock1 , A. McGavigan1 , K. Roberts-Thomson1 , J. Kalman1 , FCSANZ 1 The

Royal Melbourne Hospital, Australia; 2 University of Melbourne, School of Veterinary Science, Melbourne, Australia Background: Emerging evidence suggests that AF is linked to sleep apnoea. We aimed to characterize atrial electrical changes with hypercapnia (HC) and hypoxemia and to determine their role in AF development. Methods: Seventeen sheep (six control, five normoxic HC-end tidal CO2 90–100%, six eucapnic hypoxemiasaturation 50–60%) underwent electrophysiologic evaluation under autonomic blockade. A 64-electrode endocardial basket catheter was positioned in the RA and 3 × 128electrode epicardial plaques were sutured to the RAA, LAA and Bachmann’s bundle and 1 × 64-electrode plaque to LA free wall. Atrial effective refractory periods (ERP), conduction times (CT) and AF vulnerability were assessed. Results: Representative data (mean ± S.E.) from 1 CL (350 ms) and three sites are presented. HC was associated with marked lengthening of ERP, increased CT during shortest propagated S2 and prolonged interatrial CT. ERPs returned rapidly to baseline with resolution of HC but recovery of conduction was delayed. AF vulnerability was reduced during HC (with ↑ ERP) but increased significantly with subsequent return to eucapnia (when ERP normalised but CT remained prolonged). No significant change in ERP, atrial CT or AF vulnerability occurred in hypoxaemic or control groups. Conclusion: HC causes (1) marked increase in ERP which recovers rapidly with return to eucapnia and (2) atrial conduction slowing which persists after return to eucapnia. The differential recovery of these parameters results in increased vulnerability to AF in the phase after return to eucapnia. This may explain the AF tendency in chronic pulmonary disease and sleep apnoea. There were no acute electrophysiologic changes in response to hypoxemia.

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Abstract 14 Table Eucapnia

Hypercapnia

Recovery

P ANOVA

Posterior RA ERP (ms)

166.2 ± 11.3

239.0 ± 10.7

145.4 ± 4.6

<0.01

LAA ERP (ms)

121.2 ± 7.9

202.4 ± 10.5

117 ± 20.1

<0.01

Septal RA ERP (ms)

176.3 ± 12.2

244.7 ± 18.4

148.7 ± 15.3

<0.01

CT LAA S2 (ms)

57.4 ± 4.7

70.0 ± 8.8

73.8 ± 5.5

<0.05

CT RAA S2 (ms)

55.5 ± 2.2

75.2 ± 6.6

69.9 ± 5.1

<0.05

Interatrial CT

123.4 ± 9.9

156.0 ± 8.4

135.8 ± 6.7

<0.05

AF vulnerability with S2

5%

0%

21%

<0.01

Normoxia

Hypoxemia

Recovery

P ANOVA

Posterior RA ERP (ms)

145.8 ± 4.8

132.7 ± 7.1

139.7 ± 7.5

NS

LAA ERP (ms)

112 ± 6.3

109.6 ± 8.6

107.7 ± 5.0

NS

Septal RA ERP (ms)

157.4 ± 3.8

143.1 ± 3.8

148.6 ± 4.6

NS

CT LAA S2 (ms)

56.1 ± 6.0

56.3 ± 5.7

61.1 ± 6.0

NS

CT RAA S2 (ms)

55.8 ± 3.7

56.2 ± 2.4

60.4 ± 2.3

NS

Interatrial CT

111.7 ± 5.1

109.2 ± 6.3

113.7 ± 5.9

NS

AF vulnerability with S2

5%

7%

10%

NS

15 Does Myocardial Scarring Cause Increased Ventricular Refractoriness? Evaluation in a Chronic Ovine Model Jim Pouliopoulos1,* , A. Thiagalingam1 , V.E. Eipper2 , C. Campbell1 , P. Kovoor1 , FCSANZ 1 Department

of Cardiology, Westmead Hospital, Westmead. NSW, Australia; 2 The University of Sydney, NSW, Australia

Heterogeneous myocardial refractoriness has been shown to coincide with altered myocardial excitability post myocardial infarction (MI). We assessed the influence of left ventricular (LV) scar on the local refractoriness and electrogram characteristics of myocardium at multiple intramural sites. MI was induced by percutaneous left anterior descending artery occlusion for 3 h. Mapping was performed on 8 sheep without ventricular tachycardia at a mean of 20 ± 10 days post MI. A total of 20 quadripolar transmural needles were deployed at thoracotomy in the LV within and surrounding the infarct zone. Needle positions were localised using the Ensite system. Bipolar pacing was performed from each needle to assess the effective refractory period (ERP) of the endocardium and epicardium. Unipolar electrograms were recorded simultaneously from the other 19 needles during pacing. Myocardial scarring was quantified histologically and correlated with mapping criteria. Analysis was performed on 5 sheep. The remaining three sheep were excluded from analysis due to ventricular fibrillation that developed during the mapping procedure. Increased scar density was independently associated with increased ERP (Endocardial = 5.1 ms; Epicardial = 6.6 ms, per 10% increase in scar; p < 0.0001), decreased subendocardial contact electrogram amplitude (p < 0.001, ROC area = 0.779) and max-

imum negative slope (p < 0.001, ROC area = 0.751). Prolongation of the ERP in scar with density >50% was measured with high sensitivity (ROC area: Endocardial = 0.835, Epicardial = 0.873). Myocardial scarring post MI is associated with altered transmural refractoriness. The relationship between ERP and myocardial scar was greater than other commonly measured electrophysiological variables. The clinical application of this finding in VT mapping requires further evaluation. 16 Comparison of Pulmonary Vein Electrogram Pattern Before and After Cardioversion in Patients with Atrial Fibrillation X. Hu1 , S. Thomas2,* 1 Department

of Cardiology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; 2 Department of Cardiology and University of Sydney, Westmead Hospital, Sydney, NSW, Australia Introduction: The purpose of this study was to determine the relationship between pulmonary vein (PV) electrical activation during atrial fibrillation (AF) and after cardioversion into sinus rhythm. Methods and results: Electrograms were recorded using a circular mapping catheter during AF and after conversion in 53 PVs from 41 patients. Two activation patterns were observed in atrial fibrillation. Group 1 had a fixed consistent uniform activation sequences most (>70%) of the recording time. Group 2 had no fixed activation sequence. In Group 1 a constant single activation sequence pattern was seen in 22 PVs (Group 1a). The earliest PV activation

sites were the same during AF and after cardioversion to sinus rhythm in 17 (77%) PVs from Group 1a. Fourteen of these 17 (82%) cases also had a common site of electrogram polarity reversal. In Group 2, a relationship between PV activation before and after cardioversion was not found. Segmental radiofrequency ablation was performed during sinus rhythm after cardioversion. There was no difference in the number of atriovenous breakthroughs between the two groups (1.9 ± 0.7 breakthroughs versus 2.0 ± 0.6 breakthroughs, P = NS). PV disconnection was achieved in all PVs with a mean RF duration of 13.5 ± 4.5 min per vein in Group 1 and 14.0 ± 4.9 min per vein in Group 2 (P = NS). Conclusion: A uniform PV electrogram pattern recorded during AF usually predicts the activation sequence and/or the polarity reversal sites during sinus rhythm. This pattern does not necessarily suggest a single atriovenous breakthrough point. 17 The Effect of Fish Oil Supplementation on Myocardial Fatty Acids in Humans G.D. Young1,* , M.K. Stiles1 , R.G. Metcalf2 , L.G. Cleland2 , P. Sanders1 , FCSANZ, J. Edwards3 , FCSANZ, R.A. Gibson4 , M.J. James2 1 Dept. of Cardiology, Royal Adelaide Hospital, Adelaide, Australia; 2 Rheumatology Dept, Royal Adelaide Hospital, Adelaide, Australia; 3 Cardiac Surgery Dept, Royal Adelaide Hospital, Adelaide, Australia; 4 Child Health Research Institute, Adelaide, Australia

Background: Substantial evidence relates an association between increased fish oil (n − 3 fatty acid) consumption and reduced risk of cardiac arrhythmia. The relationship between fish oil consumption and the level of incorporation of n − 3 FA into human cardiomyocytes is unknown. Methods: Forty patients undergoing elective cardiac surgery were randomly allocated to receive fish oil for 7, 14 or 21 days prior to surgery or to no treatment. Erythrocyte FA levels were determined at baseline and immediately prior to surgery. At surgery atrial tissue was obtained to measure cardiomyocyte FA composition. Results: Rescheduling of surgery resulted in a continuum of treatment time from 7 to 63 days. n − 3 FA in right atrial appendage and erythrocytes increased in a curvilinear relationship with days of fish oil consumption displacing mainly arachidonic acid (n − 6 fatty acid). Atrial and erythrocyte n − 3 fatty acids were highly correlated and regression analysis revealed approximate 1:1 relationships; EPA (r = 0.97, slope = 0.92), DHA (r = 0.77, slope = 0.99) and EPA + DHA (r = 0.92, slope = 1.08). Conclusion: EPA and DHA accumulate rapidly into atrial phospholipids, and exchange directly with long chain n − 6 FA. There is high correlation between erythrocyte and myocardial n − 3 FA over a wide range of values confirming the validity of erythrocyte levels of n − 3 fatty acids as a suitable surrogate for cardiac myocyte n − 3 fatty acid levels.

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18 Waveform Characteristics of Ventricular Fibrillation P.D. Larsen1,* , N.A. Lever2 , E.G. Newall1 , G. Orsbourn1 , D.C. Galletly1 1 Department

of Surgery and Anaesthesia, Wellington School of Medicine; 2 Department of Cardiology, Wellington, Hospital, New Zealand For those with increased risk of sudden ventricular arrhythmia, implanted cardioverter/defibrillators (ICD) are the treatment of choice. Inappropriate therapy remains a significant problem. In an initial pilot study, we extracted data from 11 patients who had received shocks in response to events diagnosed as ventricular fibrillation (VF) by their ICD, although in 5 of these cases patients had received inappropriate shocks for atrial tachyarrhythmias. For each event we extracted the electrogram from the ventricular ICD lead. We then calculated, for each episode, indices relating to the degree of statistical uncertainty (or irregularity) within the signal using non-linear time series methods derived from statistical mechanics. We observed that spontaneous episodes of VF were more irregular or uncertain than VF events that were induced electrically in the laboratory during implant testing. This implies that the spiral waves associated with spontaneous events were less stable than those associated with electrically induced events, and this may have implications for defibrillation threshold testing. We also found that episodes of atrial arrhythmias that had been treated as VF on the basis of cycle length were significantly more regular than episodes of VF, raising the possibility that within the VF zone regularity based algorithms may help reduce the incidence of inappropriate shock therapy. These results need to be interpreted with some caution, as the available dataset from our patient population is small. The benefit of exploring information content from VF waveform characteristics may have future clinical utility. 19 Epicardial Mapping of the Posterior Left Atrium in Patients Undergoing Cardiac Surgery Kurt C. Roberts-Thomson1,* , Peter M. Kistler1 , Irene H. Stevenson1 , Steven Spence1 , Richard J. Hillock1 , John Goldblatt1 , Prashanthan Sanders2 , FCSANZ, Jonathan M. Kalman1 , FCSANZ 1 Department

of Cardiology, Royal Melbourne Hospital, Parkville; 2 Department of Medicine, University of Melbourne, Melbourne, Australia Objective: To evaluate the electrophysiological properties of the posterior left atrium (PLA) in patients undergoing cardiac surgery. Background: The PLA has a complex myocardial fibre arrangement and has been implicated in the initiation and maintenance of atrial fibrillation. Methods: Fifteen patients undergoing cardiac surgery were included. Prior to the institution of cardiopulmonary bypass a custom made, triangular, epicardial plaque was placed on the PLA between the pulmonary veins. This

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high-density plaque contained 128 electrodes with 2.5 mm spacing. Electrograms were acquired via a computerized mapping system (UnemapTM , Uniservices). Pacing was performed at 2 cycle lengths from the atrial appendages and the corners of the plaque. Results: Five patients had valvular heart disease, five patients had left ventricular dysfunction without valvular lesions and five patients had normal left ventricular function. All patients were in sinus rhythm. During pacing, a functional line of block developed on the PLA in all patients. This line extended vertically down the PLA between the pulmonary veins. Conduction velocity across the PLA was slower in patients with left ventricular dysfunction and valvular heart disease than in patients with normal left ventricular function. This corresponded with the presence of double potentials and fractionated signals. Conclusion: Patients with structural heart disease have slowed conduction across the PLA with the development of functional lines of block. This provides a potential substrate for reentry and may explain the role of the PLA in atrial fibrillation. 20 The Independent Impact of the COACH Program (TCP) and Cardiac Rehabilitation (CR) on Self Assessed Health, Mood, and Fitness: The Coach Study M. Jelinek* , FCSANZ, M. Vale, J. Best, D. Hare, FCSANZ Department of Cardiology, St Vincents Hospital, Fitzroy, Vic., Australia Background: We have previously shown that TCP reduced readmissions and bed-days in hospital 4 years after randomisation in the COACH study. The reduction in beddays in hospital correlated with self assessed health, mood and fitness 6 months after randomisation. We have assessed retrospectively the interactions of TCP and CR on self assessed health mood and fitness in the COACH study. Methods: We report on the 679 (86%) of the 792 patients who attended for final assessment 6 months after randomisation in the COACH study. Perceptions of general health and mood were assessed on a 5-point ordinal scale and the perception of fitness on a 4-point ordinal scale at the final review. Although all patients were encouraged to attend CR, only 375 (55%) did attend CR. Ninety percent of those who attended CR appeared at least 50% of the CR sessions. Results: One hundred and seventy-six (26%) of the patients attended both TCP and CR; 155 (23%) attended TCP only; 199 (29%) attended CR only; and 149 (22%) attended neither TCP nor CR. There was an independent and additive impact of TCP and CR on general health (χ2 = 43.39, d.f. = 12, P < 0.001), mood (χ2 = 41.91, d.f. = 12, P < 0.001) and fitness (χ2 = 46.97, d.f. = 9, P < 0.001). Conclusion: The impact of TCP and CR on self reported health mood and fitness 6 months after the COACH study were additive. It is likely that both treatments contributed to the reduction in hospitalisation 4 years after randomisation. The health of patients receiving neither TCP nor CR is poorer.

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21 Incidence of Ventricular Tachycardia at Electrophysiology Testing after Primary Angioplasty for ST Elevation Myocardial Infarction James Chong* , Gopal Sivagangabalan, Fiona Cox, Vicki Eipper, Norman Sadick, FCSANZ, Pramesh Kovoor, FCSANZ Department of Cardiology, Westmead Hospital, Westmead, NSW, Australia Patients with reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction are at increased risk of sudden death from ventricular arrhythmias. This prospective observational study aimed to establish the incidence of inducible ventricular tachycardia (VT) at electrophysiology testing (EPS) in the primary angioplasty era. Methods/Results: Four hundred and seventy-seven consecutive patients treated with primary angioplasty (±stenting) for ST elevation myocardial infarction (STEMI) in Westmead hospital between September 1999 and December 2005 were included. The mean age was 57.1 ± 12 years. After the third day post-infarction, left ventricular ejection fraction (LVEF) was assessed by gated heart pool scan (GHPS) in 390 patients and by echocardiogram/ventriculogram in 27 patients. The mean LVEF was 48 ± 13%. One hundred and sixteen patients (24%) had a LVEF of less than 40% and were eligible for EPS. Of these 108 underwent EPS. During EPS, programmed ventricular stimulation was performed with up to four extrastimuli. Thirty-eight patients (8%) had inducible VT (cycle length >200 ms) of at least 10 s duration. Defibrillators were implanted in these patients. Conclusion: VT inducible at EPS is present in a significant proportion of patients treated by primary angioplasty for STEMI. Further studies are needed to investigate the frequency of spontaneous ventricular arrhythmias. 22 Complications of Permanent Pacemaker Therapy M. Govindan* , A. Gleason, D.S. Coulshed, FCSANZ Cardiology Department, Nepean Hospital, Penrith NSW, Australia Introduction: Cardiac device implantation is a rapidly expanding field within cardiology as landmark clinical trials demonstrate increasing indications for them. Recent published data has suggested SWAHS has had higher than acceptable pacemaker complication rates. Our complication rates were reviewed to assess the safety of the service provided. Methods: One hundred and twenty patients with endocardial pacemakers and implantable cardiac defibrillators (ICD) were reviewed between July 2004–December 2005 at Nepean Hospital.

All procedures were performed under local anaesthetic by a cardiologist or supervised trainee. Standard lead testing, ECG and CXR were done post implant. Patients were followed up at 1, 3, 6 and 12 months. Medical records were reviewed for hospital re-admissions or re-operations. Results: Complications were defined as requiring repeat procedures or further investigation. Early complication rate (within 30 days) was 3.3% (n = 4). One patient required a repeat procedure for failed vascular access on first attempt. There was one atrial, two ventricular lead dislodgements and one ICD lead requiring re-positioning. All occurred within the first week of implantation. No deep pocket infections were documented. Two superficial wound infections required antibiotics. No wound haematomas required surgical evacuation. Late complication rate was 2.5%. This included one atrial lead dislodgment and an ICD requiring re-position. One device failure required replacement under warranty. Conclusion: Pacemaker complications occur more in dual chamber devices and in the early post implant period. Our complication rates appear consistent with previous reviews. Clearly, our results are at variance with recent data about SWAHS. The reasons for this are explored further. Basic Science – Myocardial 23 Early Infarct Healing and LV Remodelling is not Responsive to Activated Protein C (APC) Treatment Gabrielle Gallagher1,* , Stuart Menzie1 , Yifei Huang1 , Stephen Hunyor1 , Chris Jackson2 1 Cardiac Technology Centre, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, Australia; 2 Sutton Arthritis Research Laboratory, University of Sydney at Royal North Shore Hospital, Sydney, Australia

Background: Appropriate healing of myocardial infarction (MI) is required to minimise LV remodelling and progression to failure. APC possesses anti-coagulant, antiinflammatory, pro-angiogenic and anti-apoptotic properties, and recent evidence suggests that it improves cutaneous wound healing and reduces cerebral infarct size. The aim of this study was to investigate APC’s potential to improve infarct healing and early remodelling post-MI through altering the portfolio of inflammatory cytokines and matrix metalloproteinases (MMPs) expressed, thereby preserving cardiac function. Methods: Eighteen sheep were anaesthetised and instrumented to measure haemodynamic function and regional myocardial segmental shortening. Intracoronary vehicle (n = 10) or 2.5 mg APC (n = 8) was administered 2 min prior to coronary ligation. Functional parameters were recorded for 3 h post-MI, when hearts were collected and tissue analysed using real-time RT-PCR, gelatin zymography and Western blot. Results: Efficacy of human recombinant APC in sheep was demonstrated in pilot studies with a dose-dependent increase in APTT. MI induced regional cardiac dysfunc-

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tion, which was associated with specific alterations in cytokines and MMPs. Namely, IL-6 and MMP-9 were elevated in the infarcted and border regions, while MMP-2, MT1-MMP and TIMP-1 tended to decrease relative to noninfarcted regions. However, these functional and molecular alterations were not significantly different between vehicle and APC treated sheep. Conclusion: The results of this study indicate that while APC was safe and efficacious in sheep, the short-term regimen employed did not alter the progression of events in the early post-MI period. Further studies should investigate alternative administration protocols, longer post-MI time points and additional cytokines/MMPs. 24 Norepinephrine Transporter Expression in the Failing Myocardium is Uncoupled From That in Sympathetic Ganglia T. Marshall, S. Finch, X.-J. Du, D. Kaye* , FCSANZ Baker Heart Research Institute, Melbourne, Vic., Australia Background: Congestive heart failure (HF) is the ultimate manifestation of a complex pathophysiological process, initiated by myocardial contractile failure. One of the hallmark features of HF is activation of the sympathetic nervous system (SNS). In particular, we have previously shown that the amount of norepinephrine (NE) released by sympathetic nerves in the failing heart is a key determinant of survival. In this context we and others have shown that the rate of re-uptake of NE by the cardiac sympathetic nerves is significantly reduced in HF, suggesting reduced expression of the NE transporter (NET). This study was conducted to establish the basis for this defect using the rat infarct model of HF. Methods and results: Ten weeks after coronary ligation induced myocardial infarction (MI), MI rats exhibited significant left ventricular dysfunction compared to sham (SH) (LVEDP MI versus SH: 8.1 ± 1.3 mmHg versus 2.4 ± 0.9 mmHg, p < 0.01; LVEDD 10.8 ± 0.4 mm versus 9.4 ± 0.5 mm, p < 0.05. To determine the functional activity of NET, we examined the influence of desipramine (a specific NET inhibitor) on NE overflow from that rate heart during sympathetic nerve stimulation. During nerve stimulation (8 Hz), desipramine caused an 2.7 ± 0.3 fold increase in NE overflow, compared to a 2.3 ± 0.2 fold increase in HF rats (p < 0.05), consistent with functional impairment of NET activity. Despite the presence of a functional depression in NET activity, real time PCR analysis and Western blot analysis for NET mRNA and protein did not reveal evidence of a difference in NET expression in the myocardium of MI compared to SH rats. In contrast, however, immunohistochemistical analysis of the stellate ganglia showed a significant increase in the number of NET positive cell bodies in the stellate ganglia of MI rats (MI versus SH: 5.0 ± 0.3 versus 3.7 ± 0.2 positive cell bodies per 10,000 ␮m2 , p < 0.05). Conclusion: This finding suggests the presence of an uncoupling of NET expression in sympathetic ganglia compared to that in the myocardium in congestive heart failure.

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25 Therapeutic and Diagnostic Potential of ActivationSpecific Anti-Mac-1 (␣M ␤2 ) Single-Chain Antibodies in Atherosclerosis Steffen U. Eisenhardt1,* , Meike Schwarz2 , Nils Schallner2 , Nicole Bassler1 , Karlheinz Peter1 1 Centre for Thrombosis & Myocardial Infarction, Baker Heart Research Institute, Melbourne, Australia; 2 Department of Cardiology, University of Freiburg, Germany

The integrin Mac-1 is a major adhesion receptor involved in monocyte adhesion and transmigration and is thus an attractive target for anti-inflammatory therapies, e.g. to stabilise unstable atherosclerotic plaques. Mac-1 undergoes a conformational change upon stimulation that turns the receptor into a high affinity state and exposes its major ligand binding-site. An activation-specific antibody might reduce side effects, such as immunocompromisation, a major problem of anti-inflammatory therapy. In addition such an antibody might serve as diagnostic tool in clinical settings, as Mac-1 activation reports on the activation state of leukocytes. Using human single-chain antibody (ScFv) phagelibraries, we developed subtractive strategies with depletion of phages binding to non-activated Mac-1 and selection of phages binding to activated Mac-1. With this technique we were able to obtain highly activation-specific anti-Mac-1 single-chain antibodies. The potential therapeutic use was tested in adhesion assays under static and flow conditions, demonstrating the blockade of activated monocytes only. Furthermore, HCDR3-derived peptides selectively block activated Mac-1, providing a unique template for lead compounds of orally active Mac-1 inhibitors that are specific for activated monocytes. We conclude that activation-specific single-chain antibodies and scFv-derived peptides are promising agents for the treatment of various inflammatory diseases, such as atherosclerosis. 26 Effective Anticoagulation without Bleeding Time Prolongation by Activated GPIIb/IIIa-Targeted Direct fXa Inhibition C.E. Hagemeyer, P. Stoll, N. Bassler, K. Peter* Baker Heart Research Institute, Melbourne, Vic., Australia Targeting of the potent factor Xa (fXa) inhibitor tick anticoagulant peptide (TAP) to a clot may further increase anticoagulant activity at the clot and decrease systemic anticoagulation and bleeding complications because fXa has a central, up-stream, and rate-determining position in the coagulation cascade. Ligand-induced binding sites (LIBS) on the activated GPIIb/IIIa receptor provide a unique target that is specific and highly abundant on clots. Based on a hybridoma cell line, we cloned a new single-chain antibody (scFv) directed against a LIBS epitope on GPIIb/IIIa and fused it to TAP (scFv-LIBS-TAP).

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Antibody binding was tested by flow cytometry, comparing the binding of scFv-LIBS-TAP to activated and nonactivated platelets. Anti-fXa activity of scFv-LIBS-TAP was tested in fXa inhibition assays. In vivo anticoagulative efficiency was investigated by Doppler-flow analysis in a mouse model measuring occlusion time in ferric chloride induced thrombosis of the carotid artery. Bleeding time was measured by tail transsection. ScFv-LIBS-TAP prolonged occlusion time comparable to enoxaparin, recombinant TAP, and mut-scFv-TAP, a fusion protein including a mutated, non-binding single-chain antibody. In contrast, scFv-LIBS-TAP did not prolong bleeding time. In conclusion, clot targeting of the potent fXa inhibitor TAP via a single-chain antibody against a LIBS epitope on GPIIb/IIIa provides a promising strategy for effective anticoagulation with reduced bleeding risk. 27 Relationship between Cardiac Function, Myocardial Matrix Metalloproteinases (MMPs) and Circulating MMPs Post Myocardial Infarction (MI) Gabrielle Gallagher1,* , Stuart Menzie1 , Yifei Huang1 , Chris Jackson2 , Stephen Hunyor1 1 Cardiac

Technology Centre, Kolling Institute, University of Sydney at Royal North Shore Hospital, Australia; 2 Sutton Arthritis Research Laboratory, University of Sydney at Royal North Shore Hospital, Sydney, Australia Background: LV remodelling post-MI is associated with increased morbidity and mortality. Monitoring molecular alterations associated with LV remodelling, such as MMP activation, may be possible through plasma profiling. However, the correlation between myocardial and plasma levels, and the ability of plasma profiles to reflect myocardial function, is uncertain. Methods: Twelve anaesthetised sheep were instrumented to measure haemodynamics and myocardial segmental shortening. MI was induced through coronary ligation and functional parameters recorded for 3 h, at which time venous and myocardial samples were collected. Three non-operated sheep served as controls. Plasma and myocardial samples were analysed for MMP abundance using gelatin zymography. Results: MMP-9 was only detectable in latent form in myocardial samples, and was elevated in post-MI sheep (P = 0.011). In plasma samples, both latent and active MMP-9 were present. Surprisingly, post-MI plasma showed lower levels of MMP-9 than controls (P = 0.087 and P < 0.001 for latent and active enzyme). Levels of MMP-2 were not different between control and post-MI sheep in either myocardium or plasma. No correlation between plasma and myocardial MMP levels was found. Myocardial segmental shortening correlated with myocardial latent and active MMP-2 (P = 0.023 and 0.041, respectively), however, no plasma MMP levels correlated with this functional parameter. Conclusion: This study suggests plasma MMP-2 and MMP-9 do not accurately reflect myocardial levels 3 h

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post-MI. While myocardial MMP-2 was associated with functional performance, plasma MMPs failed to demonstrate such a relationship, questioning their potential as prognostic post-MI indicators. Further studies with additional time-points and MMP subtypes are warranted. 28 Beneficial Impact of Cardiac-Isolated Recirculating Delivery of AAV-SERCA2a Gene Therapy in a Large Animal Model of Heart Failure Justin A. Mariani1,* , Anka T. Smolic1 , Tanneale Marshall1 , Arthur C. Preovolos1 , Roger J. Hajjar2 , Adam Bilney2 , Ken R. Chien2 , John M. Power1 , David M. Kaye1 , FCSANZ 1 Baker

Heart Research Institute, Melbourne, Vic., Australia; Medical School, Boston, MA, USA

2 Harvard

Background: Myocardial contractile failure due to defective Ca2+ handling is a key feature of heart failure (HF). While the benefit of manipulating Ca2+ -handling proteins by gene delivery has been shown in small animals, the successful translation to clinical practice has been limited by the lack of a safe, efficient delivery system. We assessed left ventricular function after adeno-associated virus (AAV) mediated gene transfer of sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) in an ovine model of HF using a novel recirculation technique. Methods: HF was induced by one month of rapid pacing in 14 sheep, determined by conductance catheter and transthoracic echocardiography. At day 34, the treatment group (n = 7) received AAV-SERCA2a gene therapy (5 × 1012 drp), delivered using a novel, percutaneous, cardiac-isolated, antegrade recirculation method. Pacing continued for a further 28 days in all sheep. At day 62, cardiac function was reassessed. Results: AAV-SERCA2a gene therapy resulted in a significant improvement in ventricular function (Table: Fractional shortening (FS); Slope (Ees) of End-systolic pressure volume relationship). Further, minimal systemic expression (kidney, liver, lung) of the transgene was evident. Conclusion: We have demonstrated that delivery of SERCA2a gene therapy using a novel recirculation technique improves cardiac function in a large animal model of HF, laying a strong foundation for translation into clinical studies.

FS (%) Ees (mmHg/ml) +ve dP/dt (mmHg/s)

Control D34

Control D62

AAV-SERCA D34

AAV-SERCA D62

14.8 ± 0.9

13.2 ± 2.2*

11.0 ± 1.7

20.0 ± 2.6*#

3.5 ± 0.2

2.6 ± 0.4

2.9 ± 0.4

1117 ± 79

894 ± 294

1116 ± 198

4.3 ± 0.6*# 1042 ± 178

Data is mean ± S.E.M.; p < 0.05 between groups is indicated by (*), and between treatments by (#).

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29 Inhibition of PKC Beta by Ruboxistaurin Preserves Cardiac Function and Reduces Extracellular Matrix Production in Diabetic Cardiomyopathy K.A. Connelly1,* , D.J. Kelly1 , Y. Zhang1 , D.L. Prior1 , FCSANZ, H. Krum2 , FCSANZ, R.E. Gilbert1,3 1 University of Melbourne Department of Medicine, St. Vincent’s Hospital, Vic., Australia; 2 NHMRC CCRE in Therapeutics, Department of Epidemiology & Preventive Medicine and Department of Medicine, Monash University, Faculty of Medicine, Nursing and Health Sciences, The Alfred, Vic., Australia; 3 Department of Medicine, University of Toronto, St. Michael’s Hospital, Canada

Background: Diabetic cardiomyopathy (DCM) is increasingly recognized as contributing to the morbidity/mortality of diabetic patients. While multifactorial in its pathogenesis, the ␤ isoform of protein kinase C (PKC) has been implicated as a central mediator in the development of diabetic complications. Accordingly, we hypothesized that its inhibition with the orally active, selective inhibitor of PKC-beta, ruboxistaurin (RBX) would preserve cardiac function and reduce collagenous matrix deposition. Methods: Homozygous Ren-2 (n = 34) rats were randomized to receive STZ (diabetic) or vehicle (non-diabetic) and followed for 6 weeks. Two days post STZ injection, rats were further randomized to vehicle or RBX (20 mg/kg daily). Prior to tissue collection, animals underwent in vivo cardiac catheterization with pressure-volume loop acquisition. Results: Blood glucose was elevated in the diabetic group (p < 0.01). Compared with untreated diabetic rats, RBXtreated Ren-2 diabetic animals demonstrated preserved systolic and diastolic function, as measured by the slope of preload recruitable stroke work (PRSW) relationship (p < 0.05), and the slope of the end-diastolic pressure volume relationship (p < 0.01). Collagen I and III levels were reduced in Ren-2 diabetic animals treated with RBX (p < 0.01). Cardiomyocyte hypertrophy and high levels of phospho-Smad2 (a marker of transforming growth factorbeta [TGF beta] activity) were similarly reduced in RBXtreated animals (p < 0.01). There were no significant differences between control and RBX treated non-diabetic rats. Conclusions: Inhibition of PKC beta isoform with RBX in the diabetic Ren-2 rat preserves systolic and diastolic function and attenuates extracellular matrix accumulation, along with a reduction in the expression of the prosclerotic cytokine TGF beta. PKC-beta inhibition may present a novel therapeutic strategy for the treatment and/or prevention of DCM.

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30 TGF Beta Inhibition with Tranilast Improves Diastolic Function in the Diabetic (mRen-2)27 Transgenic Rat D.J. Kelly1,* , Y. Zhang1 , K.A. Connelly1 , R.E. Gilbert1,2 1 University

of Melbourne Department of Medicine, St. Vincent’s Hospital, Vic., Australia; 2 Department of Medicine, University of Toronto, St. Michael’s Hospital, Canada Objective: The pathological accumulation of extracellular matrix (ECM) and cellular apoptosis is a characteristic feature of diabetic cardiomyopathy. Tranilast (n-[3,4anthranilic acid), has been shown to inhibit transforming growth factor-beta (TGF-beta)-induced matrix production in the diabetic (mRen-2)27 (Ren2) transgenic rat. We hypothesized that inhibition of TGF beta in the diabetic Ren2 rat using tranilast would inhibit ECM production and reduce cellular apoptosis, leading to improved diastolic function. Methods: Heterozygous Ren2 rats were randomized to streptozotocin or vehicle (STZ) at age 6 weeks. At age 8 weeks, animals were randomized to tranilast (400 mg/kg/day) or vehicle for a further 8 weeks. Prior to tissue collection, animals underwent echocardiography to assess diastolic function. Results: At 16 weeks, diabetic animals demonstrated impaired diastolic function with reduced “E/A” ratio (1.5 ± 0.27 versus 1.04 ± 0.05) and prolonged deceleration time (35.7 ± 2.6 versus 55.7 ± 1.97 ms) when compared to control (p < 0.05). Tranilast treatment was associated with improved diastolic function as evidenced by the increased “E/A” ratio (1.04 ± 0.05 versus 1.48 ± 0.5) and reduced deceleration time (55.7 ± 1.97 ms versus 42.9 ± 1.18 ms),(p < 0.05) Furthermore, the tranilast treated group demonstrated a reduction in collagen types I and III (p < 0.01) along with a reduction in cardiomyocyte diameter (p < 0.01) and reduced cellular apoptosis (p < 0.01). Conclusion: These findings indicate that tranilast has antifibrotic and anti-apoptotic actions in this model of experimental diabetic cardiac disease, which lead to improvements in diastolic function. This may represent a novel therapy in the treatment of diabetic cardiomyopathy and diastolic dysfunction. 31 Effect of Oxidative Stress on Arginine uptake in Cardiomyocytes: Consequences for NO K. Venardos* , T. Marshall, D. Kaye, FCSANZ Wynn Department of Metabolic Cardiology, Baker Heart Research Institute, Melbourne, Vic., Australia The term ‘no-reflow’ describes compromised tissue perfusion following reperfusion of a previously ischemic tissue. In both experimental studies and clinical investigations, the incidence and extent of early no-reflow proves to be a strong predicator of contractile dysfunction, necrosis and worse clinical outcome. An early event during reperfusion is the development of endothelial dysfunction and formation of reactive oxygen species (ROS), both

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of which contribute to no-reflow. The endothelial dysfunction and enhanced inflammatory response associated with this phenomenon is thought to be largely caused by reduced bioavailability of nitric oxide (NO). However, the mechanisms responsible for reduced NO during ischemia-reperfusion remain unknown. This study investigated the effect of hypoxia-reoxygenation and oxidative stress on the uptake of the NO substrate L-Arginine (L-Arg), and NO production by neonatal ventricular cardiomyocytes (NVCM). NVCM were subjected to either 3 h hypoxia (in a hypoxic chamber) ± reoxygenation (of various lengths), or were treated with 50–150 ␮M H2 O2 . Both L-Arg uptake and NO production were decreased during reoxygenation, with lowest levels observed after 2 h reoxygenation. ROS production increased during reoxygenation, peaking after 2 h reoxygenation. NVCM treated with H2 O2 also showed a concentration-dependent decrease in L-Arg uptake and NO production, suggesting the decreased L-Arg uptake and NO production observed during hypoxia-reoxygenation may result from increased ROS production. It is also known that in the absence of L-Arg, NOS becomes uncoupled and also produces superoxide, which may further contribute to oxidative stress. In parallel to the decrease in NO and increase in ROS, these cells also exhibit lower mitochondrial membrane potentials. These results suggest that hypoxia-reoxygenation of NVCM leads to reduced mitochondrial integrity and increased ROS production, which subsequently leads to decreased L-Arg uptake and NO production. Increasing L-Arg availability may restore NO levels and improve the outcome following hypoxic or ischemic insults. 32 Effects of Specific Rho Kinase Inhibition on Collagen Synthesis in Isolated Neonatal Rat Cardiac Fibroblasts Arintaya Phrommintikul* , D. Cantwell, A. Kompa, H. Krum, FCSANZ NHMRC CCRE in Therapeutics, Department of Medicine, Central and Eastern Clinical School, Monash University, Alfred Hospital, Melbourne, Vic., Australia Diastolic dysfunction is a prominent feature of congestive heart failure with or without left ventricular systolic dysfunction and affecting morbidity and mortality. Myocardial fibrosis had been demonstrated to be an important factor for diastolic stiffness and dysfunction. Neurohormonal (angiotensin II (ANG-II)) and Proinflammatory cytokines (transforming growth factor ␤1 -(TGF␤1 )) are up-regulated in hypertensive heart failure and are known to stimulate collagen synthesis in isolated cardiac fibroblasts (CFbs). We have demonstrated that Rho kinase inhibition improves diastolic parameters in a pressure overload hypertrophy model. However, it is unclear whether this effect is mediated via inhibition of pathological myocardial collagen deposition. We investigated the effect of a specific Rho-kinase inhibitor (GSK576371) on collagen synthesis in isolated CFbs. Rat CFbs were isolated from neonatal pups and stimulated with ANG II (10−7 M) and TGF␤1 (2 × 10−10 M) in the presence and

absence of GSK576371 (10−7 to 10−5 M) for 48 h. Collagen synthesis was measured by [3 H]-proline incorporation and cell proliferation was measured by [3 H]-thymidine incorporation. GSK576371 significantly reduced ANG-II and TGF␤1 -stimulated collagen synthesis and cell proliferation in a dose dependent manner. Figure shows the effects of Rho-kinase inhibition on collagen synthesis in the presence of ANG II and TGF␤1 , respectively.

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(2 mg/kg), and CAR2 donor hearts (n = 6) were preserved in Celsior with GTN (100 mg/L) and cariporide (10 ␮mol/L). Animals were monitored for 3 h after successful weaning from cardiopulmonary bypass. 5/5 CAR1 and 5/6 CAR2 transplanted hearts were successfully weaned from cardiopulmonary bypass compared with only 1/5 CON animal (p < 0.05). Left ventricular contractility (preload recruitable stroke work) was superior in CAR2 compared with CAR1 animals (p < 0.0001) but there was no difference in cardiac output or blood pressure between these groups post-transplantation. GTN plus cariporide in Celsior combined with donor HR provides optimal recovery of the transplanted heart after 14 h storage in a clinically relevant model. These results support the trial of these treatments in clinical transplantation to test its safety and efficacy. Basic Science – Vascular 34 Platelet Activation, Inflammation and Cardiac Dysfunction, and their Relation to the Extent of Acute Pulmonary Embolism T. Chung1,* , D. Connor2 , J. Joseph2 , L. Emmett3 , D. Ma2 , L. Kritharides1 , FCSANZ 1 Department

Figure. Conclusion: Inhibition of the Rho-kinase pathway via a specific Rho-kinase inhibitor improves diastolic function, at least in part via attenuation of pathological myocardial collagen deposition. 33 Preserving the Donor Heart for Transplantation Using Cariporide and Glyceryl Trinitrate Alfred Hing1,3,* , Mark Hicks1 , Ling Gao1 , Steven Faddy1 , Aisling McMahon2 , Scott Kesteven2 , Michael Feneley2 , FCSANZ, Michael Wilson3 , Peter Macdonald1,3 , FCSANZ 1 Transplant

Program, The Victor Chang Cardiac Research Institute; 2 Cardiovascular Mechanics Program, The Victor Chang Cardiac Research Institute; 3 Heart Transplant Unit, St. Vincent’s Hospital, Darlinghurst NSW, Australia Donor brain death and ischaemia-reperfusion injury subject the transplanted heart to a series of injuries that may result in graft dysfunction and failure. We have previously shown that pre-treatment of donors and recipients with cariporide can improve cardiac preservation. The aim of this study was to assess whether the use of glyceryl trinitrate (GTN) with cariporide could further improve longterm preservation of the transplanted heart. A porcine model of orthotopic heart transplantation was used. Brain dead donors were managed for 6 h using noradrenaline and hormone resuscitation (HR). All hearts were then subjected to 14 h ischaemic storage in Celsior. Control transplants (CON, n = 5) received no cariporide or GTN, CAR1 (n = 5) donors and recipients were given cariporide

of Cardiology, Concord Hospital, ANZAC Research Institute, University of Sydney; 2 Department of Haematology, St. Vincent Hospital, University of New South Wales, Australia; 3 Department of Nuclear Medicine, Concord Hospital, ANZAC Research Institute, University of Sydney Background: Platelet activation and acute inflammation are implicated in acute pulmonary embolism (PE); however, their relationship to the extent of pulmonary artery obstruction, its resolution and associated right ventricular (RV) dysfunction is unclear. Methods: Thirty patients (age 63 ± 18 years) with acute PE were prospectively studied for platelet activation by flow cytometry (p-selectin (CD62p) expression, glycoprotein IIb/IIIa complex conformational change (detected by PAC-1 binding) and platelet-leukocyte complexes formation), D-dimer, C-Reactive protein (CRP), and markers of RV dysfunction (RV to left ventricular (LV) area ratio; B-type naturetic peptide (BNP); troponin-T) on day 1 of diagnosis. The extent of pulmonary artery obstruction (day 1) and its resolution (day 42) were quantified on ventilation/perfusion (VQ) pulmonary scintigraphy. Results: At day 1, the extent of pulmonary artery obstruction correlated with RV:LV area ratio (r2 = 0.33, p = 0.001), d-dimer (r2 = 0.48, p = 0.0005), BNP (r2 = 0.30, p = 0.005), and troponin-T (r2 = 0.23, p = 0.01). Patients with acute PE had mildly elevated PAC-1 binding (1.5 ± 1.8% versus 0.4 ± 0.4%, p = 0.03) and CRP (59 ± 67 mg/L versus 3 ± 2 mg/L, p = 0.03) compared with age-matched controls (n = 12), however, markers of platelet activation and CRP did not correlate with the extent of pulmonary artery obstruction or RV:LV area ratio. Patients with eventual complete PE resolution at day 42 (12/25) had greater CD62p expression (2.9 ± 1.8% versus 1.1 ± 0.6%, p = 0.005) at day 1 than did patients with incomplete resolution.

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Conclusion: D-dimer and markers of RV dysfunction are strong correlates of the extent of PE. PE is associated with mild platelet activation, especially in small PE. Antiplatelet therapy is unlikely to be relevant for management of large PE. 35 Investigation of Genetic and Biochemical Determinants of Depressed L-Arginine Transport in Human Hypertension Z. Yang1,* , B. Morris2 , D. Kaye1 , FCSANZ 1 Baker

Heart Research Institute, Melbourne, Australia; of Sydney, Sydney, Australia

2 University

Background: Endothelial dysfunction due to reduced nitric oxide (NO) bioavailability is a cardinal feature of essential hypertension (EH) and several mechanisms have been proposed. Recently, we demonstrated that this might be due to decreased endothelial uptake of the nitric oxide precursor, L-arginine, while others have proposed a role for the nitric oxide synthase (NOS) inhibitor, asymmetric dimethyl L-arginine (ADMA). Given that EH shows a significant familial link. Methods and results: We tested the hypothesis that a genetically determined impairment of L-arginine uptake, via the arginine transporter CAT-1, may occur in EH. Accordingly we sequenced the entire CAT1 gene and identified a novel C/T polymorphism in the 3 UTR region of the CAT1 gene. In 407 healthy subjects the frequency of the TT genotype was 0.3% while in 285 hypertensives it was 1.8% (p < 0.05). To determine the biological effect of this 3 UTR polymorphism, luciferase reporter assays were conducted to investigate the effect on gene expression. By this analysis, presence of the T allele was accompanied by significantly lower luciferase activity (p < 0.05). In conjunction with this study, we assessed forearm Larginine uptake during an intra-arterial infusion of [3 H]Larginine, endothelial function and measured the plasma concentration of arginine and related metabolites including ADMA and N-monomethyl-L-arginine (NMMA) in 10 young patients with EH (mean ± S.D.; age: 25.4 ± 4.5 years; blood pressure: 154/88 ± 11/9 mmHg) and 14 healthy control subjects (CON: age: 25.3 ± 5.8 years; blood pressure: 122/73 ± 6/5 mmHg). In keeping with previous findings, Larginine uptake was substantially reduced in EH (p < 0.01), and while plasma ADMA concentration tended to be elevated in EH (p = 0.065), the decrease in arginine transport did not correlate with ADMA levels. Conclusion: In this study we have identified a novel polymorphism in the CAT1 gene, which may contribute to the reduction in arginine transport observed in hypertension. 36 PKC-Regulated L-Arginine Transport is Mediated via a Calpain Associated Pathway C. Enriquez* , B. Ahlers, T. Marshall, J. Chin-Dusting, D. Kaye, FCSANZ Baker Heart Research Institute, Melbourne, Vic., Australia Background: The endothelium plays a vital role in the maintenance of vascular tone and structural vascular

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integrity, principally mediated via the actions of nitric oxide (NO). L-arginine (L-Arg) is the immediate substrate for NO synthesis, and it has been clearly shown that the availability of extracellular L-Arg is critical for the sustained production of NO. We have recently shown in human heart failure and hypertension that L-Arg uptake via is significantly reduced providing a mechanistic explanation for the endothelial dysfunction that accompanies these cardiovascular disorders. Activation of protein kinase C (PKC) dependent signaling pathways are a feature of a number of cardiovascular disease states, and in this study we hypothesized that PKC modulates endothelial L-Arg transport. Methods and results: In response to PKC activation (PMA 100 nM, 30 min), [3H]L-Arg uptake by bovine aortic endothelial cells (BAEC) was reduced to 45 ± 4% of control (p < 0.05). This resulted from a 53% reduction in the Vmax (p < 0.05), with no change in the Km for L-Arg. Western blot analysis and confocal microscopy revealed no change in the expression or membrane distribution of CAT-1, the principal BAEC L-Arg transporter. Moreover in 32 P-labeling studies, PMA exposure did not result in CAT-1 phosphorylation. We have subsequently demonstrated that inhibition of calpain either pharmacologically or via adenoviral-mediated infection with the endogeneous inhibitor, calpastatin, significantly attenuates the effect of PKC activation of arginine transport. Conclusion: PKC dependent mechanisms regulate the transport of L-Arg, via a calpain-sensitive intermediate pathway. 37 The Coronary Slow Flow Phenomenon is Associated with Endothelial and Platelet Dysfunction Victoria Kopetz* , Scott Willoughby, Sue Leslie, John Beltrame, FCSANZ Cardiology Unit, The Basil Hetzel Institute, The Queen Elizabeth Hospital, Department of Medicine, The University of Adelaide, SA, Australia Background: The Coronary Slow Flow Phenomenon (CSFP) is a microvascular disorder associated with disabling angina despite angiographically normal coronary arteries. The mechanisms responsible for the microvascular dysfunction are unknown. The objective of this study is to determine if patients with the CSFP have evidence of endothelial or platelet dysfunction. Methods: Pulse-wave analysis was used to assess endothelial vasodilator function in fifteen CSFP patients and fifteen age-matched controls (Ctrls). The maximum decrease in Augmentation Index (AIx: measurement of arterial stiffness) after administration of endotheliumindependent [50 ␮g sublingual glyceryl trinitrate] and endothelium-dependent (400 ␮g nebulised salbutamol) vasodilators was determined. Platelet function was assessed via adenosine diphosphate (ADP)-induced optical aggregometry. Inhibition of aggregation by the nitric oxide donor sodium nitroprusside (SNP) was also assessed.

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Results: Maximal arterial relaxation responses to glyceryl trinitrate were similar between groups (AIx: Ctrls = −12.1 ± 1.2% versus CSFP = −13.5 ± 0.9%, p = 0.3). Salbutamol administration produced a relaxation response in Ctrls but a paradoxical constrictor response in the CSFP patients (AIx: Ctrls = −3.6 ± 1.3% versus CSFP = 1.2 ± 1.3%, p = 0.02). The maximal platelet aggregatory response to ADP did not differ significantly between groups (Ctrls = 33.2 ± 5.9% versus CSFP = 38 ± 6.0%, p = 0.5), however, inhibition of platelet aggregation by SNP was significantly impaired in CSFP patients (Ctrls = 54 ± 6.4% versus CSFP = 36 ± 5.3, p = 0.04). Conclusion: This study demonstrates that CSFP patients have impaired inhibitory platelet aggregatory responses to SNP and paradoxical endothelium-dependent vasoconstrictor responses to salbutamol. These findings suggest that endothelial and/or platelet dysfunction may contribute to the pathophysiology of the CSFP. 38 Mechanism of Inhibition of Microvascular Constrictor Responses by Pravastatin N. Ghaffari* , C. Ball, J. Kennedy, J.F. Beltrame, FCSANZ Cardiology Unit, The Queen Elizabeth Hospital, School of Medicine, The University of Adelaide, Australia Background: The clinical benefits observed with statin therapy are possibly derived from multiple mechanisms. Recently we have shown that acute pravastatin exposure impairs phenylephrine (PE) constrictor responses in rat mesenteric microvessels. The objective of this study was to determine if this pravastatin effect is mediated via an endothelium-dependent mechanism and in particular via nitric oxide. Methods: Rat mesenteric microvessels (200–500 ␮m) either intact or denuded of endothelium were mounted in wire myograph and endothelial integrity was confirmed by acetylcholine responses. Concentration-response curves to PE were determined pre- and post-pravastatin (112 nM) incubation. Microvessels with intact endothelial responses were incubated with pravastatin, L-Nitro Arginine Methyl Ester (L-NAME; 0.3 mM) or both agents and the response to PE assessed. Results: (Mean ± S.E.M.) Pravastatin inhibited PE contractile responses in (n = 6) endothelium-intact vessels (Pre-pravastatin 120 ± 6%, Post-Pravastatin 93 ± 10%, p = 0.0021* ). This response was abolished in endothelium-denuded vessels (Pre-pravastatin 138 ± 6%, Post-Pravastatin 135 ± 9%, p = 0.43). Inhibition of nitric oxide synthesis with L-NAME-NAME in endothelium intact microvessels (n = 7) also abolished pravastatin’s effect on PE constrictor responses (Table). Endothelium-Intact Microvessels

Pre-Treatment (%)

Post-Treatment (%)

p 0.0001*

Pravastatin (n = 7)

122 ± 4

90 ± 6

L-NAME-NAME (n = 7) L-NAME-NAME + Pravastatin (n = 7)

126 ± 5

129 ± 4

0.24

119 ± 5

122 ± 5

0.47

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Conclusion: Pravastatin’s inhibition of the PE constrictor response is mediated via endothelium-dependent mechanisms, namely endothelium-derived nitric oxide. 39 HDL Exerts Rapid and Profound Anti-Inflammatory Effects on Acute Arterial Inflammation via an NFkB Mediated Pathway R. Puranik, K.-A. Rye, P.J. Barter, FCSANZ, D.S. Celermajer, FCSANZ, A.K. Heather Heart Research Institute, Sydney, NSW, Australia HDL and its chief apolipoprotein apoA-1 are inversely related to coronary risk, but their mechanism of action is incompletely characterised. We investigated the antiinflammatory properties of HDL in vitro and in vivo. In particular, the effects on the key pro-atherogenic and pro-inflammatory IKK/IkB/NFkB signaling pathway were explored. In vitro, reconstituted HDL (rHDL) containing apoAI (16 ␮M) and phosphatidylcholine, suppressed TNFstimulated IKK activation by 58% (p < 0.05) and IkB phosphorylation by 60% (p < 0.05), ultimately decreasing NFkBmediated DNA transcription by 85% in human coronary artery endothelial cells (HCAECs) (p < 0.001). In keeping with suppression of NFkB signaling, we showed by macroarray that rHDL substantially reduced expression of many NFkB-regulated genes including VCAM-1, via its effect at reducing VCAM-1 promoter activity by 75% (p < 0.001). Accordingly, rHDL decreased VCAM-1 protein levels by 40% (p < 0.05). The rHDL-mediated decrease in VCAM-1 protein was associated with a significant decrease (p < 0.001) in monocyte adhesion to HCAECs. In vivo, we assessed the effects of single low dose (8 mg/kg apoA-1) infusions of rHDL or apoA-1 in a wellcharacterised model of arterial inflammation induced by non-occlusive peri-arterial carotid collars in the rabbit. Remarkably, rHDL and apoA-1 decreased endothelial VCAM-1 expression (>85%, p < 0.0001) when given 24 h before the collar. Further, apoA-1 could rescue vascular inflammation when given even 9 h post-collar application. Thus HDL attenuates signaling via the major inflammatory NFkB pathway in human coronary artery endothelial cells and has profound anti-inflammatory effect in arteries, even as “rescue” therapy. These findings suggest a novel potential therapeutic modality for HDL in clinical vascular disease. 40 Endothelial Progenitor Cell is a Dominant Source for Endothelial Replacement in Mice Subjected to Acute Lipopolysaccharide Insult Colin Tso* , FCSANZ, P.J. Barter, FCSANZ Heart Research Institute, Camperdown, NSW, Australia Endothelial progenitor cells (EPCs) participate in endothelial repair. We have previously reported engraftment of stem cell antigen-1 expressing (Sca-1+) progenitor cells in the endothelium of C57BL/6J (B6) mice after

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lipopolysaccharide (LPS) administration. This study aims to explore the effects of LPS on the endothelial layer and circulating progenitor cell level. LPS (50 ␮g/animal) was administered intraperitoneally to male B6 mice (n = 12) with untreated mice (n = 8) from the same batch serving as controls. Immunohistochemistry and TUNEL staining was performed on paraffin-embedded thoracic aortic sections obtained from mice sacrificed 18 h after LPS. Flow cytometry analysis was performed on circulating blood cells obtained from left ventricular puncture in mice sacrificed 5 h after LPS. There was a significant increase in endothelial TUNEL+ apoptotic cells 18 h after LPS treatment (50 ± 17.5% after LPS versus 11 ± 16% in the controls; P < 0.01). The proportion of endothelial Sca-1+ cells was increased to a similar level (50 ± 13% after LPS versus 19 ± 13% in the controls; P = 0.02). Clusters of endothelial cells were positive for another endothelial progenitor marker Flk-1. There was no significant expression of the cellular proliferative antigen Ki67 in the endothelium. The proportion of circulating Flk-1+ cells was significantly reduced 5 h after LPS (0.2% ± 0.06 after LPS versus 1.1% ± 0.3 in the controls; P < 0.01). In conclusion, we found substantial LPS-induced endothelial cell loss that is not matched by cellular proliferation. The high level of progenitor engraftment into the damaged endothelium together with the drop in circulating progenitor cells after LPS indicate that EPC is a dominant source of endothelial cell replacement in this model. 41 Endothelial Engraftment of Stem Cell Antigen-1 Expressing Progenitor Cells Increased with Age in Apolipoprotein E Deficient Mice Colin Tso* , FCSANZ, P.J. Barter, FCSANZ Heart Research Institute, Camperdown, NSW, Australia Stem cell antigen-1 expressing (Sca-1+) progenitor cells represent a source of endothelium. We have previously reported substantial endothelial engraftment of Sca-1+ progenitor cells in mice subjected to acute lipopolysaccharide (LPS) insult that is consistent with a repair mechanism. The endothelium of the atherosclerosis-prone apolipoprotein E deficient (apoE−/− ) mice is under chronic stress and a high level of endothelial Sca-1+ cells has been observed in these animals. The aim of this study is to quantitatively assess endothelial engraftment of Sca-1+ progenitor cell in apoE−/− mice of increasing age. Paraffinembedded thoracic aortic sections from 11 weeks (n = 4), 15 weeks (n = 3) and 23 weeks (n = 3) old male apoE−/− mice fed on normal chow were analyzed immunohistochemically and the proportion of Sca-1+ cells in the endothelium was quantified. Sca-1+ cells were seen in the endothelial layer and displayed an endothelial phenotype. The proportion of endothelial Sca-1+ cells increased significantly with advancing age.

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Age of apoE−/− Mice

% Sca-1+ Cells in Aortic Endothelium

11 weeks

35 ± 8.4*

15 weeks

50 ± 3.7

23 weeks

83 ± 7.7*

∗

P < 0.01.

Early atherosclerotic plaques were seen in the 15 weeks old apoE−/− mice and more advanced plaques in the 23 weeks old apoE−/− mice. The endothelium overlying these plaques expressed Sca-1 and Sca-1+ and c-kit+ cells were seen within the plaques. In conclusion, our results show that the extent of endothelial injury and progenitor-mediated endothelial repair increase with age in atherosclerotic mice. These observations also raised the possibility that progenitor-mediated endothelial repair and the atherosclerotic process may be mechanistically linked. 42 Relation of Testosterone to Traditional and Alternative Markers of Atherosclerotic Risk Roger E. Peverill1,* , FCSANZ, Carolyn A. Allan2 , Erica Malan1 , Elise Forbes2 , Robert I. McLachlan2,3 1 Monash Cardiovascular Research Centre; 2 Prince Henry’s Institute; 3 Department of Obstetrics & Gynaecology, Monash University & Monash Medical Centre, Clayton, Victoria, Australia

Men with coronary artery disease have subnormal levels of testosterone (T), but little is known about the mechanisms which might underly an association between reduced T and atherosclerosis. We therefore investigated the relationship of T with traditional and alternative markers of atherosclerosis in a cohort of men with symptoms consistent with hypoandrogenism. Methods: There were 93 non-obese, non-smoking men of age 63 ± 7 years, of whom 62 had low-normal T levels (average total T < 15 nM). We measured total T, sex hormone binding globulin, lipids, fibrinogen, D-dimer (a marker of fibrin turnover), plasminogen activator inhibitor-1 (PAI1; marker of fibrinolytic potential), von Willebrand factor (vWF; marker of endothelial activation) and C-reactive protein (CRP). The free T level was calculated. Results: Free T (but not total T) was negatively correlated with age (r = −0.28, p < 0.01). Total T was negatively correlated with triglycerides (r = −0.27, p = 0.01), but not with other lipids, and free T was not related to any of the lipids. The relation of total T with triglycerides was independent of anthropometric measures. Fibrinogen was negatively correlated with total T (r = −0.27, p < 0.01), but more strongly correlated with free T (r = −0.36, p < 0.001). Fibrinogen was also positively correlated with CRP (r = 0.40, p < 0.001) and D-dimer (r = 0.30, p = 0.005). In a multivari-

ate analysis, fibrinogen was independently related to free T, CRP and D-dimer. CRP was correlated with free T (r = −0.21, p < 0.05), but not with total T, and free T was no longer a predictor of CRP in a multivariate analysis after including fibrinogen. PAI-1, D-dimer and vWF were not related to total or free T. Conclusion: In ageing men, total T is an independent inverse determinant of triglycerides and free T is an independent inverse determinant of fibrinogen. These relationships may explain an unfavourable effect of subnormal T levels on atherosclerosis. 43 Relationship of Adiponectin to Coagulation and Fibrinolysis in Post Menopausal Women Roger E. Peverill1,* , FCSANZ, Erica Malan1 , Barry P. McGrath2 , FCSANZ, Helena J. Teede3 1 Monash Cardiovascular Research Centre, Monash Medical Centre; 2 Centre for Vascular Health; 3 Jean Hailes Research Group, Monash University, Clayton, Victoria, Australia

We recently reported an association between waistto-hip ratio (WHR) and coagulation activation, potentially explaining the relationship between obesity and atherothrombosis, but the mechanism underlying this association remains unclear. Adiponectin is a cytokine synthesized in adipose tissue and adiponectin levels are inversely associated with coronary risk. Whether adiponectin could provide a link betwen adiposity and coagulation activation has not been studied. Methods: We measured height, weight, waist (WC) and hip circumference (HC), and calculated body mass index (BMI) and WHR in a cohort of 74 healthy post-menopausal non-smoking women not taking hormone therapy. Blood samples were collected for measurement of lipids, insulin, adiponectin, prothrombin fragments 1 + 2 (F1 + 2; a marker of thrombin generation), soluble fibrin (SF) and plasminogen activator inhibitor-1 (PAI-1; a marker of fibrinolytic inhibitory potential). Linear regression analysis was performed and only statistically significant (p < 0.05) correlations are presented below. Results: Adiponectin was negatively correlated with WC, HC and BMI to a similar degree (r = −0.26 to −0.28) and was also negatively correlated with insulin (r = −0.31) and positively correlated with HDL (r = 0.44). Adiponectin was not related to F1 + 2 or SF, but was negatively correlated with PAI-1 (r = −0.46). PAI-1 was positively correlated with BMI (r = 0.53), WC (r = 0.47), HC (r = 0.48), insulin (r = 0.66) and triglycerides (r = 0.53) and negatively correlated with HDL (r = −0.56). In multivariate regression analysis, PAI-1 was inversely and independently correlated with insulin and adiponectin, but no longer related to BMI, triglycerides or HDL. Conclusion: Adiponectin is an independent determinant of lower PAI-1 levels, and thus may favourably modify the fibrinolytic process, but does not appear to play a role in the activation of coagulation seen in abdominal obesity.

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44 Development of Aortic Valve Stenosis (AS) Induced by Vitamin D2 in a Rabbit Model Doan T. Ngo1,* , Ronald D. Wuttke1 , Helen Weedon2 , Irene Stafford1 , Angus K. Nightingale1 , Anke R. Rosenkranz1 , Aaron L. Sverdlov1 , Yuliy Y. Chirkov1 , Jennifer A. Kennedy1 , John Horowitz1 , FCSANZ 1 The

Queen Elizabeth Hospital, University of Adelaide, South Australia; 2 Repatriation Hospital, Flinders University, SA, Australia The principal aim was to develop a clinically relevant animal model of AS. We hypothesized that vitamin D2 (VitD) [25,000 IU/4 days weekly (VitD-hd)] supplementation induces AS in rabbits; effects on vascular and valvular endothelial function (EnF) were also studied. Male New Zealand white rabbits (n = 8 each) were treated for 8 weeks with VitD-hd (A) or normal chow/drinking water (B). Additional groups (n = 4 each) received 0.5%-cholesterol/VitD-hd (C); or VitD-ld [5,000 IU/4 days weekly (D)]. Aortic valve pressure gradients (AVp), flow (AVv), and aortic valve backscatter scores (BS) were measured and valvular pathology assessed. Valvular EnF was assessed via release of anti-aggregatory autacoids. Vascular EnF was examined with acetylcholine (ACh) (0.001–100 ␮mol/L)-induced relaxation in pre-constricted vessels. VitD-hd (A) significantly increased AVp, AVv (p < 0.01 for both) and BS scores (17.6 ± 4.1 (S.D.) versus 6.7 ± 2.3 (S.D.), p < 0.0001) compared to controls, with nonsignificant changes in groups (C) and (D). Valvular sections stained positive for marked calcification, lipids, macrophage and leukocyte infiltrations compared to controls; while groups (C) and (D) were similar to (A) and (B), respectively. Valvular anti-aggregatory autacoid function was increased in group A (64.7 ± 7% versus 48.4 ± 4% in (B), p < 0.05), while maximum relaxation (Emax) to ACh was significantly impaired in group (A) versus (B) (70.9 ± 1.5% versus 18.2 ± 9.4%, respectively). In this model, VitD-hd induces aortic stenosis in 8 weeks, with pathological features similar to those of AS in humans, and is associated with impaired vascular but not valvular EnF. Additional high cholesterol diet does not potentiate these changes. 45 Incidence of Carotid Artery Stenoses in a Tertiary Referral Centre: Age and Gender Effects N.J. Bull, P. Diu* , C. Hiew John Hunter Hospital, Newcastle, NSW, Australia A total of 6962 consecutive carotid duplex studies performed at the John Hunter Hospital were studied. Data collected include age, gender, systolic and diastolic velocities and degree of reported stenosis. Calculated data include the degree of stenoses according to both the internal/common carotid artery ratio and peak systolic

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and diastolic blood flow velocities. The mean age was 68 years (S.D. = 13.6 years, range 0–102). Women were significantly older (mean difference 2.3 years) at test than males (t = −7.172, d.f.(6922), p < 0.0001). The incidence of detectable carotid atheroma increases linearly with age (at a rate of 10% of patients per decade). Haemodynamically significant internal carotid (>60% reduction ICA luminal diameter) disease increased throughout the age range for men, but not for women. In women the incidence of significant disease peaked at 50 years of age and remained level thereafter (Fig. 1). Significant disease occurred earlier in the left internal (30 years) carotid than in the right (50 years) (χ2 = 7772.0(81) , p < 0.001). Three thousand seven hundred and nine (53.3%) patients were found to be completely free from atheroma.

Heart, Lung and Circulation 2006;15S:S1–S167

Methods: Human aortic smooth muscle cells were incubated for 10 weeks with the active metabolites ramiprilat (R, 35 ng/ml) and perindoprilat (P, 52 ng/ml). Doses corresponded to the plasma concentrations achieved with clinical oral dose equivalents of these drugs (ramipril 10 mg, perinopril 8 mg). Matrix protein deposition was determined using histochemistry and immunohistochemistry. MMP-2 and MMP-3 gene expression and protein levels were also measured. Results: Both perindoprilat and ramiprilat reduced collagen deposition compared to control, but perindoprilat was more potent (control, 56 ± 4%; P, 17 ± 4%; R, 28 ± 5%; p < 0.05). Similarly, both drugs increased elastin deposition and again perindoprilat was more potent (control,

Figure 1. Incidence of significant internal carotid stenosis as a function of age. 46 Differential Effects of Perindopril and Ramipril on Human Aortic Smooth Muscle Cell Matrix Protein and Matrix Metalloproteinase Expression A.A. Ahimastos, A.K. Natoli, B.G. Drew, B.A. Kingwell* Baker Heart Research Institute, Melbourne, Australia Objective: Angiotensin-converting enzyme (ACE) inhibitors have anti-fibrotic and elastogenic effects which lower arterial stiffness contributing to reduced vascular risk. Whether these effects are consistent across the class is not known. We determined the effects of ramipril and perindopril on the expression of specific arterial matrix proteins (elastin, collagen, fibrillin-1) and their regulators (matrix metalloproteinases, MMP-2 and MMP-3).

8 ± 1%; P, 51 ± 10%; R, 30 ± 1%; p = 0.001). In contrast, only ramiprilat increased deposition of fibrillin-1 (control, 13.0 ± 0.3%; P, 16 ± 1%; R, 64 ± 5%,) and this was associated with increased gene expression (control, 1.1 ± 0.1; R, 5.7 ± 0.9; p < 0.001). Both drugs decreased gene and protein expression of MMP-2 and MMP-3. Ramiprilat was more potent in inhibiting MMP-2 gene and protein expression compared to perindoprilat, which could explain the higher fibrillin-1 deposition with ramiprilat. Conclusions: Ramipril and perindopril reduce collagen deposition and increase elastic matrix proteins. Perindopril increases elastic fibre deposition through elastin while ramipril increases fibrillin-1. These actions may differentially influence arterial biomechanical properties clinically.

47 The Role of c-jun in Flow-Dependent and FlowIndependent Restenosis after Angioplasty and Stenting Melanie Murrell1,* , Levon Khachigian2 , Michael Ward1 . 1 Vascular

Biology Laboratory, Royal North Shore Hospital, University of Sydney; 2 School of Pathology, University of New South Wales, Sydney, NSW, Australia

Low flow exacerbates restenosis after both balloon angioplasty and stenting. We have previously shown that the antioxidant pyrrolidine dithiocarbamate (PDTC) prevents flow-dependent inward remodelling and lumen loss after angioplasty but has no effect on in-stent intimal hyperplasia. We examined whether inhibition of c-jun expression might explain the effects of PDTC. We performed over-sized (1.3–1.5:1) stenting (S) and balloon injury (B), in the carotid arteries of cholesterol-fed rabbits subjected to either low or normal flow. C-jun mRNA expression 4 h after injury (measured by real-time RT-PCR) was significantly enhanced by low flow and injury (stent 20-fold, balloon 5-fold >uninjured) and inhibited by the antioxidant PDTC (∼80% reduction). We then locally delivered DZ13 (a DNAzyme specific for c-jun) or scrambled DZ13 (inactive DNAzyme) via a microporous weeping catheter to another group of injured vessels and vessel areas were compared to those in uninjured segments (U) in the same artery and those from vessels undergoing injury without local delivery by histomorphometry at 28 days. Low flow significantly increased intimal hyperplasia in B and S relative to normal flow (P < 0.05). The active DNAzyme DZ13 reduced intimal hyperplasia by >80% (P < 0.001) and increased lumen size (P < 0.05) in balloon-injured vessels subject to low flow. Interestingly, however, in stented vessels there was no apparent effect of DZ13 on intimal hyperplasia. These studies suggest that c-jun plays a pivotal role in the redox-sensitive flow-dependent restenosis after angioplasty but not after stenting. 48 Dissociation of ALDH Activity From GTN Effect, Bioconversion, and Tolerance in Humans A.C. Philpott* , P.R. Sage, I. Stafford, G. Murphy, I. De La Lande, R. Stuklis, J. Edwards, J.D. Horowitz, FCSANZ Central Northern Health Service, Adelaide, SA, Australia Aldehyde dehydrogenase (ALDH) has recently been reported to be the principal mediator of GTN bioconversion, and central to the development of nitrate tolerance. These conclusions have been made in the absence of human studies. Methods: Patients undergoing elective coronary artery bypass were randomised to receive 18 h of intravenous glyceryl trinitrate (GTN: nitrate group), or no nitrate therapy (control group). Segments of saphenous vein (SV) and radial artery (RA) were used to examine (1) vascular responsiveness to GTN, and sodium nitroprusside; (2) bioconversion of GTN to 1,2- and 1,3-glyceryl dinitrate; and (3) vascular ALDH activity. Additional nitrate free vessels

Abstracts

S21

were used to assess the effect of ALDH inhibitors on vascular responsiveness to, and bioconversion of GTN. Results: ALDH inhibitors modestly reduced vascular responsiveness to GTN and reduced GTN bioconversion in SV by 50%. Responses to GTN were unchanged in saphenous vein and only modestly reduced in RA from the nitrate group compared with the control group (p = 0.01 for RA). Tissue content of 1,2-glyceryl dinitrate was unchanged in SV from the nitrate group compared with the control group. Despite unchanged vascular responsiveness and bioconversion of GTN following GTN exposure, the ALDH activity within saphenous veins was markedly depressed in the nitrate group compared with the control group. Conclusions: Vascular ALDH activity is highly sensitive to GTN exposure, which rapidly inactivates the enzyme, however as vascular responsiveness to GTN, and bioconversion of GTN are preserved in these vessels, ALDH can not be the exclusive mediator of GTN bioconversion or tolerance in humans. 49 Acute Iron Overload Induces Oxidative Stress, but Does Not Affect Endothelial Function in Humans S. Mukherjee* , J. Ziolkowski, B.A. Kingwell, K.D. Croft, H.A. Headlam, D.K. Vizi, A.M. Dart, FCSANZ, S.J. Duffy, FCSANZ Alfred & Baker Medical Unit, The Alfred Hospital & Baker Heart Research Institute, Melbourne, Australia Background: Reactive oxygen species have been implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Redox-active iron increases production of reactive oxygen species (via Fenton chemistry) and causes lipid peroxidation. F2 -isoprostanes are a reliable method for assessment of oxidant stress in vivo. We recently demonstrated that iron chelation with desferrioxamine reversed endothelial dysfunction in patients with coronary artery disease (CAD). We aimed to determine whether acutely increasing iron would result in oxidative stress in vivo and produce endothelial dysfunction. Methods: In 27 healthy volunteers (22 ± 4 [mean ± S.D.] years) and 11 patients with CAD (56 ± 8 years) we infused iron sucrose at doses aimed at increasing serum iron by two-fold (0.3 mg/min) and four-fold (1.3 mg/min). Forearm blood flow responses to graded intra-brachial infusions of acetylcholine and sodium nitroprusside (measured by venous occlusion plethysmography) were assessed before and after iron infusion. Forearm venous blood was sampled to measure iron and F2 -isoprostanes. Results: Iron infusion increased forearm (venous) serum iron from 19.7 ± 2.0 to 40.3 ± 2.8 mmol/L, and from 16.4 ± 2.3 to 54.2 ± 5.7 mmol/L for the respective doses (mean ± S.E.M., p < 0.0001 for both). F2 -isoprostanes in the venous effluent increased from 2503 ± 137 to 3073 ± 223 pmol/L after iron (p = 0.0003), indicating induction of oxidative stress in vivo. However, iron infusion at either dose did not attenuate the forearm blood flow response to the endothelium-dependent vasodilator

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

S22

Abstracts

ABSTRACTS

acetylcholine or the endothelium-independent vasodilator sodium nitroprusside in either healthy controls or patients with CAD. Conclusion: These data demonstrate that acute iron infusion induces oxidative stress in vivo, without affecting nitric oxide vascular reactivity. Given our previous evidence, this suggests that chronic iron overload is necessary to affect endothelial function, and by inference, atherosclerosis. 50 The Relationship Between Androgen Exposure and Cholesterol Esterification in Human Hepatocytes Daniel P. Sieveking1,* , Martin K.C. Ng1,2 , FCSANZ, Alison K. Heather1,3 , David S. Celermajer1,2,3 , FCSANZ 1 Heart

Research Institute, Sydney, Australia; 2 Royal Prince Alfred Hospital Sydney, Australia; 3 Department of Medicine, University of Sydney, Australia Male gender is a classical risk factor for coronary artery disease. The precise role of androgens in atherosclerosis remains unclear, however, with both beneficial and deleterious effects on cardiovascular risk factors being observed. As we demonstrated previously that androgens exert pro-atherogenic effects on lipid metabolism both by increasing acyl coenzyme A:cholesterol acyl transferase I (ACAT-1) expression and foam cell formation in human macrophages, we now hypothesised that androgens might similarly upregulate ACAT-2 in hepatocytes and thereby predispose to the overproduction of atherogenic lipoproteins by the liver. HepG2 cells (a human hepatocyte cell line, male donor) were therefore cultured in the presence of 0, 4, 40 or 400 nM of the non-aromatisable androgen dihydrotestosterone (DHT) for 24 h and we assessed the gene expression of ACAT-2 via real-time reverse transcription PCR (RT-PCR). After DHT treatment, cells were loaded with LDL (200 ␮g/ml) for a further 24 h and then analysed for storage or secretion of cholesterol (C) and cholesteryl esters (CE) via HPLC. Compared with control conditions, treatment with 4 nm DHT produced a modest 1.5 fold increase in ACAT-2 expression (P < 0.05). This had no significant effect, however, on the amount of cholesteryl esters stored (103 ± 10%, 98 ± 11%, 107 ± 17% versus 100% control value) or secreted (115 ± 13%, 85 ± 20%, 97 ± 11% versus 100% control value for DHT at 4, 40, and 400 nM, respectively, P > 0.05) by HepG2 cells. These data suggest that androgens do not exert pro-atherogenic effects on lipid homeostasis in human hepatocytes.

Heart, Lung and Circulation 2006;15S:S1–S167

51 Greater Inflammatory Infiltrate in Pericoronary Epicardial Compared with Distant Depots of Adipose Tissue Daniel Sieveking1,* , Bob Bao2 , Lisa Nguyen3 , Gareth Denyer3 , Matthew S. Bayfield3,5 , Paul G. Bannon3,5 , David S. Celemajer1,3,6 , FCSANZ 1 Heart Research Institute, Sydney; 2 Department of Pathology, University of Sydney; 3 School of Molecular and Microbial Biosciences, University of Sydney; 4 Royal Prince Alfred Hospital Sydney, NSW; 5 The Baird Institute for Heart and Lung Surgical Research; 6 Department of Medicine, University of Sydney, Australia

Adipose tissue secretes numerous bioactive proteins. We hypothesised that perivascular epicardial adipose tissue might have an excessive inflammatory infiltrate and thereby influence plaque development, composition and/or behaviour. We therefore collected adipose tissue from 5 depots from 8 patients undergoing coronary artery surgery: surrounding coronary artery angiographically confirmed to have plaque, surrounding the same artery free of plaque, the epicardium not associated with any vessels, around the mammary artery and subcutaneous fat. Tissue was analysed via immunohistochemistry (n = 8) and a subset via cDNA microarray and RT-PCR (n = 3). There were increased numbers of inflammatory cells in the epicardial adipose tissue compared to the subcutaneous and mammary depots (14.8 ± 5% versus 9.6 ± 6% and 11.3 ± 6%, respectively, P < 0.001). The greatest numbers of inflammatory cells were seen in the plaque and nonplaque samples (20.4 ± 7% and 18.6 ± 7%, respectively, P < 0.05 plaque versus non-plaque) (Fig. 1). RT-PCR analysis revealed that MCP-1 was upregulated in perivascular samples when compared to subcutaneous adipose tissue (8 ± 2.6 fold). However, comparison of plaque and nonplaque samples via cDNA microarray analysis showed no significant differential gene expression. Thus, perivascular epicardial adipose tissue is more inflammatory than perimyocardial epicardial adipose tissue, especially near plaques. This suggests that advential influences from epicardial adipose tissue might impact disease within the coronary arteries.

Figure 1.

Abstracts

S23

52 A Novel In Vitro Human Angiogenesis Assay Incorporating a Co-Culture of Fibroblasts and Endothelial Cells

53 Short-Term Feeding of a High Cholesterol Plus Methionine Diet Abolishes Endothelial Function in Rabbits

Daniel Sieveking1,* , Andrew Buckle1 , David Celermajer1,2 , FCSANZ, Martin Ng1,2 , FCSANZ

A. Zulli1,3,* , B.F. Buxton2 , D.L. Hare1,3 , FCSANZ

1 Heart

Research Institute, Sydney, Australia; Alfred Hospital, Sydney, Australia

2 Royal

Prince

Background: Angiogenesis assays are central to the investigation of the mechanisms underlying neovascularisation. To date, a simple and accurate model for the study of in vitro angiogenesis is lacking. A specific test for angiogenesis is the measurement of the ability of endothelial cells (ECs) to form tubes, however current methods based on culturing ECs on extracellular matrix (e.g. Matrigel) are limited and lack specificity, in that tubules formed do not resemble those in vivo, and tubule formation is observed for cells other than those of endothelial origin. Here we report a novel co-culture angiogenesis assay that overcomes the caveats of current methods, utilising a human foetal lung fibroblast cell line to support tubule formation. Methods and results: Co-culture of human fetal lung fibroblasts (MrC5) and Human Umbilical Vein Endothelial Cells (HUVECs) were evaluated using two techniques: (i) adding HUVECs to pre-seeded MrC5 monolayers, or (ii) seeding an admixed suspension of MrC5s and HUVECs. Both cultures were maintained using EGM-2 media. We observed formation of branched interconnecting EC tubules, beginning at day 4 with maximal growth at day 7 (Fig. 1). Pre-seeded cultures resulted in earlier and more robust tubule formation. Conclusion: This novel angiogenesis assay provides a simple and powerful in vitro method to assay endothelial cell function. The fetal lung fibroblastic cell line is readily attained and can be expanded in culture, providing a reproducible, and easily manipulated assay environment. The tubules formed are also representative of the in vivo setting, with similarities in tubule length and branching frequency.

1 Department

of Cardiology, University of Melbourne, Austin Health, Melbourne, Victoria, Australia; 2 Department of Cardiac Surgery, University of Melbourne, Austin Health, Melbourne, Victoria, Australia; 3 Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia We previously reported that a high cholesterol and methionine diet for 12 weeks abolishes endothelial relaxation. As endothelial dysfunction is implicated in the development of atherosclerosis, we sought to determine, in rabbits, the effects of this diet on endothelial function in the abdominal aorta and left main coronary artery (LMCA) after a 4-week dietary regimen, and whether a lower concentration of dietary cholesterol impaired endothelial function. Rabbits were fed for 4 weeks a diet supplemented with either 1% methionine + 0.5% cholesterol (0.5MC) or a diet supplemented with either 1% methionine + 0.1% cholesterol (0.1MC). Control animals received a normal chow diet. The endothelial function of the abdominal aorta and LMCA was examined using organ bath techniques. Endothelium dependent relaxation in response to acetylcholine was significantly decreased to 2.9 ± 3.8% in the 0.5MC group (p < 0.01), and vasoconstriction rather than vasodilation was observed in the left main coronary artery. Atherosclerosis was present in both types of vessels. Similarly, in the 0.1MC group, endothelium dependent relaxation in response to acetylcholine was significantly decreased to 15 ± 14% (p < 0.01). Likewise, vasoconstriction rather than vasodilation to acetylcholine was observed in the left main coronary artery. In only four weeks of dietary manipulation, the combination of high dietary cholesterol plus methionine leads to marked endothelial dysfunction in the abdominal aorta and vasoconstriction to acetylcholine in the LMCA. These studies highlight the importance of combining dietary risk factors in the pathogenesis of atherosclerosis. Cardiac Imaging 54 What is the Relationship Between Capillary Blood Volume, Red Cell Velocity and Transmural Extent of Scar in Patients with Hibernating Myocardium: A Quantitative MCE and MRI Study S. Moir* , J. Chan, C. Jenkins, D. Rakhit, B. Haluska, T.H. Marwick, FCSANZ University of Queensland, Cardiac Imaging Group, Princess Alexandra Hospital, Brisbane, Australia

Figure. 1

Background: There is limited available data regarding the relationship between quantitative myocardial contrast echocardiography (MCE) and transmural extent of scar by MRI (TMES) in patients with chronic CAD and hibernating myocardium.

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

S24

Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

Methods: Nineteen patients with a remote history of myocardial infarction and no mechanical revascularization underwent resting MCE and cardiac MRI scanning. MCE was performed in three apical views using Optison. Wall motion was scored from opacified images. Corrected capillary blood volume (A), red cell velocity (␤) and their product, myocardial blood flow were calculated in all segments. MRI was performed, with scar thickness measured as Nil, <25%, 26–50%, 51–75%, 76–100%. Segments with scar thickness >50% were considered non viable. Results: Two hundred and ninety-two myocardial segments were analysed, 131 with abnormal resting function (ARF). Segments with ARF had significantly impaired A, ␤ and A*␤ cw those with normal function. There was a significant correlation between myocardial blood flow and TMES (r = 0.187, p = 0.01), mostly reflecting the relationship between A and TMES (r = 0.31, p < 0.001), with no correlation for ␤ (related with wall motion only). Among the segments with ARF, 52 were considered non viable and 79 were viable based on MRI. There was no significant difference in ␤ or A*␤ between the viable and non viable segments, however the A was significantly lower in nonviable segments, reflecting fibrosis. Conclusion: Quantitative MCE derived capillary blood volume represents the extent of myocardial fibrosis, is related to the TMES in patients with chronic CAD, and can discriminate viable from non-viable hibernating myocardial segments. Normal Fn 161 Normalised A

0.78 ± 0.25

Abnormal Fn

p

131 0.59 ± 0.32

<0.001

0.66 ± 0.30

Contrast (n = 4645)

No Contrast (n = 17096)

p

Age

66 ± 12

63 ± 14

Female

1929 (41%)

7983 (47%)

<0.001

BMI

32 ± 7

28 ± 6

<0.001

PHx MI

751 (16%)

1902 (11%)

<0.001

DM

1284 (28%)

2777 (16%)

<0.001

HT

3179 (68%)

9726 (57%)

<0.001

Hyperlipidaemia

3220 (69%)

10641 (62%)

<0.001

Dobutamine stress

2837 (61%)

6351 (37%)

<0.001

MRI scar >50%, n = 52

Wall motion score index—rest

1.13 ± 030

1.10 ± 0.28

<0.001

Rest EF

58 ± 8

59 ± 9

<0.001

0.51 ± 0.33

Stress EF

69 ± 11

69 ± 12

Positive study

1697 (37%)

5350 (31%)

<0.001

Angiography

347 (7%)

1113 (5%)

0.10

True positive

227 (75%)

738 (73%)

0.76

False positive

77 (25%)

279 (27%)

0.28

True negative

20 (46%)

39 (46%)

0.06

Abnormal Fn MRI scar <50%, n = 79

Results: Four thousand six hundred and forty-five patients (21%) received contrast with no serious side effects (death, MI, stroke). Contrast was deemed detrimental to study quality in <2% cases, beneficial in 90%. Patients requiring contrast tended to be male, older and with higher BMI, more risk factors and/or previous history of MI, and more likely to be undergoing DSE. Contrast studies were more likely to be positive (37% versus 31%, p < 0.001). Of the 1460 patients referred for angiography, there was no difference in parameters of test accuracy (see Table) between the contrast and non-contrast groups. Conclusions: Contrast for LVO during SE is safe, and may be required in approximately 20% of patients presenting for SE. Whilst contrast studies are more likely to be positive for CAD, this likely reflects higher pre-test probability in patients requiring it, with accuracy compared to angiography not significantly different compared to non contrast patients.

p

0.04

␤

0.84 ± 0.78

0.51 ± 0.48

0.01

0.46 ± 0.45

0.60 ± 0.52

NS

A*␤

0.66 ± .86

0.29 ± 0.32

0.008

0.30 ± 0.34

0.29 ± 0.28

NS

55 Contrast Stress Echo in the Era of Harmonic Imaging: Rate of Usage, Safety and Impact on Test Interpretation at a High Volume Stress Laboratory S. Moir* , S. Abdelmoneim, R. Mcully, P. Pellikka, S.L. Mulvagh

<0.001

0.84

56 Changes in Left Atrial Volumes with Mild Hypertension S. Eshoo* , D.L. Ross, FCSANZ, L. Thomas

Mayo Clinic Echo Laboratory, Rochester, MN, USA

Westmead Hospital, University of Sydney, Australia

Background: In North America contrast administration for left ventricular opacification (LVO) during stress echocardiography (SE) is increasingly utilized. We examined the rate of usage, safety, and impact on test interpretation of contrast at a high volume SE laboratory. Methods: We examined 21,741 SE studies from patients (64 ± 14 years; 54% male) referred for SE from 1/1/03 to 1/11/05, including 9188 (42%) dobutamine studies (DSE). Contrast was administered if ≥2 segments were not visualized during harmonic imaging. Effect of contrast on study quality was recorded by reviewer as beneficial, unchanged or detrimental. Results from angiograms performed within 30 days (stenosis >50% = significant) were obtained.

Background: Left atrial (LA) enlargement has been documented to occur in hypertension. We sought to evaluate the changes in total LA volume and LA volumes in the various phases of atrial filling in a cohort with mild hypertension (HT). Methods: Hundred patients with mild HT (mean SBP = 147 mmHg, mean DBP = 84 mmHg, MAP = 105 mmHg) were prospectively recruited and compared to 92 normal volunteers. All recruits had a transthoracic echo. Attention was paid to maximizing LA size. Exclusions were left ventricular dysfunction, valvular disease, implantable devices and arrhythmias. Maximum (LAESV), minimum (LAEDV) and pre ‘P’ LA volume (prior to active atrial contraction) were calculated using Simpson’s biplane method of discs. The passive filling, active filling and conduit volumes were also measured.

Abstracts

Results: Results were adjusted for age, gender and BMI (see Table). Normal (Mean ± S.E.)

HT (Mean ± S.E.)

p-value

LA diameter (M-mode) (mm)

37.7 ± 0.5

39.9 ± 0.5

0.005

LAESV (mL)

43.8 ± 1.7

53.3 ± 1.6

0.000

LAEDV (mL)

20.8 ± 0.9

22.0 ± 0.9

0.377

Pre P LAV (mL)

31.0 ± 1.4

37.0 ± 1.3

0.003

Passive emptying volume (mL)

12.8 ± 0.7

16.5 ± 0.7

0.001

Conduit volume (mL)

33.5 ± 1.4

30.0 ± 1.3

0.087

Active emptying volume (mL)

10.5 ± 0.7

15.0 ± 0.6

0.000

Active emptying fraction (%)

32.6 ± 1.1

40.2 ± 1.1

0.000

On subgroup analysis, comparing hypertensives without and with LVH, LAESV (p < 0.02), LAEDV (p < 0.0002), LAEDVI (p < 0.006) and Pre P LAV (p < 0.007) were significantly increased. There were no significant differences in passive, active and conduit volumes. Conclusion: Hypertension results in increased LV stiffness with a corresponding decrease in LV compliance and reduced LV diastolic filling. This results in an increase in LA size (as demonstrated by both LAD and LAESV) and LV filling is augmented by an increase in both active and passive LA transport. 57 Changes in Left Atrial Function with Mild Hypertension S. Eshoo* , D.L. Ross, FCSANZ, L. Thomas Westmead Hospital, University of Sydney, Australia Background: Left atrial (LA) enlargement is documented in moderate to severe hypertension. We sought to evaluate LA function in a group with mild hypertension compared to that in a cohort of healthy controls. Methods: Hundred patients with mild HT (mean SBP = 147 mmHg, mean DBP = 84 mmHg, MAP = 105 mmHg) were prospectively recruited and compared to 92 normal volunteers. All recruits underwent a TTE with attention paid to maximizing the LA size on echo. Those with LV dysfunction, significant valvular disease, implantable devices and arrhythmias were excluded. Traditional measures of atrial function including the trans mitral peak A-wave velocity. A wave velocity time integral (VTI) and atrial emptying fraction were measured. Newer parameters of atrial function namely the A velocity obtained from pulsed wave Doppler tissue and the left atrial composite index (LACI) were also estimated. The LACI = LAEF X LVOT VTI/LAESVI. Results: LAESV and LAEDV were increased in the hypertensive group. The A VTI, atrial fraction and LACI were increased in the hypertensive group (see Table). Normal (Mean ± S.E.)

HT (Mean ± S.E.)

p-Value

Peak A (m/s)

0.7 ± 0.0

0.7 ± 0.0

0.839

A VTI (cm)

9.9 ± 0.3

8.3 ± 0.3

0.001

42.7 ± 0.9

37.6 ± 0.9

0.000

9.4 ± 0.2

9.4 ± 0.2

0.880

102.6 ± 3.7

89.6 ± 3.4

0.014

Atrial fraction (%) A (cm/s) LACI

S25

Subgroup analysis comparing those with and without LVH demonstrated no significant differences between groups. Conclusion: In patients with mild HT, LA size is increased with a concomitant reduction in LA function. There is a decrease in LV compliance with HT resulting in an increase in LA size. LA dilatation however, is associated with reduced LA function which in turn is likely to provide the substrate for the subsequent development of atrial arrhythmias. 58 Is Cardiac Torsion and Untwisting by Speckle Tracking Echocardiography More Sensitive than TDI in Detection of Subclinical LV Dysfunction in Apparently Healthy Obese Subjects? Chiew Y. Wong* , Rodel Leano, Thomas H. Marwick, FCSANZ University of Queensland, Brisbane, Australia Background: LV torsion and rotational velocities by speckle tracking echocardiography (STE) has been proposed as a sensitive marker of LV function. We sought to evaluate the LV rotational motion and untwisting in obese subjects comparing to TDI. Methods: After exclusion of overt myocardial dysfunction or ischemia, 44 asymptomatic obese subjects underwent conventional and novel echocardiographic assessment. Apical and basal rotation and rotational velocities by STE were measured from short axis images by automatic frame-to-frame tracking of grey-scale speckle patterns. LV torsion was calculated as the difference between clockwise rotation at base and counter-clockwise rotation of apex. Comparisons made with 43 non-obese controls. Associations sought between myocardial measures with STE and longitudinal tissue velocity (TDI) as well as clinical characteristics. Subclinical myocardial dysfunction was defined by presence of myocardial systolic (sm) tissue velocities more than 1 S.D. below the mean age adjusted values of normal-weight healthy controls. Results: Obese subjects demonstrated reduced systolic LV torsion and basal rotation (Table), but preserved systolic apical velocities. The untwisting rotational velocities in diastole were similarly reduced. Myocardial tissue velocity sm correlated significantly with LV basal rotation (r = 0.27, p < 0.05) and overall torsion (r = 0.36, p < 0.01). LV torsion also correlated with waist circumference (r = −0.24, p < 0.05). Basal rotation and apical torsion were significantly abnormal compared to controls even in pts without LV dysfunction by TDI. Conclusion: Obese pts had reduced LV torsion, regional rotation at the base and diastolic rotational velocities. Compared to TDI, STE may be a more sensitive measure of subclinical myocardial disease in metabolic disease.

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

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Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

Obese (n = 44, 33f, 11m)

Controls (n = 43, 24f, 19m)

Conventional

p

Hand-Carried

r-Value, p-Value

Age (years)

44 ± 10

51 ± 8

<0.05

LVEDD (cm)

5 ± 0.6

4.9 ± 0.7

BMI (kg/m2 )

39 ± 8

27 ± 4

ns

LV mass (g)

220 ± 88

223 ± 82

0.86, <0.0001

BP (mmHg)

125/77 ± 13/8

126/79 ± 17/10

ns

E (cm−1 )

68 ± 15

67 ± 16

0.85, <0.0001

LVM index (g/m2 )

82 ± 17

79 ± 18

ns

E:A ratio

0.93 ± 0.26

0.92 ± 0.22

0.92, <0.0001

Ea (cm−1 )

7.1 ± 1.7

9.1 ± 1.8*

0.73, <0.0001

E:Ea ratio

9.9 ± 2.7

7.5 ± 2.0+

0.79, <0.0001

MFP (0/1/2)

7/24/7

7/22/9

–

LVD by TDI (◦ )

Non LVD

3.3 ± 3.2

4.7 ± 2.8

6.7 ± 2.8

0.001

7.2 ± 2.0

6.0 ± 3.4

7.7 ± 6.0

ns

10.0 ± 4.0

10.2 ± 4.2

14.4 ± 6.8

0.01

Apical diastolic rotational velocity (◦ s−1 )

46 ± 23

54 ± 22

65 ± 26

<0.05

Apical systolic rotational velocity (◦ s−1 )

54 ± 10

60 ± 2

65 ± 28

ns

Basal rotation

Apical rotation (◦ ) LV torsion (◦ )

0.61, <0.0001

E, E velocity; Ea, annular E velocity; MFP, Mitral filling pattern; HCE versus conventional * p = 0.04, + p = 0.04.

59 Comparison of Hand-Carried Versus Conventional Echocardiography in the Risk Assessment of Patients with Diabetes R. Gabriel1,* , G.A. Whalley2 , D. Korczyk2 , J. Somaratne2 , H. Walsh2 , A. Pearl3 , R.N. Doughty1,2 , FCSANZ 1 Greenlane

Cardiovascular Services, Auckland City Hospital, New Zealand; 2 Department of Medicine, University of Auckland, New Zealand; 3 Department of General Practice, University of Auckland, New Zealand Background: The use of hand-carried echocardiography (HCE) is rapidly expanding and has been used to screen for cardiac abnormalities. At present some small machines do not have Tissue Doppler Imaging (TDI) capability and this may limit assessment of diastolic function. It has been suggested it may be possible to imitate TDI by performing Low Filter Pulsed Wave Doppler (LF-PWD). This is achieved by setting both the velocity range and wall filter as low as possible in order to eliminate high velocity flow and focus on low velocity annular motion. In this study we tested the validity of this approach in screening for left ventricular hypertrophy and diastolic dysfunction in a diabetic population. Methods: Thirty-seven diabetic patients with or without hypertension, and no prior history of cardiovascular disease underwent HCE using a Sonosite MicroMaxx or a Sonosite Titan machine and conventional echocardiography using a Philips HDi5000 machine. Standard m-mode, pulsed wave and tissue Doppler techniques were applied. Results: Agreement between conventional and HCE was seen for spectral Doppler and LV measurements. Good correlation was seen between LF-PWD and conventional TDI measurement of the medial Ea and E:Ea ratio. However, HCE resulted in lower E:Ea ratio due to higher medial Ea measurements. Despite this, little difference was seen in the assessment of the diastolic mitral filling pattern.

Figure. Conclusion: HCE can be effectively applied for screening of LV hypertrophy and for the assessment of diastolic function in a diabetic population. However, using LF-PWD, HCE may result in underestimation of the E:Ea ratio and thus detection of raised filling pressure. 60 Does Velocity Vector Imaging Demonstrate Abnormalities in Longitudinal and Circumferential Myocardial Function in Patients with Hypertrophic Cardiomyopathy and Normal Ejection Fraction? Stuart Moir* , Steve Ommen, Jae Oh, Fletcher Miller, Sharon Mulvagh Mayo Clinic Echocardiography Laboratory, Rochester, MN, USA Background: Patients with hypertrophic cardiomyopathy commonly have preserved systolic ejection fraction despite significant longitudinal myocardial fiber dysfunction. This is believed to be due to compensatory normal or supra-normal radial and circumferential function. Velocity vector imaging (VVI) is a new modality for quantification of myocardial function, and enables assessment of longitudinal and circumferential strain and strain rates. Methods: We compared 20 patients with known hypertrophic cardiomyopathy and preserved ejection fraction (with no history of pacing or septal reduction therapy) and 20 controls (patients with no coronary risk factors and no evidence of myocardial ischemia by stress echocardiography). All patients were studied using a commercially available machine (Acuson Sequoia, Siemens) and underwent

Abstracts

off line VVI analysis, utilizing the apical four chamber view for calculation of longitudinal strain and strain rates, and the mid ventricular para-sternal short axis view for calculation of circumferential stain and strain rates. Results: There was no difference in age, gender or resting ejection fraction between the two groups—see Table. Compared with controls, patients with HCM had significantly reduced mean longitudinal strain (−15.2 ± 3.7% versus −20.2 ± 3.2%, p < 0.001) and stain rate (0.87 ± 0.27 s−1 versus 1.09 ± 0.26 s−1 , p = 0.02). Conversely, patients with hypertrophic cardiomyopathy had significantly increased circumferential strain, with no difference in circumferential strain rate compared with controls—see Table. Conclusion: In patients with HCM, velocity vector imaging analysis demonstrates significant abnormalities in longitudinal myocardial function, with concomitantly supranormal circumferential myocardial function, which contributes significantly to their normal ejection fraction. HCM (n = 20)

Control (n = 20)

p

Age (years)

48 ± 14

45 ± 14

Males

11

13

0.66

Resting EF (%)

60.8 ± 8.9

61.6 ± 3.4

0.65

−15.2 ± 3.7

−20.2 ± 3.2

Longitudinal strain (%) Longitudinal strain rate (s−1 ) Circumferential strain (%) Circumferential strain rate (s−1 )

−0.87 ± 0.28 −31.8 ± 8.7 −1.73 ± 0.64

−1.09 ± 0.26 −26.4 ± 4.3 −1.63 ± 0.24

0.58

<0.001 0.01 0.02 0.56

61 Left Ventricular Volume and Viability but not Transmural Extent of Scar Determine LV Remodeling and Exercise Capacity Responses to Revascularization and Medical Therapy in Patients with LV Dysfunction Jonathan Chan* , Rodel Leano, Lizelle Hanekom, Charles Nelson, Tom Marwick, FCSANZ Department of Cardiology, Princess Alexandra Hospital, University of Queensland, Brisbane, Qld, Australia Myocardial revascularization (RVS) is known to improve LV remodeling and exercise capacity in selected pts. We sought the relative impact of baseline LV volume, viable myocardium (VM) and transmural extent of scar (TME) on these phenomena. Methods: We recruited 84 pts with LV dysfunction after myocardial infarction. At baseline, VM was identified as contractile reserve with dobutamine echo and TME was measured by the proportion of the LV wall showing late uptake on gadolinium MRI, also expressed as as TME score (sum of segmental scores ranging from 0 [0%] to 4 [100%]). Baseline measurements of MRI volume and VO2 were compared with 12 month follow-up. Results: In 33 pts (63 ± 10 years, 27 with VM) undergoing RVS, baseline EDV was 180 ± 39 and decreased by 5 ± 18%; reverse remodeling was predicted by VM segts and baseline EDV (Table). In RVS, baseline VO2 was 13 ± 4 ml/kg/min, and increased by 2 ± 27%; change in functional capacity was associated with extensive (>25%)

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viable segts. Medical therapy was continued in 51 pts (63 ± 10 years, 43 with VM), in whom baseline EDV was 191 ± 70 ml. Remodeling was predicted by VM segts and baseline EDV (Table). In the medical group, baseline VO2 was 15 ± 5 ml/kg/min, and deteriorated by 12 ± 21%. TME was not predictive of remodeling. Conclusions: Although RVS and medical therapy have opposite effects on volume change, increasing EDV is associated with less viability and greater baseline EDV but not dependent on scar extent. Changes in exercise capacity are dependent on revascularization of extensive VM. 62 Automated Analysis of Regional LV Function: Definition of a Normal Range with 2D Strain Rodel Leano1,* , Jing-Ping Sun2 , Michael Becker3 , Rainer Hoffmann3 , James D. Thomas2 , Thomas Marwick1 , FCSANZ 1 University

of Queensland, Brisbane, Australia; 2 Cleveland Clinic Foundation, Cleveland, OH, USA; 3 RWTH Aachen, Aachen, Germany The recent development of 2D strain has improved the feasibility of automated measurement of regional function and could facilitate its assessment by less expert readers. We sought to define normal ranges of regional 2D strain (2DS) and strain-rate (SR) in an international, multicenter study of healthy subjects, and to assess the determinants of variation. Methods: SR and 2DS were measured in 18 myocardial segts in both apical and short axis views of 175 normal subjects (38% men, 49 ± 13 years) with no cardiac history, risk factors or drug therapy. The association of age, resting hemodynamics and tracking quality (TQ) with regional strain indices was sought using multiple regression. Results: TQ showed significant variation, with the worst values in the posterolateral segments, especially in the base. Average strain and SR were relatively homogeneous, with lower values in the basal septum and anteroseptum. Hemodynamic and demographic features were significantly associated with strain but only accounted for 4% of the variance. The same features and TQ were predictors of SR but only accounted for 10% of the variance. Conclusions: Mean regional resting 2DS and SR show limited variation around the heart in normal subjects. However, significant between-subject variation is attributable to only a minor degree by TQ, hemodynamic and demographic variables. Level

Wall

Peak Strain

Peak SR

1.38 ± 0.63

−18.6 ± 6.02

−1.18 ± 0.41

Anterior

1.86 ± 0.79*

−18.97 ± 5.13

−1.20 ± 0.43

Anteroseptum

1.38 ± 0.62

−15.69 ± 6.94*

−1.03 ± 0.31*

Inferior

1.56 ± 0.69*

−19.81 ± 4.88

−1.31 ± 0.42

Lateral

1.85 ± 0.78*

−19.12 ± 5.55

−1.41 ± 0.40*

−18.16 ± 7.5

−1.52 ± 0.58*

−16.64 ± 4.67*

−1.01 ± 0.39*

Global Base

TQ

0.79*

Posterior

1.85 ±

Septum

1.33 ± 0.59

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

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Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

63 Two Dimensional Strain Rate Imaging and Magnetic Resonance Imaging can be Used to Differentiate Subendocardial Infarction by Assessing Left Ventricular Mechanics Jonathan Chan1,* , Chiew Wong1 , Leanne Du1 , Rodel Leano1 , Mark Strudwick2 , Thomas H. Marwick1 , FCSANZ 1 Department

of Cardiology, Princess Alexandra Hospital, University of Queensland, Brisbane, Australia; 2 Centre of Magnetic Resonance Imaging, University of Queensland, Brisbane, Qld., Australia Recent studies have shown that myocardium is composed of a complex orientation of several layers of myocardial fibres with differential contribution to cardiac axis of motion. Differentiation of subendocardial infarction has important clinical and prognostic implications. We aim to use 2D strain rate imaging to identify subendocardial infarction by investigating how left ventricular mechanics are affected by transmural extent of infarction (TME). Methods: Eighty (n = 80) patients post myocardial infarct underwent tissue doppler imaging (TDI) and gadolinium contrast enhanced cardiac magnetic resonance imaging (Ce-MRI). TME was measured by the degree of delayed gadolinium enhancement on Ce-MRI. Long axis function was assessed by measuring peak longitudinal strain (LongS) and strain rate (LongSR) on TDI. Regional shortaxis contractile function was assessed by measuring peak circumferential strain (cirS), circumferential strain rate (cirSR), and percentage radial systolic thickening of the myocardium (%ST) on MRI. Results: Increasing TME is associated with deterioration of long axis function in both subendocardial and transmural infarcts, but short axis function is preserved in subendocardial infarcts compared to transmural infarcts. This suggests that fibres that contribute to short axis function reside predominantly in the outer layers as opposed to long axis fibres which reside in the inner layers of myocardium. Conclusions: We conclude that 2D strain imaging can identify TME and subendocardial infarcts and help elucidate the anatomical orientation of myocardial fibres. Table. Comparison of Short and Long Axis in Different TME TME Subendocardial infarct (n = 212) Transmural infarct (n = 213) P value

%ST

cirSR

cirS

LongSR

LongS

31 ± 33

−1.4 ± 0.8

−15.4 ± 6.9

−0.9 ± 0.5

−13.2 ± 5.6

23 ± 28

−1.0 ± 0.4

−10.7 ± 6.3

−0.8 ± 0.4

−11.8 ± 5.5

NS

NS

0.02

0.02

<0.0001

64 High Resolution Transthoracic Echocardiography Assessment of the Left Anterior Descending Coronary Artery: A Novel and Non-Invasive Approach to Study Coronary Vasomotion in Humans Rebecca Perry1,* , Derek Yiu2 , Majo X. Joseph1 , FCSANZ, Carmine G. De Pasquale1 , FCSANZ, Derek P. Chew1 , FCSANZ, Philip E. Aylward1 , FCSANZ, Arduino A. Mangoni2 1 Cardiac

Services, Flinders Medical Centre, South Australia, Australia; 2 Clinical Pharmacology, Flinders Medical Centre, SA, Australia Invasive studies of the coronary arteries have previously demonstrated vasodilatation by salbutamol (endothelialdependent vasodilator) and glyceryl trinitrate (GTN, endothelial-independent vasodilator). Using a novel technique of high resolution transthoracic echocardiography (HRTTE), combined with assessment of peripheral augmentation index (AIx) by means of applanation tonometry from the radial artery (Pulse Wave Analysis), we sought to study the vasomotion of the proximal left anterior descending coronary artery (LAD) in healthy volunteers. Eleven male subjects (age 31 ± 6 years) underwent HRTTE measurement of the wall thickness, luminal diameter and external diameter of the proximal LAD, and AIx at baseline and 5, 10 and 15 min after administration of inhaled salbutamol (400 ␮g) and, following return to baseline, sublingual GTN (300 ␮g). This protocol has been previously validated for the non-invasive assessment of peripheral endothelial function in humans. Salbutamol induced a significant increase in LAD luminal diameter (0.32 ± 0.08 cm to 0.42 ± 0.08 cm, p < 0.001) and a significant reduction in AIx (−13 ± 6%). GTN induced more significant changes in both parameters (i.e. mean 43% increase in luminal diameter from baseline, 0.32 ± 0.08 cm to 0.51 ± 0.11 cm, p < 0.001; and reduction in AIx −23 ± 9%). Changes in LAD diameter and AIx were significantly correlated after both salbutamol (r = −0.51, p = 0.044) and GTN (r = −0.68, p = 0.01). No significant change was detected in wall thickness. This is the first non-invasive study directly showing the combined effects of recognised vasodilators on both coronary and peripheral circulation. The HRTTE technique is sufficiently sensitive to detect coronary artery vasomotion and warrants further investigation as a new window to coronary artery structure and function. 65 Utility of Myocardial Fibrosis and Fatty Infiltration Detected by Cardiac Magnetic Resonance Imaging in the Diagnosis of Arrythmogenic Right Ventricular Dysplasia Andrew J. Taylor1,* , Justin Phrommintikul1 , Ken Thomson2

Mariani1 ,

Arintaya

1 Alfred Hospital Heart Centre and Baker Heart Research Institute, Melbourne, Australia; 2 Department of Radiology, Alfred Hospital, Melbourne, Australia

Background: The diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) remains a challenge. We evalu-

Abstracts

ated the utility of changes detected with cardiac magnetic resonance imaging (CMR) in suspected ARVD. Methods: We performed CMR on 26 subjects with suspected ARVD on the basis of right ventricular (RV) morphology on echo and/or ventricular arrhythmias. CMR evaluated ventricular morphology and wall motion, with delayed hyperenhancement sequences to detect regional myocardial fibrosis and T1 -weighted imaging with and without fat saturation to detect fatty infiltration. The diagnosis of ARVD was according to European Society of Cardiology (ESC) guidelines. Results: Four of 26 subjects fit current ESC guidelines for the diagnosis of ARVD. Of these, all four (100%) had RV fibrosis whilst only one (25%) had fatty infiltration of the RV. Of the remaining 22 subjects without ARVD, only 1 (5%) had RV fibrosis, and none had fatty infiltration. There was a significant difference in the incidence of RV fibrosis between those with and without ARVD (P < 0.001, Fisher’s Exact Test). The most common CMR finding in subjects without ARVD was biventricular dilatation with normal systolic function (15 subjects [68%]), isolated RV dilatation (five subjects [23%]), and normal study (two subjects [9%]). Conclusion: CMR is useful in the diagnosis of ARVD with RV fibrosis a good indicator of ARVD diagnosed according to current clinical guidelines. The presence of fatty infiltration with CMR is an uncommon finding and of limited clinical utility. 66 MRI Assessment of Ostium Secundum Type ASD Prior to Percutaneous Closure W. Strugnell, L. Medoro* , R. Slaughter The Prince Charles Hospital and Queensland X-Ray, Qld, Australia Introduction: Diagnosis and evaluation of ASD has routinely been made by TTE and TOE, however occasionally the defect can be difficult to assess. We performed MRI on patients with ostium secundum type ASD and compared the findings with those obtained at percutaneous catheter closure. Method: Eleven patients with ostium secundum type ASD were referred for MRI assessment prior to percutaneous closure. Imaging series consisted of: Breath-hold ECG gated multiplanar multislice FIESTA sequences to assess atrial septal anatomy, exclude other cardiovascular anomalies such as anomalous pulmonaryvenous connections and to calculate RV function. Flow imaging parallel to the interatrial septum to demonstrate flow through the ASD; FIESTA and flow imaging

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through the ASD and adjacent vascular structures to obtain measurements around the margins of the ASD. Aortic and pulmonary artery flow measurements to assess intracardiac shunts. Results: MRI and catheter findings correlated well in all cases. ASD measurements by MRI were 13–33 mm (mean 21.7 mm) compared with catheter dimensions of 13–32 mm (mean 21.5 mm). MRI measurements of distances between the ASD and adjacent vascular structures confirmed a sufficient atrial septal rim to enable successful device placement in all cases. MRI measurements of pulmonary artery and aortic flow volumes ranged from 1.2:1 to 3.1:1 (mean 1.9:1) compared with catheter measurements of 1.7:1–2.7:1 (mean 2.3:1). Conclusion: MRI has the potential to provide a comprehensive assessment of patients with ostium secundum ASD’s prior to percutaneous device closure by evaluating the size and location of the ASD, calculating intracardiac shunts and measuring RV volume and function. 67 Reproducibility of Right Ventricular Volumes and Ejection Fraction using real-time 3D Echo; Comparison with Cardiac MRI C. Jenkins* , K. Bricknell, J. Chan, T.H. Marwick, FCSANZ University of Queensland, Brisbane, Australia Objectives: We sought whether real-time 3D echo (RT3D) would be superior to 2D echo (2DE) for follow-up of RV function by validation versus cardiac MRI. Methods: Patients (n = 50, age 62 ± 11) for evaluation of cardiac function were studied with 2DE and RT3D. 2DE methods included area-length (A-L), modified subtraction method (2DS) and Simpson’s method of discs. RT3D images were measured off-line. MRI images were obtained using true FISP during breath-hold and were measured using CIM software. Test-retest variation was performed by a complete re-study and inter- and intraobserver variation was performed (n = 20). Results: RT3D had less test-retest variation than any 2DE measures (Table). All echo techniques underestimated RV volumes (except for 2DS). RT3D had higher correlation with each parameter than the 2DE techniques (Table). There was also better intra- and inter-observer with RT3D. Conclusions: RT3D more accurate than 2D approaches and reduces test-retest variation of RV volumes and EF measurements in follow-up RV assessment in daily practice.

Abstract 67 Table Test-Retest (Difference From Mean)

Measurements

A-L

2DS

Simpson’s

RT3D

MRI

EDV (ml)

1±6

1 ± 22

1±6

0±5

87 ± 22

29 ± 11, r = 0.36*

139 ± 50, r = 0.40*

30 ± 12, r = 0.34*

81 ± 23, r = 0.60*

ESV (ml)

0±3

-1 ± 13

0±3

0±3

46 ± 17

15 ± 7, r = 0.42*

75 ± 31, r = 0.54*

15 ± 6, r = 0.48*

39 ± 13, r = 0.55*

EF (%)

0 ± 12

0 ± 10

0±9

0±4

49 ± 12

46 ± 17, r = 0.08

44 ± 18, r = 0.13

47 ± 14, r = −0.06

52 ± 10, r = 0.72*

∗

p < 0.05.

A-L

2DS

Simpson’s

RT3D

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

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Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

68 3D Echo Provides a Common Language for LV Volume Measurement: An International Multicenter Study Carly Jenkins* , Tsui-Lieh Hsu, Jun Kwan, Satoshi Nakatani, Hao Wang, Thomas H. Marwick, FCSANZ Princess Alexandra Hospital University of Queensland, Princess Alexandra Hospital, Brisbane, Australia Background: Standard 2D echo (2DE) has limited reproducibility for LV quantitation; recent single center studies have documented the reliability of real-time 3D (RT3D). In a multi-center trial we sought to (a) validate RT3D against magnetic resonance imaging (MRI), (b) compare with 2DE, and (c) examine the variability of LV measurements. Methods: Patients from five international sites (n = 44) were studied with RT3D (Philips 7500). RT3D volumes and ejection fraction were measured in all studies at all sites (Tomtec). A subgroup (n = 20), cardiac MRI images which were obtained using true FISP during breath-hold, and 3D volumes and EF were measured off-line. Results: MRI (EDV 155 ± 62 ml, ESV 84 ± 42 ml and EF 51 ± 6%) correlated better with RT3D (EDV, r = 0.89* ; ESV, r = 97* ; EF, r = 0.91* ) than 2DE (EDV, r = 0.69* ; ESV, r = 0.86* ; EF, r = 0.91* ). The mean differences between MRI and 3D (EDV, −17 ± 39 ml; ESV, −37 ± 54 ml; EF, −3 ± 5%) were less than between MRI and 2DE (−53 ± 52 ml, ESV, −31 ± 41 ml; EF, −4 ± 5%). There was high correlation between centers for all LV parameters (Table). Conclusions: The validation of RT3D measurement of volumes and EF has been confirmed in this multicenter study. Semi-automated measurement of RT3D is a feasible approach to reduce variation of LV volume and EF measurements between centers. n = 44

Mean ± S.D.

Correlation Ranges Between Sites

Different From Mean ± S.D.

EDV (ml)

136 ± 32

r = 0.79* –0.96*

−3 ± 12

ESV (ml)

73 ± 27

r = 0.83* –0.97*

−1 ± 5

EF (%)

50 ± 7

r = 0.54* –0.98*

−1 ± 3

∗

P < 0.01.

69 Effect of Heart Rate on Echocardiographic Measures of Diastolic Function A.T. Burns* , K.A. Connelly, A. La Gerche, D.J. Mooney, A.I. MacIsaac, FCSANZ, D.L. Prior, FCSANZ Cardiac Investigation Unit, St Vincent’s Hospital, Melbourne, Australia Abnormal diastolic function is recognized as an important cause of heart failure symptoms. Assessment of LV diastolic parameters is a routine part of echocardiographic examination. The independent effect of heart rate (HR) on parameters of diastolic function, particularly mitral annular velocities measured by tissue Doppler imaging (TDI), is unclear. Methods: We studied 16 patients (mean age 68.1) with dual chamber pacemakers and a mean LVEF of 48.4%. Atrial pacing was performed at low (average 67 bpm) and high (80 bpm) HR. Echo parameters of systolic and diastolic

function were recorded at each HR and analysed offline. Values at low and high HR were compared by a paired t test. Results: Parameters of systolic function (LVEF & annular S velocity) were unaffected by increased HR. Mitral inflow (E wave, A wave, IVRT) and tissue Doppler (MV E , MV A ) measures were altered by changes in HR. Mitral inflow propagation velocity (Vp) and the E/E ratio were unaffected by increased HR. Low HR

High HR

LVEF (%)

48 ± 10

49 ± 10

NS

MV E wave (cm/s)

71 ± 20

64 ± 18

<0.02

MV A wave (cm/s)

70 ± 16

77 ± 16

<0.05

MV DT (ms)

229 ± 69

219 ± 58

NS

IVRT (ms)

101 ± 23

132 ± 56

<0.05

P

Vp (cm/s)

50 ± 20

46 ± 14

NS

MV E (cm/s)

7.0 ± 2.1

6.3 ± 2.2

<0.005

MV S (cm/s)

6.7 ± 1.7

6.8 ± 1.6

NS

 ratio E/Elat

8.5 ± 3.3

9.2 ± 3.5

NS

Conclusions: Despite no change in systolic function, increased HR results in significant acute changes in conventional and tissue Doppler parameters of LV diastolic function. As patient heart rates can vary between examinations, our findings suggest that variations in HR should be considered when interpreting echo measures of LV diastolic function and classifying diastolic function as normal or abnormal. 70 Assessment of Early Diastolic Left Ventricular Function by 2D Echocardiographic Speckle Tracking Rebecca Perry* , Carmine G. De Pasquale, FCSANZ, Derek P. Chew, FCSANZ, Majo X. Joseph, FCSANZ Cardiac Services, Flinders Medical Centre, Bedford Park, SA, Australia Early diastolic filling is directly related to the active process of left ventricular relaxation leading to a ‘suction’ effect causing blood to flow from the left atrium into the left ventricle across a pressure gradient. This ‘suction’ effect is thought to be caused by rapid untwisting of the left ventricular apex in early diastole. Left ventricular apical systolic rotation has been previously assessed using magnetic resonance imaging and more recently 2D echocardiographic speckle tracking, however the relevance of diastolic rotation has not been elucidated. Data from seventy one hospital inpatients (mean age 64 ± 14 years) who underwent standard 2D echocardiography was analysed using an off-line speckle tracking software package (Echo Pac, GE Healthcare Australia). Early diastolic mitral inflow velocity (e), mitral septal annular tissue Doppler velocity (e ) and the rate of early diastolic apical untwist in degrees per second (rotR) from a parasternal short axis view of the apex were all measured. RotR was defined as the first negative

deflection on the 2D speckle tracking rotation rate graph immediately after mitral valve opening (MVO).

Abstracts

to other non-RFP (AR/N) (OR 5.92, 95% CI: 3.56, 9.85) (see Table). Conclusions: This LMA brings together results from five prospective studies and demonstrates the prognostic deficit associated with each advancing grade of diastolic filling abnormality, highlighting the poor prognosis associated with pseudonormal filling and further supporting the clinical utility of these measures. Deaths/Number at Risk

Figure. Of the 71 patients, 14 had normal diastolic function, 25 had an abnormal relaxation pattern, 27 had a pseudonormalised pattern and 5 had a restrictive pattern as defined by standard echocardiography criteria. Both e and the ratio of e:e correlated with the rate (speed) of early diastolic apical untwist (rotR) (r = 0.7, p < 0.001 and r = 0.5, p < 0.001, respectively). This non-invasive assessment of apical diastolic untwist is related to established echocardiographic measures of diastolic function and warrants further investigation as a clinically useful measure of diastolic function. 71 Pseudonormal Mitral Filling is Associated with Similarly Poor Prognosis as Restrictive Filling in Patients with Heart Failure and Post AMI: A Literature-Based Meta-Analysis Gillian Whalley* , Jithendra Somaratne, Greg Gamble, Helen Walsh, Robert Doughty, FCSANZ The University of Auckland, Auckland, New Zealand Background: Diastolic mitral filling pattern (MFP) has been linked to prognosis in patients (pts) with chronic heart failure (CHF) and post-AMI. We recently showed in two literature-based meta-analyses (LMA) that the presence of RFP was associated with a 4-fold increase in the risk of death in both groups. This similar analysis evaluated the link between different MFPs and death. Methods: We searched online databases for prospective studies of pts post-AMI and with CHF and comprehensive echocardiography. All cause death was then compared in the patient group with pseudonormal (PN) filling compared to restrictive filling pattern (RFP) and abnormal relaxation/normal filling (AR/N). Review Manager Version 4.2.7 software was used for the analysis. Results: Five studies (4 CHF and 1 post-AMI) were identified and 545 pts (193 deaths) were included. PN filling confers a four-fold increased risk of death compared to AR/N (OR 4.08, 95% CI: 2.45, 6.77) but RFP has no significant additional prognostic power compared to PN (OR 1.32, 95% CI: 0.82, 2.18) but does have higher risk compared

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Deaths/Number at Risk

OR

95% CI

PN: 68/140

AR/N: 37/218

4.08

2.45, 6.77

RFP: 88/187

PN: 68/140

1.33

0.82, 2.18

RFP: 88/187

AR/N: 37/218

5.92

3.56, 9.85

72 Comparison of Myocardial Perfusion Imaging and ProBNP in Risk Stratefication Krisana Roysri1,* , Charoonsak Somboonporn2 , J. Westcott1 , Deborah Stenning3 , Meir Lichtensten1 , Frank Panetta4 , FCSANZ, Nathan Better1,4 , FCSANZ 1 Royal

Melbourne Hospital; 2 Srinakarind Hospital, Thailand; Pathology, Australia; 4 St Frances Xavier Cabrini Hospital, Melbourne, Australia 3 Melbourne

Myocardial perfusion imaging (MPI) is a predictor of cardiac events in patients with and without coronary disease (CAD). Pro-BNP is also evolving as a tool in the management of CAD. We aimed to establish a correlation between the two technologies and compare them in predicting cardiac events (CE). Method: Hundred patients undergoing clinically indicated MPI were prospectively enrolled and had blood samples 0 and 24 h post-test. Serum was analysed for proBNP (Roche) and divided into tertiles. MPI was reported qualitatively and semi-quantitatively. Medical record or telephone follow-up was available for 92 patients at 6–25 months to establish 2 groups with (A) or without (B) CE. Results: CE included death (n = 1), myocardial infarct/unstable angina (n = 2) and revascularisation (n = 9, 7 occurred >2 months post-MPI). The mean proBNP did not change significantly at 24 h and did not independently predict CE (Mean pro-BNP 196 [A] versus 106 [B], p = 0.146). Ischaemia on MPI remained a powerful predictor of CE (p = 0.001), while pro-BNP further predicted the time of CE on Kaplan-Meier analysis (p = 0.049). Quantitatively, summed stress score correlated best with pro-BNP (p = 0.008). Pro-BNP tertiles (pg/ml) Lower (0–67)

Mid (68–230)

Upper (246–3683)

CE Rate (Group A/Group A + B) Normal

0/21

0/16

0/7

Fixed defect

0/1

0/2

1/3

Ischaemia

2/8

3/13

6/21 (p = .06)

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

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Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

Conclusion: MPI is superior to pro-BNP to predict CE, but the tests offer complimentary information for cardiac risk stratification. 73 Acute Resting Myocardial Perfusion Imaging Versus Troponin I Assay to Assess Acute Chest Pain Syndromes? Krisana Roysri* , DanBing Zhou, Jonathan Knott, Meir Lichtenstein, Leeanne Grigg, Nathan Better, FCSANZ Royal Melbourne Hospital, Melbourne, Australia The injection of Tc-99m based tracers during chest pain (CP) has a high sensitivity in diagnosing coronary artery disease with good correlation to patient outcome and a high impact on patient management. We aimed to see whether the added information of Troponin I (TnI) to acute myocardial perfusion imaging (MPI) further stratefied patient outcome. Patients with or without prior history of myocardial infarct (MI) were injected with 800 MBq Tc-99m sestamibi during CP and gated SPECT performed at 1–6 h. If required, a painfree study was performed the next day. TnI was assayed 9 h after CP onset. One-year outcome data was available for 123 such patients. Cardiac events (CE) were defined as cardiac death, myocardial infarct (elevated CKMB or future admissions) or cardiac revascularisation. Results: Outcome

MPI−/TnI−

MPI−/TnI+

MPI+/TnI−

Good (CE−)

63

21

11

Bad (CE+)

2

1

7

MPI+/TnI+ 7 11 p < 0.05

The sensitivity and specificity to predict CE was 86% and 83% for MPI and 59% and 73% for TnI, respectively. With a history of prior MI (n = 34), these figures are 93%, 55%, 57% and 75%. Conclusion: The role of MPI is again shown to have a high sensitivity to predict CE. Although TnI offers complementary information, MPI is significantly superior. History of prior MI reduces only the specificity of MPI. 74 Does hs-CRP Add Prognostic Information to Myocardial Perfusion Imaging? Krisana Roysri1,* , Charoonsak Somboonporn2 , Meir Lichtenstein1 , Frank Panetta3 , FCSANZ, Alicia Jenkins4 , James Westcott1 , Nathan Better1,3 , FCSANZ 1 Royal

Melbourne Hospital; 2 Srinakarind Hospital, Thailand; Frances Xavier Cabrini Hospital; 4 Dept Medicine, St Vincent’s Hospital, Melbourne, Australia 3 St

High sensitivity-CRP (hsCRP) and myocardial perfusion imaging (MPI) are established to predict cardiac event rate (CER) in coronary disease. We aimed to see whether these two tests offer complementary information to predict patient (pt) outcome.

Method: Serum of 100 pts undergoing gated rest-exercise Tc-99m sestamibi MPI was collected and analyzed by immunonephelometry. hsCRP >3 mg/L was interpreted as positive. MPI was interpreted qualitatively and semiquantitatively as positive (mild, moderate or severe) or negative for ischemia (including normal or fixed defects, indicating prior infarct). CER, including cardiac death, myocardial infarct (MI), unstable angina (UA) warranting admission and revascularization (PCI/CABG) were recorded at 6–25 months by review of medical record, telephone or letter. Results: Outcome data was available for 97 pts. One died post-MI (MPI+/hsCRP−), 9 had PCI/CABG, and 2 admitted with UA. Event MPI−/hsCRP−

1

34

MPI−/hsCRP+

0

18

MPI+/hsCRP−

7

22

MPI+/hsCRP+

4

11

No Event

p = 0.006

The sensitivity for detecting CER for hsCRP and MPI are 33% and 91% (p = 0.001), while specificity is slightly better for hsCRP at 66% versus 61% (p = 0.26). Of note, the negative predictive value for hsCRP and MPI are 88% and 98% (p = 0.03). As expected, the positive predictive value for CER remains low for both tests (12% versus 25%). Conclusion: While both tests may offer complimentary information, MPI is significantly superior to hsCRP to predict CER with higher sensitivity and negative predictive value. 75 Tissue Doppler Determination of Arterial Elasticity is Reproducible and Robust for Following Patients at Risk for Cardiovascular Disease Brian A. Haluska1,* , Leanne Jeffriess1 , Melodie Downey1 , Stephane G. Carlier2 , Thomas H. Marwick1 , FCSANZ 1 University

of Queensland Department of Medicine, Brisbane Australia; 2 Cardiovascular Research Foundation, New York, New York, USA Background: Tissue Doppler (TDI) is a sensitive technique for diagnosing subclinical myocardial pathology and can be used to measure arterial wall displacement. We sought whether TDI of a large artery correlated with other measures of arterial stiffness and could be used to follow patients at risk of cardiovascular disease. Methods: We studied 48 Type-II diabetic patients (29 men; age 54 ± 7.7) under usual care with no known cardiovascular disease at baseline (V1), and after a follow-up (V2) of 6 ± 4 months. Tissue Doppler of the carotid artery was digitally acquired 2–10 cm below the bifurcation and analyzed off line. Custom software was used to extract the tissue Doppler velocities and calculate arterial displacement (in ␮m) over the cardiac cycle. Arterial displacement

was then corrected for vessel diameter and blood pressure (CDisp). Peterson’s elastic modulus (EmP) and local arterial compliance (LAC) were also calculated according to previously described methods. Results: Correlation between CDisp and EmP was r = −.90, and −.83 for LAC (both p < .01) and the correlation between CDisp from V1 to V2 was r = .81 (p < .0001). There were no significant differences in height, weight, BMI, HbA1c, or cardiovascular risk factors between baseline and followup for the group; the results for displacement and other methods are summarised in the Table.

Max Displ (␮g)

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Visit 1

Visit 2

Difference

p

387 ± 103

382 ± 105

4.72 ± 78

NS

Mean Displ (␮g)

185 ± 53

186 ± 55

CDisp

2.56 ± .85

2.51 ± .92

−0.51 ± 45 0.05 ± 0.55

NS NS

EmP

891 ± 370

901 ± 312

−10.9 ± 217

NS

LAC

0.11 ± 0.03

0.11 ± 0.03

0 ± 0.02

NS

Conclusions: Tissue Doppler assessment of the carotid artery is simple, non-invasive, and reproducible. Tissue Doppler measurement of arterial displacement correlates with other methods of assessing arterial elasticity and may be useful in following patients at risk for cardiovascular disease. 76 CT Coronary Angiography Following Coronary Artery Surgery M. Nicolae1 , J.H.N. Bett1,* , FCSANZ, R. Slaughter2 , A. Khoo2 1 Department

of Cardiology, Prince Charles Hospital, Brisbane, Qld., Australia; 2 Department of Radiology, Prince Charles Hospital, Brisbane, Qld., Australia Aim: To determine whether computed tomography (CT) angiography can demonstrate diseased bypass grafts and whether we may avoid invasive angiography in patients with recurrent angina after coronary artery surgery. Background: CT angiography is useful for detecting disease in native coronary arteries and grafts, with reports of high sensitivity and specificity for detection of graft disease. Methods: We subjected patients with recurrent symptoms after surgery to CT coronary angiography and compared the findings with those of conventional angiography. Results: We studied 125 grafts (average three per patient) in 42 patients (88% male, aged 67.8 ± 9.1 years), of whom 66% were smokers, 85% dyslipidaemic, 38% diabetic and 71% hypertensive. Of 84 venous grafts 30 (36%) were occluded and 7 (8%) showed high-grade stenosis, whereas only 8 (20%) of 41 arterial grafts (39 internal thoracic artery and 2 radial) were occluded. In most patients, CT angiography provided sufficient information to guide management. When we compared CT to invasive angiography in 24 (57%) patients, we found that the sensitivity and specificity of CT for the detection of graft occlusion was 97%

and 100%, and for high-grade stenosis was 100% and 97%, respectively. Comment: CT angiography is valuable for assessing chest pain after surgery. We demonstrated excellent correlation with invasive angiography and a plausible explanation for recurrent symptoms in most patients while often avoiding invasive studies. 77 The Mean Gradient to Ejection Fraction Ratio Accurately Predicts Severe Aortic Stenosis in the Presence of Impaired Systolic Left Ventricular Function J.C. Cooke1,2,* , FCSANZ, J. Ch’ng2 , R.D. Pascoe2 1 Hearts 1st, Greenslopes Private Hospital; 2 Department of Cardiology, Mater Adult Hospital* Brisbane, Qld. Australia

Background: In the presence of impaired left ventricular systolic function, aortic stenosis gradients are reduced. As such, determination of severity of valvular stenosis depends on expert assessment of 2D appearances, valve calcification, aortic valve area (AVA) and dimensional performance index (DPI). We hypothesized that a ratio of mean aortic valve gradient to left ventricular ejection fraction (LVEF) of ≥1.0 would predict severe aortic stenosis. Method: Eight thousand eight hundred and eight echo studies reported by three experienced echocardiologists at two institutions from December 2003 to January 2006 were retrospectively reviewed. A total of 842 studies with aortic stenosis (AS) were identified. We excluded studies containing ≥moderate mitral regurgitation (56), ≥moderate aortic regurgitation (9), patients with tachycardia >100 bpm (40) or insufficient data (22). The 715 remaining studies were divided by aortic stenosis grade (severe, moderately severe, moderate, mild to moderate and mild) and by LVEF (impaired function if LVEF <50%). Results: AS grade (N)

Sev AS (43)

Mod Sev (31)

Mod (36)

Mild-Mod (21)

Mild (50) 1.19

AVA (cm2 )

0.59

0.74

0.97

1.01

DPI

0.166¥

0.210¥,§

0.255§

0.285

0.345

Mean Grad (±S.D.)

41.2 (±12.2)

25.5 (±7.9)

18.5 (±7.3)

16.4 (±3.0)

12.0 (±3.6)

LVEF % (±S.D.)

32.7 (±8.7)

35.0 (±7.5)

32.1 (±9.0)

36.4 (±7.7)

32.0 (±7.4)

MG/LVEF ratio

1.29#

0.73#

0.58

0.46

0.39

p values: # p < 0.0005; ¥ p < 0.04; § p < 0.04.

In 181 patients with impaired systolic function, a MG/LVEF ratio of ≥1 correctly identified 39 of 43 patients with severe AS (PPV 0.95) and only included 2 of 136 patients without severe aortic stenosis (NPV 0.97) giving an overall accuracy of 95.6% (sens 0.91; spec 0.99). This ratio did not reliably identify severe AS in patients with LVEF ≥50% (81 patients; sens 0.22; spec 1.00). Conclusions: Mean Gradient/LVEF ratio of ≥1 accurately predicts severe AS in patients with impaired LV function.

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78 Left Ventricular Systolic Dyssynchrony after Non-ST Elevation Myocardial Infarction is Correlated with the Extent of Coronary Artery Disease and Presence of Proximal Lesion of the Left Circumflex Artery C.T. Arnold Ng* , Giao Le, Mark Newman, FCSANZ, Christine Allman, Thao Tran, Sidney T. Lo, FCSANZ, Andrew P. Hopkins, FCSANZ, Dominic Y. Leung, FCSANZ Department of Cardiology, Liverpool Hospital, Liverpool NSW, Australia Assessment of left ventricular (LV) dyssynchrony is useful to guide cardiac resynchronisation therapy in end-stage heart failure patients. Its value in acute coronary syndromes has not been evaluated. Methods: We evaluated intraventricular dyssynchrony in non-ST elevation myocardial infarction (NSTEMI) patients presenting within 48 h. Twenty-five patients (age 61 ± 12 years, 16 men) with NSTEMI and sinus rhythm were recruited. Intraventricular dyssynchrony was measured as the standard deviation of time to regional peak systolic velocity during the ejection phase using 12 segments Tissue Doppler Imaging model (SDTs). All but one patient underwent coronary angiography with significant stenosis defined as ≥70%. Results: The SDTs was 36.9 ± 18.6 ms (10.2–69.5 ms) with a QRS duration of 88.6 ± 11 ms (73–114 ms). Intraventricular dyssynchrony is present in 15 of the 25 patients (SDTs ≥34 ms). There is no correlation between SDTs and QRS duration. SDTs are significantly correlated with the number of diseased vessels (r = 0.58, p = 0.003). The mean SDTs are significantly different between patients with none, one, two or three diseased coronary arteries (p = 0.02, Fig.). Patients with significant stenosis of the proximal left circumflex artery (LCx, n = 6) has a higher SDTs compared with others (n = 18, 50.6 ± 12.5 ms versus 31.3 ± 18 ms, p = 0.02). SDTs are negatively correlated with LV ejection fraction (r = −0.57, p = 0.003) but not with mitral regurgitation (MR) severity. Conclusion: Early after NSTEMI, intraventricular dyssynchrony occurs early despite a normal QRS duration and is associated with greater number of proximally diseased vessels. A greater degree of intraventricular dyssynchrony is associated with significant stenosis of the proximal LCx but not with severity of MR.

Figure. Dys-synchrony is significantly different according to the number of diseased vessels. 79 An Ovine Model of Acute Myocardial Infarction (AMI) for Adult Stem Cell Therapy (SCT) is Assessable by SPECT/CT Imaging L.A. Ladd1,* , K.D. Tinworth1 , D.L. Bailey2 , G.J. Bautovich2 , E.A. Bailey2 , P.J. Roach2 , S.N. Hunyor1 1 Cardiac

Technology Centre/Kolling Institute, University of Sydney, Sydney, Australia; 2 Departments of Nuclear Medicine and Cardiology, Royal North Shore Hospital, Sydney, Australia Background: Non-invasive assessment of SCT for repair of AMI in animal models is desirable. [99m Tc]-sestaMIBI (MIBI) gated SPECT/CT myocardial perfusion imaging (MPI) is capable of detecting relative decreases in perfusion after AMI in myocardium. 201 Tl studies can also determine cellular viability. MPI SPECT has not previously been tested in an ovine model. Methods: AMI generated by 1 h balloon occlusion of a dominant branch of paraconal or transverse arteries in sheep is examined by MPI at pre-occlusion baseline, 3–5 days post-occlusion, and 6 weeks after injection of adult stem cells (or DMEM) into the peri-infarct zone. Yearling ewes are scanned under light anaesthesia at rest with 1GBq and dobutamine stress with 4 GBq of MIBI, with a redistribution pre-scan with 250 MBq 201 Tl after treatment. The concurrently acquired CT is converted to an attenuation map for correction in OSEM image reconstruction. MPI SPECT data are analysed using PERFIT and QPS/QGS software. Results: MPI demonstrates LV wall and chamber clearly. MPI SPECT and conductance are compared for volume and EF measurements. LVEF% mean differences are 4.25%. We measured segmental perfusion changes of −17% in the AMI zone compared with normal ±0.5%. Conclusions: MPI gated SPECT clearly demonstrates infarcts in this model. Twelve-hour 201 Tl scans confirm non-viability in the myocardial deficits at 6 weeks. This model should be amenable to detection of stem cell revascularisation at 6 weeks post-AMI since decreased myocardial perfusion is extremely well visualised. This animal

model appears an excellent choice for longitudinal studies of SCT using MPI. 80 Myocardial Delayed Enhancement Using MRI in HCM C. Hamilton-Craig1,* , R. Slaughter2 , W. Strugnell2 1 Department

of Cardiology, The Prince Charles Hospital, Brisbane, Australia; 2 Cardiovascular MRI Research Centre, The Prince Charles Hospital, Brisbane, Australia Aim: To examine the pattern and distribution of enhancement on delayed enhancement MRI in patients with a confirmed clinical diagnosis of hypertrophic cardiomyopathy (HCM). Background: Delayed enhancement (DE) following gadolinium injection has been demonstrated in patients with HCM. This finding is reported to represent collagen deposition and fibrosis in the myocardium. Presence of DE may have significant prognostic implications for risk assessment in patients with HCM. Method: We retrospectively reviewed the MR images of 26 consecutive patients with HCM. Steady state free precession (SSFP) imaging was used to provide functional assessment. Delayed enhancement imaging was performed in short axis, four chamber and vertical long axis planes, 8–15 min after IV administration of 0.2 mmol/kg of gadolinium-DTPA. Results: Eleven out of 26 patients (42%) exhibited significant DE. The pattern of enhancement was mid-wall in distribution, and differed significantly from that seen in ischaemia due to epicardial coronary disease. In three cases it was at the junction of the RV free wall and the interventricular septum. In six cases enhancement was multifocal and involved the septum. In two cases there was intense apical enhancement in patients with septal (non-apical) HCM, which to our knowledge has not been previously described. Conclusion: In this cohort the DE patterns were typical of those reported in HCM, being mid-wall and most commonly involving the anterior wall and septum. However, in two patients DE was only found at the LV apex, which may be a new variant.

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81 MRI Gadolinum Enhancement Patterns in Patients with Dilated Cardiomyopathy P.J. Larsen* , A. McCann, R. Slaughter, W. Strugnell Cardiology and Cardiovascular MRI Research Centre, The Prince Charles Hospital, Brisbane, Qld., Australia Background: Cardiac Magnetic Resonance with delayed enhancement imaging is useful in differentiating ischaemic from dilated cardiomyopathy (DCM). However, the delayed enhancement patterns in DCM are not well characterised. We sought to further document the delayed enhancement patterns seen in DCM and assess its relationship to ventricular function. Methods: We reviewed the patterns of myocardial enhancement post gadolinium in 100 patients with a referral diagnosis of dilated cardiomyopathy (average EF 21%, EDV/m2 181). The extent of gadolinium enhancement was assessed in the left ventricular mid septal, anteroseptal, anterior, lateral, inferior wall and apex using an arbitrary grading system. The location was described as mid wall or subendocardial. Results: Of the first 51 cases examined, 41% showed no enhancement. In the cases showing gadolinium enhancement, 2 patterns were seen: mid-wall, longitudinal enhancement in a non-coronary artery distribution (49%), and sub-endocardial enhancement (10%). The most common LV segments that showed mid-wall enhancement were the septum (92%) and lateral wall (29%). Mid septal enhancement was associated with more severe systolic function (EF 19% versus 23% p = 0.04 Mann–Whitney U-test). Conclusions: We found three distinct patterns of delayed enhancement in patients with DCM. Mid-septal enhancement occurred most commonly, followed by no enhancement. A minority demonstrated severe enhancement in a sub-endocardial distribution mimicking ischaemic cardiomyopathy. The findings validate previous reports and suggest delayed gadolinium enhancement in DCM occurs in stereotypical patterns. Furthermore the presence of mid-septal enhancement may identify patients with more severe left ventricular dysfunction. 82 Radial Artery Pulse Upstroke is Not a Good Marker of Left Ventricular Dysfunction: A Comparison of Radial Tonometry, Angiographic and Echocardiographic Measures of dP/dt J.E. Sharman1,2,* , A.M. Qasem3 , L. Hanekom1 , D.S. Gill4 , R. Lim4 , FCSANZ, T.H. Marwick1 , FCSANZ 1 Department

of Medicine, The University of Queensland;

2 School of Human Movement Studies; 3 University of New South

Wales, Graduate School of Biomedical Engineering, Sydney, Australia; 4 Department of Cardiology, Princess Alexandra Hospital, Brisbane, Australia The first derivative of pressure over time (dP/dt) is a marker of left ventricular (LV) systolic function that can be assessed during cardiac catheterization and echocar-

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diography. Radial artery dP/dt (Radial-dP/dt) has been proposed as a possible marker of LV systolic function (Nichols & O’Rourke, McDonald’s Blood Flow in Arteries) and we sought to test this hypothesis. Methods: We compared simultaneously recorded RadialdP/dt (by high-fidelity tonometry) with LV-dP/dt (by highfidelity catheter and echocardiography parameters analogous to LV-dP/dt) in patients without aortic valve disease. In study 1, beat to beat Radial-dP/dt and LV-dP/dt were recorded at rest and during supine exercise in 12 males (aged 61 ± 12 years) undergoing cardiac catheterization. In study 2, 2D-echocardiography and Radial-dP/dt were recorded in 59 patients (43 men; aged 64 ± 10 years) at baseline and peak dobutamine-induced stress. Three measures at the basal septum were taken as being analogous to LV-dP/dt: (1) peak systolic strain rate, (2) strain rate (SR-dP/dt), and (3) tissue velocity during isovolumic contraction. Results: Study 1; there was a significant difference between resting LV-dP/dt (1461 ± 383 mmHg/s) and Radial-dP/dt (1182 ± 319 mmHg/s; P < 0.001), and a poor, but statistically significant, correlation between the variables (R2 = 0.006; P < 0.001) due to the high number of data points compared (n = 681). Similar results were observed during exercise. Study 2; there was a moderate association between baseline Radial-dP/dt and SRdP/dt (R2 = −0.17; P < 0.01), but no significant relationship between Radial-dP/dt and all other echocardiographic measures analogous to LV-dP/dt at rest or peak stress (P > 0.05). Conclusion: The radial pressure waveform is not a reliable marker of LV contractility. 83 Percutaneous Closure of Atrial Septal Defects Leads to Reduction in Right Ventricular Volumes and Corresponding Normalisation of Left Ventricular Volumes: Ventricular Interdependence and Cardiac MRI Karen S.L. Teo* , Cynthia Piantadosi, Michael A. Brown, FCSANZ, Matthew I. Worthley, FCSANZ, Patrick J. Disney, Christopher J.K. Hammett, Peter J. Waddy, Prashanthan Sanders, FCSANZ, Stephen G. Worthley, FCSANZ Cardiovascular Research Centre, Royal Adelaide Hospital and The University of Adelaide, Adelaide, SA, Australia Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing leftto-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function, but to date this has not been proved convincingly. Cardiac magnetic resonance imaging (MRI) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using MRI. Consecutive patients (n = 23) underwent cardiac MRI pre- and 6 months post-ASD closure. Steady state free precession cine MR imaging was performed using contiguous

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slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial and ventricular end diastolic volumes (EDV), end systolic volumes (ESV). Data is presented as mean ± S.D., volumes as mL, and t-testing performed between groups. Statistical significance was taken as p < 0.05. There was a significant reduction in right ventricular volumes 6 months post ASD closure (RVEDV – 221 ± 67 versus 166 ± 55, p = 0.008) and similar to that of normal controls (172 ± 51, p = NS). The left ventricular volumes were less than normal controls at baseline (LVEDV – 118 ± 34 versus 97 ± 18, p = 0.004) and normalized post closure (123 ± 25, p = NS versus controls). The RV EF improved significantly post closure, although there was no significant improvement in LV EF. Cardiac MRI is a safe, noninvasive imaging tool that can document changes in cardiac volumes after percutaneous ASD closure. Further follow-up is required to assess how this predicts outcomes after such procedures. 84 Heart Rate, Rather Than Strength of Cardiac Contractility, Determines the Magnitude of Arterial Wave Reflections During Dobutamine-Induced Stress J.E. Sharman1,2,* , J. Jackson2 , T.H. Marwick1 , FCSANZ 1 Department

of Medicine, The University of Queensland;

2 School of Human Movement Studies, Princess Alexandra Hos-

pital, Brisbane, Australia Augmentation of the late systolic pressure peak at the ascending aorta is known to increase left ventricular (LV) load and is associated with LV hypertrophy and death. LV contractility may contribute to the extent of arterial wave reflection and LV load but this has never been examined in humans before, which was the aim of this study. Methods: Simultaneous 2D-echocardiography and radial tonometry were recorded at baseline and peak dobutamine-induced stress in 48 patients (37 men; aged 64 ± 10 years). LV contractility (LVcontract ) was determined by tissue Doppler imaging of the basal septum during isovolumic contraction (analogous to LV dP/dt). The magnitude of arterial wave reflection was determined by ascending aortic augmentation index (AIx). Results: From baseline to peak stress there was a significant increase in heart rate (72 ± 12 versus 129 ± 15 beats/min; P < 0.001) and LVcontract (3.9 ± 2.4 versus 11.1 ± 3.9 cm/s; P < 0.001), whereas AIx decreased significantly (28 ± 8 versus −6 ± 15%; P < 0.001). The AIx was strongly associated with LVcontract (r = −0.69; P < 0.001) and heart rate (r = −0.82; P < 0.001), but when AIx was normalized to a heart rate of 75 beats/min, the relationship with LVcontract was not significant (r = 0.11; P = 0.48). The strongest independent correlate of AIx (by multiple regression) was heart rate, accounting for 26% of the variance (β = −0.95; P < 0.001). Whereas, LVcontract , mean arterial pressure and body height were weak independent predictors of AIx (P < 0.05) only accounting for ≈5% of AIx variance (for the model R2 = 77%; P < 0.001).

Conclusion: The amplitude of arterial wave reflections and LV afterload is more determined by chronotropic rather than inotropic affects during dobutamine stress testing. 85 Multi-Detector CT Imaging Fails to Accurate Quantify Vessel Wall Calcification: Analysis of Multiple Algorithms and Comparison with microCT Karen S.L. Teo1,* , Stuart M. Grieve1 , Matthew I. Worthley1 , FCSANZ, Mishelle B. Korlaet1 , Michael A. Brown1 , FCSANZ, Robert Fitridge2 , Anthony Thomas3 , Angelo Carbone1 , Stephen G. Worthley1 , FCSANZ 1 Cardiovascular

Research Centre, Royal Adelaide Hospital and The University of Adelaide, Adelaide, South Australia; 2 Department of Vascular Surgery, The Queen Elizabeth Hospital, Woodville, South Australia; 3 Department of Anatomical Pathology, Flinders Medical Centre, Bedford Park, South Australia Multi-detector CT (MDCT) has become the gold-standard for angiographic imaging in most arterial beds. However, in the coronary arteries in particular, excessive calcification and blooming artifacts still limit the diagnostic accuracy of the technique for assessing stenotic severity. We sought to evaluate the burden of calcification in carotid atherosclerotic lesions using MDCT compared with endarterectomy specimen microCT, to assess the frequency of microcalcification. Patients (n = 24) scheduled for carotid endarterectomy had MDCT (Siemens Sensation-16). The endarterectomy specimens were then imaged ex-vivo with microCT (Skyscan) with an in-plane resolution of 5 ␮m. MDCT images were analysed for calcium volume with three different methods: (1) coronary calcium software, (2) Hounsfield unit threshold-based editing software (Siemens), and (3) manual tracing with Image Pro Plus. MicroCT images were analysed with CT-An (Skyscan). Data is presented as mean calcium volume (mm3 ± S.D.) and simple linear regression and Bland-Altman analysis performed between the different methods. Due to inability to exclude lumen from the calcification analysis, the coronary calcium software failed in all cases. Varying the Hounsfield unit threshold with proprietory software showed no significant relationship to calcium estimation by manual tracing, although mean values of the data set were similar (103.4 ± 114.8 versus 111.4 ± 114.2). The burden of calcification by microCT was much less (62.9 ± 68.2). However, there was no relationship between the invivo techniques and microCT. All patients except one had significant micro-calcification by microCT that was not discernible with invivo imaging. Invivo MDCT imaging of carotid atherosclerotic calcification remains limited by spatial resolution and microcalcification.

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86 Combination High-Density Lipoprotein Infusion and Atorvastatin Significantly Reduces Experimental Atherosclerosis Compared to Either Therapy Alone: Serial Analysis with High-Resolution MRI Karen S.L. Teo1,* , Stephen J. Nicholls2 , Patrick Kee1 , Kerry-Anne Rye2 , Philip J. Barter2 , FCSANZ, Stephen G. Worthley1 , FCSANZ 1 Cardiovascular

Research Centre, Royal Adelaide Hospital and The University of Adelaide, Adelaide, South Australia; 2 Heart Research Institute, Camperdown, New South Wales, Australia Modest manipulations of serum HDL levels are associated with a significant impact on cardiovascular risk. High intensity lipid-lowering with statins however remains first line in the management of at risk individuals. We analysed the effect of combination HDL infusion and atorvastatin versus either therapy alone and placebo in a rabbit model of atherosclerosis using MRI of the aortic atherosclerosis as the end-point. Aortic atherosclerosis was established in New Zealand white rabbits (n = 12) over 17 weeks by balloon denudation and cholesterol feeding and baseline MRI performed. Then rabbits received: (1) no treatment; (2) oral atorvastatin 5 mg/kg/day; or (3) infusions of HDL (8 mg/kg apolipoprotein A-I) twice per week; or (4) both, for a total of 12 weeks. A further MRI was performed. High-resolution vessel wall MR imaging of the aorta allowed analysis of the vessel wall area (VWA) and abdominal aortic slices (n = 8 per rabbit) were compared pre and post treatment. Data is presented as mean ± S.E.M. (mm2 ) and paired t-testing performed. There was a small, nonsignificant increase in VWA over the 12 weeks in the control group (6.10 ± 0.16 versus 6.36 ± 0.72, p = NS). There were non-significant decreases in VWA in both the atorvastatin only (4.69 ± 0.14 versus 4.45 ± 0.14, p = NS) and HDL only (5.54 ± 0.19 versus 5.22 ± 0.28, p = NS) groups. However, there was a significant decrease in VWA in the combination group (5.09 ± 0.14 versus 4.60 ± 0.15, p = 0.03). Even infusing small amounts of HDL provides incremental regression of atherosclerosis to atorvastatin using MRI in this rabbit model of atherosclerosis. 87 Effects of Obesity and Diet-Induced Weight Loss on Vascular and Cardiac Function Cynthia Piantadosi1,* , Matthew I. Worthley1 , FCSANZ, Andrew McAinch1 , Eugene Nalivaiko2 , Gary A. Wittert1 , Stephen G. Worthley1 , FCSANZ 1 Department of Medicine, University of Adelaide; 2 Department of Human Physiology, Flinders University, SA, Australia

Although obesity has been related to abnormalities of cardiac ventricular and also vascular structure and function, the extent of reversibility of these abnormalities with

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weight loss remains uncertain. The aim of this study was to determine the effects of diet-induced weight loss on cardiac and vascular function in obese males. Fourteen obese men age 42.1 ± 11.8 years (mean ± S.E.M.), range 18–65 years; BMI 38.65 ± 4.7 kg/m2 (mean ± S.E.M.), range 30–45 kg/m2 ; and waist circumference 127.1 ± 12.9 cm (mean ± S.E.M.), range 104–152 cm were evaluated. The men had no prior diagnosis of disease, were all nonsmokers and were not using any prescription medication. At screening 4 men had elevated BP ≥140/90. Weight loss was induced using a low calorie diet (∼800 kcal/day) over 8 weeks. Ventricular structure and function and flow-mediated dilation (FMD) of the brachial artery were assessed by MRI. All men completed the study and lost weight (12 ± 4.6 kg, mean ± S.E.M. range 5.1–21.8 kg) and had a decrease in waist circumference (10.4 ± 4.5 cm, mean ± S.E.M., range 5.0–20.5 cm). Ejection fraction (EF) increased in all of the men, from a mean (±S.E.M.) of 50.9 ± 7.6% at baseline to 58.6 ± 6.4% following weight loss (p < 0.05). Brachial artery FMD increased from 3.1 ± 1.6% (mean ± S.E.M.) at baseline to 10.1 ± 3.4% (mean ± S.E.M.) after weight loss (p = 0.06). This data suggests that weight loss in obese males can improve left ventricular systolic function with trends towards improvement in endothelial function. 88 The Inter-Relationship of Transient Ischemic Dilation (TID) and Ischaemia on Myocardial Perfusion Imaging (MPI): Prevalence of TID Without Ischaemia, and the Impact of Diabetes and Left Ventricular Hypertrophy (LVH) Louise Emmett1 , William J. Van Gaal1,* , Michael Magee1 , Sarah Bass1 , Onn Ali2 , S. Ben Freedman2 , FCSANZ, Kiran Swaraj1 , Hans Van der Wall1 , Leonard Kritharides2 , FCSANZ 1 Concord

Hospital Nuclear Medicine Department, NSW, Australia; 2 Concord Hospital Cardiology Department, Concord, NSW, Australia Objectives: To determine the incidence of TID on MPI in the absence of ischaemia, and tevaluate the impact of diabetes, and left ventricular hypertrophy (LVH) on the relationship between ischaemia and TID. Background: Patients with TID without ischaemia on MPI demonstrate a low rate of cardiac events. The prevalence of TID without ischaemia, and impact of LVH and diabetes on this, has not been evaluated. Methods: We recruited 200 patients referred for routine MPI. All had transthoracic echocardiography, with HbA1c in diabetics. A ratio of ≥1.22 on MPI was defined as TID. Summed difference scores (SDS) were determined using a 17 segment 5 point scoring system. LVH was defined as posterior and septal wall thickness >11 mm on echocardiography. Results: TID was present in 28/200 (14%). 10/28 (36%) had no ischaemia (SDS ≤2), and 18/28 (64%) ischaemia (SDS >2). Patients with TID without ischaemia had smaller left

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ventricular volumes (LVEDV 93 ± 22 ml versus 166 ± 66 ml, p < 0.002. LVESV 36 ± 15 ml versus 89 ± 53 ml, p < 0.001), and a higher post stress left ventricular ejection fraction (LVEF) (62% ± 7% versus 49% ± 12%, p < 0.005), than patients with both TID and ischaemia. The post stress LVEF correlated strongly w,h the presence of ischaemia (p < 0.003), but not with TID (p = ns). In patients with TID, 25/28 (90%) had diabetes and/or LVH. Conclusion: TID occurs frequently without ischaemia on MPI, suggesting TID may not always be related to ischaemic ventricular stunning. Subendocardial hypoperfusion is likely to contribute to TID, particularly given the strong association with LVH and diabetes. 89 Does the Severity of Intra-Ventricular Dysynchrony Change with Stress? M. Burgess* , T. Marwick, FCSANZ Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia The stability of intraventricular dysynchrony (IVD) during stress could influence the response to resynchronization therapy but the behaviour of IVD during stress with or without ischemia (ISC) is unclear. Methods: Tissue Doppler imaging was performed in 135 pts with LV dysfunction (aged 62 ± 10 years, 81% male, LVEF 32 ± 9) prior to dobutamine echo. At rest and peak stress the interval between QRS onset and maximal systolic velocity was measured off-line in the basal septal, lateral, inferior and anterior segments. The standard deviation between segments (TsSD) was used to assess IVD. Intervals were corrected for heart rate using Bazett formula. Results: Rest and stress heart rates were 76 ± 14 and 133 ± 18 bpm, respectively. 65 pts developed ISC. In 70 pts without ISC who had significant IVD at rest (TsSDcorr >32 ms, n = 32) there was a significant decrease in TsSDcorr during stress compared to at rest (45 ± 28 ms versus 61 ± 15 ms, p < 0.01)—see figure. There was no such decrease in pts without significant IVD at rest. There was a significant fall in TsSDcorr during stress in pts with limited ISC (1–2 segments, n = 37) but no change in pts with a higher ISC burden (>2 segments, n = 28). Conclusion: In pts with LV dysfunction IVD does not worsen with stress. It may often improve with higher degrees of resting IVD and limited ISC.

90 Is One Measure of Ventricular Dysynchrony Enough? M. Burgess* , C. Wong, T. Marwick, FCSANZ Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia Background: The stability of intra-ventricular dysynchrony (IVD) over time is undefined. We sought to characterise these temporal changes and identify clinical correlates of changes in IVD. Methods: We identified 72 pts (age 59 ± 12 years, 68% men, LVEF 46 ± 15%, QRS duration 96 ± 23 ms, 31% heart failure) who underwent colour tissue Doppler in the course of clinically indicated echocardiograms on 2 separate occasions. The interval between QRS onset and maximal systolic velocity was measured in the basal septal, lateral, inferior and anterior segments from velocity curves. The standard deviation between segments (TsSD) was used as a measure of IVD. Results: Median interval between studies was 16 months. There was no significant change in magnitude of IVD with time in the whole population (TsSD 30 ± 23 ms at baseline versus 33 ± 24 ms at follow-up). TsSD increased from baseline in 38 (53%) pts by 21 ± 18 ms and decreased in the remainder by 17 ± 18 ms. Ventricular remodeling (defined by increase in end-systolic volume index [ESVI]) occurred in 26 pts. In pts with no increase in ESVI TsSD was stable between studies (mean change −2 ± 28 ms, 48% of pts showing TsSD measurement within 10 ms of baseline). In pts with remodeling TsSD increased (mean change 10 ± 21 ms, p = 0.04). Change in TsSD over time but not baseline TsSD correlated with change in ESVI (Fig.). Conclusion: Measures of IVD are stable over time if cardiac status is stable. Increases in IVD are associated with remodeling.

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explores variation in these parameters with measures of case complexity. Method: The fluoroscopy time, number of frames and dose-area product (DAP) measurements for adult diagnostic cardiac imaging procedures performed in one cardiac imaging suite for the 12-month period from 1st November 2004 were analysed. The effective dose (E) for each study was estimated using a DAP conversion factor of 0.183 mSv/Gy cm2 (Betsou: BJR 1998;71:634–9). Results: In total, data relating to 1102 coronary angiography (CA) procedures, 103 graft studies, 286 angioplasty procedure and 166 CA/angioplasty procedures were examined. The median E (mSv) results for these procedures (including inter-quartile range) were, respectively, 3.3 (2.1–5.1), 5.9 (4.2–8.5), 7.5 (4.5–14.1) and 11.6 (6.9–16.1). With regard to CA procedures, a relationship between E and number of vessels involved was noted (Spearman’s rho: p < 0.01). A similar finding was documented for angioplasty procedures (p < 0.01), with the number of lesions treated (p < 0.01) and number of stents deployed (p < 0.01) also impacting proportionally upon radiation exposure. Conclusion: The results indicate a large variation in exposures for diagnostic and interventional procedures with a strong link between exposure and procedure complexity. These findings provide a benchmark against which to assess the risk of alternative diagnostic practices such as the use of CT angiography where effective doses as high as 22 mSv (Kunz: RSNA 2005) have been estimated. 92 2-d Strain Rate Analysis is Superior to Doppler Techniques in Assessing Myocardial Dysfunction Induced by Endurance Exercise A. La Gerche, K. Connelly, A. Burns, D. Mooney, A. MacIsaac, FCSANZ, D. Prior, FCSANZ Cardiac Investigation Unit, St Vincent’s Hospital, Melbourne, Vic., Australia

Figure. 91 Radiation Exposure Metrics for Cardiac Imaging Procedures I.R. Smith, J.T. Rivers* , FCSANZ, M.B. Davison St Andrew’s Medical Institute, Brisbane, Queensland, Australia Introduction: To effectively justify the risks associated with the imaging procedures they perform or prescribe, cardiologists should appreciate the radiation exposures delivered. This study reports the various radiation measures associated with common cardiac imaging procedures and

Introduction: Integrated strain (SI ) and strain rate (SR) are accepted measures of myocardial function. Colour tissue Doppler imaging (TDI) and 2-d pixel tracking are two differing methods of acquiring SI and SR. Their relative roles in clinical applications need to be defined. Methods: Echocardiograms were obtained from 26 athletes pre and post completion of an endurance triathlon. New regional wall motion abnormalities (WMA’s) defined a group of seven athletes with post-race myocardial dysfunction. In this group, ejection fraction (LVEF) was compared with TDI and 2-d derived SI and SR values. Results: In the seven athletes with WMA’s, there was a post-race reduction in LVEF consistent with exercise induced myocardial dysfunction. 2-d analysis revealed a reduction in SI and SR whereas TDI did not (Table 1). The changes in LVEF and wall motion index correlated well with 2-d derived SI and SR but not with TDI (Table 2). Conclusions: 2-d pixel tracking measures of SI and SR complement traditional measures of LV dysfunction in the post-exercise setting whereas TDI techniques do not.

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Table 1. Pre-race

Post-race

LVEF (%)

56.5

45.9**

2-d SI (%)

15.5

11.0**

2-d SRs TDI SI (%) TDI SRs *

0.66*

0.81 10.8

12.5

0.88

0.67

p < 0.05, ** p < 0.01.

Table 2. LVEF

Wall Motion Index

2-d SI

r = 0.59**

r = 0.76**

2-d SRs

r = 0.56**

r = 0.68**

TDI SI

r = 0.15

r = 0.12

TDI SRs

r = 0.20

r = 0.26

*

p < 0.05, ** p < 0.01.

93 Detection and Quantification of Fat Embolisation During Total Knee Arthroplasty Using Transthoracic Echocardiography Onn Akbar Ali1,* , Tommy Chung1 , Peter Walker2 , Warwick Bruce2 , Sebastian Herman2 , Hans Van Der Wall3 , Leonard Kritharides1 , FCSANZ 1 Department

of Cardiology, Concord Hospital, Sydney NSW, Australia; 2 Department of Orthopedics, Concord Hospital, Sydney NSW, Australia; 3 Department of Nuclear Medicine, Concord Hospital, Sydney NSW, Australia Background: Fat embolisation during bone and joint surgery is potentially life threatening. Strategies to reduce this complication suffer from a lack of non-invasive and quantitative measure of systemic release of particulate matter perioperatively. Aim: To develop a transthoracic echocardiographic (TTE) method for quantifying fat embolisation during total knee arthroplasty (TKA) and use this method to compare the incidence and severity of fat embolisation during two different techniques of TKA. In contrast to conventional TKA (C-TKA), computer navigated TKA (CN-TKA) does not violate intramedullary canal by use of guides. Method: Base line TTE was performed prior to and continuously after release of the tourniquet in 28 patients undergoing TKA. Echodense particulate matter appearing in the right atrium (RA) was digitally recorded, and the density of this particulate material was then quantified using off-line image analysis.

Result: All patients had demonstrable particulate material in the RA during surgery. Overall, RA particulate density increased from 31.7 ± 2.7 luminosity units per square cm (LU) at baseline, to a maximum density of 55.8 ± 4.3 LU after tourniquet release (P < 0.0001). Comparison of the two techniques indicated that the c-TKA was associated with greater increase in peak density than the CN-TKA (31.4 ± 4.4 versus 18.4 ± 3.5 LU, p = 0.027). Conclusion: Particulate embolisation is ubiquitous after TKA and can be quantified non-invasively using TTE. Preliminary data in our cohort suggests than novel techniques that preserved integrity of the intramedullary canal may be associated with reduced peak embolic load. 94 Decompression Illness—Transoesophageal Echocardiography Referral Pattern and Incidence of Patent Foramen Ovale George Youssef1,* , Greg Cranney1 , FCSANZ, Gita Mathur1 , Robert Turner2 , Michael Bennett2 1 Department of Cardiology, Prince of Wales Hospital, NSW, Australia; 2 Department of Diving & Hyperbaric Medicine, Prince of Wales Hospital, NSW, Australia

Patent Foramen Ovale (PFO) is associated with increased risk for decompression illness (DCI) in divers, particularly neurological decompression events, where paradoxical arterial gas embolisation is suspected. We conducted a retrospective review of the referrals for TOE and incidence of PFO detection in divers being treated for DCI in the hyperbaric unit. Between January 1998 and December 2005, 290 patients were treated for DCI. Referral for TOE (n = 37) was based on the treating physicians discretion. PFO was detected in 11 patients (29.7%), 7 of 11 (64%) were associated with an atrial septal aneurysm (ASA), and 8 of 11 (73%) were positive for right to left flow of bubble contrast without provocation. Frequency of TOE referral as well as incidence of PFO detection increased over the last 3 years (Table). In 2005, 10 divers were referred for TOE with 7 (70%) of these patients positive for a PFO. Six (86%) were positive without provocation and 5 (71%) had evidence of an ASA. Conclusion: Appropriate referral for TOE with resultant detection of PFO in DCI patients has increased in recent years. This may reflect increased awareness of pathophysiological mechanisms and availability of therapeutic options. Year 1998 1999 2000 2001 2002 2003 2004 2005 TOE 1

2

1

2

5

7

9

10

PFO

0

0

0

0

0

3

7

1

95 Use of CT Coronary Angiography in the Evaluation of Low-Risk Acute Chest Pain K.H. Soon1,* , N. Cox1 , A.-M. Kelly2 , K.W. Bell3 , Y.L. Lim1 1 Centre

for Cardiovascular Therapeutics; 2 Joseph Epstein Centre for Emergency Medicine Research; 3 Radiology Department, Western Hospital, Footscray, Victoria, Australia Introduction: This pilot study aimed to assess the practicality, safety and accuracy of performing CT-CA in the evaluation of acute chest pain of patients with low risk profile. Methods: Low risk patients (TIMI score <3) admitted within 48 h with chest pain were recruited in a prospective observational study from November 2004 to October 2005. Patients were pre-medicated with beta-blockers and scanned with a 16-slice CT. A cardiologist reported CTCA findings immediately after the reconstruction CT-CA images. Findings: Thirty-four convenient patients were recruited. Thirty of 34 patients (88%) successfully underwent CT-CA. Failed CT-CA were due to high heart rate (×3 cases) and shivering post timing bolus injection of contrast (1 case). Of those 30 CT-CA performed, 26 (87%) were of diagnostic quality; non-diagnostic CT-CA studies were due to heart rate related artefacts (3 cases) and respiratory movements (1 case). The average preparation time (premedication) from consenting to CT scanning was 1.9 h. No myocardial infarction, arrhythmia, hypotension, severe contrast induced side effects and acute renal failure were reported. Fourteen of those 26 patients with diagnostic CT-CA subsequently had a SCA. Ten of SCA studies were diagnosed as positive studies and 4 SCA studies were diagnosed as negative studies. The sensitivity and specificity of CT-CA in identifying patients with significant coronary artery disease were both 100%. Discussion: Two-third of acute chest pain patients were successfully scanned to produce CT-CA studies with diagnostic quality and accuracy. Failure in performing and achieving diagnostic CT-CA was predominantly heart rate related. CT-CA is safe to be performed in acute chest pain patients with low risk profile. 96 Pre-Stenting Assessment of Plaque Dimension with CTCoronary Angiography Kean H. Soon1,* , Nicholas Cox1 , Michael Nguyen1 , K.W. Bell2 , Y.L. Lim1 1 Centre for Cardiovascular Therapeutics; 2 Radiology Department, Western Hospital, Melbourne, Victoria, Australia

Introduction: CT coronary angiography (CT-CA) visualizes coronary plaques and measure plaque dimension better than conventional selective coronary angiography (SCA). We hypothesised that SCA under-estimated lesion length compared to CTCA. Method: A prospective observational study from October 4 to September 05 involved 36 lesions of 25 patients scanned with a 16-slice CT prior to PCI. A cardiologist blinded

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to SCA findings measured CT lesion lengths. A separate cardiologist blinded to CT findings assessed SCA lesion lengths with quantitative coronary angiography (QCA) [efilm workstation]. Stent types and sizes used in PCI were left to the discretion of the treating interventionists independent of CTCA findings. Differences in lesion lengths between CT and SCA were analysed with paired t-tests; ratio of stent length to SCA length and ratio of stent length to CT length were analysed with 1-sample t-tests. Results: Mean [CT length − SCA length] was 6.8 mm (95% CI: 4.1 mm–9.5 mm); mean [Stent length − CT length] was −1.4 mm (95% CI: −4.3–1.4 mm). Overall stent length to SCA lesion length ratio was 1.71 [95% 1.46–1.95]. Overall stent length to CT lesion length ratio was 1.10 [95% CI: 0.92–1.30]. In the subgroup of lesions stented with bare metal stents (BMS) (n = 24), the mean ratio of stent length to CT-CA lesion length was 1.09 [95%: 0.86–1.33]. For drug eluting stents (DES) subgroup (n = 12), the mean ratio of DES length to CT-CA lesion length was 1.08 [95%: 0.82–1.33]. Conclusions: CT-CA lesion length was longer than SCA length. Stent length selection based on SCA findings resulted in suboptimal stent to lesion length ratio especially when DESs were used. 97 E is not a Pure Marker of Left Ventricular Relaxation: Relationship to Systolic Function in Hypertrophic Obstructive Cardiomyopathy and End Stage Renal Failure Roger E. Peverill* , FCSANZ, Lesley Donelan, John S. Gelman, FCSANZ, Philip M. Mottram, FCSANZ, Matthew Erickson, Ian T. Meredith, FCSANZ Monash Cardiovascular Research Centre, Monash University, Clayton, Victoria, Australia The peak early diastolic mitral annular velocity (E ) is believed to be a marker of left ventricular (LV) relaxation. However, our recent report that the extent of systolic mitral annular excursion is an independent positive correlate of E in healthy subjects suggests that E is at least partly determined by systole. We further investigated this relationship between systolic excursion and E in two groups with cardiac pathology: hypertrophic obstructive cardiomyopathy (HOCM) and end stage renal failure (ESRF). Methods: Echocardiography was performed in 30 patients with HOCM (age 22–84 years) and in 18 patients with ESRF (age 29–75 years). M-mode LV mass index (LVMI) was calculated in patients with ESRF. TDI signals were recorded at the septal and lateral mitral annulus for measurement of the systolic velocity (S ) and velocity time integral (SVTI), and the early diastolic velocity (E ) and velocity time integral (EDVTI). Linear regression analysis was performed and only statistically significant (p < 0.05) correlations are presented. Results: In HOCM and ESRF there were positive correlations at both the septal and lateral annulus between SVTI and EDVTI (r = 0.70–0.81) and between SVTI and E (r = 0.59–0.83). In HOCM, age was negatively correlated

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with EDVTI (r = −0.44 to −0.45) and E (r = −0.54 to −0.61). In multivariate analyses E was positively correlated with SVTI and negatively correlated with age. In ESRF, age was inversely correlated with septal and lateral SVTI (r = −0.45 and −0.73), EDVTI (r = −0.50 and −0.68) and E (r = −0.50 and −0.62), while LVMI was inversely correlated with septal and lateral E (r = −0.56 and −0.69) and EDVTI (r = −0.45 and −0.59), but not with SVTI. In multivariate analyses E was positively correlated with SVTI and inversely correlated with LVMI. Conclusion: This study provides evidence that in cardiac disease E is a marker of both systolic and diastolic properties of the left ventricle. 98 Relationship between Reductions in Left Ventricular Long Axis Systolic and Diastolic Excursion in Early Friedreich Ataxia Cardiomyopathy Roger E. Peverill1,* , FCSANZ, Lesley Donelan1 , John S. Gelman1 , FCSANZ, Philip M. Mottram1 , FCSANZ, Janette Bain1 , Louise Corben2 , Martin B. Delatycki2 1 Monash Cardiovascular Research Centre, Monash University & Monash Medical Centre, Clayton; 2 Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia

Friedreich ataxia (FRDA) causes increased left ventricular wall thickness and this is accompanied by a reduction in tissue Doppler imaging (TDI) systolic and early diastolic long axis velocities. We sought to determine the effects of FRDA on the timing and extent of mitral annular excursion and the relationship between the changes in systolic and diastolic motion. Methods: We compared 62 FRDA patients with normal fractional shortening to 62 healthy subjects. TDI signals were recorded at the septal and lateral mitral annulus for measurement of the systolic velocity (S ), velocity time integral (SVTI) and duration (SDur), and the early diastolic velocity (E ), VTI (EDVTI), acceleration (EDacc), and duration (EDDur). Results: FRDA patients had a similar age, body surface area and blood pressure to controls, but a higher heart rate (70 ± 12 versus 61 ± 11, p = 0.002). As previously reported, septal and lateral S and E were lower in FRDA. SVTI, EDVTI and EDacc were also lower in FRDA at both septal and lateral sites, while the SDur was lower in FRDA at the septal annulus only (p < 0.05 for all). There were moderate positive correlations at both annular sites of SVTI with EDVTI (r = 0.75–0.78) and SVTI with E (r = 0.61–0.65). After including SVTI in multivariate regression models, FRDA was still a significant determinant of a lower EDVTI and E at the lateral annulus and a lower EDacc at both the medial and lateral annulus. Conclusion: Systolic and early diastolic mitral annular excursion and early diastolic acceleration are reduced in FRDA. Reduced systolic excursion in FRDA partly mediates the lower E , however, FRDA also independently affects left ventricular diastolic properties.

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99 Validation of Magnetic Resonance Imaging for the Assessment of Arterial Stiffness A.J. Nelson1,* , A. Carbone1 , S.G. Worthley1 , FCSANZ, C. Piantadosi1 , S.A. Hope2 , J.D. Cameron2 , FCSANZ, I.T. Meredith2 , FCSANZ, M.I. Worthley1 , FCSANZ 1 Cardiovascular

Research Centre, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia; 2 Monash Cardiovascular Research Centre, Monash Medical Centre, Melbourne, Australia Applanation tonometry (TONO) evaluation of pulse wave velocity (PWV) has been widely used and accepted as an effective method for non-invasively assessing arterial stiffness (AoS). Newer non-invasive tools such as magnetic resonance imaging (MRI) have the capabilities to evaluate measures of AoS such as aortic distensibility, but to date have not been formally evaluated against TONO. Fifteen patients were enrolled in the study. All subjects had TONO (Millar Mikro-tip, Millar Instruments) performed with simultaneous carotid and femoral waveform data acquired. MRI (1.5 T Seimens Sonata) measurements of arterial stiffness were evaluated by aortic distensibility, utilizing the equation (aortic area at end systole − aortic area at end diastole)/brachial pulse pressure (mmHg) × aortic area at end diastole. The aorta areas were measured at three separate locations, the ascending (AA) and proximal descending (PDA) aorta at the crossing of the pulmonary artery and distal descending aorta (DDA) within the first 10 cm of the aorta below the diagram. The mean PWV of this cohort was 7.51 ± 0.8 SE m/s. The mean aortic distensibility measurement at each site was 5.9 ± 0.9 × 10−3 mmHg−1 at the AA, 5.8 ± 0.9 × 10−3 mmHg−1 at the PDA and 7.7 ± 1.1 × 10−3 mmHg−1 at the DDA. All of these distensibility results significantly correlated with TONO results, AA r = 0.59 p = 0.02; PDA, r = 0.65, p = 0.008; and DDA, r = 0.71, p = 0.002. Aortic distensibility as measured by MRI is an accurate measure of AoS, possibly more so in the descending than ascending aorta. 100 Restoration of Sinus Rhythm Acutely Improves Left Ventricular Systolic Function in Patients in Atrial Fibrillation Toon Wei Lim1,* , Liza Thomas2 1 The University of Sydney, NSW, Australia; 2 Department of Cardiology, Westmead Hospital, Westmead, NSW, Australia

Background: Cardioversion (CV) of atrial fibrillation (AF) to sinus rhythm (SR) improves left ventricular (LV) function but its immediate effects are uncertain. Methods: One hundred and thirty-six patients (98 male, mean age 65.0 ± 11.8 years) underwent elective CV; 12 patients remained in AF (Grp 1) and 124 were restored to SR (Grp 2). TTE was performed before and 4 h after CV. Parameters of LV function that were measured included

Abstracts

LV ejection fraction (LVEF), peak systolic velocity of the septal mitral annulus (S ) using Doppler tissue imaging (DTI), peak E velocity (E) and deceleration time (DT) of mitral inflow and peak early diastolic velocity (E ) using DTI. Results: Baseline measurements were similar between the two groups. Post CV, Grp 2 showed improvements in LVEF and S with a decrease in peak E and E velocities. Conclusion: Restoration of SR results in immediate improvement of LV systolic function, but its effect on diastolic function needs further evaluation. Parameters ±

Pre Cardioversion

Post Cardioversion

Group 1

Group 2

Group 1

Group 2

43.6 ± 14.1

41.4 ± 12.1

46.5 ± 15.4

45.1 ± 10.3*,§

S velocity/m/s

0.050 ± 0.011

0.051 ± 0.011

0.052 ± 0.010

0.053 ± 0.015*,§

E velocity/m/s

0.97 ± 0.20

0.97 ± 0.28

0.97 ± 0.16

0.94 ± 0.31*

DT/ms

204 ± 59

210 ± 65

193 ± 36

0.086 ± 0.021

0.085 ± 0.023

0.080 ± 0.021

LVEF biplane/%

E velocity/m/s

207 ± 54 0.072 ± 0.021*

* p < 0.05 for Grp 1 post CV vs. pre CV. § p < 0.05 for Group 2 vs. Group 1 post CV.

101 Restoration of Sinus Rhythm Immediately Improves Left Atrial Function in Patients Undergoing Electrical Cardioversion for Atrial Fibrillation Toon Wei Lim1,* , Liza Thomas2 1 The University of Sydney, NSW, Australia; 2 Department of Cardiology, Westmead Hospital, Westmead, NSW, Australia

The aim of this study was to investigate the immediate effect of restoration of sinus rhythm (SR) on left atrial (LA) function in atrial fibrillation (AF). Methods: One hundred and thirty-six patients (98 male, mean age 65.0 ± 11.8 years) underwent elective cardioversion (CV). Twelve patients remained in AF (Group 1) while124 were restored to SR (Group 2). TTEs were performed immediately before and within 4 h after CV. Rhythm independent parameters of LA function and pulmonary vein (PV) flow characteristics were used as surrogate measures of LA compliance. Results: Pre CV measurements were similar in the two groups. Restoration of SR resulted in a significant immediate increase in LA stroke volume and ejection fraction. A significant increase was noted in PV systolic flow parameters. Conclusion: LA function improves in SR and is likely due to an increase in LA compliance. Parameters ±

Pre Cardioversion

Post Cardioversion

Group 1

Group 2

Group 1

Group 2

19 ± 6.4

19.3 ± 9.3

24.5 ± 16.7

22.8 ± 9.4*,§

25.1 ± 8.1

24.1 ± 10.1

26.7 ± 11.7

30.2 ± 9.1*,§

PV peak systolic velocity/m/s

0.34 ± 0.11

0.32 ± 0.08

0.32 ± 0.06

0.39 ± 0.12*,§

PV systolic VTI/cm

8.00 ± 3.75

7.08 ± 2.27

7.81 ± 2.29

8.80 ± 3.44*

PV systolic fraction

34.1 ± 8.1

35.0 ± 7.6

39.1 ± 5.6

39.7 ± 10.9*

Left atrial stroke volume/ml Left atrial ejection fraction/%

* p < 0.05 for post cardioversion vs. pre cardioversion. § p < 0.05 for Group 2 vs. Group 1.

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102 Prevalence of Double Chambered Right Ventricle in the Adult Population: Is it More Common than First Thought? K.T. Davies1,* , C.J.B. Ward2 , J.C. Cooke1 , FCSANZ 1 Mater

Adult Hospital, Australia; 2 Mater Children’s Hospital, Brisbane, QLD, Australia Background: In recent years, double chambered right ventricle (DCRV) has become increasingly recognised in the adult population. DCRV is commonly associated and also confused with peri-membranous VSDs (PMVSD). Its prevalence in a general adult echo population is unknown. Importantly, specialised views of the right ventricle can assist with successfully identifying DCRV. We sought to determine the prevalence of both DCRV and VSD in our adult echo population. Methods: Echo studies performed at MAH from the time of our first recognised DCRV patient (March 2003) to January 2006 were reviewed. All patients with VSDs (past or present) were carefully imaged utilising the additional RV views to facilitate identification of a DCRV. Particularly useful is the anterior para-apical view of the mid RV cavity to the pulmonary valve in the identification of flow acceleration in these patients. Results: Of 4502 echo studies, 46 studies related to VSDs: 27 perimembranous, 8 muscular and 10 patients had undergone surgical closure (4/10 had residual shunts). 5/4502 demonstrated DCRV, 4/5 had a concomitant PMVSD. In 1/5 the PMVSD had closed spontaneously, the DCRV giving rise to her residual murmur. The overall prevalence of VSDs was 1.02% in our studies. Amongst our VSD population, 10.9% also had DCRV when carefully scanned for its presence. Conclusions: The prevalence of DCRV is higher than expected reinforcing that specialised imaging of the RV is important to confirm or exclude its presence in patients with a current or past history of PMVSDs. 103 Echocardiography in Percutaneous Aortic Valve Replacement R.R. Moss* , C.R. Thompson, B.I. Munt, M. Chandavimol, S. Pasupati, J.G. Webb St Paul’s Hospital Vancouver, Canada Background: Percutaneous aortic valve placement has the potential to revolutionize the treatment of aortic valve disease but has been guided only by fluoroscopy and limited by technical constraints. Precise positioning of the valve should minimize the occurrence of paravalvar regurgitation or device migration. We sought to determine the usefulness and limitations of echocardiography in optimizing percutaneous placement of 23 or 26 mm Cribier-Edwards stent mounted equine pericardial prostheses retrograde from the femoral artery. Methods and results: Patients had transthoracic echocardiography (TTE) prior to the procedure to assess aortic

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annular dimension, valve hemodynamics, and bulky aortic valve calcium. Patients with small annuli or bulky calcium were unsuitable for device placement. Twenty-eight patients underwent successful percutaneous valve placement. Eighteen patients had TEE during device placement. TEE accurately determined annular dimension, was useful in device size selection, and successfully guided device placement in most. Utility was limited if heavy calcification acoustically shadowed the device. All patients had a significant increase in aortic valve area from 0.63 to 1.64 cm2 (p < 0.001). Aortic regurgitation (predominantly posterior paravalvar) was detected in 25 of 28 patients undergoing successful deployment and was graded trivial or mild in most cases. Minimal apparent device recoil immediately following placement has been observed. Careful long-term observation will be required to elucidate the potential effect of recoil, however no late valve failure has been observed. Conclusion: Echocardiography has an important role in case selection, in guidance of device placement and detection of complications of percutaneous aortic valve placement. 104 Relationship Between Left Ventricular Geometry and Measures of Diastolic Function J. Hare* , T. Marwick, FCSANZ University of Queensland, Brisbane, Australia Background: Abnormal LV mass (LVM) and LV geometry are associated with adverse outcome, but the mechanism of these effects is undefined. We sought the functional associations of these findings, specifically the relationship with abnormal diastolic function, early diastolic velocity (Em; assessed by tissue Doppler of mitral annulus) or estimated filling pressure (E/Em; ratio of transmitral and tissue E velocity), all of which have prognostic significance. Methods: We studied 163 pts (age 52 ± 15; 71 men) with assessable echocardiographic indices of LV mass and diastolic function. LV mass was measured using the Devereux method and patients were stratified into four LV geometric groups on the basis of LVM and relative wall thickness. Tissue Doppler imaging of the mitral septal annulus was used to measure Em and calculate E/Em ratio. Patients were categorized to normal or abnormal LV diastolic function. Results: Mean LVMI was 115.9 ± 32.1 g/m2 with LV hypertrophy observed in 108 pts (66%). Normal LV geometry was present in 22 pts (13.5%), concentric remodeling in 33 (20.3%), concentric hypertrophy in 78 (47.8%) and eccentric hypertrophy in 30 (18.4%). Mean Em was 8.9 ± 2.4 cm/s and E/Em was 9.1 ± 3.4. Compared to normal geometry, concentric hypertrophy was characterized by significantly reduced Em (p = 0.001), and increased E/Em (p = 0.009). There was no significant difference between concentric remodeling and normal geometry in both Em and E/Em. Moreover, Em and abnormal diastolic function (p < 0.001) were a greater problem in concentric hypertrophy than concentric remodeling.

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Conclusion: Myocardial characteristics, filling pressure and transmitral flow are relatively normal despite the adverse prognosis associated with concentric remodeling. Em (cm/s)

%Abn. Diastology

7.29 ± 1.97

54.5

Concentric remodeling

9.76 ± 2.78†

8.32 ± 3.27

51.5

Concentric hypertrophy

8.15 ± 2.15*

9.89 ± 3.80*

83.3#

Eccentric hypertrophy

8.82 ± 1.82

9.38 ± 2.85

80.0

Normal geometry

10.37 ± 2.90

E/Em

* p≤0.001, # p < 0.01 for comparison to normal geometry. † p < 0.01 for comparison to concentric hypertrophy.

105 Segmental Atrial Contraction after Linear Ablation and after Cardioversion for Atrial Fibrillation: A Colour Doppler Tissue Imaging Study A.C. Boyd* , S.P. Thomas, D.L. Ross, FCSANZ, L. Thomas Department of Cardiology, Westmead Hospital/University of Sydney, Sydney, Australia Colour Doppler Tissue Imaging (CDTI) is used to quantify regional mean peak myocardial velocities. Our aim was to evaluate segmental atrial contractility in patients with chronic atrial fibrillation (CAF) after restoration and maintenance of sinus rhythm (SR). Method: CAF patients maintained in SR ≥6 months after intraoperative linear radiofrequency ablation (LRFA, n = 28) or DC cardioversion (CV, n = 39) were prospectively studied and compared to a normal cohort (n = 33). Using CDTI, segmental atrial contraction was measured from annular, mid and superior segments of lateral and septal walls of the left atrium (LA) and right atrium (RA) in the apical 4-C and the anterior and posterior walls from the apical 2-C view. Results: Differences between the three groups were examined by one-way ANOVA with Bonferini correction. The LRFA group had significantly lower atrial contraction velocities in all segments, compared to both the CV and Normals group. The CV group also had significantly lower LA contraction velocities compared to Normals; however there was normalization of atrial contraction velocities in the RA. Table. CDTI (cm/s) from left atrium apical 4-chamber view (mean ± S.D.) Normals Septal annular Septal mid Superior Lateral mid Lateral annular *

7.2 5.0 1.4 6.8 7.7

± ± ± ± ±

1.3 1.5 0.8 1.9 2.2

CV 5.6 4.5 1.3 5.4 6.0

± ± ± ± ±

1.8* 1.7 0.8 2.7* 2.1*

LRFA 2.6 1.7 0.5 1.5 1.8

± ± ± ± ±

1.6*,† 1.1*,† 0.4*,† 1.3*,† 1.3*,†

p < 0.05 compared to normals. † p < 0.05 compared to CV.

Conclusion: Patients with CAF have significant long-term LA dysfunction, despite restoration and maintenance of SR. There is differential recovery of LA and RA function. The LRFA group had the lowest atrial contractility and is likely due to the pre-existing disease and additive effect of ablation lesions.

106 Cardiac MRI Findings in Acute Myopericarditis J. Ginns* , R. Slaughter, W. Strugnell The Prince Charles Hospital, Chermside, Qld., Australia Objectives: To retrospectively review the cardiac MRI findings in 10 cases of suspected acute myopericarditis at our institution. Background: The diagnosis of acute myopericarditis can be difficult and is based on a constellation of typical clinical, biochemical and electrocardiographic finding, all of which can be mimicked by other common cardiovascular disorders. Endomyocardial biopsy is a specific but non-sensitive test which carries some risk. Establishing reliable alternative “gold standard” diagnostic test would enable this common disease to be readily distinguished and treated appropriately without risk of side effects from inappropriate therapies. Methods: We retrospectively reviewed the cardiac MRI findings in 10 patients who had presented to this hospital with suspected acute myopericarditis. All had electrocardiography and measurement or cardiac enzymes performed. Eight of the ten had coronary angiography performed. Findings: The MRI findings of myopericarditis in these cases included: (a) Patchy mid and subepicardial delayed gadolinium enhancement predominantly involving the basal inferolateral segments in a non-coronary distribution. (b) Absence of associated regional wall motion abnormalities on cine MRI. (c) In two cases, follow up MRI scans were obtained demonstrating partial or complete resolution of enhancement without typical scarring and contraction usually associated with infarction. Conclusion: In our experience, the typical finding of myopericarditis were similar to those in other reported series. Cardiac MRI using delayed gadolinium enhancement provides characteristic findings in this condition which may distinguish such cases from other conditions with similar clinical presentations without the need for more invasive tests.

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107 Validation of Transoesophageal Echocardiography in the Assessment of Systolic Function in Patients Undergoing Coronary Artery Bypass Surgery: A Comparative Study Using Pressure-Volume Loop Analysis Kim A. Connelly1,2,* , Colin Royse1,3 , Alistair G. Royse1,4 , Graeme MacLaren1 1 Cardiovascular

Therapeutics Unit, Department of Pharmacology, University of Melbourne; 2 Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Australia; 3 Cardiac Investigation Unit, St Vincent’s Hospital Melbourne, Australia; 4 Department of Anaesthesia and Pain Management, Royal Melbourne Hospital; 5 Department of Cardiac Surgery, Royal Melbourne Hospital, Melbourne, Australia Transoesophageal echocardiography (TOE) measures of systolic left ventricular (LV) function obtained during coronary artery bypass surgery (CABG) are influenced by alterations in loading conditions, as a result of anaesthesia, blood loss or cardiopulmonary bypass. To date, no validation of TOE measurements against load independent indices obtained by pressure volume (PV) loop analysis has been undertaken in humans. Methods: Ten patients undergoing CABG underwent simultaneous TOE and PV loop analysis of cardiac function at different loading conditions (reduced preload, increased afterload, atrial pacing at 100 beats per minute). All TOE measures; fractional area change (FAC), afterload corrected FAC (FACaC), and lateral basal wall peak systolic myocardial velocity (Peak S ), and dP/dt were compared to the preload recruitable stroke work relationship (PRSW). Results: Nine patients were included in the final analysis. The mean age was 59 ± 9 years. Altered loading conditions resulted in no significant changes in the PRSW. There were no significant differences between FAC, FACac and Peak S compared to the PRSW. dP/dt was significantly different when compared to PRSW (p < 0.001). Conclusions: TOE derived indices of cardiac contractility adequately assessed systolic function across loading conditions commonly seen during CABG. 108 BNP Predicts Exercise Time, Mitral Valve Area and Left Atrial Pathology in Mitral Stenosis V. Sharma1 , A.J. Kerr1,* , O.C. Raffel1,2 , S.P. Wong1 , J. White1 , R.A.H. Stewart2 , FCSANZ 1 Middlemore

Hospital, Auckland, New Zealand; 2 Auckland City Hospital, Auckland, New Zealand Introduction: Plasma levels of Brain Natriuretic Peptide (BNP) are known to increase in patients with left ventricular dysfunction but there is limited data on BNP in mitral stenosis (MS), which is characterised by increased left atrial pressure and volume, and normal LV function. Methods: Trans-thoracic echocardiogram and blood samples for BNP were obtained in 34 patients with pure MS and 14 age and gender matched controls. Exercise toler-

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ance tests were performed in controls and 30 patients. Results: MS patients were predominantly NYHA class I and II (97%) with a mean mitral valve area of 1.24 ± 0.29 cm2 . Compared to controls, MS patients had larger left atrial (LA) area (19.7 ± 3.6 cm2 versus 35.4 ± 10.5 cm2 , p < 0.0001) and higher right ventricular systolic pressure (RVSP) (22.6 ± 4.4 mmHg versus 35.5 ± 11.7 mmHg; p = 0.0002). There was no difference in LV ejection fraction (68.3 ± 4.0% versus 64.1 ± 7.7%, p = 0.08). BNP levels were higher (6.0 ± 3.0 pmol/L versus 20.6 ± 13.5 pmol/L, p < 0.001) and exercise times shorter (654 ± 179 s versus 376 ± 174 s, p < 0.001). For MS patients higher BNP was associated with shorter treadmill times (r = 0.48; p = 0.008). BNP correlated with increased LA area (r = 0.70; p < 0.0001), was higher in patients with atrial fibrillation compared to those in sinus rhythm (31.2 ± 16.8 pmol/L versus 16.2 ± 9.0 pmol/L; p = 0.002) and associated with decrease in mitral valve area (r = 0.42; p = 0.02). There was no clear association between BNP and RVSP, RV size, or LV EF. Conclusion: In MS plasma levels of BNP increase with LA size and the presence of atrial fibrillation. These observations and the lack of association with measures of LV or RV function suggest an atrial origin for raised BNP in MS. 109 Mitral Annular Tissue Doppler Imaging is Abnormal in Patients with Mitral Stenosis and Normal Left Ventricular Ejection Fraction V. Sharma1 , A.J. Kerr1,* , O.C. Raffel2 , S.P. Wong1 , M. Oldfield1 , G. Whalley3 , R.A.H. Stewart2 , FCSANZ 1 Middlemore 3 Department

Hospital, Auckland; 2 Auckland City Hospital; of Medicine, University of Auckland, New

Zealand Introduction: Mitral annular tissue Doppler imaging (TDI) is a routine part of the echocardiographic assessment of left ventricular (LV) systolic and diastolic function. However, it remains unclear how to interpret this information in the presence of valve disease, including mitral stenosis (MS). Methods: Echocardiograms were performed on 35 patients with pure MS and 15 age and gender matched controls. TDI signals were recorded from the septal mitral annulus. The peak systolic (S ), peak early diastolic (E ) and systolic time velocity integrals (S TVI) were measured. LV end diastolic volume (EDV), end systolic volume (ESV) and LV ejection fraction (EF) were calculated. Mitral valve area (MVA) was measured quantitatively. Results: The mean MVA in MS patients was 1.24 ± 0.29 cm2 . There was no difference between MS patients and controls in LVEDV (87.3 ± 26.4 ml versus 81.8 ± 16.5 ml), LVESV (32.0 ± 13.6 ml versus 26.3 ± 6.9 ml), or LVEF (63.9 ± 7.8% versus 67.9 ± 4.6%, p = 0.07). MS patients had lower mitral S velocities (6.2 ± 1.0 versus 8.1 ± 1.6 cm/s) and E velocities (5.4 ± 2.5 versus 9.4 ± 3.5 cm/s) than controls (p < 0.0001). The mitral S VTI,

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a measure of longitudinal systolic excursion, was also reduced in patients (1.6 ± 0.30 cm versus 2.0 ± 0.36 cm; p < 0.0001). There was no correlation between the S velocity and LVEF or LVEDV. The mitral S velocity decreased with increasing left atrial area (r = 0.44, p = 0.008) and with decrease in MVA (r = 0.45, p = 0.007). Conclusions: In MS, with normal LVEF and LV volumes, mitral annular TDI indices of longitudinal LV systolic and diastolic LV function are reduced, and correlate with increasing LA area and MS severity. This suggests that in MS, mitral annular TDI data may be determined by factors other than LV performance. 110 Toward Automated Analysis of Global LV Function: Definition of a Normal Range with 2D Strain Rodel Leano1,* , Jing-Ping Sun2 , Michael Becker3 , Rainer Hoffmann3 , James D. Thomas2 , Thomas Marwick1 , FCSANZ 1 University

of Queensland, Brisbane, Australia; 2 Cleveland Clinic Foundation, Cleveland, OH, USA; 3 RWTH Aachen, Aachen, Germany Automated measurement of LV function could extend the clinical utility of echo by less expert readers. We sought to define normal ranges of global 2D strain (2DS) and strainrate (SR) in an international, multicenter study of healthy subjects, and to assess the determinants of variation. Methods: SR and 2DS were measured in 18 myocardial segts in both apical and short axis views of 175 normal subjects (38% men, 49 ± 13 years) with no cardiac history, risk factors or drug therapy. The association of age and resting hemodynamics with global strain indices was sought using multiple regression. Differences in variance were expressed as F values. Results: Baseline SBP was 126 ± 17 mmHg, pulse was 68 ± 12/min and ejection fraction 55 ± 11%. Although global longitudinal strain was influenced by SBP (F = 10.8, p < 0.001), height (F = 5.0, p = 0.03) and weight (F = 19.2, p < 0.001), these factors accounted for only 7% of variance. Global SR was influenced by SBP (F = 7.8, p = 0.005), heart rate (F = 21.4, p < 0.001) and gender (F = 4.3, p = 0.04), but again these factors accounted for only 5% of variance. Diastolic SR variables were influenced by age and hemodynamics, accounting for 10% of variance (E wave) and 19% (A wave). The subgroup with optimal average tracking quality (TQ) had greater measurements than the remainder (Table) but these differences were clinically unimportant. Conclusions: Normal ranges of resting 2DS and SR show significant inter-individual variation, but only a minor degree appears attributable to hemodynamic and demographic variables. Strain

Syst SR

E Wave SR

A Wave SR

Longitudinal (all)

−19 ± 3

−1.01 ± 0.23

1.26 ± 0.41

0.83 ± 0.28

Longitudinal (TQ = 1)

−20 ± 3

−1.03 ± 0.21

1.35 ± 0.39

0.85 ± 0.28

p (TQ1 vs. rest)

0.001

0.0007

0.26

0.09

111 Early Atherosclerotic Disease in the Carotid and Coronary Territories in At-Risk Individuals Timothy H. Greenwell1,* , Karen S.L. Teo1 , Derek P. Chew2 , FCSANZ, Christopher J.K. Hammett1 , Cynthia Piantadosi1 , Angelo Carbone1 , Matthew I. Worthley1 , FCSANZ, Stephen G. Worthley1 , FCSANZ 1 Cardiovascular

Research Centre, Royal Adelaide Hospital, University of Adelaide; 2 Department of Cardiology, Flinders Medical Centre, Flinders University, Adelaide, SA, Australia The detection of early atherosclerotic disease, such as carotid intima-media thickness (IMT) and coronary artery calcium scoring (CAC), predicts cardiovascular events. Ultrasound based carotid IMT is operator-dependent and assesses posterior vessel wall thickness. High-resolution internal carotid MRI can completely assess vessel wall abnormalities, more accurately reflecting the atherosclerotic process. The relationship of early atherosclerotic disease in different territories is poorly understood, and may provide incremental risk prediction. We studied at-risk individuals with carotid and cardiac MRI and CAC. Asymptomatic individuals (n = 147) underwent comprehensive cardiovascular risk assessment including physician-review of conventional cardiac risk factors, coronary calcium scoring using MDCT, and cardiac and carotid MRI. T1-weighted MR images of both ICAs were generated using a dedicated phased-array carotid coil (1.5 T Siemens Sonata MRI), and were analysed offline using ImagePro Plus (Media Cybernetics) to determine IMT and vessel wall area (VWA). Data is presented as mean ± S.D. or medians as appropriate. Cohort characteristics were: age = 53 ± 11 years; M:F = 3:1. The mean vessel wall area of the ICAs = 24.3 ± 8.6; CAC = median 1.1 (interquatile range 0–96.4). There was no significant relationship between early atherosclerosis in the ICA and coronary territories using ICA MRI and CAC (p = NS). There were no demographic factors associated with ICA indices. The only demographic factor associated with CAC was age (p = 0.02). Early atherosclerotic disease in the ICA using MRI does not correlate with CAC scores. These two techniques may provide incremental risk prediction, although the costeffectiveness of such an approach requires further study. 112 Effects of Enzyme Replacement Therapy in Patients with Fabry Disease L. Thomas1,* , T. McKay1 , D. Silence2 , N. Sadick1 , FCSANZ

1 Department

of Cardiology, Westmead Hospital/University of Sydney; 2 Department of Medical Genetics, Westmead Children’s Hospital, NSW, Australia Enzyme replacement therapy (ERT) has recently been approved for patients with Fabry disease and renal or cardiac involvement.

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Methods: Four Fabry patients were evaluated with ECG, TTE and RV biopsy at baseline and 3 years after commencement of ERT. LV systolic function (LVEF, S velocity), wall thickness, mass and diastolic function (peak E velocity, DT, flow propagation (FP) and E velocity were evaluated by TTE. Results: All four patients felt symptomatically better on ERT. LVH on ECG was unchanged. There was moderate concentric LVH with preserved systolic function at baseline. No significant difference was noted at 3-year follow up. Although transmitral flow patterns and IVRT were normal, the septal E velocity and FP were reduced. No significant differences were noted in parameters of diastolic function over 3 years, though the FP was increased. Histopathology demonstrated no significant changes in the samples obtained. Table. Mean ± S.D. Pre ERT IVS thickeness (mm) LV mass (gms) DT (ms) E velocity (cm/s) FP (cm/s)

15.4 221.7 230 6.9 50.2

± ± ± ± ±

2.3 11 13 2.4 5.8

Post ERT 14.1 246.6 215 6.6 66.8

± ± ± ± ±

3.5 26.8 52 1.8 3.4

Conclusion: ERT appears to prevent progression of Fabry disease. In this small group we were unable to demonstrate regression of LVH or improvements in diastolic function at the current dosage schedule. 113 Current Practice Patterns in Echocardiography: A Prospective Survey of Clinical Echocardiography Around New Zealand (SCANZ) Gillian A. Whalley1 , Akbar N. Ashrafi1,* , Paul Bridgman2 , FCSANZ, Stewart Mann3 , FCSANZ, Tom Gentles4 , FCSANZ, Raewyn Fisher5 , FCSANZ, on behalf of the SCANZ collaborators 1 University

of Auckland; 2 Christchurch Hospital; 3 Wellington School of Medicine; 4 Starship Hospital; 5 Waikato Hospital, New Zealand Background: In New Zealand, disparities between regional echocardiography are believed to exist. At present, we have neither guidelines, nor data regarding the provision of echocardiography. The purpose of this survey is to provide a cross-sectional “snapshot” of clinical use of echocardiography within NZ, with particular emphasis on referral indication and assessment of left ventricular (LV) function. Methods: Over a one-week period (5/12/05–11/12/05) all echocardiography laboratories around New Zealand (tertiary and secondary hospitals and private practices) sent copies of their echo reports and referral forms (with patient identifiers removed) to a central site. Demographic information, clinical indication, measurements performed and interpretation were collated, recorded, reviewed, tabulated, and entered into an Access database. Approval was obtained from the National Ethics Committee.

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Results: Over 1300 echoes were performed during this week. This preliminary report presents data on the first 500 patients analysed. Ninety-five percent were adults and 22% had normal echo reports. Patient demographics: 55% male, mean age 59 ± 23 years (median 64 years). The main primary clinical indications were: LV function (39%), valve disease (12%), murmur (5%), pre-operative assessment (5%) and source of emboli (5%). Nearly all reports commented on LV size and function, but only 30% included an interpretation of LV diastolic function. Right ventricular function was reported in 52%. Conclusion: This prospective survey provides a contemporary overview of the clinical indications, and methods currently employed in clinical echocardiography. It will serve as a platform for development of echocardiography within New Zealand. 114 Characterization of Myocardial Perfusion in Patients with Refractory Angina Utilizing Rest-Stress Cardiac Magnetic Resonance Imaging Paul Klaassen1,* , Andrey G. Zenovich2 , Terri Streufert2 , Duana M. Walton2 , Betsy V. Wilson2 , Chad Carlson2 , John R. Lesser2 , and Timothy D. Henry2 1 Abbott 2 The

Northwestern Hospital, Minneapolis Heart Institute; University of Minnesota, USA

Background: The subset of patients with refractory angina on maximal medical therapy not amenable to repeat revascularizations is increasing. Investigations of novel treatments for these patients are often impeded by limitations of imaging techniques to assess myocardial perfusion. We investigated rest-stress cardiac MRI in patients with refractory angina who received standard medical management, growth factors (FGF, VEGF-2), CD-34+ stem cells and external extracorporeal counterpulsation (EECP) therapies. Methods: Rest-stress (adenosine, 3 min infusion with maximal dose of 140 mcg/kg/min) CMR scans with Gd-DTPA (0.1 mmol/kg) were employed in 62 patients (11 medical therapy, 29 FGF, 12 VEGF-2, 3 CD-34+ cells and 7 EECP) at baseline and at trial-specific follow-up points. The FGF, VEGF-2 and CD-34+ cell therapy patients are participants of randomized clinical trials. Semi-quantitative myocardial perfusion assessment was performed by two readers (PK, AGZ) blinded to treatment allocation by scoring (0-darkest with least perfusion versus 3-brightest) the myocardium according to a 16 segment model. Further quantification by determining signal intensity (by constrained deconvolution modeling) was applied to estimate myocardial blood flow. RANOVA, chi-square and regression analyses were applied, and p ≤ 0.05 considered significant. Results: At baseline, patients were classified by age, gender, coronary disease severity, CCS class of angina, prior CABG (%), prior PTCA + stenting (%), prior MI (%) and EF (by cath or echo).

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Baseline

Score 0

Score 1

Score 2

Score 3

Resting scan

17.3%

33.2%

37.2%

12.4%

Adenosine scan

14.1%

36.4%

36.4%

13.2%

Reversible ischemia was present in 36.7% of segments. However, ischemia worsened with adenosine in 45% of segments. The semiquantiative and quantitative approaches had high correlation of r = 0.658 on resting scans and of r = 0.692 on adenosine scans. Conclusion: Refractory angina patients carry a heavy segmental ischemic burden. Presence of resting flow and/or reversible ischemia may be a characteristic of likely response to angiogenic therapies. The results of myocardial perfusion assessment at the follow-up end-points for each unblinded therapy will be presented at the meeting. Cardiac Surgery 115 Paradpxocal Septal Motion after Cardiac Surgery O.B. Tofler, FCSANZ Mount Hospital, Crawley, WA, Australia Background: Paradoxical septal motion (PSM) is frequently observed following cardiac surgery, but is not well characterised. Methods: A retrospective review was performed of the most recent patients seen in a cardiology practice following cardiac surgery. Surgery was performed between 1995 and 2004. Echocardiography was performed on the first visit (approximately 2 weeks post discharge), and then as clinically indicated for up to 7 years. Study population: Forty-eight patients were analysed who did not have LBBB or a pacemaker. Patients were aged 40–80 years (median 72 years). Twenty percent were female. In the 80% who had preoperative echocardiograms, no PSM was identified. Systolic function was normal in the remaining 20% who had ventriculography. Thirty-one had coronary artery bypass surgery (CABG), 12 had valve surgery and five had CABG and valve surgery. Results: After CABG, PSM was observed in 30 of 31. Septal motion returned to normal in 10, while variable dysfunction persisted in 20. After valve surgery alone, septal motion was normal in 3 of 12 on the first echo after surgery and became normal in 4 more. After CABG/valve surgery, none of 5 achieved normal septal motion. The posterior and lateral walls were usually vigorous, so ejection fraction was in most cases >50%. Exercise tolerance appeared to be positively associated with normal septal motion. Conclusion: PSM is common following both CABG and valve surgery. When PSM is present on the first postoperative echocardiogram, septal motion returned to normal in only 14 of 41 patients who had further echocardiograms. This observation merits further prospective study.

116 Cardiac Surgery Abbreviates Post-Mitotic Maturation of Neutrophils During Stimulation of Bone Marrow Neutrophil Release Y. Orr1,* , D.P. Wilson1 , J.M. Taylor1 , P.G. Bannon3,4 , C. Geczy2 , M.P. Davenport1 , L. Kritharides1,5 , FCSANZ 1 Center

for Vascular Research; 2 Inflammatory Diseases Research Unit, School of Medical Sciences, The University of New South Wales; 3 Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown; 4 The Baird Institute for Applied Heart and Lung Surgical Research, Newtown; 5 Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia Background: Extracorporeal circulation (ECC) during cardiac surgery is a potent stimulus for bone marrow neutrophil release however the quantitative contribution of distinct phases (hypothermia, re-warming, and reperfusion) is unknown. In the present study, bone marrow neutrophil release during ECC was investigated using the CD10− /CD16low phenotype as a marker of neutrophil immaturity, and mathematical modeling of kinetic data to quantify the abbreviation in post-mitotic maturation time. Methods: Total and newly emergent (CD10− /CD16low ) neutrophils were quantified in cardiac surgery patients (n = 10) during procedural (hypothermic), re-warming and weaning (reperfusion) phases of ECC using flow cytometry and differential full blood counts. Results were applied to a differential equation mathematical model to quantify changes in neutrophil age at exit from the bone marrow relative to time during ECC. Results: Constant linear growth in total circulating neutrophils (2.46 ± 0.42-fold) occurred throughout ECC which, when applied to our mathematical model, indicated a progressive decrease in neutrophil mean age at release from the bone marrow. Post-mitotic maturation time was abbreviated by 6.7 h after 71 min of ECC. A progressive linear increase in CD10− /CD16low neutrophils, from 0.5 ± 0.1 × 109 /L to 3.3 ± 0.7 × 109 /L was observed throughout ECC indicating age-dependent first in-first out kinetics for bone marrow neutrophil release. Conclusions: ECC induces bone marrow neutrophil release uniformly during hypothermia, re-warming and reperfusion phases and accelerates neutrophil transit time through the bone marrow. Targeting the acceleration of neutrophil transit during ECC may be required to regulate the inflammatory response to cardiac surgery. 117 Relationship Between Ascending Aortic Anatomy and Blood Flow William S. Peters* , F. Paget Milsom Green Lane Cardiothoracic Surgical Unit, Auckland City Hospital, New Zealand Background: The left ventricle and aorta are known to propel blood in a vortical manner. This study defined the ascending aortic anatomy in an adult population and analysed the effect of varying aortic geometry on wall shear stress, pressure drop and blood flow.

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Methods: Measurements were made from thoracic MRI in 20 adult patients: mid-ascending aortic diameter (d); outer arc length from sinotubular junction to brachiocephalic artery (l); outer arc radius of curvature (r1 ); and degree of ‘lift’ in the ascending aorta (r2 ). Computational fluid dynamic analysis was made, varying r1 /d, r2 and l about their mean values. Blood density and viscosity and the swirling ventricular outflow velocity were held constant. Results: Mean d = 32.1 ± 3 mm; mean l = 79 ± 10 mm, mean r1 = 54.9 ± 7 mm, mean r2 340 ± 108 mm. Reducing the r1 /d ratio toward 1.0 caused a logarithmic rise in mean wall shear stress and pressure drop, and reducing r2 had a similar effect. Varying the arc length from 70 to 110 mm had negligible effect. Particle tracer plots demonstrated that the spiral-shaped aorta enhanced swirling blood flow. Discussion: Vortical flow may impart momentum on the blood, centralization of the suspended ‘mass’ of blood cells, modulation of fluctuations in wall shear stress and a washing effect on the aortic wall. Nature seemingly provides a balance between aortic anatomy and blood composition that achieves minimal pressure loss and modulated wall shear stress, whilst enhancing the advantages of vortical flow on the blood. 118 Myocardial Strain Predicts Left Ventricular Responses to Valve Surgery in Asymptomatic Severe Mitral Regurgitation L. Hanekom* , S. Wahi, FCSANZ, C. Smith, B. Haluska, R. Leano, T.H. Marwick, FCSANZ University of Queensland, Princess Alexandra Hospital, Brisbane, Qld., Australia We sought to assess the value of strain rate imaging (SRI) for the prediction of left ventricular (LV) dysfunction in asymptomatic severe mitral regurgitation (MR). Methods: Exercise echo and SRI were performed in 31 asymptomatic severe MR patients (age 60 ± 13 years, 14 female, EF 62 ± 5%) at baseline and after MV surgery (MV repair or replacement). 18 pts had myocardial biopsy performed at surgery for evaluation of fibrosis. Long-axis end-systolic strain and peak systolic strain-rate by SRI (ESS and SR) and 2D-strain (2D-ESS 2D-SR) were measured in the basal and mid-segment of each myocardial wall, and averaged per patient at baseline and follow-up echo. ROC curve analysis was performed to assess optimal cut-off points for SRI parameters in the prediction of LV deterioration post-operatively. Results: Of 31 patients studied, 39% had deterioration of LV function on follow-up echo (mean deterioration −8 ± 6%, 8 ± 5 months after surgery). MR patients with subsequent deterioration in LV function had significantly lower SR, ESS, 2D-SR and 2D-ESS (Table). Myocardial fibrosis was present in 5 pts and absent in 13 pts. Fibrosis+ pts had significantly lower SR (−0.82 ± 0.03/s versus −1.3 ± 0.2/s, p < 0.0001), ESS (−10.2 ± 1% versus −18.1 ± 3%, p < 0.001), 2D-SR (−0.6 ± 0.07/s versus −1.17 ± 0.2/s, p < 0.0001) and 2D-ESS (−11.6 ± 2% versus −17 ± 3%, p < 0.001) compared with fibrosis-pts.

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Conclusions: Myocardial strain is predictive of LV recovery after MV surgery. The pathological correlate appears to be development of myocardial fibrosis.

120 Skin Damage Associated with External Defibrillation and Pacing P.F. Meyer1,* , P.D. Gadsby1 , D. Van Sickle2 , W. Schoenlein2 , T.P. DeMonte3 , M.L. Joy3 , K. Foster2 , G. Graber2

SRI parameters

BaselineSR (/s)

BaselineESS (%)

Baseline2DSR (/s)

Baseline2DESS (/s)

LV deterioration (12)

−0.95 ± 0.3*

−12.8 ± 4*

−0.86 ± 0.3**

−12 ± 2**

1 Tyco

LV preservation (19)

−1.36 ± 0.31

−18.5 ± 4

−1.23 ± 0.2

−17.7 ± 3

3 University

AUC Optimal cut-off

0.85 −1.2

0.85 −16

0.9

0.93

−0.9

−14

Significance compared between patients with LV deterioration and LV preservation. ** p < 0.0001, * p < 0.001

Cardiac Technology 119 Validation of 2D Independent CW Doppler CO Measurements in Preterm Neonates by Comparison with Echocardiography R.A. Phillips1,* , M. Paradisis2 , N.J. Evans2 , D.L. Southwell2 , D.J. Burstow3 , FCSANZ, M.J. West3 , FCSANZ 1 The University of Queensland, Brisbane, Australia; 2 Royal Prince Alfred Hospital, Sydney, Australia; 3 The Prince Charles Hospital, Brisbane, Australia

Objective measurement of cardiac output (CO) in preterm neonates is important for clinical management. Doppler ultrasound is the preferred method for measurement of CO however the pulmonary and aortic valve diameters for calculating flow volumes are small, and measurement using 2D ultrasound, particularly of the pulmonary valve, requires expertise and experience. The USCOM (USCOM Ltd, Sydney, Australia) is a novel 2D independent CW Doppler device which calculates flow volumes using anthropometrics. The device is simple to operate and less expensive than conventional echo. This study was to compare 2D echo and USCOM CO measurements in pre-term neonates. After IRB approval 66 paired measures of transpulmonary CO were acquired in 37 pre-term neonates (weight 1.13 ± 0.47 kg) using conventional echocardiography, combining 2D and CW Doppler, and the USCOM device. Signals were acquired and analysed independently and in a blinded fashion, and values compared by two tailed t-tests and Bland-Altman bias analysis. Mean values of transpulmonary CO were 0.36 ± 0.19 l/min by echo and 0.37 ± 0.14 l/min by USCOM and not significantly different (r = 0.9134, p < 0.005). The mean difference between measures was 0.00 ± 0.08 l/min, with a mean % error of −3.7%. The smaller SD associated with USCOM convert to smaller 95% CIs and a possible increased sensitivity for detection of haemodynamic change. These results suggest that USCOM is as accurate for measurement of neonatal CO as conventional echo, and may make a cost-effective contribution to neonatal haemodynamic management.

Healthcare, IN, USA; 2 Purdue University, IN, USA; of Toronto, Canada

External defibrillation and synchronized cardioversion involve the rapid transfer of large amounts of energy across the chest wall. While providing potentially lifesaving therapy, these shocks commonly produce noticeable skin damage. Transthoracic pacing is known to produce skin lesions as well, albeit of very different appearance. In a series of studies, we explored the nature of the skin damage produced by these therapies and the potential of a new disposable electrode design to mitigate the damage. Using thermographic imaging and histological examination of domestic swine after repeated high-energy biphasic defibrillation shocks, we quantified the relative propensity for several different electrode designs to produce electrothermal skin damage. Skin biopsies indicated the presence of second as well as the expected first degree skin burns. A new high-edge impedance electrode design was found to reduce the degree of electrothermal skin irritation. In another study, the ability of the new electrode to control electrical current distribution was confirmed through MRI-based current density imaging. A third study demonstrated that skin lesions associated with prolonged transthoracic pacing are electrochemical in nature, resulting from the breakdown of electrode constituents. The new electrode design appears to delay electrode polarization, thereby extending the duration of pacing without skin damage. 121 Fluorescent Dye Tracking of Mesenchymal Stem Cells (MSCs) for Heart Repair in an Ovine Model C. Weir1,2,* , M.-C. Morel-Kopp2 , K. Tinworth1 , L. Ladd1 , C. Ward2 , S. Hunyor1 1 Cardiac Technology Centre, Kolling Institute, University of Sydney at Royal North Shore Hospital, Sydney, Australia; 2 Northern Blood Research Centre, Haematology Department at Royal North Shore Hospital, Sydney, Australia

Background: Cell replacement or rejuvenation therapies have gained impetus in treatment of heart disease. MSCs are pluripotent and can differentiate into cardiomyocytes, avoiding the ethical, immunological and tumourigenic concerns associated with embryonic stem cells. Most studies using MSCs for cardiac repair have been in rodents. However, large animal models are more applicable to human studies, and better suited for refining cardiac repair strategies. One limitation of large animal, especially sheep studies, is the lack of methods for cell tracking (i.e. GFP models). Methods: Following extraction and flow cytometric characterisation of MSCs isolated from the marrow of male sheep, the cells were grown up in culture. Fluorescent

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tracking dyes such as CFSE, DiD and DiI were used to label MSCs and tested for detectable ‘in vitro’ and ‘in vivo’ signal for up to 6 weeks. The effect of MSC labelling on cell division and differentiation was also tested. Results: Several dyes trialed did not maintain fluorescence over time and slowed cell division compared to control. An alternative thiol reactive dye DiI (Molecular probes) has shown detectable in vitro fluorescence levels for 4 weeks. ‘In vivo’ trialling showed that MSCs labeled with this dye were detectable by fluorescence microscopy 12 days and 42 days after injection into sheep skeletal muscle. DiI labelled MSCs differentiated ‘in vitro’ showed that the labeling was retained over a 28-day period. Conclusion: Fluorescent membrane dyes such as DiI provide an alternative to traditional cell marking methods such as GFP for tracking MSCs in therapeutic studies. 122 Pre-Implantation Determination of Myocardial DysSynchrony Reliably Predicts Improvement in Left Ventricular Function Indices and Exercise Performance Following Bi-Ventricular Pacing for Symptomatic Heart Failure G.D. Gordon* , A. Hamer, J. Williamson, T. Carger, L. Liu, N. Smith, G. New, FCSANZ Cardiology Department, Box Hill Hospital, Melbourne, Victoria, Australia Inter and intra ventricular dys-synchrony studies were performed on 30 subjects being assessed for cardiac resynchronization therapy (CRT). No significant dys-synchrony or extensive postero-lateral wall infarction was present in 8 (27%). Despite these findings a clinical decision to proceed with CRT was made in 4 subjects. Post implantation, cardiac function and exercise capacity was reevaluated at 4 and 12 weeks post CRT. Combination bi-ventricular pacemaker and cardioverter/defibrillator devices were implanted in all subjects. Mean posterolateral LV wall activation delay was 111 (68–184) ms in the group considered to have significant dys-synchrony. Inter-ventricular delay was 66 (23–122) ms. QRS duration of <120 ms was present in 7 subjects (29%) with significant dys-syncrony (>80 ms). Optimal AV delay intervals were determined and set at the time of implantation. LVEF (%)

LVEDV (ml)

6 min walk (m)

Pre CRT

24 (16–31)

224 (186–291)

341 (214–510)

Post CRT

31 (21–50)

201 (121–263)

455 (352–607)

P < 0.05

P < 0.05

P < 0.1

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There was no correlation between inter-ventricular delay and subsequent LV function or symptom status post CRT. There were no additional predictors (clinical or echo-cardiographic) for these outcomes as determined by multivariate analysis. In the group receiving CRT without significant dys-synchrony the delay was 34 (26–51) ms. There was no significant change in any indices of LV function or exercise performance as assessed with a 6 min walk test in this small group (4). Conclusion: In this observational study, the presence of significant left ventricular dys-synchrony reliably predicted a significant short-term improvement in functional capacity and LV function after CRT with bi-ventricular pacing. 123 An Evaluation of ARCHITECT BNP Assay M. Saleem, P. George* , S. Southby Canterbury Health Laboratories, Christchurch, New Zealand B-type natriuretic peptide (BNP) is an important marker in the diagnosis and management of patients with heart failure. An automated immunoassay for BNP has been developed for use in the Abbott ARCHITECT instrument system. We evaluated this assay with respect to precision, analytical sensitivity and its correlation with the AxSYM BNP assay. To evaluate the precision, three control levels were assayed in replicates of two on two separate runs over five days and the total %CV was calculated. Analytical sensitivity or Limit of detection was established as two standard deviations of low-level BNP samples above the mean concentration of calibrator A (0 pg/mL). Calibrator A was run in replicates of twenty on three separate runs. Three plasma pools of low-level BNP were also run in replicates of five in three separate runs. The correlation between ARCHITECT BNP and AxSYM BNP was determined by testing 98 samples (3.8–3445 pg/mL) and performing Passing and Bablok regression analysis. The %CV for the low (94 pg/mL), medium (497 pg/mL) and high (3387 pg/mL) controls were 2.9%, 3.8% and 2.5%, respectively. Measured values were Cal A (0.1 pg/mL) and LOD (1.94 pg/mL). The Passing and Bablok regression analysis between ARCHITECT and AxSYM BNP showed a slope of 0.8427 (95% CI: 0.8000–0.8852) and a correlation coefficient of 0.97 (95% CI: 0.95–0.98). The Abbott ARCHITECT BNP assay is a precise method for measurement of BNP with a total %CV <5% and correlates well with the Abbott AxSYM BNP assay.

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Cardiovascular Nursing 124 Comparison of Complications in Percutaneous Coronary Intervention Patients Mobilised at 6, 4 and 3 h Following Femoral Arterial Sheath Removal Sandra Walker1 , Colleen Jen2 , Fiona McCosker2 , Sonja Cleary3,* 1 School of Nursing & Health Studies, Central Queensland Uni-

versity, Rockhampton, Australia; 2 Coronary Care Unit, Princess Alexandra Hospital, Brisbane, Australia; 3 School of Nursing & Health Studies, Central Queensland University, Bundaberg, Australia The purpose of this research study was to explore groin complication rates of patients mobilised at 3, 4 and 6 h post femoral arterial sheath removal following percutaneous coronary intervention (PCI). Participants recruited from those undergoing PCI were randomly allocated either to the 3, 4 or 6 h mobilisation group. Participants’ groins were assessed for evidence of complications including haemorrhage, haematoma formation and pseudoaneurysm immediately following removal of the femoral arterial sheath and again the next day. Of the 338 participants recruited into the study 9.5% (n = 32) were excluded due to excessive bleeding at the groin puncture site or haematoma development prior to sheath removal. Results show that the length of bed rest postarterial sheath removal had no significant effect on bleeding (F (304) = 5.39, p = 0.21) or haematoma formation (F (304) = 0.258, p = 0.612) for participants who mobilised at either 3, 4 or 6 h post PCI arterial sheath removal. These findings will guide delivery of health care services for the elective PCI patient, supporting day only service delivery. 125 The Nexus between Cognitive Impairment and Self-Care in Chronic Heart Failure J. Cameron1,* , L. Worrall-Carter1 , S. Stewart2 , FCSANZ 1 Deakin University, Melbourne, Australia; 2 University of South

Australia, Adelaide and University of Queensland, Brisbane, Australia Background: Patients with Chronic Heart Failure (CHF) are encouraged to become active participants in their care through self-care management. Cognitive impairment however, frequently co-exists with CHF and the consequences of it on self-care ability are uncertain. Aim: To determine whether low performance of CHF selfcare is correlated with impaired cognitive function. Method: Fifty patients admitted with symptomatic CHF were screened for cognitive impairment, self-care and depressive symptoms using three validated clinical instruments: Mini Mental State Examination (MMSE), Self-care of Chronic Heart Failure Index (SCHFI), Cardiac Depression Scale (CDS). A standard linear regression model was used to analyse how much of the variance in SCHFI scores could be explained by mild cognitive impairment (scores <26) or depressive symptoms (scores >100).

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Results: The mean age ± S.D. was 73 ± 11 years, 76% were male. Half the group had been diagnosed with CHF less than 2 months. Eighteen (36%) had mild cognitive impairment and 19 (38%) reported significant depressive symptoms. The regression model was non-statistically significant (p = 0.15), explaining only 8% of the variance in self-care. Depressive symptoms appeared to make the strongest unique contribution to the model (beta = −0.27) although it was not statistically significant (p = 0.06). Conclusion: There was no correlation between impaired cognition and any of the dependent self-care variables. The results were unexpected and may have been due to the clinical tool chosen to measure cognitive function. Future research is recommend to further investigate the nexus between mild cognitive dysfunction and CHF selfcare using a clinical screening tool that measures executive functioning. 126 Establishing an Elective Coronary Angioplasty Unit in a Non Coronary Care Setting G. New* , FCSANZ, B. Collins, A. Tinney, C. Scully, T. Lawrence, S. Pritchard, L. Roberts, S. Hall, L. McPherson, J. Stevens, H. Parker, V. Pandeli, B. Chou, M. Swale, H.B. Liew, C. Lim, A. Teh Box Hill Hospital, Box Hill, Vic., Australia Background: Following elective percutaneous coronary intervention (EPCI), patients have traditionally recovered in Coronary Care (CCU). Reduction in complications following EPCI has led to a lower level of nursing supervision. The aims of establishing an EPCI Unit in a general cardiac ward (GCW) at Box Hill Hospital are to reduce demands on CCU, the likelihood of cases being postponed and costs without compromising patient care and safety. Method: A Clinical Nurse Consultant was employed to train and support the nursing staff in the GCW. The role included developing policy and facilitating change. After a literature review and “benchmarking” process, a program that included patient care, arterial sheath removal, cardiac monitoring and advanced life support, mobilisation and patient discharge was developed. The GCW nurses were required to pass a competency assessment. Safety outcomes 1 day and at 30 days post-discharge and a cost difference were analysed. Results: From the 5th December 2005, 37 elective patients were assessed. Fifteen were selected. Nine were excluded prior to procedure, and 13 were excluded due to training resources. In 4 of the 15 cases there were CCU bed demands that may have resulted in postponing the PCI. There were no adverse events at the 24 h post discharge follow-up phone call. Thirty-day follow-up also confirmed no adverse events. There was a cost saving of $1200 per patient for a one night stay the GCW compared with CCU. Conclusion: Recovery of Elective PCI patients in GCW with trained PCI staff is safe and reduces hospital costs.

127 Nursing Audit of Arterial Sheath Removal Using the FemoStop Device Following Percutaneous Coronary Intervention (PCI) in Which Drugs are Rarely Used and Complications Minimal S. Forde* , M. Cumming, D. McClean Cardiology Department, Christchurch Hospital, Christchurch, New Zealand We audited the current nursing practice of arterial sheath removal post PCI using the FemoStop device to obtain haemostasis. Methods: All nurses removing sheaths were educated in the FemoStop use, and followed a detailed protocol. They were required to first gain proficiency in digital pressure. Patients were assessed for discomfort prior to and during sheath removal. Site prior to sheath removal, time to haemostasis, mobilisation time, and complications over the next 24 h were documented. Results: The 74 patients audited all had aspirin and clopidogrel pre PCI, all had intravenous heparin during procedure, some had recent low molecular weight heparin and 5 had reopro infusions. With questioning, 89% of patients found the FemoStop device comfortable. Of the 11% who did notice discomfort with the device, only 3% required intravenous pain relief. Eighty-one percent reported no complications over the following 24 h. Complications were bruising 11%, haematoma 8%, and bleeding 4%. When pre-sheath removal bleeding, haematoma, and/or bruising sites were excluded, over 24 h there were only 4% haematomas and 3% bruising. Haemostasis time averaged 21 min (range 11–90). Fifty-nine percent took only 15 min. There were no vasovagal episodes or pseudoaneurysms. Seventy-three percent were mobilised at 6 h with no problems. Nurses found the device user friendly and eliminated muscular strain associated with digital pressure. Conclusion: With expert training, the FemoStop device is a safe method of arterial sheath removal that is relatively painless with few complications. 128 Implementation of Nurse Referral for Exercise Tolerance Testing in a Chest Pain Assessment Unit J.I. Millar* , W.A. Cuthill, N. Greenberg, P.G. Bridgman, FCSANZ Christchurch Hospital, Christchurch, New Zealand Background: The creation of a chest pain assessment unit with protocol driven management has been shown by us and others to be an effective and safe means of managing hospital presentation of low risk chest pain. Previously, although our exercise tolerance tests were nurse supervised, only a Cardiologist could refer for the test. We report the institution of a protocol under which nursing staff can also refer patients for exercise tolerance testing (ETT). Method: Patients acutely admitted to the chest pain assessment unit were eligible for nurse referral in the absence of ongoing pain, ECG changes and troponin elevation. We

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prospectively audited the first 101 patients undergoing ETT after instituting this protocol change. Results: With the change in protocol in most cases the decision to proceed to ETT became a nursing rather than a medical decision, 82 versus 19 cases. In the nurse decision patients the time from admission to ETT was 21 h compared to 24 h in the medical group. All exercise tests were uncomplicated. In the nurse decision patients there were 10 positive tests with 8 going on to coronary angiography. Of these 5 patients underwent revascularisation prior to discharge. In the doctor group 1 patient underwent angiography and subsequent revascularisation. As per protocol all patients were seen by a Cardiologist at some point during their admission. Discussion: A protocol permitting nurses to refer for inpatient exercise tolerance testing was successfully and safely implemented. It resulted patients getting appropriate testing earlier. 129 Interhospital Transfer of the Intra Aortic Balloon Pump Patient: From Fear and Foreboding to Embracing The Clinical Challenge E. Scholes* , K. Cowie, S. Cecchin Western Hospital, Footscray, Vic., Australia Aim: To establish a clinical competency in order to promote safe management of the intra aortic balloon pump (IABP) patient; and to develop clinical practice guidelines for the interhospital transfer of these patients. Background: Primary PCI was adopted for the management of STEMI patients at Western Health in 2004. This has led to the increased use of the IABP as adjunct therapy and the interhospital transfer of some of these patients for cardiac surgical intervention. Previously interhospital transfer of the IABP patient occurred rarely with uncertainty surrounding the transfer and management process. Method: Using a case study approach we process mapped the transfer of an IABP patient. Problems were identified with pre-transport co-ordination and communication, transport equipment, monitoring required during transport, allocation of accompanying staff and manual handling risks. These issues, in conjunction with a literature review, informed the development of a clinical competency for IABP patient management and clinical practice guidelines for the interhospital transfer process. Diffusion of innovation theory guided the strategies employed to educate staff about the competency and guidelines. Results: Focus groups to establish staff perceptions of the education process and their understanding of the IABP patient management and transfer process revealed that staff felt well informed. However, all staff perceived that clinical experience was the most effective means of acquiring confidence in managing the IABP patient and interhospital transfer. Since implementation of the clinical competency and practice guidelines 11 IABP patient transfers have occurred with no associated adverse outcomes.

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130 System Barriers to the Efficient Utilization of a Chest Pain Assessment Service within a Tertiary Referral Hospital D.L. Walters* , FCSANZ, E. Gordon, S. Spreadborough, H. Dunlevie Cardiology Department, The Prince Charles Hospital, Brisbane, Queensland, Australia The aim of this study was to identify barriers to the efficient utilization of the chest pain assessment service (CPAS) at our institution. Methods: A Nurse Case Manager was appointed to the CPAS service for a 4-month period. Data was collected on factors that led to a delay in patient access to the CPAS, reasons for delays in performing stress testing and the effect of a Case Manger on average length of stay (ALOS) of patients entering the service was also assessed. Results: Of the 162 patients managed through the CPAS, delays in accessing the service from the emergency room were caused by waiting for medical staff review (27%) and bed access block (6.5%). Reasons for stress test delays were a late hour of presentation (40%), a lack of availability of medical staff (14%), and access block to the treadmill facility (8%). At the completion of the assessment most patients were classified as low risk and discharged (63%), however a significant proportion were reclassified high risk and admitted for further evaluation (25%). Inefficient utilization of the resource occurred in patients who either were unable to walk on a treadmill (4.5%) or were removed from the pathway and admitted to a ward due to bed pressure. Case management of the service reduced ALOS from1.4 days to 13 h. Conclusion: Nursing-led Case Management was able to reduce ALOS of patients requiring the service. The key barriers to optimum service utilization in that setting was medical staff availability and access block to beds and diagnostic equipment. 131 Patient Perceived Quality of Life One Year after Coronary Artery Bypass Graft Surgery G. Lee La Trobe University/Alfred Clinical School of Nursing, Melbourne, Vic., Australia Background: Coronary artery disease remains a leading cause of death and morbidity worldwide and can lead to a decline in health related quality of life (HRQoL). One common intervention is Coronary Artery Bypass Graft Surgery (CABGS) with 16,000 operations performed annually in Australia. Aim of the study: To evaluate patient perceived HRQoL before and one year after CABGS using the Short-Form 36 Health Survey (SF-36). Methodology: Patients were recruited at the Alfred Hospital, Melbourne in 2004 and completed the SF-36 preoperatively and one year after their operation. The SF-36 has eight domains which measure physical and mental

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HRQoL and results were analysed using paired sample t-tests. Results: Forty-eight participants at one-year follow-up were included in the data analysis. The sample population was predominantly male (87.9%) with a mean age of 66.3 ± 10.5 years at the time of surgery. The findings revealed that the SF-36 mean scores had improved significantly across all the health domains except ‘mental health’ at one-year after CABGS (p < 0.001). The HRQoL of patients at one-year follow-up compared closely to the Australian population norms. Conclusion: Patients in this follow-up study perceive a significant improvement in their HRQoL one year after CABGS. The findings demonstrate the benefits of CABGS for patients and for informing health professionals on HRQoL in this cohort. The lack of significant improvement n the mental health domain warrants further investigation. 132 Which Variables Predict Quality of Life Five Years after Coronary Artery Bypass Graft Surgery? G. Lee La Trobe University/Alfred Clinical School of Nursing, Melbourne, Vic., Australia Background: Coronary Artery Bypass Surgery (CABGS) is a surgical intervention used to alleviate or partially relieve angina and breathlessness and potentially improve quality of life (QoL). Aim of the study: The study sought to examine patientperceived QoL, psychological well-being, physical activity and dietary behavior and to identify variables which predict the patients’ QoL five years after CABGS. Methodology: Participants were asked to complete two QoL questionnaires, the Short-Form 36 (SF-36) and the Dartmouth Primary Care Co-operative Information Project Questionnaire (COOP), and a diet and physical activity questionnaire. Psychological well-being (anxiety and depression) was measured using the Spielberger Trait Anxiety Inventory and Beck Depression Inventory, respectively, pre-operatively and five years post-operatively. The Physical Component Summary (PCS) and Mental Component Summary (MCS) were identified as dependent variables for hierarchical regression. Results: One hundred and nine patients agreed to participate in a follow-up study five years after CABGS. Hierarchical regression analysis revealed that pre-operative angina scores and the following data at five years post CABGS; concomitant illness, anxiety and depression and physical activity, accounted for 37% of the variance in PCS. Pre-operative anxiety, interim myocardial infarction and the following data five years post CABGS: age, diet scores, anxiety and depression, accounted for 60% of the variance in MCS. Conclusion: Using hierarchical regression, 37% of the variance in PCS could be predicted and 60% of the MCS variance five years post CABGS.

133 Patient and Spouse Perceived Quality of Life Five Years after Coronary Artery Bypass Graft Surgery G. Lee La Trobe University/Alfred Clinical School of Nursing, Melbourne, Vic., Australia Background: The number of individuals undergoing coronary artery bypass surgery (CABGS) is steadily increasing. Aim of the study: The purpose of this study was to examine the patients’ and their respective spouses’ perspectives of quality of life (QoL) five years after CABGS. Methodology: Participants were asked to complete the Short-Form 36 (SF-36) five years after CABGS. The SF-36 has eight domains and two component summary scores measuring physical and mental QoL (PCS and MCS, respectively). Paired t-tests were used in the analysis. Results: A total of seventy-five couples completed the data at five years post CABGS. Significant differences were evident between patients’ and spouses’ perception of the patients’ QoL. The patients and spouses reported statistically significant results in emotional role, mental health, social functioning, energy/vitality and general health perceptions (p < 0.001). The spouses recorded higher scores (i.e. better scores) than the patients in the domains related to physical functioning but none of the differences were significant. With the summary scores, PCS results were very similar for both the patient and spouses sample (p = .829) and there was a significantly higher mean in MCS patient sample compared to the spouse sample (p < .001). Conclusion: The spouse could precisely score physical health using the SF-36 but contradictory data emerged on reporting their partner’s mental health five years post CABGS. 134 Nursing Audit for Tract Bleeding Complications Associated with the Use of the StarClose Arterial Device after Percutaneous Intervention (PCI) L. Farra* , M. Cumming, D. McClean Ward 12, Cardiology Dept, Christchurch Public Hospital, Christchurch, New Zealand A StarClose vascular closure system is designed to mechanically bind the surface of femoral artery following percutaneous coronary intervention (PCI). Methods: Patients who had a StarClose device inserted to femoral artery site following PCI were audited by nursing staff for signs of tract bleeding from the time they returned to the ward and subsequent 24 h. Results: Forty patients who had received six French femoral arterial sheaths had a StarClose device inserted. Twenty-one (53%) patients had no tract bleeding complications. Eighteen (46%) developed tract bleeding complications. Of these patients 4 (10%) required no intervention for minor ooze, 4 (10%) required use of FemoStop, mean time 161 min (60–240 min), 6 (15%) required digital pressure mean time 7 min (2–12 min). Additional nursing inter-

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vention for 8 patients (20%) was noted as combination of FemoStop, digital pressure, icepack/sandbag, and Syvek patch. Two adverse events occurred. One patient was readmitted to hospital with diagnosis of deep vein thrombus two days post PCI and insertion of StaClose. One patient was readmitted to hospital five days post PCI with infected haematoma at groin insertion site. Conclusion: The nursing audit revealed a number of patients who have required close monitoring to ensure that haemostasis had been achieved after tract bleeding following the insertion of StarClose femoral arterial closure device. This has future implications on nursing time and management. 135 Predictors of Femoral Artery Pseudo Aneurysm in Interventional Cardiology T. Williams* , L. Savage, S. Fenning, J. Gordon, N. Bull, R. Prashar, S. Mylabathula, G. Bellamy, FCSANZ John Hunter Hospital, Newcastle, Australia Femoral artery Pseudoaneurysm (PA) is a complication encountered in interventional cardiology, which could have consequences. Several correlates for such complications have been reported, but little in the form of independent predictors. We studied a cohort of such complications, in order to identify factors that predict pseudoaneurysm post procedure. From 2004 to 2005, 21 PA have been identified from 3000 invasive procedures requiring femoral access. Traditional variables such as peripheral vascular disease, antiplatelet therapies, sheath size, sex, height, weight, age, closure devices, access difficulties, recent thrombolysis and diabetic state was recorded. During the same period, patients with a large femoral artery hematoma served as controls. In the study group, there were 21 patients with pseudoaneurysm, and 17 patients were controls. Independent samples t-test was performed for each of the recorded variables. No significant differences were found between the groups on any of the predictors alone. To determine if the predictors interacted to predict pseudoaneurysm logistic regression analysis was performed. A significant model was found that included height, weight, BMI and age which predicted femoral artery pseudoaneurysm with a 70% accuracy. Of the above 4 co-variates BMI was the strongest predictor. The mean BMI was 29 in the study group and 26 in the control group. BMI is an independent predictor of femoral artery pseudoaneurysm following invasive cardiac procedures, and patients with a high BMI may require additional care while following post sheath removal compression protocols.

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136 Post-Stent Chest Symptom Frequency and Characteristics R. Gallagher1 , F. Lynch2,* , M. Atrill3 , J. Fildes4 , B. James5 , B. Kandyl6 , S. Lang6 , D. Petkovski7 , T. Riley-Hendersons8 1 University

of Technology, Sydney; 2 The Sutherland Hospital; Vincents Hospital; 4 Prince of Wales Hospital; 5 Northern Sector Illawarra Health; 6 Southern Sector Illawarra Health; 7 St George Hospital; 8 Sutherland Hospital, NSW, Australia 3 St

Patients who have had coronary angioplasty and stent implantation experience varied chest symptoms postdischarge. Patients need to determine when these symptoms warrant seeking care. There is a lack of research in this area to help health staff advise patients appropriately. The aim of this study is to describe the frequency and characteristics of post-stent chest discomfort. Post-stent patients attending cardiac rehabilitation in South East Sydney and Illawarra Health service were invited to complete a survey and the McGill Pain Questionnaire (MPQ) 4 and 10 weeks following the procedure. Patients (n = 61) in the study were aged mean 62.5 years (S.D. 10.64) and mostly male (75%). Most patients had 1 stent (41.7%), which was most likely drug eluting (53.3%) and placed in the left anterior descending coronary artery (52.5%). In the 4 weeks post-stent 50% experienced chest symptoms, rated 2 (median) for discomfort on MPQ, which caused 47% of the patients to be concerned. In the time from 4 to 10 weeks post-stent 35.1% experienced chest symptoms, rated 1 (median) for mild on MPQ, which caused all patients to be concerned. Patients reporting symptoms at 4 weeks were more likely to report symptoms at 10 weeks (24.5% of total cohort) (χ2 p = .015). In conclusion post-stent chest symptoms are common and may persist to 10 weeks post-discharge. The symptoms cause patients discomfort and concern so health care professionals need to inform and support these patients. 137 Interventions by Heart Failure Nurse Specialist: Potential for Reducing Hospital Admissions A. Sullivan* , R. Cleary, G. Gillies, S. Hales, I. Pryde, V. Baker, P. Davidson, G. Tofler Management of Cardiac Function (MACARF), NSCCAHS Northern Sydney, NSW, Australia Background: Heart failure programs based on specialist nurse community follow-up have been shown to reduce readmission however the reasons are not fully understood. The purpose of this study was to determine the number and range of nurse interventions. Methods: We retrospectively reviewed 135 patients enrolled in our home-based heart failure program in 2005. Mean age was 79 years, 53% male, causes of heart failure were ischaemia (65%), hypertension (37%). Twenty-one percent had both ischaemia and hypertension. Patients received a home visit within one week of discharge and

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telephone calls (average 6) over 12 months. Nurses noted whether contact resulted in an intervention. Results: Eighty-one of the 135 patients (58%) received an intervention (total of 243 interventions). Principal interventions related to medication (69), ancillary service provision (52), and exercise prescription (46). Most interventions occurred at the home visit (104), or during other contact within1 month (64), but also from 2–6 (65) and 6–12 months (10). Forty medication interventions addressed cardiac status, including 17 for patients to take extra Lasix (7 per their nurse-educated Action Plan and 10 directed by the nurse). Assuming the 40 cardiac medication interventions prevented an admission, we estimate, based on DRG costs, a saving of $350,000. Conclusions: A heart failure nurse specialist program based on home visits and telephone calls resulted in an intervention in over 50% of patients. The most common intervention was medication-related. With assumptions related to the link between intervention and readmission, nurse specialist contact results in reduced hospital readmission and net savings exceeding program costs. 138 Who are the Frequent Fliers? Characteristics of Patients with Multiple Heart Failure Admissions R. Cleary* , A. Sullivan, G. Gillies, S. Hales, I. Pryde, V. Baker, P. Davidson, G. Tofler Management of Cardiac Function (MACARF) Program, NSCCAHS, Sydney, NSW, Australia Background: It is recognised that a small number of patients have multiple heart failure admissions. The clinical characteristics of these “frequent fliers” are not well defined, nor is the potential to reduce readmission rate. The purpose of this study was to analyse the clinical characteristics of these patients as seen in a heart failure program. Methods: We retrospectively reviewed records of 1046 patients enrolled between January 2004–December 2005 in the Northern Sydney Management of Cardiac Function (MACARF) program. Eleven patients had frequent heart failure admissions, defined as ≥3 heart failure admissions over a 12-month period. Results: Characteristics were: average age 82.3 years (range 61–94), female 64%, cause of heart failure— ischaemia 73%, hypertension 55% (both ischaemia and hypertension 27%); raised creatinine during ≥1 admission 91%; diabetes 18%; mean ejection fraction 40% (27% had EF ≥55%); non-English speaking background 27%; atrial fibrillation on ≥1 admission 45%; depression 27%; living alone 18%; death within 12 months 27%. Conclusions: Patients with multiple heart failure admissions are a heterogenous group, with a high prevalence of adverse clinical and psychosocial factors, in particular impaired renal function. They are elderly and 45% had atrial fibrillation. Although average ejection fraction was reduced, one quarter had preserved systolic function. Identification of these high-risk patients, together with a multi-disciplinary approach including access to palliative

care and specialist heart failure nurse support, may be particularly helpful and warrants further study. 139 The Development and Piloting of the Heart Awareness for Women Program: A Cardiac Rehabilitation Intervention Tailored to the Needs of Women L. Everist1,6,* , M. DiGiacomo2 , S. Tewhaiti1 , L. Rull1 , L. Warner1 , K. Lamb3 , R. Zecchin4 , A.R. Dennis5 , FCSANZ, J. Daly6 , P.M. Davidson2 , on behalf of the Heart Awareness for Women Program1 1 Cardiac

Rehabilitation, Blacktown/Mt.Druitt Hospital, Sydney West Area Health Service, Sydney, Australia; 2 Nursing Research Unit, School of Nursing, University of Western Sydney & Sydney West Area Health Service, Sydney, Australia; 3 Women’s Health Advisor, Sydney West Area Health Service, Sydney, Australia; 4 Area Cardiac Rehabilitation/Chronic Care Programs, Sydney West Area Health Service, Sydney, Australia; 5 Sydney West Area Health Service and the University of Sydney, Sydney Australia; 6 School of Nursing, University of Western Sydney, Sydney, Australia Background: The poor participation of women in cardiac rehabilitation programs (CR) is well documented. Reasons for this are multifaceted and can be attributed to system, provider and patient factors. A 6 week Heart Awareness for Women Program has been developed following an extensive review of the literature, consumer focus groups and key informant interviews. Aim: To assess the acceptability and utility of the program to address risk factor modification of women following an acute coronary event. Method: A purposive sample of women, all of whom had experienced a cardiac event and were treated in either of two hospitals in Western Sydney, Australia, were invited to attend the program. A mixed-method evaluation has been undertaken using psychometrically validated tests. Participation rates and attendance logs were monitored in addition to the conduct of semi-structured interviews. Results: To date 65 women have been enrolled with no drop outs related to dissatisfaction with the program. The capacity to offer this program to female patients has increased participation rates in the CR program. Women have positively evaluated the program and in particular valued the support derived from other women in the program. A positive impact has been demonstrated in respect of physical activity and the capacity to develop and negotiate risk factor modification goals. Conclusion: A CR program tailored to the needs of women can increase participation rates and increase the capacity of women to adjust to the diagnosis of heart disease.

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Cardiovascular Genetics 140 Polyadenine Length Variation in Estrogen Receptor Alpha 3 UTR Influences Endothelial Function: Possible Influence on Message Stability G.A. Figtree1,2,* , T. Guzik2 , B.R. Robinson1 , K. Channon2 , H. Watkins2 1 Kolling

Institute, Royal North Shore Hospital, Sydney, Australia; 2 Cardiovascular Medicine, University of Oxford, United Kingdom

The role of the 3 UTR in regulating the stability of estrogen receptor alpha (ER␣) mRNA led us to investigate for polymorphisms in this region which may influence estrogen responses in the cardiovascular system. We identified a novel variable length variation in a polyadenine tract (14–15) in a region identified as important to regulation of ER␣ mRNA stability. The allelic frequency of the variant 15 A allele was 47%. We next examined for an association between polyadenine legnth variation and endothelial-dependent vasorelaxation in a cohort of patients in whom saphenous vein had been harvested for CABG. Polyadenine genotype was significantly associated with endothelial-dependent relaxation to acetylcholine in females predicting 40.6% of the variability of relaxation in this model (p = 0.015). Females homozygous for the short allele had over a 100% increase in endothelium-dependent vasorelaxation compared with those possessing a copy of the long allele (29.7 ± 5%, n = 8; versus 14.1 ± 2%, n = 12; p < 0.01). No significant association was observed in the male subgroup (n = 70; p > 0.05). In a separate cohort, homozygosity of the short allele was associated with a 50.3% increase in endothelial-dependent vasodilation in response to metacholine influsion (measured by venous occlusion plethysmography) in females homozygous for the short allele (n = 7), compared with those with one copy of the long allele (n = 15, p < 0.05). This study has identified a novel variable repeat polymorphism in a polyadenine track important in regulating ER␣ mRNA stability. Variation in the length of the polyadenine tract, commonly observed in the population, was associated with altered endothelial function in two cohorts. 141 Leu39ter Mutation Identified in the Phospholamban Gene in a Family with Hypertrophic Cardiomyopathy C. Chiu1,* , J.M. Lind1 , J. Ingles1 , J.W. Arthur2,3 , C. Semsarian1,4 , FCSANZ 1 Agnes

Ginges Centre for Molecular Cardiology, Centenary Institute; 2 Central Clinical School, Faculty of Medicine, University of Sydney; 3 Sydney University Biological Informatics and Technology Centre; 4 Department of Cardiology, Royal Prince Alfred Hospital (RPAH), NSW, Australia Purpose: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder. Genetic screening of the eight most common sarcomeric genes in HCM, results in no

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mutation being identified in up to 60% of cases, indicating other genes are involved. Given the role of calcium homeostasis in the pathogenesis of HCM, this study screened the phospholamban (PLB) gene for causative mutations in a large HCM cohort. Methods: Patients referred to the HCM Clinic at RPAH, Sydney were included in this study. Genomic DNA was extracted and the coding exon of the PLB gene was amplified by PCR and products were screened for sequence variants using high-performance liquid chromatography, followed by direct DNA sequencing and/or restriction enzyme digestion in selected cases. Results: From 308 HCM probands studied, one sequence variant was identified in a 65-year-old female patient with mild clinical disease. The variant changed a conserved amino acid at codon 39 from a leucine to a termination codon (Leu39Stop), resulting in a truncated protein, which is predicted to disrupt its interaction with SERCA. The patient was heterozygous for the PLB mutation. This variant was not identified in over 100 healthy controls. No other variants were identified in the PLB gene in the remaining probands. Conclusion: The heterozygous Leu39Stop mutation in the PLB gene is a rare mutation that leads to the development of HCM. Previous studies have shown individuals homozygous for this mutation develop dilated cardiomyopathy. These findings strongly suggest PLB function and regulation of calcium homeostasis are important in the pathogenesis of cardiomyopathies. PLB should therefore be considered as a candidate gene when screening HCM cohorts. 142 Clinical and Genetic Studies in Families with Left Ventricular Noncompaction Natalie Cochrane1,* , Jodie Ingles1 , Joanne M. Lind1 , Christine Chiu1 , Robert Weintraub2 , FCSANZ, Christopher Semsarian1,3 , FCSANZ 1 Agnes

Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia; 2 Department of Cardiology, Royal Children’s Hospital, Melbourne, Australia; 3 Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Background: Left ventricular noncompaction (LVNC) is a rare cardiomyopathy caused by an arrest in cardiac morphogenesis. The clinical phenotype and genetic basis of LVNC are not well understood. Genes involved in cardiac development have been implicated in LVNC pathogenesis however the majority of causative mutations remain unknown. Methods: Seven unrelated families with LVNC were clinically assessed and investigated by ECG, 2Dechocardiography and MRI (in adult cases). Genetic screening of three candidate genes, G4.5, Nkx2.5 and GATA4, was performed using direct DNA sequencing in the family probands. Results: Isolated adult-onset LVNC was identified in three probands and suspected in two probands, while paediatric

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LVNC was diagnosed in the remaining two probands, one of which had associated congenital heart disease. Marked clinical heterogeneity was observed, including age of onset (1 month–77 years), clinical presentation (asymptomatic to cardiac arrest), presence of ECG abnormalities and clinical outcome (asymptomatic to heart failure and sudden death). No disease-causing mutations were found in the three candidate genes studied. During the course of the study, the R302Q mutation in the PRKAG2 gene, known to cause glycogen storage disease, was identified in one of the families. The R302Q mutation caused clinically variable disease within this family including hypertrophy and LVNC. Conclusion: Clinical heterogeneity is an important feature in families with LVNC. Mutations in cardiac development genes may be a cause of LVNC, although this was not observed in our small cohort. Further clinical and genetic studies of LVNC families are likely to enhance our understanding of disease pathogenesis, and improve both our diagnostic and clinical management of this rare cardiomyopathy. 143 Postmortem Molecular Analysis of Sudden Unexplained Death in Young Australians Alessandra Doolan1,* , Neil Langlois2 , Christine Chiu1 , Jodie Ingles1 , Joanne M. Lind1 , Christopher Semsarian1,3 , FCSANZ 1 Agnes

Ginges Centre for Molecular Cardiology, Centenary Institute; 2 Department of Forensic Medicine, Westmead Hospital; 3 Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Background: The cause of sudden death in young people remains unknown in up to 50%. Mutations in the ion channel genes, KCNQ1 and SCN5A, are known to cause arrhythmogenic disorders such as long QT and Brugada syndromes, which can present with sudden death and a negative autopsy. The aim of this study was to determine whether inherited arrhythmogenic disorders account for a proportion of young sudden unexplained death. Methods: From 1994–2002, 59 sudden unexplained deaths occurring in Australians aged ≤35 years with a negative autopsy were included. Genomic DNA was extracted from paraffin-embedded tissue. Genetic analysis of KCNQ1 and SCN5A was performed using denaturing HPLC and direct DNA sequencing. All sequence variants were confirmed using DNA extracted from an alternative tissue. Results: Nine DNA sequence variants were identified in KCNQ1 and 9 sequence variants in SCN5A. Eight of these variants were in coding exons (Table), one of which (His558Arg) changed the amino acid sequence. In total, 23 of 59 cases were found to have at least one DNA variant in KCNQ1 or SCN5A, with 12 having two or more. None of the DNA variants were determined to be diseasecausing as they were also identified in control populations. In addition to the confirmed variants, false sequence variants were identified due to formalin fixation used in postmortem tissue.

Abstracts

Gene

Region

Nucleotide

KCNQ1

Exon 13

G>A

Ser546Ser

Exon 16

C>T

Tyr662Tyr

Exon 12

A>G

His558Arg

Exon 17

A>G

Glu1065Glu

Exon 23

G>A

Val1382Val

Exon 23

G>A

Gly1410Gly

Exon 23

G>A

Glyl412Gly

Exon 28

T>C

Asp1823Asp

SCN5A

Amino Acid

Conclusion: No disease-causing mutations were found in KCNQ1 or SCN5A in this cohort. The DNA variants found may modify symptoms when inherited with a diseasecausing mutation. A more selective screening approach, including only individuals with a clinical or family history, may yield a higher mutation pick-up rate in sudden unexplained deaths. 144 Association of the Androgen Receptor Gene (CAG)n Repeat Region with Severity of Left Ventricular Hypertrophy in Males with Hypertrophic Cardiomyopathy Joanne M. Lind1,* , Christine Chiu1 , Jodie Ingles1 , Alison K. Heather2 , Christopher Semsarian1,3 , FCSANZ 1 Agnes

Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia; 2 Gene Regulation Group, The Heart Research Institute, Sydney, Australia; 3 Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia Background: Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder characterised by thickening of the left ventricular wall. Gender is known to be a risk factor in the incidence and severity of HCM, with males developing more severe disease. We sought to investigate an association between the length of the (CAG)n repeat region in the androgen receptor gene (AR), with the severity of hypertrophy in HCM patients. Methods: Patients referred to the HCM clinic at RPAH, Sydney, with definite HCM were included in this study. Maximal left ventricular wall thickness (LVWT) was measured by 2D-echocardiography. Genomic DNA was extracted from blood and PCR was performed to amplify the (CAG)n repeat region in the AR gene. Fragment length was determined using GeneScan. Results: A total of 210 HCM probands, 128 males and 82 females, were studied. The mean LVWT was not significantly different between males (21.4 ± 0.5 mm) and females (20.7 ± 0.7 mm). The mean number of CAG repeats was 21.8 in both males (range 15–29) and females (range 13–30). A significant association was found between the number of CAG repeats and the extent of hypertrophy in males (P = 0.007). For every increase of one repeat, wall thickness decreased by 0.5 mm. No association was observed in females. Conclusion: The length of the (CAG)n repeat region is inversely associated with the severity of hypertrophy in

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male HCM patients. Previous reports have shown that AR activity is inversely associated with the length of this region. AR activity may be important in the development and progression of hypertrophy in male HCM patients. Understanding the role of androgens in HCM pathogenesis is likely to improve risk stratification and clinical management. 145 Association of the Y Chromosome with Risk Factors for Sudden Cardiac Death in Males with Hypertrophic Cardiomyopathy Joanne M. Lind1,* , Trevor Kwok1 , Emily Tu1 , Jodie Ingles1 , Christopher Semsarian1,2 , FCSANZ 1 Agnes

Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia; 2 Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia Background: Analysis of single nucleotide polymorphisms (SNPs) on the non-recombining region of the Y chromosome allows males to be assigned to a Y haplogroup. The aim of the present study was to examine whether the predominant Y haplogroup in European males (haplogroup R) is associated with risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). Methods: Male patients referred to the HCM clinic, RPAH, Sydney, with definite HCM were included in this study. Data on the incidence of sudden cardiac death events was obtained. The Y chromosome SNP (m170), which defines haplogroup R males, was amplified from genomic DNA using PCR followed by restriction enzyme digestion. Ambulatory 24-h ECG monitoring and 2Dechocardiography were performed to measure presence of non-sustained ventricular tachycardia (NSVT) and maximal left ventricular wall thickness, respectively. Results: A total of 145 male HCM probands were studied, 63% of which belonged to haplogroup R. NSVT was found to be significantly associated with Y haplogroup (P = 0.008), where 93% of males with NSVT belonged to haplogroup R (Odds ratio 10.71, 95% CI 1.35–84.98). No association was found between other risk factors of sudden cardiac death and Y haplogroup, in particular, severity of hypertrophy and incidence of sudden cardiac death events. Conclusion: Male HCM patients with a Y chromosome belonging to haplogroup R are more susceptible to NSVT. These results suggest the haplogroup R, Y chromsome, may be a marker for risk of sudden cardiac death in males, and may therefore further refine the risk stratification process in patients with HCM.

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146 Lack of Association Between ZASP/LDB3 Gene Mutations and Dilated Cardiomyopathy with Conduction System Disease M. Leticia Castro1 , Robyn Otway1 , Guanglan Guo1 , Haley Crotty1 , Olivia Baddeley1 , Christopher Hayward2 , FCSANZ, Anne Keogh2 , FCSANZ, Peter MacDonald2 , FCSANZ, Diane Fatkin1,* , FCSANZ 1 Molecular

Cardiology Program, VCCRI, Darlinghurst; Transplant Unit, St Vincent’s Hospital, Darlinghurst, NSW, Australia

2 Cardiac

Dilated cardiomyopathy (DCM) is a myocardial disorder characterised by dilation and contractile dysfunction of the left ± right ventricles. Heart failure as a result of DCM is a major cause of morbidity and mortality in our society. DCM can occur as an isolated disorder or can be associated with conduction-system disease (CD). Recently, it has been recognised that inherited gene defects account for a significant proportion of DCM cases. ZASP (Z-band alternatively spliced PDZ-motif) reinforces protein interactions at the myofibril Z-line and connects the sarcomere to the cytoskeletal network. Deficiency of ZASP/LDB3 in mice results in a severe form of congenital cardiomyopathy, and mutations in ZASP/LDB3 have been identified in individuals with familial and sporadic DCM ± CD. In order to evaluate the prevalence of mutations in ZASP/LDB3 as a cause of familial DCM + CD we evaluated the ZASP/LDB3 gene for mutations in probands from 42 families. Sixteen exons of the ZASP/LDB3 gene were amplified by PCR and evaluated by sequence analysis. We identified five synonymous exonic variants and 13 intronic variants. No disease-causing mutations were found. Although further screening in a larger patient population is warranted, our data indicate that ZASP/LDB3 mutations are not a common cause of DCM + CD. 147 Heme Oxygenase-1 Genotype is Associated with Coronary Artery Disease in a Caucasian Population S. Mukherjee* , A.J. White, A. Natoli, B.A. Kingwell, A.S. Walton, FCSANZ, A.M. Dart, FCSANZ, S.J. Duffy, FCSANZ Alfred & Baker Medical Unit, The Alfred Hospital & Baker Heart Research Institute, Melbourne, Australia Background: Oxidative stress is associated with atherosclerosis and is higher in patients with acute coronary syndromes. Heme oxygenase-1 (HO-1) is a heme degradation enzyme considered to be vascular protective as a result of its potent antioxidant and antiinflammatory effects observed in consort with vascular risk factors and established atherosclerotic disease. Compared with long (L) (GT)n repeats (≥25), short (S) (GT)n

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(<25) repeats in the HO-1 gene promoter show highly significant up-regulation of HO-1 to oxidative stress and have been associated with protection from coronary artery disease in a Japanese population. However, this effect was not shown in a Caucasian population. We hypothesized that SS homozygotes would be more prevalent in healthy Caucasian individuals compared to a matched group with established coronary disease. Methods: Patients with de novo, angiographically confirmed coronary artery disease (maximum stenosis ≥50%) were studied (n = 179, 64 ± 12 years; mean ± S.D.). A matched, healthy control group was recruited from the community (n = 125, 62 ± 10 years). Patients were genotyped and classified as S/S, S/L or L/L. Results: There was no difference in age or sex ratio between the three genotypes. The prevalence of S/S homozygotes was over double in healthy individuals than in patients with established coronary disease (15% versus 6%, P = 0.01). In contrast to the previous Japanese study, this difference was lost when the data was analysed as an S dominant model (i.e. grouping S/S and S/L together). Conclusion: This is the first time that the S/S genotype of the HO-1 promoter polymorphism has been associated with relative cardiovascular protection in a Caucasian population. While this effect was dominant in Japanese, the protective effect appears to be recessive in Caucasians. 148 Evaluation of TRPC1, a Mechanosensitive Ion Channel, as a Candidate Gene for Familial Atrial Fibrillation Clive Yu1 , Robyn Otway1 , Bruce Walker2 , Dennis Kuchar2 , FCSANZ, Charles Thorburn2 , Diane Fatkin1,2,* , FCSANZ 1 Molecular

Cardiology Program, Victor Chang Cardiac Research Institute; 2 Cardiology Department, St Vincent’s Hospital, Darlinghurst, NSW, Australia Atrial Fibrillation (AF) is the most common cardiac arrhythmia and a major source of morbidity and mortality. Four-disease causing genes have recently been identified, however current data suggests that the prevalence of mutations in these genes is low. Further gene discovery studies are required. The TRP (transient receptor potential) family of genes encodes ion channels that act as cellular sensors in diverse tissues. Defective function of TRP genes is increasingly becoming linked to diseases. TRPC1 was recently shown to be the mechanosensitive cation channel in vertebrates and is expressed in the heart. GsMtx-4, a tarantula toxin and non-selective cation channel inhibitor, prevents AF in vitro. We hypothesised that TRPC1 could be a candidate gene for familial AF. DNA sequence analysis of the coding region of the TRPC1 gene was performed in probands from 50 families. No disease-causing mutations were found. One nonsynonymous variant, A14T, was identified in two families.

However, this variant did not segregate with disease status in family members and was present in eight population control samples. Although further screening in a larger patient population is warranted, our data indicate that TRPC1 is unlikely to be a common cause of familial AF. Evaluation of other TRP family members in familial AF is warranted.

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p = 0.003). An incremental increase in the proportion with RV dysfunction (RV S < 10 cm/s) was seen with advancing diastolic dysfunction (4% in NF versus 17% in RF, p = 0.009). Conclusion: In patients with preserved systolic function, PASP is normal in those with mild diastolic dysfunction. Increased PA pressure develops during the PSN stage and PVR increases at the RF stage. RV dysfunction is uncommon and associated with RF and increased PASP and PVR.

Figure 1.

Clinical Cardiology 149 Prevalence and Severity of Pulmonary Vascular Disease in Diastolic Dysfunction with Preserved Left Ventricular Function N. Mai* , T.H. Marwick, FCSANZ Princess Alexandra Hospital, University of Queensland, Brisbane, Qld. Australia Pulmonary hypertension and RV dysfunction are adverse prognostic features in heart failure. Their prevalence and determinants in diastolic dysfunction are unclear. We sought to define their prevalence according to the degree of diastolic filling abnormalities and myocardial characteristics. Methods: In an unselected population, we classified 1008 consecutive pts with preserved LV systolic function according to diastolic filling abnormality; normal filling (NF), delayed relaxation (DR), pseudonormal filling (PSN) and restrictive filling (RF). PASP, pulmonary vascular resistance (PVR) and RV function (RV S ) were measured. Between-group comparisons were made by ANOVA and comparison between categories was made by chi-square. Results: The prevalence of NF, DR, PSN and RF were, respectively, 39%, 35%, 22% and 4%. Fig. 1 shows mean PASP is greatest in those with increased filling pressure (p < 0.0001). Prevalence of increased PASP was 36% in PSN and 41% in RF versus 20% in NF and 17% in AR (NF versus PSN p = 0.001; NF versus RF p = 0.01). Fig. 2 shows PVR to be greater in RF than all other groups (2.4 versus 1.7 Wood units, p = 0.01). Prevalence of increased PVR was higher in RF (79%) than NF (38%), DR (29%) and PSN (41%,

150 Pregnancy: What Really Happens to Cardiovascular Function? D. Zentner1,4,* , M. du Plessis1 , J. Wong1 , S. Brennecke2,3 , L. Grigg1 , S. Harrap4 1 Department of Cardiology, Royal Melbourne Hospital, Parkville, Australia; 2 Department of Perinatal Medicine, Royal Womens’ Hospital, Carlton, Australia; 3 Department of Obstetrics and Gynecology, University of Melbourne, Parkville, Australia; 4 Department of Physiology, University of Melbourne, Parkville, Vic., Australia Background and aims: Pregnancy is understood to involve maternal cardiovascular adaptation. However, many studies are small, utilised invasive methodology or inadequately rested subjects before hemodynamic measures. We sought to determine cardiovascular function in appropriately rested women non-invasively. Methodology: In 10 non-pregnant (NP) women (follicular phase, menstrual cycle) and 100 women in early pregnancy (EP: median gestation 16 weeks) we used echocardiography with TDI (Vivid 7, GE) and pulse wave analysis (Sphygmocor, AtCor Medical) to determine parameters of myocardial function and aortic systolic blood pressure (aSBP). A cohort of 32 representative women was reassessed in late pregnancy (LP: median gestation 37 weeks). Measures include cardiac output (CO), septal wall TDI during systole (S ) and early diastole (E ), preload (E/E ) and left ventricular afterload (MWS). Statistics: Statistics are expressed as median and interquartile range (IQR), with group comparisons made using non-parametric tests with statistical significance at 2p < 0.05. Results: NP and P women were well matched for age, weight, height (data not shown).

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Conclusion: Cardiovascular adaptation to P is characterized by an early increase in HR and contractility. The resulting CO increase predates changes in maternal weight (data not shown). Preload remains normal. Wall stress increases, particularly in LP at which time myocardial velocities (S , E ) fall to NP levels. The LP decrease in function provides a framework for understanding pathological states such as peripartum cardiomyopathy. 151 Body Mass Index is an Independent Determinant of Left Atrial Size in Adults and Children J.G.J. Ayer* , H. Almafragy, A. Patel, FCSANZ, G. Sholler, FCSANZ, D.S. Celermajer, FCSANZ Department of Cardiology, Royal Prince Alfred Hospital and The Adolph Basser Cardiac Institute, The Children’s Hospital at Westmead, Sydney, Australia The incidence of both atrial fibrillation (AF) and obesity have increased markedly over the last 25 years. As obesity is an important risk factor for AF, we hypothesised an independent relationship between body mass index (BMI) and left atrial (LA) size and that LA enlargement might mediate the association between obesity and AF. Methods: Two studies were undertaken: Adults: Consecutive ambulatory patients without ventricular dysfunction or mitral valve disease underwent echocardiography (n = 2685), including LA area, LV dimensions and LVPW thickness. Children: As childhood obesity is less often associated with potentially confounding co-morbidities, we then studied 55 obese children (BMI Z-score >2.0, age 5–15 years) with normal cardiac structure and function.

Results: In adults (age 46 ± 18 years, BMI 27 ± 6, 55% male), LA size was 18.5 ± 4.3 cm2 in those with normal BMI, 20.9 ± 4.8 cm2 in the overweight and 22.3 ± 4.9 cm2 in the obese (p < 0.001). Univariate predictors of LA size were BMI (r = 0.35, p < 0.0001), LVEDD (r = 0.42 p < 0.0001), LVPW thickness (r = 0.32, p < 0.0001), age (r = 0.24, p < 0.0001) and sex (r = 0.24, p < 0.0001). On multivariate analysis, BMI was independently associated with LA area (β = 0.12, p < 0.001). In obese children, height-indexed LA size was associated with weight on univariate analysis (r = 0.22, p < 0.0001). This association remained significant after accounting for LVEDD and LVPW thickness. Conclusions: In adults and obese children, BMI shows a significant, continuous and independent association with LA size, likely contributing to the higher risk of AF in overweight and obese subjects. 152 Impact of Patient Flow Unit on Adverse Events Reduction in Patients admitted to Regional Centres for Urgent Pacemaker Implantation C. Hiew* , P. Diu, S. Mylabathula, S. Adera, J. Morrow, P. Fletcher, FCSANZ Cardiovascular Department, John Hunter Hospital, Newcastle, NSW, Australia Introduction: Patients from regional based hospitals requiring urgent pacemaker implantation have been shown to have more adverse events than similar patients admitted to tertiary cardiac centres. Such differences are largely attributed to prolong waiting time. Limited measures were available to overcome such challenges.

Abstracts

Aim: Area-wide Patient Flow Unit (PFU) has been created as a pilot program to coordinate inter-hospital transfer and monitor any potential ‘early warning signs’ of adverse events. We aim to determine its impact on waiting time and adverse events. Methods: Data were collected from ninety-three consecutive patients transferred from regional hospitals to our institution for urgent permanent pacemaker implantation. Forty-six patients were admitted before and forty-seven were admitted after PFU commenced. Results: There was no significant difference in terms of age, co-morbidities or indications for pacing between the two groups. There was a significant reduction in time spent in regional hospitals, waiting time for procedures and total adverse events since PFU was introduced. Significant reduction in adverse events include: urinary tract infection, congestive heart failure and ambulation difficulties. Variables

Pre-PFU (n = 46)

Post-PFU (n = 47)

P-value

Regional hospitals stay (days)

5.9 ± 3.5

4.2 ± 4.5

0.04

PPM Waiting time (days)

8.8 ± 4.6

6.6 ± 5.0

0.03

Total adverse events

76

39

0.0001

UTI

10

3

0.02

CCF

13

6

0.04

Ambulation difficulties

16

6

0.009

Conclusions: Early transfer for urgent pacemaker implantation is associated with less morbidity. PFU appears to be a promising solution for facilitating inter-hospital transfer leading to reduced procedure waiting time and adverse events.

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153 Non-Invasive Arterial Pressure is a Poor Surrogate of Cardiac and Vascular Function in Elite Athletes at Rest and After Moderately Increased Oxygen Demand R.A. Phillips1,* , K. Knobloch2 , J.F. Fraser1 , D.J. Burstow1 , FCSANZ, M.J. West1 , FCSANZ 1 Department of Medicine, University of Queensland, Brisbane,

Australia; 2 Trauma Surgery Department, Medical School, Hannover, Germany Background: Arterial pulse pressure has recently been proposed as a method for objective assessment of cardiovascular performance despite the dissociation of vascular and cardiac function. This is particularly important in sepsis, where oxygen supply demand mismatches require focus on discrete cardiac or vascular therapies. This study was to compare non-invasive arterial pressures with CW Doppler ultrasound determined cardiac output (CO) and systemic vascular resistance (SVR) in elite athletes at baseline and after increased oxygen demand induced by incremental exercise. Method: Baseline sphygmomanometric blood pressures (BP) and transaortic Doppler COs (COuscom) were acquired contemporaneously in 26 elite rowers at rest. Measures were repeated after achieving 52%, 62% and 72% of peak oxygen consumption and mean arterial pressures (MAP) were compared to COuscom and SVRuscom using paired sample t-tests and linear regression. Results: MAP poorly correlated with SVR, HR, SV, CO and CI over 77 paired measures. MAP vs. SVR

MAP vs. HR

MAP vs. SV

MAP vs. CO

MAP vs. CI

r −0.216

0.219

0.302

0.322

0.287

0.059

0.056

0.008

0.004

0.011

p

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Conclusion: Arterial pressures showed poor correlation with CO and SVR at baseline and during increased oxygen consumption, suggesting that arterial pulse pressure measurement is a poor physiologic analogue of either cardiac or vascular function.

USCOM may be a non-invasive alternative to PAC for measurement and monitoring of haemodynamics in animals and humans. Table. Correlation with FP Measures

154 Measurement of CO by Flow Probe, CW Doppler and Pac in Conscious Sheep at Rest and after Dobutamine

USCOM 0.925 PAC 0.114

Sheep 1 Sheep 2 Sheep 3 Sheep 4 Sheep 5 Total 0.764 0.722

0.850 0.818

0.528 0.517

0.659 0.207

0.745 0.323

R.A. Phillips1,2,3,* , S.G. Hood1,2,3 , B.M. Jacobson1,2,3 , P.R. Lichtenthal1,2,3 , D.J. Burstow1,2,3 , FCSANZ, M.J. West1,2,3 , FCSANZ, C.N. May1,2,3

155 Ezetimibe in the ‘Real World’: The COACH Program Experience

1 The University of Queensland, Brisbane, Australia; 2 The University of Arizona, Tucson, USA; 3 The Howard Florey Institute, Melbourne, Australia

K. O’Grady* , M.V. Jelinek, FCSANZ, J.D. Best, J.P. Di Giulio, M.J. Vale

The PAC remains in clinical use as a measure of CO and haemodynamic trends, despite reports of inefficacy and associated patient risk. The flow probe (FP) is an accurate measure of haemodynamics but is restricted to animal use by the necessity for surgical implantation. The USCOM device (USCOM Ltd., Sydney, Australia) is a novel noninvasive 2D independent Doppler device specialised for measurement of CO and haemodynamic change. This study was to compare USCOM and the PAC Baxter intermittent thermodilution system (PAC) with FP measurement of baseline CO and dobutamine induced changes in conscious sheep. FPs were implanted on the ascending thoracic aorta of five sheep, and after 2 weeks recovery, a PAC was inserted. In conscious sheep, transcutaneous trans-pulmonary USCOM signals were acquired and calibrated at baseline to the FP as USCOM calculates flow volumes from a human anthropometric algorithm. Simultaneous FP, USCOM and PAC signals were acquired at baseline and after dobutamine (5, 10 and 20 mg/h). FP and PAC signals were acquired to spike two software and the Doppler data recorded on the USCOM device. Mean values for baseline measures by FP (n = 862), USCOM (n = 829) and PAC (n = 741) were 4.26 ± 0.67 l/min, 4.51 ± 0.90 l/min and 5.34 ± 1.26 l/min, respectively, increasing to 5.33 ± 1.55 l/min, 5.25 ± 1.45 l/min and 6.09 ± 1.61 l/min after dobutamine infusion. Mean error between paired FP and USCOM measures at baseline was 5.5%, and between FP and PAC 20.4%, and after dobutamine was 0.6% and 17.9%. For all measures FP and USCOM showed good correlation (r = 0.745), while FP and PAC poorly correlated (r = 0.323).

Department of Cardiology and The University of Melbourne Department of Medicine, St. Vincent’s Hospital Melbourne, Melbourne, Vic., Australia Aim: To measure the “real world” impact of ezetimibe as prescribed according to Pharmaceutical Benefits Scheme (PBS) criteria. Methods: Ezetimibe became available on the PBS on August 1, 2004. The COACH Program which coaches patients with coronary heart disease on lipid prescribing to meet the National Heart Foundation of Australia’s (NHFA) targets for secondary prevention has monitored the impact of this new medication in 64 patients who needed the addition of ezetimibe to reach NHFA targets, and 15 patients who were intolerant of statins and took ezetimibe alone. The lipid profiles of these patients before and after ezetimibe therapy were compared by paired t-tests. Results: Table 1. Patients on Ezetimibe Plus Statin Lipids Total cholesterol Triglyceride HDL-cholesterol LDL-cholesterol

Pre-Ezetimibe (mmol/L)

Post-Ezetimibe (mmol/L)

Paired Difference (mmol/L)

P

5.16 1.92 1.36 2.91

4.34 1.62 1.44 2.09

↓ 0.81 ↓ 0.30 ↑ 0.05 ↓ 0.79

0.0001 0.0008 0.03 0.0001

Pre-Ezetimibe (mmol/L)

Post-Ezetimibe (mmol/L)

Paired Difference (mmol/L)

P

5.14 1.64 1.32 3.03

5.08 1.62 1.53 2.78

↓ 0.06 ↓ 0.02 ↑ 0.20 ↓ 0.16

0.8535 0.9102 0.0824 0.6445

Table 2. Patients on Ezetimibe Only Lipids Total cholesterol Triglyceride HDL-cholesterol LDL-cholesterol

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Conclusion: The combination of statin and ezetimibe has a large favourable impact on all lipid moieties. Ezetimibe alone has no measurable impact but there is a trend for ezetimibe to raise HDL-cholesterol.

157 The Effect of Statin Therapy on the Progression of Aortic Valve Sclerosis: A Retrospective Study

156 Utility of Transoesophageal Echocardiography in Staphylococcal Sepsis

University of Queensland, Brisbane, Australia

N. Collins, M. Sharma, C. Hiew* , S. Adera, P. Hayes Cardiovascular Unit, John Hunter Hospital, Newcastle, NSW, Australia Background: Infective endocarditis is common in staphylococcus aureus bacteraemia. The incidence of infective endocarditis in patients with staphylococcal sepsis is up to 64%. Transoesophageal echocardiography (TOE) has been recommended to exclude the presence of endocarditis in patients with staphylococcal bacteraemia. Methods: We assessed the role of TOE in diagnosing endocarditis in patients with staphylococcal sepsis. We reviewed all patients who underwent TOE for evaluation of staphylococcal bacteraemia over a 12 months period. We excluded patients with mechanical valve prostheses and those with staphylococcal endocarditis as the primary diagnosis. Thus, we sought to evaluate the incidence of occult staphylococcal endocarditis in patients with staphylococcal bacteraemia. Results: Fifty transoesophageal echocardiograms were performed for this indication, in the time period January 2003 to December 2004. Of the 50 patients who underwent TOE, five yielded a positive result. In all five patients, there were a number of high risk features present. Patient #1

Persistent fever despite antibiotic therapy

K. Kostner* , FCSANZ, Y. Liu, T. Marwick, FCSANZ

Background: Recent retrospective studies have suggested that the treatment with HMG CoA reductase inhibitors (statins) can slow the progression of aortic valve calcification. Data on the effectiveness of statins on the hemodynamic progression of aortic sclerosis (ASC) are scarce. We sought to identify whether statins can delay the progression of aortic sclerosis. Methods and results: The medical notes of a total of 106 consecutive patients (mean age 69 ± 8 years) with ASC and two separate echocardiograms, at least six months apart (mean follow-up 21 ± 11 months) were retrospectively reviewed. Patients with rheumatic valve lesions, previous aortic valve surgery, reduced left ventricular function (EF < 30%), obstructive cardiomyopathy and renal/liver transplantation were excluded. Of the 106 patients identified, 57 were treated with a statin, and 49 received no statin therapy. The outcome measure of annualised increase in aortic valve peak velocity for the entire group was 0.07 ± 0.20 m/s/year. Patients treated with statins experienced a significantly lower annualized increase in aortic valve peak velocity (0.028 ± 0.19 m/s/year) than the nonstatin group (0.12 ± 0.20 m/s/year, P = 0.04). Furthermore, stepwise multiple linear regression modeling identified a history of hypercholesterolaemia and statin use to be independent predictors of ASC progression. Conclusion: Statins therapy significantly reduced the haemodynamic progression of aortic sclerosis as measured by annualized increase in aortic valve peak velocity.

Central venous access

158 Reduced Tricuspid Annular Motion and Right Ventricular Myocardial Tissue Velocities Predict the Extent and Resolution of Acute Pulmonary Embolism

Patient #3

Central venous access

T. Chung1,* , L. Emmett2 , L. Kritharides1 , FCSANZ

Patient #4

Renal failure

1 Department

Intravenous drug use Patient #2

Renal failure

Central venous access Patient #5

Persistent fever despite antibiotic therapy Vascular bypass graft

Conclusions: Transoesophageal echocardiography should be reserved for patients in whom there are high risk clinical features in order to opitmise the yield of this diagnostic modality and would not recommend routine transoesophageal echocardiography for further evaluation of staphylococcal sepsis.

of Cardiology, Concord Hospital, ANZAC Research Institute, University of Sydney, NSW, Australia; 2 Department of Nuclear Medicine, Concord Hospital, ANZAC Research Institute, University of Sydney, NSW, Australia Background: Acute pulmonary embolism (PE) which is extensive or associated with right ventricular (RV) dysfunction has an adverse prognosis. Novel echocardiographic (TTE) parameters of RV longitudinal function (tricuspid annular motion (TAM) and RV myocardial velocities: early-diastolic (Em), late-diastolic (Am) and peaksystolic (Sm)) may be sensitive measures of PE extent and predict PE resolution.

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Methods: Thirty patients (age 63 ± 18 years) with acute PE were prospectively investigated with TTE on day 1, 2, 5, 42, 84 and 182 of diagnosis. The extent of pulmonary artery obstruction was quantified on day 1 and 42 by ventilation/perfusion (VQ) pulmonary scintigraphy. Results: The extent of pulmonary artery obstruction strongly correlated by univariate analysis with multiple conventional and novel parameters of RV size and function (not shown). Multivariate stepwise analysis identified TAM (p = 0.004), RV basal Am (p = 0.008) and right to left atrial area ratio (p = 0.03) as the strongest independent, predictors of the extent of obstruction, with a combined correlation R2 = 0.59 (p < 0.0001). Incomplete PE resolution at day 42 (13/25 patients) was associated with lower day 1 RV basal Sm (7.6 ± 2.0 cm/s versus 10.9 ± 1.9 cm/s, p = 0.0003) and TAM (1.8 ± 0.5 cm versus 2.5 ± 0.4 cm, p = 0.003). Day 1 RV basal Sm <8.3 cm/s and TAM <2.3 cm cut-points had sensitivities, specificities, positive predictive and negative predictive values of 77, 100, 77, and 100% and 77, 75, 69 and 75%, respectively, in predicting incomplete PE resolution at day 42. Conclusion: TAM and RV myocardial velocities predict the extent and resolution of PE, potentially guiding the intensity and duration of treatment; improving patient outcomes. 159 Current trends in Infective Endocarditis – From Acute Illness to Delayed Sequelae South Auckland Perspective Govind Srinivasan* , Daniel Lin, Tim Sutton, FCSANZ Dept of Cardiology, Middlemore Hospital, Auckland, New Zealand Introduction: Infective Endocarditis (IE) is usually fatal if not treated aggressively with prolonged antibiotic therapy with/without surgery. Prolonged follow up data is sparse. We sought to review patients with IE, their presenting illness and outcome. Methods: The cases were identified from discharge coding. Notes were systematically reviewed, acquiring data on demographics, co-morbidities, presentation, microbiology, echocardiography, treatment and outcome. Results: One hundred and three adult patients met criteria for probable or confirmed IE from 2000 to 2005. Age distribution was bimodal. Male female ratio was 1.5:1. Thirty percent Pacific Islanders, 44% European, 17% Maori and 9% Asian. Fifty-five percent had no known pre-existent valve lesion, 26% of affected valves were prosthetic. Nine percent were on haemodialysis and 4% were IVDU. Streptococci were the predominant bacteria (47%) then Staphylococci (31%) and Enterococci (12%). Pyrexia was the commonest presentation (51%), 16% heart failure and 19% musculoskeletal symptoms. TOE was the mode of imag-

Heart, Lung and Circulation 2006;15S:S1–S167

ing in the majority (71%). Thirty-three percent underwent surgery as an inpatient and 8% needed valve surgery within a year post-discharge. 2/3 of medically treated patients received home IV therapy. Mortality at 1 year was 8%. Conclusions: • Contrary to reported international trends, over the last 15 years the microbiology of endocarditis has not changed at our institute. • Prosthetic valve IE has a relatively high incidence in our population. • Pacific Islanders have a higher incidence of IE than expected. • With current therapy our mortality rates are lower than historical data. • The high rate of deferred operation for consequences of IE stresses the need for close follow up of these patients. 160 Carotid IMT and Indices of Arterial Stiffness and Compliance: Do They Predict Cardiovascular Outcome in Patients with Chronic Renal Failure? S. Zoungas1,* , J. Cameron1 , FCSANZ, P. Kerr3 , R. Wolfe2 , C. Muske2 , J. McNeil2 , B. McGrath1 , FCSANZ 1 Centre

for Vascular Health, Monash University, Dandenong Hospital, Dandenong; 2 Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Prahran; 3 Department of Nephrology, Monash Medical Centre, Clayton, Vic., Australia The predictive value of carotid arterial intima-medial thickness (IMT) and indices of arterial function [pulse wave velocity (PWV a-f) systemic arterial compliance (SAC), and arterial pressure augmentation index (AIx )] for cardiovascular events, was assessed in patients with chronic renal failure (CRF) enrolled in the Atherosclerosis and Folic acid Supplementation Trial. Three hundred and fifteen subjects with CRF, aged 24 to 79 (mean ± S.D.: 56.6 ± 13.6 years), were followed for a median of 3.6 years and underwent annual B-mode ultrasound measurement of carotid IMT. A subgroup (n = 207) had baseline and sequential measurements of PWV (a-f), SAC and AIx . During follow up, 95 fatal and non-fatal cardiovascular events occurred. On univariate analysis baseline mean maximum IMT, PWV (a-f) and SAC were all predictors of survival, but AIx was not. The risk of cardiovascular events increased with increasing tertile of IMT [RR 2.8, p < 0.001, 95% CI: 1.6, 4.9] and PWV (a-f) [RR 4.8, p < 0.001, 95% CI: 2.3, 9.9], and decreasing tertile of SAC [RR 0.3, p = 0.002, 95% CI: 0.2, 0.7]. After adjustment for age, gender, mean blood pressure,

diabetes and past history of cardiovascular disease, SAC remained a significant predictor of cardiovascular events (adjusted RR 0.51, p = 0.03, 95% CI: 0.28, 0.94) but IMT and PWV (a-f) did not (IMT: adjusted RR 0.98, p = 0.94, 95% CI: 0.57, 1.68; PWV (a-f): adjusted RR 1.46, p = 0.26, 95% CI: 0.75, 2.84). SAC is an independent predictor of cardiovascular outcome in patients with CRF but carotid IMT, PWV (a-f) and AIx are not. 161 Effects of Insulin on L-Arginine Transport in the Human Forearm A. Chong1,* , J. Starr2 , D. Vizi2 , W.-Z. Zhang1 , D. Kaye1 , FCSANZ 1 Baker Heart Research Institute; 2 Heart Centre, Alfred Hospital,

Melbourne, Australia Background: Impaired L-arginine transport has been found in both heart failure and hypertensive subjects with established endothelial dysfunction. This finding provides a possible mechanism for reduced nitric oxide (NO) production. Given that both states are also associated with insulin resistance, and as insulin is known to induce vasodilation via a NO-dependent pathway, we hypothesized that abnormal insulin-mediated regulation of Larginine transport could play a role in cardiovascular disease. Methods: Forearm blood flow (FBF) responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were measured in the presence and absence of insulin in healthy normotensive (n = 16) volunteers using straingauge venous occlusion plethysmography. The effects of insulin on forearm arginine metabolism were studied by HPLC analysis. Results: Intra-brachial infusion of 5 mUnits/min insulin led to an increase in FBF at 60 min (P = 0.02), and drop in forearm vascular resistance (FVR) during insulin infusion (P = 0.04). FBF rose in a dose-dependent manner during ACh and SNP infusion in the presence (P = 0.007) and absence of insulin (P < 0.001). There was no significant difference in arterial or venous plasma concentrations of L-arginine or metabolites during insulin or saline infusion. However, there was a significant increase in the flux of NOHA (the NO precursor) (P = 0.01). Conclusion: This is the first biochemical study to provide evidence that the vasodilatory effects of insulin are endothelium-dependent by demonstrating increased production of the L-arginine-NO pathway intermediate, NOHA, in normotensive individuals.

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162 Increased B-Type Natriuretic Peptide is Associated with an Abnormal Blood Pressure Response to Exercise in Asymptomatic Aortic Stenosis N.C. Van Pelt1,2,* , A. Kerr2 , M.E. Legget1 , FCSANZ, S. Pasupati1 , G. Whalley3 , S. Wong2 , FCSANZ, J. White2 , R.A. Stewart1 , FCSANZ 1 Green

Lane Cardiovascular Service, Auckland City Hospital; Hospital, Auckland; 3 Dept of Medicine, University of Auckland, Auckland, New Zealand 2 Middlemore

Introduction: Both plasma levels of B-type natriuretic peptide (BNP) and an abnormal exercise response have prognostic importance in aortic stenosis (AS). This study examines the relationship between echocardiographic indices of AS severity, plasma BNP and exercise performance. Methods: Thirty-four patients with asymptomatic AS (mean (S.D.) aortic valve gradient (AVA, 0.96 ± 0.3) and 15 age matched controls underwent echocardiography, treadmill testing, and BNP analysis. Results: Compared to the control subjects, AS patients had a higher left ventricular mass index (LVMI, 133 ± 50 g/m2 versus 106 ± 24 g/m2 , p = 0.03), higher E/E ratio (10.6 ± 3.6 versus 6.7 ± 1.8, p = <0.0001), a higher ejection fraction (EF, 65 ± 6% versus 59 ± 6%, p = 0.03), elevated resting BNP (11.4 ± 6.5 pmol/L versus 7.4 ± 4.0 pmol/L, p = 0.03) and shorter exercise duration (8.2 ± 3.0 min versus 10.9 ± 2.6 min, p = 0.002). Treadmill exercise was stopped for AS patients because of dyspnoea in 22, angina in 2, leg discomfort in 1, BP fall in 8 and ventricular ectopics in 1. AS patients with an increase in systolic BP of ≤20 mmHg during exercise (n = 17) had higher plasma levels of BNP than patients with a normal BP response (14.1 ± 6.1 pmol/L versus 10.4 ± 9.5 pmol/L, p = 0.002). The BNP measured at peak exercise was also associated with an abnormal BP response (p = 0.003). AVA, EF, LVMI and E/E were not associated with the BP response to exercise. Conclusion: In patients with AS there is an association between BNP and an abnormal BP response to exercise. It is possible that increased wall stress during exercise is associated with both an increased release of BNP and an abnormal baroreceptor response. 163 Longitudinal Contractile Dysfunction after Exercise in Aortic Stenosis N.C. Van Pelt1,2,* , R.A. Stewart2 , FCSANZ, M.E. Legget2 , FCSANZ, G. Whalley3 , S. Wong1 , FCSANZ, M. Oldfield1 , A. Kerr1 1 Middlemore Hospital, Auckland; 2 Green Lane Cardiovascular

Service, Auckland City Hospital; 3 Dept of Medicine, University of Auckland, Auckland, New Zealand Introduction: Long axis left ventricular systolic function assessed by tissue Doppler imaging (TDI) may be abnormal in patients with severe aortic stenosis (AS) when LV ejection is maintained. This study evaluates the role of TDI measured after treadmill exercise for identifying early LV dysfunction in asymptomatic AS.

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ABSTRACTS

Methods: Twenty patients with AS (mean ± S.D. aortic valve gradient (AVA, 0.95 ± 0.3) and 15 aged matched normal controls underwent a symptom limited treadmill exercise stress echocardiogram. Echo measurements included TDI at the lateral mitral annulus, LV volumes and right ventricular pressures (RVSP). B-type natriuretic peptide (BNP) was also measured. Results: At rest AS patients compared to controls had a higher E/E ratio (10.5 ± 2.8 versus 6.7 ± 1.8, p = 0.0004), a higher ejection fraction (EF, 69 ± 7% versus 62 ± 5%, p = 0.011), and a trend for higher BNP (9.2 ± 5.8 pmol/L versus 7.4 ± 4 pmol/L, p = 0.15). Both systolic mitral annular velocity and RVSP at rest were similar for patients with AS and controls. Exercise duration was shorter for AS compared to controls (8.9 ± 3.2 s versus 11 ± 2.6 min, p = 0.05). Immediately after exercise, S was lower in AS compared to controls (12.1 ± 3.5 cm/s versus 17.0 ± 2.8 cm/s, p = 0.0006). Lower exercise S was associated with higher plasma levels

patients (10,509 measurements) aged 20–96 years with real or suspected cardiovascular diseases, mostly hypertension, coronary atherosclerosis and cardiac failure. Aortic pressure and wave reflection indices (AP and AI) were determined by the SphygmoCor process. In clinic patients, higher aortic SP is explicable on the basis that many had hypertension (>65 years, male 122 mmHg S.D. 18.7, female 131 mmHg S.D. 22.4), while all “normal” subjects had brachial systolic pressure <140 mmHg. Although the range of AP was greater for the clinic patients than normal subjects, the average values of aortic AP and AIx (Fig.) were similar (over 65 years, AP male 15.1 mmHg, female 26.7 mmHg; AIx male 21.7%, female 33.2%). Values of AIx above 50% were rare, and >2S.D. at all ages for both groups, and considered probably artefactual. The similarity of AP and AIx in normal subjects and clinic patients is attributed to various degrees of arterial degeneration with age in the normal subjects, and to the deliberate use of drugs to normalise AIx in clinic patients.

of BNP (r = −0.54, p = 0.015), and a smaller exercise increase in systolic blood pressure (r = 0.55, p = 0.012). Increase in EF after exercise was lower (4 ± 7% versus 11 ± 8%, p = 0.02) and peak RVSP higher (47 ± 15 versus 35 mmHg + RA mean, p-0.03) in AS patients compared to controls. Conclusion: In patients with moderate or severe AS, TDI after treadmill exercise allows earlier detection of latent LV dysfunction than resting TDI or resting EF.

165 Patients with Coronary Slow Flow Phenomenon Demonstrate Normal Myocardial Blood Flow and Arterial Wave Reflection Between Acute Episodes

164 Change in Aortic Pressure and Augmentation Index with Age in Outpatient Clinic Compared to Normal Population Audrey Adji1,* , Michael F. O’Rourke1,2 , FCSANZ 1 St Vincent’s Clinic, UNSW, Australia; 2 VCCRI, Sydney, NSW, Australia

McEniery et al. (JACC 2005;46:1753–60) have published values of aortic systolic pressure (SP), augmented pressure (AP) and augmentation index (AI) obtained in a normal population of 4001 subjects. Our study was performed to compare these with values in outpatients attending a cardiovascular clinic. Data were recorded from 1600

J.E. Sharman1,2,* , S.W. Moir1 , K.M. Kostner1 , FCSANZ, E. McGrath2 , T.H. Marwick1 , FCSANZ 1 University of Queensland, Department of Medicine; 2 School of Human Movement Studies, Brisbane, Australia

Patients with coronary slow flow (CSF) present with a syndrome (often recurrent) of resting angina with no significant coronary stenoses. The nature of myocardial blood flow (MBF) and MBF reserve between acute presentations is unclear. We sought to measure MBF, arterial stiffness and wave reflection, in patients who had presented with CSF. Methods: Ten patients with angiographically proven CSF (aged 57 ± 14 years) and 20 controls (aged 55 ± 13 years) underwent dipyridamole-exercise stress myocardial contrast echocardiography. MBF was quantified off-line from 10 mid and apical segments with calculation of myocar-

dial blood volume (A), red cell velocity (beta) and their product, MBF, at rest and post stress. MBF reserve was calculated as the ratio of peak stress to resting MBF. Central arterial pressure waveforms were derived by radial tonometry. The magnitude and timing of arterial wave reflection was calculated by augmentation index (AIx) and timing of the reflected wave (TR ), respectively. Central and peripheral arterial stiffness were determined by aortic and radial pulse wave velocity (PWV), respectively. Results: There was no significant difference between CSF and control groups in mean resting beta (0.60 ± 0.24 versus 0.56 ± 0.26), A, MBF, MBF reserve central or peripheral arterial stiffness (p > 0.7 for all; see Fig. 1). Similarly, AIx (26 ± 12% versus 23 ± 9%) and TR (144 ± 12 ms versus 148 ± 14 ms) were not significantly different (p > 0.3) and there were no significant differences after stress (p > 0.2 for all). Conclusion: MBF and arterial wave reflection are normal in CSF patients between their acute episodes.

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p-values were similar for those patients with mitral valve, aortic valve or coronary disease, r = 0.7–0.8 in each case, p < 0.001). Male gender and increased heart rate (p < 0.01) but not age or central aortic pressure were significantly and independently associated with PAP. Using 95% confidence intervals, a PA pressure “higher than expected” could be defined for a given wedge pressure. Thus, PA pressure varies with PCWP in a definable manner, potentially allowing meaningful diagnosis of pulmonary artery hypertension in the presence of left heart disease.

Figure. Mean Pulmonary Capillary Wedge Pressure (mmHg) 167 Does Body Size Explain Cardiac Output Changes in Pregnancy? D. Zentner1,4,* , M. du Plessis1 , J. Wong1 , FCSANZ, S. Brennecke2,3 , L. Grigg1 , S. Harrap4 Figure 1. Haemodynamics between CSF patients and controls (p > 0.05 for all) 166 Relationship Between Pulmonary Artery and Pulmonary Capillary Wedge Pressure (PCWP) – When is PA Pressure (PAP) ‘Out of Proportion’ to Left Heart Disease? Rahn Ilsar* , Brian P. Bailey, Mark Woodward, David S. Celermajer, FCSANZ Royal Prince Alfred Hospital and The George Institute, Sydney, NSW, Australia Certain forms of pulmonary artery hypertension (PAH) are now amenable to treatment with selective pulmonary vasodilators, for example idiopathic and scleroderma associated PAH. A common clinical observation is PAH associated with left heart disease, however it is unclear when PA pressure is “out of proportion” in relation to a given wedge pressure and thus might represent increased pulmonary arteriolar vasoconstriction amenable to treatment. We thus studied the relationship between PAP and PCWP. In 310 consecutively catheterised patients (61 ± 15 years, 50% males) in whom right heart pressures were measured and whose primary diagnosis was suspicion or confirmation of coronary or left sided valvular heart disease, we examined the determinants of PA pressure. PAP rose linearly with PCWP (r = 0.69, p < 0.001) and this relationship was independent of underlying diagnosis (i.e. the r- and

1 Dept

of Cardiology, Royal Melbourne Hospital, Parkville; of Perinatal Medicine, Royal Womens’ Hospital, Carlton; 3 Dept of Obstetrics and Gynecology, University of Melbourne, Parkville; 4 Dept of Physiology, University of Melbourne, Parkville, Vic., Australia 2 Dept

Background and aims: Increased maternal weight is associated with adverse pregnancy outcomes, including preeclampsia. Cardiac output (CO) normally correlates with body size. Pregnancy in the western world is usually accompanied by significant weight increase and increased CO. We examined cardiovascular correlates of weight in pregnancy (P). Methodology reported pre-pregnancy (PP) weight and measured weight (wt) in early (EP: median 16 weeks, n = 100) and late (LP: median 37 weeks, n = 32) P was collected. CO was measured by echocardiographic (Vivid 7, GE Medical) estimation of left ventricular outflow tract diameter and blood velocity. Controls were 10 nonpregnant (NP) women (follicular phase, menstrual cycle). Statistics and results: Results are expressed as median and interquartile range (IQR), examined using nonparametric comparative and correlational tests with statistical significance as 2p < 0.05. NP and P1 subjects were well matched for age and weight (see Table). In NP women CO correlated with height (r = 0.8, 2p < 0.01) only. EP CO correlated with PP (r = 0.4, 2p < 0.01) and EP wt (r = 0.4, 2p < 0.01), but not height. PP wt also correlated with stroke volume (r = 0.2, 2p < 0.05), in EP. In LP, neither wt nor height correlated with CO. wt did not correlate with CO or CO during pregnancy.

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Abstarct 161 Table Variable

NP (n = 10)

EP (n = 100)

2p

EP Subset (n = 32)

LP (n = 32)

2p

Age (years)

32.5 (28.5–34)

30 (27–33)

ns

32 (28–34)

–

–

Weight (wt) (kgs)

67 (58–81)

65 (58–74)

ns

64 (58–81.5)

77 (68–90)

<0.001

Weight gain (kg)

NA

3.1 (1.1–5.8)

–

3.2 (0.8–5.6)

9.8 (7.6–13.2)

<0.001

CO (L/min)

4.4 (3.7–4.9)

5.1 (4.5–5.6)

0.018

5.3 (4.3–6.3)

5.7 (4.7–6.3)

ns

Conclusion: CO correlates more strongly with lean than fat body mass. This is seen in our NP population where CO correlates with height. In contrast, wt (in particular PP wt) predicts CO in pregnancy. Changes in CO with P in overweight women may underpin the association of wt and pregnancy complications such as pre-eclampsia. 168 Perindopril-Based Blood Pressure-Lowering Therapy Reduces Amino-Terminal-Pro-B-Type Natriuretic Peptide Levels in Subjects with Cerebrovascular Disease Duncan J. Campbell1,2,* , FCSANZ, M. Woodward3 , J. Chalmers3 , FCSANZ, S. Colman3 , A.J. Jenkins2 , B.E. Kemp1 , A. Patel3 , FCSANZ, S. MacMahon3 , FCSANZ 1 St. Vincent’s Institute of Medical Research; 2 Department of Medicine, University of Melbourne, St. Vincent’s Hospital, Fitzroy, Vic.; 3 The George Institute for International Health, University of Sydney, Camperdown, NSW, Australia

We previously showed plasma amino-terminal-pro-Btype natriuretic peptide (NT-proBNP) level predicts congestive heart failure, myocardial infarction, and ischemic stroke in participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebocontrolled study of the effects of perindopril-based blood pressure-lowering on cardiovascular events among individuals with cerebrovascular disease. Active treatment reduced cardiovascular events, and we therefore investigated whether active treatment modified cardiovascular risk factors. Plasma levels of NT-proBNP, lipids, Creactive protein (CRP), homocysteine, and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured at randomization and after 13 months of therapy in a subset of 357 PROGRESS participants. Baseline systolic and pulse pressures were higher in individuals with elevated baseline NT-proBNP levels. In comparison with placebo, active treatment reduced blood pressure and NT-proBNP levels, and increased renin levels. Reduction of NT-proBNP levels by active treatment was most evident in subjects with baseline NT-proBNP levels in the highest quarter (>26 pmol/L), with a median reduction of 16 pmol/L (interquartile range 0–51 pmol/L, P = 0.004), corresponding to a median decrease of 39% (interquartile range 0–69%). Active treatment reduced blood pressure similarly for subjects in each of the four quartiles of baseline NT-proBNP. Active treatment had little or no effect on plasma lipid, CRP, homocysteine, or sVCAM-1 levels. We conclude that active treatment reduced NT-proBNP levels

in those subjects with elevated baseline NT-proBNP levels associated with increased cardiovascular risk. Plasma NT-proBNP level, in addition to predicting cardiovascular risk, may provide a measure of risk reduction by blood pressure-lowering therapy. 169 Does Urotensin II Contribute to Altered Cardiovascular Homeostasis in Patients with Chronic Liver Disease? W. Kemp1,2,* , S. Roberts1 , A. Kompa2 , J. Colman1 , M. Richards3 , FCSANZ, H. Krum1 , FCSANZ 1 Alfred

Hospital Gastroenterology Department – Melbourne, Australia; 2 NHMRC CCRE Therapeutics Monash University – Melbourne, Australia; 3 University of Otago, Dunedin, New Zealand Introduction: Chronic liver disease (CLD) is characterised by a hyperdynamic circulation with increased cardiac output and low systemic vascular resistance. The contribution of the novel vasoactive peptide Urotensin II (UII) on this disordered CV homeostasis is unknown. Methods: The effect of UII on skin vascular tone in vivo in chronic liver disease subjects was investigated using iontophoresis and Laser Doppler Velocimetry (n = 9). To further investigate the role of UII in CLD, serum UII levels were measured by RIA at the time of portal pressure determination (HVPG) in CLD patients (n = 81). In addition mean arterial pressure (MAP) and right atrial pressure (RAP) were measured. Results: UII resulted in a significant dose-dependent peripheral vasoconstriction in chronic liver disease patients versus normal subjects. Arbitrary flux units for UII 10−12 , 10−9 and 10−7 mol/L were −21.4, −86.1, −145.8, respectively. Mean peripheral serum UII was higher than the hepatic UII (2.05 ± 0.6 pmol/L and 1.88 ± 0.7 pmol/L, p = 0.03). Peripheral serum UII was negatively correlated with RAP (r = −0.32, p < 0.01) and MAP (r = −0.32, p < 0.01). UII was significantly higher in those with RAP <5 mmHg (2.22 ± 0.62 pmol/L versus 1.93 ± 0.48 pmol/L, p = 0.01) and MAP < 90 mmHg (2.28 ± 0.64 pmol/L versus 1.87 ± 0.47 pmol/L, p < 0.005). UII correlated positively with HVPG (r = +0.35, p = 0.001). Conclusion: We have shown abnormal peripheral vasoconstriction by UII in CLD patients. Given the vasoactive nature of this compound UII may be contributing to the disordered vascular tone and altered cardiovascular homeostasis observed in patients with chronic liver disease.

170 Discrepancy Between Aortic and Upper Limb Systolic Pressure Audrey Adji1,* , Michael F. O’Rourke1,2 , FCSANZ 1 St Vincent’s Clinic, UNSW; 2 VCCRI, Sydney, NSW, Australia

Recent trials have validated the importance of aortic systolic pressure. The present study was performed to examine differences over a wide range of central systolic pressures between cuff upper limb and aortic systolic pressure. Data were recorded from 1,600 patients (10,509 measurements) age 20–96 years attending an outpatient clinic with various real or suspected cardiac conditions; principally hypertension, ischemic heart disease and cardiac failure. Aortic pressure was determined from the radial tonometry pressure pulse using the SphygmoCor system. The difference and variability between brachial and aortic systolic pressure (mean difference 12.8, S.D. 6.0 mmHg) peaked in the mid range, with the least variability (S.D. 3.5 mmHg) at extremes (brachial systolic pressure <80 or >220 mmHg). The difference between brachial and aortic systolic pressure could not reliably be predicted from brachial cuff pressure, however, it could be predicted from the radial pressure waveform (Fig.). At high levels of radial wave augmentation (>100%) with the radial peak in mid to late systolic, pressure difference was 7.3 (S.D. 2.9) mmHg. For augmentation <50% of the radial pressure wave, systolic pressure difference was 21.2 (S.D. 6.4) mmHg, while between 50 and 100% augmentation, difference was 13.0 (S.D. 4.5) mmHg. The discrepancy between aortic and brachial systolic pressure cannot be predicted from brachial cuff pressure, but can be estimated from the pressure pulse waveform in the upper limb.

Figure. Radial AI(%) vs. difference between systolic pressure in radial and aorta (n = 10509).

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171 Plasma Asymmetric Dimethylarginine is an Independent Marker for the Presence and Severity of Peripheral Artery Disease M.K.C. Ng1,2,* , FCSANZ, T. Assimes2 , B.Y. Wang2 , S. McGee2 , R.K. Harada2 , A.C. Yeung2 , B. Narasimhan2 , J.W. Olin3 , J.P. Cooke2 1 Royal

Prince Alfred Hospital, Sydney, Australia; 2 Stanford University School of Medicine, Stanford; 3 Mt Sinai School of Medicine, New York, USA Background: Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase causally linked to endothelial dysfunction, are elevated in those with risk factors for atherosclerosis and may be a novel risk factor for atherosclerosis. We studied the relationship between plasma ADMA and the presence and severity of peripheral artery disease (PAD). Methods and results: In a prospective multicenter study, subjects referred for cardiac catheterization (n = 280; age, 66 ± 1 years; percentage male patients: 57%) underwent history and physical examination, determination of serum chemistries and ADMA levels, and measurement of ankle-brachial indices (ABI). Mean ABI of the cohort was 0.95 ± 0.01 and 28% (n = 80) of patients had PAD (defined by ABI<0.9). ADMA concentrations were elevated in PAD patients (0.63 ± 0.03 ␮mol/L) compared to those without PAD (0.55 ± 0.01 ␮mol/L) (P = 0.03 for PAD versus non-PAD). Univariate and multivariate analyses revealed that plasma levels of ADMA were positively correlated with body mass index (P = 0.002), mean arterial pressure (P = 0.01) and male gender (P = 0.03) but negatively correlated with glomerular filtration rate (P < 0.0001). In multivariate analysis plasma ADMA was negatively correlated with ABI (P = 0.0003). In a multivariate logistic regression, increasing plasma ADMA was independently associated with the presence of PAD (P = 0.02). After adjustment for risk factors, patients in the quartile with the highest ADMA values were four times more likely to have PAD than those in the lowest quartile (adjusted OR 4.2 [95% CI 1.4–12.2]; P = 0.009) (Table 1). Conclusion: Plasma ADMA is significantly correlated with the presence and severity of PAD as measured by ABI. Our findings are consistent with the hypothesis that ADMA may be a novel biomarker for atherosclerosis. Table 1. Adjusted Odds Ratios for Presence of Peripheral Artery Disease According to Plasma ADMA Quartile of ADMA (␮mol/L) 1. 2. 3. 4.

≥0.44 0.45–0.55 0.56–0.65 ≥0.66

Adjusted Odds Ratio 1.0 2.1 1.7 4.2

95% CI

P-value

– 0.8–5.9 0.6–5.1 1.4–12.2

– 0.12 0.33 0.009

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172 Clozapine-Induced Myocarditis: Fact or Fallacy? A Review of 116 Cases of Suspected Myocarditis Associated with the Use of Clozapine in Australia 1993–2003 Steven J. Haas1,* , Richard Hill2 , Henry Krum1 , FCSANZ, Danny Liew1 , Andrew Tonkin1 , FCSANZ, Lisa Demos1 , Karen Stephan1 , John McNeil1 1 NHMRC

Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology & Preventive Medicine & Department of Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia; 2 Adverse Drug Reactions Unit, Therapeutic Goods Administration, Canberra, Australia Purpose: Clozapine is an antipsychotic medication associated with a lower suicide rate compared with other agents. Used specifically for cases where previous therapy was inadequate or intolerable, clozapine is also known to have a causal relationship with myocarditis development. Methods: Retrospective review of adverse drug reaction reports and electronic database entries submitted to the Adverse Drug Reactions Advisory Committee of Australia suspecting myocarditis for clozapine treated patients from January 1993 through to December 2003, inclusive. Results: One hundred and sixteen case reports meeting specified criteria were identified (incidence between 0.7 and 1.2% of treated patients). Median patient age was skewed at 30 years (S.D. 11.1 years), compared to 37 years of age from the Clopine registry. The condition developed within a median average of 16 days (S.D. 17.3 days) for the bulk of patients developing myocarditis within 6 months (n = 93). Three-quarters of cases were prescribed clozapine within the range of 200–400 mg/day. Sixty cases recovered from their episode when reported or during follow-up reports, whilst 17 cases had not yet recovered – 27 cases had unknown outcome when reported and the remaining 12 cases were fatalities. Cardiac diagnoses (e.g., abnormal ECG/echo, tachycardia and cardiac failure), cardiac/vascular investigations and psychoactive medications were leading reported details. Conclusions: Clozapine is uncommonly but importantly related to myocarditis, often fatal in some young people with early onset after treatment initiation. Additional pharmacovigilance and further investigation of mechanisms of drug-induced myocarditis and related cardiovascular conditions is clearly warranted. A case-control study would be suitable for investigation of baseline predictors. 173 Stress Induced Cardiomyopathy—The “Apical Ballooning” Phenomenon in Australian Patients R. Gurvitch* , G. Lee, W. Ahmar, J. Morgan Department of Cardiology, Royal Melbourne Hospital, Melbourne, Australia Background: Emotional stress may precipitate acute left ventricular (LV) dysfunction and presents with features of acute myocardial infarction (AMI). This “apical ballooning” syndrome is under-recognised in clinical practice.

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Results: We describe four patients presenting as AMI with LV impairment occurring in response to emotional stress. All were women, three post-menopausal (age 47–80, mean 63). Precipitants were—unexpected death (2), armed robbery, and abdominal surgery with recurrent pain. The latter occurred 10 days post-operatively, presenting as an anterior STEMI with LV failure. The remainder presented with non-STEMI. Chest pain began within 12 h of the event. All patients had troponin-I elevation (mean 3.8 ug/L), but only two had CK elevation (max 448 IU/L). Twelve lead electrocardiographs showed widespread deep T wave inversion. QTc prolongation was noted in all cases. Echocardiography revealed similar patterns of wall motion abnormalities – significant decreases in overall LV function (mean EF 45%), with preserved or hyperdynamic basal function and akinesis of the mid and distal segments. Coronary angiography was normal in three cases and revealed mild disease in one. One patient underwent transoesophageal echocardiography to exclude cardiac embolism, another was anticoagulated for thromboembolic prophylaxis due to apical akinesis. In all cases, LV function returned to normal within 6 weeks. All patients remained event free at 6 months. Conclusions: Recognition of this condition is important to guide appropriate management and limit unnecessary further investigations and treatment. To our knowledge, this condition has not previously been described late in the post-operative period. 174 Natural History of Aortic Stenosis in an Elderly Cohort: A 17-Year Follow Up L. Kearney1,* , M. Durairaj3 , J. Castro1,2 , J. Johns1 , FCSANZ, B. Buxton3 , R. Low1 , FCSANZ, P. Srivastava1,2 1 Department

of Cardiology;

2 Department

of Medicine;

3 Departmnt of Cardiac Surgery, Austin Health, Melbourne, Vic-

toria, Australia Background: Aortic stenosis (AS) is a common cause of morbidity and mortality in the elderly population. Decisions regarding aortic valve replacement (AVR) in this cohort are difficult. This prospective cohort study documents the natural history of death, requirement for AVR and rate of progression of AS. Methods: Subjects with AS were enrolled from 1988 to 1994, then prospectively followed until 2005 with composite primary (death/AVR) and secondary clinical endpoints (AVR, death, progression of echocardiographic mean gradient and aortic valve area) assessed. Data was collated via medical record review and telephone interview. Results: Two hundred and fifty-two subjects were recruited. The mean age was 73.3 ± 7 years, the mean aortic valve gradient was 29.2 (8–140) mmHg and the mean AVA was 1.25 cm2 . Forty-one percent of subjects had mild, 37% moderate and 21% severe AS. The mean follow up was 9 ± 4.7 years. Five and 10 year rates for the primary end point were 54 and 36%, respectively. Overall five and ten year survival rates were 66% and 46%. Patients undergoing AVR (27%), had improved five and ten year survival rates of 91% and 72%, compared to patients managed

conservatively (59% and 40%). The mean aortic valve gradient progression was 4.0 mmHg/year with AVA reduced by 0.09 cm2 /year. Conclusion: AS is a progressive condition associated with significant mortality. Establishment of its natural history in this elderly population will help to guide management decisions. Elderly patients with severe AS should not be excluded from AVR as this may confer an improved prognosis despite other co-morbidities. 175 Aortic Stenosis: Is it Mandatory to Cross the Valve? S. Adera* , R. Prashar, C. Hiew, P. Diu, P. Varghese, S. Mylabathula, B. Bastian Cardiovascular Department, John Hunter Hospital, Newcastle, Australia Traditionally, aortic stenosis severity was graded using catheterisation techniques. Echocardiographic measurements correlate closely with catheterisation data. Echocardiography has the advantage of being non invasive. Recent developments in echocardiographic technology necessitates that a paradigm shift be made in the diagnostic work up of aortic stenosis. Data from 136 patients with mean valve gradients of ≥30 mmHg by catheterisation were reviewed. The procedure times were compared with those of 136 diagnostic angiograms as control. The mean gradients and grading of aortic stenosis severity were compared with the echocardiographic results. The median duration for catheterisation in aortic stenosis was 55.0 min with a standard error of 1.92 while that for diagnostic angiography was 26.0 min with a standard error of 0.89. Independent sample t-testing showed that it takes significantly longer to quantify aortic stenosis severity by catheterisation. The mean gradient was 45.7 mmHg with a standard error of 1.07 by catheterisation while it was 44.2 mmHg with a standard error of 2.17 by echocardiography. Independent sample t-test showed no difference between both techniques. Determination of aortic stenosis severity by catheterisation methods takes twice the time for diagnostic angiogram for no additional benefit over echocardiographic results. It is time to shift the diagnostic work up of aortic stenosis from cathetherisation to echocardiographic laboratory. The time and resources should be spent on other interventional cardiac procedures in order to reduce waiting times. 176 Clinical Features and Outcome of Patients with Left Ventricular Noncompaction: Regional Centre Experience C. Hiew1,* , G. Warner1 , FCSANZ, B. Bastian1 , M. Puvaneswary2 , P. Diu1 , L. Quiqueree1 , P. Hayes1 1 Cardiovascular

Department, John Hunter Hospital, Newcastle, Australia; 2 Department of Radiology, John Hunter Hospital, Newcastle, Australia Background: Left ventricular noncompaction (LVNC) is a disorder of endomyocardial morphogenesis resulting in

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prominent trabeculations. Current literature suggests that LVNC is rare and associated with a high mortality rate. Methods: Seventeen patients have been identified by echocardiography and/or magnetic resonance imaging at three regional sites over five year period (in 0.03% of echocardiograms performed). Mean age was 39.8 ± 26.6 years (range 3–82 years) and half being male. Clinical and morphological features, associated congenital cardiac abnormalities and outcome are described. Results: Mean age at diagnosis was 38.4 ± 27.0 years (range 1–82), and follow-up was 23.0 ± 13.9 months. The main presenting symptom was dyspnoea in 9 patients (56.3%) and abnormal ECG in 12 patients (75.0%). Left ventricular end-diastolic diameter was 58.8 ± 12.6 mm and left atrial diameter was 36.9 ± 10.0 mm. Six patients (37.5%) had normal left ventricular systolic function. Apex and midventricular segments of inferior and lateral walls were affected in all cases. Four patients had associated congenital heart defects: ventricular septal defect in two, patent ductus arteriosus in one and coronary artery anomalies in one. Non-sustained ventricular tachycardia in two patients, left bundle branch block in three patients and supraventricular tachycardia in four patients were the rhythm abnormalities recorded on Holter monitor. A family history of cardiomyopathy was identified in three patients. Major complications were heart failure in four, thromboembolic events in three and ventricular fibrillation in one patient. Four patients had automated defibrillators implanted. One patient died from end-stage heart failure. Conclusions: Our study demonstrated a diverse clinical spectrum of this disorder. Early recognition may allow risk stratification, early therapy and screening of family members. 177 Estimation of Ascending Aortic Mean Cycle Flow and Cardiac Output from Radial Artery Applanation Tonometry: A Modelling Study Michael F. O’Rourke1,* , FCSANZ, Audrey Adji2 , Junichiro Hashimoto2 1 St Vincent’s Clinic, UNSW; 2 VCCRI, Sydney, NSW, Australia

For over a century, attempts have been made to determine cardiac output from arterial pressure recordings. None have survived into regular practice. Arterial tonometry reopens prospects through ability to identify aortic pressure at peak flow velocity together with ventricular ejection period, then use published normative data and the classic “waterhammer formula” (velocity = pressure/characteristics impedance) to derive peak and mean cycle velocity, and cardiac output (CO). Such estimations were made, using SphygmoCor in 446 patients aged 16–94 years, attending a cardiovascular clinic, mostly with suspected or confirmed hypertension, ischemic heart disease or cardiac failure. Values of mean cycle flow velocity (V) and CO (13.9 cm/s and 6.9 L/min, respectively) were realistic, and with highest values in young patients with systolic hypertension and lowest values in older persons with cardiac failure. Mean cycle flow

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decreased markedly with age (V = 31.0–0.24*age) while CO fell to a lesser degree (CO = 9.1–0.03*age), and with difference largely attributable to progressive aortic dilation with age. For individuals, stable on therapy, coefficient of variation (CV) for repeated measures was low and comparable to CV for blood pressure and heart rate. Until further studies are completed, we believe that the major value of this technique will be for estimating change in aortic flow in individuals, or after calibration against a recognised technique such as thermodilution. 178 Serum Creatinine is a Predictor of Early Outcome of Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction R.K. Reed* , S.A. Hope, M.C.H. Leung, Y. Malaiapan, I.T. Meredith, FCSANZ Monash Cardiovascular Research Centre, Monash Medical Centre, Melbourne and Monash University, Vic., Australia Background: Elevated serum creatinine and reduced creatinine clearance are associated with increased mortality in patients with ST elevation myocardial infarction (STEMI) treated with thrombolysis. Whether renal function predicts early outcome in STEMI treated with primary percutaneous intervention (PCI) is not known. Aim: We aimed to examine whether admission serum creatinine was associated with outcome following primary PCI in patients with STEMI. Methods: One hundred and four consecutive patients with STEMI treated with primary PCI were studied. Relationships between serum creatinine and outcome including procedural and clinical success (absence of major cardiovascular adverse events in hospital) and left ventricular systolic function were analysed using ANOVA and regression techniques. Results: Of the 104 patients, 81 were male, the mean age was 63 ± 12 years. Ninety-three patients had procedural and 89 patients clinical success. Only 8 patients had renal impairment (serum creatinine > 150 ␮mol/L). Serum creatinine predicted both procedural (p < 0.01) and clinical (p < 0.01) success. This relationship remained when age, gender and severity of coronary disease were considered. Serum creatinine was also associated with left ventricular systolic function independent of procedural outcome (p < 0.05). Conclusion: Admission serum creatinine, even in those with a normal level in patients with ST elevation myocardial infarction predicts both procedural and early clinical outcome in patients undergoing primary percutaneous coronary intervention.

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179 Clinical Presentation and Aetiology of Acute Coronary Syndromes in Patients with Angiographically Normal Coronary Arteries A. Sahar* , M. Shaw, D.J. Clark, M.C.G. Horrigan, FCSANZ, G. Proimos, FCSANZ, J. Johns, FCSANZ, D.L. Hare, FCSANZ, H.M.O. Farouque Department of Cardiology, Austin Health, Heidelberg, Victoria, Australia An acute coronary syndrome (ACS) in the setting of angiographically normal coronary arteries (NCA) is a recognized entity. The aim of this study was to examine prevalence, clinical features and precipitating causes of this phenomenon. Clinical and angiographic data were retrospectively reviewed on 1149 consecutive patients with ACS (STEMI, NSTEMI, unstable angina) undergoing cardiac catheterisation during hospital admission. Fifty-seven patients with ACS (5%) had angiographically NCA. In this group, 74% presented with features of unstable angina/NSTEMI, and 26% with STEMI. Peak cardiac enzymes were mildly raised with a troponin I of 7.78 ± 0.01 ␮g/L and creatinine kinase of 209 ± 5 U/L (mean ± S.D.). Normal left ventricular function was present in 41 of 57 patients (72%). Of those with left ventricular dysfunction, 75% had segmental impairment (56% anteroapical) and 25% had global impairment. Compared to the group with ACS and coronary artery disease (n = 1092), patients with ACS and angiographically NCA were younger (56 ± 14 years versus 64 ± 12 years; p < 0.001), more frequently female (44% versus 28%; p = 0.013), had lower systolic blood pressure (118 ± 22 mmHg versus 126 ± 25 mmHg; p < 0.001) and left ventricular end diastolic pressure (15 ± 6 mmHg versus 19 ± 8 mmHg; p < 0.001). Clinical presentation was consistent with a diagnosis of stress-induced (tako-tsubo) cardiomyopathy in 18% (10/57). Autoimmune disease was present in 12%, valvular disease in 11%, coronary spasm in 4%, coronary artery anomaly in 2% and no cause was found in the remainder (53%). Angiographically NCA are uncommon in patients with ACS. Stress-induced (takotsubo) cardiomyopathy accounts for a significant minority of these patients. 180 Directly Measured Central Aortic Blood Pressure, but not Augmentation Index Predicts Cardiovascular Events W. Thai* , S.A. Hope, I.T. Meredith, FCSANZ, J.D. Cameron, FCSANZ Monash Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Vic., Australia Background: Central aortic pressure waveform characteristics, in particular central systolic blood pressure (cSBP) and central augmentation index (cAI) are often proposed to predict cardiovascular events. However, there is as yet little directly measured data to support this assertion.

Methods: Forty-five study participants (32 male) had central aortic pressure waveforms (Millar Mikro-tip® catheter transducer) acquired with follow up after 38 months (32–45) for major adverse cardiovascular events (MACE) defined as acute coronary syndrome, cerebral vascular event, percutaneous intervention or coronary artery by-pass grafting. Central waveforms were analysed for parameters of interest, specifically cSBP, central pulse pressure (cPP), subendocardial viability index (cSVI) and cAI. Predictors of outcome were examined using regression techniques. Results: Mean age of the subjects was 61 ± 12 years and 15 experienced a MACE. Higher cSBP and cPP but lower cSVI were associated with occurrence of MACE (P < 0.05, P < 0.02, P < 0.05, respectively). Measured cAI was not associated with MACE even after accounting for height and heart rate. Increasing age was associated with increased MACE (P < 0.05) with trends for previous coronary interventions and raised cholesterol (P < 0.06). On multiple regression analysis cPP was the only predictor of MACE. Conclusion: Directly measured central aortic augmentation index was not associated with MACE. Directly measured central aortic systolic blood pressure, central pulse pressure and subendocardial viability index predicted MACE and may aid clinical cardiovascular risk stratification. 181 Timing of the Directly Measured Central Aortic Pressure Wave Inflection Point is Not Related to Aortic Pulse Wave Velocity S. Hope* , I. Meredith, FCSANZ, J. Cameron, FCSANZ Monash Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Victoria, Australia Background: It is believed that the inflection point, often termed reflection point, on the central aortic pressure waveform denotes the time of return (Tr) of a pressure wave reflected from the periphery. Increased arterial stiffness, with increased pulse wave velocity (PWV), would therefore be expected to reduce Tr. Methods: Pressure waveforms were acquired using 2F Millar Mikro-tip® catheter transducers in 40 subjects (26 male), 65 ± 12 years, from both the aortic root and bifurcation, at 2000 Hz for PWV and resampled at 200 Hz for analysis of waveform morphology. Waveforms were analysed for pressures, augmentation index (AI) and Tr, and PWV calculated as the quotient of the foot-to-foot pressure wave delay and distance (catheter withdrawal distance). The data were analysed by regression and correlation techniques. Results: Tr was not associated with PWV. Both were associated with systolic blood pressure (SBP), both central aortic and non-invasively measured brachial (P < 0.01 Tr and PWV). Using multiple regression, no relationship was apparent between Tr and PWV, even after inclusion of heart rate, SBP, and subject height or aortic root-

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bifurcation distance. Augmentation index was related to SBP, height and heart rate, but not PWV. Conclusion: The timing of the directly measured central aortic inflection point is not determined by pulse wave velocity, suggesting that factors other than reflection may be more important, and that the time to inflection point does not describe arterial mechanical properties currently known to be associated with increased cardiovascular risk. 182 Percutaneous Transvascular Septal Myocardial Ablation for Hypertrophic Cardiomyopathy. A Single Centre 5 Year Experience S. Hope* , W.-e. Thai, S. Seneveretne, P. Antonis, J. Gelman, FCSANZ, I. Meredith, FCSANZ Monash Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Victoria, Australia Background: Percutaneous transvascular septal myocardial ablation (PTSMA) has evolved as an alternative to surgery for the effective relief of symptoms secondary to left ventricular outflow tract (LVOT) obstruction. However, long-term follow up data remains limited. Methods: Baseline and follow up clinical and echocardiographic data was reviewed on all patients who have undergone PTSMA at Monash Medical Centre. Data were analysed by repeated measures analysis. Results: Thirty-seven PTSMA procedures have been undertaken at Monash Medical Centre on 36 patients, 60 ± 16 years (22–84), median follow-up 32 months (1 week–71 months). Thirty-three procedures were successful (4 patients with unsuitable coronary anatomy). Five patients had permanent pacemakers prior to PTSMA, and 6 patients required a pacemaker during their admission for PTSMA. No pacemakers have been required later. Peak resting LVOT gradient fell immediately following PTSMA (P < 0.001) with a further fall at 6 weeks (P < 0.05). No change was seen in gradient between 6 weeks and annual follow up to 5 years. Peak LVOT gradient with Valsalva fell immediately post PTSMA (P < 0.001) with no further change at 6 weeks or annual follow up to 5 years. Those patients who underwent stress testing achieved a reduction in peak LVOT gradient post stress (P < 0.05) with no significant change on annual follow up. There have been no early or late deaths. Conclusion: In our cohort PTSMA is a safe and effective procedure in symptomatic hypertrophic cardiomyopathy with good long-term relief of left ventricular outflow tract obstruction.

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183 Accuracy of Discharge Medication Summaries: The Westmead Hospital Cardiology Departments Experience with Electronic Discharge Summaries A. Kanthan* , A. Thiagalingam, P. Kovoor, FCSANZ Cardiology Department, Westmead Hospital, Westmead, NSW, Australia Background: The Westmead Hospital Cardiology Department has utilized a computerised discharge summary for 8 years. Medication entry is facilitated by a drop down list of available medications. However, manual entry of medication dosages and frequencies is required. Aim: To quantify the discharge medication error rate with the system (CARDS), identify strengths and weakness of current system, and define improvements for a new cardiology database. Method: A retrospective analysis of 86 randomly selected discharge summaries from the period January 2004 to December 2004 was performed. CARDS discharge summaries were compared directly to inpatient medication charts. Discrepancies were further analysed by reviewing medical staff entries in the admission notes. Resident medical officer surveys were also performed to help identify strengths and weaknesses. Results: A total of 42 drug errors were identified in 24 of the 86 discharge summaries. Nine errors were classified as serious. Twenty-eight errors were drug omissions, 6 were incorrect drugs ordered, 5 were incorrect dosages, and 3 were erroneously continued drugs. Residents identified the main strength as a readily accessible and legible medication summary. The most common complaint was that the systems electronic medication list was not up to date. Conclusion: The identified error rate would justify introducing a checking mechanism via a nurse or pharmacist and providing an up to date electronic medication list with selectable dosages and frequencies. 184 Evidence for a Treatment Gap in Contemporary Lipid Management After Acute Coronary Syndromes in Australia L. Bittinger1,* , J. Miels1 , A. Brennan2 , A. Meehan2 , C. Reid2 , FCSANZ, D. Eccleston1 , FCSANZ 1 Cardiology Department, Northern Hospital Epping; 2 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia

Aim: Despite extensive evidence for aggressive lipidlowering in patients with coronary artery disease, clinical management has lagged behind accepted guidelines. We aimed to assess whether a gap still exists between recent guidelines and contemporary practice in patients treated for acute coronary syndromes (ACS) at a large suburban centre. Methods: Data was prospectively collected on all 309 patients admitted with ACS (Unstable Angina (UA), non-

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ST and ST-elevation myocardial infarction (NSTEMI and STEMI)) between January 2004 and 2005. Following Ethics approval, data was collected at baseline and 12 month follow-up on lipid levels, treatment received and outcomes. Comparison was made between actual lipid levels and both current and 2004 guidelines for lipid management, and between ACS groups. Results: The mean age was 64.5 ± 14 years, 68% were male, mean statin dose was 40 mg. N (%)

MI (n = 227)

UA (n = 111)

P value

Statin treated at discharge

204 (90%)

85 (77%)

0.001

Statin treated at 12 months

181 (79%)

77 (69%)

0.04

Baseline total cholesterol mmol/l

4.86

4.65

0.10

Baseline LDL-C mmol/l

2.78 ± 1.06

2.63 ± 1.1

0.22

Lipids tested at by 12 months LDL-C at 12 months mmol/l

157 (69%) 2.07 ± 0.9

74 (67%) 2.5 ± 0.43

ns <0.001

% At 2004 LDL goal (2.6 mmol/l)

111 (49%)

43 (38%)

0.07

% At 2006 LDL goal (2.0 mmol/l)

71 (31%)

26 (23%)

0.13

Conclusion: Despite overwhelming evidence for intensive lipid reduction following ACS, insufficient patients achieve recommended targets. Patients with MI are more likely to achieve lipid targets than those with UA. Whilst there is a reduction in lipids one year following ACS, there remains a significant gap between current guidelines and lipid levels achieved in clinical practice. 185 Prevalence and Predictors of Aspirin Resistance in Australians with Acute Coronary Syndromes using a Rapid Point of Care Analyser R. Gurvitch1,* , W. Ahmar1 , B. Yan1 , A. Brennan2 , A. Meehan2 , C. Reid2 , FCSANZ, D. Eccleston1 , FCSANZ 1 Department

of Cardiology, Royal Melbourne Hospital; Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia

2 NHMRC

Background: Aspirin is widely used for prevention of cardiovascular events, however some patients are resistant (AR) to its anti-platlelet effects. Estimates of AR prevalence vary widely from 5 to 60% and there is no consensus as to the optimal test for clinical use. We aimed to determine for the first time the prevalence and predictors of aspirin resistance in an Australian population presenting with acute coronary syndromes (ACS) using a practical point-of-care assay, the AccumetricsTM Ultegra RPFA Aspirin Test. Methods: Eighty-one consecutive patients (mean age 63, male 70%) presenting with ACS (unstable angina, non-ST and ST elevation myocardial infarction) were assessed for AR (defined as >550 ARU) using the AccumetricsTM RPFA within 48 h of presentation. Patients not using aspirin were loaded with 300 mg and tested 12 h later. Demographics, 30 day and 6-month outcomes were correlated with AR status.

Abstracts

Results: The prevalence of aspirin resistance was 15%. N (%)

AR (n = 12)

Non-AR (n = 69)

Male

6 (50%)

51 (74%)

P Value 0.09

Current smoker

5 (42%)

23 (33%)

0.58

Prior Vascular event

9 (75%)

35 (51%)

0.11

Diabetes

3 (25%)

26 (38%)

0.40

MACE at 30 days

4 (33%)

12 (17%)

0.20

There was no difference in AR between patients loaded with aspirin or chronically on aspirin. Baseline characteristics were similar, although patients with AR were more likely to have other vascular disease. There was a trend for higher MACE (Death, MI, CABG, CVA) at 30 days in those with AR (33%) versus no AR (17%, p = 0.2). Conclusion: AR was found in 15% of Australians with ACS using the RPFA. AR was associated with a higher prevalence of prior and 30 day vascular events. Six month follow-up data will be presented. 186 Correlates of Aortic Sclerosis: A Population Study Doan T. Ngo* , Aaron L. Sverdlov, Scott R. Willoughby, Angus K. Nightingale, Yuliy Y. Chirkov, John D. Horowitz, FCSANZ The Queen Elizabeth Hospital, Department of Medicine, University of Adelaide, South Australia Previous studies have suggested that factors predisposing to the development of aortic stenosis (AS) include coronary risk factors and renal insufficiency. However, little information is available concerning the epidemiology of aortic sclerosis (ASc), which is both a precursor to AS development and an independent marker of cardiovascular risk. In a population study, we planned to investigate factors associated with presence of ASc. Randomly selected people (n = 200) aged 55–77 years (mean 64 ± 6 (S.D.)) underwent echocardiography to assess their aortic valves (AV). We quantitated AV integrated backscatter scores (BS) as an index of valve echogenicity. These data were correlated with clinical (e.g. coronary risk factors, treatments), biochemical (e.g. creatinine clearance (CrCL), calcium/phosphate), and physiological markers (hs-CRP, platelet aggregability). Correlates of increased BS were evaluated utilizing backward multiple linear regression. ASc was present in 32% (n = 64) based on conventional echocardiographic criteria (visual assessment), with associated BS of 14.5 ± 4.2, versus 10.5 ± 3.8 dB for subjects without ASc (p < 0.0001). On univariate analysis, BS increased significantly with age, inversely associated with CrCL, and body mass index. On multiple linear regression, increased BS were significant with: low CrCL and smoking history (p = 0.02, both). Surprisingly, history of hyper-

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cholesterolemia was predictive of low BS scores (p < 0.01), which could possibly be explained by statins therapy. Development of ASc is statistically associated with some, but not all, conventional coronary risk factors, and not with evidence of inflammatory activation. The data suggests that the incremental value of ASc as a predictor of coronary events is likely to reflect largely the impact of renal insufficiency. 187 Integrated Cardiac Assessment Regional Network P.A. Tideman* , P.E.G. Aylward, FCSANZ, D.P.B. Chew, FCSANZ, C.G. De Pasquale, FCSANZ, J.C. Vaile, M.X. Joseph, FCSANZ, R.Tirimacco Department of Cardiology, Flinders Medical Centre, Bedford Park, SA, Australia Integrated Cardiac Assessment Regional Network (iCARnet) was designed to improve access to specialised cardiac care in rural communities by having a Cardiologist on-call 24 h a day, 7 days per week and providing bedside Troponin T testing. By improving access to specialized cardiac care we hoped to help address the inequalities in Cardiovascular Disease Outcomes between metropolitan and rural, regional and remote populations. In 2003 we reported the results of a clinical audit between iCARnet sites and a comparative rural area. Our audit showed that iCARnet sites showed reduced cardiac readmissions and reduced time to coronary angiography. Since this audit the non-ICARnet site has joined the network and we report preliminary results of a clinical audit performed in the first 12 months post joining the network. Pre-iCARnet

Post-iCARnet

No. of patients

397

212

Males

237 (60%)

138 (54%)

Average Age (year)

63

65

No of Admissions

495

255

No of Patients Readmitted

60 (15%)

33 (13%)

Angiography

43 (11%)

15 (7%)

Time to Angiography

6.3 days (n = 34)

2.5 (n = 13)

Although readmission to the emergency department for chest pain or symptoms suggestive of ACS were not significantly reduced (15% versus 13%), ACS readmissions were significantly reduced 27% pre-iCARnet, 9% post iCARnet. These results confirm the results of the first audit indicating that the iCARnet network reduces time to angiography for rural and remote cardiac patients as well as reducing ACS readmissions. Our results suggest that improving access to specialized cardiac care improves time to invasive cardiac testing potentially improving patient cardiac outcomes in rural and remote areas in line with current evidence base regarding ACS.

ABSTRACTS

Heart, Lung and Circulation 2006;15S:S1–S167

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Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

188 Both Pre-Loading and Prolonged Treatment with Clopidogrel Improve Outcomes after Percutaneous Coronary Intervention D. Eccleston1,* , FCSANZ, A. Ajani1,6 , FCSANZ, D. Clark2 , S. Duffy3 , FCSANZ, M. Sebastian4 , FCSANZ, R. Lew5 , FCSANZ, A. Brennan6 , A. Meehan6 , C. Reid6 , FCSANZ, H. Krum6,3 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators

189 Dual Therapy for Pulmonary Arterial Hypertension Eugene Kotlyar1,* , FCSANZ, Anne Keogh1 , FCSANZ, Peter Macdonald1 , FCSANZ, Christopher Hayward1 , FCSANZ, Carolyn Corrigan1 , Annette Pidoux1 , Karen Brown1 , Trevor Williams2 , Eli Gabbay3 , Keith McNeil4 1 St Vincent’s Hospital, Sydney, Australia; 2 Alfred Hospital, Melbourne, Australia; 3 Royal Perth Hospital, Perth, Australia; 4 Prince Charles Hospital, Brisbane, Australia

1 Department

of Cardiology, Royal Melbourne Hospital; of Cardiology, Austin Hospital; 3 Department of Cardiology, Alfred Hospital; 4 Department of Cardiology, Geelong Hospital; 5 Department of Cardiology, Frankston Hospital, Melbourne; 6 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia 2 Department

Background: Clopidogrel is important post-coronary stent implantation to prevent stent thrombosis and recurrent coronary events. However, the duration of therapy recommended in the literature and in practice continues to vary widely, particularly for Drug-eluting stents (DES). Methods: We prospectively studied 2765 patients undergoing coronary angioplasty (PCI) from July 2004 to January 2006, and examined determinants of the duration of clopidogrel therapy (CT) and the relationship of this and pre-loading to clinical outcomes at 12 months. Results: Stents were used in 2668 (96.5%) PCI and DES in 1289 (46.6%). Prolonged CT (12 months) was received in 40.1%. Clopidogrel pre-loading was given in 988 (35.7%) and compared with no pre-treatment was associated with reduced 30 day TVR (p = 0.03) and MACE (p = 0.001), and less 12 month mortality (1.5 versus 4.1%, p = 0.08) and MACE (1.8% versus 9.1%, p = 0.06). Total Duration of Clopidogrel

p*

Background: Monotherapy with endothelin receptor antagonists, phosphodiesterase-5-inhibitors or prostacyclin analogues have been shown to be efficacious in the treatment of idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue disease (CPAH). Combination therapy has been used where patients fail monotherapy. However, it has not been used pre-emptively in stable, treated PAH patients to achieve the goal of disease regression or remission. Methods: Fifty-nine patients (35 idiopathic, 4 familial, 3 chronic thromboembolic, 17 CPAH), aged 50 ± 18 years (mean ± S.D.), functional Class III-IV, received one PAHspecific medication followed by the addition of a second agent if the patient’s pulmonary arterial systolic pressures (PASP) had not returned to normal. WHO class, six-min walk distance (6MWD) and PASP were determined in all patients at baseline, prior to initiation of the second agent and after 3 months of dual therapy. The sequence of agents varied: bosentan + sildenafil (n = 35); sildenafil + bosentan (n = 9), sildenafil + iloprost (n = 5) or sildenafil + ambrisentan (n = 1); ambrisentan + sildenafil (n = 4) or ambrisentan + iloprost (n = 2); sitaxsentan + iloprost (n = 3). Results: Table demonstrates functional class, PASP and 6MWD at the start of monotherapy, then at start of dual therapy, after an initial treatment of 17 ± 12 months (range 1–56), then after three months of dual therapy. Fifty-two percent of patients had >10% improvement in 6MWD.

≤3 Months

6 Months

Diabetes mellitus %

23.0

28.0

49.0

<0.01

n = 59

Acute coronary syndrome %

28.5

28.3

43.1

<0.001

WHO functional class

3.2 ± 0.6

2.9 ± 0.7#

2.4 ± 0.7*

Bare Metal Stent %

51.2

22.8

26.0

<0.01

6MWD (metres)

330 ± 116

322 ± 120

377 ± 140*

PASP (mmHg)

80.4 ± 21.1

83.6 ± 18.1

73.7 ± 14.1*

12 Months

DES overall %

10.7

33.5

55.7

<0.01

Stent diameter <3.0 mm %

25.1

32.6

42.4

<0.01

Total stent length >20 mm %

23.0

32.2

44.8

<0.004

12 month TVR % 12 month MACE % ∗

– 12.8

2.5

5.4

0.06

–

8.2

0.08

p values are 12-month data for variable vs. overall group.

Conclusion: In the MIG registry, diabetes, DES, ACS, small vessels and longer stented segments predicted a longer duration of clopidogrel therapy. Clopidogrel pre-loading and 12 months of clopidogrel therapy was associated with improved 30 day and 12 month outcomes.

Baseline

Start of Dual Therapy

At 3 Months

* p < 0.05 compared with baseline and at start of dual therapy. # p < 0.05 compared with baseline.

Conclusions: After 3 months of treatment with combination PAH specific therapy, there was a significant improvement in functional class, 6 min walk distance and PASP suggesting clinical benefit of dual therapy in the majority of patients.

Abstracts

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190 Prevalence and Effect of Aspirin Resistance Determined Using a Rapid Point-of-Care Aggregometer in Australian Patients with Stable Angina

191 Initial Experience with Cardiologist Office-Based Pointof-Care BNP Measurement in Managing Patients with Suspected or Established Cardiac Dysfunction

W. Ahmar1,* , R.Gurvitch1 , A. Brennan2 , A. Meehan2 , C. Reid2 , FCSANZ, D. Eccleston1 , FCSANZ

Gregory Szto* , FCSANZ, Vikki O’Shea Peninsula Private Hospital, Frankston, Vic., Australia

1 Department

of Cardiology, Royal Melbourne Hospital; 2 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Aim: Aspirin resistance (AR) is associated with increased risk of cardiovascular events, however estimates of AR prevalence vary widely from 5 to 60% with no consensus as to the optimal test for clinical use. We aimed to validate a rapid point-of-care platelet function analyser (AccumetricsTM RPFA) and then use it to assess the prevalence and clinical importance of AR in Australian patients with stable angina. Method: Validation of the RPFA was performed by comparing test results with standard laboratory aggregometry (LA) in 21 patients with SA taking aspirin for ≥2 weeks. The prevalence of AR (RPFA > 550 AR units) was assessed in 50 patients with SA undergoing diagnostic coronary angiography. We assessed the relationship between AR and previous and subsequent cardiovascular events at 30 days and 6 months. Results: The AccumetricsTM RPFA demonstrated good correlation with LA (R = 0.65, p = 0.001) in both aspirin sensitive and resistant patients.

Introduction: Brain natriuretic peptide (BNP) measurement is increasingly useful in determining a cardiac cause of a patient’s dyspnoea, as well as tailoring response to heart failure therapy. We initiated an office-based pointof-care BNP measurement system (12 min) to determine its utility in managing patients. Method: Over 8 weeks, 83 patients were evaluated with 89 samples. Indications were: (1) diagnose dyspnoea (n = 21), (2) establish baseline severity of LV dysfunction prior to treatment (n = 40), and (3) determine response to treatment (n = 28). Data on LV function was recorded as close to the test as possible. Reference levels for BNP are agedependent. Results: For the 1st indication—mean BNP level was 563 pg/ml (range 60–1599), mean LVEF 58% (range 44–79). BNP excluded cardiac dysfunction in most patients. For the 2nd indication, mean BNP was 1514 (range 62–3000). Mean LVEF was 36% (range 20–67%). For the 3rd indication, uptitration of beta-blocker was recommended in four patients (13%), down-titration was recommended in one patient who normalised his cardiomyopathy. Seventy-two percent did not have any change in medications as they were on maximal medical therapy. Of the 32 patients on carvedilol during BNP testing, uptitration of dosage (7 patients, 22%) and downtitration in 2 patients were performed. Six patients (19%) were started on carvedilol after BNP was done. Further information will be tabulated. (Note: max result is 3000 pg/ml). LVEF (%)

Mean BNP (pg/ml)

Range of BNP (pg/ml)

≤40% (n = 36)

1722

82–3000

≥55% (n = 36)

980

60–3000

Conclusion: Office-based point-of-care BNP levels offer a rapid and useful addition to other investigations in the management of patients with cardiovascular dysfunction. Figure. The prevalence of AR was 16%; overall mean age was 58 years and 76% were male. At 30-day follow-up, patients with AR had an increased risk of coronary events (PCI or CAGs) 63% versus 0% for the non-AR group (p = 0.001). Conclusion: This study supports the use of the AccumetricsTM RPFA as a rapid practical tool for determining Aspirin Resistance. AR assessed with this technique predicted an increased risk of cardiovascular events in SA patients at 30 days. Six-month follow-up will be presented.

ABSTRACTS

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Abstracts

ABSTRACTS

Clinical Cardiology – Coronary Artery Disease 192 Prospective Evaluation of a Policy of the Selective Use of Drug-Eluting Stents ¨ John French* , FCSANZ, Victar Hsieh, Noemi Wouters, Rozemarijn van der Vijver, Lisa Connolly, Sue-Anne Gavigan, David Taylor, FCSANZ, Rohan Rajaratnam, FCSANZ, Andrew Hopkins, FCSANZ, Sidney Lo, FCSANZ, Dominic Leung, FCSANZ, Craig Juergens, FCSANZ Liverpool Hospital, Sydney, Australia Background: Drug-eluting stents (DES) for percutaneous coronary intervention (PCI) are more expensive than bare metal stents (BMS) and they require a longer duration of clopidogrel therapy. Also low restenosis rates with BMS occur in certain patient subsets. Methods and results: We assessed the feasibility of a selective DES deployment policy, while aiming to maintain low clinical restenosis rates, by using the following criteria in our cardiac catheterisation laboratory (CCL): left main lesions; ostial lesions in any of the three major epicardial arteries; proximal left anterior descending (LAD) lesions; lesions >20 mm in length where the reference segment diameter was <3.0 mm; lesions where the reference segment diameter was ≤2.5 mm, diabetic patients with any lesion with reference segment diameter <3.0 mm; and in-stent restenosis. Among the 1112 patients (21% diabetics) receiving PCI for all indications including cardiogenic shock (40 patients) in our CCL in the 18-month period from October 2003, 28% received at least one DES. The clinical restenosis rate was 4.4% after a minimum of 8 months follow-up. Compliance with the guidelines for DES use was assessed by two interventional cardiologists, blinded to outcomes; 2.8% did not comply. Mortality was 5.9 and 1.5% had a late myocardial infarction. Conclusion: A policy of selective DES use is feasible, while maintaining low clinical restenosis rates, and has implications for costs and anti-platelet therapy. The high mortality rate reflects the case-mix of our CCL, but may have lead to an underestimate of the restenosis rate. 193 Does the Framingham Risk Score Predict Coronary Artery Disease in Early Menopausal Women Referred for Stress Echocardiography? A Contrast Echocardiography, Cardiac CT and Serum Biomarker Study Stuart Moir* , Sue Ann Ness, Patricia A. Pellikka, Sahar Abdelmoneim, Dalene M. Bott-Kitslaar, Sharonne N. Hayes, Sharon L. Mulvagh Mayo Clinic Echocardiography Laboratory, Rochester, Minnesota, USA Background: The Framingham risk score (FRS) is a frequently utilized clinical tool for predicting coronary heart disease risk. Recent work has suggested that application of this score to women may underestimate the presence of CAD.

Heart, Lung and Circulation 2006;15S:S1–S167

Methods: We prospectively studied postmenopausal women aged 40–60 referred for clinical stress echocardiographic examination. All patients agreed prospectively to undergo contrast stress echocardiography (CSE), cardiac CT for calcification scoring (CACS) and serologic evaluation for highly sensitive C-reactive protein (hsCRP) and lipids. Results: Seventy-five women (age 54 ± 4 years, BMI 32 ± 7 kg/m2 ) with no known CAD underwent stress echocardiography (20 dobutamine, 55 treadmill), cardiac CT and biomarker assessment. FRS < 1%/year, defined as “low risk” was present in 66 (88%). Despite this, 9 (14%) of these “low risk” patients had evidence of myocardial ischemia by contrast stress echocardiography, 34 (52%) had demonstrable CAC, including 10 (15%) with CACS > 100, while the mean hsCRP of the “low-risk” population, was 2.95 mg/dl [22 (33%) had hsCRP > 3 mg/dl]. The FRS was not correlated with an abnormal CSE (r = 0.04, p = 0.7) or CACS (r = −0.07, p = 0.6). BMI was significantly correlated with both of these parameters (CSE r = 0.24, p = 0.04, CACS r = 0.28, p = 0.02). Conclusion: The FRS significantly underestimates the presence of obstructive and non obstructive coronary atherosclerosis (manifest as inducible myocardial ischemia and coronary calcification) in early menopausal women referred for stress echocardiography. Interestingly BMI alone was a better predictor of CAD in this patient population. Low Framingham Risk (n = 66)

Greater than Low Framingham Risk (n = 9)

p

Age

54 ± 5

55 ± 3

0.40

BMI

32.0 ± 7.4

35.4 ± 6

0.18

BMI > 30

39 (59%)

8 (89%)

0.08

FHx of CAD

42 (63%)

3 (33%)

0.08

DM

6 (9%)

3 (56%)

0.04

LDL

113.2 ± 31.6

144.0 ± 27.3

0.016

HDL

64.3 ± 17.9

47.0 ± 6.8

0.012

3.36 ± 2.2

0.08

CACS present

34 (52%)

4 (44%)

0.69

Abnormal SE

9 (14%)

3 (33%)

0.13

hsCRP

2.95 ± 2.6

194 Strain Rate Imaging Improves Septal Analysis in Patients with Left Bundle Branch Block Undergoing Stress Echo—An Angiographic Comparison L. Hanekom* , M. Burgess, C. Jenkins, T.H. Marwick, FCSANZ University of Queensland, Princess Alexandra Hospital, Brisbane, Qld, Australia Difficulty in distinguishing dyssynchrony due to left bundle branch block (LBBB) from septal wall motion (WM) abnormalities can compromise the accuracy of dobu-

Abstracts

tamine echocardiography (DbE) for diagnosis of coronary artery disease (CAD). Strain rate imaging (SRI) quantifies thickening and timing of contraction. We compared the accuracy of SRI quantitation and color map assessment with WM scoring (WMS) in pts with LBBB undergoing coronary angiography. Methods: In 54 pts (21 women, age 64 ± 9 years) with LBBB and known or suspected CAD, undergoing DbE, 40 underwent coronary angiography (significant CAD = QCA > 50%) and 14 with normal WMS were used to define normalcy. Previously defined SRI cut-offs were used to assess accuracy of SRI. SRI color maps (SRCM) at each stage of DbE were assessed by an independent observer for color changes indicative of ischemia, and accuracy compared with WMS. Results: Feasibility of SRI was 88%. Thirty-one pts had CAD (17 with LAD disease). Abnormal segments had significantly lower SR (−0.7 ± 0.5 s−1 versus −1.4 ± 0.8 s−1 , p < 0.0001, AUC 0.83), end systolic strain (ESS) (−8.9 ± 7% versus −14.3 ± 8%, p < 0.0001, AUC 0.73) and higher time to end of systole (tes) (0.25 ± 0.06 s versus 0.20 ± 0.05 s, p < 0.0001, AUC 0.74) and post-systolic index (PSI) (0.52 ± 0.3 versus 0.4 ± 0.3, p0.07, ROC 0.65) at peak stress compared with normal segts. Table 1 summarizes the accuracy of SRI parameters and color maps versus WMS in the diagnosis of CAD and LAD disease (** p < 0.01, * p < 0.05). Conclusion: SRI may improve the accuracy of DbE for the diagnosis of CAD in pts with LBBB, especially in the LAD territory. Table 1. WMS

SR < −0.9 s−1

ESS < −9%

tes > 0.22 s

PSI > 0.2

SRCM

97

94

90

85

80

82

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Methods: Two hundred and sixty-five patients with de novo presentation of coronary disease undergoing angiography (age 64 ± 11, mean ± S.D.) were classified as stable angina (n = 111) and unstable coronary syndrome (n = 154) using Braunwald criteria. In a subset (n = 31 stable; n = 36 unstable), intravascular ultrasound (IVUS) of the culprit stenosis was performed prior to percutaneous coronary intervention (PCI) and trans-lesional blood samples were collected before and after PCI (3 and 10 min) from aorta and distal coronary. Results: Serum ferritin was higher in unstable patients in both baseline aortic (236 ± 216 versus 168 ± 135 ␮g/L, p = 0.003) and distal coronary samples (10 min post PCI: 282 ± 290 155 ± 117, p = 0.05). Plaque burden was higher (p = 0.05) and positive remodelling was more frequent in unstable patients (p = 0.001). In both aortic and distal coronary samples, ferritin consistently correlated with plaque area (r = 0.33–0.40, p = 0.02–0.04) and was higher in patients with positive versus negative remodeling (p = 0.01–0.007). There was a positive coronary trans-lesional gradient of ferritin 3 and 10 min post PCI (11.8 ± 28.3 ␮g/L, p = 0.005 and 12.4 ± 20.7 ␮g/L, p = 0.0004, respectively), and a corresponding positive trans-lesional gradient of F2 isoprostanes (a reliable measure of oxidant stress in vivo) at baseline (103 ± 274 pg/L, p = 0.01). These gradients did not vary with clinical presentation. Conclusions: Markers of iron stores and oxidative stress are increased in coronary atherosclerotic plaque, and are released with plaque disruption. Redox-active iron may contribute to higher coronary plaque burden, positive remodelling and unstable presentation.

Specificity (%)

56

78

78

25

56

50

Normalcy (%)

83

91

78

35

65

62

196 Strain rate Imaging for the Diagnosis of Coronary Artery Disease During Dobutamine Stress Echocardiography: An Angiographic Comparison L. Hanekom* , S. Moir, L. Jeffries, D. McNab, T.H. Marwick, FCSANZ

CAD Sensitivity (%)

LAD Sensitivity (%)

94

94

72

83

71

80

Specificity (%)

40

70*

78**

24

60

78**

Normalcy (%)

62

81

84

35

76

84

195 Ferritin is Associated with Greater Coronary Plaque Burden, Positive Remodelling and Unstable Clinical Presentation S. Mukherjee* , B.A. Kingwell, A.J. White, K.D. Croft, H.A. Headlam, A.S. Walton, FCSANZ, J.A. Shaw, A.M. Dart, FCSANZ, S.J. Duffy, FCSANZ Alfred & Baker Medical Unit, The Alfred Hospital, Melbourne, Vic., Australia Background: Redox-active iron increases reactive oxygen species, causes lipid peroxidation and has been implicated in the pathogenesis of atherosclerosis. We hypothesised that aortic and coronary trans-lesional ferritin levels, a marker of iron stores, would relate to coronary plaque characteristics and clinical presentation as stable versus unstable angina.

University of Queensland, Princess Alexandra Hospital, Brisbane, Qld, Australia Strain-rate imaging (SRI) is sensitive to changes in myocardial deformation. We sought whether this could enhance the accuracy of wall-motion scoring (WMS) at dobutamine stress echocardiography (DbE), and to identify the optimal SRI-parameter. Methods: We studied 227 patients—197 with known or suspected coronary artery disease (CAD), undergoing DbE and angiography, and 30 at low probability of CAD. ROC analysis was performed in 98 patients without previous infarction (Group 1), and assessed by area under curve (AUC) to derive SRI-parameter cut-offs. The accuracy of SRI versus WMS in prediction of CAD was assessed in 64 patients without referral bias or previous infarction (Group 2), and extent of disease was assessed in Group 2 and 35 patients with previous infarction (Group 3). SRI was assessed as peak and increment of strain rate (SR), end-systolic strain (ESS) and post-systolic index (PSI).

ABSTRACTS

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Heart, Lung and Circulation 2006;15S:S1–S167

ABSTRACTS

Results: Feasibility of SRI was 89% at peak stress. Ischemic segments (Group 1) had significantly lower SR (−1.14 ± 0.96 versus −1.68 ± 1.2 s−1 , p < 0.0001, AUC 0.77), ESS (−12.9 ± 9 versus −16.5 ± 10%, p < 0.0001, AUC 0.64) and SR increment (−0.35 ± 0.9 versus −0.79 ± 1.1 s−1 , p = 0.001, AUC 0.72) and higher PSI (0.38 ± 0.26 versus 0.23 ± 0.23, p < 0.0001, AUC 0.72) at peak stress. SRI nonsignificantly increase the accuracy of WMS in Group 2 (Table 1), but did not improve the sensitivity of extent of disease (Table 2). Combination of WMS and SR into an ischemia model [(1.6 × peak systolic SR) − (0.5 × WMS)], did not enhance the accurary of DbE interpretation. Conclusions: Use of SRI during DbE is feasible and accurate, and peak SR appears to be the optimal parameter. However, SRI is not superior to expert visual assessment. Table 1. Accuracy

Sensitivity (%) Specificity (%)

WMS

SR < −0.9 s−1

ESS < −9%

PSI > 20%

SRincr > −0.2/s

Model < −1.5

82 81

97 85

92 73

61 77

95 31*

89 84

Single vessel Multi-vessel LAD Postero-lateral

198 Preliminary Investigation into the Relationship Between Chronic Inflammation, Periodontal Disease and Coronary Artery Disease Belinda Smith1,* , Harris Schlen2 , Robert Whitbourn1 , FCSANZ, Michael Jelinek1 , FCSANZ, Gregory J. Seymour3 , Mary Cullinan3 , Bella Schlen2 , Jim Best2 , Alicia Jenkins2

Table 2. Extent Group 2 (n = 51)

SAA dose-dependently induced significant expression of TF procoagulant activity on PBMC from both controls and patients, accompanied by increased TF protein synthesis, and upregulation of TF mRNA levels. There was no significant difference in basal or stimulated TF between SA and ACS for any stimulant, so the groups were combined. SAA at all doses tested, and LPS, induced higher TF activity in patients than in controls, and SA and ACS patients had higher basal TF activities than controls. SAA induced higher TF activity and mRNA levels in adhered than in non-adhered monocytes, implying it may mainly target macrophages in inflammatory sites. We conclude that SAA may contribute to the hypercoagulable state in coronary disease by inducing TF on monocytes/macrophages, but it does not appear to have a differential effect in ACS compared to SA.

Group 3 (n = 35)

WMS

SR < −0.9 s−1

ESS < −9%

WMS

SR < −0.9 s−1

ESS < −9%

78 87 53 80

96 100 82 97

91 93 82 77

100 100 82 100

92 100 82 92

83 100 86 84

197 Enhanced Induction of Monocyte Tissue Factor by Serum Amyloid A (SAA) in Patients with Coronary Artery Disease Changjie Song1,* , Ying Shen1 , Onn Akbar Ali1 , Paul Witting1 , Carolyn L. Geczy2 , S. Ben Freedman1 , FCSANZ 1 Department of Cardiology and ANZAC Research Institute Vas-

cular Biology Group, Concord Hospital, University of Sydney, Sydney; 2 School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia Elevated SAA predicts coronary events, and we have shown that SAA itself can induce procoagulant tissue factor (TF) expression on monocytes in PBMC preparations. We studied 37 male subjects: 14 with stable angina (SA), 10 with acute coronary syndrome (ACS) and 13 controls. PBMC were stimulated with SAA (1, 25 or 250 ng/ml) or lipopolysaccharide (LPS, 100 ng/ml) for 4 h.

1 Department

of Cardiology, Melbourne, Australia; of Medicine, St Vincent’s Hospital, Melbourne, Australia; 3 Department of Dentistry, University of Otago, New Zealand 2 Department

Many patients presenting with cardiovascular disease do not exhibit a classical risk factor profile. Recent studies have reconsidered the role of chronic infection and inflammation in the pathogenesis of atherosclerosis. Chronic periodontal disease is one of the most prevalent chronic infections in the general community. Aims: (1) Assess relationships between periodontal health, inflammation and endothelial dysfunction in healthy pts and those with CAD. (2) Examine effects of periodontal treatment on measures of inflammation and endothelial dysfunction. Methods: History, examination and pulse-wave analysis, including small artery elasticity (SAE) and inflammatory markers were measured. Dental health assessed by examination, X-ray and Florida Probe. Pts received periodontal intervention, and above investigations were repeated at 6 months. Preliminary results: There is a significant difference in SAE between healthy controls and pts with documented cardiac disease (p = 0.0001). There was a trend towards sig-

Abstract 197 Table. TF activity on monocytes (mU/106 PBMC) from patients with SA or ACS and controls Groups

n

Unstimulated

SAA, 1 ng/ml

SAA, 25 ng/ml

SAA, 250 ng/ml

LPS, 100 ng/ml

Control SA + ACS

13 24

26.3 ± 2.7 41.0 ± 4##

31.2 ± 3.7* 56.9 ± 5.6**,##

141.4 ± 12** 202.3 ± 20.4*,#

206.6 ± 20.9** 312.3 ± 47.1**,#

216.7 ± 19** 323.7 ± 39**,#

Mean ± S.E.M. of TF activity. * P < 0.05, ** P < 0.01 vs. unstimulated, # P < 0.05, # P < 0.01 vs. controls.

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nificance between pts with cardiac disease versus those with periodontal, but no documented cardiac disease (p = 0.073). Our first pt with periodontal disease eligible for 6-month follow-up has shown substantially improved dental health, reduced CRP levels by 60% and increased SAE by 27% following periodontal intervention.

angiography. HRTTE measurement of the LAD wall thickness may represent a valuable non-invasive, inexpensive and rapid technique in detection of coronary atherosclerosis and therefore warrants further investigation.

199 Non-Invasive Detection of Coronary Artery Atherosclerosis: A High Resolution Transthoracic Echocardiography Study

200 Clinical, Electrocardiographic and Angiographic Predictive Factors of Late Mortality in Rescue PCI Patients

Rebecca Perry* , Carmine G. De Pasquale, FCSANZ, Derek P. Chew, FCSANZ, Lynn Brown, Philip E. Aylward, FCSANZ, Majo X. Joseph, FCSANZ Cardiac Services, Flinders Medical Centre, Bedford Park, SA, Australia The ability of angiography to detect early atherosclerotic changes in the coronary arteries is limited by arterial remodeling. Failure to detect early atherosclerosis may represent a missed opportunity for pre-emptive treatment. We used HRTTE to visualize and measure LAD anterior and posterior wall thickness and vessel luminal and external diameters to determine if any difference exists between healthy volunteers (control group) and patients with angiographically proven coronary artery disease (CAD group) as defined as a coronary artery stenosis >50% in any coronary artery branch other than the LAD. Forty six volunteers, 28 in the CAD group (25 male) and 28 control subjects (13 male), underwent a HRTTE assessment of their LAD. The anterior and posterior wall thickness significantly differed between the CAD group and controls (0.18 ± 0.06 cm versus 0.11 ± 0.02 cm, p < 0.001 and 0.18 ± 0.04 versus 0.11 ± 0.03 cm, p < 0.001, respectively). The external LAD diameter significantly differed between the CAD group and controls (0.46 ± 0.13 cm versus 0.18 ± 0.06 cm, respectively, p = 0.03). However, there was no significant difference in the luminal diameter between the CAD group and the controls (0.18 ± 0.07 cm versus 0.21 ± 0.09 cm, respectively, p = 0.1). The LAD wall thickness and the external diameter of patients with CAD are significantly larger than that of normal volunteers. The luminal diameter however is maintained in both groups indicating that the CAD group has undergone positive remodeling at the site measured and this wall thickening would possibly be missed during

Victar Hsieh∗ , Noemi Wouters, Rozemarijn van den Vijver, Lin Hoe Soo, Feng Yi, Andrew Hopkins, FCSANZ, Sidney Lo, FCSANZ, Dominic Leung, FCSANZ, Craig Juergens, FCSANZ, John French* , FCSANZ Liverpool Hospital, Sydney, Australia Background: Rescue percutaneous coronary intervention (PCI) has become increasingly used to treat failed reperfusion after fibrinolytic therapy for ST elevation myocardial infarction (MI) (STEMI). Methods and results: In all 131 patients with STEMI (59.5% anterior MI) who underwent rescue PCI from 2001 to 2005 in our regional cardiac catheterisation laboratory, we determined, blinded to patient outcomes, electrocardiographic and angiographic factors predictive of late mortality. These factors included the amount of ST elevation prior to fibrinolytic therapy, ST recovery 60 min post-fibrinolysis, >70% ST recovery post-PCI (achieved in 55%), Selvester QRS score (median final infarct size was 18%), CTFC <40 pre- and post-PCI, and pre- and postPCI TIMI 3 flow. The median time from symptom-onset to fibrinolytic therapy (88.5% tenecteplase) was 2.1 h [IQR 1.3–3.5]; nine patients (6.9%) had cardiogenic shock (CS). At angiography at 3.4 h [IQR 2.5–5.1] after fibrinolytic therapy, 48 patients (38%) had infarct related artery TIMI-3 flow, which increased to 88% post-PCI (89% stenting and 71% glycoprotein IIb/IIIa inhibitors). After exclusion of CS which accounted for 50% of deaths, the only independent predictor of 6 months survival was post-PCI TIMI-3 flow (p = 0.018). Conclusion: The 6-month mortality we report in unselected patients undergoing rescue PCI in the era of liberal use of stents, is markedly influenced by the presence of CS. These data, perhaps surprisingly, suggest that the lack of achievement of TIMI-3 flow post-rescue PCI predicted 6-month mortality rather than electrocardiographic parameters such as ST recovery or Selvester QRS score determined infarct size.

ABSTRACTS

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ABSTRACTS

201 Risk Stratification of Patients with Acute Anterior Myocardial Infarction and Right Bundle Branch Block: Importance of QRS Duration, Baseline ST Segment Elevation and Resolution after Fibrinolytic Therapy C.-K. Wong1,* , FCSANZ, W. Gao2 , R. Stewart3 , FCSANZ, N. van Pelt3 , J. French4 , FCSANZ, P. Aylward5 , FCSANZ, H. White3 , FCSANZ 1 Dunedin

School of Medicine, University of Otago, Dunedin; of Public Health and Psychosocial Studies, Akoranga Campus, Auckland University of Technology, Auckland; 3 Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand; 4 Department of Cardiology, Liverpool Hospital, Liverpool, NSW; 5 Flinders Medical Centre, Adelaide, Australia 2 Division

Background: Patients with an acute anterior ST elevation acute myocardial infarction (AMI) and right bundle branch block (RBBB) have a high mortality. It is not known whether further risk stratification can be performed by assessment of early ECG changes. Methods and results: In the Hirulog Early Reperfusion Occlusion (HERO-2) trial, 17,073 patients with AMI within 6 h of symptoms onset were treated with streptokinase and randomised to receive bivalirudin or heparin. There was no difference in the primary endpoint of 30-day mortality. ECGs were recorded at randomisation and 60 min after beginning fibrinolysis. Patients with RBBB and anterior AMI (n = 415) at randomization had a 30-day mortality of 31.6% and patients with an anterior AMI who developed new RBBB at 60 min (n = 100) had a mortality of 33%. Increasing QRS duration by 20 ms increments was associated with increasing 30-day mortality (P < 0.005). Patients with QRS duration ≥160 ms had higher mortality than those with QRS duration <160 ms (37.2% versus 27.2%, P = 0.03 for 415 patients presenting with RBBB and 46.2% versus 24.5%, P = 0.025 for 100 patients developing new RBBB). RBBB resolved at 60 min in 40 patients but 30-day mortality was unchanged (31.6%). For those with persisting RBBB at 60 min, 30-day mortality was lower if ST segment elevation had resolved by ≥50% (20.4% versus 35.3%, P = 0.006). Conclusion: In patients with anterior infarction and RBBB, increasing QRS duration is associated with increasing 30-day mortality. Early ST segment resolution after fibrinolytic therapy (despite persisting RBBB) is associated with lower mortality.

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202 Predictors of Poor LV Function in Local and Transferred Patients Undergoing Primary Angioplasty for ST Elevation Myocardial Infarction A. Yeung* , A. Kam, P. Taverner, M. Rahman, A. Farshid Department of Cardiology, Canberra Hospital, Canberra, Australia Background: Previous studies have suggested significant LV function recovery after primary coronary angioplasty (PPTCA) for acute myocardial infarction. Our aim was to assess LV function in local and transferred patients undergoing PPTCA and to identify predictors of poor LV function. Method: Between July 2003 and July 2005 we studied 113 patients after PPTCA at the Canberra Hospital. Transthoracic echocardiography was undertaken within 24 h and 6 weeks post procedure. Wall Motion Score Index (WMSI) was determined by visual grading and blinded reporting of 16 LV segments. Patient profile: Mean age 60 ± 11, male 75%, smoker 35%, diabetes 13%, anterior MI 43%, transferred for PPTCA 39%, initial TIMI flow 0–1 66%. Results: There was no significant difference in LV function between local and transferred patients. The mean WMSI 1 day following PPTCA were 1.51 ± 0.35 for local versus 1.48 ± 0.34 for transferred patients (p = NS). On univariate analysis predictors of poor LV function included anterior MI (p < 0.001), late presentation (pain to door >160 min) (p < 0.007), female sex (p = 0.011), and age >65 (p < 0.03). Importantly, transfer status was not a significant predictor of poor LV function. On multivariate analysis independent predictors of poor LV function were anterior MI (OR 9.4, 95% CI 3.0–34.8), initial TIMI flow 0–1 (OR 20.5, 95% CI 4.5–156), age >65 (OR 4.2, 95% CI 1.01–19.5) and late presentation (OR 7.7, 95% CI 1.14–158). Conclusion: For patients who were treated with PPTCA for myocardial infarction, we did not demonstrate any significant difference in LV function between local and transferred patients. We found that anterior MI, age>65, an occluded artery and late presentation were independent predictors of poor LV function.

Abstracts

203 Combining Warfarin and Antiplatelet Therapy After Coronary Stenting in the Global Registry of Acute Coronary Events: Is it Safe and Effective to Use Just One Antiplatelet Agent? Nguyen1,* ,

Lim1 ,

Walton1 ,

Michael C. Yean L. Antony FCSANZ, Jeffrey Lefkovits2 , FCSANZ, Giancarlo Agnelli3 , Shaun G. Goodman4 , Andrzej Budaj5 , Dietrich C. Gulba6 , Jeanna Allegrone7 , David Brieger8 , FCSANZ, for the GRACE Investigators 1 Center

for Cardiovascular Therapeutics, Western Hospital, Melbourne, Australia; 2 Royal Melbourne Hospital, Melbourne, Australia; 3 University of Perugia, Perugia, Italy; 4 Canadian Heart Research Centre and Terrence Donnelly Heart Centre, St. Michael’s Hospital, University of Toronto, Toronto, Ont., Canada; 5 Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland; 6 Krankenhaus Duren, Duren, NRW, ¨ ¨ Germany; 7 University of Massachusetts Medical School, Worcester, MA, USA; 8 Concord Hospital, Sydney, Australia Background: The optimal regimen in terms of efficacy and safety of combination warfarin/antiplatelet therapy following coronary stenting in acute coronary syndrome (ACS) needs further investigation. We describe factors that determine whether single or dual antiplatelet therapy is prescribed in patients who required warfarin following coronary stenting. We also investigated whether single (aspirin or thienopyridine) compared with dual antiplatelet therapy in combination with warfarin is associated with an excess of adverse outcomes. Methods: We analyzed data from 592 patients in the multinational Global Registry of Acute Coronary Events who underwent coronary stenting following presentation with an ACS and were subsequently discharged on either warfarin and dual antiplatelet therapy (n = 404) or warfarin and single antiplatelet therapy (n = 188). Results: Use of single antiplatelet therapy combined with warfarin was more common outside the USA (40% versus 20% of patients receiving warfarin/antiplatelet, P < 0.001). Patients discharged on warfarin/single antiplatelet were less likely to receive unfractionated heparin (65.2% versus 75.8%, P = 0.008) or glycoprotein IIb/IIIa antagonists (47.3% versus 62.6%, P < 0.001) while in hospital, but the use of low-molecular-weight heparin did not differ (53.3% warfarin/single antiplatelet versus 53.8% warfarin/dual antiplatelet, P = 0.91). There was a trend towards less inhospital bleeding in the warfarin/single antiplatelet group (4.8% versus 8.1%, P = 0.16) with no difference in 6-month mortality or myocardial infarction. Conclusion: The use of single compared with dual antiplatelet therapy in combination with warfarin following stent placement is common with significant geographic variation. There was a strong trend towards reduced bleeding without excess mortality or myocardial infarction at 6 months in patients on warfarin and single antiplatelet therapy.

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204 Acute STEMI with Angiographically Normal Coronary Arteries: Causes and Outcomes of this Poorly-Understood Syndrome W. Ahmar* , J. Lefkovits, FCSANZ Department of Cardiology, Royal Melbourne Hospital, Melbourne, Australia Background: The syndrome of ST elevation myocardial infarction (STEMI) in patients with angiographically normal coronary arteries is well-recognised, but poorly understood. Methods: We retrospectively reviewed all cases at our institution from 1995–2005 with chest pain, acute ST elevation in ≥2 contiguous ECG leads for ≥15 min, a rise in creatine kinase, and who had coronary angiography during that admission. For patients with angiographically normal coronary arteries, long-term outcomes were determined by review of hospital records and phone call follow-up. Results: A total of 41 of 714 STEMI patients (5.7%) had angiographically normal coronary arteries. The mean age was 44 years; most were male (70.7%) and smokers (51.2%). There was a low prevalence of diabetes (7.3%) and vascular disease. Three groups were identified according to eventual diagnosis.

Cause

Cryptogenic STEMI (No Cause Found)

Peri-Myocarditis

Cardiomyopathy

n

28 (68%)

11 (27%)

2 (5%)

Mean age (years)

48.4

32.0

49.5

Mean ST elevation

2.4 mV

2.2 mV

2.0 mV

Takotsubo’s

Mean CK rise (IU/L)

766.5

627.5

493.0

LV wall motion abnormality

50% (all segmental)

45% (all global)

100% (apical ballooning)

Thrombolysis

11 (39%)

1 (9%)

0

Mortality/Re-AMI

1

0

0

Mean follow-up was 44 months. In the cryptogenic STEMI group one died and one developed cardiomyopathy. Two patients with perimyocarditis had recurrent chest pain.

Conclusion: Patients presenting with STEMI and angiographically normal coronary arteries infrequently have a cause identified. However, long-term outcomes appear favourable.

ABSTRACTS

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Abstracts

Heart, Lung and Circulation 2006;15S:S1–S167

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205 Current Management of Acute Coronary Syndromes in Australia: The ACACIA Registry

206 The Relative Contribution of Risk Stratification Components to 6-Month Mortality in ACS

Derek P. Chew1,* , FCSANZ, John Amerena2 , FCSANZ, David Brieger3 , FCSANZ, Stephen Coverdale4 , FCSANZ, Jamie Rankin5 , Kiernan Hughes6

Carolyn Astley* , Danni Molloy, Julian C. Vaile, Phil Aylward, FCSANZ, Derek P. Chew, FCSANZ

1 Flinders

Medical Centre, SA, Australia; 2 Geelong Hospital, Vic., Australia; 3 Concord Hospital, NSW, Australia; 4 Nambour Hospital, Qld., Australia; 5 Royal Perth Hospital, WA, Australia; 6 Sanofi-aventis Australia Background: The clinical management of acute coronary syndromes (ACS) is now well informed by guidelines extrapolated from clinical trials. However, the majority of these data have been acquired outside the local context. Hence, we sought to describe the current patterns of care for ACS patients in Australia. Methods: The ACACIA study is a prospective multicentre registry of patients with ST segment elevation MI (STEMI), and high/intermediate risk non-ST-segment elevation ACS (NSTEACS). Centres include metropolitan, regional and rural sites. The enrolment of 4000 patients is planned from 40 sites and will complete in March 2006. Data includes hospital characteristics, geographic and demographic factors, clinical risk stratification, in-hospital management and clinical events at 6 and 12 months. Results: In the preliminary cohort of 338 patients enrolled to date, the median age was 68.1 years and 33.1% were female. By strata of ACS at enrolment, 76/338 (22.5%) were STEMI patients, 155/338 (45.9%) were high-risk NSTEACS patients and 106/338 (31.4%) were intermediate-risk NSTEACS patients. At discharge, 83.1% were on Aspirin, 49.6% on Clopidogrel, 54.0% on a Beta-Blocker, 55.5% on an ACE inhibitor and 78.3% on a Statin. Under-use of evidence-based therapies was observed, particularly in the NSTEACS patients. Conclusions: The ACACIA registry provides a unique opportunity to assess the current management of ACS patients presenting to Australian hospitals. This initiative will enable the correlation of guideline application and clinical events, define under-served subsets of patients and permit local sites to benchmark their practice against a national average. The results of the entire cohort will be presented in August 2006.

Flinders Medical Centre, Flinders University, Adelaide SA, Australia Background: The initial triage and management of suspected ACS patients relies on early accurate risk stratification to appropriately match treatment with risk. While the prognostic significance of ECG changes and cardiac biomarker elevation are clearly established, the relative importance of other components of risk are less defined. Methods: We prospectively assessed 1438 patients presenting with suspected ACS to the Flinders Medical Centre Cardiac Intensive Care. Patients were classified into low, intermediate and high-risk non-ST elevation ACS (NSTEACS), and ST elevation MI (STEMI) according to the established definition of ACS stratum currently employed in the National Health Data Dictionary. Using logistic regression, the adjusted association between 6-month mortality and risk stratification components including ECG changes, biomarker elevation, haemodynamic compromise, ventricular arrhythmia, revascularization, coronary lesion >50%, diabetes, renal impairment (creatinine clearance <60 ml/min), and 2+ risk factors. These estimates were combined with their frequency to calculate the attributable fraction of each component. Results: By 6 months, 85/1438 (5.9%) had died, 37.5% were female, while STEMI, high, intermediate and low-risk ACS comprised 287/1438 (20%), 771/1438 (53.6%), 284/1438 (19.8%) and 96/1438 (6.7%) of the patients, respectively. The attributable risk of each component is displayed (Fig. 1). All components combined accounted for 96.0% of all the mortality observed. Conclusions: The vast majority of mortality observed in an ACS population is attributable to age, renal impairment and possibly cardiac marker elevation. The presence of diabetes, 3 or more risk factors, prior revascularization and known coronary stenosis do not appear to account for much late mortality risk.

Figure 1.

Abstracts

207 Measuring ST Resolution in 12 Lead ECGs in Primary PCI for Acute STEMI A. Yeung* , A. Farshid, D. Coles, I. Jeffery, D. McGill, FCSANZ, S. O’Connor, FCSANZ, R.P. Tan Department of Cardiology, The Canberra Hospital, Canberra, Australia Prompt ST segment resolution [STR] post reperfusion therapy in ST elevation MI [STEMI] has been shown to be an independent predictor of mortality. Aim: To compare two different methods for measuring STR in primary percutaneous coronary intervention [PCI] for acute STEMI. Method: We compared the traditional Method A [% resolution of sum ST elevation [STE] in all leads before and after PCI] to Method B [% resolution of STE in a single lead with the maximal STE] in paired 12 lead ECGs of 120 consecutive patients undergoing primary PCI for acute STEMI from January 2004 to June 2005. STR was defined as complete [>70%], partial [30–70%] and none [<30%]. Results: Mean age 62 years (range 28–90 years), male gender 66.7%, diabetes 15.0%, smoking 32.5%, anterior MI 41.7%, inferior MI 58.3%, mean time from pre to post PCI ECGs was 3:26 h:min, successful primary PCI 95.8%. The STR results for the two respective methods are outlined below: >70% STR

30–70% STR

<30% STR

Method A* % Patient nos 30 day mortality Method

21.2

17.8

4.1

3.7

15.0

56.3

22.7

21.0

4.4

3.8

12.5

B*

% Patient nos 30 day mortality ∗

61.0

Kappa = 0.66 with p < 0.0001.

Conclusion: Method B is more practical and as accurate as Method A for measuring STR post-primary PCI for acute STEMI.

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208 Relationship Between White Cell Count, Blood Sugar Level, and Mortality in Acute Coronary Syndromes. The Global Registry of Acute Coronary Events Onn Akbar Ali1,* , Enrique P. Gurfinkel2 , Joel M. Gore3 , Keith A.A. Fox4 , Andrzej Budaj5 , Giancarlo Agnelli6 , Frederick A. Anderson2 , Rebecca Dedrick2 , David Brieger1 , FCSANZ, for the GRACE Investigators 1 Concord Hospital, Sydney, Australia; 2 ICYCC Favaloro Foun-

dation, Buenos Aires, Argentina; 3 University of Massachusetts Medical School, Worcester, Massachusetts, USA; 4 The University of Edinburgh, Edinburgh, UK; 5 Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland; 6 University of Perugia, Perugia, Italy Background: Elevations of both white cell count (WCC) random blood sugar level (BSL) are associated with increased in-hospital mortality in acute coronary syndromes (ACS). Both reflect a response to stress, yet little is known about the relationship between the two measurements. Aim: To test the hypothesis that random blood sugar level is closely related to WBC count, and elevations in both provide similar prognostic information in terms of in-hospital mortality. Method: The association between admission WCC and random BSL were examined in 16, 513 patients with ACS participating in the GRACE registry. Patients with BSL <70 mg/dl were excluded. Outcomes were stratified according to BSL and WCC and adjusted using GRACE risk score (GRS). Result: There was a graded association between admission BSL and WCC: (BSL <100 mg/dl: WCC 8 (6.5–9.9), BSL 100.1–109.9: WCC 8.6 (6.8–10.6), BSL 110–140: WCC 9.1 (7.3–11.4), BSL >140: WCC 9.9 (7.8–12.6). Mortality increased with increasing WBC count; the relationship between blood sugar level and rate of death was Ushaped, with the death rate being lowest in patients with a blood sugar level 100.1–109.9 mg/dL. Patients with a blood sugar level >140 mg/dL had the highest adjusted mortality: OR 1.35 (1.03–1.77 after adjusting for GRS) and OR 1.65 (1.27–2.15 after adjusting for GRS and WCC). Conclusion: There was a graded association between WBC count and random blood sugar level. Allowing for this, the hospital mortality is increased in patients with blood sugar level >140 mg/dL, indicating that significant hyperglycaemia in response to stress is associated with a poor prognosis.

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209 The Effect of Cardiac Arrest in Hospitalised Patients on Mortality in an Australian Cohort S. Lehman1,* , P. Aylward1 , FCSANZ, C. Astley1 , C. Bridgman1 , P. Molaee1 , J. Vaile1 , S. Worthley2 , FCSANZ, D. Chew1 , FCSANZ 1 Flinders Medical Centre, Flinders University; 2 Royal Adelaide Hospital, University of Adelaide, SA, Australia

Background: Among patients with acute coronary syndromes, cardiac arrest at presentation or during hospital admission remains a catastrophic event associated with significant short-term mortality. We sought to explore the excess short term and late mortality risk of cardiac arrest in an Australian cohort in the context of modern acute coronary syndrome management. Method: We prospectively assessed 1543 patients presenting with suspected acute coronary syndrome to the Flinders Medical Centre Cardiac Intensive Care. All-cause mortality among patients experiencing a cardiac arrest at or during the admission was compared with those not experiencing these events by chi-square analysis. Outcomes among these patients at 6 and 12 months were also assessed by unadjusted cox proportional hazards modeling. Results: By hospital discharge, 45 (2.9%) patients experiencing a cardiac arrest during their index hospital admission were identified. Cardiac arrest was associated with an in-hospital mortality rate of 46.6% (n = 21) compared with 1.2% (n = 19) in those without cardiac arrest. At both 6 and 12 months, the mortality rate did not substantially increase among cardiac arrest patients (n = 22, 48.8%) with a small increase evident among non-cardiac arrest patients (6.5%). By proportional hazards modeling, cardiac arrest was associated with a hazard ratio of 12.3 (95% C.I. 7.7–19.6, p < 0.001) for mortality by 12 months. Conclusions: Of patients presenting with cardiac arrest or as an event during admission, approximately half will not survive 12 months. Of this substantial excess risk, almost all of it is seen in the early in hospital period, with little increase in late mortality observed. 210 Which Guideline Strategies are Associated with the Greatest Effect in 6-Month Mortality from Acute Coronary Syndromes? J.C. Bridgman* , A. Large, P. Molaee, S. Lehman, D. Chew, FCSANZ Department of Cardiac Services, Flinders Medical Centre, Adelaide, SA, Australia Clinical guidelines advocate the use of many therapies, however the application of these treatments is often hampered by logistic, economic or compliance issues. We sought to explore the relative importance of each guideline advocated for Acute Coronary Syndrome management.

Heart, Lung and Circulation 2006;15S:S1–S167

Methods: Data was obtained from the Flinders Medical Centre ACS registry of consecutive patients presenting with myocardial infarction between July and December in the years 2002–2004. Patients who died within 48 h of admission were excluded. The guidelines were grouped as statin, antiplatlet (aspirin and/or clopidogrel), antihypertensive (beta-blocker and/or ACE inhibitor) and revascularisation. Mortality was assessed as ‘in hospital’ and six month mortality by the National Death Index. Univariate analysis was undertaken using chi-squared. Logistic regression was used to adjust for known clinical predictors of risk including age >75, female sex, creatinine clearance <60 ml/min and haemodynamic compromise (Killip Class >2). Results: In total 862 patients were identified. Among these patients 35.5% were female, mean age was 66.7 years (S.D. 13.7), median Killip class was 1 and 31% had diabetes. By six months 44 patients had died. Prior to adjustment for baseline characteristics, statin therapy and revascularisation were associated with the greatest mortality benefit at six months. (Statin HR: 0.39, 95% C.I. 0.20–0.75, p = 0.005) (Revascularisation HR: 0.37, 95% C.I. 0.16–0.88, p = 0.023). After adjustment for the other clinical guideline treatments, statins were the only therapy that showed significant mortality benefit. HR: 0.50, 95% C.I. 0.25–0.96, p = 0.039. Conclusion: Amongst patients presenting with myocardial infarction, statins appears to provide the greatest independent mortality benefit in our experience. Larger studies may define more significant benefit from the other treatment strategies. 211 Patient Factors and the Usage of Acute Coronary Syndrome Clinical Guidelines Luan T. Huynh, Carolyn M. Astley, Carmine G. De Pasquale, FCSANZ, Julian C. Vaile, Philip E. Aylward, FCSANZ, Derek P. Chew, FCSANZ Department of Cardiac Services, Flinders Medical Centre, Bedford Park, SA, Australia Background and aims: Despite widespread availability of clinical guidelines for acute coronary syndromes, studies consistently demonstrate under-use of guideline therapy. The key underserved groups require further clarification. We sought to clarify these characteristics. Method: Myocardial infarction patients surviving to 48 h from July to December 2002 to 2004 were included. Key risk groups explored included age >75 years, female sex, renal dysfunction (GFR <60 ml/min), and diabetes (self reported). Concordance with guideline treatment was compared (antiplatelets, antihypertensives, antilipid medications, and revascularisation). Mortality at six months was analysed using Cochrane-Armitage test of trend. Those receiving two or less compared to those receiving three or more treatments were analysed with logistic regression modelling to assess the adjusted relationship between patient characteristics and guideline discordance.

Abstracts

Results: A cohort of 857 patients was identified. Patients receiving no guideline dictated therapy, one therapy, two, three, and four made up 7.6, 15.2, 29.6, 25.7, and 20.0%, respectively. There was a trend towards higher mortality among those receiving less guideline therapy (see Table). Under-treated patients were more likely to have previous bypass surgery (OR 1.50, 1.02–2.18 CI, p = 0.04), Killip class ≥II (OR 1.69, 1.06–2.69 CI, p = 0.03), or be female (OR 1.32, 1.05–1.68 CI, p = 0.02). Results for patients with renal dysfunction was borderline (OR 1.28, 0.96–1.70 CI, p = 0.09). Age and diabetes were not associated with decreased guideline use. Conclusion: Previous bypass surgery, Killip class ≥II, and female patients are more likely to receive guideline discordant care. These groups should be targeted for quality improvement programs. No. Guideline Therapies

0

1

2

3

4

6-Month Mortality [n (%)]

6 (9.1)

9 (6.0)

16 (6.3)

10 (4.5)

3 (1.7)

p for trend = 0.005

212 High Coronary Compliance Differential Between Stenotic and Distal Arterial Segments May Contribute to Unstable Coronary Artery Disease A.J. White* , S.J. Duffy, FCSANZ, A.S. Walton, FCSANZ, S. Mukherjee, J.A. Shaw, G.L. Jennings, FCSANZ, A.M. Dart, FCSANZ, B.A. Kingwell Baker Heart Research Institute and Alfred Hospital, Melbourne, Australia Coronary arterial biomechanical properties may contribute to plaque disruption and unstable presentation. We hypothesised that there would be a greater differential in coronary artery compliance between stenotic and adjacent arterial segments in patients presenting with unstable compared with stable angina. Methods: Forty-one patients undergoing a percutaneous intervention were classified as acute coronary syndrome (n = 19) or stable angina (n = 22) (age 63 ± 10 years, mean ± S.D., 85% male) using Braunwald criteria. Intravascular ultrasound was used to assess external elastic membrane (EEM) cross-sectional area (CSA) before onset of the Q wave (end-diastole) and at the peak of the T wave (systole). Intra-aortic blood pressure was determined from the fluid-filled coronary guiding catheter. Compliance (C), calculated as the difference between systolic and diastolic CSA, divided by pulse pressure, was determined both within the stenotic lesion and in both proximal and distal reference segments. Results: Coronary compliance was higher in the distal reference segment than at the stenotic site (7.7 ± 13.1 versus 0.0 ± 12.3 mm2 mmHg−1 × 10−3 , mean ± S.D., p = 0.006). When the data were dichotomised by clinical presentation, the compliance difference between the distal and stenotic segments was only significant in the unstable group (unstable, distal 11.9 ± 12.0 versus stenotic 0.00 ± 11.6, p = 0.003; stable, distal 4.1 ± 13.3 versus stenotic 0.0 ± 13.2, p = 0.28). The compliance difference between the proximal and

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stenotic segments did not vary with clinical presentation. Conclusion: A difference between stenotic and distal reference coronary compliance is evident in unstable, but not stable angina patients. Arterial compliance differential would increase shear forces in the vulnerable plaque shoulder region and may promote plaque disruption. 213 Closing the Gap: Are Diabetics Still at Excess Risk with Guideline Mandated Medical Therapy in Acute Coronary Syndromes P. Molaee* , S. Lehman, C. Bridgman, C. Astley, C.G. De Pasquale, FCSANZ, D.P. Chew, FCSANZ Cardiac Services, Flinders Medical Centre, Bedford Park, SA, Australia Background: Coronary heart disease (CHD) is a major cause of morbidity and mortality in diabetics. Previous studies have demonstrated poorer outcomes in diabetics following myocardial infarction (MI). We sought to determine the outcomes of diabetics with acute coronary syndromes (ACS) during the modern era of revascularization and pharmacotherapy. Methods: We assessed patients with ACS admitted to the Flinders Medical Centre from July 2002 to December 2004. Data collected included demographics, clinical characteristics, and therapies including aspirin, clopidogrel, glycoprotein IIb/IIIa inhibitors, statins, beta-blockers and angiotensin converting enzyme (ACE) inhibitors. Outcomes assessed were in-hospital reinfarction, shock, stroke, acute pulmonary oedema (APO) and all cause mortality at 6 months. Comparisons were made using chisquare test. Results: A total of 863 patients were included, with 268 diabetics. Baseline characteristics including age, gender, Killip class, and creatinine clearance were similar between diabetics and non-diabetics. Guideline-advocated medical therapies were used in the majority of patients with no difference between the groups. Non-diabetics had significantly higher rates of revascularization and glycoprotein IIb/IIIa inhibitor use (Table 1). There were no significant differences in terms of reinfarction, shock, stroke, or mortality at 6 months between the groups. The incidence of APO was almost double in diabetics (Table 1). Conclusion: In the modern era of ACS management, we found that diabetics do not appear to have an excess mortality when compared with non-diabetics, despite less revascularization and glycoprotein IIb/IIIa inhibitor use. This analysis re-iterates the importance of widespread use of proven medical therapy in ACS, and supports the use of clinical judgment with respect to revascularization in diabetics.

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Table 1. Diabetic (n = 268)

Non-Diabetic (n = 595)

Glycoprotein IIb–IIIa* (%)

82 (30.6)

279 (47.0)

Revascularization* (%)

66 (24.6)

232 (39.0)

Reinfarction (%)

10 (3.7)

24 (4.0)

APO# (%)

15 (5.6)

17 (2.9)

Six month all cause mortality (%)

10 (3.7)

34 (5.7)

Therapy

Outcomes

∗

p < 0.001.

#

p < 0.05.

214 Review of Myocardial Infarction Mortality in a Conservative Unit J.T. Counsell* , FCSANZ, C. Rasmussen, M. Martin, M. Bogart Dandenong Heart Unit Southern Health, Victoria, Australia Dandenong Hospital has operated a busy 12 bed CCU since 1978. Management of STEMI has been conservative by necessity and inclination. We have been a major contributor to thrombolysis trials. We have no intervention laboratory. Aim: To report mortality for STEMI, many treated with thrombolysis when possible. A selected few were transferred for infarct or rescue angioplasty. We aim to show that STEMI managed in this way achieved a low short term mortality and compare and contrast this with standards set in thrombolysis trials and thrombolysis arm of trials of PCI versus thrombolysis. We analyse our subgroup from thrombolysis trials—an era when recruitment was robust and PCI was rare. Method: 1. All STEMI patients from our data base treated with thrombolysis were analysed for inpatient (IP) mortality over the decade 1995 to 2005. 2. The subgroup entered into thrombolytic trials were analysed for IP and 30 day mortality (the latter since 2000) allowing comparison with “real world” trial figures. Results: One thousand one hundred and fifty-one patients IP mortality was 4.1%. Subgroup 1995–2000 mortality 5.5% (n 36)—era of rare transfers to tertiary hospital. Subgroup 2000–2005 mortality 2% (n 11)—era of increased transfer of selected patients but majority treated with thrombolysis. Subgroup participators in thrombolytic trials IP mortality 1.8% and 30-day mortality of 3.7%.

215 Western Sydney Emergency Triage of Acute Myocardial Infarction (ETAMI) Experience—Reduction in Time to Revascularisation, Improvement in LVEF and 30 Day Mortality G. Sivagangabalan1,* , A. Gerke1 , A. Narayan1 , N. Sadick1 , FCSANZ, S.P. Thomas1 , D.L. Ross1 , FCSANZ, G. Nelson2 , FCSANZ, M. Flynn3 , C. Lees3 , R. Edwards1 , R. Crampton1 , S. Boyages1 , P. Kovoor1 , FCSANZ 1 Departments

of Cardiology and Emergency Medicine, Westmead Hospital; 2 Department of Cardiology, Royal North Shore Hospital; 3 NSW Ambulance Service, NSW, Australia The ETAMI project is a collaboration between the NSW Ambulance Service, Northern and Western Sydney area Health Services with the aim of providing pre-hospital triage of patients with chest pain to expedite revascularisation. During the first 18 months of the trial, the Regional Heart Centre (RHC) in Western Sydney treated 297 patients with acute ST elevation myocardial infarction. We divided these patients into 3 groups: 69 presented to the RHC, 128 to the 3 district hospitals (DH), and 71 were triaged pre-hospital to the cardiac catheterisation laboratory using the ETAMI model. There was a median reduction in door to table time in the ETAMI group of 72 min compared to the DH patients, and 29 min compared to the RHC patients (p < 0.001). Table to open artery (TIMI-3) times were similar. Left ventricular ejection fraction (LVEF) was measured by Gated Isotope Scanning at a mean of 4 days post infarct. The median LVEF was 53% in the ETAMI group, 51% in the RHC group and 47.5% in the DH group. The 5.5% difference between the ETAMI and DH group was significant (p = 0.015). There was a difference in all cause mortality at 30 days, with 8 deaths in the RHC group, 5 deaths in the DH group, and no deaths in the ETAMI group (p = 0.038). There were no deaths in the ETAMI group during transport and bypass of DH. The ETAMI model is safe and improves LV function and 30 day mortality in an Australian metropolitan population with RHC and DH structure. 216 Impact of Clinical Guideline Adherence on 6-Month Survival: Case Control Analysis from the GRACE Registry Derek P. Chew1,* , FCSANZ, Rebecca Dedrick1 , Frederick A. Anderson1 , Alvaro Avezum1 , Kim A. Eagle1 , Dietrich Gulba1 , Joel M. Gore1 , David Brieger2 , FCSANZ, for the GRACE Investigators 1 Flinders 2 Concord

Medical Centre/Flinders University, Adelaide, SA; Hospital, Concord, NSW, Australia

Background: Evidence supporting clinical guidelines in acute coronary syndrome (ACS) has been gathered in an iterative manner, with each new therapy being compared with standard “best clinical practice” at the time within the context of a clinical trial. We assessed the relative impact of each recommendation in real-world practice.

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Methods: We conducted a case-control study of ACS patients. Cases were defined as patients with ST elevation myocardial infarction (STEMI) or non-ST elevation ACS with ECG changes and/or elevated troponin, who survived to hospital discharge but died within 6 months of admission. These patients were compared with those surviving to 6 months (controls) matched for sex, age, GRACE risk score and baseline serum creatinine. Use of angiography, PCI, CABG, aspirin, beta-blockers, ACE inhibitors, statin therapy, IV GP IIb/IIIa blockers, clopidogrel and referral for cardiac rehabilitation were compared between cases and controls using conditional logistic regression, adjusting for prominent clinical characteristics, risk factors and regional factors. Results: One thousand one hundred and eighty-three cases and 3530 controls were identified. Patients with STEMI represented 40% of the of matched population. PCI was associated with the greatest survival benefit (Table). Conclusion: Within modern clinical management of ACS, invasive management with PCI provides substantial improvements in 6-month survival. When compliance with multiple therapies is problematic, the pharmacotherapy associated with the greatest impact on survival appears to be statins. Guideline Treatment

Odds Ratio (95% Confidence Interval)

Percutaneous coronary intervention

1.54 (1.16–2.04)

Coronary artery bypass graft

1.43 (0.91–2.26)

Statins

1.26 (1.06–1.49)

Clopidogrel

1.20 (0.99–1.46)

Angiotensin-converting enzyme inhibitor

1.17 (0.86–1.60)

Referral for cardiac rehabilitation

1.08 (0.90–1.30)

Aspirin

1.07 (0.80.1.42)

Beta-blockers

1.05 (0.86–1.28)

IV glycoprotein IIb/IIIa inhibitors

0.98 (0.77–1.24)

Cardiac catheterization

0.97 (0.78–1.22)

217 Determinants of Coronary Flow Mediated Dilatation in Humans with Atherosclerosis M. McGrady* , P. Thanyasiri, B.P. Bailey, D.S. Celermajer, FCSANZ, M.R. Adams, FCSANZ Department of Cardiology, Royal Prince Alfred Hospital. Sydney, NSW, Australia Introduction: Flow mediated dilatation (FMD) is a fundamental adaptive mechanism for arteries which is dependent on intact endothelial function. Coronary artery FMD has not been measured in humans before, other than in the non-physiological setting of rapid RV pacing. We thus aimed to characterize FMD in human coronary arteries. Method: We measured coronary diameter with quantative angiography before and after relief of chronic total or subtotal (≥99%) occlusion in 171 patients, in whom TIMI0 or TIMI-1 flow was restored to TIMI-3 (with attendant hyperaemia hypothesised to result in FMD). Results: Of the 171 patients, 73% were male, 62% were current or ex-smokers, 47% were diabetic, 53% had hypertension, 64% had dyslipidaemia (documented hyper-

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cholesterolaemia or total cholesterol >5.0 mg/dL) and 49% were taking statin therapy. Mean vessel diameter was 2.8 ± 0.7 mm and flow mediated dilation was 15.1% ± 20.1%. FMD was strongly and inversely related to baseline vessel diameter (r = −0.48, p < 0.001). The degree of vessel dilatation correlated negatively with the presence of diabetes (r = −0.33, p < 0.001) and smoking (r = −0.30, p < 0.001) and positively with the use of statins (r = 0.27, p = 0.001). These factors remained significant on multivariate analysis. Conclusions: Flow mediated dilatation occurs in human coronary arteries. The magnitude of FMD appears related to vascular risk factors and their treatment. 218 The Poor Man’s Multi-Marker Approach to Risk Stratification in Acute Coronary Syndromes P. Molaee* , S. Lehman, C. Bridgman, C. Astley, P. Tideman, P. Aylward, C.G. De Pasquale, D.P. Chew Cardiac Services, Flinders Medical Centre, Bedford Park, South Australia Background: A multi-marker approach using cardiac troponins (cTn), brain natriuretic peptide (BNP) and Creactive protein (CRP) has been proposed for risk stratification in acute coronary syndromes (ACS). We propose the use of a simpler and cheaper multi-marker strategy using cTn, white blood cell count (WCC) and serum creatinine. Methods: We assessed ACS patients admitted to the Flinders Medical Centre from July 2002 to December 2004. Abstracted data included demographics, clinical characteristics, and therapies. Six-month mortality was assessed. Baseline cTnT, WCC, and creatinine were used. These markers were dichotomized, with cTnT of >0.1 ␮g/l, WCC of >11,000/␮l, and creatinine clearance of <60 ml/min being considered positive. All cause mortality at 6 months was compared between groups, using chi-square test and the Cochrane-Armitage test of trend. Adjustment of known confounders was undertaken by Cox proportional hazards modeling. Results: A total of 1029 patients were identified. The median age was 67.2 years (±14.2), 36.4% were female, 25.5% were smokers, 24.9% were diabetic, and the median Killip class was 1.4. The majority of patients (83%) had one or two positive markers. Eight percent had no positive markers and 9% had three positive markers. Patients with more positive markers had significantly higher 6-month mortality (table). The findings were consistent after adjusting for confounding factors including age, Killip class, smoking, diabetes and family history of coronary artery disease (Hazard ratio per additional marker: 2.1, 95% C.I.: 1.5–2.9, p < 0.001). Conclusion: The use of troponin, white cell count, and creatinine clearance at admission, as a multi-marker approach for risk stratification in ACS is simple, inexpensive and highly predictive for late mortality.

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Number of Positive Markers

0

1

2

Mortality at 6 months (%)

1.22

2.76

9.59

3 19.79

220 Use of the Duke Activity Status Inventory to Guide Selection of Stress Protocol C. Pfeffer1 , A. Kennington1,* , T. Marwick2 , FCSANZ

p < 0.001 for all groups. Test of trend p < 0.001.

219 Are We Reaching Target LOL-Cholesterol Levels in Patients Presenting with Acute Coronary Syndromes (ACS)? John M. Elliott* , Rachel M. Elliott, FCSANZ, Lorraine Skelton, C. Frampton, A. Mark Richards, FCSANZ Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand Background: Previous audit has demonstrated that 85% of ACS patients admitted to Christchurch Hospital are discharged on a statin. However, it is not known what proportion of these patients achieve target LDL-cholesterol (LDLC) of <2.5 or <2.0 mmol/L during the year after admission. Methods: We assessed cholesterol levels and statin dose at discharge, and at 4 months and one year after discharge in 100 consecutive patients enrolled in the ACS Study. Data was collated from study records, case notes, pathology lab databases and by phone follow-up. Results: Of 100 consecutive patients, 29% were women, median age was 68 years, 30% had a past history of myocardial infarction, 54% had prior angina, and 37% prior revascularization. Fifty percent were on a statin at admission, increasing to 88% at discharge, 92% at 4 months and 89% at one year follow-up. Dose adjustments were made in 22% during the first year after discharge: 3 started statins, 3 stopped statins including one who started ezetimibe, statin dose was increased in 4 and decreased in 6, and low dose atorvastatin was changed to simvastatin in 6. In 62 patients who had lipids measured at one year, 71% had an

1 Princess Alexandra Hospital, Brisbane; 2 UQ Dept of Medicine, Brisbane, QLD, Australia

Background: The results of exercise testing (ExECG) are most meaningful when pts exercise for >5 min. Avoidance of short exercise times is dependent on appropriate test selection by an experienced test supervisor. We sought whether the prediction of exercise capacity from the Duke Activity Status Inventory (DASI) could be used to tailor protocol selection to ensure that the patient exercised for >5 min. Methods: Observational data were obtained in consecutive ExECG using the Bruce protocol over 12 months (n = 298) and compared with a second 12-month period (n = 204) where pts underwent Bruce, Balke-Ware or Naughton protocols according to DASI score. Based on anticipated exercise capacity, DASI score <18 were selected for Naughton, 18–36 for Balke and >36 for Bruce. Results: The two groups were comparable for demographics, exercise capacity and cardiac workload. Anticipated (DASI) versus actual exercise capacity correlated moderately (r = 0.51) but DASI overestimated workload at low level (see Fig. 1). Using Bruce protocol in 1st 12 months, 84 pts (28%) failed to Ex for >7 min. In the selective protocol period, 44 failed to Ex for >7 min (22%, p = NS). However, of 120 pts selected for Bruce protocol based on the DASI score, only 20 (17%) exercised <7 min (p < 0.03) versus unselected use of Bruce protocol. Conclusions: DASI has moderate reliability for estimating Ex capacity during stress testing. Restriction of Bruce protocol to high DASI limits the number of ExT of brief duration. Intermediate DASI may have poor Ex capacity and should have a less vigorous test.

Figure 1. LDL-C <2.5 and 39% <2.0 mmol/L. In those not on a statin at index admission, mean total cholesterol and LDL-C levels fell from 5.43 and 3.57 mmol/L at admission to 4.16 and 2.30 mmol/L at one year; 69% had an LDL-C <2.5 mmlol/L at one year. Conclusions: One year after admission for ACS, 89% were still receiving a statin but only 62% had had LDL-C levels retested and only 71% of these had LDL-C levels <2.5 mmol/L. This suggests that greater efforts need to be made to achieve LDL-C targets recommended in guidelines for the treatment of ACS.

221 Predictors of ST Segment Resolution in Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction in Patients Achieving TIMI 3 Flow A.C. Gay* , S.A. Hope, Y. Malaiapan, I.T. Meredith, FCSANZ Monash Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Vic., Australia Background: It is suggested that electrocardiographic (ECG) determination of reperfusion status better predicts

clinical outcomes than Thrombolysis in myocardial infarction (TIMI) flow grade at angiography as this better represents myocardial perfusion. Single lead ST segment resolution (STR) is a validated measure of successful reperfusion with thrombolysis; however there is little data on predictors of STR in patients undergoing primary percutaneous coronary intervention (PCI). Methods: Thirty patients presenting within 12 h of symptom onset with ST elevation on an interpretable ECG who underwent primary PCI and achieved TIMI 3 flow were studied. ECG analysis was performed using lens intensified calipers with ST elevation measured 40 ms from the J point in the lead with the greatest ST elevation. All ECGs prior to and the first ECG following PCI were assessed. Possible predictors were assessed using regression techniques. Results: Mean age was 56 ± 15 years, 22 (73%) were male, infarct location was anterior in 14 (47%) and mean symptom to balloon time was 252 ± 163 min. Six patients (20%) achieved no STR (<30%), 10 (33%) achieved partial STR (≥30–<70%) and 14 (47%) achieved full STR (≥70%). Increasing age, male gender and anterior infarct location were independent predictors of failure of full STR (p < 0.01, p < 0.001 and p < 0.05, respectively). Cardiovascular risk factors and time to balloon did not predict STR. Conclusion: Age, gender and infarct location predict STR in individuals undergoing primary PCI. Despite TIMI 3 flow, full STR was observed in less than half of the patients, further illustrating that epicardial flow inadequately represents myocardial perfusion. 222 Leukocyte (CD) Antigen Expression in Patients with Stable and Unstable Coronary Syndromes Michele McGrady1,* , Chris G. dos Remedios2 , Angus Brown2 , Jo-Dee L. Lattimore1,2 , FCSANZ 1 Cardiology 2 University

Department, Royal Prince Alfred Hospital; of Sydney, Sydney, Australia

Background: Inflammation has a key role in atherogenesis. Our aim was to assess clusters of CD antigen expression that may differentiate patients with stable and unstable coronary syndromes from controls. Method: Forty patients with a clinical history of a coronary syndrome and who were also undergoing coronary angiography at Royal Prince Alfred Hospital were consented. Twenty of this group had an unstable coronary syndrome defined by clinical history and a positive troponin. Venous blood was collected prior to the angiographic procedures. Leukocytes were isolated and hybridised onto a micro-array to simultaneously examine for the expression of 82 different CD antigens. Bioformatic analysis (ANOVA and hierarchical clustering) was undertaken to assess for clusters of CD expression when compared with normal controls (blood donors). Results: Unstable angina patients had significantly different leucocyte CD antigen expression compared to controls (36 CD antigens p < 0.001). Stable angina patients

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also differ significantly from control (28 CD antigens p < 0.001). Stable compared unstable patients, however, demonstrated few differences in expression with 6 CD antigen having a p < 0.05. Conclusion: Patients with atherosclerosis have a pattern of CD antigen expression on leukocytes that is different from a control population. Patients with stable and unstable coronary syndromes, however, are only weakly differentiated between using leukocyte CD antigen expression. 223 The Impact of Coronary Heart Disease Events on Australian Life Expectancy S. Lehman1,* , P. Aylward1 , FCSANZ, S. Worthley2 , FCSANZ, D. Chew1 , FCSANZ 1 Flinders Medical Centre, Flinders University; 2 Royal Adelaide

Hospital, University of Adelaide, Adelaide, SA, Australia Background: Coronary heart disease (CHD) continues to be an important cause of loss of life among the Australian population. We sought to model the effect of presentation with coronary artery disease on life expectancy at various ages among men and women. Method: We used the life-table methodology to estimate the years of life lost from the age of 40 associated with experiencing a CHD event at various ages. The age specific mortality rates for the entire Australian population were obtained from the Australian Bureau of Statistics. Age specific 12-month case fatality rates were obtained from the Australian Institute of Health and Welfare. The residual yearly excess risk following a cardiac event was estimated from clinical trials with long-term follow-up (CAPRIE and RITA-3). The years of life lost was then modelled by adding the case fatality rate and residual yearly excess risk to the estimated non-cardiac yearly mortality rate. Results: The years of life lost modelled at various ages are presented in the table. Males Life-Expectancy (Years)

Females Years Lost

Life-Expectancy (Years)

Years Lost

Healthy from age 40 years

44.8

CHD Event at 40 years

26.6

18.2

45.9 27.3

18.6

CHD Event at 50 years

31.6

13.2

32.4

13.5

CHD Event at 60 years

35.9

8.9

36.9

9.0

CHD Event at 70 years

36.9

7.9

38.4

7.5

CHD Event at 80 years

40.0

4.8

41.2

4.7

Conclusions: The years of life lost are far greater the earlier the coronary event occurs. The effect among women is similar to that of men. This data will be important for evaluating the value of primary prevention strategies in coronary artery disease at various ages in Australia.

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224 Do Patients with Heart Failure Appropriately Undergo Invasive Procedures Post Myocardial Infarction? MultiCentre Audit of Australian Hospitals John French1,* , FCSANZ, Henry Krum2 , FCSANZ, Adam Meehan2 , John Varigos2 , for the post MI audit group 1 Liverpool

Hospital and South West Sydney Clinical School, Sydney; 2 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology & Preventive Medicine Monash University, Melbourne, Australia Background: The degree of adherence to the recommendation of the 2004 ACC/AHA guidelines, that patients with heart failure (HF) following myocardial infarction (MI) have angiography (and angioplasty) performed during the index hospitalisation, is not known. Methods and results: We prospectively evaluated the use of invasive procedures in all admissions post-MI (with and without ST elevation) over a one-month period in 20 Australian hospitals, stratified by the clinical diagnosis of HF made at admission, or at any time during the hospitalisation. Of 475 patients (248 [52.2%] with STEMI) included in the analysis HF occurred in 112 (23.6%), including in 57 (23.0%) with STEMI. HF patients were older (67.5 years versus 62.9 years P = 0.002), more likely female (34.8% versus 23.7% P = 0.03), had more hypertension, and diabetes, but similar smoking and dyslipidaemia to non-HF post-MI patients. Compared to all post-MI patients (nonSTEMI and STEMI) without HF, in patients with HF the frequencies of the following were: angiography 72.3% versus 85.1% (p = 0.003); and angioplasty 33.9% versus 52.9% (p = 0.001). Compared to patients with STEMI without HF, the frequencies of the following were: angiography 72.3% versus 89.5% (p < 0.001); angioplasty 33.9% versus 69.1% (p < 0.001). Also in the 121 (25.5%) post-MI patients aged ≥75 years, compared to those <75 years, the frequencies of angiography and angioplasty procedures 66.1% versus 87.6% (p < 0.001) and 33.9% versus 53.4% (p = <0.001), respectively; 66% of the elderly with, and without HF, had angiography. Conclusions: Presence of HF did not appear to result in an increase in the use of invasive procedures recommended by the guidelines, which can enhance survival in patients with HF post-MI. In particular, there was a lower rate of use of these procedures in the elderly. 225 Abciximab in Combination with Nitric Oxide Potentiation Therapy Increases Haemorrhagic Adverse Effects K.A. Taylor1,* , C.J. Zeitz1,2 , FCSANZ 1 The

Queen Elizabeth Hospital, Adelaide, of Adelaide, Adelaide, Australia

Australia;

2 University

Glycoprotein IIb/IIIa receptor antagonists such as abciximab have an established role especially in the management of high risk ACS/STEMI, during high risk PCI, as a component of intensive antiplatelet therapy. Published risks of major and minor bleeding suggest that the risk/benefit favours therapy. However, concomitant

antiplatelet therapy is usually limited to heparin, aspirin and thienopyridines. However, treatment of high-risk patients may also include IV nitroglycerine (GTN), N-acetylcysteine (NAC), oral verapamil (in the absence of cardiac failure) and perhexiline. Each of which has previously been demonstrated to produce antiplatelet effects and as such may contribute to the overall antiplatelet risk of treatment in these high-risk patients. We therefore sought to determine (1) the overall risk of major bleeding in patients with abciximab (2) factors predictive of occurrence of bleeding episodes. Sixty consecutive patients (7/2002–12/2005) receiving abciximab following coronary angioplasty were reviewed. Intensity of their nitric oxide donor potentiation therapy (NO) was scored (GTN, NAC, perhexiline). Thirty-two patients (53%) developed significant bleeding as defined by TIMI criteria (major—28 (47%); minor—4 (7%)). Univariate analysis revealed the significant predictors of bleeding events to be: urgent (versus elective cases) (p < 0.05), intensity of NO-potentiation therapy (p < 0.05) but not coadministration of non-dihydropyridine calcium antagonists, age or serum creatinine. On multivariate analysis elective/urgent cases and intensity of NO donor/potentiation therapy remained significant correlates of bleeding (p < 0.05 for both) with the later also predicting need for transfusion (p < 0.05) on multivariate analysis. Thus, the risk of bleeding with abciximab is modulated, not only by concomitant therapy with anticoagulants and other anti-aggregatory agents, but by anti-ischaemic drugs which also exert anti-aggregatory effects. 226 Acute Activation of Systemic T Cells During Plaque Instability is Associated with Increased Net Plasma MMP-9 Activity Alice Y. Tiong1,2,* , Changjie Song1,2 , Paul Witting1,2 , S. Ben Freedman1,2 , FCSANZ, David Brieger1,2 , FCSANZ 1 University

of Sydney, Vascular Biology Laboratory, Anzac Research Institute; 2 Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia

Background: Macrophage accumulation and increased net matrix metalloproteinase-9 (MMP-9) activity are features of vulnerable plaques. Activated circulating T cells, present in patients with acute coronary syndromes (ACS), may be direct sources and/or regulators of net MMP-9 activity. We therefore postulated that (1) presence of activated systemic T cells in ACS is associated with increased net plasma MMP-9 activity, and (2) these cells can regulate macrophage MMP-9 production, thus contributing to plaque instability. Methods and results: We recruited 30 patients with ACS and 20 with stable angina (SA). Levels of MMP9 and its endogenous inhibitor, TIMP-1, were determined with ELISA. T cells (CD3+ ) expressing the early (CD69+ ) and late (HLADR+ ) activation markers were determined using flow cytometry. MMP-9:TIMP-1 ratio, CD3+ CD69+ cells and CD3+ HLADR+ cells (%CD3) were increased in ACS compared to SA (76.8 ± 13.6 × 10−3 ver-

sus 34.5 ± 6.0 × 10−3 , p = 0.02; 2.5 ± 0.3 versus 1.4 ± 0.1, p = 0.004; 9.8 ± 0.9 versus 5.6 ± 0.6, p = 0.0006, respectively). We found a significant correlation between MMP-9:TIMP1 ratio and CD3+ CD69+ cells (r = 0.53, p = 0.003), but not with CD3+ HLADR+ cells in ACS. Preliminary results from cell culture studies suggest that human monocyte-derived macrophages and THP-1 monocytic cells produce greater quantities of MMP-9 when co-cultured with activated compared to unactivated T cells (1.84 ± 0.15 ng/ml versus 0.47 ± 0.20 ng/ml, p = 0.005). Conclusion: Acute activation of systemic T cells during plaque instability is associated with increased net plasma MMP-9 activity. These cells can amplify macrophage MMP-9 production. We illustrate for the first time that T cells may contribute to plaque instability by augmenting MMP-9 activity in the peripheral circulation, and in coronary plaques through their regulation of macrophages. Clinical Cardiology – Electrophysiology 227 The Impact of CT Image Integration into an Electroanatomic Mapping System on Clinical Outcomes of Catheter Ablation of Atrial Fibrillation: A Case Controlled Study Peter M. Kistler* , Kim Rajappan, Mark J. Earley, Stuart Harris, Dominic Abrams, Mohammed Jangir, MBBS, Stephen Ellis, Simon C. Sporton, Richard J. Schilling The Department of Cardiology St Bartholomew’s Hospital and Queen Mary University, London, United Kingdom Background: A detailed appreciation of left atrial anatomy may be important in improving the safety and success of catheter ablation (CA) for AF. Objectives: The aim was to determine the impact of CT image integration into a 3D mapping (3DM) system on the clinical outcome of CA for AF. Methods: Ninety-four patients (age: 56 ± 10 years) with symptomatic AF (paroxysmal 46, persistent 48) underwent wide encirclement of ipsilateral PV pairs with the endpoint of electrical isolation. Ablation was guided by 3DM alone (carto 24, NAVX 23) in 47 (3DM group) patients and by CT image integration (cartomerge® ) in 47 (CT group). In persistent AF, a combination of linear ablation at the LA roof, cavotricuspid isthmus, mitral isthmus and targeted ablation of fractionated electrograms was also performed. Results: Successful PV electrical isolation did not differ between the two groups. Fluoroscopy times were significantly reduced in the CT group (49 ± 27 min versus 62 ± 26 min in 3DM group, p = 0.03). Arrhythmia recurrence was reduced in the CT group (32% versus 51% in the 3DM group (p < 0.01). In 30 symptomatic patients (12 CT and 18 3DM) repeat procedures for AF (13 in 3DM and 5 CT, p ≤ 0.10) and AT (5 in 3DM and 7 CT) were performed. Sinus rhythm on 7 day monitor off antiarrhythmic drugs was achieved in 60% in the 3DM group compared with 83% in the CT group (p < 0.05) at a follow up of 25 ± 9 weeks. Conclusion: CA for AF guided by CT integration into a 3DM system was associated with reduced fluoroscopy times, arrhythmia recurrence and increased restoration of sinus rhythm.

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228 Pulmonary Vein Electrical Reconnection in Arrhythmia Recurrence Following Catheter Ablation of Atrial Fibrillation Peter M. Kistler* , Kim Rajappan, Mark J. Earley, Stuart Harris, Dominic Abrams, Dhiraj Gupta, Mohammed Jangir, Simon C. Sporton, Richard J. Schilling The Department Of Cardiology, St Bartholomew’s Hospital and Queen Mary University, London, United Kingdom Introduction: Pulmonary vein (PV) reconnection is important in AF recurrence following catheter ablation (CA) of AF although little is known of the role of the PVs in postprocedural ATs. The aim was to determine the incidence of PV electrical reconnection in atrial arrhythmias following CA of AF. Methods and results: Ninety-four patients (age: 56 ± 9 years) with symptomatic AF underwent ablation by wide encirclement of ipsilateral PV pairs with the endpoint of electrical isolation. If AF was persistent (48) a combination of linear ablation of the cavotricuspid isthmus (CTI), mitral isthmus (MI), LA roof, and fractionated electrograms was also performed. At a mean of 5 ± 9 weeks, AF/AT recurred in 41 (44%) patients. Repeat procedures were performed in 30 symptomatic patients (AF18, AT12). PV reconnection was demonstrated in all 30 (4PVs 57%, 3PVs 20%, 2PVs 20% and 1PV 3%). Electrical isolation was achieved by ablation of conduction gaps in 100%. In 12 patients with 18 ATs, ablation was successful at the MI (6), LA roof (4), CTI (2) and focally at the PV ostium (2), CS ostium (2), perinodal (1) and crista (1). In 18 pts with AF, reisolation of PVs resulted in organisation to AT in 6 and sinus rhythm in 2. Cardioversion was performed in the remaining 10. Overall success on 7-day monitor off antiarrhythmic medication was achieved in 71% at a mean follow up of 25 ± 9 weeks. Conclusion: PV electrical reconnection was demonstrated in all patients with recurrent arrhythmias following CA of AF. The PVs not only play an important role in AF recurrence but may also act as triggers for ATs following linear ablation. 229 Transvenous Cryoablation for Atrioventricular Nodal ReEntrant Tachycardia: Are the Results in Normal Practice as Good as in Published Trials? Peter M. Kistler* , Dhiraj Gupta, Rasha K. Al-Lamee, Mark J. Earley, Stuart J. Harris, Simon C. Sporton, Richard J. Schilling, Anthony W. Nathan St Bartholomew’s Hospital, West Smithfield, London, UK Background: Cryoablation (cryo) is reported to be as effective as radiofrequency ablation (RF) for the treatment of atrioventricular nodal reentrant tachycardia (AVNRT). This coupled with “reversible” AV nodal damage has led to Cryo being considered the modality of choice for AVNRT in many institutions.

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ABSTRACTS

Methods and results: We performed a retrospective case control study comparing Cryo and RF for catheter ablation of AVNRT. Seventy-one consecutive Cryo AVNRT patients (52 ± 16 years) were compared with 71 RF AVNRT patients (52 ± 15 years). Four mm tip Cryo catheters were used in 61 cases and 6 mm tip catheters used in 10. Primary failure of Cryo necessitating RF at the same sitting was seen in 11 (15.4%) patients while there was 1 (1.4%) primary failure in the RF group (p < 0.01). The procedure time, screening time and radiation dose were not significantly different among the two groups and there was no AV block. At follow up (66 ± 12 days), 15 (21.1%) patients in the Cryo group had documented recurrence compared to 3 (4.7%) patients in the RF group (p < 0.01). Thus, primary and/or secondary failure was seen in 26 (36.9%) patients treated with cryo and in 4 (5.6%) patients treated with RF (p < 0.001). There were four cases of primary failure in the 10 cases where 6 mm tip Cryo catheters were used. Conclusions: Primary failure and arrhythmia recurrence was significantly increased with Cryo as compared to RFA for AVNRT. Whether the larger 6 mm tip Cryo catheters have greater efficacy while preserving the safety of the technology remains to be seen. 230 Development and Prospective Assessment of a P-Wave Algorithm to Predict Anatomic Site of Origin of Focal Atrial Tachycardia Peter M. Kistler* , Kurt Roberts-Thomson, Haris Haqqani, Simon P. Fynn, Jitendra K. Vohra, FCSANZ, Joseph B. Morton, FCSANZ, Paul B. Sparks, Jonathan M. Kalman, FCSANZ The Department of Cardiology, Royal Melbourne Hospital and the Department of Medicine, University of Melbourne, Melbourne, Australia Introduction: We performed a detailed analysis of the Pwave morphology (PWM) in consecutive patients undergoing successful RF ablation for focal atrial tachycardia (AT) and constructed and prospectively evaluated an algorithm for identification of the anatomic site of origin. Methods: Based on the PWM from 126 patients, an algorithm was developed to determine anatomic site of tachycardia origin. The algorithm was prospectively applied by two blinded observers to a new population of 30 consecutive focal ATs. Results: The distribution of ATs in the prospectively evaluated population (30) was Crista 11, tricuspid annulus (TA) 5, CS ostium 3, RAA 3, perinodal 1, MA 2, RSPV 1, LSPV 1, LIPV 1, LAA 1 and LS 1. The correct site of tachycardia origin was determined in 28/30 and 28/30 tachycardias, respectively (93%). For both observers, the algorithm incorrectly suggested a CS on location for a tachycardia on the TA immediately adjacent to the CS os and a LPV location for a tachycardia at the RSPV. Conclusion: PWM provides a useful guide to localisation of focal AT. A PW algorithm correctly identified the site of tachycardia origin in 93%.

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231 Clinical Experience with the Use of Implantable Defibrillators for Primary Prevention of Sudden Death Peter J. Psaltis1,2,* , Ben K. Dundon1 , Kurt C. RobertsThomson1 , Martin K. Stiles1,2 , Daniel Cehic1 , Sepehr Shakib3 , Leo J. Mahar1 , FCSANZ, Peter M. Steele1 , FCSANZ, Glenn D. Young1 , Prashanthan Sanders1,2 , FCSANZ 1 Cardiovascular

Research Centre, Department of Cardiology, Royal Adelaide Hospital, Adelaide, SA, Australia; 2 Department of Medicine, University of Adelaide, Adelaide, SA, Australia; 3 Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia Introduction: MADIT II and SCD-HeFT trials have advocated the use of implantable defibrillators (ICDs) for primary prevention. However, its utility and outcomes in clinical practice, outside the trial situation, is unknown. Methods: A case-record review was conducted of patients undergoing de novo ICD implantation for primary prevention by a single Electrophysiology Unit. Patients were selected based on a left ventricular ejection fraction ≤35%. Follow-up was until death or 1st November 2005. Results were compared to ICD patients enrolled in the MADIT II and SCD-HeFT trials. Results: Fifty-nine patients were included for analysis. Forty-four percent had combined ICD-biventricular devices. The table below compares the characteristics and outcomes of our patients, with those from MADIT II and SCD-HEFT. Characteristics

RAH

MADIT II

SCD-HeFT

Number

59

742

829

Males (%)

86

88

77

Age (year)

59 (51–66)

64 ± 10

60 (52–69) 24 (19–30)

Ejection fraction (%)

23 (21–29)

23 ± 5

Follow-up (mth)

18 (14–28)

20

NYHA II–IV CCF (%)

64

65

100

Ischaemic (%)

73

100

52

Non-ischaemic (%)

27

45.5

48

Outcomes Complications (%) Early Late

10

2.5

8.5

5 9

Appropriate therapies (%)

20

N/A

Inappropriate shocks (%)

5

N/A

21 10

Mortality (%)

5

14.2

22

Conclusions: Our clinical experience reveals a relatively high rate of appropriate device therapies in ICD patients with impaired left ventricular function. The observed mortality rate was lower than expected, possibly because of differences in patient and device characteristics between the compared study groups. 232 Cardiac Resynchronisation Therapy—Improvement in Left Ventricular Systolic Function is Determined by Both Intra-Ventricular Systolic and Intra-Ventricular Early Diastolic Dyssynchrony P. Palka* , A. Lange, C.A. Kingsford, K.E. Taylor, J.E. Donnelly, FCSANZ, M. Adsett, J.R. Hayes, FCSANZ, W.J. Stafford, FCSANZ St Andrew’s Medical Institute, Brisbane, Qld, Australia Cardiac resynchronization therapy (CRT) is a new therapeutic approach in patients with heart failure. Selection criteria for CRT are based on the assumption that patients with left ventricular (LV) conduction delay have LV systolic dyssynchrony. The aim was to evaluate whether Doppler tissue echocardiography (DTE) intra- and interventricular dyssynchrony indices can assist in improving LV systolic function. Forty-six patients (mean age 67 ± 11 years) with functional New York Heart classification ≥3 were studied. The lateral, medial LV and tricuspid annular velocities (for systole Sl , Sm , St and early diastole El , Em , Et , respectively) were measured. Intra-ventricular dyssynchrony was defined as the difference between the onset of Sl and Sm (for systole) and El and Em (for early diastole). Inter-ventricular dyssynchrony was defined as the difference between the onset of Sl and St (for systole) and El and Et (for early diastole). Post-CRT the LV ejection fraction (EF) increased (28 ± 7% versus 30 ± 8%; p < 0.01) but QRS duration (current index of LV asynchrony) did not change. Inter- and intra-ventricular dyssynchrony normalised post-CRT. The improvement in LV EF post-CRT was correlated with the degree of both baseline intraventricular systolic dyssynchrony (r = 0.33, p < 0.01) and the degree of inter-ventricular early diastolic dyssynchrony (r = −0.35, p < 0.01). The degree of baseline systolic intra-ventricular dyssynchrony (primary factor) and early diastolic interventricular dyssynchrony (secondary factor related to reducing diastolic constriction effect of the right ventricle to early diastolic LV filling) can predict improvement in LV systolic function. These new indices reflect the mechanism of CRT benefit and may be of value in selection criteria for CRT.

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233 Accurate Early Detection of Paroxysmal Atrial Fibrillation Using Home Monitoring N. Varma1,* , S. Higano2 , C. Stavens3 , N. Assi4 1 Loyola

University, MC, USA; 2 Town and Country Group, Maywood, USA; 3 CV Specialists, Maywood, USA; 4 Gateway Cardiology, Maywood, USA Background: Atrial fibrillation (AF) burden and associated ventricular rates (VR) are difficult to track. Biotronik Home Monitoring (HM) technology enhances data retrieval from implanted devices by wireless, automatic and rapid (<12 h), event notification (EN). Biotronik PAIRED is a prospective study evaluating HM’s ability to accurately report AF. Methods: Daily HM reports contain mode switch (MS, >160 bpm) burden measurements (MS frequency × duration), as %/24 h. A HM AF EN is triggered for >10% MS (2.5 h) per 24 h (=“AF day”). VR is reported as mean bpm/AF day. After first AF EN, patients receive an event monitor. Accuracy of the HM system is determined by correlating HM AF ENs with event monitor records. Results: One hundred and fifty patients (58% male, age = 75.9 ± 11.6 years, 31.3% with previous AF) enrolled to date. At implant, P waves were 2.0 ± 1, range 0.3 to 4.9 mV. HM reported first AF (mean 53 ± 42, range 0–150 days after implant) in 16 patients (three symptomatic), all within 24 h. Seventy-one AF days were paired with event monitors. Mean AF burden was 40 ± 32%, range 11–100%, per AF day. VR during AF days was 84 ± 15 versus non-AF day 74 ± 8 bpm (p = NS). Conclusion: Data indicate low incidence of symptoms and generally well controlled VR during AF in this pacemaker population. HM used for atrial fibrillation permits early notification, accurate quantification, and measurement of associated VR, with fine temporal resolution. HM may have important applications to atrial fibrillation management, e.g. detection of silent episodes, anticoagulation, cardioversion, and rate control. 234 Aborted ICD Shocks: Management with Home Monitoring N. Varma1,* , C. Machado2 , S. Neelaguru3 , W. Bailey4 , S. Ehrlich5 , R. Sauberman6 1 Loyola

University, MC, IL, USA; 2 Heart Cardiology Consultants, MI, USA; 3 Lone Star Arrhythmia, TX, USA; 4 Heart and Vascular Center, LA, USA; 5 Mission Medical Group, CA, USA; 6 Heart Group, NJ, USA Background: Aborted ICD shock therapy may indicate impending storm, change in cardiac status, or hardware problems. Remote monitoring may facilitate management. Biotronik Home Monitoring (HM) technology, provides wireless, automatic and rapid (<12 h) event notification via daily and event-based reports.

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Method: We evaluated incidence, and physician response to notification, of aborted shocks in the multicenter WAMMI study (177 patients). Results: One hundred and forty-one aborted shocks were recorded from 42 patients (78% male, age 67 ± 13 years, LVEF 32 ± 12%) over follow-up period of 231 days. Five patients accounted for 56 (40%) of aborted shocks. Recurrent events resulted from non-sustained VT or lead problems. Without HM notifications, these patients would not have been evaluated for 51 ± 21 days until the next conventional follow-up. However, only six of 42 patients (each with at least two aborted shocks) received interventions, i.e. lead revision, or reprogramming: ventricular sensitivity adjusted to avoid noise, VT detection time extended, second VT detection zone added, medication adjustment. All interventions were successful in eliminating subsequent aborted shocks. Conclusions: The Biotronik HM system is capable of providing timely notification of aborted shock events to physicians, resulting in efficacious treatment. However, overall physician response to transmitted data was low, indicating requirement for system organization and response mechanisms to data retrieved by remote monitoring technologies from implantable devices. 235 Selective Site Pacing with a Catheter Delivered Lead: The Australian PASSES Study Robert Gelder* , Glenn Young, Nigel Lever, for the PASSES Study Investigators Epworth Hospital, Melbourne, Wakefield Hospital, Adelaide, Australia and Wellington Hospital, Wellington, New Zealand Methods: A prospective, randomised multicentre study of 250 patients with standard indications for a dualchamber device from 15 Australian and New Zealand centres was initiated. Patients are randomised to receive Right Atrial High Septal and RVOT High Septal pacing with either the Medtronic SelectSecureTM lead or an Investigator selected Stylet Lead. Electrical measurements are recorded at implant, pre-discharge, 3, 6 months, and 6monthly thereafter. Results: Interim results up to the 3-month follow-up on 57 patients are summarised in the next Table, showing the mean electrical values: Atriala

Ventricular

SelectSecure

Stylet Leads

SelectSecure

imp

2.2b (n = 40)

3.2b (n = 17)

10.6 (n = 40)

3-mo

3.1 (n = 16)

3.8 (n = 7)

15.1 (n = 16)

Stylet Leads

Sensing (mV) 9.9 (n = 17) 15.3 (n = 7)

Pacing threshold at 0.5 ms (V) imp

0.8 (n = 39)

0.7 (n = 16)

0.6 (n = 40)

0.6 (n = 17)

3-mo

0.6 (n = 16)

0.9 (n = 7)

0.8 (n = 16)

0.5 (n = 7)

Bipolar impedance () imp

661 (n = 40)

658 (n = 17)

782 (n = 40)

777 (n = 17)

3-mo

571 (n = 16)

511 (n = 7)

567 (n = 16)

624 (n = 7)

a

Not all stylet leads could be positioned in the High Atrial septum.

b

p < .05; all other differences are non-significant.

Conclusions: Interim results on the electrical performance at selective pacing sites of SelectSecure leads and stylet leads indicate the electrical values are not statistically different between these types of leads, apart from the initial sensing in the atrium which indicated larger p-wave amplitudes with the stylet leads. However, about 70% of the stylet leads could not be positioned in the high atrial septum, which may have influenced the sensed amplitudes. 236 Pacing Selective Sites with a Catheter Delivered Lead: The PASSES study in Australia and New Zealand Glenn Young1,2,* , Rob Gelder1,2 , Nigel Lever1,2 , for the PASSES study investigators 1 Wakefield

Hospital, Adelaide, Epworth Hospital, Melbourne, Australia; 2 Wellington Hospital, Wellington, New Zealand

Methods: A prospective, randomized multicenter study was initiated in 15 implanting centers in Australia and New Zealand. A total of 250 dual-chamber pacemaker patients will be randomized to be paced at selective sites (high Atrial septum, and high Ventricular septum) with either SelectSecure catheter delivered pacing leads, or standard stylet leads. A third group will receive stylet leads in the atrial appendage and RV apex. Primary objective is to compare success rates in reaching the target sites and lead handling between groups. Secondary objectives include long-term performance and clinical benefit of selective site pacing. Results: After enrolling 68 patients the interim results are summarized in the next Table. Successful Positioning (%)

Overall Handling Scorea

Atrium (high septal) SelectSecure (n = 36)

97.2

Stylet leads (n = 14)

28.6

p = <0.05

3.61

p = <0.05

3.00

Ventricle (high septal) SelectSecure (n = 36)

97.2

Stylet leads (n = 14)

92.9

a

p = N.S.

4.06

p = N.S.

4.21

Score: 1, unacceptable; 5, very good.

Conclusion: First results indicate a significantly higher success rate of reaching a selective pacing site in the atrium, with significantly better lead handling, when using the SelectSecure leads. In the ventricle, no significant differences were detected.

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237 Implant Experience with Deflectable Sheath-Delivered Pacemaker Leads

238 Outcome after Complete Percutaneous Removal of Infected Pacemaker Systems

David O’Donnell1,2,3,4,* , FCSANZ, Glenn Young1,2,3,4 , Robert Gelder1,2,3,4 , Nigel Lever1,2,3,4 , for the PASSES Study Investigators

C. Alexopoulos1,* , J. Post2 , C. Fewtrell1 , R. Giles1 , FCSANZ, P.D. Jones3

1 Warringal

pital, Randwick, NSW, Australia; 2 Department of Infectious Diseases, Prince of Wales Hospital and School of Medical Sciences, University of New South Wales, Randwick, NSW, Australia; 3 Department of Infectious Diseases, Prince of Wales Hospital, Randwick, NSW, Australia

2 Wakefield

Hospital, Melbourne, Australia; Hospital, Adelaide, Australia; 3 Epworth Hospital, Melbourne, Australia; 4 Wellington Hospital, Wellington, New Zealand Methods: A prospective, randomised multicentre study of 250 patients with standard indications for a dual-chamber device from 15 Australian and New Zealand centres was initiated. Patients are randomised to receive Right Atrial High Septal and RVOT High Septal lead positioning with either the Medtronic SelectSecureTM lead or Investigator selected Stylet Lead. Methods of implant, implant and fluoroscopy times, electrical measurements and adverse events are recorded at implant. Interim results on 50 patients are summarised in this abstract. Results: Results show SelectSecure leads were implanted using the left subclavian venous access in 75% of the cases, while a left cephalic approach was successfully used in 11% of cases. A 9fr introducer was used 86% of the time, and no introducer was used in the remainder of cases. Skin-toskin times of SelectSecure lead implants decreased from a mean of 72 min for the first implant, to 54 min for the second, and to 49 min for all subsequent cases per implanter, which was not sign. Different from a mean of 47 min for stylet leads. Similarly, mean fluoro times decreased from 18.5, to 13.6, to 6.1 min, respectively, as compared to 8.4 min for stylet leads (N.S.). The mean electrical values measured at implant are summarized in the following table: Atriala SelectSecure (n = 36)

Ventricular

Stylet leads (n = 14)

SelectSecure (n = 36)

Stylet leads (n = 14)

Sensing (mV)

2.1b

3.2b

10.1

9.9

Pacing threshold at 0.5 ms (V)

0.81

0.81

0.60

0.56

Bipolar impedance ()

632

677

758

770

a

Not all stylet leads could be positioned in the High Atrial septum.

b

Atrial sensing p = 0.05; other comparisons are N.S.

Conclusions: Preliminary results indicate the learning curve associated with the implant technique for SelectSecure Lead placement is limited to two implants. The results also demonstrate the electrical values measured at implant at Selective pacing sites are similar for SelectSecure leads as for stylet leads, apart from the atrial sense amplitudes which proved to be smaller in this analysis.

1 Department of Cardiovascular Medicine, Prince of Wales Hos-

Background: Infection of permanent pacemaker systems is uncommon. However, the mortality and morbidity of retained infected pacemaker systems is high. We assessed the safety and rate of relapse after complete percutaneous removal of infected pacemaker systems. Our duration of follow-up was significantly longer than previous studies so as to reliably exclude the possibility of late recrudescence of infection. Methods: We retrospectively reviewed all cases of pacemaker lead removal from June 1992 to April 1997 in our institution. Outcome information was obtained from medical records or referring practitioners. Results: Forty-one patients had pacemaker leads removed for the indication of infection. The medical record was unavailable for one patient. The mean age was 60.8 years (range 19–84 years). The mean duration of pacing prior to removal of infected pacemakers was 8 years (range 2 weeks to 22 years). In conjunction with antibiotic therapy, patients either had immediate replacement of the pacing system, or a period of temporary pacing before a second procedure to replace the pacemaker was undertaken. Nine deaths were reported with none of the 40 subjects experiencing procedure related mortality. There were no cases of relapse of infection after a median duration of follow-up of 8 years (range 3 months to 12 years). Procedure related complications and other adverse events during treatment are also reported. Conclusion: Percutaneous removal of infected pacemakers in conjunction with appropriate antibiotic therapy is a safe and effective treatment for permanent pacemaker infections without a significant risk of late relapse of infection. 239 Left Ventricular Resynchronization Predicted by Individual Performance of Right and Left Ventricular Leads Karen P. Phillips, David B. Harberts, Leonie P. Johnston, David O’Donnell* , FCSANZ Austin Health, Melbourne, Australia Objectives: To evaluate the effect of varying sequential biventricular pacing (BVP) settings on echocardiographic parameters of ventricular dyssynchrony and to identify predictors of the optimal setting. Background: There is increasing evidence that improvement in left ventricular (LV) mechanical dyssynchrony is correlated with LV functional recovery in patients receiv-

ABSTRACTS

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ing cardiac resynchronization therapy (CRT). Recent studies have suggested that sequential BVP may be important for further optimizing parameters of ventricular dyssynchrony. Methods: Twenty-nine patients referred for CRT were evaluated with standard echocardiography and tissue Doppler imaging before and after implantation. Indices of inter- and intra-ventricular dyssynchrony were assessed for trends during simultaneous and sequential BVP. Results: Twelve patients (41%) demonstrated linear trends of decreasing systolic dyssynchrony index with increasing LV preactivation. The mean additional decrease in dyssynchrony index at the optimized setting compared with simultaneous BVP was 26% (p < 0.04). Twenty-two patients (76%) demonstrated linear trends to decreasing inter-ventricular dyssynchrony with increasing LV preactivation. The trends were strongly correlated with the magnitude of difference of the respective dyssynchrony measures in RV only and LV only univentricular pacing. Significantly superior capacity of LV only pacing for ventricular resynchronization was found in this subgroup of patients. Conclusions: In patients receiving CRT, differences in the performance of univentricular pacing are associated with linear trends in ventricular dyssynchrony parameters in sequential biventricular pacing. Quantitative differences in LV univentricular pacing exist, that impact on the capacity of biventricular pacing to correct ventricular dyssynchrony.

metric response (objective improvement in left ventricular function). Objectives: To analyse the response types in patients receiving CRT and to clarify the contribution of different echocardiographic parameters to response. Methods: Forty-three patients referred for CRT were evaluated clinically and with standard echocardiography and tissue Doppler imaging before and after implantation. NYHA class, ECG, ejection fraction and indices of inter-V and intra-V dyssynchrony were assessed. Results: Twenty patients were clinical and volumetric responders; 12 patients were clinical only responders; 4 patients were volumetric only responders; 7 patients were nonresponders. Clinical and volumetric responders had significant intra-V and inter-V dyssynchrony at baseline, with significant improvement noted with CRT (p < 0.05). Clinical only responders had significant intra-V and interV dyssynchrony at baseline, with improvement only in inter-V dyssynchrony with CRT (p < 0.05). Volumetric only responders had significant intra-V but not inter-V dyssynchrony at baseline, with significant improvement in intraV dyssynchrony with CRT (p < 0.001). Nonresponders had no significant intra-V or inter-V dyssynchrony at baseline. Conclusions: In patients receiving CRT, early clinical response is associated with significant inter-ventricular dyssynchrony that was corrected by CRT. Volumetric non-response was documented in association with significant intra-ventricular dyssynchrony that remained uncorrected by CRT.

Abstract 239 Table Variable

Clinical and Volumetric (n = 20)

Clinical Only (n = 12)

Volumetric Only (n = 4)

Nonresponder (n = 7)

p-value

QRS width (ms)

166 ± 25

158 ± 32

132 ± 21

130 ± 27

EF baseline (%)

27 ± 7

29 ± 8

26 ± 5

34 ± 9

0.26

EF CRT (%)

40 ± 10

30 ± 7

40 ± 9

29 ± 9

0.01 <0.001

0.02

IVMD baseline (ms)

56.4 ± 32

44.3 ± 29

4.3 ± 23

0.9 ± 23

IVMD CRT (ms)

22.1 ± 28

23.5 ± 18

−1.3 ± 13

8.7 ± 29

0.14

Largest delay baseline (ms)

118 ± 54

120 ± 25

137 ± 45

76 ± 41

0.06

83 ± 32

97 ± 38

82 ± 34

0.62

Dyssynchrony Index baseline (ms)

40.5 ± 16

40.1 ± 11

45.1 ± 7

28.1 ± 19

0.28

Dyssynchrony Index CRT (ms)

29.4 ± 15

36.9 ± 18

31.3 ± 8

23.6 ± 12

0.28

Largest delay CRT (ms)

98 ± 25

EF, ejection fraction and IVMD, inter-ventricular mechanical delay.

240 Contribution of Dyssynchrony to Response Type in Cardiac Resynchronization Therapy

241 Effect of Intravenous Magnesium on Atrioventricular Nodal Function

Karen P. Phillips, David B. Harberts, Leonie P. Johnston; David O’Donnell* , FCSANZ

Martin K. Stiles* , Prashanthan Sanders, FCSANZ, Patrick Disney, Bobby John, Glenn D. Young

Austin Health, Melbourne, Australia

Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and Department of Medicine, University of Adelaide, SA, Australia

Background: The purported benefits of Cardiac Resynchronization Therapy (CRT) include correction of atrioventricular, interventricular (inter-V) and intraventricular (intra-V) dyssynchrony. Reporting of response to CRT has been variable and includes clinical response and volu-

Magnesium sulphate (MgSO4 ) has been advocated for the treatment of various arrhythmias but its electrophysiological effects are not fully defined.

Abstracts

Methods: Twenty-three patients (15 women, 40 ± 13 years) with supraventricular tachycardia were studied before and after MgSO4 (10 mmol/1 min) was given during tachycardia. The following were evaluated: tachycardia CL; AH, HV, and VA intervals; antegrade and retrograde Wenckebach threshold; refractory periods of the slow pathway, fast pathway, accessory pathway, right atrium, and right ventricle; blood pressure; and serum MgSO4 . Results: AVNRT was induced in 14 and AVRT in 9; one of the latter had dual atrioventricular nodal (AVN) physiology. Magnesium increased from 0.88 ± 0.11 mmol/L to 1.79 ± 0.14 mmol/L (p < 0.0001). In patients with dual AVN physiology, MgSO4 increased tachycardia CL from 339 ± 56 ms to 369 ± 63 ms (p = 0.003) but with no effect in those without dual AVN physiology (346 ± 28 ms to 358 ± 31 ms, p = NS). The AH interval during tachycardia increased in those with dual AVN physiology (241 ± 59 ms to 269 ± 61 ms, p = 0.002) and did not alter in those without (137 ± 19 ms to 140 ± 20 ms, p = NS). Baseline AH interval during tachycardia was different between these groups (p < 0.0001) but tachycardia CL was not. MgSO4 terminated tachycardia in 6 (26%); five with dual AVN physiology. MgSO4 did not alter antegrade or retrograde Wenckebach threshold, HV or VA interval during tachycardia, refractory periods or blood pressure. Abstract 242 Table Variable

NYHA Class

RV pacing Septal

3.0 ± 0.4

3.0 ± 0.1

EF (%)

25.4 ± 6

29.1 ± 7

Largest delay (ms)

121 ± 31

117 ± 33

Dyssynchrony Index (ms) IVMD (ms)

Background: Biventricular pacing has proven beneficial in patients with advanced heart failure and electromechanical delay. Whilst the importance of left ventricular stimulation site has been addressed in studies, the impact of RV pacing site is currently unclear. Methods: Thirty patients referred for CRT were evaluated clinically and with standard echocardiography and tissue Doppler imaging before and after implantation of transvenous biventricular pacing systems. The RV lead was positioned in the apex (RVA) in 15 patients and in the mid inter-ventricular septum (RVS) in 15. At follow-up changes in NYHA class and ejection fraction (EF) were assessed, and indices of inter- and intra-ventricular dyssynchrony measured during univentricular and biventricular pacing. Results: Twelve RVA-paced and 13 RVS-paced patients improved ≥1 NYHA class (p = ns). Twelve RVA-paced and 9 RVS-paced patients had significantly improved EF (p = ns). Indices of intra-ventricular dyssynchrony were comparable in both groups at baseline and in univentricular and biventricular pacing. Significantly worse interventricular dyssynchrony was documented during univentricular RVS-pacing than RVA-pacing (p = 0.02), with a similar trend noted during biventricular (p = 0.05). Conclusions: RV apical and septal pacing are associated with equivalent clinical outcomes in CRT. Comparable improvements in ventricular dyssynchrony were documented during BVP from both pacing sites.

Baseline Apical

S101

Apical

Septal

Biventricular pacing Apical

Septal

1.9 ± 0.6*

1.9 ± 0.4*

37.5 ± 12 111 ± 29

42.2 ± 10

38.4 ± 10

42 ± 11

39 ± 41

47 ± 30

35 ± 25

103 ± 43

85 ± 30†

34.4 ± 14

13‡

55 ± 19§

30 ±

9 ± 28*

35.2 ± 10 72 ± 17† 24.7 ± 8† 27 ± 21*

p < 0.001 vs. Baseline. † p < 0.01 vs. Baseline. ‡ p < 0.05 vs. Baseline. § p < 0.05 vs. Apical. RV = right ventricular. NYHA = New York Heart Association. EF = ejection fraction. IVMD = inter-ventricular mechanical delay.

*

Conclusions: MgSO4 increases tachycardia cycle length and AH interval in patients with dual AVN physiology. This suggests that the dominant acute effect of MgSO4 is prolongation of slow AVN pathway conduction. 242 Impact of Right Ventricular Pacing Site in Cardiac Resynchronization Therapy Karen P. Phillips, David B. Harberts, Leonie P. Johnston, David O’Donnell* , FCSANZ Austin Health, Melbourne, Australia Objectives: To evaluate the effect of right ventricular (RV) pacing site on parameters of ventricular dyssynchrony and clinical outcomes in patients receiving cardiac resynchronization therapy (CRT).

243 Changed in QT Interval During Hypothermia for Cerebral Protection in Cardiac Arrest Patients P. Kertes1,2,* , FCSANZ, K. Phillips2 , S. Valentine1 , S. Bernard1 1 Knox

Private Hospital; 2 Austin Health, Victoria, Australia

Aims: Severe hypothermia is known to cause QT prolongation. Induced hypothermia improves neurologic outcomes in patients (pts) resuscitated from ventricular fibrillation (VF) – we studied the effects of this therapy on the QT interval. Methods: Fourteen consecutive VF arrest pts managed with 24 h of induced hypothermia (target core temperature 32–34 ◦ C) were studied retrospectively. Twelve-lead ECGs were obtained from ICU arrival, during cooling and

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24–48 h post-cooling, and examined (blinded) for heart rate (HR), measured and corrected QT intervals (QTm and QTc) in the lead with the longest QT and in lead V2. Repeatability error was ≤5%. Statistical analysis was by Friedman ANOVA for repeated measures. Results: Mean age was 65 years (43–83 years) with 8M, 6F. VF causes were ischaemia (9), cardiomyopathy (2), iatrogenic (1) and unknown (2). Four pts died: post-cooling ECGs were available in 13/14. Mean ± S.D. values for heart rate (bpm), longest QT and V2-QT (ms) are shown pre-, during and post-hypothermia: Pre-Cooling

During Cooling

Post-Cooling

245 Delay in Pacemaker Implantation is Strongly Associated with Adverse Events in Patients Admitted to Regional Hospitals

P value

C. Hiew* , P. Diu, M. Barlow, J. Leitch, FCSANZ Cardiovascular Department, John Hunter Hospital, Newcastle, Australia

Longest QTm

415 ± 35

522 ± 95

401 ± 54

0.003

Longest QTc

508 ± 41

547 ± 58

472 ± 58

0.01

V2 QTm

380 ± 55

505 ± 98

399 ± 35

0.002

V2 QTc

489 ± 44

527 ± 59

449 ± 54

0.006

90 ± 11

68 ± 15

84 ± 10

0.002

Heart rate

Conclusions: Lead complications are not significantly greater with AF compared to contemporaneously implanted PF leads. However, AF lead complications tend to be more catastrophic. Selective rather than routine use of AF leads would seem the more sensible approach until outcomes data emerge.

QTc was >480 ms in 11/14 pts pre-cooling, 13/14 during, and 5/13 post-cooling. Longest QTc observed were during cooling – up to 658 ms, and >520 ms in 10/14 pts. Conclusion: Post-VF arrest pts tend to have slightly prolonged QTc but normal QTm. However, induced hypothermia produces substantial and significant QTm and QTc prolongation in almost all pts. This must be considered when determining aetiology of the VF arrest. 244 Lead-Related Pacemaker Implant Complications Comparing Active with Passive Fixation Leads T. Watts* , K. Phillips, W. Mohammed, V. Nadurata, FCSANZ, A. Hamer, FCSANZ, D. O’Donnell, FCSANZ, P. Kertes, FCSANZ Electrophysiology Unit, Austin Health, Victoria, Australia Background: Since recent data suggesting deleterious effects of permanent right ventricular apical (RVa) pacing, many centres have switched to RV septal (RVs) sites, using active fixation (AF) leads. Whether RVs pacing is superior remains to be (dis)proved, but in the interim, routine RVs pacing seems reasonable, assuming no added risk. Methods: We examined retrospectively the lead-related complications comparing contemporaneously implanted passive fixation (PF) versus AF pacing leads in all new pacemaker implants since 2002. Findings: Between 7/2002 and 11/2005, 1172 leads were implanted in 641 pts (531 atrial (A) and 641 V leads). There were 682 AF leads (Medtronic model 5076), of which 358 were V (almost all RVs) and 324 were A leads. There were 490 PF leads – 207 A (Medtronic 5524/5554) and 283 RVa (5092/5054). Complications were 8/683 AF (1.2%) versus 9/490 PF (1.8%), p = ns. All 9 PF lead complications were dislodgements (5A, 4V), all requiring repositioning. For the AF leads, 3 dislodged and 5 perforated, two causing tamponade and another two symptomatic pericarditis; 1 pt required emergency surgery. Seven AF leads required repositioning (3A and 4V), including the 3 dislodged and 4 of the 5 perforated leads.

Introduction: Limited information is available on the effects of waiting time and related morbidity in patients admitted to tertiary versus regional centres for urgent pacemaker implantation. Aim: To determine if delays in urgent permanent pacemaker implantation are associated with significant adverse events. Methods: One hundred and one consecutive patients needing urgent pacemaker implantation admitted directly to either a tertiary hospital with pacemaker laboratory or to regional hospitals were analysed. Charts were examined to determine the waiting time and adverse events. Results: There were no significant differences in age or co-morbid conditions in the two groups. Patients in the tertiary centre (44 patients) had a mean hospital stay of 5.2 ± 3.9 days and mean waiting time of 3.3 ± 2.9 days; while patients in regional centre (57 patients) had a mean hospital stay of 8.6 ± 5.3 days (p = 0.0007) and mean waiting time of 6.5 ± 4.7 days (p = 0.0001). Delays in pacemaker implantation were associated with higher rate of adverse events including cannula site infection, congestive heart failure, acute renal failure and ambulation difficulties.

Adverse Events

Tertiary Hospital (n = 44)

Regional Hospitals (n = 57)

Cannula site infection (%)

2 (4.6%)

9 (15.8%)

0.03

CCF (%)

3 (6.8%)

9 (15.8%)

0.08

Acute renal failure (%)

3 (6.8%)

8 (14.1%)

0.11

Ambulation difficulties (%)

4 (9.1%)

12 (21.1%)

P value

0.05

Total adverse events

19

55

0.0001

% Pts spent >4 days waiting for PPM with at least 1 adverse event

25.0%

52.9%

0.0013

Conclusions: Delays in implanting urgent pacemakers are strongly associated with adverse events. Measures need to be implemented to provide equality in access for patients from regional hospitals needing urgent pacemaker implantation.

246 Efficacy of the Selective Sinus Node Inhibitor Ivabradine for Treatment of Drug Refractory Inappropriate Sinus Tachycardia: Early Experience D. Whalley1,* , FCSANZ, J. Kalman2 , FCSANZ 1 Departments of Cardiology, Royal North Shore Hospital, Syd-

ney, Australia; 2 Royal Melbourne Hospital, Vic., Australia Inappropriate sinus tachycardia (IST) may be associated with debilitating symptoms of palpitations, dyspnoea, fatigue and dizziness. Patients are often resistant to, or intolerant of beta-blockers and other rate controlling agents. We have examined the efficacy and tolerability of ivabradine in patients with drug refractory IST. Seven female patients aged 30.7 ± 3.2 years were treated with ivabradine in a starting dose of 2.5 mg bd p.o. All were refractory to at least two drugs. Patients undertook a Holter monitor, completed a survey quantitating their symptom severity and an SF36 questionnaire to assess quality of life at baseline and after 4–6 weeks of ivabradine treatment. Ivabradine therapy resulted in a significant reduction in minimum (47.0 ± 3.1, versus 57.4 ± 3.2 bpm, p < 0.01), mean (77.4 ± 4.7 versus 96.3 ± 4.2 bpm, p = 0.02) and maximum (136.2 ± 11.2 versus 166 ± 13.5, p < 0.01) 24 h heart rate. 5/7 patients reported improved symptom status and/or quality of life. Two patients noted transient visual disturbances but remained on medication. During a follow-up period of 7 ± 1 months 3 patients ceased medication, 1 due to drug inefficacy, 1 due to pregnancy and 1 due to resolution of IST symptoms. We conclude that ivabradine is a promising new agent for the treatment of IST in patients refractory to existing rate controlling medication. 247 Utility of Three Dimensional Mapping Systems for Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation R.J. Hillock* , A.D. McGavigan, K.C. Roberts-Thomson, J.B. Morton, FCSANZ, J.M. Kalman, FCSANZ, P.B. Sparks Department of Cardiology, Royal Melbourne Hospital, Parkville, Victoria, Australia Introduction: 3D mapping systems are now routinely used in combination with standard fluoroscopy for pulmonary vein isolation (PVI) procedures for paroxysmal AF (PAF). Whether X-ray exposure can be reduced using nonfluoroscopic 3D mapping is not known. Methods: A retrospective analysis of 100 consecutive patients with undergoing PVI with fluoroscopic guidance alone (50) to 50 undergoing PVI using 3D guidance was performed. Fluoroscopic, radiofrequency (RF), and procedural time (defined as total time spent on the table) were compared. Procedural endpoint was complete isolation of all pulmonary veins. Results: Age and incidence of a patent foramen ovale or structural heart disease did not differ significantly between the groups. Complete PVI (4 PVs) was achieved

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in all pts. Fluoroscopic times were 20% shorter in the mapping group: 59.2 ± 2.1 min versus 73.9 ± 2.4 min (p < 0.001). RF time was not different between the two groups (nonmapping 43.4 ± 1.6 min versus mapping 45.0 ± 2.0 min, p = 0.51). Procedural time was 42 min longer in the mapping group (258 ± 7 min versus 216 ± 5 min, p < 0.001). Conclusion: 3D mapping systems for PVI for PAF significantly reduce X-ray exposure. This is despite an increase in procedural time. The ability to localise the catheter without fluoroscopic guidance reduces fluoroscopy times, however the procedure times are longer presumably due to time required for setup and creation of virtual LA geometry.

Age (year)

Non-Mapping

Mapping

Mean ± S.E.M. (n = 50)

Mean ± S.E.M. (n = 50)

51.9 ± 1.4

54.9 ± 1.4

PFO (n)

5

6

Structural HD (n)

5

5

Radiofrequency time (min) Fluoroscopy time (min) Procedure time (min)

43.4 ± 1.6 73.9 ± 2.4 216 ± 5

45.0 ± 2.0 59.2 ± 2.1 258 ± 7

p n.s. n.s. n.s. 0.51 <0.001 <0.001

248 The Efficacy of Catheter Ablation to Hemodialysis Patients with Atrial Fibrillation Shinji Kaneko* , Masanori Shinoda, Atsushi Iseki, Hiroki Kamiya, Yoshizumi Asano, Toshimasa Shigeta, Hitoshi Kanayama Department of Cardiology, Kamo Hospital, Hiroshima, Japan Background: Treating AF of hemodialysis patients with left atrial circumferential ablation (LACA) have been avoided, although patients with hemodialysis have enhanced chronic heart strain compared to non-dialysis patients, as well as being restricted to the use of antiarrhythmic agent. Objectives: The purpose of this study was to examine the efficacy of LACA to hemodialysis patients with AF. Methods: We performed LACA to 75 consecutive cases from October, 2002 to September, 2005. There were 10 cases in Dialysis group (DG), with 15.7 years of average dialysis period, and 65 cases in Non-dialysis group (NDG). Results: The preoperative BNP was significantly higher in DG compared to NDG (1043 pg/dl and 88 pg/dl, p < 0.0001), which revealed severer heart strain with dialysis. The AF duration, left atrial diameter, and EF were 1.9 years and 4.2 years (p = 0.052), 41 mm and 38 mm (p = 0.18), and 63% and 68% (p = 0.25), for DG and NDG, respectively. In addition, the recurrence of AF was not admitted in 80% in DG, with average of 23.1 months of observation, and 77% in NDG, with average of 25.6 months, which showed no significant difference (p = 0.83). Conclusion: This study evidently indicated the efficacy of LACA to hemodialysis patients with AF. Because the complication of AF may lead to poor prognosis, LACA should be aggressively performed to treat AF of hemodialysis patients.

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249 The Effect of Dietary N-3 Polyunsaturated Fatty Acids on Inducible Ventricular Arrhythmias in Humans Glenn D. Young1,* , Robert G. Metcalf2 , Leslie G. Cleland2 , Prashanthan Sanders, FCSANZ, Martin K. Stiles, Bobby John, Michael J. James 1 Cardiovascular

Research Centre, Adelaide University, Adelaide, Australia; 2 Dept of Rheumatology, Royal Adelaide Hospital, Adelaide, SA, Australia Background: Fish and/or fish oil consumption has been associated with a reduced risk of sudden death. The effect of dietary fish oil supplementation on the inducibility of ventricular tachycardia (VT) is not known. Methods: Twenty-six patients (63 ± 13 years; 22 male) with inducible VT at electrophysiology study ≥3 months post myocardial infarction were studied. Twelve patients underwent therapy with 3 g/day of n − 3 fatty acids ≥4 weeks while the other 14 acted as controls. There were no other changes made to the medications. The following were evaluated before and after therapy: inducibility of VT; drive CL and number of extra stimuli to induce VT and red blood cell phospholipids levels. Results: There were no differences in the baseline characteristics between study patients and controls. After 43 ± 19 days of n − 3 fatty acid supplementation (180 mg EPA, 120 mg DHA) the proportion of long chain n − 3 PUFAs EPA and DHA compared to total phospholipids in red blood cells significantly increased (9.3 ± 1.1% to 11.5 ± 2%, p = 0.001). After n − 3 therapy 5/12 study patients were no longer inducible and 5 required more aggressive stimulation to induce the arrhythmia (p = 0.003, Wilcoxon’s Sign Rank Test). In 1/14 controls VT was no longer inducible and in three controls a more aggressive induction protocol was required (p = 0.65, Wilcoxon’s Sign Rank test). Conclusions: Dietary n − 3 fatty acid supplementation suppresses the inducibility of VT. This effect may be responsible for the reduction in sudden death associated with increased fish/fish oil consumption. 250 Focal Atrial Tachycardias Arising from the Right Atrial Appendage: Electrocardiographic and Electrophysiologic Characteristics and Radiofrequency Ablation

Kurt C. Roberts-Thomson* , Peter M. Kistler, Andrew D. McGavigan, Richard J. Hillock, Irene H. Stevenson, Steven Spence, Joseph B. Morton, FCSANZ, Jitendra K. Vohra, FCSANZ, Paul B. Sparks, Jonathan M. Kalman, FCSANZ Department of Cardiology, Royal Melbourne Hospital, Parkville, Victoria, Australia Objective: To characterize the electrocardiographic and electrophysiological features and frequency of focal atrial tachycardia (AT) originating from the right atrial appendage (RAA). Methods: Seven patients (3.4%) of 205 undergoing radiofrequency ablation (RFA) for focal AT are reported.

Heart, Lung and Circulation 2006;15S:S1–S167

P waves were classified as negative, positive, isoelectric or biphasic. Results: The mean age was 39 ± 21 years, 6 males, with symptoms for 4.5 ± 5.6 years. Tachycardia was incessant in 5 patients, spontaneous in 1 patient and induced by programmed extrastimuli in 1 patient. These foci had a characteristic P wave morphology. The P wave was negative in lead V1 in all patients, with gradual transition to positive across the precordial leads. The P waves in the inferior leads were positive in 5/7 patients. Mean activation time on the ablation catheter at the successful RFA site = −44 ± 14 ms. Irrigated catheters were used in 5 patients to achieve adequate power when the catheter was positioned between trabeculae. RFA was acutely successful in all patients. Long-term success was achieved in all patients over a mean follow up of 10 ± 6 months. Conclusions: The RAA is an uncommon site of origin for focal AT (3.4%). It can be suspected as a potential anatomic site of AT origin from the characteristic P wave and activation timing. Irrigated catheters are often required for successful ablation. Long-term success was achieved with focal ablation in all patients. 251 Prognostic Value of Electrophysiological Studies on Amiodarone Kurt C. Roberts-Thomson* , Peter J. Psaltis, Martin K. Stiles, Bobby John, Prashanthan Sanders, FCSANZ, Glenn D. Young Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and the Department of Medicine, University of Adelaide, Adelaide, SA, Australia Objective: To determine the usefulness of inducibility testing of ventricular arrhythmias in patients undergoing electrophysiological studies on amiodarone. Methods: We conducted a retrospective study of 49 consecutive patients undergoing inducibility testing of ventricular tachycardia (VT) while on amiodarone. Inducibility was tested by one to three extrastimuli at two right ventricular sites during two paced cycle lengths. The outcomes in patients with inducible and non-inducible VT were compared. Events during follow up were defined as documented VT/VF, appropriate defibrillator therapy or sudden cardiac death. Results: Thirty-four patients had inducible VT and 15 patients were noninducible. 30/34 patients in the inducible group received an automatic cardioverter defibrillator as did 3/15 patients in the noninducible group. There was no significant difference between the two groups in amiodarone dose, aetiology of cardiac disease, left ventricular function, or Angiotensin converting enzyme inhibitor use. Beta-blocker use was higher in inducible VT group (50% versus 20%, p < 0.05). After 48 ± 20 months, the inducible VT group had significantly higher incidence of events than the noninducible group (27/34 patients versus 4/15 patients, p < 0.001). Sudden cardiac death occurred in two patients in the noninducible group. There was no differ-

ence in mortality between the two groups (8/34 inducible patients died versus 3/15 noninducible patients). Conclusion: In patients on amiodarone, inducible VT is a good predictor of future episodes. Non inducibility defines a group at lower risk of future arrhythmic events. 252 Pulmonary Vein and Left Atrial Morphologic Remodelling in Patients Presenting for Ablation of Atrial Fibrillation Ross L. Roberts-Thomson* , Martin K. Stiles, Glenn D. Young, Pawel Kuklik, Kurt Roberts-Thomson, Bobby John, Stephen G. Worthley, FCSANZ, Prashanthan Sanders, FCSANZ Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and Department of Medicine, University of Adelaide, SA, Australia The pulmonary veins (PV) are a dominant source of triggers initiating atrial fibrillation (AF). These structures have also been implicated in the maintenance of paroxysmal AF. The morphologic changes of left atria (LA) and PV in patients with AF have not been fully defined. Method: Consecutive patients (n = 35: 27 M, 57 ± 8 years) presenting for PV isolation for AF underwent thin (<1.5 mm) sectioned contrast enhanced CT scans. LA size and PV distribution, branches, cross-sectional area and ellipticity index (maximum/minimum diameter) were compared with age and sex matched controls. Results: LA of patients with AF are significantly larger in the transverse (55 ± 9 mm versus 50 ± 7 mm, p = 0.004) and longitudinal (55 ± 7 mm versus 52 ± 5 mm, p = 0.03) dimension than controls but not anteroposterior (34 ± 7 mm versus 34 ± 5 mm, p = 0.8). Distribution and number of PV (left 1.8 ± 0.4 versus 1.9 ± 0.2, p = NS; right 2.3 ± 0.9 versus 2.2 ± 0.5, p = NS) were not different between groups. Patients with AF had greater PV cross-sectional area than controls (7.6 ± 2.4 cm2 versus 6.8 ± 3.4 cm2 , p = 0.03) despite minimum PV diameter remaining unchanged (13 ± 3 mm versus 13 ± 4 mm, p = NS). Ellipticity index was greater in patients than controls (1.4 ± 0.3 versus 1.3 ± 0.3, p = 0.01). Distance to first branch was further for left veins than right across all subjects (25 ± 7 mm versus 15 ± 5 mm, p < 0.0001). Curious PV anomalies were evident in four patients with AF and one control. One patient with AF had an absent LA appendage. Conclusion: LA enlargement in patients with AF occurs in the transverse and longitudinal dimensions rather than the anteroposterior. PV have greater cross-sectional area and are more elliptical in patients with AF, which may contribute to their arrhythmogenicity.

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253 Insertion of Permanent Pacemakers as a Routine Day Case is Safe and Feasible P.J. Larsen1,* , K. Homann2 , P. West2 , FCSANZ 1 Department

of Cardiology, The Prince Charles Hospital; Brisbane and Women’s Hospital, Brisbane, Qld., Australia

2 Royal

Background: Insertion of Permanent Pacemakers (PPM) usually requires an overnight hospital admission. We investigated the safety and feasibility of inserting PPM as a day-case procedure. Methods: We retrospectively identified 26 out-patients that underwent insertion of a PPM that was booked as a routine day case over a 12-month period. All patients were admitted on the morning of the procedure and received prophylactic intravenous antibiotics. Post implantation, patients were monitored while resting in-bed for 6–7 h, being nursed 45 degrees upright. A CXR was performed and reviewed by the admitting doctor and the device was checked prior to discharge. All patients were reviewed at 3 months at a pacemaker clinic. Results: The average age of the patients was 73 years (range 26 to 89 years). The indications for pacing were symptomatic: sick-sinus syndrome 35%; atrial fibrillation or atrial flutter with documented pauses 27%; intermittent complete heart block 23%; and intermittent second-degree AV block 15%. A dual-chamber device was inserted in 58% of cases and a cut-down cephalic vein approach was used in 81%. At 3 months, the underlying rhythm in the patients was: sinus 42%; AF 31%; paced 27%. There were no acute complications within 72 h that required re-programming or re-insertion of the device. One patient required readmission 2 weeks after insertion because of pacemaker infection, necessitating device removal. Conclusions: This data suggests that for out-patients booked for PPM insertion, this can be safely performed as a day-case procedure. This approach may be more costeffective and be more acceptable to patients. 254 Clinical Audit of the Use of Implantable Defibrillators at a Single Centre Peter J. Psaltis1,2,* , Kurt C. Roberts-Thomson1 , Ben Dundon1 , Martin K. Stiles1,2 , Daniel Cehic1 , FCSANZ, Leo J. Mahar1 , FCSANZ, Peter M. Steele1 , FCSANZ, Sepehr Shakib3 , Prashanthan Sanders1,2 , FCSANZ, Glenn D. Young1 1 Cardiovascular

Research Centre, Department of Cardiology, Royal Adelaide Hospital; 2 Department of Medicine, University of Adelaide; 3 Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia Introduction: There are widening indications for the use of implantable defibrillators (ICD) for primary and secondary prevention against sudden cardiac death. However, ICDs pose a significant cost to the health care sys-

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tem. We reviewed the indications and outcome of patients being managed with an ICD at a single centre. Methods: A retrospective case-record review was conducted of consecutive patients undergoing de novo ICD implantation at the Royal Adelaide Hospital. Indications for ICD insertion were defined as Primary Prevention (left ventricular ejection fraction of 35% or less with no prior history of sustained ventricular arrhythmia) and Secondary Prevention (history of sustained ventricular tachyarrhythmia, cardiac arrest or syncope attributed to ventricular tachyarrhythmia). Results: One hundred and fifty-seven patients had their first ICD inserted prior to March 2005. Mean age at insertion was 59 ± 14 years. Median time of follow-up was 32 months (25th–75th quartile range 19–53 months). Sixteen percent patients (n = 25) fulfilled Primary Prevention indications and 81% (n = 127) Secondary Prevention. The prevalence of appropriate device therapies was 47% for the overall group, with median time to first therapy 6 months (2–13 months). In the Primary and Secondary groups the rate of use was 20% and 53%, respectively. Overall mortality rate was 15% (n = 23), with median time to death 31 months (13–51 months). Of patients who died, 74% had at least one appropriate device therapy, with the median time delay between first therapy and death 30 months (21–40 months). Conclusions: This single centre experience confirms the findings of large trials of the utility of ICD therapy for primary and secondary prevention in the clinical setting. Appropriate ICD therapies were common in both Primary and Secondary Prevention groups. 255 Dominant Frequency Distribution in Spontaneous Ischemic Ventricular Fibrillation A.P. Gunasekara* , G. Wu, P. Kovoor, FCSANZ, D.L. Ross, FCSANZ, S.P. Thomas Department of Cardiology, Westmead Hospital, Westmead, NSW, Australia Background: A previous study demonstrated sustained stationary high frequency activation during ventricular fibrillation (VF) in a chronic ovine infarct model. The purpose of this study was to identify whether similar sites were detectable during spontaneous VF in an acute ovine infarct model. Methods: We studied 12 sheep acutely after creating an LAD territory infarction. Electrical activation was recorded using 32 multielectrode transmural plunge needles (four electrodes/needle). Unipolar electrograms were recorded in 15 s segments beginning 5 s before onset of spontaneous VF. Attempts were made to terminate VF with DC cardioversion and subsequent episodes of spontaneous VF were recorded. The highest dominant frequency (HDF) was determined using Fast Fourier Transform. Results: Mean frequency for each animal for the first VF episode varied from 2.85 ± 0.7 Hz to 8 ± 1.7 Hz. HDF in most animals (8/12) was located to intramural elec-

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trodes (92%) of base of the heart with a frequency gradient from base to apex. Mean frequency at the base and apex was 8 Hz versus 4.8 Hz, respectively (p = 0.01). There was a trend of mean HDF diminishing with repeated episodes of VF. HDF for VF1, VF2 and VF3 were 9 ± 1 Hz versus 8 ± 1.4 Hz versus 6.5 ± 3.4 Hz, respectively (p = 0.1). Sites of HDF were similar but not identical in second and third episodes of VF. Conclusion: HDF during acute ischemic VF were usually localised to intramural sites. A wide range of DFs were identified. The site of HDF was located close to basal septum in most cases. Repeat episodes of VF did not have identical HDF sites. 256 Is Routine ICD Defibrillation Testing Warranted PreDischarge and at Follow-Up? H. Dimitri* , V. Booth, M. McGuire, FCSANZ, M. Kilborn, FCSANZ Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia There is varying opinion as to whether pre-discharge (day 1) and/or 3–6 month follow-up defibrillation testing is necessary in recipients of new ICDs. At our center, such testing is still routinely performed where we observe two successful defibrillations of ventricular fibrillation (VF) with a 10J safety margin. In this analysis we assess its clinical value. Defibrillation testing was performed on 278 patients pre-discharge and 169 patients at follow-up over 36 months (2003–2006). The protocol involved fluoroscopic screening of the lead followed by tests of lead impedance, pacing, sensing and satisfactory defibrillation of 2 episodes of induced VF with at least a 10J safety margin. Pre-discharge, 5/278 (1.8%) were found to require lead revision. Two of these had normal sensing and pacing but failed to achieve successful defibrillation. Three patients had pace/sense lead problems and were referred for lead revision on these grounds. At follow-up, 6/169 (3.5%) required lead revision. Of these, four had satisfactory pace/sense parameters but were unable to achieve a successful defibrillation and two had unsatisfactory pacing thresholds. This series demonstrates that a small number of patients have significant ICD problems detected at pre-discharge and follow-up defibrillation checks. Of the total 278 patients, 6 (2.2%) were found to have unsatisfactory safety margins for defibrillation that would not have been detected with routine bedside and office testing. The data suggest that follow-up and pre-discharge defibrillation testing still provides some potential clinical benefit. Further study is required to determine whether the resulting lead revisions produce a cost-effective improvement in outcome.

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257 Atrial Remodeling in Chronic Rheumatic Mitral Stenosis Bobby John* , Martin K. Stiles, Pawel Kuklik, Sunil T. Chandy, Glenn D. Young, Stephen G. Worthley, FCSANZ, Jonathan M. Kalman, FCSANZ, Prashanthan Sanders, FCSANZ Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and the Department of Medicine, University of Adelaide, Adelaide, SA, Australia Aim: To assess atrial electrical remodeling in severe mitral stenosis (MS) patients. Methods: Seventeen (30 ± 8 years) rheumatic MS patients (MVArea 0.9 ± 0.1 cm2 ) having mitral commissurotomy (MC) and 17 controls underwent electrophysiologic or electroanatomic mapping. Catheters were placed at lateral right atrium (LRA), crista, coronary sinus, left atrium (LA) and septal right atrium (SRA). We measured: ERP at LA appendage, septal/lateral LA roof, posterior LA, inferior LA, proximal/distal coronary sinus, low/high LRA and SRA at 600 and 450 ms; P wave duration (PWD); and double potentials or fractionated signals (DP/FS) along crista. RA/LA voltage and activation maps were created. Studies were repeated immediately and 6 months (9 patients) after MC. Results: See table (450 ms consistent with 600 ms). MS patients had larger LA (p < 0.0001), electrical scar (p = 0.03), more points with DP/FS in LA/RA (LA 30 ± 10 versus 12 ± 7%; p = 0.0001) and AF (p = 0.03) than controls. After MC, no change in ERP or number/duration of DP/FS along crista was observed, but improved atrial conduction velocity was noted (LA 1.3 ± 0.3 m/s to 1.6 ± 0.3 m/s; p = 0.009). Late after MC, RA ERP and number/duration of DP/FS along crista decreased while bipolar voltage and conduction velocity increased with no change in PWD, scar or AF inducibility. Conclusion: Atrial remodeling in MS is characterized by LA enlargement, loss of myocardium and scarring, widespread and site-specific conduction abnormalities and increased ERP. This is associated with inducibility of AF and may be responsible for the propensity for AF in MS. MS

Controls

P

PWD (ms)

140 ± 22

108 ± 3

0.002

RA ERP at 600 (ms)

232 ± 19

191 ± 8

<0.0001

LA ERP at 600 (ms)

264 ± 18

221 ± 13

0.0001

LA conduction velocity (m/s)

1.3 ± 0.3

1.7 ± 0.4

0.01

RA conduction velocity (m/s)

1.0 ± 0.1

1.6 ± 0.3

<0.0001

LA bipolar voltage (mV)

1.8 ± 0.6

3.6 ± 0.6

<0.0001

RA bipolar voltage (mV)

1.9 ± 0.6

3.4 ± 0.5

<0.0001

Crista DP/FS @ LRA pace

9.8 ± 0.4

4.5 ± 1.9

0.0006

Crista DP/FS duration @ LRA pace (ms)

78 ± 21

54 ± 4

0.0005

258 Ultrasound-Guided Venous Access for Permanent Pacemaker Leads Martin K. Stiles* , David Jones, James T. Stewart, FCSANZ, Guy P. Armstrong, FCSANZ Greenlane Cardiovascular Service at Auckland City Hospital, Auckland, New Zealand Existing methods of venous access have disadvantages. This study documented procedure time for ultrasoundguided permanent pacemaker lead insertion to compare with cephalic venotomy technique. Methods: Two implanters learnt ultrasound-guided axillary venepuncture. Consecutive patients for first-time pacemaker implantation had leads placed utilising ultrasound as initial strategy. When procedural times stabilised, initial strategy was changed to cephalic. Lead placement and screening time from skin incision until all leads in SVC was measured. Results: Initial strategy was ultrasound for 60 then cephalic for 38; no significant differences between groups in baseline characteristics or number of leads implanted were observed. Lead placement and screening times were significantly shorter for ultrasound despite inclusion of all ultrasound learning cases (Table). There was a high success rate for both strategies (88% ultrasound, 87% cephalic). There was significantly greater use of pressure dressings with ultrasound, but no difference in haematoma or pneumothorax. There was a trend for more predictable lead implant times for ultrasound. Independent predictors of lead placement time were BMI, operator, initial strategy (ultrasound < cephalic) and procedure number (faster with experience). Initial Strategy

Ultrasound

Cephalic

N

60

38

Two leads

38%

26%

Lead placement (min)

8 (6)*

Screening (min)

0.1 (0.3)*

Pressure dressing

43%*

12 (9) 0.2 (0.6) 13%

Median (inter-quartile range). ∗

p < 0.05 for comparison between initial strategies.

Conclusion: Ultrasound-guided venepuncture for placement of permanent pacing leads is quick to learn and achieves faster lead placement times with shorter and more predictable fluoroscopy time when compared with the cephalic venotomy technique. 259 Recovery of Atrial Mechanical Function after Catheter Ablation of Atrial Fibrillation ´ eric ´ Prashanthan Sanders1,* , FCSANZ, Fred Sacher2 , Pierre Ja¨ıs2 , Glenn D. Young1 , Patrick Disney1 , Julie ´ eze ` Bradley1 , Stephen G. Worthley1 , FCSANZ, Mel Hocini2 , Martin K. Stiles1 , Bobby John1 , Michel Ha¨ıssaguerre2

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1 Cardiovascular

Research Centre, Department of Cardiology, Royal Adelaide Hospital and the Department of Medicine, University of Adelaide, Adelaide, SA, Australia; 2 Hopital Cardiˆ ologique du Haut-L´evˆeque and the Universit´e Victor Segalen Bordeaux II, Bordeaux, France Atrial mechanical dysfunction due to atrial fibrillation (AF) is implicated in thromboembolic complications. The effect of AF ablation on atrial mechanical function is unknown. Methods: Thirty patients undergoing AF ablation were enrolled into three groups: sinus rhythm ≥2 weeks (SR); AF 1–12 months (persistent); AF ≥24 months (chronic). Left atrial (LA) size, Mitral-A-wave velocity; LA appendage emptying velocity (LAAEV); LA spontaneous echo contrast (LASEC) were evaluated at baseline, immediately after ablation, and ≥3 months after SR. Results: See Table. Ablation had no effect on the SR group. For persistent and chronic AF, ablation and reversion to SR caused atrial “stunning” characterized by decreased LAAEV (p < 0.0001) and increased LASEC (p = 0.02 persistent; p = 0.003 chronic). AF terminated by ablation in 5 and cardioversion in 15, no difference in development or severity of stunning was observed. With SR maintenance, LA size decreased in persistent (47 ± 9 to 41 ± 6 mm, p = 0.03) and chronic AF (50 ± 6 to 43 ± 4 mm, p = 0.01). Atrial function recovered: Mitral-A-wave velocity (p = 0.02 persistent, p < 0.0001 chronic); LAAEV (p = 0.02 persistent, p = 0.008 chronic), LASEC (p = 0.02 persistent, p = 0.005 chronic). However, these did not reach the size/function of SR patients. Conclusion: Atrial mechanical dysfunction on AF termination is independent of mode of termination and its severity dependent on arrhythmia duration. Ablation had no adverse effect on atrial function. SR maintenance after persistent and chronic AF improves atrial function. SR

Persistent

Chronic

P <0.0001

Mitral-A-wave (Post; m/s)

0.51 ± 0.1

0.2 ± 0.06

0.12 ± 0.03

Mitral-A-wave (F/U; m/s)

0.56 ± 0.09

0.44 ± 0.05

0.38 ± 0.08

0.0004

LAAEV (Pre; m/s)

0.58 ± 0.1

0.41 ± 0.15

0.22 ± 0.07

<0.0001

LAAEV (Post; m/s)

0.58 ± 0.11

0.15 ± 0.07

0.08 ± 0.03

<0.0001

LAAEV (F/U; m/s)

0.64 ± 0.08

0.51 ± 0.08

0.43 ± 0.16

0.005

LASEC (Pre)

0

1.0 ± 1.1

1.2 ± 0.8

0.003

LASEC (Post)

0

1.9 ± 1.1

2.9 ± 0.5

<0.0001

LASEC (F/U)

0

0.3 ± 0.5

0.4 ± 0.5

0.09

260 A Single Centre Experience of Ventricular Tachycardia (VT) Ablation Using Advanced Mapping Systems G. Sivagangabalan* , D.L. Ross, FCSANZ, P. Kovoor, FCSANZ, S.P. Thomas, A.R. Denniss, FCSANZ Cardiac Services, Westmead Hospital, Westmead, NSW, Australia We retrospectively reviewed the results of VT ablation procedures using the CARTO or Endocardial Solutions advanced mapping systems. Between 2000 and 2005 there

were a total of 81 procedures performed on 72 patients. With operator preference, 66 were performed with the CARTO system and 15 were performed with the Endocardial Solutions system. We defined procedural success as the inability to induce the clinical VT at the end of the procedure. There were three complications during these procedures. Two patients had cardiac perforation and tamponade requiring percutaneous drainage. One post infarct patient had a peri-procedure cardio-embolic stroke and died 36 h later. Procedure mortality rate 1/81 (1.2%). The difference in procedural success rate between RVOT tachycardia and post infarct VT reflects the different mechanisms of these distinct conditions. RVOT tachy-cardia is a focal curable condition, whereas post infarct VT is caused by complex re-entry circuits in scarred myocardium, and is difficult to ablate. Within the whole group there was a mean difference in procedure duration of 77 min between a successful and failed procedure (p < 0.001) {95% CI 33.2–121.1}. With advanced mapping systems success of VT ablation has improved. However, further improvements in mapping and ablation are necessary to further improve procedure success in post infarct VT. Indication

Number

Mean Duration (min)

Procedural Success

RVOT Tachycardia

32

261

32/32 (100%)

Post Infarct

23

360

16/23 (70%)

Idiopathic LV VT

11

332

10/11 (91%)

Idiopathic Dilated Cardiomyopathy

7

363

5/6 (83%)

ARVD

5

352

2/5 (40%)

Congenital heart disease

2

425

1/2 (50%)

Sarcoidosis

1

315

1/1 (100%)

261 Psychological Implications of ICD Implantation in a New Zealand Population E.G. Newall1,* , N. Lever2 , S. Prasad2 , C. Hornabrook3 , P.D. Larsen1 1 Department

of Surgery and Anaesthesia, Wellington School of Medicine; 2 Department of Cardiology; 3 Psychological Medicine, Capital and Coast District Health Board, Wellington, New Zealand Aim: A significant incidence of anxiety (13–38%) and depression (9–15%) has been reported in implanted cardioverter-defibrillator (ICD) recipients, and these symptoms were related to delivered therapy, age, and gender.1 This study was conducted to determine the prevalence of anxiety and depression and to analyse quality of life in a New Zealand patient population. Methods: Fifty ICD and 50 pacemaker patients attending outpatient clinics were asked questions about device and treatment satisfaction, depression, anxiety (hospital anxiety and depression scale) and quality of life (SF 36). Results: The prevalence of depression and anxiety in the ICD group was 6% and 16%, respectively, and did not differ from the pacemaker group. ICD patients had higher mean

anxiety scores (4.72), than pacemaker patients (3.40), however this score indicated subclinical anxiety levels. Quality of life scores were normal for 49 ICD patients with respect to mental health, and 46 ICD patients with respect to physical function, and not different from the pacemaker group, nor the general population. Anxiety, depression, and quality of life scores were unrelated to time from implantation, delivered therapy, age or gender. ICD patients with poor mental function felt more depressed at diagnosis (p = 0.0014) and felt the same or worse since implant (p = 0.0169). Overall 94% of the ICD patients thought the device was worthwhile. Discussion: New Zealand ICD patients report a lower prevalence of anxiety and depression than described in the American population. Poor mental function predicts self-reported depression at diagnosis and poor progress. 262 Imaging of the Oesophagus Prior to Left Atrial Ablation—A Simple Technique A. Liu* , A. Thomas, H. Teague, W. Heddle, FCSANZ, C. Singleton Department of Cardiac Services, Flinders Medical Centre, Bedford Park, SA, Australia Background: Atrio-oesophageal fistula is a rare and potentially fatal complication of catheter ablation for atrial fibrillation. The anatomical proximity of the oesophagus is of clinical relevance during the procedure. Radio frequency ablation of the left atrial posterior wall risks damaging the oesophagus, possibly leading to an atrio-oesophageal fistula. Previously described methods of identifying oesophageal location have relied on registration of the oesophageal course with other imaging modalities (e.g. Computerised Tomography) and superimposing this on a 3D mapping system. As the oesophagus is a mobile structure, images acquired prior to the procedure may not accurately reflect its position on the day of the procedure. Method: Patients were under general anaesthesia for the procedure. A nasogastric (NG) tube was positioned into the oesophagus of five patients and the location of the oesophagus mapped using a Navistar* catheter by positioning it in the left atrium over the flouroscopic image of the NG tube. Images were acquired in the left anterior oblique 30◦ , anterior posterior and right anterior oblique 30◦ views. The oesophageal position was recorded using labelled CARTO* points, with the NG tube being removed prior to ablation. Result: We were able to locate the oesophagus accurately prior to ablation with only minimal added procedure time. This allowed us to avoid direct ablation over the oesophagus reducing the risk of injury to this structure. Conclusion: This technique is simple with negligible risk of injury to the patient and should be considered as a method of minimising oesophageal injury and severe complications.

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263 CARTO Assisted Left Atrial Circumferential Ablation for Atrial Fibrillation A. Liu* , J. Bowyer, D. Chase, W. Heddle, FCSANZ, C. Singleton Department of Cardiac Services, Flinders Medical Centre, Bedford Park, SA, Australia Background: Catheter ablation is a successful treatment for highly symptomatic, drug refractory atrial fibrillation (AF). Multiple ablation strategies continue to evolve. We previously reported a series of 16 patients undergoing lasso catheter guided pulmonary vein isolation (PVI) with a success rate of 67% over a mean follow period of 40 weeks. We describe our experience with the alternative technique of 3D mapping guided ablation of AF. Methods: Between, February 2005 and February 2006, we prospectively collected data on patients undergoing elective ablation for atrial fibrillation. Circumferential left atrial antral ablation was performed according to published methods utilizing the Navistar, 5 mm irrigated tip catheter* and CARTO XP* 3D mapping system. Sites of fractionated electrograms were also targeted in some patients. Results: Twenty-two patients (17 male), with symptomatic AF on medication underwent 25 ablation procedures. The mean age was 57.3 ± 11 years. Eighty-six percent had paroxysmal AF, 8% persistent AF and 5% permanent AF. In addition to circumferential antral ablation, 66% of patients also underwent linear ablation. At a mean follow up of 3.6 months, the clinical success for this series of patients was 75%. Fifty-eight percent were symptom free without medication, while 22% required at least one antiarrhythmic drug. One patient developed cardiac tamponade. One case of retroperitoneal haematoma was seen. Conclusion: Though our numbers are limited, the clinical success rate of circumferential left atrial antral ablation ± targeting of fractionated electrograms compares favorably with our previously published results utilizing a strategy of PVI. A small risk of serious complications remains. 264 The Influence of Baseline Beta-Blocker Dose on Outcomes in Patients with AICDs Inserted for Primary Prevention P.J. Larsen, J. Ginns* , R. Denman Department of Cardiology, The Prince Charles Hospital, Brisbane, Qld., Australia Background: Previous studies have documented a relationship between baseline beta-blocker dose and outcomes in patients with automatic implantable cardioverter defibrillators (AICDs). We sought to assess this relationship in patients with AICDs inserted for primary prevention at our institution.

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ABSTRACTS

Methods: We retrospectively reviewed the medical records of 198 consecutive patients undergoing AICD implantation for primary prevention at our institution. Baseline beta-blocker dose was arbitrarily graded as none, low (less than half the recommended dose), moderate (half the recommended dose or more but not full dose), or high (recommended dose). All patients were followed up in an AICD clinic at this institution and outcome data was collected. Results: Of the first 52 cases reviewed (mean age 63 years; mean EF 25%; mean follow-up 298 days) there were 3 appropriate ICD therapies (4.65%/year). These patients tended to be receiving less than half the recommended beta-blocker dose compared to the other patients in this cohort. Conclusion: This study suggests that baseline beta-blocker dose influences the likelihood of appropriate therapy in patients with AICDs inserted for primary prevention. 265 The Prevalence of Undiagnosed Obstructive Sleep Apnoea in patients with Lone Atrial Fibrillation A. Liu1,* , P. Allcroft2 , D. Chase1 , W. Heddle1 , FCSANZ, C. Singleton1

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Clinical Trials 266 Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Therapeutic Angiogenesis in Coronary Artery Diseases (PROTECTCAD) Hung-Fat Tse1 , Sukumaran Thambar2,* , Yok-Lam Kwong1 , Philip Rowlings2 , Greg Bellamy2 , FCSANZ, Jane McCrohon2 , Paul Thomas2 , Bruce Bastian2 , John K.F. Chan3 , Gladys Lo3 , Chi-Lai Ho4 , Wing-Sze Chan1 , Raymond Y. Kwong5 , J. Anthony Parker6 , Thomas Hauser6 , Chu-Pak Lau1 1 Department

of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong; 2 Cardiovascular Division, Hunter Heart-Lung Research Guild, John Hunter Hospital, Newcastle, Australia; 3 Department of Radiology & Radiotherapy, Hong Kong Sanatorium & Hospital, Hong, Kong; 4 Department of Nuclear Medicine & Positron Emission Tomography, Hong Kong Sanatorium & Hospital, Hong, Kong; 5 Raymond Y. Kwong, Cardiac Magnetic Resonance Imaging Cardiovascular Division Brigham and Women’s Hospital; 6 Nuclear Medicine, Boston, USA; 7 Cardiology Divisions, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA

1 Department of Cardiac Services, Flinders Medical Centre, Bed-

ford Park, SA, Australia; 2 Mycroft Sleep Centre, Blackwood Hospital, Blackwood, SA, Australia Background: There is an emerging link between obstructive sleep apnoea (OSA) and cardiovascular disease. However, previous studies have shown a variable prevalence of OSA amongst populations of patients with atrial fibrillation (AF) 30–50%. A previous large trial examining the prevalence of OSA in AF patients did not distinguish between those with or without structural heart disease. We hypothesised that amongst patients with lone atrial fibrillation (i.e. patients without structural heart disease) a high prevalence of undiagnosed OSA would exist. Methods: We conducted a prospective, observational study of 24 consecutive patients with lone atrial fibrillation referred to our arrhythmia clinic, without a previous diagnosis of OSA, between February 1st and December 31st 2005. Patients with a clear culprit for AF, such as pulmonary embolism were excluded from the study. All patients underwent echocardiography, and where possible, ambulatory sleep studies and estimations of Body Mass Index (BMI). Results: None of the patients had significant structural heart disease (mean LA diameter 3.5 cm; LV EF: 61%). The mean BMI was 30.7. Three patients declined investigation with a sleep study. Amongst our study population, 80% had OSA graded moderately severe or severe. The prevalence of OSA amongst our study population was much higher than that of that of the general population in this age group (30%). Conclusion: A high prevalence of OSA exists amongst patients with otherwise unexplained AF. Screening for OSA in lone AF patients is worthwhile.

Introduction and methods: Twenty-eight points with CAD and myocardial ischemia on SPECT, not amenable to conventional revascularization and suffering from class III or IV angina refractory to maximum medical therapy were included in this study. Pts underwent harvesting of BM MNC (CD34+ve cells: 3.86 ± 0.72%), and then were randomized to low dose (1 × 106 cells/0.1 ml injection) (n = 9) and high dose (2 × 106 cells/0.1 ml injection) (n = 10) autologous BM MNC, or control (0.1 ml plasma/injection) (n = 9), direct endomyocardial injection. Primary endpoint was exercise treadmill time at 6 months. Secondary endpoints included CCS and NYHA class, weekly nitroglycerin consumption, myocardial function and perfusion assessed by SPECT and MRI. Results: Baseline group characteristics were not different with age 66.4 ± 1.5 years, 82% males, 68% CABG, 61% PCI, 50% diabetic, 71% with hypertension. A total 422 (mean: 14.6 ± 0.7 per patient) injections were successfully performed at 41 targeted ischemic regions without complication. At 6-month follow-up, treadmill exercise time was significantly increased in patients received BM MNC (464 ± 45 versus 393 ± 31 s, p = 0.048) compared with baseline, but not in controls (439 ± 61 versus 404 ± 81 s, p = 0.23). However, both pts receiving BM MNC and control injections reported significant improvement in CCS class, NYHA class and weekly nitroglycerin consumption at 6 month compared with baseline (all p < 0.05). MRI at 6 month demonstrated significant improved LVEF in patients receiving BM MNC (56 ± 2 versus 52 ± 2%, p = 0.037) compared with baseline, but not in controls (49 ± 3 versus 48 ± 3%, p = 0.89). Conclusions: Direct endomyocardial implantation of autologous BM MNC significantly improved exercise time

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and left ventricular ejection fraction in pts with severe CAD. 267 Meta-Analysis of Randomized Control Trials Using Adult Haemopoietic Stem Cells in the Setting of Acute Myocardial Infarction H. Zimmet1,2,* , FCSANZ, S. Haas1,2 , S. Itescu3,4 , H. Krum1,2 , FCSANZ 1 Department of Epidemiology & Preventive Medicine, Monash

University, Melbourne, Australia; 2 Department of Medicine, Monash University, Alfred Hospital, Melbourne, Australia; 3 Department of Medicine, University of Melbourne, St.Vincent’s Hospital, Melbourne, Australia; 4 Columbia University, New York, USA Aim: Cell-based therapy for acute myocardial infarction (AMI) has used various approaches with regard to cell type and delivery method. Most randomized control trials (RCTs) have utilized haemopoietic stem cells (HSC). It is unclear from individual trials which approach is optimal and if clinically significant improvements in ejection fraction (EF) are attainable. We therefore performed a meta-analysis. Methods: RCTs were identified via MEDLINE and abstract publications. Trials needed at least 20 patients with postAMI EF data (mean ± S.D.) recorded before therapy and at 4–6 months. Results were pooled using the Cohen method. Results: Six trials, with a total of 494 patients, met the specified criteria. EF was measured by MRI in three trials, echocardiography in two and ventriculography in one. Five trials used intracoronary autologous mononuclear bone marrow cells (mBMC), and one used endogenous mobilization of HSC via subcutaneous granulocyte colony-stimulating factor (G-CSF). Baseline EF of patients were well matched between intervention and control groups, and relatively well preserved. Change in EF (%) with HSC are shown in [Fig. 1]. Mean weighted difference in EF (%) of control groups in all trials and in mBMC trials was −0.1 (−1.8 to 1.6) and 1.6 (−0.9 to 4.2), respectively. Statistical differences were observed via z-test between intervention and control groups for all trials (p < 0.001) as well as the sub-category of five trials involving mBMC (p = 0.047). No statistical significance was observed when results for the intervention group of mBMC therapy were compared to G-CSF (p = 0.094). Conclusion: This meta-analysis shows, that in present RCTs, HSC-based therapy post-AMI results in a significant improvement in EF. There appeared to be no added benefit of intracoronary mBMC administration over subcutaneous G-CSF treatment alone.

Figure 1. 268 Recombinant Human Granulocyte-Colony Stimulating Factor (G-CSF) and Intracoronary CD133 Cell Infusion in ‘No-Option’ Patients with End Stage Chronic Refractory Ischaemic Heart Disease Jason C. Kovacic1,3,* , Peter Macdonald1,3 , FCSANZ, John Moore2 , David W.M. Muller1,3 , Michael P. Feneley1,3 , FCSANZ, Helen Tao2 , Anthony Dodds2 , Sam Milliken2 , Judith Freund4 , Silviu Itescu5 , David Ma2 , Robert M. Graham1,3 , FCSANZ 1 Victor

Chang Cardiac Research Institute; 2 Department of Haematology and Haemopoietic Stem Cell Transplantation; 3 Departments of Cardiology; 4 Department of Nuclear Medicine, St Vincent’s Hospital, Sydney, NSW, Australia; 5 Columbia University, New York, NY, USA G-CSF is a novel therapy for ischaemic heart disease patients (IHDPs) and may promote angiogenesis via stem cell or cytokine related pathways. However, the safety and efficacy of G-CSF, in acute or chronic IHDPs (CIHDPs), is unclear. Aims: To assess the safety and efficacy of G-CSF in 20 CIHDPs. Methods: After baseline cardiac assessment (CA) [Seattle-angina-questionnaire, exercise stress test (EST), persantin-sestamibi and dobutamine-echocardiographic imaging], stable ‘no-option’ CIHDPs receive open-label G-CSF commencing at 10 ␮g/kg for 5 days, with an EST on days 4 and 6 (to facilitate myocardial cytokine generation and stem cell trafficking). After 3 months, CA and the same regimen of G-CSF and ESTs is repeated, but in addition, leucopheresis and a randomized double-blinded intracoronary-infusion of CD133+ or unselected cells is performed. Final CA is 3 months thereafter.

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Results: Eighteen male (2 female) CIHDPs (mean age 62) were enrolled. With the trial virtually complete, 8 events have fulfilled pre-specified ‘adverse event’ criteria: 4 ischaemic (troponin-I+) episodes (all non-Q-wave events), 2 episodes of transient thrombocytopaenia (1 profound, but both without sequelae), 1 of gout and 1 unscheduled hospitalisation for exhaustion. Troponin-I was positive on 9 further occasions (all CK-MB negative), however, at these instances angina was identical to baseline. Intracoronary cell infusion was consistently uneventful. There were significant improvements in angina, nitrate use and EST performance (all p < 0.01), with analysis of imaging data imminent. Conclusions: Administering G-CSF to CIHDPs warrants careful monitoring, but improves angina, although troponin-I+ events are frequent. Whether G-CSF exacerbates background ischaemia in CIHDPs is unknown. 269 The rosUvastatiN Impact on VEntricular Remodeling cytokineS and neurohormonEs (UNIVERSE) Study Henry Krum1 , FCSANZ, Emma Ashton1 , Christopher Reid1 , FCSANZ, Victor Kalff2 , Jim Rogers3 , FCSANZ, John Amarena4 , Bhuwan Singh5 , FCSANZ, Andrew Tonkin1 , FCSANZ 1 NHMRC

Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University, Melbourne; 2 Dept of Nuclear Medicine, Alfred Hospital, Melbourne; 3 Cardiology Department, Gosford Hospital, Gosford; 4 Cardiology Department, Geelong Hospital, Geelong; 5 Cardiology Department, Launceston General Hospital, Launceston, Australia Background: Statins decrease mortality in patients (pts) with coronary artery disease. However, chronic heart failure (CHF) pts were often excluded in such trials. Statins possess pharmacological properties (independent of cholesterol-lowering) that may be beneficial on ventricular remodeling in such pts. Methods: We conducted a 6 month randomised placebo (PBO)-controlled study of rosuvastatin (ROS, target dose 40 mg/day) in pts with systolic (left ventricular ejection fraction [LVEF] <40%) CHF of ischemic or nonischemic etiology. The primary end-point was change in LVEF by radionuclide ventriculogram (RNVG). Secondary end-points included change in echocardiographic (echo) parameters, neurohormonal and inflammatory markers, Packer composite score, death and HF hospitalization. Cholesterol-lowering efficacy and safety parameters were also assessed. Results: Pts were well matched for baseline values. Compared to PBO (n = 46), ROS pts (n = 40) had a ↓ in LDL plasma cholesterol (PBO +3, ROS −54%, P < 0.001). There was no sig. change in LVEF by RNVG (PBO +5.3, ROS +3.2%), fractional shortening by echo (PBO +2.7, ROS +1.8%), LVEDD (PBO −1.7, ROS +0.8 mm), LVESD (PBO −1.9, ROS +0.1 mm). Plasma norepinephrine, endothelin1, BNP, hsCRP, TNF␣ and IL-6, patient global assessment,

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Packer composite and death/HF hospitalization as well as adverse events were similar between PBO and ROS. Conclusions: Despite being safe and effective at ↓ plasma cholesterol in systolic CHF pts, high dose ROS did not beneficially alter parameters of LV remodeling. Reason(s) for absence of benefit are uncertain but may include patient population studied, high dose of ROS used and/or high use of effective background CHF medications. 270 Recruiting a Specific Target Population for a Phase II Clinical Study: An Experience with Multi-Media Advertising Mariska M. ter Bals1,* , Helen J. Walsh1 , Jenn Hogg1 , Diane F. Caveney2 , Anne Turner3 , Pauline A. Edmunds4 , Lynne McLeod5 , Alexis White6 , Gillian A. Whalley1 , Robert N. Doughty1 , FCSANZ 1 Department of Medicine, University of Auckland; 2 Cardiac Trust, Middlemore Hospital; 3 Cardiology Research, North Shore Hospital; 4 Department of Medicine, University of Otago; 5 Cardiology Clinical Trials, Waikato Hospital; 6 Protemix Corporation Limited, New Zealand

Background: Recruitment for specific research populations can be difficult. Slow recruitment was experienced in a recent multicentre trial. A strategy utilising multi-media advertising was employed to enhance recruitment. Methods: The trial enrolled patients with type 2 diabetes (T2DM) and heart failure (HF). A poster advert was run in local newspapers. An advertising agency developed a radio and television advertisement. All responses were handled by registered nurses who collected standardised information to assess suitability for the trial. Results: Commercials were broadcast over 30 days. Two thousand six hundred and forty-three calls (82 newspaper, 2561 TV) were received (total time 74 h). One thousand nine hundred and seventy-four (75%) patients were excluded after initial response revealed they were not suitable. Detailed information was collected on 676 subjects; 60% were male, average age 59 years (range 26–87). Ninety-two percent of these subjects reported having T2DM but only 186 (28% of eligible; 7% of all calls) reported having coexisting T2DM and HF. One hundred and sixty-eight were evaluated further: 33 (20% of eligible; 1% of all calls) were seen for a study screening visit and 13 (7.7% of eligible; 0.5% of all calls) were randomised into the study. Conclusions: A large group of potential research subjects was reached using this multi-media approach. Processing the responses is a time consuming process and requires dedicated staff time. This resulted in a small increase in recruitment of the required population, but importantly reached the recruitment goal.

271 Superior Effect of an Angiotensin Converting Enzyme Inhibitor Over Diuretic for Reducing Aortic Systolic Pressure in Hypertensive Subjects X.J. Jiang1 , Y. Zhang1 , Michael F. O’Rourke2,* , FCSANZ, L. Liu1 1 Fuwai 2 St

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Hospital & Cardiovascular Institute, Beijing, China; Vincent’s Clinic, UNSW, VCCRI, Sydney, NSW, Australia

Superior benefit of modern compared to conventional drug classes for cardiovascular events reduction in clinical trials are inexplicable. One possibility is that modern drug classes decrease aortic systolic pressure (ASP) to a greater degree than brachial systolic (BSP) by reducing wave reflection. No data are available for comparisons of an ACEI against diuretic. A randomised double-blind controlled study of enalapril (E) 10 mg daily compared to indapamide (I) 2.5 mg daily was performed in 101 hypertensive (55 male) patients (mean age 54, baseline BSP 156/95) over 8 week period. BSP and brachial pulse pressure (BPP) were measured with cuff sphygmomanometer. ASP, aortic pulse pressure (APP), augmented pressure (AP) and augmentation index (AIx,%) were measured with SphygmoCor. Both groups were identical at baseline. Fall of BSP, brachial diastolic, mean and BPP was identical; heart rate did not change. ASP and APP fell by 3 mmHg more than brachial. The reduction in ASP and APP was attributed to decrease in wave reflection. Difference was not attributed to change in heart rate. For similar reduction in brachial blood pressures, measured conventionally in hypertensive patients with an ACEI and diuretic, there was greater (3 mmHg) fall in aortic pressure with ACEI compared to diuretic. Difference is attributable to reduction in wave reflection with the ACEI.

Diabetes and Metabolic Syndromes 272 Hyperglycemia has a Detrimental Effect on Cardiac Remodelling and Mortality after Myocardial Infarction J. Martin1,2,* , K. Connelly1 , A. Boyle1 , A. Kompa1,2 , M. Zhang1 , D. Kelly2 , R. Gilbert2 , H. Krum1 , FCSANZ 1 University of Melbourne Department of Medicine, St Vincent’s

Hospital, Melbourne, Australia; 2 NHMRC Centre for Clinical Research and Excellence in Therapeutics, Department of Medicine/Monash University Melbourne, Australia Background: The presence of diabetes mellitus (DM) in patients with acute myocardial infarction (MI) increases mortality two to four-fold. Whilst subjects with DM have known cardiovascular risk factors, little is known about the impact of diabetes on cardiac remodelling and on clinical outcomes. Hypothesis: To investigate whether hyperglycaemia may adversely and additionally affect LV remodelling post-MI using a streptozotocin (STZ)-induced hyperglycaemic rat, which has heart failure induced by coronary artery ligation. Methods: Eight week old rats were randomized into four groups—control (non-diabetic)/sham (C-S) (no ligation), control-MI (C-MI), diabetic-sham (D-S), and diabetic-MI (D-MI). An echocardiogram was performed prior to the induction of DM, 8 weeks later (prior to the MI surgery) and 4 weeks later, prior to pressure–volume loop analysis and sacrifice. Tissue was analysed for total cardiac collagen, collagens I and III and phospho-SMAD, a marker of TGF-␤1 activation. Results: Key results are summarised in Table 1.

Abstract 271 Table E Baseline

I Baseline

BSP (mmHg)

156.6 ± 15.6

155.8 ± 15.2

E After 8 Weeks (p c.f. Baseline) 140.6 ± 13.8 (p < 0.001)

I After 8 Weeks (p c.f. Baseline) 141.8 ± 15.7 (p < 0.001)

E vs. I at 8 Weeks NS

BPP (mmHg)

61.5 ± 12.0

60.4 ± 11.5

55.4 ± 12.8 (p < 0.001)

54.2 ± 11.7 (p < 0.001)

NS

ASP (mmHg)

146.8 ± 14.9

145.9 ± 15.1

127.5 ± 12.8 (p < 0.001)

131.6 ± 14.4 (p < 0.001)

APP (mmHg)

49.5 ± 13.8

48.2 ± 14.5

40.2 ± 11.2 (p < 0.001)

41.9 ± 12.0 (p < 0.001)

<0.01 NS

AP (mmHg)

16.7 ± 8.2

15.8 ± 7.6

11.4 ± 5.8 (p < 0.001)

13.7 ± 6.9 (p < 0.01)

<0.05

AIx (%)

33.7 ± 9.8

32.8 ± 14.5

28.3 ± 9.4 (p < 0.01)

32.7 ± 8.1 (p = NS)

<0.01

Abstract 272 Table 1. Effects of Hyperglycaemia on Mortality and Measures of Cardiac Function Survival (n), refer Fig. 1 Body weight (g, week 12) Ejection fraction (%) End diastolic pressure Dp/dt max (mmHg/s) Heart rate (bpm) Trichrome-stained matrix (% total matrix) Collagen I Collagen III p-SMAD

C-S (1)

D-S (2)

C-MI (3)

D-MI (4)

94% 286 ± 5 50.48 ± 0.79 5.7 ± 1.6 7068 ± 1139 319 ± 20.6 1.2 ± 0.09 0.8 ± 0.1 0.38 ± 0.015 0.23 ± 0.06

91% 282 ± 3 57.73 ± 3.2 9.37 ± 0.97 p < 0.05 (1,2) 7179 ± 138 305 ± 13.9 1.4 ± 0.1 p = 0.01 (2,4) 2.4 ± 0.18 p = 0.02 (2,4) 2.0 ± 0.2 p = 0.01 (2,4) 1.1 ± 0.1

70% 269 ± 10 36.36 ± 6.1 p < 0.01 (1,3) 10.3 ± 2.56 p = 0.02 (1,3) 11219 ± 1061 325 ± 30.4 2.4 ± 0.1 4.1 ± 0.14 2.8 ± 0.16 0.67 ± 0.1 p < 0.01 (1,3)

22% p = 0.01 (3,4) 231 ± 5 p < 0.05 (3,4) 26.99 ± 4.5 p < 0.01 (2,4); p = 0.07 (3,4) 8.61 ± 1.7 p = NS (3,4) 5940 ± 1020 p = 0.16 (3,4) 265 ± 15.3 P < 0.01 (3,4) 4.8 ± 0.09 p = 0.01 (3,4) 8.3 ± 0.16 p = 0.06 (3,4) 10 ± 0.19 p < 0.01 (3,4) 4.0 ± 0.05 p < 0.01 (1,4; 2,4; 3,4)

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The major finding of this study was that hyperglycaemia increased mortality in MI and exacerbated LV remodeling. Fibrosis, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic cytokine TGF-␤ by the hyperglycaemic milieu. This study confirms the importance of early and intensive treatment of hyperglycaemia in patients with MI.

Figure 1. Effect of hyperglycaemia on mortality after MI. 273 Evaluation of Differences in Coronary Plaque Mechanical Behaviour in Individuals with and without Type 2 Diabetes Mellitus J. Shaw1,2,* , A. White2 , R. Reddy1 , S. Duffy1,2 , FCSANZ, A. Walton1 , FCSANZ, B. Kingwell2 , A. Dart1,2 , FCSANZ 1 The Alfred Hospital, Melbourne, Vic., Australia; 2 Baker Heart Research Institute, Melbourne, Vic., Australia

Purpose: We have previously shown that cyclical changes occur in plaque area during the cardiac cycle with plaque cross-sectional area being significantly less in systole than in diastole. Whether these changes in plaque area are more pronounced in high risk groups such as diabetic subjects is not known. Methods: Individuals with and without type 2 diabetes undergoing percutaneous coronary intervention (PCI) were recruited. Following PCI, intravascular ultrasound (IVUS) was performed on the proximal left anterior descending (LAD) artery. IVUS was used to calculate external elastic membrane (EEM) and luminal areas in

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systole and diastole and from this plaque areas were calculated. Results: A total of 53 patients (45 male 18 type 2 diabetic subjects) of average age 59 ± 10 years (mean ± S.D.) were studied. There were no differences in EEM diastolic area (17.5 ± 1.3 versus 17.3 ± 0.8 mm2 ) or plaque area (5.3 ± 0.6 versus 5.6 ± 1.0 mm2 ) between the diabetic and non diabetic subjects. However, change in plaque area between diastole and systole, was significantly higher in the diabetic group (1.3 ± 0.4 mm2 versus 0.2 ± 0.2 mm2 , p < 0.01). Coronary artery cross-sectional compliance tended to be higher in the diabetic subjects but this did not reach statistical significance: (2.0 × 10−3 ± 5.9 × 10−4 mm2 versus 1.2 × 10−3 ± 2.0 × 10−4 mm2 /mmHg). Conclusion: Change in plaque area within the cardiac cycle is significantly greater in diabetic than in nondiabetic individuals indicating a difference in plaque biomechanical behaviour. This could increase vulnerability of diabetic atheroma to plaque disruption and may help explain the increased coronary event rate seen in diabetic patients. 274 Cardiac Function in Pregnant Women with Higher Pre Pregnancy Body Mass Index D. Zentner1,4,* , M. du Plessis1 , J. Wong1 , FCSANZ, S. Brennecke2,3 , L. Grigg1 , S. Harrap4 1 Department

of Cardiology, Royal Melbourne Hospital, Parkville, Australia; 2 Department of Perinatal Medicine, Royal Womens Hospital, Carlton, Australia; 3 Department of Obstetrics and Gynecology, University of Melbourne, Parkville, Australia; 4 Department of Physiology, University of Melbourne, Parkville, Vic., Australia Background and aim: Obesity is linked to adverse maternal and fetal outcomes. We hypothesised maternal weight might affect cardiovascular adaptation to pregnancy. Methodology 32 pregnant (P) women had echocardiography (Vivid 7, GE) and pulse wave analysis to determine heart rate (HR), aortic systolic blood pressure (aSBP), cardiac output (CO), TDI of systolic (S ) and early diastolic (E ) myocardial velocities, preload (E/E ) and left ventricular afterload (MWS) at 16 and 37 weeks. CO was indexed to maternal weight and body mass index (BMI) calculated.

Statistics and results: These are expressed as median and interquartile range (IQR) and comparisons made using non-parametric tests with statistical significance at 2p < 0.05. Conclusion: In early P, overweight women have higher CO and lower S and E than normal BMI P women. CO/weight is higher in the leaner women, increasing (ns) during P. In contrast, the overweight women have an initially lower CI, which falls further. The lack of difference in preload and afterload between the BMI groups suggests changes in function are well tolerated. However, maternal overweight may be involved in decompensation of cardiac function in women with baseline impairment. Limiting weight gain in pregnancy in the overweight population is associated with better P outcomes, and may prevent some of the cardiac changes illustrated here. 275 Prognostic Implications of Admission Glucose Level on Short-Term Mortality in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Angioplasty M.I. Worthley1,2,* , FCSANZ, F.M. Shrive1 , T.J. Anderson1 , M. Traboulsi1 1 Department

of Cardiovascular Sciences and the Libin Cardiovascular Institute, University of Calgary, Calgary Alberta, Canada; 2 Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia It is now well accepted that an elevated blood sugar level (BSL) is associated with increased mortality in patients presenting with an acute ST segment elevation myocardial infarction (STEMI) treated with thrombolytics. This study was designed to investigate this potential association in STEMI patients treated exclusively with primary angioplasty. Consecutive patients presenting with STEMI and treated exclusively with primary angioplasty were evaluated. This was a single centre study conducted between January 2002 and December 2004. The primary endpoint was in-hospital mortality. Nine hundred and eighty patients were evaluated with a mean age of 62 ± 12.8 (S.D.) years. The mean admission BSL was 9.1 ± 4.4 mmol/L. At admission, 16% of this group were known to have diabetes. The inhospital mortality rate was 3.8% (n = 37). Patients were divided into quartiles based on their admission BSL; group 1 (≤6.6 mmol/L, n = 258), group 2 (6.7–7.8 mmol/L, n = 244), group 3 (7.9–10.0 mmol/L, n = 246) and group 4 (≥10.1 mmol/L, n = 232). In-hospital mortality rates were significantly increased in patients with an elevated admission BSL (p < 0.001). Independent factors predictive of mortality included admission BSL, peak creatine kinase level, creatinine, heart rate, gender, TIMI flow post procedure and cardiogenic shock. Diabetes was not an independent predictor of mortality. Risk adjusted (age, gender, cardiogenic shock and TIMI flow post procedure) survival curves showed a significant difference in survival between patients in groups 1 and 4.

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In this cohort of patients admitted with STEMI and treated exclusively with primary angioplasty, admission BSL is an independent predictor of in hospital mortality. 276 Atorvastatin Ameliorates Adverse Cardiac Remodelling and Survival after Myocardial Infarction in the Hyperglycaemic State J. Martin1,2,* , K. Connelly1 , A. Boyle1 , A. Kompa1,2 , M. Zhang1 , D. Kelly2 , R. Gilbert2 , H. Krum1 , FCSANZ 1 University

of Melbourne Department of Medicine, St Vincent’s Hospital, Melbourne, Australia; 2 NHMRC Centre for Clinical Research and Excellence in Therapeutics, Dept of Medicine/Monash University Melbourne, Australia Statins reduce mortality both post-myocardial infarction (MI), and in subjects with diabetes (D). We aimed to investigate whether atorvastatin (ATV) could reduce (1) mortality and (2) the adverse cardiac remodelling seen in a rodent model of hyperglycaemic heart failure. Eight week old rats were randomized into 5 groups – control (non-D)/sham (C-S) (no MI), control-MI (C-MI), D-sham (D-S), D-MI and D-MI with ATV (D-MI/ATV). An echocardiogram was performed prior to the induction of D, 8 weeks later (prior to the MI surgery) and 4 weeks later, prior to pressure-volume loop analysis and sacrifice. Tissue was analysed for total cardiac collagen, collagen I and III and phospho-SMAD, a marker of TGF-␤1 activation. Addition of ATV to the D-MI group significantly improved mortality. ATV also ameliorated the adverse cardiac remodelling seen in the D-MI group by a reduction in measures of adverse cardiac remodelling (p < 0.05 for change in total collagen content, collagen I, III and pSMAD 2, a marker of TGF-beta activation). Functional markers of myocardial performance, as measured by pressure-volume analysis and echocardiogram showed trends towards improvement. The major finding of this study was that hyperglycaemia increased mortality in MI and exacerbated LV remodeling, and that this was attenuated by the addition of ATV. Fibrosis, a prominent feature of this model, may be a consequence of activation of the pro-sclerotic TGF-␤ by the hyperglycaemic milieu, a cytokine known to be downregulated by ATV. This study suggests that in subjects with both D and MI the addition of a statin may be beneficial. 277 The Impact of Diabetes on the Anti-Inflammatory Properties of HDL In Vivo R. Puranik1,* , E. Nobecourt1 , S. Bao1,2 , S.J. Nicholls1 , M.J. Davies1 , P.J. Barter1 , FCSANZ, D.S. Celermajer1 , FCSANZ, K.-A. Rye1 1 Heart

Research Institute, Sydney, Australia; 2 Department of Pathology, University of Sydney, NSW, Australia The athero-protective benefits of high density lipoproteins (HDL) and apolipoprotein (apo) A-I are partly due to their anti-inflammatory properties. In diabetic subjects apoA-I is frequently non-enzymatically gly-

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cated (GLYC). We investigate how GLYC impacts on the anti-inflammatory properties of apoA-I. Acute inflammation was induced in rabbit carotid arteries with a non-occlusive collar. Twenty four hours before collar insertion the animals received a single infusion of: (i) saline, (ii) unmodified lipid-free apoA-I (UMapoA1, 8 mg/kg), (iii) GLYC-lipid-free apoA-I (GLYC-apoA-1, 8 mg/kg), (iv) reconstituted HDL (UMrHDL) containing phosphatidylcholine and UMapoA-I (8 mg/kg), (v) reconstituted HDL (GLYC-rHDL) containing phosphatidylcholine and GLYC-apoA-I (8 mg/kg). The animals were sacrificed 24 h post-collar insertion. Arterial inflammation was quantitated immunohistochemically. There was significant pan-arterial inflammation in the saline-treated, collared animals. Infusion of UMapoA-I reduced neutrophil infiltration by 88 ± 1% and expression of VCAM1 by 90 ± 3% and ICAM-1 by 66 ± 2% (all p < 0.0001). Infusion of GLYC-apoA-I markedly reduced these antiinflammatory effects, with respective reductions in neutrophil infiltration and VCAM-1 expression of 53 ± 1% and 13 ± 4%, and no reduction in ICAM-1 expression (p < 0.001 for all comparisons with unmodified apoA-I). Infusion of rHDL containing UMapoA-I decreased neutrophil infiltration by 68 ± 1% (p < 0.0001), and expression of VCAM-1 by 88 ± 3% (p < 0.0001) and ICAM-1 by 57 ± 2% (p < 0.001). These effects were less apparent with rHDL that contained GLYC-apoA-I, with neutrophil infiltration and VCAM-1 expression reduced by 53 ± 2% and 48 ± 4%, respectively, and no reduction in ICAM-1 expression. It is concluded that GLYC-apoA-I significantly impairs the anti-inflammatory properties of HDL in vivo and hence contributes to the vascular inflammation associated with diabetes. 278 Influence of Statins on Progression of Aortic Sclerosis in Patients with Type II Diabetes – An Ultrasonic Backscatter Study Chiew Y. Wong* , Leanne Jeffriess, Karam Kostner, FCSANZ, Thomas H. Marwick, FCSANZ University of Queensland, Brisbane, Australia Background: The effect of statins and endothelial function on progression of aortic sclerosis (AScl) is unclear, with a recent randomized trial of calcified valves showing no effect. Ultrasonic backscatter of aortic valve leaflets can be used for detection and follow-up of AScl. We sought to quantify the progression of valvular changes in AScl according to whether pts were treated with a statin with/without ACEi. Methods: Calibrated integrated backscatter (cIB) measures of the aortic leaflets were compared at baseline and 15-month follow-up in 59 pts with type II diabetes (DM) in a lifestyle risk factor modification program. Images of the aortic leaflets were obtained in the parasternal long-axis view. Backscatter measures of leaflets were calibrated to the blood pool backscatter and averaged values were obtained. Association was sought between sclerosis

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degree, statins use and clinical and biochemical characteristics at baseline. Results: The group on statins (n = 27) had a higher prevalence of hypertension, smoking history and significantly higher serum total cholesterol and ACEi use. The baseline cIB correlated significantly with BMI (r = −0.31, p < 0.01), HbA1c (r = −0.41, p < 0.01) and age (r = −0.34, p < 0.01) and was not significantly different between the two groups. cIB significantly correlated to use of statins and ACEi (r = −0.38, p < 0.01 both). The statins group had significant change in the averaged cIB compared to the non-statins group (−1.6 versus +0.15 dB, p < 0.01) at follow-up. Within the statins group, those on ACEi experienced more reduction in cIB (−2.7 ± 1.6 versus −0.75 ± 1.6 cIB, P < 0.01). Conclusion: Statins and ACEi use are associated with AScl progression in pts with DM. Non-Statins Group (n = 32, 19 m, 13 f)

Statins Group (n = 27, 16 m, 11 m)

p

Age (years)

53 ± 10

58 ± 8

<0.05

BMI (kg/m2 )

31 ± 5

32 ± 7

ns

Waist (cm)

106 ± 16

107 ± 13

ns

Total Chol. (mmol/L)

4.9 ± 0.8

4.3 ± 0.8

<0.05

BP (mmHg)

131/81 ± 12/5

131/80 ± 16/10

ns

HTn (%)

38

59

ns

Smoking Hx (%)

63

37

ns

ACEi use (%)

25

56

<0.05

Baseline cIB (dB)

16 ± 4

18 ± 5

0.11

cIB at follow-up (dB)

+0.15 ± 2.8

−1.8 ± 2.0

<0.01

279 Screening for Subclinical Coronary and Myocardial Disease in Subjects with Diabetes and Metabolic Syndrome Chiew Y. Wong* , Rodel Leano, Brian Haluska, Z.Y. Fang, Thomas H. Marwick, FCSANZ University of Queensland, Brisbane, Australia Background: Type II diabetes (DM) and metabolic syndrome (MS) are associated with risks of coronary artery disease (CAD), subclinical LV dysfunction (LVD), and LV hypertrophy (LVH). The prevalence of subclinical coronary and myocardial disease in these pts would define the effectiveness of screening, but is not well defined. We sought the prevalence of these problems in apparently healthy subjects. Methods: Asymptomatic subjects with DM and MS, but no known cardiac disease (n = 504) underwent stress testing, standard echocardiography and tissue Doppler imaging. After exclusion of ischemia and abnormal stress echocardiography, subclinical LVD was assessed by myocardial diastolic velocity (em), the most robust measure of global LV function. It is defined by presence em of more than 2S.D. below the mean age adjusted values of normalweight healthy controls. Association was sought between subclinical disease with clinical and biochemical characteristics. Results: Stress echo evidence of ischemia was present in 20/315 subjects with DM, but none with obesity. LVH

Abstracts

was present in 26% of DM and 21% of MS pts. Subclinical LVD was present in 22% DM and 10% of MS. The important correlates for LVD are BMI (r = −0.13 p < 0.01), age (r = −0.13, p < 0.01), female gender (r = 0.14, p < 0.01) and Hba1c (r = −0.29, p < 0.01) while important correlates for LVH were female gender (r = 0.24, p < 0.001) and BP (r = 0.17, p < 0.01). Conclusions: The risk of CAD is disproportionably associated with DM as compared with MS. Subclinical LVD is quite prevalent in both the DM and obese populations even in the absence of LVH. Obese without MS (n = 117, 77f, 40m)

Diabetes (n = 295, 153f, 142m)

Obese with MS (n = 72, 35f, 37m)

Age (years)

56 ± 10

43 ± 10

44 ± 9

BMI (kg/m2 )

31 ± 6

43 ± 11

36 ± 7

BP (mmHg)

126/91 ± 12/10

126/81 ± 15/9

120/78 ± 12/9

Hypertension (%)

24

48

19

CAD (%)

9 (20 of 315)

0

0

LVH (%)

26

21

21

Subclinical LVD (%)

22

10

8

Subclinical LVD without LVH (%)

22

8

8

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Table. Comparison of Vascular Profiles of Non DM/DM Groups According to MS Profile Non DM (n = 114, 60F) MS− BMI ACEi % Statin % BAR Abn cIMT % TAC mmHg/ml

34 ± 8 0 0 7.0 ± 4.4 6 1.8 ± 0.5

MS+ 45 ± 12 7 4 5.7 ± 4.2 22 1.5 ± 0.4

DM (n = 180, 90F) p <0.001 ns ns ns 0.01 0.02

MS− 27 ± 7 40 7 6.4 ± 4.8 38 1.2 ± 0.6

MS+ 32 ± 5 63 8 4.8 ± 4.5 38 1.3 ± 0.7

p <0.001 <0.05 ns <0.05 ns ns

pts and may attenuate the effect of MS. In a regression model, MS was an independent predictor for TAC after adjustment for ACEi and statin use. Conclusion: MS components synergistically impact vascular changes in pts in both DM and non DM groups, although the effects of these disorders may be modulated by therapy.

281 Insulin Resistance is a Determinant of Myocardial Dysfunction in Apparently Healthy Obese Subjects Chiew Y. Wong* , Rodel Leano, Thomas H. Marwick, FCSANZ University of Queensland, Brisbane, Australia

280 Impact of Metabolic Syndrome on Subclinical Vascular Structural and Functional Changes in Diabetic and NonDiabetic Subjects C.Y. Wong* , B. Haluska, L. Jeffriess, T.H. Marwick, FCSANZ University of Queensland, Princess Alexandra Hospital, Brisbane, Qld., Australia Objectives: The metabolic syndrome (MS) is associated with adverse effects on the vasculature. We sought whether clustering of multiple components of MS had an additional impact on vascular structure and function in subjects with atherosclerotic risk factors, with and without diabetes mellitus (DM). Methods: Vascular structure and function were assessed quantitatively in 144 men and 150 women with atherosclerotic risk factors. None had overt cardiovascular disease and all had a negative stress test. High-resolution ultrasound was used to assess vascular structure (carotid intima-medial thickness [IMT]) and function (brachial artery reactivity [BAR]), which was also assessed by tonometry (total arterial compliance [TAC]). Results: Pts with MS (NCEP III criteria) had a higher risk for early atherosclerotic changes/reduced vascular function. The vascular parameters IMT, BAR and TAC were overall significantly different compared to those without MS. In non DM pts, MS was associated with reduced TAC and higher% of abnormal IMT (>0.70 mm) (Table). Pts with DM and MS had no significant differences in cIMT and TAC, although BAR was worse compared to pts without MS. ACEi and statins were more commonly used in DM

Background: Obese pts have subclinical myocardial dysfunction that may account for their risk of heart failure. We sought the contribution of insulin resistance (IR) to myocardial dysfunction in obesity. Methods: Asymptomatic obese subjects without known cardiac disease underwent clinical evaluation, homeostasis model assessment (HOMA score) as a measure of insulin sensitivity and echocardiographic assessment. After exclusion of DM, overt myocardial dysfunction or ischemia, subclinical myocardial function was assessed by myocardial systolic (Sm) and diastolic velocity (Em) in 79 pts. Association was sought between myocardial function with clinical and biochemical characteristics. Results: HOMA score categorized 36 pts as non-IR (HOMA < 2) and 43 as IR. Although BMI was similar, metabolically healthier pts had lower waist circumference, systolic blood pressure and greater LV and RV diastolic tissue velocities. LV em correlated significantly with HOMA (r = −0.3, p < 0.01), BMI (r = −0.28, p < 0.05) and waist circumference (r = −0.24, p < 0.05) independent of blood pressure. Conclusion: Non-IR obese pts had better myocardial diastolic function compared to those with IR. Preserved insulin sensitivity could be protective against myocardial disease in obese pts.

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Non IR (n = 36, 24f, 12m) Age (years) BMI (kg/m2 ) Waist (cm)

44 ± 10

IR (n = 43, 24f, 19m) 46 ± 8

34 ± 5

36 ± 5

105 ± 9

113 ± 10

p ns ns 0.001

HOMA

1.4 ± 0.4

4.0 ± 1.6

0.001

SBP (mmHg)

119 ± 10

125 ± 12

<0.05

72 ± 19

79 ± 18

LVM index (g/m2 )

ns

LV sm (cm/s)

6.0 ± 1.0

6.0 ± 1.0

ns

LV em (cm/s)

7.3 ± 1.4

6.5 ± 1.3

0.02

RV sm (cm/s)

8.9 ± 2.0

8.8 ± 1.5

ns

RV em (cm/s)

9.1 ± 2.0

8.2 ± 1.3

0.02

282 Hyperglycaemia is Associated with Increased Foam Cell Formation in Human Macrophages J.G.J. Ayer* , D. Sieveking, D.S. Celermajer, FCSANZ Department of Cardiology, Royal Prince Alfred Hospital and Heart Research Institute, Sydney, Australia Diabetes is an independent risk factor for atherosclerosis. As foam cell formation (cholesteryl ester uptake by monocyte-derived macrophages) is a key early event in atherogenesis, we explored the effects of glucose and insulin on human foam cell formation, using an established in vitro model. Methods: Human monocytes from healthy adults were obtained by elutriation and cultured for a total of 13 days. From days 1 to 6 the monocytes were incubated with standard culture medium. From day 7, the monocytes were incubated with media containing glucose at 5 mmol/L (“low glucose”) or 11 mmol/L (“intermediate glucose”) or 20 mmol/L (“high glucose”) and at each glucose level, insulin was added at the following doses: 30 ␳mol/L (normal), 120 ␳mol/L (obese), 600 ␳mol/L (postprandial). Appropriate controls were used for each condition. On days 10 and 12 the monocyte-derived macrophages were loaded with acetylated LDL (50 micrograms/ml). After a further 24 h the macrophages were lysed, cell viability was checked by LDH assay and samples analysed for cholesteryl ester (CE) content by high performance liquid chromatography; CE content was normalised for cell lysate protein. Results: The CE content was 22.36 ± 2.90 nmoles/mg protein in low glucose, 38.50 ± 14.39 nmoles/mg protein in intermediate glucose and 59.09 ± 23.49 nmoles/mg protein in high glucose (p < 0.01 for all comparisons). The addition of insulin at any dose in these conditions did not alter the CE content. Conclusion: Hyperglycaemia is associated with significantly increased foam cell formation in human macrophages.

283 Urotensin II is a Vasoconstrictor in Diabetic Patients without Heart Failure or Essential Hypertension Ella Zomer1 , Iris deRidder1 , Andrew Kompa1 , Paul Komesaroff2 , Henry Krum1 , FCSANZ 1 NHMRC

Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Australia; 2 Alfred Hospital, Melbourne, Australia Background/Aim: Urotensin II (UII), is a potent vasoconstrictor peptide. Increased plasma levels and kidney expression of UII and its receptor have been observed in diabetes mellitus (DM). However, the direct effect of exogenous UII on the microcirculation in patients (pts) with DM has not been previously explored. Methods: The vasoactive effect of UII (10−12 , 10−9 , 10−7 M) on skin microvascular tone was evaluated in 12 healthy controls and 12 pts with DM (Type 1 or 2) without concomitant heart failure or essential hypertension, where vasoconstriction responses to exogenous UII have been previously demonstrated. We used the non-invasive technique of iontophoresis and laser Doppler velocimetry. Acetylcholine (Ach) and sodium nitropusside (SNP) responses were also evaluated. Results: DM and controls were well matched for age. UII dose-dependently dilated blood vessels in controls (baseline, −51.8 + 59.4; UII 10−12 , 138.6 + 101.5; UII 10−9 , 204.2 + 115.7; UII 10−7 mol/L, 207.5 + 81.6 arbitrary flux units [AFUs]). In contrast, UII demonstrated a dose-dependent vasoconstrictor response in DM (baseline, 100.8 + 81.2; UII 10−12 , 46.2 + 85.1; UII 10−9 , 35.4 + 81.4; UII 10−7 mol/L, 26.6 + 79.6 AFUs). The difference between groups was significant overall (p = 0.017, two-way ANOVA), and at the UII 10−9 and 10−7 mol/L dose level (p = 0.035, 0.003). Diet-controlled DM pts demonstrated results similar to healthy controls cf those receiving anti-diabetic medication. Ach vasodilator responses were attenuated in DM pts, whilst SNP responses were similar between groups. Conclusions: UII demonstrates a relative vasoconstrictor response in DM pts. The increased peripheral tone observed with UII administration may be contributory to increased cardiovascular complications associated with DM progression. 284 The Metabolic Syndrome is Associated with Elevated CRP and Extent of Coronary Atheroma but not Central Aortic Augmentation Index P. Antonis* , J. Cameron, FCSANZ, I. Meredith, FCSANZ, S. Hope Monash Cardiovascular Research Centre, Monash Medical Centre and Monash University, Melbourne, Victoria, Australia Background: Metabolic syndrome is associated with increased risk of acute coronary syndromes and poorer

subsequent outcome. In those with acute coronary syndromes metabolic syndrome is associated with greater burden of atheroma. The relationships between coronary artery disease burden, metabolic syndrome and central aortic waveform morphology have not been examined in patients with stable coronary artery disease. Methods: Forty-four consecutive patients (age 60 ± 12 years, 25 male) undergoing elective coronary angiography for suspected native coronary artery disease (CAD) were studied. C-reactive protein (CRP) was measured (highly sensitive assay) and coronary angiograms scored for extent (Sullivans method) and severity of disease (Modified Gensini). Central aortic waveforms were acquired (Millar Mikro-tip® catheter transducer) and analysed for pressures and augmentation index. Associations were explored using regression techniques. Results: Twenty-one patients had the metabolic syndrome (ATPIII criteria), with more women (13, 62%, P < 0.05) in the metabolic syndrome group. Age was associated with increased extent and severity of disease (P < 0.01), and metabolic syndrome with higher CRP levels (P < 0.05). Metabolic syndrome was associated with increased extent (P < 0.05) but not severity of atheroma when age and gender were considered. There was no association with central aortic blood pressure or augmentation index, even after consideration of height and heart rate. Conclusion: Metabolic syndrome was not associated with central aortic augmentation index. In this cohort of patients those with stable CAD and metabolic syndrome had a greater extent, but not severity of coronary atheroma. Higher CRP levels may reflect higher levels of vascular inflammation and thus increased plaque vulnerability. Heart Failure 285 Relative Contributions of Pulmonary Artery Pressure and Pulmonary Vascular Resistance to Right Ventricular Dysfunction N. Mai* , T.H. Marwick, FCSANZ

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increased PVR (groups 1 and 3). Despite similar elevations in PASP in both groups 1 and 2, elevation of PASP without an increased PVR showed a preserved RV S (14.8 cm/s, p = 0.004 versus group 1), and similar to that in normal subjects. Despite having similar PASP, group 3 (elevated PVR) had lower RV S than group 4 (12.4 cm/s versus 14.2 cm/s, p = 0.094). The multivariate model demonstrated that PVR and not PASP was an independent predictor of RV S . Conclusion: PVR is an independent predictor of RV function as compared to PASP. The presence of both raised PASP and PVR is associated with RV systolic dysfunction, but raised pulmonary pressures without increased PVR is not associated with RV systolic dysfunction.

286 Dynamic Myocardial Ischemia Secondary to Left Circumflex Artery Stenosis Documented by a Novel Permanent Implantable Left Atrial Pressure Sensing Device Jay L.T. Ritzema-Carter1,* , David Smyth1 , Iain C. Melton1 , FCSANZ, Ian G. Crozier1 , FCSANZ, Saibal Kar2 , James Whiting2 , Neal Eigler2, Richard W. Troughton1 , FCSANZ

Princess Alexandra Hospital, University of Queensland, Brisbane, Australia

1 Christchurch

Hospital, Christchurch, New Zealand; 2 Cedars Sinai Medical Centre, Los Angeles, CA, USA

RV myocardial tissue Doppler (RV S ) may be used to quantify RV dysfunction, but its determinants are unclear. We sought the relative role of pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) as its determinants. Methods: We analyzed 222 consecutive patients. PVR was calculated from the TR velocity and RVOT TVI. RV systolic function (RV S ) was measured from the tissue Doppler signal at the TV annulus. Patients were grouped as follows: 1 = high PASP and high PVR, 2 = high PASP and normal PVR, 3 = normal PASP and high PVR and 4 = normal PASP and normal PVR. Comparisons between groups were analysed by ANOVA and the independent role of each component was analysed in a general linear model. Results: RV systolic function in each group is summarised in the figure. Reduction of RV S is associated with

Background: Myocardial ischaemia may be associated with raised left atrial pressure (LAP). We report the first use of a novel implantable LAP monitoring device to document myocardial ischaemia and successful culprit artery stenting. Methods: An 81-year-old man with ischaemic cardiomyopathy (LVEF 24%) and a percutaneously implanted, direct LAP monitoring device (HeartPODTM , Savacor Inc, Los Angeles, CA) was admitted with an acute coronary syndrome. LAP waveforms uploaded from the HeartPODTM device showed wide daily variation in LAP from 2 to 60 mmHg with dynamic large c-V waves due to ischaemic mitral regurgitation (MR) seen on echocardiography. The patient underwent percutaneous coronary intervention to a culprit left circumflex artery stenosis with simultaneous LAP measurement by HeartPODTM .

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Results: Immediately prior to PCI, mean LAP by the HeartPODTM was 7.1 mmHg (Fig. 1a), with a simultaneous pulmonary artery opening pressure from Swan-Ganz catheter of 7 mmHg. During 20 s balloon inflation of the stenotic lesion, the mean LAP rapidly rose to 42.6 mmHg and high fidelity waveforms demonstrated giant c-V waves (Fig. 1b). Immediately following successful stent deployment and restoration of TIMI III flow, mean LAP by HeartPODTM fell to 14.8 mmHg and waveforms normalised with loss of giant c-V waves (Fig. 1c).

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to record high-fidelity LAP waveforms. At 3-month follow-up (five patients) mean PAOP was 12.8 ± 4 and mean device LAP was 13 ± 3.

Figure 1. Direct LAP, LAP measured by the device and intracardiac electrogram tracings at implantation in one subject. Conclusion: A new LAP monitoring device was safely implanted in seven patients and accurately measured LAP at implantation and intermediate follow-up. This device could be a useful tool to accurately monitor and optimise treatment in heart failure patients. Figure 1. Conclusions: A new implantable LAP monitoring device detected myocardial ischaemia and helped to confirm successful culprit artery revascularization. 287 First Human Experience with a New Left Atrial Pressure Monitoring Device: Validation with Simultaneous Pulmonary Artery Occlusion Pressure in Subjects With Heart Failure Jay L. Ritzema-Carter1,* , Iain C. Melton1 , FCSANZ, Ian G. Crozier1 , FCSANZ, Saibal Kar2 , Neal Eigler2 , James Whiting2 , Henry Krum3 , FCSANZ, William T. Abraham4 , Richard W. Troughton1 , FCSANZ 1 Christchurch

Hospital, Christchurch, New Zealand; 2 CedarsSinai Medical Center, Los Angeles, USA; 3 The Alfred Hospital, Melbourne, Australia; 4 The Ohio State University, OH, USA We describe the first human experience with a permanent implantable direct left atrial pressure (LAP) monitoring device. Methods: Seven male subjects with heart failure (LVEF 22 ± 7%, NYHA II-III) underwent device implantation. Via an 11 French right femoral vein sheath, the device was sited in the atrial septum by trans-septal puncture with fluoroscopic guidance and intra-cardiac echo (in 6) confirmed deployment of the tip and distal anchors 1 mm into the LA. Recordings were made of simultaneous mean direct LAP and mean pulmonary artery occlusion pressure (PAOP, Swan-Ganz catheter) at trans-septal puncture and of simultaneous PAOP and device LAP at implantation. Results: Device implantation was successful in all patients, with no procedural complications. High fidelity waveforms were obtained from all seven devices. PAOP accurately approximated direct LAP. Mean PAOP was 17.5 ± 7.4 mmHg and mean device LAP was 17 ± 6.5. Mean direct LAP was 17 ± 4.9. After 120 ± 103 days, there are no device- related complications and all devices continue

288 The Utility of Aminoterminal Pro-B-type Natriuretic Peptide for the Detection of Preclinical Systolic and Diastolic Dysfunction in the Community W. Abhayaratna1,2,* , N. Becker1 , I. Jeffery2 , D. McGill2 , FCSANZ, W. Smith3 1 National Centre for Epidemiology and Population Health, Aus-

tralian National University; 2 The Canberra Hospital, NSW, Australia; 3 University of Newcastle, NSW, Australia Background: There are scant data regarding methods to identify subjects in the community with preclinical left ventricular (LV) systolic and diastolic dysfunction. Methods: A population-based sample of 1229 older adults underwent examination with transthoracic echocardiography and measurement of circulating aminoterminal proB-type natriuretic peptide (N-BNP) levels. Heart failure status was ascertained according to past history and clinical examination. The ability of N-BNP to detect preclinical LV ejection fraction (EF) ≤40% and/or moderate-severe LVDD in the entire cohort and a high-risk subset (hypertension, diabetes and/or coronary disease) was assessed using age/gender-specific optimal discriminatory levels. Results: Of the 1150 subjects (48.9% men; mean age 69.2 years) without prior history or current clinical evidence of congestive heart failure, 71 subjects (6.2%; 95% CI 4.9–7.7%) had evidence of preclinical advanced LV dysfunction, of which 6 (0.5%; 95% CI 0.2–1.1%) had an EF ≤40%. The overall N-BNP performance to identify subjects with preclinical EF ≤40% and/or moderate-severe DD was good (AUC 0.83–0.91). However, given the relatively low prevalence of preclinical disease and characteristics of the test, 41–74% of subjects identified with N-BNP screening would have “negative” confirmatory echocardiograms at the expense of missing 9–22% of cases (Table). Conclusions: N-BNP performs well as a marker of LV dysfunction but its screening utility is suboptimal in the community.

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Abstract 288 Table N-BNP Detection of Preclinical EF ≤ 40% and/or Moderate-Severe LVDD Preclinical Disease (%)

N-BNP Cut-off (pg/mL)

AUC

Sens (%)

Spec (%)

LR+

Echo F/U (%)

Negative Echo (%)

Missed Disease (%)

All men: 60–74 years

4.6

173

0.91

85

88

7.2

15.2

74.2

15.0

High-risk men: 60–74 years

6.4

173

0.87

80

85

5.4

19.1

73.3

20.0

All men: 75–86 years

8.6

388

0.83

91

78

4.1

28.1

72.2

9.1

High-risk men: 75–86 years

12.7

467

0.85

78

79

4.1

28.1

65.0

22.2

All women: 60–74 years

4.6

271

0.89

81

92

9.5

11.9

68.5

19.0

High-risk women: 60–74 years

5.9

271

0.90

86

92

10.6

13.1

61.3

14.3

All women: 75–86 years

14.3

375

0.90

84

88

6.9

22.6

46.7

15.8

High-risk women: 75–86 years

17.7

403

0.90

87

87

6.7

25.9

40.9

13.3

289 Benefit of Cardiac Resynchronisation Therapy in Patients with Intraventricular Conduction Delay—Single Centre Over 1-Year Follow-Up Experience

290 Direct Left Atrial Pressure Monitoring With a Novel Implantable Device in Ambulant Patients with Heart Failure: Daily Variation and the Effect of Posture

P. Palka* , A. Lange, C.A. Kingsford, K.E. Taylor, J.E. Donnelly, M. Adsett, J.R. Hayes, FCSANZ, W.J. Stafford, FCSANZ

Jay Ritzema1 , Iain Melton1 , FCSANZ, Ian Crozier1 , FCSANZ, Neal Eigler2 , James Whiting2 , Rob Doughty3 , FCSANZ, Henry Krum4 , FCSANZ, Mark Richards1 , FCSANZ, Richard Troughton1 , FCSANZ

St Andrew’s Medical Institute, Brisbane, Qld, Australia It is unclear whether patients with intraventricular conduction delay but not due to left bundle branch block (LBBB) may also benefit from cardiac resynchronization therapy (CRT). Forty-six patients 18 in atrial fibrillation were studied. The LBBB was present in 30 (65%)—Group 1, right bundle branch block (RBBB) in eight (17%)—Group 2, and eight patients (17%) already had dual/single chamber pacing—Group 3. The aim was to investigate potential differences between all three groups in (i) objective assessment of LV function by echocardiogram and (ii) long term symptomatic follow-up (mean 696 ± 207 days). There were no differences in the improvement in LV ejection fraction between all groups (by 6.4 ± 9.7% versus 2.1 ± 8.4% versus 2.3 ± 4.4%, p = NS Groups 1–3, respectively). The degree of combined intra- and inter-ventricular systolic dyssynchrony were similar in all (Group 1 17 ± 55 ms versus Group 2 −17 ± 95 ms versus Group 3 25 ± 70; p = NS). Group 2 compared to Groups 1 and 3 had a higher degree of inter-ventricular early diastolic dyssynchrony (−60 ± 74 ms versus 38 ± 74 ms versus 25 ± 53 ms; p < 0.01). Similar symptomatic benefit of CRT was observed not only in patients in sinus rhythm and LBBB (‘classic’ criteria for CRT) but also in patients with RBBB, those who already had dual/single chamber pacing and/or patients in atrial fibrillation. Conclusion: We believe that the degree of intra- and/and inter-ventricular dyssynchrony rather than the type of intraventricular conduction abnormalities should be used as selection criteria for CRT.

1 Christchurch

Hospital, Christchurch, New Zealand; 2 CedarsSinai Medical Center, Los Angeles, USA; 3 Auckland City Hospital, Auckland, New Zealand; 4 The Alfred Hospital, Melbourne, Australia Knowledge of left atrial pressure (LAP) diurnal variations and the effect of posture in ambulatory patients is limited. We report the first data showing daily variation and the effect of posture on direct LAP from a novel implantable device. Methods: Seven male patients (72 ± 7 years, LVEF 23 ± 4%) with heart failure (HF) underwent implantation of a permanent direct LAP monitoring device. Subjects uploaded high fidelity LAP waveforms to a hand-held computer. LAPs were recorded five times per day on 5 consecutive days: on waking, 2 h after morning medications, after lunch, dinner and at bedtime. Matched recordings were made supine and standing. Results: All subjects received diuretics, ACEI and betablockers, and were clinically stable during monitoring. Paired LAPs 1.5 min apart (n = 51) were highly repeatable (−0.2 ± 1.2 mmHg). Five of seven subjects had significant (p < 0.05) diurnal variation in their LAPs. Daily variation conformed to an individualised pattern with some subjects having their highest LAP in the morning and others in the evening. Mean 24 h range was 11.3 ± 8.4 mmHg (range 4.9–26.2) among the seven patients. Supine LAP was higher than matched standing LAP by 7.1 ± 4.5 mmHg (p < 0.01).

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Conclusions: CHF patients with and without DM achieve similar functional, hemodynamic and prognostic improvements with intensive management. This may negate potential adverse outcomes of CHF patients with DM treated with standard CHF therapy. 292 Cardiac Magnetic Resonance Imaging in the Prediction of Response to Cardiac Resynchronization Therapy for Severe Heart Failure

Figure. Diurnal LAP variation in one subject. Conclusion: LAP measured by an implantable device was reproducible, with individualised patterns in diurnal variation. Time of day and posture during ambulant haemodynamic monitoring may affect therapeutic choices.

Andrew J. Taylor1,* , Archer Broughton1 , Di Holst, Justin Mariani1 , Ken Thomson2 1 Alfred Hospital Heart Centre and Baker Heart Research Institute, Melbourne, Australia; 2 Department of Radiology, Alfred Hospital, Melbourne, Australia

291 Effect of Diabetes Mellitus on Contemporary Management of Chronic Heart Failure

Background: Cardiac resynchronization therapy (CRT) is of proven benefit in severe heart failure; however a third of cases do not respond. We examined the relationship between the degree of mechanical left ventricular (LV) dyssynchrony with cardiac magnetic resonance imaging (CMR) and clinical response to CRT. Methods: We performed CMR on 14 subjects with cardiomyopathy and severe heart failure (New York Heart Association [NYHA] Class 3 or 4), despite full medical therapy. CMR evaluated LV dyssynchrony, as well as regional myocardial viability. LV dyssynchrony was defined as an 80 ms or greater delay between septal and lateral wall contraction. Response to CRT was defined by improvement in NYHA class.

A.C.C. Ng* , H. Wong, A.P. Sindone, FCSANZ Heart Failure Unit, Department of Cardiology, Concord Hospital, NSW, Australia Objectives: Diabetes (DM) may affect outcomes or response to therapy in chronic heart failure (CHF). We assessed the impact of diabetes in stable CHF patients and their response to therapy. Methods: We recruited 168 CHF patients, 46 with DM and 122 without DM (NDM), followed-up for 40 ± 19 months. Results: ICM: ischaemic cardiomyopathy; † P < 0.05 baseline versus study end; * P < 0.05 DM versus NDM Abstract 291 Table Parameter

All Patients (n = 168)

DM (n = 46)

*P

NDM (n = 122)

(baseline)

Age (years)

68 ± 12

70 ± 9

68 ± 14

Male sex–no. (%)

116 (69)

31 (67)

85 (70)

0.852

ICM–no. (%)

90 (54)

27 (59)

63 (52)

0.489

LVEF (%)

27 ± 12 → 33 ± 13†

24 ± 11 → 31 ± 11†

28 ± 12 → 34 ± 13†

0.053

Mean NYHA

2.24 ± 0.73 → 2.05 ± 0.73†

2.50 ± 0.65 → 2.26 ± 0.66†

2.14 ± 0.74 → 1.97 ± 0.74†

0.003*

BMI

28.0 ± 5.2

29.6 ± 5.7

27.5 ± 4.8

0.03*

eGFR (ml/min/1.73 m2 )

62.9 ± 27.1

57.6 ± 22.1

65.0 ± 28.7

0.087

Total cholesterol

4.3 ± 1.1

4.3 ± 1.2

4.3 ± 1.1

0.86

Five-year survival rate was 78%, with no significant difference between CHF patients with or without DM. Mortality rates did not differ between ICM and non-ICM DM patients.

0.277

Results: Fourteen subjects underwent CMR prior to referral for CRT. Three subjects died prior to implantation, and one patient was found to have extensive viability on CMR scanning that prompted a change of management

Abstract 291 Table Medication (mg)

%RxDM

%RxNDM

*P

Ramipril

67 → 54

70 → 56†

0.710

1.000

5.2 → 6.7

5.4 → 6.7†

Carvedilol

70 → 89†

60 → 80†

0.286

0.252

37.6 → 54.3†

35.1 → 52.0†

Candesartan

17 → 41†

24 → 52†

0.412

0.299

9.5 → 16.4

16.8 → 14.7

Spironolactone

41 → 28

37 → 16†

0.722

0.078

17.8 → 12.8

18.9 → 12.8†

Frusemide

76 → 74

55 → 43

0.013*

0.0005*

66.9 → 68.8

54.3 → 83.9

Simvastatin

59 → 87†

50 → 59

0.387

0.0001*

26.7 → 35.5

26.6 → 33.7

(Baseline)

*P

(Study End)

Mean Dose (DM)

Mean Dose (NDM)

to that of high-risk revascularisation. The mean septallateral wall delay in the remainder was 124 ± 21 ms (range 0–203 ms). There was significant improvement in NYHA Class with CRT in all but one subject with LV dyssynchrony compared to those without (mean improvement in NYHA class 1 ± 0.2 versus 0 ± 0, P < 0.01). No subjects without LV dyssynchrony prior to device implantation improved clinically with CRT, with two progressing to cardiac transplantation. Conclusion: CMR is useful in identifying patients with severe cardiomyopathy who will respond to CRT. The wider application of this technology in the assessment of LV dyssynchrony should result in significant cost savings as well as improvement in patient outcomes. 293 First Paediatric Experience with the VentrasssistTM Left Ventricular Assist System P.N. Ruygrok* , FCSANZ, P.M. Alison, D.S. Esmore, A.K. Finucane, S.P. McGuinness, A.J. Carter, A.D. McGeorge, H.C. Gibbs New Zealand Heart and Lung Transplant Service, Auckland City Hospital, New Zealand Introduction: Phase III clinical trials of the VentrassistTM left ventricular assist system, a third generation continuous flow centrifugal pump, as both bridge to transplant and destination therapies, are currently in progress. Methods: In these multi-centre, prospective, open, observational studies of patients with end-stage heart failure, the first two patients aged ≤14 to receive the device, both from our institution, were identified and their clinical courses described. Results: Case 1. A 10-year-old girl (weight: 36 kg, BSA: 1.1 m2) with a 3 months history of progressive cardiac failure (LVEDV: 217 ml, LVESV: 186 ml) requiring increasing inotropic support (adrenalin, dopamine and milrinone) and ventilation received a VentrassistTM device. She was extubated on day 7 and discharged home without complication 5 weeks after implantation. She awaits transplantation with NYHA class I symptoms (pump flow 5.8 l/min, 2100 rpm). Case 2. A 14-year-old boy (weight: 48 kg, BMI: 1.5 m2) with a long-standing dilated cardiomyopathy (LVEDV: 317 ml, LVESV: 276 ml) suffered progressive heart failure and a cardiac arrest. He was established on ECMO and allowed to wake. He remained neurologically intact and 6 days later received a VentrassistTM LVAS (pump flow 6.2 l/min, 2250 rpm) and was extubated 4 days later, and discharged 28 days after implantation. He continues to strengthen and awaits cardiac transplantation. Conclusion: We report the first paediatric VentrassistTM LVAS experience with good outcomes. We believe the device is safe and efficacious and provides a significant advance in the management of larger children with endstage heart failure.

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294 Effects of Testosterone and Nandrolone on Cardiac Function: A Randomized, Placebo-Controlled Study T. Chung1,* , S. Kellerher2 , A.J. Conway2 , L. Kritharides1 , FCSANZ, D.J. Handelsman2 1 Department

of Cardiology, Concord Hospital & ANZAC Research Institute, University of Sydney, Australia; 2 Department of Andrology, Concord Hospital & ANZAC Research Institute, University of Sydney, Australia Background: Androgens have striking effects on skeletal muscle but their cardiovascular effects are unclear. We assessed the effects of testosterone and nandrolone, a non-amplifiable and non-aromatisable pure androgen, on cardiac function in healthy young men. Methods: A double-blind, randomized, placebocontrolled study was performed on three groups of 10 healthy young men. Each group received weekly intramuscular injections of: testosterone (T; 200 mg mixed esters), nandrolone (N; 200 mg nandrolone decanoate) or matching placebo (P) for 4 weeks. Comprehensive cardiac function assessment was performed on transthoracic echocardiograms (myocardial tissue velocity, peak systolic strain and strain rates), and bioimpedance measurement (cardiac output and systematic vascular resistance). Results: Left ventricular (LV) function (LV ejection fraction), right ventricular (RV) function (RV:LV ratio) as well as cardiac afterload (systemic vascular resistance) and overall cardiac contractility (cardiac output) were within age- and gender-specific reference ranges and were not significantly altered by either androgen or placebo over 4 weeks treatment. Minor changes remaining within normal range were observed solely within the T group for: increased LV end-systolic diameter (30 ± 7 mm versus 33 ± 5 mm, p = 0.04) and RV end-systolic area (12.8 ± 1.3 cm2 versus 14.6 ± 3.3 cm2 , p = 0.04), reduced LV septal early-diastolic (Em) velocity (9.5 ± 2.6 cm/s versus 8.7 ± 2.0 cm/s, p = 0.006) and increased E/Em ratio (7.1 ± 1.6 versus 8.3 ± 1.8, p = 0.02). Conclusion: Four weeks of treatment with T or N does not cause significant cardiac dysfunction in healthy young men so that studies examining the role of androgens in enhancing rehabilitation from cardiac failure may have acceptable cardiac safety. 295 Interval Therapy with Non-blood Contacting Biventricular (BiVAD) Support Pending Destination Therapy for Severe Heart S. Hunyor1,* , G. Gallagher1 , Y. Huang1 , P. Brady2 , K. Tinworth1 , R. Zielinski1 1 Cardiac Technology Centre Department of Cardiology, Kolling Institute University of Sydney, Royal North Shore Hospital, Sydney, Australia; 2 Department of Cardiothoracic Surgery, Royal North Shore Hospital, Sydney, Australia

Background: Rapid developments in stem cell therapy and “destination” LVADs for the failing/damaged heart open up possibilities for interim support from simple,

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safe and BiVAD-capable implantable mechanical assist devices. The principal issues are: blood contact, simplicity of implantation/explantation, cost of device and aftercare, BiVAD capability, fail-safe operation, and safe “idling”. We developed and tested a non-blood contacting direct cardiac compression (DCC) BiVAD device encapsulating such desirable features. Methods: Two groups of instrumented sheep (five each) were induced into severe chronic or acute HF (coronary micro-embolisation, LVEF ≤35%; or i.v. Esmolol infusion to reduce CO by 50%, respectively). Actuator “paddles” equipped with ECG electrode and sonomicrometer sensors were attached to ventricular free walls

296 Impact of Gender on Outcomes in Chronic Systolic Heart Failure A.C.C. Ng* , H. Wong, A.P. Sindone, FCSANZ Heart Failure Unit, Cardiology Department, Concord Hospital, NSW, Australia Background: It is unclear whether gender influences heart failure (CHF) treatment or outcome. Methods: We recruited 168 patients (116 men; 52 women) followed-up for 40 ± 19 months. Results: † P < 0.05 Baseline vs. Study End; * P < 0.05 Female vs. Male; ICM: Ischaemic Cardiomyopathy.

Abstract 296 Table Parameter

All Patients (n = 168)

Female (n = 52)

*P

Male (n = 116)

(Baseline)

Age (yers)

68 ± 12

69 ± 12

68 ± 13

ICM–no. (%)

90 (54)

29 (56)

61 (53)

0.74

Mean creatinine (␮mol/L)

120 ± 61

106 ± 60

125 ± 61

0.003*

LVEDD (mm)

60.5 ± 10.1

57.5 ± 10.2

61.8 ± 9.8

0.01*

LVEF (%)

27 ± 12 → 33 ± 13†

31 ± 14 → 35 ± 13†

26 ± 11 → 32 ± 13†

0.01*

Mean NYHA

2.24 ± 0.73 → 2.05 ± 0.73†

2.45 ± 0.65 → 2.08 ± 0.67†

2.15 ± 0.75 → 2.03 ± 0.75†

0.02*

Mortality–no. (%)

28 (17)

9 (17)

19 (16)

0.54

0.40

LVEDD: left ventricle (LV) end-diastole diameter; LVEF: LV ejection fraction; NYHA: New York Heart Association class.

using integrating biomaterial. Haemodynamic, mechanical and energetic data was collected during pneumatic inflation/deflation of actuators in normal and HF sheep. Results: Chronic HF sheep tolerated 6w continuous DCC assist well. Effective failure reversal during compression

In multivariate analysis, NYHA class was the strongest predictor of mortality: patients with baseline NYHA class III/IV had 2.4-fold increased mortality versus NYHA class I/II (95% CI 1.09–5.51, P = 0.03). For men, NYHA class was the strongest mortality predictor. For women, it was age.

Abstract 296 Table *P

(Baseline)

*P

Medication (mg)

%RxFemale

%RxMale

Carvedilol

60 → 85†

64 → 82†

0.61

0.83

36.4 → 50.1†

35.6 → 53.9†

Ramipril

65 → 42†

72 → 61

0.47

0.03*

5.0 → 7.1

5.4 → 6.6†

Candesartan

21 → 56†

22 → 46†

1.00

0.25

15.6 → 15.0

15.1 → 15.1

Spironolactone

27 → 21

43 → 18†

0.06

0.67

17.9 → 15.3

18.8 → 11.5†

Frusemide

64 → 50

60 → 52

0.73

0.87

60.6 → 69.2

57.7 → 81.7

Digoxin (mcg)

33 → 33

31 → 38

0.86

0.60

121.3 → 97.4

124.7 → 88.8†

Simvastatin

52 → 69

53 → 66

1.00

0.72

21.9 → 29.9

28.7 → 36.5

of ischemic fibrotic hearts required less pressure than Esmolol infused hearts (120 versus 161 mmHg). DCC did not impair coronary blood flow or myocardial oxygen extraction. Even in the normal heart DCC improved stroke work (by 62 ± 46%), and CO and LVSP (by 18% each). Conclusion: A novel implanted DCC BiVAD safely and effectively augments the severely failing hearts work output without compromising myocardial oxygen supply/demand. It has a potential role as interval therapy when use of blood-contacting “destination” LVADs or cell therapies is contemplated.

(Study End)

Mean Dose (Female)

Mean Dose (Male)

Conclusions: In a contemporary tertiary CHF clinic, women were observed to have better cardiac function and mean creatinine but worse functional class than men. Both genders exhibited functional and hemodynamic improvements with only minor differences in their medical therapies. Predictors of mortality differed between genders.

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297 Reversible and Irreversible Left Ventricular Dysfunction following Autologous Haemopoietic Stem Cell Transplantation

298 Restrictive Filling Pattern is a Powerful Predictor of Development of Heart Failure Post-Acute Myocardial Infarction: A Literature-Based Meta-Analysis

T. Chung1,* , Wee-Ching Lim2 , Ilona Cunningham2 , L. Kritharides1 , FCSANZ

J. Somaratne* , G. Whalley, H. Walsh, G. Gamble, R. Doughty, FCSANZ

1 Department

Department of Medicine, University of Auckland, New Zealand

of Cardiology, Concord Hospital, ANZAC Research Institute, Sydney, NSW, Australia; 2 Department of Haematology, Concord Hospital, ANZAC Research Institute, Sydney, NSW, Australia Background: Autologous haemopoietic stem-cell transplantation with non-anthracycline conditioning chemotherapy is an accepted treatment for haematological malignancies; however, the incidence of associated left ventricular (LV) dysfunction and its predictors is unknown. Methods: Twenty-four consecutive patients (aged 58 ± 11 years) with normal LV ejection fraction (LVEF 62 ± 6%) were investigated during autologous haemopoietic stemcell transplantation. Transthoracic echocardiography (including myocardial tissue-Doppler velocity and strain measurements), troponin-T and B-type naturetic peptide (BNP) were performed at baseline (day 0), day 1, weekly for 6 weeks and at 9 months following the transplantation. Results: BNP increased from 52 ± 45 pg/ml (baseline) to a peak of 163 ± 139 pg/ml at 5 ± 6 days after transplantation (p = 0.003). LV dysfunction (defined as LVEF < 50%) developed in 12 (50%) patients (transiently for 14 ± 9 days in 11 and permanently in 1) to a nadir LVEF of 39 ± 11% at 19 ± 9 days after transplant. Two of these patients developed severe pulmonary oedema, and 1 died of LV dysfunction. The rise in BNP did not predict later LV dysfunction (p = 0.52). Troponin increased in 2 (8%) patients at the time of LV dysfunction. Patients who developed LV dysfunction had lower baseline LVEF (59 ± 5 versus 65 ± 5%, p = 0.01) compared to those with persistently normal LV. A baseline LVEF of <61% had sensitivity, specificity, positive predictive and negative predictive value of 75, 92, 82 and 77% in predicting LV dysfunction after transplantation. Conclusion: Reversible LV dysfunction is common following non-anthracycline conditioning chemotherapy for autologous haemopoietic stem-cell transplantation and may be predicted by low normal LVEF at presentation. Life threatening LV dysfunction can occur, especially at the nadir of LV function.

Background: Restrictive filling pattern (RFP) has been linked to prognosis in patients with chronic heart failure (CHF) and post-AMI. We recently showed in two literature-based meta-analyses (LMA) that the presence of RFP was associated with a 4-fold increase in the risk of death in both groups. This similar analysis evaluated the link between RFP and morbidity. Methods: We searched online databases for prospective studies of patients post-AMI and with CHF. HF events (post-AMI: development of HF; CHF: HF readmissions) were compared between RFP and non-RFP. Review Manager version 4.2.7 software was used for the analysis. Results: Twelve post-AMI studies (1286 patients, 271 events) and 5 CHF studies (647 patients, 176 events) were identified. Mean age was similar between the two groups but average pooled LVEF was lower in the CHF group (see Table). While RFP was less prevalent in the post-AMI group (22%) compared with the CHF group (39%) it was associated with a higher OR for HF events than in the CHF group (see Table). Interestingly, the HF event rate in the RFP group was the same regardless of disease category (49% post-AMI, 42% CHF). Conclusions: RFP is associated with high rate of HF admissions in both post-AMI patients and patients with existing HF. This LMA confirms that RFP is a powerful predictor of HF development especially in patients post-AMI and should be incorporated into routine clinical practice. Table. Restrictive Filling Pattern and HF Event Rate Disease Category

RFP (Events/N)

Post-AMI 140/287 (49%) CHF 104/250 (42%)

Non-RFP (Events/N) 131/999 (13%) 72/397 (18%)

Age (Years) EF % (Pooled (Pooled Average) Average) 63 64

45 30

Odds Ratio (95% CI) 10.10 (7.02, 14.51) 2.96 (2.02, 4.33)

299 Feasibility and Short-term Efficacy of Percutaneous Mitral Annular Reduction for the Therapy of Functional Mitral Regurgitation in Patients with Heart Failure S. Duffy1,2 , FCSANZ, J. Federman2 , FCSANZ, C. Farrington1 , D. Rueter3 , D. Kaye1,2,* , FCSANZ 1 Baker

Heart Research Institute, Melbourne, Australia; 2 Heart Centre, Alfred Hospital, Melbourne, Australia; 3 Cardiac Dimensions Inc, Seattle, USA Background: While functional mitral regurgitation (MR) commonly accompanies heart failure and contributes to heart failure progression, mitral repair in the setting of HF is not routinely practiced due to the attendant significant morbidity and mortality. This limitation has fostered the development of percutaneous devices to reduce MR,

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and our group has recently reported the short- and longterm effectiveness of a percutaneous mitral annuloplasty device placed in the coronary sinus (Percutaneous Mitral Annuloplasty Device (PMAD), Cardiac Dimensions® , Inc., Kirkland, WA) in reducing MR in experimental animal models of heart failure with associated MR. In this paper we report results of a “first in human” study of temporary placement of the PMAD device. The aim of this study was to demonstrate the feasibility and safety of temporary deployment of this device in patients with functional MR in association with heart failure. Methods: Five patients undergoing scheduled coronary angiography with heart failure and functional MR (mean age 52 ± 9 [S.D.] years) were recruited, and four had anatomy suitable for deployment of the device. Transthoracic echocardiography and coronary angiography were performed before and after temporary placement and tensioning of the PMAD via the right internal jugular vein. Results: Temporary deployment of the device resulted in a significant reduction in the mitral annular area from 35.5 ± 4.7 mm2 to 32.2 ± 4.6 mm2 (p = 0.02), with evidence of a reduction in the MR color Doppler area from 98.3 ± 43.6 mm2 to 83.3 ± 35.1 mm2 (p = 0.09). There were no complications. Conclusions: This first in human study of a novel device for percutaneous treatment of functional MR has shown that temporary placement of this device in the coronary sinus/great cardiac vein of patients with heart failure and MR is feasible and safe. Evidence of temporary reduction in MR and a reduction in mitral annular area indicate promise for device effectiveness in chronic implantation. 300 Are Heart Failure Programs Targeting Appropriate Patients? A. Driscoll1,* , L. Worrall-Carter1 , D. Hare2 , FCSANZ, P.M. Davidson3 , B. Riegel4 , A. Tonkin5 , FCSANZ, S. Stewart6 , FCSANZ 1 Deakin

University; 2 University of Melbourne, Victoria; of Western Sydney, NSW; 4 University of Pennsylvania, USA; 5 Monash University, Victoria; 6 University of South Australia, Adelaide, Australia & University of Queensland, Qld., Australia 3 University

Background: Chronic Heart Failure (CHF) is at epidemic proportions in Australia. High mortality and morbidity, frequent readmissions and poor quality of life are all common. Chronic heart failure management programs (CHFMPs) have demonstrated improvement in survival and reduction of hospital admissions. Method: The BENCH study is a national multi-centre study designed to develop national benchmarks for CHFMPs. Baseline characteristics in an initial cohort of 584 consecutive patients were examined. Eligibility criteria included a diagnosis of CHF and enrolment in a CHF-MP. Results: Patients were aged between 19 and 100 years of age (mean 69 ± 13.2S.D.) with >90% aged <84 years and 30% of these patients aged between 75–84 years. Sixtyeight percent of the patients were male, 62% married and

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19% widowed. The majority of patients (85%) had participated in the CHF-MP for <2 years. 29, 44, 21 and 6% were NYHA class I, II, III and IV, respectively. Most common aetiologies were ischaemia (52%) and hypertension (11%) with a mean of 2.4 years survival (±2.9S.D., IQR 1–3) since diagnosis. Systolic heart failure was diagnosed in 75% of the patients. Charlson co-morbidity score ranged from 1–11 with a mean score of 2.9. Ejection fraction (EF) was only known in 50% of patients. In this group the mean ejection fraction was 31.7 ± 12.2S.D. Conclusion: The clinical and demographic characteristics of this cohort are ideally suited for evidence based CHFMPs to reduce hospital readmission and improve survival and quality of life. The fact that EF was documented in only half the cohort identifies this as a key area of quality improvement. 301 National Prescribing Patterns for Evidence Based Drug Therapy in Patients with Chronic Heart Failure: Are Target Doses and Multiple Medication Therapies Realistic? A. Driscoll1,* , L. Worrall-Carter1 , D. Hare2 , FCSANZ, P.M. Davidson3 , B. Riegel4 , A. Tonkin5 , FCSANZ, S. Stewart6 , FCSANZ 1 Deakin

University; 2 University of Melbourne, Victoria; of Western Sydney, NSW; 4 University of Pennsylvania, USA; 5 Monash University, Victoria; 6 University of South Australia, Adelaide, Australia & University of Queensland, Qld., Australia 3 University

Background: Chronic Heart Failure (CHF), is more deadly than cancer. Large scale randomised controlled trials have proven the benefits of beta blockade and ACE inhibitors in reducing mortality in patients with CHF and international and national expert guidelines advocate their use. In spite of these recommendations, important therapies are under-prescribed and under-utilised. Aims and method: Five hundred and eighty-four consecutive patients enrolled in CHF management programs were surveyed during 2005 to describe patterns in heart failure medications. Results: The survey revealed that beta-blockers were prescribed to 80% of patients (more than 85% were on low dose), 79% were prescribed loop diuretics, and 70% were prescribed ACE inhibitors of which approximately 50% were at low dose. Spironolactone was prescribed to 41% of patients, and only 19% of patients were prescribed Angiotensin II antagonists. Combination pharmacotherapy of two medications showed a lower prescribing pattern. Beta-blockers and ACE inhibitors, and loop diuretics and beta-blockers were both prescribed in combination in 60% of patients while ACE inhibitors and loop diuretics were prescribed to 53%. A combination of spironolactone and beta-blockers was prescribed to 35% of patients, and 30% of patients received ACE inhibitors and spironolactone. Conclusion: Whilst prescribing rates for a single medication strategy of beta-blockers, ACE inhibitors or diuretics were greater than 65%, the utilisation of combination ther-

apy was low at less than 60%. On the basis of these findings and in the absence of ready access to a polypill focussing on evidence-based practice to increase utilisation of multiple medication therapy is critical. 302 Left Ventricular Size as a Predictor of Intraventricular Dyssynchrony C.R. Coleman* , M.P. Feneley, FCSANZ, C.S. Hayward, FCSANZ St Vincent’s Clinic, Sydney, NSW, Australia Objectives: This study was designed to determine whether left ventricular (LV) size contributes to the degree of intraventricular dyssynchrony in patients with poor LV function. Background: Cardiac resynchronization therapy has been shown to be effective in patients with baseline dyssynchrony, regardless of the QRS duration. Better ways are needed to identify patients likely to have significant cardiac dyssynchrony. Methods: Ninety-four patients with both normal and prolonged QRS duration were assessed. We measured LV area, parasternal diameter and base-apex length to determine whether there was a relationship between LV size and commonly accepted parameters used to assess dyssynchrony. Results: LV size was associated with intraventricular dyssynchrony with a linear correlation between increasing LV area and an increase in septal-to-lateral delay on tissue Doppler imaging (p = 0.0003). In patients with a normal QRS duration, increasing LV area was correlated with all three markers of cardiac dyssynchrony (septal-to-lateral delay p = 0.003, maximum dyssynchrony p = 0.0005, septalto-posterior wall motion delay p = 0.02). Conclusions: Patients with increased LV size have increased incidence and severity of intraventricular dyssynchrony. The presence of LV dilatation in a heart failure patient, regardless of the QRS duration, should raise suspicion and prompt investigation for cardiac dyssynchrony. 303 Assessment of Body Fluid Composition Changes with Impedance Plethysmography in Decompensated Heart Failure N.J. Birkin1,* , N. Piller2 , C.G. De Pasquale1 , FCSANZ 1 Cardiac

Services, Flinders Medical Centre, Adelaide; Assessment Clinic, Flinders Medical Centre, Adelaide, SA, Australia

2 Lymphoedema

Background: Compartmental body composition analysis with impedance plethysmography is increasingly useful in lymphoedema patient management. While impedance plethysmography is used in cardiology to reflect central haemodynamics, little work has been done applying this technology to the whole body in cardiac diseases. Our

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study aimed to assess the rapid changes in body fluid composition in decompensated chronic heart failure (CHF) using impedance plethysmography. Methods: Consecutive patients admitted to Flinders Medical Centre with decompensated CHF had measurements of body composition by segmental multifrequency bioelectrical impedance analysis on admission and discharge, using InBody 3.0 Body Composition Analysis (Biospace, South Korea). Measurements of blood pressure, heart rate and renal function were also made. Results: Six patients aged 63 (57, 75) years median (25th, 75th percentile), EF 24 (19, 29)% were treated in hospital for decompensated CHF for 11 (9, 15) days. Total body weight fell 6.8 (5.4, 12.5)%, p < 0.05. There was no change in blood pressure, heart rate or renal function. Impedance plethysmography showed a reduction in lean body mass; 6.3 (4.8, 12.8)%, soft lean mass; 6.3 (4.7, 12.9)% and extracellular fluid; 12.2 (9.7, 26.5)%, all p < 0.05. There was no change in fat mass or intracellular fluid. Segmental fluid distribution suggested fluid loss from the patients lower limbs, p < 0.05, rather than the upper limbs or trunk. Conclusion: Decompensated CHF and its in-patient management is characterised by rapid alterations in fluid distribution within the body. Impedance plethysmography accurately reflects body mass compartment fluid loss and may therefore be useful in evaluating response to and duration of treatment. 304 What Specific Domains of Cognition are Impaired in Patients with Chronic Heart Failure? S. Elkadi1 , E. Storey1,* , H. Krum2 , FCSANZ 1 Van

Cleef Roet Centre for Nervous Diseases, Department of Neuroscience, Monash University, Melbourne, Australia; 2 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia Background: Chronic heart failure has been associated with generalised cognitive decline. However, little is known regarding the impact of this condition on specific domains of cognition. The aim of the present study was therefore to examine the effect of CHF on key parameters of cognitive function. Methods: Patients (pts) with CHF (n = 44) were compared with controls (n = 22) matched on age (56.3 ± 11.7 versus 54.8 ± 10.4 years) and level of education (12.7 ± 3.3 versus 12.9 versus 2.9 years). Mean EF of CHF was 35.8 ± 12.4% and NT-proBNP was 834 ± 811 pmol/L. Patients and controls were administered the Rey Auditory Verbal Learning Test to assess verbal memory and the Rey Complex Figure Test to assess visuo-spatial memory as well as GDS (15 point) and mini-mental state exam (MMSE). Results: GDS was 4.32 ± 2.38 in CHF pts versus 1.09 ± 1.63 in controls (p < 0.0001). MMSE was 29.5 ± 0.60 in CHF pts versus 29.9 ± 0.29 in controls (p < 0.005). There was significantly poorer verbal [t(20) = 4.49, p < 0.001] and visuo-

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spatial [t(16) = 2.19, p < 0.05] short-term memory in CHF patients. Long-term memory scores were also significantly lower for CHF patients on verbal memory, [t(21) = 3.43, p < 0.01]. Inattention (omissions and commissions) was also significantly greater in CHF pts versus controls. Conclusion: CHF is associated with a clinically significant adverse impact upon cognitive function, particularly in relation to the registration, retention and retrieval of information as well as sustained, directed attention. Improvement in specific domains of cognitive function should be a therapeutic goal in the management of CHF.

Conclusions: Restrictive filling pattern occurs frequently in patients with heart failure and is associated with a fourfold increase in mortality in patients with heart failure and thus should be an important part of the echocardiographic assessment of patients with heart failure. 306 5 Year Follow Up of Systolic, Diastolic and Right Heart Failure; Do They Carry the Same Prognosis? P.M. Srivastava1,2,* , D. Toia2 , J. Gibcus2 , A. Stewart2 , L.M. Burrell1 , D.L. Hare1,2 , FCSANZ 1 Department

305 Restrictive Filling Pattern is a Powerful Prognostic Indicator in Patients with Heart Failure: A Literature-Based Meta-Analysis

of Medicine, University of Melbourne, Austin Health, Heidelberg, Melbourne, Australia; 2 Department of Cardiology, Austin Health, Heidelberg, Melbourne, Australia

Robert N. Doughty* , FCSANZ, Greg D. Gamble, Gillian A. Whalley

Introduction: Systolic heart failure (SHF) has a poor prognosis, however the prognosis in diastolic (DHF) and right heart failure (RHF) is less well known. The aim of this study was to study outcomes in patients with SHF, DHF and RHF attending a teaching hospitals heart failure clinic. Methods: Patients were prospectively enrolled (2000–2005). Data collected at visits included type and aetiology of heart failure, NYHA functional class and medication use. The primary endpoint was mortality, with outcome data referenced to medical records. Results: Six hundred and fifty-nine patients were enrolled with a mean age of 71 ± 14 years, with 65% male and 35% female. Twenty-two percent were in class I, 55% class II, 22% class III and 2% class IV. The mean followup period was 11 ± 14 months. Five hundred and sixty-eight (86%) had SHF, 76 (12%) DHF and 15 (2%) RHF. SHF aetiologies were ischaemia (62%), idiopathic (22%), hypertension (6%), alcohol (5%), post chemotherapy (2%) and other (3%). DHF aetiologies were hypertension (74%), respiratory (4%), and other (22%). All RHF were due to respiratory causes. Ten percent of subjects with SHF were not on B Blockers due to side-effects (25%) or contraindications (75%), 3% were not on ACE/ARB due to side-effects (44%), renal impairment (31%) or contraindications (25%), whilst 43% were on spironolactone. The primary endpoint of mortality occurred in 159 (28%) patients with SHF, 11 (14%) with DHF and 7 (47%) with RHF (x2 = p < 0.001; Fig. 1). At final visits 23% were in class I, 52% class II, 22% class III and 3% class IV. Conclusions: Patients with DHF have a better prognosis than patients with SHF, whilst those with RHF have a worse prognosis. Heart failure of any aetiology carries a poor prognosis and is best treated in a specialised, multidisciplinary clinic setting.

Department of Medicine, University of Auckland, New Zealand Background: Several studies have reported that the presence of a restrictive filling pattern is associated with poor outcome in patients with heart failure. These studies, of variable sample size, have involved different heart failure patient groups with variable associated mortality rates and follow-up time and while powered for effects on combined end-points such as death or hospital admission, many were under-powered to reliably determine the overall effect of the restrictive filling pattern on total mortality. Consequently, we performed a meta-analysis to determine the prognostic power of the restrictive filling pattern with regard to total mortality in patients with heart failure. Methods: We searched several online medial databases for prospective studies of patients with heart failure. All authors were contacted to seek confirmation of their data. We compared all-cause mortality in groups with restrictive filling pattern compared to non-restrictive filling patterns. Reference manager version 4.2.7 software was used for the analysis. Results: Two thousand nine hundred and twenty-four patients in 27 studies were identified (579 idiopathic cardiomyopathy, 2645 mixed aetiology heart failure). Average follow-up was between 3 months and 5 years: 10 studies had longer than 2 years follow-up. One thousand two hundred and eighty-four (44%) patients had a restrictive filling pattern and 688 (24%) deaths occurred. The overall odds ratio was 4.36 (95% CI 3.60, 5.29) and it was higher in the idiopathic group and similar in the mixed aetiology group (see table). The overall odds ratio for death/transplantation was 4.95 (95% CI 4.06, 6.02); idiopathic group: 9.31 (95% CI 5.54, 15.6); mixed group: 4.95 (95% CI 4.06, 6.02). Aetiology

RFP

Non-RFP

Odds Ratio

95% CI

Idiopathic, deaths/number at risk

66/152

25/227

6.65

3.86, 11.47

Mixed, deaths/number at risk

400/1132

197/1513

4.10

3.34, 5.54

Combined total

466/1284

222/1740

4.36

3.60, 5.29

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308 E/Ea Ratio Does Not Decrease During Treatment For Decompensated Heart Failure in Parallel to Decreasing Symptoms and BNP Cara A. Wasywich1,* , Gillian A. Whalley2 , Helen A. Walsh2 , Greg D. Gamble2 , Robert N. Doughty2 , FCSANZ 1 Green

Lane Cardiovascular Service, Auckland City Hospital; of Medicine, University of Auckland, New Zealand

2 Department

Figure. 307 Routine Screening of Heart Failure Patients for Sleep Disordered Breathing in a Ward Setting V.A. Booth* , J. Lattimore, FCSANZ, I. Wilcox, FCSANZ Cardiology Department, Royal Prince Alfred Hospital, NSW, Australia Sleep disordered breathing (SDB) is common in patients with CCF and treatment with continuous positive airway pressure (CPAP) can improve cardiac function and symptoms. Polysomnography is often impractical in this patient population. This study details the results of a ward-based screening program for SDB in patients presenting with exacerbations of CCF. Methods: Consecutive patients were screened overnight by ward nursing staff using a portable sleep screening device (ApneaLinkTM , ResMed Ltd) which measures snoring, flow limitation, apnoeas and hypopnoeas. When downloaded, a report is produced based on the Apnoeahypopnea Index (AHI). Results: Analyzable data was obtained in 30/32 (94%) patients. The mean age was 64 years (range: 40–86) and 73% were male. Most patients (76%) were overweight (body mass index >25 kg/m2 ). Twenty eight patients had echo evidence of systolic left ventricular (LV) dysfunction and a further two patients had normal systolic function and LV hypertrophy. The majority of patients (83%) showed evidence of sleep disordered breathing (SDB), 9 (30%) mild SDB (AHI 6–15/h) and 16 (53%) moderate to severe SDB (AHI >15/h). Conclusion: This study demonstrates that it is feasible to routinely screen patients with CCF for SDB on a cardiac ward using relatively simple, non-invasive technology. Sleep apnoea was common (83% of patients). Patients with evidence of SDB were offered a referral for formal sleep studies after consultation with their treating physician.

Introduction: Brain natriuretic peptide (BNP) and diastolic echo indices are related to LV filling pressure (LVFP) and are useful for risk stratification of heart failure (HF) patients: discharge BNP and E/Ea ratio provide incremental prognostic information, and BNP changes during HF hospitalisation (HFH) are prognostic. This study aimed to determine the relationship between BNP and E/Ea ratio during HFH. Methods: We recruited 24 patients (17 male) at the time of HFH. Within 24 h of admission and at discharge all patients underwent a study evaluation (clinical exam, echo, and BNP-32). Investigators were not involved in patient care during HFH. Results: Mean age was 69 ± 3.2 years, EF 36 ± 18% and HF aetiology ischemic in 50%. Duration of HFH was 5.5 ± 4.2 days. At discharge patient symptoms had improved and BNP had decreased (although remained markedly abnormal). E/Ea did not change. Admission Weight, kg

79.6 ± 18.9

Heart Rate, bpm 88 ± 15

Discharge

P

79.5 ± 16.1

0.25

85 ± 15

0.53

SBP, mmHg

130 ± 21

124 ± 23

0.27

DBP, mmHg

78 ± 18

69 ± 11

0.067

0/0/10/14

0/10/13/1

NYHA class I/II/III/IV

<0.001

BNP, pmol/L

721 (315, 1150) 508 (222, 1015)

0.013

E/A ratio

1.46 ± 0.90

1.53 ± 1.19

0.83

E/Ea ratio

22 ± 13

22 ± 16

0.61

Data are presented as mean ± standard deviation or median (inter-quartile range).

Conclusion: In patients with acutely decompensated HF E/Ea does not appear to decrease in parallel with improvement in symptoms and BNP. These finding suggest that while both E/Ea and BNP are related to LVFP they may not be interchangeable indices and may have a different time course of response to therapy in HF.

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309 Percutaneous Transluminal Septal Myocardial Ablation (PTSMA) Confers Time and Chamber Specific RV Protection During High Level Mechanical LV Unloading J. Mau1,* , S. Menzie1 , M. Ward2 , FCSANZ, S. Hunyor1 1 Cardiac Technology Centre, Kolling Institute University of Sydney, NSW, Australia; 2 Department of Cardiology at Royal North Shore Hospital, Sydney, NSW, Australia

Background: Severe RV failure is common (≈25%) following acute LV assist device (LVAD) unloading. Because the role of IVS dysfunction remains uncertain, we studied ventricular interactions and response to incremental LV unloading following IVS damage. Methods: Following PTSMA with 0.6 ml ethanol in 12 sheep and also using 12 sham controls (59.2 ± 8.3 kg), biventricular ejection fraction (EF), preload recruitable stroke work (PRSW) and Tau were measured after 15 min and 4w using closed chest conductance. Similar indices were calculated in 6 ablated and 6 sham open chest animals during 0/25/50/75/100% LV unloading using a BioMedicus pump. Here, volume based indices were derived from a 3-axis ellipsoidal subtraction model using 7 epicardial and septal sonomicrometer crystals during caval occlusion. Pulmonary and aortic flow probes measured steady-state flows. Results: After acute IVS injury RVEF, RVPRSW and RVTau increased. In contrast, LV systolic parameters declined but LVTau increased. All indices, except Tau normalised by 4w (Fig. 1). During high (≥75%) level LV unloading, RVEF and RVPRSW decreased in sham, but remained stable in PTSMA animals (Fig. 2). (Figures indicate mean ± S.D., * P < 0.05).

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Conclusions: Acute IVS injury causes increased RV, but decreased LV systolic function. Acute diastolic impairment is maintained while systolic abnormalities resolve by 4 w, demonstrating a chamber and time specific effect. Commencement of LV unloading compromises RV function only in the sham, while IVS fibrosis confers protection, presumably by limiting effects on RV chamber geometry. Functional evaluation of the IVS could guide choice of standby or prophylactic support with a biventricular assist device (BiVAD). 310 Evidence Based Practice for Chronic Heart Failure Beyond City Limits Robyn A. Clark1,* , Simon Stewart1,2 , FCSANZ, for the The CASE and CHF/GISCA Study Teams3,4 1 University

of South Australia; 2 University of Queensland; University and University of Adelaide; 4 Monash University, Australia 3 Deakin

Background: There are currently few data to describe the number of individuals with chronic heart failure (CHF) living outside of capital cities and whether they are managed differently than their urban counterparts. Method: A secondary analysis of the 1998 Cardiac Awareness Survey and Evaluation data was conducted, and variables were stratified using the Australian Rural, Remote and Metropolitan Areas Classification. Estimates of prevalence and the location of CHF management programs (CHF-MPs) and General Practices (GPs) were illustrated using Geographical information technology. Results: There was a significantly higher prevalence of CHF in rural towns than in capital cities (16.1% versus 12.4%, p < 0.001). Of the estimated 335,000 Australians affected by CHF, 5000 had been previously managed by one of the 62 identified CHF-MPs; equivalent to 8% of patients admitted annually. Only four CHF-MPs (6%) were located outside of major cities; caring for 0.1% (80) of a potential 16,000 rural patients. There was a significantly (p < 0.001) higher rate of echocardiogram use in the capital cities. Referral to a cardiologist and prescription of an angiotensin converting enzyme inhibitor (ACEI) were also lower in rural versus city dwellers (p < 0.001 for both comparisons). At the time of the study, prescription rates for beta-blockers were consistently low across all geographical areas. Conclusions: These studies suggest a higher prevalence of CHF in rural areas and, conversely, a significantly lower use of recommended diagnostic and pharmacological therapies. Improving the adoption of best practice needs to consider the specific needs of rural doctors and their patients.

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311 Evolving Use of Pharmacotherapy in the Management of Chronic Heart Failure

312 Progression of Functional Mitral Regurgitation in Heart Failure

B.K. Dundon1,* , J.S. Thomas2 , P.J. Psaltis1 , K. RobertsThomson1 , P.M. Steele1 , FCSANZ, L.J. Mahar1 , FCSANZ, P. Sanders1 , FCSANZ, S. Shakib2

Justin Mariani* , Helen Thomson, FCSANZ, Peter Bergin, FCSANZ, David Kaye, FCSANZ

1 Cardiovascular

Research Centre, Royal Adelaide Hospital, University of Adelaide; 2 Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, Australia Congestive cardiac failure (CCF) poses an escalating burden in public health care and an increasingly complex therapeutic dilemma in clinical practice. Over the last 20 years, large-scale published trials have demonstrated efficacy for numerous pharmaco-therapeutic agents, but the degree of uptake of this trial evidence into routine clinical practice is unclear. An audit was undertaken of all patients discharged from the Royal Adelaide Hospital with the principal diagnosis of cardiac failure in a 1-year cohort in 1994, and 6-month cohorts in 1998 and 2001. Diagnostic procedures, discharge pharmacotherapy and medication contraindications were recorded. Treatment appropriateness was assessed on the basis of the best available evidence at the time. A total of 867 patients were studied. Since 1994, the appropriate prescription of ACE inhibitors rose steadily from 75% to more than 93% in 2001 (p < 0.001). The use of digoxin was largely unaffected by evidence regarding its efficacy, but the use of spironolactone increased markedly between 1998 and 2001 (p < 0.001). While contraindications to ␤-blockers were common in all cohorts, only one quarter of patients without contraindications were prescribed these agents at discharge in 2001. This represents a steady increase since 1994 (p < 0.001), but occurred predominantly

Heart Centre, The Alfred Hospital, Melbourne, Vic., Australia Background: Mitral regurgitation (MR) is common in patients with heart failure (HF). Its presence is associated with accelerated progression and portends a worse prognosis. The impact of left ventricular (LV) remodelling on MR progression is unclear. Our hypothesis is that LV, left atrial (LA) and mitral annular remodelling are associated with progression of functional MR. Method: We performed a longitudinal observational study of 52 patients with HF (median age 59 years; male n = 39; NYHA class II-IV; baseline LV end-diastolic diameter (LVEDD) 71.9 ± 1.4 mm). Patients were in sinus rhythm, had at least moderate MR, a structurally normal mitral valve, and systolic HF. Patients were divided into three groups: progression group (PG, n = 17), stable group (SG, n = 18) and regression group (RG, n = 17), depending on change of MR grade over two serial transthoracic echocardiograms (TTE) (median 12 months, range 7–28 months). Standard TTE measurements, including LV ejection fraction (LVEF), fractional shortening (FS), LA size, and right ventricular systolic pressure (RVSP), were recorded. Digital post hoc analysis of mitral annular diameter from apical 4 (MAn4) and 2 (MAn2) chamber views was performed. Results: No significant baseline differences existed between the three groups. Comparison from baseline () data is tabulated (mean ± S.E.M.; * denotes p < 0.05 between PG and RG, and # between PG and SG). Conclusion: Progression of functional MR in patients with HF is associated with cardiac remodelling of the LV, LA and mitral annulus.

Abstract 312 Table LVEDD (mm)

LA size (mm2 )

MAn4 (mm)

MAn2 (mm)

LVEF (%)

FS (%)

RVSP (mmHg)

PG

3.9 ± 1.7*

2.7 ± 1.4*

2.2 ± 0.9*

2.4 ± 0.7*

1.8 ± 3.5

−1.5 ± 2.3*

11.2 ± 3.9*

SG

0.9 ± 1.1

0.6 ± 1.8

0.4 ± 0.9

2.5 ± 0.7

2.7 ± 3.4

−0.5 ± 1.5

7.4 ± 3.8

RG

−4.1 ± 1.6

−4.4 ± 1.7

−1.8 ± 0.9

5.3 ± 4.3

6.1 ± 2.1

in patients with another indication for ␤-blockade such as ischaemic heart disease or hypertension. The translation of clinical trial evidence demonstrating therapeutic efficacy into universal clinical practice in the management of CCF is slow and erratic. Improved systems to increase the utilisation of current and novel therapies in CCF appear necessary to ensure optimal patient care.

−0.9 ±

1.1#

−12.3 ± 3.8#

313 Influence of proBNP Testing on Clinical Assessment by Heart Failure Specialists G.R.D. Jones1,* , L. Boscato1 , A. Keogh2 , FCSANZ, E. Kotlyar2 , FCSANZ, C. Hayward2 , FCSANZ, P. Macdonald2 , FCSANZ 1 Department

of Chemical Pathology and Cardiopulmonary Transplant Unit; 2 St Vincent’s Hospital, Sydney, NSW, Australia Background: Plasma BNP and proBNP correlate well with the severity of heart failure (HF) and provide strong prog-

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nostic information. It is unclear, however, whether provision of a routine BNP testing service will change the assessment and management of HF patients by expert clinicians. Methods: A weekly service for proBNP testing (Roche Elecsys) was provided to four hospital-based HF specialists. The influence of testing was assessed with a pre-test questionnaire to determine the reason for the request and physician assessment of HF severity and post-test questionnaire to assess the influence of the test result on patient management. Results: One hundred and twelve proBNP results were provided for 80 patients over 7 months. Valid pre-test and post-test questionnaires were received for 78% and 88% of samples, respectively. Sixty-five percent of requests were for assessment of severity of known HF, 18% for assessment of HF in patients with multi-system pathology and 12% for assessment of the cause of shortness of breath. Twenty-eight percent of results did not confirm the pretest diagnosis; 35% changed or modified pre-test assessment and 35% lead to a change in management. Where the result did not lead to a change in management, the clinician was more confident in the management plan in 77% of cases. Discussion: When used by HF specialists, proBNP testing lead to changes in patient assessment and management in a significant proportion of cases, and produced greater clinical confidence in most cases where no management change was made. This study does not address patient outcomes but indicates that proBNP testing provides additional information which is considered significant by HF specialists. 314 Characteristics of Patients Dying While Enrolled in a Home Based Heart Failure Program P.M. Davidson1,* , G. Paull2 , D.M. Rees2 , P.J. Newton1 , S. Stewart3 , FCSANZ, P.S. Macdonald4 , FCSANZ, on behalf of the PROCARE Investigators 1 School

of Nursing, University of Western Sydney, Sydney; George Hospital, Sydney; 3 University of Queensland and University of South Australia; 4 St Vincents Hospital and the University of NSW, Sydney, Australia 2 St

Background: Heart failure is characterized by high rates of morbidity and mortality, particularly in the elderly. Determining prognosis and the introduction of a palliative approach can be challenging in this patient population. Aim: Deaths occurring in patients enrolled in a homebased heart failure program were reviewed to identify biochemical and demographic characteristics to assist in developing prognostic models. Method: Clinical notes of deaths occurring over the period 2000–2004 were reviewed to document factors noted to be indicative of an adverse prognosis such as raised creatinine and decreased haemoglobin. Results: Data were collected on 396 patients who died during the observation period. N = 214 (54%) were male and

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the mean age was 84 (±9) years. A history of functional decline was evident in all patients rendering them eligible for the home-based program. The mean serum levels recorded are as follows: haemoglobin 115 ± 19 g/L; sodium 137 ± 6 mmol/L and creatinine 231 ± 162 mmol/L. Documentation of serum albumin was obtainable in 70 cases and the mean level recorded was 28.6 ± 8 mmol/L. Since the diagnosis of heart failure patients had an average of 6 ± (4) admissions to hospital until death. Conclusions: In concordance with other published studies factors such as advanced age, increased health care usage and functional decline in association with biochemical anomalies such as raised serum creatinine are indicative of a poor prognosis and should flag to the clinician the need to address end of life care planning and palliative care issues. 315 Urocortin 2 Infusion in Humans with Mild Heart Failure: Haemodynamic, Neurohormonal and Renal Responses Mark E. Davis* , Christopher J. Pemberton, Timothy G. Yandle, Steve F. Fisher, John G. Lainchbury, FCSANZ, Christopher M. Frampton, Miriam T. Rademaker, A. Mark Richards, FCSANZ Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand Purpose: Urocortin 2 (UCN2) infusion has previously been shown to induce marked increases in cardiac output (CO) and left ventricular ejection fraction (LVEF) with decreased systemic vascular resistance (SVR) in normal humans. In the first controlled study of UCN2 infusion in humans with HF we examined its effects on haemodynamic status, cardiovascular hormones and renal function. Methods: We studied 8 male volunteers with HF (LVEF < 40%, New York Heart Association Class II–III) on 3 occasions 2–5 weeks apart on day 3 of controlled metabolic diets. Subjects received placebo, 25 ␮g low dose (LD) and 100 ␮g high dose (HD) of UCN2 intravenously over 1 h in a single-blind, placebo-controlled, dose-escalation design. Non-invasive haemodynamic indices, neurohormones and renal function were measured. Results: UCN2 administration dose-dependently increased CO (maximal increments relative to baseline (±S.E.M.): placebo 0.3 ± 0.1; LD 1.0 ± 0.3; HD 2.0 ± 0.2 L/min, P < 0.001) and LVEF (placebo 0.0 ± 1.5; LD 5.9 ± 2.1; HD 14.1 ± 2.7%, P = 0.001) and decreased SVR (maximal decrement relative to baseline: placebo −104 ± 37, LD −281 ± 64 and HD −476 ± 79 dynes s/cm5 , P < 0.003) and cardiac work (CW) (placebo 48 ± 12; LD 66 ± 22; HD 94 ± 13 L mmHg/min, P < 0.001). UCN2 elevated plasma N-terminal pro brain natriuretic peptide (P = 0.017) and ACTH (P = 0.032). No effect was noted on epinephrine, norepinephrine, angiotensin II or plasma renin activity. UCN2 decreased urinary volume (P = 0.005) and sodium excretion (P < 0.001).

Conclusions: Brief intravenous infusions of UCN2 in humans with HF induced dose-related increases in CO and LVEF with decreased SVR and CW. Subtle neurohormonal and renal effects were also observed. These findings warrant further investigation of UCN2’s role in circulatory regulation and its potential therapeutic application in heart disease. Indigenous 316 Percutaneous Balloon Mitral Commissurotomy in Indigenous versus Non-Indigenous Australians in Queensland: 1990–2006 A. McCann1,* , C. Aroney2 , FCSANZ, D. Walters1 , FCSANZ 1 The

Department of Cardiology, The Prince Charles Hospital Brisbane; 2 The Holy Spirit Northside Hospital, Brisbane, Qld., Australia Background: Rheumatic heart disease remains a serious health issue amongst the Australian Indigenous population. We sought to document differences between Indigenous Australians (IA) and non-Indigenous Australians (NIA) undergoing Percutaneous Balloon Mitral Commissurotomy (PBMC) from 1990 to 2006. Methods: PBMC was performed in 308 patients using the Inoue-balloon technique (256 female, 52 male, mean age 50 years (S.D. ± 15 years), range 13–89) between March 1990 and January 2006. Results: The IA population was over represented in this cohort (16% versus an estimated 3.5% of the Queensland population) and comprised the largest non-Caucasian group. Compared with the NIA population they were younger (mean age 35 years (±13) versus mean 51 years (P < 0.05). Baseline mitral valve area (MVA) was similar in the IA and NIA groups (0.96 cm2 versus 1.02 cm2 p = 0.9). Mitral valve score was also similar between the two groups (mean score 7.3 versus 7.42 p = 0.8). The IA population had higher pre-procedural mitral valve gradients (14.8 mmHg versus 11.2 mmHg, p < 0.05), but less mitral valve calcification. Procedural success (defined as adequate dilatation and ≤2/4 MR) was achieved in 91% of both groups. Post procedural mean mitral valve area (planimetry) was similar (1.81 cm2 versus 1.85 cm2 , p = 0.6), as was percent reduction in mitral valve gradient. Inadequate dilatation was seen in 1 (3%) IA and in 10 (3.6%) of the NIA group. Significant MR was seen in 2 (6%) IA patients and 11 (4%) NIA patients. There were no deaths or strokes in either group. Conclusion: The Indigenous population make up a significant proportion of patients requiring PBMC in Queensland. They present younger and with higher mitral valve gradients. The procedure is safe in both the Indigenous and non- Indigenous Australian population.

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Interventional 317 Results of Day Case Percutaneous Coronary Intervention in Patients with Stable Angina W.J. van Gaal* , R. Schrale, B. Jennings, I. Porto, R. Arnold, V. Ashar, A.P. Banning Department of Cardiology, John Radcliffe Hospital, Oxford, United Kingdom Objective: To assess the feasibility, procedural success and long term clinical outcomes of day case percutaneous coronary intervention (PCI) for outpatients with stable angina. Background: Outpatients undergoing PCI are traditionally discharged the following day, however day case PCI cuts costs and has been proposed as a safe method for select patients. Methods: Patients undergoing PCI with same day admission and discharge over a five-year period (01/01/2000 to 21/12/2004) were studied. Exclusions from day case PCI included age >80 years, impaired renal function, insulin dependent diabetes, requirement for intra-aortic balloon counterpulsation or glycoprotein IIb/IIIa inhibition. Results: A total of 485 patients were treated. Successful PCI with same day discharge was performed in 463 patients (95.5%). There were 22 patients (4.5%) who required hospital admission with a mean length of stay 2.3 days. Reasons for failed discharge included haematoma formation at the arterial access site (n = 7, 1.4%), coronary dissection (n = 4, 0.8%), post-procedural chest pain (n = 3, 0.6%), prolonged procedure (n = 2, 0.4%), and 1 each of acute stent thrombosis, coronary perforation, anaphylaxis, minor drug reaction, functional study for untreated disease, and further investigation for anaemia. Follow up was complete for 440/485 (90.7%) with a mean follow up of >3 years. At follow up 139/440 patients (31.6%) reported some residual anginal symptoms. Adverse events included hospitalisation for angina (n = 37, 8.4%), repeat revascularisation (n = 43, 9.8%), myocardial infarction (n = 9, 2.0%) and death (n = 15, 3.4%). Conclusions: Day case PCI in selected patients is feasible and safe, with a high rate of success and excellent longterm outcomes.

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318 Impact of Baseline Renal Impairment on Thirty Day and One Year Outcomes after Stent Implantation: Results from the Melbourne Interventional Group (MIG) Registry

319 Evaluation of Early versus Late Exercise Stress Testing in Post ST Elevation Myocardial Infarction Patients Treated with Primary Angioplasty

J. Shaw1,* , A. Walton1 , FCSANZ, S. Duffy1 , FCSANZ, R. Lew2 , FCSANZ, J. Lefkovits3 , FCSANZ, R. Warren3 , FCSANZ, A. Ajani3,6 , FCSANZ, D. Clark4 , A. Black5 , A.Brennan6 , C. Reid6 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators

R.P. Zecchin* , Y.Y. Chai, J. Hungerford, G. Lindsay, S. Manners, M. Owen, J. Thelander, A.R. Denniss, FCSANZ

1 Department

of Cardiology, Alfred Hospital, Melbourne, Australia; 2 Department of Cardiology, Frankston Hospital, Melbourne, Australia; 3 Department of Cardiology, Royal Hospital, Melbourne, Australia; 4 Department of Cardiology, Austin Hospital, Melbourne, Australia; 5 Department of Cardiology, Geelong Hospital, Melbourne, Australia; 6 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Background: While Renal Impairment (RI) is known to be an independent risk factor for the progression of cardiovascular disease its impact on the outcomes in patients undergoing percutaneous coronary intervention (PCI) especially in the era of drug eluting stents (DES) is not well known. Methods: We analysed patients undergoing PCI from January 2004 to February 2006 who were part of the Melbourne Interventional Group registry. RI was defined as an estimated glomerular filtration rate (e GFR), calculated using Cockroft-Gault formula, of <60 ml/min. We compared outcomes at 30 days and 12 months in patients with and without RI. Results: two thousand four hundred and twentysix patients (1699 male) average age 65 ± 12 years (mean ± S.D.) were included in the analysis. Six hundred and forty-four (27%) patients had RI, of these 396 (61%) presented with an acute coronary syndrome (ACS). Thirty days follow up was carried out in 2008 patients. Both 30 day MACE and all cause mortality were significantly higher in those with RI 10.1% versus 4.8% (p < 0.001) and 4.2% versus 0.6% (p < 0.001), respectively. In a regression analysis adjusting for age, diabetes, presentation with ACS and use of DES, RI was an independent predictor of 30 day MACE Odds Ratio 1.8 (p < 0.05). Twelve months follow up was available in 389 patients while MACE and mortality at 12 months tended to be higher in those with RI this did not reach statistical significance. Conclusions: RI is an independent predictor of 30 day MACE and death after PCI in patients with stable and unstable coronary syndromes. e GFR should be used to help risk stratify patients undergoing PCI.

Cardiac Education and Assessment Program (CEAP), Westmead Hospital, Sydney, NSW, Australia Exercise stress testing (EST) early post ST elevation myocardial infarction (STEMI) patients treated with primary angioplasty (PA) remains controversial. This study was to evaluate STEMI patients post PA who had early EST (EEST; ≤7 days) or late EST (LEST; >8 days). Methods: All STEMI patients treated with PA (n = 449) who entered our CR program, from July 1998 to December 2005, were given a sign/symptom limited EST using the Bruce protocol. Baseline data was collected prospectively and included patient demographics, EST parameters, risk factors, past medical history, medications, and quality of life (QOL) measures. Results: EEST (n = 214) was performed 4.6 ± 1.40 days post STEMI and LEST (n = 180) at 20 ± 12.45 days post STEMI. Fifty-five patients (23%) were excluded in this study for their inability to perform an early EST. There were no significant differences in age, gender, left ventricular ejection fraction, number of lesions stented, coronary artery stented, past medical history, dropout rates, EST parameters and risk factors, except smoking rates (EEST 46%: LEST 37%; p = 0.02). There was a significant difference in number of vessels diseased (EEST 48% 1VD; LEST 56% 1VD; p = 0.04). The LEST group had more patients taking beta-blockers and angiotensin inhibitors/blockers (p = 0.001). The EEST group had 16 (8%) patients who had ≥2 mm ST depression at peak EST whereas the LEST group had 5 (3%). There was no acute mortality or morbidity as a result of EEST or LEST. The LEST had lower QOL scores on SF-36 in the Physical-Functioning scale (p = 0.04) and the EEST had a lower score on Bodily Pain scale (p < 0.001), and a significant level of stress on the DASS21 (p = 0.03). Conclusions: EEST has been relatively safe in patients post STEMI treated with PA. EEST is able to detect ischaemia which requires early medical intervention. 320 Initial Australian Experience using Bivalirudin during Percutaneous Coronary Intervention—Safety and Efficacy Outcomes Compare Favourably with Unfractionated Heparin and Tirofiban J.R. Matthews* , N.S. Jepson Eastern Heart Clinic, Prince of Wales Hospital, NSW, Australia Background: Bivalirudin use during routine percutaneous coronary intervention (PCI) has been shown to be a safe and effective alternative strategy to heparin and GP IIb/IIIa receptor blockade. We report our initial experience

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using bivalirudin in consecutive patients undergoing PCI. Methods: From September 2005, 53 procedures were performed using adjunctive bivalirudin. Clinical characteristics and in-hospital outcomes were recorded prospectively. Comparison is made with a historical control group (28 patients) receiving unfractionated heparin and high loading dose (HLD) tirofiban during PCI. All patients received aspirin and clopidogrel loading. Bivalirudin was loaded with a 0.75 mg/kg bolus then 1.75 mg/kg/h infusion. Tirofiban was loaded with a 25 mcg/kg bolus followed by a 0.15 mcg/kg/min infusion for 18 h. Results: Table 1 for baseline characteristics, Table 2 outcomes. Of bivalirudin patients, 25 (47%) were unstable angina or recent MI and 8 (15%) received provisional HLD tirofiban. Complex intervention (LMS, atherectomy, SVG, bifurcation, multi-vessel) was undertaken in 11 (20%). Twenty-seven (50%) received over one vial. Rate of post-procedure troponin rise was significantly less in bivalirudin patients than control (41 versus 82% p < 0.05). Bivalirudin patients had no significant complications. Of tirofiban patients, 1 (4%) had post-procedure MI (trop >10), 3 (11%) groin or minor bleeding. Conclusion: Early clinical experience using bivalirudin during PCI, including high risk and unstable patients, demonstrates a low rate of any in-hospital complications, with favourable comparison to the historical control. The 30 days outcomes are being collected. Table 1. Baseline and Procedural Characteristics Expressed (number) (%) Characteristics

Bivalirudin (n = 53)

Tirofiban (n = 28)

p

Age, mean (S.D.) Diabetes mellitus Prior percutaneous intervention

66.2 (11.7) 15 (29) 21 (39)

66.2 (11.3) 5 (19) 4 (14)

ns ns <.05

Indication Stable angina or EST Unstable angina Recent MI (trop now <0.1)

28 (53) 19 (35) 6 (12)

15 (54) 3 (11) 10 (36)

ns <.05 <.05

5 (9) 5 (9) 1 (3) 5 (9)

6 (21) 1 (4) 1 (4) 1 (4)

Complex intervention Bifurcation Atherectomy Left main Saphenous vein graft

321 Carotid Stenting Has No Obvious Learning Curve for the Experienced Cardiac Interventionist J. Stewart* , FCSANZ, D. McNab, S. Pornratanarangsi, H. Farrell, G. Armstrong, FCSANZ Auckland City Hospital, Auckland, New Zealand Carotid stenting (CS) is a new treatment for carotid artery disease. High complication rates reported in early randomised trials of CS and carotid endarterectomy suggested a steep learning curve. We examined our first 54 CS procedures (all performed by an experienced cardiac interventionist) to determine the learning curve. Most (86%) patients had significant cardiac disease and would have been excluded from the major trials of carotid endarterectomy versus medical therapy. The 30-day event rate was low despite the high baseline risk these patients: one death from sepsis after coronary bypass surgery following carotid stenting (30-day mortality 1.9%)), and one non-fatal stroke (30-day stroke rate 1.9%). There were no myocardial infarctions and no fatal strokes. Given the low number of major complications we examined procedure and fluoroscopy times as surrogates of the learning curve. The mean (S.D.) procedure times for the first 10 and the last 10 procedures were 57.0 ± 11.4 min and 62 ± 11.3 min, respectively (p = 0.55). The fluoroscopy times were 18.7 ± 6.7 min and 16.3 ± 4.9 min, respectively (p = 0.55). Learning and experience curve statistical analysis shows an exponential reduction in the time taken to perform a particular task if it is performed repeatedly. An attempt was made to fit a learning curve to scatter plots of procedure and fluoroscopy times as a function of procedure number. No discernable relationship could be seen. Our data shows no evidence of learning curve when CS is undertaken by an experienced cardiac interventionist.

ns ns ns ns

Table 2. Outcome in Hospital Post procedure trop >0.1 Groin complication Bleeding (minor or major) Myocardial infarction (trop >10)

22 (41) 0 0 0

23 (82) 2 (7) 1 (4) 1 (4)

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<.05 ns ns ns

Figure.

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322 A Case Controlled Series Comparing Carotid Artery Stenting (CS) and Carotid Endarterectomy (CEA) in a Single Centre G. New* , FCSANZ, C. Bladin, L. Roberts, K. Coughlan, Z. Ross, B. Leaney, B. Beiles, C. Clifford, M. Westcott, M. Lovelock, M. Grigg, G. Fell Box Hill Hospital, Melbourne, Vic., Australia Background: Large randomized controlled control trials are underway comparing CS and CEA in symptomatic patients. The SAPPHIRE Trial demonstrated equivalent neurological outcomes but higher AMI rates in high-risk patients randomised to CE versus CEA. Methods: We performed a case controlled study comparing CS and CEA. We prospectively collected data in CS from July 2002 and CEA from Jan 2004. All patients were examined pre and post procedure and at one month by an independent neurologist and accredited NIH Stroke Scale certified neurology nurse. The patient characteristics are similar. Conclusion: In this series, neurological outcomes appear

Carotid Stenting (n = 81)

a

Gradient (mmHg) Isthm. diameter (mm) COA diameter (mm)

Range 20–50 5–15 1.5–5

Mean

Post-Ballooning S.D.

Range

Mean

S.D.

9.2

0–25

12.1

6.4

8.8

2.5

5–15

8.8

2.5

3.1

1.0

4–10

6.7

2.0

40

Patients: Five had luminal tear and three had mild saccular aneurysms (SA), unchanged with observation. Three infants had successful remodeling of the arch with time. One pt had SA with incomplete response requiring surgical repair. One 11 year old had early recurrence weeks post successful BA and underwent successful stenting. Patients had MRI following BA and subsequently yearly where possible. Follow up range 2–126 months, m 51.1, S.D. 36.7, late gradient range 0–30 mmHg, m 18.5, S.D. 9.4. BA in COA is a safe alternative to surgery and with careful technique and monitoring, adequate results can be obtained. With follow up some increase in gradients is observed. The good results with a select infantile group shows promise for early intervention. 324 Long Term Outcome of a Policy of Selective Drug Eluting Stents (DES) Use Andrew I. MacIsaac* , FCSANZ, J. Gutman, FCSANZ, Robert J. Whitbourn, FCSANZ, John Santamaria, J. Towner

Table 1. Results Asymptomatic High risk SAPPHIRE NASCET eligible Procedural success Crossover TIA Minor stroke Death NSTEMI Cranial nerve palsy

Pre-Ballooning Results

26 (32%) 42 (52%) 17 (21%) 79 (98%) 2 (2.5%) 3 (3.7%) 2 (2.5%) 0 0 0

CEA (n = 63) 11 (17%) 21 (33%) 14 (22%) 62 (98%) 1 (1.6%) 2 (3%) 2 (3%) 1 (1.6%)a 4 (6.3%) 6 (9.5%)

Respiratory death.

similar between CS and CEA. However, the CEA patients have higher cardiorespiratory and peripheral complications. 323 Balloon Angioplasty (BA) of Native (COA)—Personal Ten Year Experience

Coarctation

T.H. Goh* , FCSANZ Department of Cardiology, Royal Children’s Hospital, & Monash Medical Centre, Melbourne, Australia From 1995 to 2005, 21 patients aged 1.5–180 months, m 63.9, S.D. 57.8, weight range (kg) 4.2–53, m 21.3, S.D. 15, underwent BA. This included three infants. Standard BA technique was followed. Balloon diameter used equaled proximal isthmus diameter and next larger balloon was used if residual gradient was more than 50% of pre-existing gradient. Inflation slowly performed by hand until waist of COA eliminated. Balloon diameter, 6–16 mm, m 10.7, S.D. 2.6.

Department of Cardiology, St Vincent’s Hospital, Melbourne, Vic., Australia Funding constraints have limited our use of DES to onethird of PCIs. We restrict DES use to cases at high risk of restenosis, prespecified as diabetics, small (≤2.5 mm) vessel, chronic occlusion, long (>20 mm), saphenous vein graft, ostial, bifurcation and restenotic lesions. The longterm outcome of this policy is unknown. From 377 consecutive stented patients (1/1/2004 to 01/08/2004), 175 pts (31%) received Taxus DES and 359 (69%) BMS. There was no difference in age, gender or indication for the procedure between the two groups. Stented length was longer (27.1 mm versus 20.9 mm, p < 0.001), and stent diameter smaller (2.87 mm versus 3.13 mm, p < 0.001) in the DES group. At 18 month follow up of 313 pts (83%), there was no difference in Major Adverse Cardiac Events (MACE) between DES (18.7%) and BMS (24.3%) (p = 0.3), or Target Vessel Revascularisation (TLR) DES 11.0% versus BMS 8.6%, p = 0.5. Conclusions: TVR was low in both groups. There was no difference in 18 months events between BMS and DES groups when stent selection was based on clinical and angiographic features. This data suggests that a policy of selective use of DES is effective.

325 Bail-Out Left Main Coronary Stenting for Acute Dissection: Short and Long term results R.G. Schrale* , W.J. van Gaal, C. Forfar, K. Channon, O. Ormerod, A. Banning Department of Cardiology, John Radcliffe Hospital, Oxford, United Kingdom Background: Left main (LM) dissection is a rare complication of coronary intubation. Small dissections may be managed conservatively, but more extensive dissection often requires immediate revascularisation. We evaluated the short and long-term outcomes of a “bail-out” stenting approach to this catastrophic complication. Methods: A retrospective review of consecutive patients who underwent coronary catheterisation or percutaneous intervention (PCI) at the John Radcliffe Hospital from April 2001 to April 2005. In-hospital and one year outcomes were obtained from case note review and postal questionnaire. Local doctors were contacted to complete missing data. Results: During the study period 17721 patients underwent coronary catheterisation (n = 11574) or PCI (n = 6147). There were 10 instances of bail-out LM stenting (9 PCI, 1 diagnostic) using bare metal (n = 6) or drug eluting (n = 4) stents. A technically successful bail-out stenting procedure was performed in all patients. Abciximab was administered in 60% and 30% required intra-aortic balloon pump. None required ventilation. There were no inpatient deaths or inpatient coronary surgery. Forty percent had in-hospital myocardial infarction (MI). Mean length of stay was 3.6 ± 2.9 days. Long term follow-up available in 100%; mean length 665 days (range 351–1263). Event free survival was 80% (freedom from unstable angina, MI, or revascularisation). One patient died secondary to MI at two months and one had crescendo angina at 3 months with in-stent restenosis requiring surgery. Half of the patients reported some angina at follow-up. Conclusion: Selected bail-out LM stenting for acute dissection is technically feasible with acceptable acute and long-term results in a small series of patients. 326 Renal Injury Prevention in Contrast Induced Nephropathy with Acetylcysteine (RIPCINA) Trial—A Randomised Controlled Trial of N-Acetylcysteine with short and Medium Term (30 day) Follow-Up R. Schrale1,* , W. Siebert2 , J. Girardi1 , M. Joseph1 , FCSANZ, J. Vaile1 , R. McRitchie1 , FCSANZ, D.P. Chew1 , FCSANZ, P.E. Aylward1 , FCSANZ 1 Department

of Cardiology, Bedford Park, SA, Australia;

2 Division of Pharmacy, Flinders Medical Centre, Bedford Park,

SA, Australia Background: Contrast induced nephropathy (CIN) may occur secondary to coronary angiography. NAcetylcysteine (NAC), an amino acid with anti-oxidant properties, may have a renoprotective effect. Capsule

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NAC is not marketed in Australia—administration is only possible via intravenous fluids or liquid sachets. We formulated a novel capsule preparation to simplify treatment. Methods: We conducted a double blind randomised controlled trial of NAC 600 mg twelve hourly for 2 days versus identical placebo in stable non-dialysis renal failure patients undergoing coronary angiography. First dose preceded angiography. All received intravenous hydration. Results: Forty-seven patients were enrolled, with mean creatinine 0.16 mmol/L. Mean age was 76 years, 30% diabetic and 32% female. There was no significant difference between the treatment groups for these variables, intravenous fluid volume or contrast dose. Follow-up was 100% at 48 h and 94% at 30 days—in the NAC group one patient died after cardiac surgery, two declined blood sampling. At 48 h one patient in each group had CIN (creatinine increase ≥0.044 mmol/L or >25% baseline). At 30 days 2/23 and 7/21 patients had CIN in the NAC and placebo groups, respectively (OR: 0.29, 95% C.I. 0.07–0.121, p = 0.061). In both groups mean creatinine fell slightly at 48 h (−0.0054 mmol/L versus −0.0045 mmol/L, NAC/PL, p = NS). At 30 days creatinine change from baseline was not significant (+0.0024 mmol/L versus +0.014 mmol/L, NAC/PL, p = NS). Conclusion: NAC did not demonstrate an early renoprotective benefit in addition to fluid hydration. A nonsignificant benefit was observed at 30 days. Larger studies are warranted. 327 Unprotected Left Main Percutaneous Intervention—A Four Year Single Centre Experience R.G. Schrale* , W.J. van Gaal, K. Channon, C. Forfar, O. Ormerod, A. Banning Department of Cardiology, John Radcliffe Hospital, Oxford, United Kingdom Background: Stenting the unprotected left main (ULMS) coronary is a topic of controversy. We examined a high volume single British tertiary centre experience. Methods: We retrospectively reviewed the medical records of all patients who underwent percutaneous coronary intervention (PCI) from April 2001 to April 2005. For ULMS patients in-hospital and 12-month outcomes were obtained by case note review and postal questionnaire. Local doctors were contacted to complete missing data. Results: During the study period 6147 patients underwent PCI and 66 (1.07%) were ULMS procedures. Seventy-seven percent of patients were deemed unfit for surgery; in 13% patient preference decided for PCI. Mean age was 70 years, 39% female, 21% diabetic, and 32% severe systolic dysfunction. The mean Log Euroscore was 19. Procedural success was achieved in 97%, with 47% of stents drugeluting. Intra-aortic balloon pump was required in 30%; 58% received abciximab. Twelve-month follow-up was achieved in 98%. Table 1 documents in-hospital (IH) and 12-month outcomes in all-comers and a non-shock/STEMI (nonS/ST) subgroup (n = 54). Four out-of-hospital deaths

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were recorded to 12 months—two cardiac, one cancer, one gastrointestinal bleed.

329 Late Clinical Outcomes after Rescue PCI—5 years Experience from a Regional Cardiac Centre

Table 1. Outcomes

Victar Hsieh, Noemi Wouters, Rozemarijn van den Vijver, Lisa Connolly, Sue-Anne Gavigan, Andrew Hopkins, FCSANZ, Sidney Lo, FCSANZ, Dominic Leung, FCSANZ, Craig Juergens, FCSANZ, John French* , FCSANZ

All—IH Death MI TVR

All: 12 Months

NonS/ST: IH

11% (7) 17% (11) 1.5% (1) 12% (8) 15% (10) 13% (7) 3% (2CABG) 10% (7CABG, 3PCI) 4% (2CABG)

NonS/ST: 12 Months 9% (5) 17% (9) 12% (5CABG, 3PCI)

Liverpool Hospital, Sydney, Australia Conclusion: ULMS is typically reserved for the critically unwell, with predictable associated high mortality. In selected yet still high risk populations, acceptable short and long term results can be achieved. 328 A National Survey of Radiation Knowledge and Safety in the Cardiac Catheterisation Laboratory R.G. Schrale1,* , M. Shinnick2 , D.P. Chew1 , FCSANZ, P.E. Aylward1 , FCSANZ 1 Department

of Cardiology, Flinders Medical Centre, Bedford Park, SA, Australia; 2 Flinders Private Hospital, Bedford Park, SA, Australia Background: Radiation exposure is inevitable for workers in the cardiac catheterisation laboratory (CCL). The current state of radiation training, knowledge, safety practices and personal attitudes to radiation among these workers is unknown. Methods: A 39-item, investigator developed anonymous questionnaire was distributed to 25 public and private CCLs nationwide using purposive sampling. Results: One hundred and fifty-nine responses were received from 17 hospitals (68%). Respondents were interventional cardiologists and their training registrars (P 30%), radiographers (R 23%), CCL nurses (N 30%) and CCL technicians (T 17%). Overall 31% reported their CCL had a radiation safety/education program. Fortytwo percent recognised the ALARA principle. A majority could identify their CCL radiation safety officer (physicians were significantly worse at this, 83% versus 57%, p < 0.001). Only 7% could estimate a plausible diagnostic coronary angiography dose. Comparative dose estimation was poor. Sixty-one percent reported they had been concerned about personal occupational radiation exposure (P 78%, N 62%, R 47%, T 41%). However, the majority (83%) could not identify the annual allowable dose and knowledge of previous personal doses was infrequent. Forty-six percent reported not wearing their monitor for at least some time while working with radiation. Independent of profession, a radiation education program was associated with better estimated comparative radiation doses (p < 0.05), reduced occupational radiation exposure anxiety (p < 0.005), higher sense of sufficient training (p < 0.001) and better self-assessed understanding (p < 0.005). Conclusions: Radiation knowledge is suboptimal, but safety practice is better. The majority of CCL workers are anxious about their occupational exposure. Formal training programs appear to reduce this concern and should be encouraged.

Background: The use of rescue angioplasty (PCI), after being debated for a decade, has becoming increasingly accepted as treatment for failure of reperfusion after fibrinolytic therapy for ST elevation myocardial infarction (MI) (STEMI). Methods and results: We studied late clinical outcomes in all 131 patients (68% transfers) with STEMI (59.5% anterior MI) who underwent rescue PCI at our regional cardiac catheterisation laboratory between 2001 and 2005. The median times from symptom-onset to fibrinolytic therapy (88.5% TNK), and fibrinolytic therapy to angiography were 2.1 h [IQR 1.3–3.5], and 3.4 h [IQR 2.5–5.1], respectively; nine patients (6.9%) had cardiogenic shock. At 6 months mortality was 7.6% (4% in patients without shock); 3.1% (4) suffered reMI; there was one non-haemorrhagic stroke (0.8%); 11.4% (15) had severe heart failure (NYHA class III-IV); three patients (2.3%) had target vessel revascularisation. The rate of transfusion-related bleeding was 11.5% (15). The rates of stent deployment and glycoprotein (gp) IIb/IIIa inhibitor use were 91% and 73%, respectively. Univariate predictors of 6-month mortality were cardiogenic shock (p < 0.001), prior aspirin (p = 0.01), prior MI (p = 0.030), and severe heart failure (p = 0.029). The multivariate predictors of mortality were cardiogenic shock (p < 0.001), prior aspirin (p = 0.014) and bleeding (p = 0.026). Conclusion: The 4% 6-month mortality we report in unselected patients undergoing rescue PCI in the era of liberal use of stents and gp IIb/IIIas, is similar to that of STEMI patients treated with primary PCI or achieving early pharmacological reperfusion, and that reported in the rescue PCI-arm of the REACT trial. These data suggest that rescue PCI is reasonable strategy where there are access difficulties to regional cardiac centres for primary PCI. 330 General Practitioners and Cardiologists Hold Contrasting Views of the Prognostic Value of Percutaneous Coronary Intervention for Mild Stable Angina Nikhil Sapre* , Stewart Mann, FCSANZ, C. Raina Elley Wellington School of Medicine, Wellington, New Zealand Aim: We wished to assess how General Practitioners (GPs) and Cardiologists (Cs) perceive and communicate the prognostic benefits of percutaneous coronary intervention (PCI) in a patient with mild angina. Methods: We interviewed 20 General Practitioners (GPs) and 22 cardiologists (Cs) about how they would advise a patient with angina now well controlled on medication

both given limited availability in the public system and if there were unrestricted access. Main results: Both groups were evenly divided about the need for angiography (in the public system) although five of the 10 cardiologists recommending it would require some further evidence of reversible ischaemia. With unrestricted access, two further Cs would recommend it. Assuming a finding of an isolated 75% stenosis in the mid right coronary artery, 12 GPs and 4 Cs would expect prognostic benefit or increase in life expectancy from PCI, 7 GPs estimating >5 years of extended life. With an alternative finding of moderate triple-vessel coronary disease (not involving left main stem or proximal anterior descending branch) 13 GPs but no Cs would expect prognostic benefit from bypass surgery. Most Cs cited guidelines from American or European cardiac organisations as sources of information. GPs did not generally quote source material and relied on advice from local specialists. Conclusion: Cs were aware of the lack of prognostic benefit from PCI in this case, but GPs believed there would be much greater benefit despite citing local specialists as their main source of information. 331 Left Main Stem PCI in the Real World: A Single Centre Experience Paul Das, Adam Gay* , Yuvaraj Malaiapan, Ian Meredith, FCSANZ Cardiovascular Research Centre, Monash Medical Centre, Melbourne, Australia Background and method: Left main stem (LMS) PCI is growing in popularity and has been recognized by recent guidelines. How successful is it in practice? We conducted a review of LMS PCI cases in 2004–2005. Results: There were 27 LMS cases (25 patients): 16 unprotected, 11 protected; 16 elective, 11 acute. Indications were: stable angina 11 cases, unstable angina 4, NSTEMI 3, acute STEMI 5, in-stent restenosis/thrombosis 4. PCI was chosen because of: patient preference 8 cases, age/risk 5, acute failure/shock 4, early restenosis 3, isolated LMS stenosis 2, LIMA occlusion 1. Lesions were: ostial 10, body 2, distal 12 and all 3. Stenosis range 60–99%. The ostial/proximal LAD was involved in 7 cases, Cx in 7, both 4 and ramus 1. Two wires were used in 10 cases. Stents were used in 24 cases, drug eluting (DES) 19: median [quartiles] stent diameter 3.5 mm [3.0, 4.0], total stent length 19 mm [14, 24]. Final stent diameter was 4.0 mm [3.5, 4.5]. IVUS was used in 10 unprotected/3 protected cases. Procedural success rate was 26/27, with no complications. Follow up data is available for 26 cases, range 3 days–14 months. There were 7/26 clinical events, including one death (four unprotected and three protected). The unsuccessful case underwent surgery. Thirteen patients had repeat angiography, with restenosis in three cases: target vessel failure (TVF) rate was 4/25; IVUS/DES had been used in one.

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Conclusions: LMS represent <1.5% of PCI at this centre, but a range of cases has been attempted, often acute. LMS PCI has been safe, with a high procedural success rate but early TVF rate of 16%. This small study would support use of DES and IVUS in LMS PCI. 332 Impact of Targeted Drug Eluting Stent Use in High Risk Diabetic Patients Paul Das, Rebecca Reed* , Yuvaraj Malaiapan, Ian Meredith, FCSANZ Cardiovascular Research Centre, Monash Medical Centre, Melbourne, Australia Background: Drug eluting stents (DES) offer lower rates of target vessel failure (TVF) than bare metal stents (BMS), particularly in higher risk long lesions in small vessels, and diabetic patients. However, the greater cost of DES prohibits their routine use. We reviewed a policy of targeted DES use in diabetic patients. Method: All stenting procedures in diabetic public patients in 2003 and 2004 were examined retrospectively. DES were routinely restricted to lesions ≤2.5 mm diameter and ≥20 mm length, plus cases of bifurcations, ostial stenosis and in-stent restenosis. The dimensions of DES and BMS used were compared. Outcome data from patients who had represented were compared. Results: Two hundred eighteen procedures were performed. One hundred and eleven (50.9%) received BMS and 107 (49.1%) DES. Median [quartiles] stent diameter was 2.875 [2.5, 3.5] mm versus 2.75 [2.5, 3.0] mm (p = 0.074) and total stent length was 16 mm [13, 20] versus 20 mm [16, 24] (p = 0.024). There were three DES bifurcation cases and 1 BMS bifurcation case. Sixty-five (30%) patients represented, at mean 7.6 months, with symptoms requiring repeat angiography: 27 with BMS versus 38 with DES (p = 0.076). Documented TVF rates were 12 (10.8%) for BMS versus 11 (10.3%) for DES (p = ns). Documented subacute stent thrombosis rates were 2 (1.8%) versus 1 (0.9%) (p = ns). Conclusion: A policy of targeted DES use in diabetic patients with highest risk lesions enables BMS use in 50% of cases whilst achieving a similar TVF rate of approx 10% in both groups. This rate compares favourably with trial and registry data for DES in all diabetic lesions. 333 Elective and Emergency Percutaneous Intervention in a Rural Cardiac Angiography Unit with Off-Site Surgical Backup Over 80 km Away. Our Experience to Date D. Wang* , B. Gunalingam, FCSANZ, A. Hill, N. Wilkes Gosford Hospital, Gosford, NSW, Australia Background: Several studies have demonstrated the safety and efficacy of both elective and emergency infarct percutaneous coronary intervention (PCI) without on-site surgical backup. Gosford Hospital Cardiac Angiography Unit (CAU) is unique, in that our surgical backup is over 80 km away.

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Aims: To review the safety and efficacy of elective and emergency infarct PCI in a rural setting, where the nearest surgical backup is over 80 km away. Methods: We retrospectively reviewed data from all PCIs performed both electively and as emergency primary infarcts presenting to Gosford Hospital CAU between September 2002 and July 2005. Results: A total of 849 cases were performed. Seven hundred and eighty-nine cases were elective and 60 cases were emergency infarcts, 43 being primary and 17 being rescue PCIs. Of the emergency PCIs, there were 3 deaths, unrelated to the procedure. There were no urgent transfers related to PCI complications. Of the remaining 789 elective cases, PCI was performed successfully in 751 cases. In 38 cases, the lesion could not be crossed. This gave an overall procedural success rate of over 95%. There were nine major complications, including 1 death unrelated to the procedure. There were no urgent transfers to surgery for PCI related complications. Conclusion: Our PCI data on nearly 850 patients, with a zero percent emergency transfer rate and low morbidity and mortality rates, shows that PCI can be safely performed without on-site surgical backup. This issue is a contentious one, with the recently released ACC/AHA guidelines giving elective PCI without on-site surgical backup a Class IIIC recommendation despite an increasing trend of peripheral hospitals setting up CAUs and performing PCI without surgical backup. 334 A Comparison of Percutaneous Patent Foramen Ovale Closure with and Without Transoesophageal Echocardiography Guidance S. Eggleton* , R. Allan, FCSANZ, G. Cranney, FCSANZ Eastern Heart Clinic and Prince of Wales Hospital, Sydney, Australia Background: In April 2005 we commenced performing percutaneous closure of patent foramen ovale (PFO) without transoesophageal echocardiographic (TOE) guidance. We sought to compare intra-procedural outcomes between those undergoing the procedure with TOE guidance and those without. Methods: We retrospectively identified 35 consecutive patients who underwent percutaneous PFO closure without TOE guidance between April 2005 and January 2006 and compared available data with 31 patients who underwent the procedure with TOE guidance between February 2003 and March 2005. All closures were performed by the same experienced proceduralist and all patients received the Amplatzer PFO device (AGA Medical Corp., Minnesota). Results: The mean age ± S.D. was 53 ± 15. Females comprised 44%. The most common indication was a cerebrovascular accident. There were no significant differences in baseline data. There was a significant reduction in procedure time, 46 ± 12 min without TOE guidance versus 54 ± 13 min in those with (p = 0.016). There was no signif-

Heart, Lung and Circulation 2006;15S:S1–S167

icant change in screening time (5.3 min versus 6.7 min, p = 0.2), Dose Area Product (9.5 Gy cm2 versus 13.4 Gy cm2 , p = 0.6) or the number of devices trialled (1.03 versus 1.13, p = 0.13). There was a significant shift in the use of a smaller device in those without TOE guidance (p = 0.001). The only complication encountered was transient ST elevation in one patient having the procedure without TOE guidance. Conclusions: Percutaneous closure of PFO without TOE guidance results in a reduction in procedure time without any change to screening time or intra-procedural complications. 335 Clinical Outcomes of a Selective Approach to Drug Eluting Stent (DES) Usage P. Roy1,2,* , B.P.Y. Yan1,2 , A. Bowyer1 , A.E. Ajani1,2 , FCSANZ, J. Lefkovits1,2 , FCSANZ, R.J. Warren1,2 , FCSANZ 1 Departments 2 Melbourne

of Cardiology, Royal Melbourne Hospital; Private Hospital, Parkville, Victoria, Australia

Background: Proven reductions in restenosis have resulted in the widespread use of drug eluting stents (DES). This has increased procedural costs. Ideally, DES use should be minimized without compromising clinical outcome. Objective: To assess the clinical outcome of restricting DES to patients with an increased risk of restenosis. Methods: The 12 month clinical outcomes of patients where DES use was restricted (SEL – 249 patients, 271 lesions) were compared with two separate patient cohorts where bare metal stents (BMS – 279 patients, 316 lesions) and DES were used exclusively (272 patients, 302 lesions). The three groups consisted of consecutive patients. The SEL group comprised patients where DES use was restricted to those at increased risk of restenosis. Patients in SEL had to meet at least one of the following criteria: Diabetes, stent length ≥20 mm, vessel diameter ≤2.5 mm, bifurcation or ostial lesions, chronic total occlusions or in-stent restenosis. Results: The three groups were comparable. Fifty-three percent of patients in the SEL group met criteria and received DES. Table. Twelve month Clinical Outcomes BMS vs. DES vs. SEL P value

Death, % MI, % TLR, % MACE, %

BMS Group

DES Group

SEL Group

BMS vs. DES

BMS vs. SEL

DES vs. SEL

3 3 8 14

2 3 1 7

3 2 3 8

0.44 0.55 <0.0001 0.002

0.63 0.23 0.02 0.02

0.41 0.20 0.04 0.42

Conclusions: The selective use of DES results in a low incidence of clinical events and may provide a cost effective approach to DES usage.

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336 Does Female Gender Impact on Contemporary Australian Coronary Interventional Practice?

337 Drug Eluting Stents; Are they Only Cost-Effective in Clinical Trials?

B. Yan1,* , A. Ajani1,7 , FCSANZ, W. Ahmar1 , G. New2 , S. Duffy3 , FCSANZ, A. Walton3 , G. Szto4 , FCSANZ, R. Warren1 , FCSANZ, L. Ponnuthurai5 , A. Brennan6 , A. Meehan6 , C. Reid6 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators

A. Dalton1,* , D.P. Chew2 , FCSANZ, V. Sundaraja3 , R. Osborne1 1 University

of Melbourne; 2 Flinders Medical Centre/Flinders University, Adelaide; 3 Department of Human Services, Victoria, Australia

1 Department

of Cardiology, Royal Melbourne Hospital; of Cardiology, BoxHill Hospital; 3 Department of Cardiology, Alfred Hospital; 4 Department of Cardiology, Frankston Hospital; 5 Department of Cardiology, Geelong Hospital, Melbourne; 6 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia 2 Department

The aim of this study was to evaluate the impact of female gender in contemporary Australian percutaneous coronary intervention (PCI) practice, as there is evidence that females have adverse outcomes. Methods: We analysed 2765 consecutive pts undergoing 3488 PCIs who were enrolled in the Melbourne Interventional Group Registry (April 2004–December 2005). Results: Female pts compared to males, were older and had a higher rate of adverse baseline clinical characteristics (Table). At 30 days, females had a higher mortality (3.2% versus 1.4%, p < 0.01) and MACE rate (8.9% versus 5.3%, p < 0.01). At 12 months follow-up (completed in 567 pts), females had comparable mortality (3.4% versus 3.24%, p = NS) and MACE (16.8% versus 15.1%, p = NS). Conclusion: Female patients presenting for PCI have increased adverse clinical features including smaller vessels and increased mortality and 30-day MACE. Complete analysis of the cohort at 12-month follow-up will be presented.

Age, year ± S.D.

Female (n = 751)

Male (n = 2014)

p

69.5 ± 11.3

63.1 ± 11.8

<0.01

Diabetes mellitus, %

27.2

21.4

<0.01

Hypertension, %

73.4

58.1

<0.01

Smoking history, %

43.0

70.4

<0.01

Prior myocardial infarction, %

31.4

26.7

0.01

Acute coronary syndrome, %

64.5

60.8

0.04

Procedural details (n = no. of lesions)

N = 929

N = 2559

–

Mean total stent length, mm ± S.D.

17.9 ± 2.9

18.4 ± 3.0

0.14

Reference vessel diameter, mm ± S.D.

2.8 ± 0.5

3.0 ± 0.5

<0.01

Left anterior descending artery, %

33.7

30.4

0.04

Lesion type B2/C, %

46.6

46.9

0.68

Drug eluting stent use, %

50.7

50.2

0.43

The rapid uptake of drug-eluting stents (DES) has prompted study of their cost-effectiveness. These studies have relied on clinical trial data, where protocol-driven repeat revascularization may confound the true benefits. We explored the potential benefit of DES within a real cohort within the Australian health system. Methods: The actual rates of revascularization following first bare metal stent (BMS) insertion, before 30 June 2003, were obtained from a retrospective cohort of patients within the Victorian Linked Dataset. The procedures performed per 90-day cycle over two subsequent years were assessed. Risk ratios for rates of revascularization reported in systematic reviews of DES were applied. Estimates of unit cost for each revascularization procedure were taken from national casemix data, adjusted for differences in the actual device cost of DES and BMS. Published quality of life coefficients were applied. Results: In total, 19,905 patients were identified. Repeat revascularization occurred in 2890 patients. Imputation of DES efficacy resulted in 2089 fewer procedures. The average total cost per DES patient was AUD $7836, compared with AUD $6404 per BMS patient. The incremental cost of a procedure averted was AUD $13,279, while the incremental cost per quality-adjusted life year was AUD $549,470. An incremental cost effectiveness ratio commonly deemed acceptable only emerges when the cost of DES falls below $1495. Conclusions: Clinical trial rates of revascularization overestimate the risk of restenosis and the benefit of DES. This first published economic evaluation of DES using actual revascularization rates in Victoria demonstrates the routine use of DES is not cost-effective when compared to BMS.

338 Distal Embolisation During Percutaneous Saphaneous Vein Graft Intervention William J. van Gaal1,* , Robin P. Choudhury1 , Italo Porto1 , Keith M. Channon1 , Adrian P. Banning1 , Vlad Dzavik2 , Leonard M. Schwartz2 , Peter H. Seidelin2 , Rachael Ramsamujh2 , S. Bui2 , Dan J. Blackman1 1 John Radcliffe Hospital, Oxford, United Kingdom; 2 Toronto General Hospital, Toronto, Ont., Canada

Objective: To assess the frequency of distal embolisation during saphenous vein graft (SVG) PCI and the clinical, angiographic or procedural variables which may predict its occurrence.

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Background: Distal embolisation during PCI is associated with myocardial infarction and poor outcome. Distal protection devices (DPDs) in patients undergoing SVG PCI reduce embolisation and improve outcomes. It is unclear if all patients undergoing SVG PCI should have distal protection. We investigated whether clinical or angiographic variables can predict the degree of embolisation and need for a DPD. Methods: Between August 2002 and March 2005 consecutive patients undergoing SVG PCI eligible for a DPD were studied. The DPD (FilterWire EX or EZ, Boston Scientific, MA) was deployed during all balloon inflations. The FilterWire was fixed in formalin and photographed under high magnification. Embolic debris area (mm2 ) was quantified by semi-automated edge-detection analysis (ImagePro Plus, Media Cybernetics, MD). Results: Fifty-five patients (58 SVGs) underwent SVG PCI with distal protection. Macroscopically visible debris was found in all but one FilterWire (57/58). Median debris area was 4.0 mm2 (0.0–25.1 mm2 ). No clinical or angiographic variables predicted embolisation (Table 1). In particular, SVG age, ectasia, thrombus, plaque load, stent oversizing, nor clinical presentation predicted the presence or degree of embolic debris. Conclusion: Distal embolisation during SVG PCI is universal. Furthermore, embolic load cannot be predicted by clinical or angiographic variables. Distal protection should be used in all patients undergoing SVG PCI. Table 1. Clinical and Angiographic Variables vs. Debris Area Debris area (mm2 )

Variable

p

Age of SVG (years)

<10 ≥10

5.9 ± 4.9 6.4 ± 6.8

0.81

Degenerate SVG (>50% ectasia)

Yes No

5.4 ± 5.6 6.9 ± 6.7

0.42

Angiographic thrombus/filling defect

Yes No

6.4 ± 6.3 6.4 ± 6.5

0.99

TIMI flow pre-PCI

<3 3

6.8 ± 7.0 5.9 ± 5.5

0.63

Acute coronary syndrome

Yes No

6.2 ± 6.4 7.1 ± 6.5

0.67

Reference lumen diameter (mm)

<3.5 3.5–4 4.1–4.5 >4.5

6.3 5.2 7.4 7.0

± ± ± ±

7.8 6.1 7.4 5.4

NS

Lesion length (mm)

<10 10–20 20.1–30 >30

6.3 6.2 5.8 7.3

± ± ± ±

9.3 5.6 6.8 6.6

NS

Plaque volume

Quartile 1 Quartile 2 Quartile 3 Quartile 4

5.4 5.0 8.1 6.5

± ± ± ±

6.6 7.0 5.7 6.7

NS

339 Three-Month Clinical Outcome of TAXUS Stents in Rescue Angioplasty T. Wells1,* , N. Curzen2 , A. Calber2 , I. Simpson2 , H. Gray2 , K. Dawkins2 1 Department of Cardiology, Fremantle Hospital, WA, Australia; 2 Wessex Cardiac Centre, Southampton University Hospital, UK

Introduction: Currently, there are limited “real-world” data on the safety of the paclitaxel-eluting (TAXUS) stent in the setting of rescue percutaneous coronary angioplasty (PTCA) for ST-elevation myocardial infarction (STEMI). Methods: We studied 112 consecutive patients over a 24month period undergoing rescue PTCA, within 24 h of failed thrombolysis, who had TAXUS stents implanted. All patients received dual anti-platelet therapy pre- and post-procedure. Results: Mean age was 60.9 ± 10.4 years. Seventy-nine percent were male, 36% hypertensive, 37% current smokers, 79% had dyslipidaemia, 13% were diabetic and 3% had previous revascularisation. 7.1% of patients were in cardiogenic shock. A total of 169 stents were inserted (mean 1.5 per patient) with a mean stented length of 24.3 ± 10.0 mm. Multivessel disease was present in 35.7%. A total of 7.1% had “total” revascularisation. Pre-procedure 38.4% had TIMI-0 flow and post-procedure TIMI-3 flow was achieved in 87.5%. Intra-luminal thrombus was identified in 82.1%. In 65.2% the culprit vessel was the LAD. Direct stenting was performed in 21.4%. Adjunctive abciximab therapy was given in 95.5%. In-hospital mortality was 5.4%. No patient had reinfarction or required further target lesion revascularisation (TLR) prior to discharge. In total, 11.6% had bleeding complications (4.5% major and 7.1% minor) including two deaths. At follow-up, median duration of 100 days, there were no further deaths, reinfarction or TLR. Thus, both actuarial and MACE-free survival was 94.6%. Conclusions: Use of the TAXUS stent for rescue PTCA is safe with a zero incidence of acute stent thrombosis. However, risk of bleeding complications are relatively high in these patients.

340 Treatment of Unprotected Left Main Coronary Artery Disease with Drug Eluting Stents in Patients at High Risk for Coronary Artery Bypass Grafting P. Barlis, M.C.G. Horrigan, FCSANZ, S. Elis, R.K. Chan, M.C.G. Wong, H.M.O. Farouque, G. Proimos, FCSANZ, D.J. Clark* Austin Hospital, Department of Cardiology, Heidelberg, Victoria, Australia Introduction: Coronary artery disease with >50% unprotected left main stenosis (ULM) is a strong indication for coronary artery bypass grafting (CABG). Recent observational studies have treated ULM with drug-eluting stents (DES) with favourable outcomes but these were selected

patients from highly selected centres limiting their relevance to clinical practice. The objective of our study was to determine the outcomes after utilising DES to treat ULM in patients at high risk for CABG. Methods: Twenty patients with findings of >50% angiographic stenosis of the left main coronary artery and no prior history of CABG were included. Patients were divided into two groups based on the presence of AMI with cardiogenic shock (group A, n = 5) or not (group B, n = 15). Patients were followed for a median of 12 months. Results: Sixteen patients (16/20, 80%) were not ideal candidates for CABG based on severe co-morbidity, poor left ventricular function ± cardiogenic shock. Procedural success was 20/20, 100%. Three (60%) patients in group A (n = 5) died during their hospital stay from cardiogenic shock with no in-hospital mortality recorded in group B (p < 0.001). The two surviving patients in group A had no additional MACE. In group B (n = 15), one patient died suddenly 8 weeks post-procedure and the cumulative MACE at follow-up was 1/15 (7%). Conclusions: Our study demonstrates the feasibility of ULM treatment with DES with acceptable short and medium term outcomes. While CABG remains the best form of revascularisation for the majority of patients with ULM, DES should be considered in those who are high risk.

341 Long-Term Outcomes of Selective Drug Eluting Stent (DES) Use in Diabetic and Non-Diabetic Patients B. Smith, J. Gutman, FCSANZ, A.I. MacIsaac, FCSANZ, R. Whitbourn, FCSANZ, J. Towner Department of Cardiology, St Vincent’s Hospital Melbourne, Victoria, Australia Diabetics are at increased risk of restenosis and major adverse coronary events (MACE) following percutaneous coronary intervention (PCI). Cost constraints restrict the use of DES to one third of our patients. DES are reserved for pts deemed at increased risk of restenosis. The longerterm impact of this policy on the clinical outcome of diabetic patients is unknown. 534 consecutive patients presented for PCI, including 413 (77.3%) non-diabetics and 121 (22.7%) diabetics. The average age in both groups was 63.5 years. DES were used more frequently in diabetics (47.1% versus 28.6%, p = < 0.001). At 6 months (96% follow-up), target vessel revascularisation (TVR) and MACE were not significantly different between the 2 groups. Eighteen-month data was available for 82.8% of eligible pts. TVR was not different, but there were more MIs (18.1% versus 4.1%, p < 0.001) and deaths (9.7% versus 3.3%, p = 0.026) in the diabetic group, leading to significantly higher MACE.

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18 Months

Diabetes

No Diabetes

p Value

Diabetes

No Diabetes

TVR

9/117 (7.7%)

19/399 (4.8%)

MACE

20/117 (17.1%)

42/399 (10.5%)

p Value

0.22

10/73 (13.7%)

19/238 (8.0%)

0.16

0.06

21/73 (28.8%)

32/238 (13.4%)

0.002

Conclusions: Following selective utilisation of DES, MACE rates are higher in diabetics at 18 months despite an insignificant difference in TVR rates. The latter effect may be attributable to the significantly higher use of DES in the diabetic population. However, the serious adverse event rate (MI and death) remains high in diabetics following coronary artery stenting. 342 Clinical Outcomes after Percutaneous Coronary Interventions in Octogenarians B. Yan1,* , A. Ajani1,7 , FCSANZ, R. Gurvitch1 , S. Duffy2 , FCSANZ, D. Clark3 , M. Sebestian4 , FCSANZ, G. New5 , FCSANZ, R. Warren1 , FCSANZ, R. Lew6 , FCSANZ, A. Brennan7 , C. Reid7 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

of Cardiology, Royal Melbourne Hospital; of Cardiology, Alfred Hospital; 3 Department of Cardiology, Austin Hospital; 4 Department of Cardiology, Geelong Hospital; 5 Department of Cardiology, Box Hill Hospital; 6 Department of Cardiology, Frankston Hospital, Melbourne; 7 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia 2 Department

The aim of this study was to investigate clinical outcomes of octogenarians (≥80 years) undergoing percutaneous coronary interventions (PCI). Methods: We compared 312 octogenarians to 2453 nonoctogenarians who underwent PCI and were enrolled in the Melbourne Interventional Group registry (Apr 2004–Dec 2005). Baseline characteristics, 30-day and 12month outcomes were compared. Results: Octogenarians had a higher rate of adverse clinical features compared to patients (pts) <80 years, although lesion characteristics were similar (Table). At 30 days, octogenarians had a higher mortality (6.4% versus 1.3%, p < 0.01) and MACE rate (13.1% versus 5.8%, p < 0.01). To date, 567 pts (21%) have completed 12-month follow-up, with octogenarians having higher mortality (7.8% versus 1.1%, p < 0.01) and MACE (29.16% versus 14.1%, p < 0.01). Age ≥80 years was an independent predictor of 12-month mortality (OR 5.0, 95% CI 2.0–12.5). Conclusion: Octogenarians have increased mortality and adverse clinical events post PCI, mandating thorough clinical evaluation before acceptance for PCI.

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ABSTRACTS Age, years

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Age ≥80 Years (n = 312)

Age <80 Years (n = 2453)

83.1 ± 2.6

62.6 ± 10.7

Thin-Strut BMS p <0.01

Diabetes mellitus, %

25.8

22.6

0.12

Hypertension, %

76.1

60.5

<0.01

Prior myocardial infarction, %

36.7

27.9

0.01

Prior heart failure, %

8.1

2.7

<0.01

Chronic renal impairment, %

10.7

3.3

<0.01

Prior stroke, %

9.9

4.3

<0.01

Acute coronary syndrome, %

70.7

60.6

<0.01

Procedural details (n = no. of lesions)

n = 387

n = 3101

–

Mean stent length, mm ± S.D.

17.7 ± 8

18.3 ± 8

0.38

Reference vessel diameter ≤2.5 mm, %

32.0

29.2

0.48

Lesion type B2/C, %

50.9

45.3

0.07

343 The Impact of Thin-Strut Bare Metal Stents in the DrugEluting Stents Era B. Yan1,* , A. Ajani1,4 , FCSANZ, J. Lefkovits1 , FCSANZ, R. Lew2 , FCSANZ, P. Roy1 , R. Warren1 , FCSANZ, A. Walton3 , FCSANZ, J. Shaw3 , D. Eccleston1 , FCSANZ, A. Meehan4 , C. Reid4 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

of Cardiology, Royal Melbourne Hospital, Australia; 2 Department of Cardiology, Frankston Hospital, Australia; 3 Department of Cardiology, Alfred Hospital, Melbourne, Australia; 4 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Despite widespread utilisation of drug-eluting stents (DES), bare metal stent (BMS) technology continues to improve, with thinner stent struts reducing restenosis. Methods: We analysed 2226 consecutive patients (pts) undergoing percutaneous coronary interventions (PCI) who were enrolled in the Melbourne Interventional Group registry. Patients receiving only thin-strut BMS (Liberte, Vision ± Driver) were compared to pts receiving only DES. Baseline characteristics, 30-day and 12-month outcomes were compared. Results: Patients receiving thin-strut BMS compared to DES were younger (63.8 ± 12.2 versus 65.4 ± 12.0 years, <0.01), had less diabetes (15.2% versus 29.2%, p < 0.01) and had less complex lesions (Table). At 30-days, thin-strut BMS (compared to DES) had similar rates of target vessel revascularization [TVR (2.2% versus 2.1%, p = NS)] and MACE (6.1% versus 5.1%, p = NS). At 12-month follow-up (completed in 424 pts), thin-strut BMS had comparable rates of TVR (8.6% versus 7.5%, p = NS) and MACE (16.4% versus 15.4%, p = NS). Conclusion: Thin-strut BMS use in less complex lesions results in comparable clinical outcomes to DES. Complete 12-month analysis will be presented.

Number of patients

890

DES 1336

P –

Number of lesions

1084

1622

–

Mean no. of stents used, ±S.D.

1.1 ± 0.4

1.2 ± 0.3

0.02

Reference vessel diameter, mm ± S.D.

3.0 ± 0.5

2.8 ± 0.4

<0.01

Mean total stent length, mm ± S.D.

17.3 ± 7.3

19.1 ± 8.2

<0.01

Total stent length ≥20 mm, %

20.3

39.9

<0.01

Lesion type B2/C, %

40.0

50.8

<0.01

In-stent restenosis, %

0.5

6.9

<0.01

344 Invasive Assessment of the Coronary Microcirculation: Superior Reproducibility and Less Hemodynamic Dependence of Index of Microcirculatory Resistance as Compared to Coronary Flow Reserve M.K.C. Ng1,2,* , FCSANZ, A.C. Yeung2 , W.F. Fearon2 1 Royal Prince Alfred Hospital, Sydney, Australia; 2 Stanford University School of Medicine, Stanford, USA

Background: A simple, reproducible invasive method for assessing the coronary microcirculation is lacking. A novel index of microcirculatory resistance (IMR) has been shown in animals to correlate with true microvascular resistance and, unlike coronary flow reserve (CFR), to be independent of the epicardial artery. We sought to compare the reproducibility and hemodynamic dependence of IMR with CFR in humans. Methods and results: Using a pressure-temperature sensor-tipped coronary wire, thermodilution-derived CFR and IMR were measured, along with fractional flow reserve (FFR), in 15 coronary arteries (15 patients) under the following hemodynamic conditions: (1) twice at baseline; (2) during right ventricular pacing at 110 bpm; (3) during intravenous infusion of nitroprusside and; (4) during intravenous dobutamine infusion. Mean CFR did not change during baseline measurements or during nitroprusside infusion but decreased during pacing (from 3.1 ± 1.1 at baseline to 2.3 ± 1.2 during pacing, P < 0.05) and during dobutamine infusion (from 3.0 ± 1.0 to 1.7 ± 0.6 with dobutamine, P < 0.0001). By comparison, mean values for IMR and FFR remained similar throughout all hemodynamic conditions. The mean coefficient of variation between two baseline measurements was significantly lower for IMR (6.9 ± 6.5%) and FFR (1.6 ± 1.6%) than for CFR (18.6 ± 9.6%) (P < 0.01). Mean correlation between baseline measurements and each hemodynamic intervention was superior for IMR (r = 0.90 ± 0.05) and FFR (r = 0.86 ± 0.12) compared to CFR (r = 0.70 ± 0.05) (P < 0.05). Conclusion: Compared to CFR, IMR provides a more reproducible assessment of the microcirculation, which is independent of hemodynamic perturbations. Simultaneous measurement of FFR and IMR may provide a comprehensive and specific assessment of coronary physiology at both epicardial and microvascular levels, respectively.

Abstracts

345 Comparison of ST Resolution in Primary Percutaneous Coronary Intervention for Anterior versus Inferior STEMI A. Yeung* , A. Farshid, D. Coles, I. Jeffery, D. McGill, FCSANZ, S. O’Connor, FCSANZ, R.P. Tan Department of Cardiology, The Canberra Hospital, Canberra, Australia

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346 A Snapshot of Current Treatment of In-Stent Restenosis B. Yan1,* , A. Ajani1,6 , FCSANZ, D. Clark2 , S. Duffy3 , FCSANZ, R. Warren1 , FCSANZ, R. Lew4 , FCSANZ, M. Sebastian5 , FCSANZ, G. Szto4 , FCSANZ, D. Eccleston1 , FCSANZ, A. Meehan6 , C. Reid6 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

Anterior ST elevation MI [STEMI] confers a higher mortality than inferior STEMI. Early complete ST resolution [STR] post reperfusion therapy is an independent predictor for mortality. Aim: To compare STR in anterior versus inferior STEMI for patients undergoing primary percutaneous coronary intervention [PCI] and its effect on 30 day mortality. Method: One hundred and twenty consecutive patients undergoing primary PCI for STEMI from January 2004 to June 2005 were recruited for the study. Percent [%] STR was calculated by measuring the difference in sum ST elevation in all leads in paired 12 lead ECGs. Early STR was measured as STR at 1 h post-PCI and late STR 18–24 h postPCI. STR was defined as complete [>70%], partial [30–70%] and none [<30%]. Results: Anterior

Inferior

Pt Nos [%]

50 [41.6%]

70 [58.3%]

Mean age, years

62.6

61.5

Female (%)

32.9

34.0

Complete (%)

46.9

71.0

Partial (%)

32.7

13.0

None (%)

20.4

16.0

Mean time between ECGs h:min

3:02

3:56

Complete (%)

57.2

91.2

Partial (%)

26.5

4.4

None (%)

16.3

4.4

18:45

23:08

Early STR analysis*

Late STR analysis*

Mean time between ECGs h:min Overall 30 day

mortality†

8.0

4.4

>70% Early STR 30 day mortality† (%)

4.3

4.1

<70% Early STR 30 day mortality* (%)

11.5

5.3

*

(%)

p value significant. † p value non significant.

Conclusion: Anterior STEMI have less early and late STR, respectively, post primary PCI. The mortality for anterior STEMI may be higher only when early STR is not complete.

of Cardiology, Royal Melbourne Hospital, Australia; 2 Department of Cardiology, Austin Hospital, Australia; 3 Department of Cardiology, Alfred Hospital, Australia; 4 Department of Cardiology, Frankston Hospital, Australia; 5 Department of Cardiology, Geelong Hospital, Melbourne, Australia; 6 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Aim: The aim of this study was to assess contemporary treatment of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). Methods: We analysed consecutive patients (pts) treated for ISR from the Melbourne Interventional Group (MIG) PCI registry (April 2004–December 2005). Results: Of 2765 pts undergoing PCI, 131 pts (4.7%) presented for treatment of 149 ISR lesions. Mean pt age was 63.2 ± 12.7 years old, with 71.8% males, 24.4% diabetics and 53.8% presented with an acute coronary syndrome. Most ISR lesions involved native coronaries (98%), predominantly RCA lesions (32.2%). The mean reference vessel diameter was 2.9 ± 0.3 mm. Treatment of ISR involved balloon angioplasty alone in 32 (21.4%) lesions, and additional stenting in 117 (78.5%) lesions [drug-eluting stents (DES) n = 112 (75.2%) and bare-metal stents (BMS) n = 5 (3.4%)]. Additional stent length was 21.7 ± 10 mm. Thirty-day mortality in pts treated with balloon angioplasty, DES and BMS was 4.2% (n = 1), 1.1% (n = 1) and 20% (n = 1), respectively (p < 0.01). At 30-days, of the total ISR cohort, only one pt required target lesion revascularization (initially in balloon angioplasty group), and overall MACE was 4.3%. No acute or subacute thrombosis was recorded. The plan duration of clopidogrel was ≥12 months in 56% of pts treated with DES. Conclusions: ISR is uncommon in contemporary PCI practice, involving only 4.7% of patients. DES is the preferred therapy for ISR and appears effective to 30-day follow-up. Complete analysis of the cohort at 12 months will be presented, including rates of target vessel revascularization. 347 Carotid Artery Stenting—Single Centre Experience Treating High Risk (NASCET INELIGIBLE) Patients N. Jepson* , D. Friedman, FCSANZ, A. Lennox Departments of Cardiology and Vascular Surgery, Prince of Wales Hospital and Eastern Heart Clinic, Sydney, NSW, Australia Carotid artery stenting (CAS) with embolic protection devices (EPDs) has been shown to be a safe and effective alternative to carotid endarterectomy (CEA) especially in patients with a high surgical risk.

ABSTRACTS

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ABSTRACTS

We report our experience of CAS in patients who would have been excluded from the pivotal NASCET Trial which established the role CEA. From December 2002–February 2006, 62 lesions (in 60 patients) were treated by CAS at our institution. Of these, 56 lesions (90%) in 54 patients (mean age 77 ± 6 years) represented very high-risk candidates for CEA (NASCET ineligible) and form the basis of this report. Forty-eight (86%) had neurological symptoms necessitating CAS. Major reasons for NASCET unsuitability were—prior neck surgery/radiotherapy 4 (7%), high lesion 1 (2%), prior ipsilateral CEA 6 (11%), >80 years 11 (20%) and significant cardiac disease 34 (61%). Additionally, 5 (9%) had a contralateral carotid occlusion and 1 (2%) underwent planned CABG after CAS. EPDs were delivered in 55/56 (98%) treated vessels and all lesions were successfully stented. Four (7%) developed a TIA post-CAS. There were no cases of peri-procedural MI and one (2%) minor stroke. One patient (2%) sustained a fatal stroke after CAS. The 30day stroke/death rate was 3.6%. There have been no cases of late stroke, death or restenosis. In conclusion, CAS with EPDs performed by an experienced team in a “real-world” patient population unsuitable for CEA based on NASCET criteria is a safe and highly effective treatment modality for atherosclerotic carotid disease. These findings compare favourably with historic surgical and stenting controls. 348 Primary Angioplasty in Acute ST-elevation Myocardial Infarction in the Elderly (>75 years): A Single Centre Experience C. Hiew* , P. Diu, S. Mylabathula, S. Adera, B. Bastian, S. Thambar, R. Bhagwandeen, FCSANZ, G. Bellamy, FCSANZ Cardiovascular Department, John Hunter Hospital, Newcastle, Australia Background: Clinical outcome of elderly patients following primary coronary angioplasty are few with conflicting results. Methods: We analysed data of 51 consecutive patients aged 75 years or older presented to our institution with acute STEMI for primary angioplasty. Data from 52 consecutive patients aged 74 or less were collected over the same period for comparison. Clinical characteristics, angiographic finding, PTCA results and major adverse events during hospitalisation and 6 months follow up were analysed. Results: Elderly group (mean age 79 ± 3.6 years) had more co-morbidities, cardiovascular risk factors and coronary disease burden than the younger group (mean age 59.7 ± 11.3 years). (Cardiovascular risk factors: 3.1 versus 2.6, p = 0.05 and Multi-vessel disease: 62.7% versus 46.2%, p = 0.045, respectively). Elderly patients took longer time before seeking an ambulance from onset of symptoms (>3 h: 70.6% versus 44.2%, p = 0.009). Angiographically, the success rate of achieving TIMI 3 flow was similar in both

Heart, Lung and Circulation 2006;15S:S1–S167

groups (78.4% versus 86.5%, p = 0.3). In-hospital mortality were higher among the elderly patients compared with the younger (15.7% versus 3.8%, p = 0.02). For patients discharged from hospital, cumulative mortality at 30 days, 3 and 6 months in the elderly and younger group were similar (2.3% versus 2.0%, p = ns; 7.0% versus 4.0%, p = 0.7; 11.6% versus 6%, p = 0.5, respectively). There was no difference in 30-day hospital readmission rate (8.0% versus 7.0%, p = 0.2). Conclusions: Our study suggests similar procedural success rate can be achieved with primary angioplasty in the elderly. The high mortality in the elderly with STEMI may be explained by a higher disease burden and comorbidities. Primary angioplasty is a reasonable strategy for management of STEMI in elderly patients. 349 High Bolus Dose Tirofiban Achieves Superior Platelet Inhibition to Abciximab in Patients Undergoing Coronary Stenting D.L. Walters1,* , FCSANZ, M.L. Ray2 , A. McCann1 , J. Cameron1 , FCSANZ, J.H.N. Bett1 , FCSANZ, C.N. Aroney1 , FCSANZ 1 Department of Cardiology; 2 Haemostasis Research Laboratory

and The Prince Charles Hospital, Brisbane, Australia We aimed to compare a high-dose bolus regimen of tirofiban (hd-tirofiban) to standard dose of abciximab for patients undergoing high-risk percutaneous coronary intervention (PCI). We sought to compare the percentage platelet inhibition as assessed by whole blood aggregation with collagen between the two patient groups. Methods: We analyzed patients who received either hdtirofiban (25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. Platelet inhibition percentage was assessed by whole blood aggregation with collagen at 5 ␮g/mL. All patients received intravenous unfractionated heparin, aspirin and clopidogrel. In-hospital major adverse cardiac events and bleeding complications were recorded in all cases. Results: The study population consisted of 105 patients with undergoing PCI with intracoronary stenting who received adjuvant glycoprotein IIb/IIIa inhibitors for highrisk clinical or angiographic features. A total of 105 patients (age 60.7 ± 10 years, 76% men) were studied with 75 (71%) patients receiving Abciximab and 30 (29%) hd-tirofiban. The baseline clinical characteristics such as age, sex, indication for the procedure was similar in both patient groups. The percentage inhibition of platelet aggregation of whole blood by collagen was greater in patients receiving hd-tirofiban compared to those receiving standard weight adjusted abciximab (84% versus 62%, p < 0.001). There were no in hospital MACE or major bleeding events in either group. Conclusion: A high-dose bolus regimen of tirofiban provides superior platelet inhibition to standard dose abciximab for patients undergoing high-risk percutaneous

coronary intervention (PCI) when assessed by whole blood aggregation with collagen. 350 Utilisation of Non-Interventional Hospital Beds for PostPCI Care P. Diu1,* , C. Hiew1 , S. Mylabathula1 , S. Adera1 , P. Varghese1 , R. Prashar1 , S. Fenning1 , B. Wegener1 , L. Savage1 , C. Casey2 , G. Warner2 , FCSANZ, G. Bellamy1 , FCSANZ 1 John

Hunter Hospital, Newcastle Mater Misericordiae Hospital, Newcastle, NSW, Australia; 2 Newcastle Mater Misericordiae Hospital, Newcastle, NSW, Australia Background: Benefits of early catheterisation for unstable coronary disease have been well described. Timely delivery of percutaneous coronary intervention (PCI) to patients at peripheral centers remains a significant challenge. Method: We aim to assess the safety of post-PCI care utilising beds at a non-interventional center. Data of 110 consecutive patients referred from a peripheral center who received PCI at our institute was analysed. All patients were transferred to our center on the day of PCI. Sixty-four of theses patients were returned to the referring hospital on the same day after PCI and 46 were admitted to our institution. Results: Age and gender were similar in the two groups. Coronary risk profile and disease burden were slightly higher in the returned group (Multi-vessel disease 58% versus 48%). The majority received PCI for single lesions (Multi-lesions PCI: 11% returned versus 17% admitted). PCI success rate was similar. All patients received weightadjusted heparin but more in the admitted group received IIb/IIIa inhibitor abciximab (24% versus 5%). All returned patients received arterial closure devices (Angioseal) and all patients admitted had sheath removal with manual compression. There was one procedural-related myocardial infarction in the returned (treated conservatively) and no in-hospital deaths in either group. Vascular

Abstracts

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complications were similar in both groups (3% returned versus 4% admitted). Conclusion: Non-interventional cardiology centers can be utilised safely for post-PCI care in selected patients after coronary intervention with the use of arterial closure devices. This strategy may benefit both the referring and interventional sites by allowing more efficient hospital bed utilisation and potential shorter wait time for procedures.

351 Acute Infarct Presentation Delays Over 10 Years C.M. Nunn* , FCSANZ, H.A. Charleson, G.P. Devlin, FCSANZ, S.C. Heald, FCSANZ, H.A. McAlister, FCSANZ, C. Sebastian Dept of Cardiology, Waikato Hospital, Hamilton, New Zealand Background: Primary angioplasty (PA) practice has been performed at Waikato Hospital (WH) now for over 10 years. We look at trends in treatment times over this period. In particular the time delay in initial presentation to hospital is analyzed. Methods: PA was performed for all high risk myocardial infarctions (MI) defined as anterior in location or MIs with haemodynamic compromise. Using a prospectively maintained database we selected patients presenting directly to WH for analysis of time intervals and subsequent clinical events. Results: Over this period 382 pts presented directly with an acute MI. One-year follow-up was obtained in 98%. Average age was 61.9, and 71.7% were male. 13.4% were diabetic, 71.9% were anterior and 9.8% were in cardiogenic shock. Median time from pain onset to hospital arrival was 120 min and from hospital arrival to balloon inflation was 85 min. Those with pain onset out of hours had a pre-hospital delay of 135 min however time of day did not influence subsequent times to reperfusion (83 min inh versus 87 min out-of-h). The annual times are shown below.

ABSTRACTS

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ABSTRACTS

Conclusion: Presentation delays have remained constant over the past 10 years. They remain excessive and are likely to only improve with a public education program. 352 Registry Data Evaluating the Effectiveness of Drug Eluting Stents for the Treatment of Symptomatic In-Stent Restenosis

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353 Are There Rebound Thrombotic Events if Only Two Weeks of Clopidogrel Therapy was Given Post Bare Metal Coronary Artery Stenting? Stuart L.J. Tie, Cheuk-Kit Wong, FCSANZ, Joel Yap, Gerard T. Wilkins, Michael J. Williams, FCSANZ, I. Patrick Kay, FCSANZ

M.I. Worthley1,2,* , FCSANZ, T.J. Anderson1 , M. Traboulsi1 , F. Charbonneau1 , M.J. Curtis1 , J.L. Hansen1 , M.L. Knudtson1 , F.P. Spence1 , D.M. Goodhart1

Department of Cardiology, Dunedin Hospital, Dunedin, New Zealand

1 Department

Background: Recent reports on late stent thrombosis after implantation of drug eluting causing ST elevation acute coronary syndrome (ACS) with high mortality have renewed interest in the thrombotic risk associated with incomplete stent re-endothelialization and inadequate antiplatelet therapy. Discontinuation of clopidogrel at 2 weeks after bare metal stenting when reendothelialization is incomplete may precipitate stent thrombosis. We sought to determine if rebound thrombotic events occurred after cessation of a 2-week course of clopidogrel treatment in patients who had implantation of bare metal stent. Methods: One thousand consecutive patients undergoing PCI with stent implantation from January 2000 to October 2003 were analyzed. Those who had successful implantation of bare metal stent without clinical events in the first 24 h and who received 2 weeks clopidogrel treatment were included (n = 983). Results: There were 13 (1.3%) stent thromboses between 24 h and 6 weeks post PCI, resulting in 3 deaths (23%), 2 ST elevation ACS (15%) and 8 non-ST elevation ACS (62%). The median time for stent thrombosis was 18 ± 14 days. Five of the 13 cases (38%) of stent thrombosis occurred after the first 2-weeks (1 in week 3, 1 in week 5, 3 in week 6), and all had predisposing factors for stent thrombosis (2 with stent length ≥30 mm, 3 with stent diameter ≤2.5 mm and 2 with bifurcation stenting). Conclusion: Five of 13 (38%) stent thromboses occurred in week 3 to week 6 after cessation of a 2-week course of clopidogrel post bare metal stenting.

of Cardiovascular Sciences and the Libin Cardiovascular Institute, University of Calgary, Calgary Alberta, Canada; 2 Cardiovascular Research Centre, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia In this new-era of drug-eluting stents (DES) the impact of symptomatic in-stent restenosis (ISR) is diminishing. However, world wide bare metal stents remain widely used and therefore, it is imperative to establish a simple and effective form of treatment for ISR. This study evaluates the effectiveness of DES for the treatment of symptomatic ISR. All patients presenting with symptomatic ISR were evaluated between February 2003 and February 2005. Patients had 9-month angiographic follow-up with primary endpoint evaluation of binary restenosis (>50%). Secondary endpoints included in-segment late loss, target lesion revascularization (TLR) and the difference in late loss between sirolimus (n = 23) and paciltaxel (n = 36) eluting stents. Fifty-eight patients with 59 ISR lesions were evaluated. Pre-procedural lesion characteristics included a reference vessel diameter of 2.77 ± 0.44 mm, a 78 ± 13% stenosis with a lesion length of 19 ± 8 mm. Post-procedure an 18 ± 9% stenosis remained resulting in an acute gain of 1.94 ± 0.54 mm. At angiographic follow-up the median insegment late loss was 0.24 mm (IQR 0.1, 0.53), with a binary restenosis rate of 17%. At long-term follow-up, the incidence of TLR was 10%. No difference in the angiographic parameter of in-segment late loss was seen between the sirolimus 0.28 mm (IQR 0.15, 0.5) and paclitaxel 0.21 mm (IQR 0.1, 0.53) eluting stents. In this cohort of patients with long-term angiographic and clinical follow-up, DES is an effective and safe treatment for symptomatic ISR. No difference was seen, in angiographic parameters, between sirolimus and paclitaxel-eluting stents.

354 ST Resolution in Elderly Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI A. Yeung, A. Farshid, D. Coles, D. McGill, FCSANZ, S. O’Connor, FCSANZ, I. Jeffery, R.P. Tan* Department of Cardiology, The Canberra Hospital, Canberra, Australia Prompt ST resolution [STR] has been shown to be an independent predictor for mortality in acute ST elevation MI [STEMI]. The elderly population have a poorer prognosis despite reperfusion therapy for STEMI. Aim: To measure STR in the elderly population [≥70 years] compared to younger patients undergoing primary percutaneous coronary intervention [PCI] for STEMI.

Abstracts

Method: One hundred and twenty consecutive patients undergoing primary PCI for STEMI from January 2004 to June 2005 were recruited for this retrospective study. Percent [%] STR was calculated by measuring the difference in sum ST elevation in all leads in paired 12 lead ECGs pre and post PCI. STR was defined as complete [>70%], partial [30–70%] and none [<30%]. Results: See Table 1. Table 1. ≥70 Years

<70 Years No of patients [%] Mean age, years [range] Female gender [%]

82 [68.0%]

38 [32.0%]

55.3 [28–69]

76.9 [70–90]

22 [26.8%]

18 [47.4%]

Three vessel CAD

20.7%

36.8%

Anterior MI %

41.5%

42.1%

3:28

3:22

61.7%

59.5%

Mean time ECG pre/post PCI h:min STR data* >70% STR 30–70% STR

19.8%

24.3%

<30% STR

18.5%

16.2%

95.1%

94.7%

Successful primary PCI 30 day *

mortality†

[%]

2/81 [2.5%]

5/37 [13.5%]

p = 0.17 not significant. † Fisher’s exact significance = 0.03.

Conclusions: The elderly have a higher mortality in STEMI despite primary PCI achieving a similar degree of complete STR. 355 Implantable HeartPODTM Left Atrial Pressure Monitoring System: The Alfred Hospital Experience Antony Walton1,* , FCSANZ, Justin Mariani1 , Jane Brack2 , Neal Eigler3 , Saibal Kar3 , David Kaye1 , FCSANZ, Henry Krum2 , FCSANZ 1 Heart Centre, The Alfred Hospital, Melbourne, Vic., Australia; 2 Department

of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia; 3 Cedars-Sinai Medical Centre, Los Angeles, CA, USA Background: In patients with heart failure, variations in left atrial pressure predict symptoms, hospitalisation and survival outcome. The HeartPOD (Savacor Inc, CA, USA) is a percutaneously inserted, permanently implanted sensor apparatus that allows the patient to make real-time measurements of left atrial pressure with a modified handheld personal digital assistant. Associated software further serves as a patient advisory module (PAM). The sensor lead is implanted in the intra-atrial septum via transeptal catheterisation, under intracardiac echocardiographic and fluoroscopic guidance. Methods: To December 2005, the Alfred Hospital has enrolled four patients in HOMEOSTASIS I, a first-inman trial, with a primary endpoint of safety. All patients were male, with a mean age of 69.5 years and had previously had at least NYHA class 3 or 4 symptoms in the 12 months prior to enrolment. All were in sinus rhythm.

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Two of the patients had predominately systolic dysfunction from ischaemic cardiomyopathy (ejection fractions: 35% and 20%), and two of the patients had diastolic dysfunction from long-standing hypertensive heart disease. At implantation, calibration of the device was effected with simultaneous measurement of the pulmonary capillary wedge pressure (PCWP). Results: The HeartPOD was successfully implanted in all patients. At six weeks, all patients were free from MACE or neurological events. Two patients had follow-up right heart studies and tight calibration with the PCWP remained. Conclusion: The HeartPOD is a novel, implantable LAP monitoring device, and as part of the pilot HOMEOSTASIS I trial, has been successfully implanted in four patients at the Alfred Hospital. 356 Are Drug-Eluting Stents (DES) Indicated in Large Coronary Arteries? Insights from a Multi-Centre Victorian Percutaneous Coronary Intervention (PCI) Registry David Clark1,* , S. Duffy2 , FCSANZ, B. Chan1 , MCG. Horrigan1 , FCSANZ, O. Farouque1 , B. Yan3 , T. Yip4 , D. Eccleston3 , FCSANZ, J. Shaw2 , G. New5 , FCSANZ, G. Szto6 , FCSANZ, A. Meehan7 , C. Reid7 , FCSANZ, A. Ajani3,7 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

of Cardiology, Austin Hospital; 2 Department of Cardiology, Alfred Hospital; 3 Department of Cardiology, Royal Melbourne Hospital; 4 Department of Cardiology, Geelong Hospital; 5 Department of Cardiology, Box Hill Hospital; 6 Department of Cardiology, Frankston Hospital, Melbourne; 7 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Background: It is current practice in many Australian and New Zealand hospitals to restrict drug-eluting stents (DES) to smaller vessels. The aim of this study was to evaluate outcomes after implantation of ≥3.5 mm DES compared with bare metal stents (BMS). Methods: We studied 610 consecutive patients who had a ≥3.5 mm diameter stent deployed. All patients were part of a large ongoing MIG PCI registry from 7 Victorian public hospitals enrolled from April 2004 to January 2006. Outcomes were analysed in the 507 and 119 patients who were eligible for follow up at 30 days and 1 year, respectively. Four hundred patients will be eligible for 1 year follow up August 2006. Results: The mean age ± S.D. was 64.6 ± 12.0 years. Females comprised 22.1%, diabetics 20.1% and 63% had an acute coronary syndrome. The target vessel was the LAD in 25.3%. DES comprised 36.1% of PCI using ≥3.5 mm stents.

ABSTRACTS

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Outcomes

Heart, Lung and Circulation 2006;15S:S1–S167

BMS (%)

DES (%)

P Outcomes

30 day mortality

1.0

0.0

0.28

30 day MACE (Death, MI, TVR)

4.1

6.1

0.40

12 month mortality

1.4

0.0

12 month target vessel revasc. (TVR)

5.5

7.3

1.0 0.72

12 month MACE (Death, MI, TVR)

9.6

14.3

0.42

Conclusion: Deployment of ≥3.5 mm diameter stents in large coronary arteries is associated with low rate of mortality and major adverse cardiac events (MACE) at 30 days and 1 year irrespective of DES or BMS use. Findings will be confirmed and refined with as more patients are eligible for follow up. 357 Sustainability of a Large Australian Multi-Centre Percutaneous Coronary Intervention (PCI) Registry: Outcomes of the First 2765 Patients Enrolled David Clark1,* , S. Duffy2 , FCSANZ, M.C.G. Horrigan1 , FCSANZ, B. Chan1 , G. Szto3 , FCSANZ, O. Farouque1 , B. Yan4 , G. New5 , FCSANZ, A. Black6 , A. Brennan7 , A. Meehan7 , C. Reid7 , FCSANZ, A. Ajani4,7 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

of Cardiology, Austin Hospital, Australia; 2 Department of Cardiology, Alfred Hospital, Australia; 3 Department of Cardiology, Frankston Hospital, Australia; 4 Department of Cardiology, Royal Melbourne Hospital, Australia; 5 Department of Cardiology Hospital, Box Hill Hospital, Australia; 6 Department of Cardiology, Geelong Hospital, Melbourne, Australia; 7 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Background: We recently reported the feasibility of an Australian based multi-centre PCI registry. This study details the outcomes of a large cohort of patients 2 years after initiation. Methods: We prospectively enrolled 2765 patients undergoing consecutive PCI of 3136 lesions at 8 Victorian hospitals from April 2004 to January 2006. Baseline patient/procedural data and in-hospital, 30 day, and at 1 year outcomes were recorded on case report forms. Data were stored electronically in the Department of Epidemiology at Monash University. Outcomes were analysed in the 2265 and 577 patients who were eligible for follow up at 30 days and 1 year, respectively. One thousand and five hundred patients will be eligible for 1-year follow up August 2006. Results: The mean age ± S.D. was 64.9 ± 12.0 years. Females comprised 27.2%, diabetics 23% and 61.9% had acute coronary syndromes. Cardiogenic shock was present prior to the procedure in 1.3%. The target vessel was the LAD in 34.4%. A drug-eluting stent (DES) was used in 50.4% and IIbIIIa inhibitors in 26.1% of PCI.

In-Hospital (%) (n = 2765)

30 Day (%) (n = 2265)

1 Year (%) (n = 577)

PCI Success

95.5

–

–

Death – total cohort

1.5

1.9

3.3

Death – excluding pre-procedural shock

0.6

1.2

2.0

Target vessel revascularization

2.0

2.7

7.8

MACE – Death, MI, TVR

4.5

6.6

15.5

Conclusion: A prospective, multi-centre registry providing early and longer term outcomes after PCI is sustainable in Australia and could improve quality of care, accurately assess new technology, allow calculation of risk models for PCI, and facilitate clinical trials. 358 Radial Access Facilitates Same-Day Discharge Following Elective Percutaneous Coronary Intervention S. Prasad, A. Ranchord* , S.K. Seneviratne, R. Anscombe, M.B. Simmonds, FCSANZ, A. Aitken, P. Matsis, FCSANZ, S.A. Harding Department of Cardiology, Wellington Hospital, Wellington, New Zealand Background: Day-case percutaneous coronary intervention (PCI) is cost effective and popular with patients. Radial access allows earlier sheath removal, immediate ambulation and reduces access site complications. We hypothesised that use of the radial approach in patients undergoing elective PCI would facilitate same-day discharge. Methods: One thousand and sixty-five consecutive patients undergoing elective PCI via femoral or radial access between January 2001 and January 2006 were considered for same-day discharge and included in this study. Choice of vascular access was at the discretion of the operator. Patient demographics, procedural variables and outcomes, and follow-up data were obtained from review of the cardiac catheterisation laboratory database, medical records, and a telephone survey. Results: Nine hundred and sixty-eight (90.9%) elective PCIs were performed using femoral access and 97 (9.1%) via radial access. Patients approached radially were more likely to be male (p = 0.002) and to have a planned rather than ad-hoc PCI (p < 0.002). Age, risk factors, number of lesions treated, lesion location and lesion complexity did not differ significantly between the groups. Angiographic success (94.4% radial group and 96.2% femoral group, p = 0.34) and procedural success (92.8% radial group and 93.8% femoral group, p = 0.69) were similar in both groups. Radial access was associated with a significantly higher rate of same-day discharge (93.8% versus 85.2%, p = 0.02). No patients in the radial group compared to 11 (1.1%) patients in the femoral group required readmission with access site complications. However, this difference was not statistically significant. Conclusion: Radial access facilitates day-case PCI and may reduce access site complications requiring readmission.

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359 Utilization of Statins, ACEi/ARBs and Beta-Blockers Following Percutaneous Coronary Intervention (PCI), and Treatment Adherence at 12 Months: Results from a Large Multi-Centre Australian Registry Chan1,* ,

Duffy2 ,

Reid3 ,

B.R. S. FCSANZ, C. FCSANZ, N. Anavekar1 , N. Campbell1 , M. Horrigan1 , FCSANZ, G. New4 , FCSANZ, A.E. Ajani3,5 , FCSANZ, A. Black6 , A. Brennan3 , D. Eccleston5 , FCSANZ, H. Krum2,3 , FCSANZ, D.J. Clark1 , on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

of Cardiology, Austin Hospital, Ausralia; of Cardiology, Alfred Hospital, Ausralia; 3 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia; 4 Department of Cardiology, Box Hill Hospital, Ausralia; 5 Department of Cardiology, Royal Melbourne Hospital, Ausralia; 6 Department of Cardiology, Geelong Hospital, Melbourne, Ausralia 2 Department

Background: ACEi or ARBs, statins and beta-blockers are of proven benefit in many CAD subgroups. The aim of this study was to describe the use of these medications post PCI. Methods: We analysed ACEi or ARB, statin and betablocker use at 30 days in 2265 patients, and interim 1 year results, for 582 patients from the MIG registry. Patients were prospectively enrolled, between April 2004 and January 2006, from 7 Victorian public hospitals. One thousand and five hundred patients will be eligible for 1-year follow up by August 2006. Results: Beta-blocker use was significantly less frequent in the following subgroups: age ≥75 years (57.1% versus 64.4%, p = 0.02), COPD (38.7% versus 63.7%, p < 0.001), PVD (54% versus 62.9%, p = 0.045), and Cerobrovascular Disease (51.9% versus 63.1%, p = 0.023). ACEi/ARB use was significantly less frequent in patients with renal failure (creatinine >0.2 mmol/L): 63.2% versus 73%, p = 0.045. The three medications were less frequently used in patients who had NSTEMI versus STEMI: beta-blockers (67.6% versus 73.2%, p = 0.07), ACEi/ARBs (75.3% versus 83.7%, p = 0.002) and statins (87.7% versus 92.9%, p = 0.01). Overall Use of Medications

30 Days (n = 2265)

1 Year (n = 582)

Beta-Blockers

62.5%

56.2%

ACEi/ARBs

72.7%

71.1%

Statins

87.5%

85.8%

Conclusions: Overall patient compliance to beta-blockers, ACEi/ARBs and statins from 30 days through to 1 year is good after PCI. However, there is underutilization of beta-blockers, ACEi/ARBs and statins in some high-risk groups and greater use may substantially improve outcomes.

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360 Outcomes of Intubated Patients Post Cardiac Arrest Undergoing Primary PCI in STEMI: The Royal Adelaide Hospital Experience B.K. Dundon1,* , P.J. Psaltis1 , FCSANZ, M.I. Worthley1 , S. Shakib1 , L.J. Mahar1 , FCSANZ, D.P. Chew2 , FCSANZ, S.G. Worthley1 , FCSANZ 1 Cardiovascular

Research Centre, Royal Adelaide Hospital, University of Adelaide, Australia; 2 Flinders Medical Centre, Flinders University, Adelaide, Australia Primary percutaneous coronary intervention (PPCI) has been associated with improved outcomes in patients presenting with ST segment elevation myocardial infarction. However, it is resource intensive and data about outcomes in some higher risk cohorts is lacking, specifically in postcardiac arrest patients requiring intubation and ventilation. Outcomes of this high-risk group was the focus of our study. All PPCI cases at the Royal Adelaide Hospital between July 2002 and June 2005 were evaluated. An audit of the hospital case notes was performed to identify those patients that were intubated and ventilated on arrival for PPCI following cardiac arrest. The data and outcomes of these patients were analysed. A total of 353 PPCIs were reviewed with an overall mortality rate of 5.5%. From this review, 21 patients met criteria and were evaluated. In this group the cardiac arrest occurred in-hospital in 3 and out-of-hospital in 18 patients. No in-hospital arrest patients died. The worst outcome was in the 18 out-of-hospital cardiac arrest patients; 13 died pre-discharge, 3 had major brain injury (requiring longterm institutional care) and 1 had minor brain injury. In the total cohort (n = 21), only 3 patients (14%) were discharged home with no neurological deficit. Unselected patients undergoing PPCI who are intubated and ventilated following cardiac arrest have a poor prognosis. Further work is required to potentially identify predictors that may help identify who if any in this group may benefit from PPCI. 361 Platelet Aggregation Inhibition in Patients on Clopidogrel Maintenance Therapy Undergoing Percutaneous Coronary Intervention Ernesto Oqueli* , Martin Hiscock, Kim Millar, Aaron Carroll, Ron Dick Victorian Heart Centre, Epworth Hospital, Melbourne, Vic., Australia Patients on clopidogrel maintenance therapy (75 mg/day for >7 days) undergoing percutaneous coronary intervention (PCI) are assumed to have adequate platelet antiaggregation and usually no extra measures are taken. Some patients however, have their index event while on clopidogrel maintenance therapy (CMT), which could be considered a failure of therapy.

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The level of pharmacologically induced platelet aggregation inhibition (PAI) is an independent predictor of major cardiac events (MACE) after PCI. This study prospectively compares the levels of PAI immediately before PCI and the outcomes of 24 patients on CMT with those of 19 patients receiving a clopidogrel load >12 h before the procedure. Pre-PCI PAI to 20 ␮M ADP and to Collagen were determined with the Plateletworks® point-of-care (Helena Laboratories). Post-PCI myocardial injury markers (PPCIM) were assayed. MACE were defined as death, myocardial infarction or repeat revascularization. Patients on CMT were younger 64.75 ± 11.68 versus 73.05 ± 12.42 years (p = 0.03). CMT

Loading

p

PAI to ADP (mean ± S.D.)

18.5% ± 16.2%

30.5% ± 25.0%

0.06

PAI to collagen (mean ± S.D.)

67.6% ± 24.7%

77.7% ± 14.1%

0.12

There were no significant differences in in-hospital MACE or PPCIM. Conclusion: In this cohort, patients on CMT had a strong tendency towards less clopidogrel-induced PAI to 20 ␮M ADP before PCI than those receiving a loading dose. There were no differences in in-hospital outcome due to the small population. The ongoing follow-up may clarify the clinical significance of this finding. 362 A Trial of Early Inhibition of Platelet Aggregation in Patients with Acute Coronary Syndrome (ACS) Undergoing Percutaneous Intervention (PCI): High Dose Tirofiban Bolus and Infusion Compared to Standard Dose Abciximab B. Chou* , L. Roberts, M. Swale, V. Pandelli, C. Lim, A. Teh, Y.M. Cheong, C. Goods, FCSANZ, M. Rowe, FCSANZ, L. McPherson, B. Collins, G. New, FCSANZ, G. Proimos, FCSANZ Cardiology Department, Box Hill Hospital, Melbourne, Australia Background: Clinical trials have demonstrated the efficacy of GP IIb-IIIa inhibitors in patients undergoing PCI. The TARGET trial concluded that tirofiban (10 ␮/kg bolus dose) followed by infusion had higher 30 day MACE rates than abciximab. One hypothesis for this finding was suboptimal tirofiban dosing and therefore less early platelet inhibition. Objective: To determine whether a new high bolus dose of tirofiban (25 ␮g/kg) followed by standard infusion is equivalent or superior to standard abciximab regimen in achieving early platelet inhibition in ACS patients undergoing PCI. Method: ACS patients on aspirin undergoing PCI were randomized to receive tirofiban, abciximab or placebo and 300 mg clopidogrel loading. A point of care ULTEGRA machine (20 mole ADP stimulation) measured platelet aggregation at 10, 30 and 60 min post GPIIb IIIa inhibitor.

Results: To date, 12 patients have been enrolled. Seven patients received a GP IIb IIIa inhibitor (5 tirofiban, 2 abciximab), the remainder placebo. Patients receiving GP IIb IIIa inhibitor had >80% inhibition of platelet aggregation at 10, 30 and 60 min. No bleeding or thrombocytopenia occured. Conclusions: Whether high dose tirofiban is equivalent to abciximab with inhibition of early platelet aggregation will be examined and the results presented at this meeting. 363 Percutaneous Intra-Myocardial Autologous Bone Marrow Stem Cell Therapy does not Cause Intramyocardial Calcification or Neoplastic Transformation in Patients with Chronic Myocardial Ischemia S. Mylabathula* , M. Puvaneswary, P. Diu, C. Hiew, R. Jayasinghe, S. Thambar, H. Tse John Hunter Hospital, Newcastle, Australia and the Queen Mary Hospital, Hong Kong, China Autologous bone marrow (BM) stem cell transplantation in human subjects has evolved into Phase I and II clinical trials. These trials utilize catheter based, intracoronary, and surgical modes of cell delivery. While benefit is being reported, concerns remain as to the possibility of calcification and neoplastic transformation in the myocardium. We studied the possibility of intramyocardial calcification and neoplastic transformation following autologous bone marrow stem cell therapy. A total of 36 patients were enrolled in this study. This is part of a currently ongoing, phase II randomized and blinded study comparing the safety and efficacy of catheter based intramyocardial injection of Autologous BM stem cells and placebo in patients with chronic myocardial ischemia. These are group of patients with intractable angina not amenable to revascularisation, on maximal medical therapy. The delivery technique was by means of NOGA endocardial mapping and injection system (Myostar-Biosense). After completing 12 months or more, patients underwent computed tomography. Using standard General Electric software, 2 mm images were obtained from the base of the heart to the apices before and after contrast injection. An independent Radiologist analyzed the images in a blinded fashion. There was no evidence of either intramyocardial calcification or neoplastic transformation in either group. Percutaneous myocardial catheter based BM stem cell transplantation in patients with chronic myocardial ischemia does not cause calcification or neoplastic transformation.

364 Ten-Year Follow-Up of Percutaneous versus Surgical Coronary Revascularization S. Mylabathula* , P. Varghese, S. Adera, P. Diu, C. Hiew, N. Bull, S. Thambar, R. Bhagwandeen, FCSANZ, B. Bastian, G. Bellamy, FCSANZ John Hunter Hospital, Newcastle, Australia Percutaneous coronary intervention and surgical revascularization are widely accepted as close or equal alternatives in contemporary clinical practice. Randomized studies show a small benefit in favour of CABG with longest follow up of 8 years. The aim of this retrospective study was to look into the difference in survival, angina free status, and the effect of incomplete revascularization on the above outcomes at the end of 10 years. Patients who underwent PCI (N = 110) and CABG (N = 116) in 1995 were included in this study. Demographics, vessels involved, procedural success and mortality, crossover and completeness of revascularization were documented. All patients who were percutaneously revascularised received a stent. Clinical progress was followed through the subsequent ten years using medical records, and an interview. Outcomes measured were 10-year survival, 10-year angina free status, Target vessel revascularization and crossover. Patients having CABG were slightly older (74 versus 70, P = .04) and had slightly lower ejection fraction (60.2 versus 65.4, P = .05). Ten-year survival was similar in both groups (PCI = 72%, CABG = 77.6%, P = NS). Ten-year angina free status was in favour of PCI albeit insignificant (PCI = 79%, CABG = 69%, P = NS). In this single centre data with the longest follow up in literature to date mortality and angina free status at 10 years is comparable. Future randomized studies in this area need to be followed up long term to address the issue of longevity that often is the question both the physicians and patients ask before a decision is made. 365 Clinical Outcomes after Coronary Stenting of Small Vessels Using ≤2.5 mm Stents: Results from the Melbourne Interventional Group (MIG) Registry S.J. Duffy1,* , FCSANZ, D. Clark2 , A. Ajani3,7 , FCSANZ, A. Walton1 , FCSANZ, T. Yip4 , B. Yan3 , G. Szto5 , FCSANZ, G. New6 , FCSANZ, A. Meehan7 , C. Reid7 , FCSANZ, A. Dart1 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department of Cardiology, Alfred Hospital; 2 Department of Cardiology, Austin Hospital; 3 Department of Cardiology, Royal Melbourne Hospital; 4 Department of Cardiology, Geelong Hospital; 5 Department of Cardiology, Frankston Hospital; 6 Department of Cardiology, Box Hill Hospital, Melbourne; 7 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia

Background: Implantation of stents in small coronary vessels (diameter ≤2.5 mm) is a strong predictor of in-stent restenosis (ISR) and major adverse cardiac events (MACE).

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Drug-eluting stents (DES) have been shown to reduce ISR in vessels as small as 2.5 mm compared to bare-metal stents (BMS). We evaluated the clinical outcomes after implantation of ≤2.5 mm diameter DES and BMS. Methods: We analysed the outcome of 795 consecutive patients undergoing PCI of 1030 de novo coronary lesions implanted with ≤2.5 mm diameter stents who were enrolled in the Melbourne Interventional Group Registry from April 2004 to January 2006. Results: Diabetics comprised 31%, and 59% were being treated for an acute coronary syndrome. Seventy-two percent of lesions were treated with a DES. Patients with diabetes were more likely to receive a DES than non-diabetics (81% versus 68%, p < 0.0001). However, females were less likely to receive a DES (66% versus 75%, p = 0.008). DES implants were longer than BMS (17.5 ± 6.6 mm versus 15.1 ± 6.0 mm, p < 0.0001). Procedural success was 98.6%. Thirty-day follow-up was available in 655 patients, with overall mortality of 2.1%. Patients who received a BMS had higher 30-day mortality (4.6%) compared to those receiving a DES (1.2%), p = 0.009 (inclusive of in-hospital mortality), but 30-day MACE was not significantly different. Thus far, 12-month follow up is only available in 167 patients, with no significant differences in clinical outcomes. Conclusion: Small vessels are predominantly treated with DES, with high procedural success. The observed lower inpatient and 30-day mortality related to DES use is intriguing, and remains unexplained by clinical characteristics. 366 Predictors of Mortality in Primary PCI S. Mylabathula* , P. Diu, C. Hiew, S. Adera, P. Varghese, N. Bull, S. Thambar, R. Bhagwandeen, FCSANZ, B. Bastian, G. Bellamy, FCSANZ Cardiology Department, John Hunter Hospital, Newcastle, Australia Primary angioplasty offers clear mortality benefit when compared to thrombolysis in patients with acute myocardial infarction (AMI). While the benchmark door to balloon time has improved over the years, mortality in this group remains around 5–7%. The objective was to evaluate in hospital and 30 day outcomes, as well as predictors of mortality in patients undergoing primary angioplasty for AMI. This prospective observational study included consecutive patients who had primary PCI for acute myocardial infarction from 2004–2005. Demographics, door to balloon time, procedural success, antiplatelet therapy, peak CK, Cell counts, myocardial blush grade (MBG), 30-day mortality and MACE were documented for all the patients. One hundred and ninety-one patients were eligible to be included. There was 94% overall procedural success. The in hospital mortality including patients with cardiogenic shock was 5.8%. Logistic regression analysis was performed and a model found that predicted mortality at 90% accuracy. The model included; MBG, WCC, Neutrophil count and Monocyte count as independent variables and 30-day

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mortality as dependent variable. Absolute monocyte count >1.0 and a MBG of 1 were predictive of death with a sensitivity of 0.03 and 0.005, respectively. This elevated monocyte count was independent of the size of infarct as shown by independent samples t-test. This previously unreported association could reflect a sequence of pathophysiological association that may manifest as no-reflow and cardiogenic shock. Further investigation is required looking into the association of inflammatory burden and major cardiac events despite revascularization which may have therapeutic implications.

367 Anti-Aggregation Effect of a Loading Dose of 300 mg or 600 mg of Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention Ernesto Oqueli* , Martin Hiscock, FCSANZ, Aaron Carroll, Pam Trevanthan, Kate Reed, Ron Dick, FCSANZ Victorian Heart Centre, Epworth Hospital, Melbourne, Victoria, Australia Established practice in clopidogrel loading is 300 mg administered >6 h before percutaneous coronary intervention (PCI). This study prospectively compares the anti-aggregation effect ≥12 h after a dose of 600 mg of clopidogrel given immediately after PCI (15 patients), with 300 mg given >12 h before the procedure (12 patients). Platelet aggregation (PA) to 20 ␮M ADP was determined with the Plateletworks® point-of-care (Helena Laboratories) before and ≥12 h post loading. Post-PCI myocardial injury markers were assayed. Major adverse cardiac events (MACE) were defined as death, myocardial infarction or repeat revascularization. There were no differences in baseline clinical characteristics. 300 mg (Mean ± S.D.)

600 mg (Mean ± S.D.)

p

PA before loading

94.5% ± 3.1%

93.1% ± 5.3%

0.434

PA ≥12 h post loading

69.4% ± 26.5%

44.7% ± 19.7%

0.016

Difference PA1-PA2

19.8% ± 21.8%

48.1% ± 22.7%

0.005

There were no differences in in-hospital MACE or postPCI myocardial injury markers elevation. Conclusions: The anti-aggregation effect of a 600 mg clopidogrel load given after PCI is superior to that of a 300 mg given >12 h before PCI. A larger study is required to clarify the clinical relevance of this finding.

368 Percutaneous Coronary Intervention in Patients with Cardiogenic Shock: Insights from the Melbourne Interventional Group (MIG) Registry H.B. Liew1,* , D. Clark2 , S. Duffy3 , FCSANZ, M. Swale1 , L. Roberts1 , B. Yan4 , J. Shaw3 , A. Brennan5 , A. Ajani4,5 , FCSANZ, A. Meehan5 , C. Reid5 , FCSANZ, G. New1 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department

of Cardiology, Box Hill Hospital; 2 Department of Cardiology, Austin Hospital; 3 Department of Cardiology, Alfred Hospital; 4 Department of Cardiology, Royal Melbourne Hospital, Melbourne; 5 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia Background: Cardiogenic shock carries a high risk of mortality (60–80%). Emergency PCI has been shown to improve outcomes for shock complicating acute myocardial infarction. Recent development in coronary stenting and glycoprotein IIb/IIIa inhibitor (GPI) have improved procedural and clinical outcomes in ACS. Evidence is still lacking on the impact of this new era of PCI in the setting of shock. Aim: To describe the clinical, angiographic and procedural characteristics, and outcomes of patients who underwent PCI for shock. Methods: Analysis was performed from the MIG database, on patients presented with cardiogenic shock and underwent urgent PCI. Clinical characteristics and procedural details were described. Patients were followed up at 30 day. Results: Fifty-six patients with a mean age 66 ± 12 years presented in shock. Seventy-three percent were male. Sixty-nine percent were previous or current smokers, 23.2% had diabetes, 50% hypertension, 35.8% dyslipidaemia and 7.1% had renal failure. Sixteen percent had previous MI, 24.5% had family history of CAD. Patients presenting in shock with the majority (83.9%) being STEMI, 12.5% NSTEMI and 3.6% unstable angina. The LAD was the culprit artery in 43%. A drug-eluting stent was deployed in 39%. An IABP was used in 57% and GPI were used in 73%. Table 1. Outcomes Procedural success Inhospital mortality 30-Day MACE 30-Day mortality 30-Day TVR

(n = 49) 87.8% (n = 17) 30.4% (n = 22) 44.9% (n = 17) 34.7% (n = 5) 10.2%

Conclusions: In our cohort of cardiogenic shock, patients undergoing PCI had good procedural success with a 70% in-hospital survival rate. Mortality still remains high at 30days.

369 Predictors of Adverse Events at Six Months after Primary PCI for Myocardial Infarction A. Farshid* , D. Coles, I. Jeffery, D. McGill, FCSANZ, S. O’Connor, FCSANZ, R. Tan Department of Cardiology, Canberra Hospital, Garran, ACT, Australia Previous studies have shown favourable short-term outcomes for patients undergoing primary PCI for ST elevation Myocardial Infarction. There is less information available about longer-term outcome outside of clinical trials. We treated 376 consecutive patients with primary PCI at the Canberra Hospital between March 2002 and March 2005. Mean age was 62 years (range 28–89). Females comprised 26% of the patients and 14% were diabetics. The median pain to door time was 90 min and the median door to balloon time was 66 min. Patients had been transferred from nearby hospitals in 44% of cases with a median transfer time of 92 min. The procedures were successful in 97% of cases. Follow up was by letter and telephone in addition to review of hospital records. Cumulative clinical outcomes at 6 months included death in 5.9%, MI in 7.9%, repeat PCI to the target vessel in 7%, CABG in 3% and CVA in 0.5%. The overall incidence of Major Adverse Cardiovascular Events (MACE) was 19%. On univariate analysis the following were identified as predictors of MACE: age >75 (p = 0.015), hypertension (p = 0.0015) multi-vessel disease (p < 0.0001) and door to balloon time >80 min (p = 0.042), with female gender of borderline significance (p = 0.07). On multivariate analysis, multi-vessel disease (OR = 7.27, CI 1.46–53.1), door to balloon time >80 min (OR = 5.1, CI 1.26–24.3), and female gender (OR = 5.6, CI 1.1–36.7) remained significant independent predictors of MACE at 6 months. Despite favourable early results from primary PCI, there is a significant risk of adverse events during follow up. Further study is required to determine how this risk can be minimized, especially in higher risk subsets.

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370 Predictive Value of the ACC/AHA Lesion Morphology Classification in the New Era of Percutaneous Coronary Intervention: Insights from the Melbourne Interventional Group (MIG) Registry H.B. Liew1,* , B. Chou1 , C. Lim1 , L. Roberts1 , S. Duffy2 , FCSANZ, T. Yip3 , R. Lew4 , FCSANZ, J. Lefkovits5 , FCSANZ, A. Meehan7 , C. Reid7 , FCSANZ, D. Clark6 , G. New1 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators 1 Department of Cardiology, Box Hill Hospital; 2 Department of Cardiology, Alfred Hospital; 3 Department of Cardiology, Geelong Hospital; 4 Department of Cardiology, Frankston Hospital; 5 Department of Cardiology, Royal Melbourne Hospital; 6 Department of Cardiology, Austin Hospital, Melbourne; 7 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia

Background: The ACC/AHA classification stratifies coronary lesions for prediction of results in PCI. Recent progress in patient care, technology and pharmacotherapy has led to overall improvement in outcomes. Its predictive value in this new era needs to be reassessed. Aim: To assess predictive value of the classification for procedural and clinical outcomes. To examine the relationship of lesion class to clinical and procedural characteristics, particularly, use of glycoprotein IIb/IIIa inhibitor (GPI). Methods: Based on the MIG Registry, 3434 lesions (2731 patients) were classified: A, B1, B2, and C. Patients were followed up at 30-day. Results: Comparing the four lesion classes, there were significant differences in age, smoking history, congestive heart failure, and previous bypass surgery; No differences were seen in diabetes, dyslipidaemia and renal failure. The classification was an independent predictor for 30-day MACE. After excluding STEMI and shock (co-linearity), the classification still remained as a predictor. Table 1. Presentation and Procedural Details Acute coronary syndromes STEMI Cardiogenic shock GPI DES

A (%)

B1 (%)

B2 (%)

C (%)

P value

56.8 8.9 0.8 13.6 45.7

57.1 13.2 0.9 20.2 47.7

68.0 25.2 3.1 33.4 54.2

66.4 31.3 3.7 37.8 54.4

<0.001 <0.001 <0.001 <0.001 <0.01

Table 2. Outcomes Procedural success In-hospital mortality 30-day MACE 30-day mortality

A (%)

B1 (%)

B2 (%)

C (%)

P value

99.7 0.3 4.1 0.9

98.7 0.5 4.2 0.9

95.4 2.1 7.8 2.9

85.4 2.3 13.6 3.7

<0.001 <0.001 <0.001 <0.001

Conclusions: The ACC/AHA lesion class, in the modern PCI era, is still a useful predictor of procedural and clinical outcomes.

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371 New Technique in Assisting Closure of Difficult ASDs with Amplatzer Septal Occluder (ASO) T.H. Goh1,* , FCSANZ, Mansour Al-Mutairi2 1 Dept

of Cardiology, Royal Children’s Hospital; Medical Centre, Melbourne, Australia

2 Monash

Large ASDs with soft/deficient rims are difficult to close. The superior/inferior ASO left atrial disk tends to prolapse into the right atrium [RA] at initial attempt. We report a method for easing the device deployment. Technique: After deployment of long sheath in the left atrium [LA], a second catheter is introduced and positioned through the ASD into the LA. The LA disk of the ASO is opened, gently pulled back toward the atrial septum [AS]. The second reinforced catheter [SC] held in place acts as buttress, aligning LA disk parallel to AS. The central disk and RA disk are rapidly deployed. After ensuring optimal ASO position, the SC is pulled back slowly into RA with counter pressure applied to the ASO to prevent dislodgement to RA. Observation made for 30 min before release. No Minnesota wiggle was used prior to release. Patients: 13 pts with large ASDs underwent new technique of implant. Ten had successful implants. The three patients with failed implants had multiple deficient rims. Conclusion: The SC assisted technique shows promise in aligning the left atrial disk to the AS and allowing successful implant in patients with adequate rims. 372 Transradial Percutaneous Coronary Intervention in Acute Myocardial Infarction—A Safety and Feasibility Study in a Dedicated Transfemoral Percutaneous Coronary Intervention Centre Y. Malaiapan* , M. Leung, S. Seneviretne, I.T. Meredith, FCSANZ Monash Cardiovascular Research Centre, Monash University, Monash Medical Centre, Melbourne, Vic., Australia Background: Transradial angioplasty results in fewer vascular complications, greater patient comfort, earlier ambulation and discharge. However, there is limited data on the safety and efficacy of transradial infarct percutaneous coronary intervention (TRIPCI) in a dedicated high volume transfemoral percutaneous coronary intervention laboratory. Methods: A prospective study to investigate the safety and efficacy of TRIPCI was performed in 19 consecutive patients and 19 matched controls who had transfemoral infarct percutaneous coronary intervention (TFIPCI). Two experienced operators who had performed more than 50 complex transradial percutaneous coronary intervention (TRPCI) participated. More type C lesions were present in the TRIPCI group (7 versus 4). Results: Door to balloon times were 135 ± 82 versus 99 ± 73 min (P = 0.144), puncture times were 5 ± 3 versus 3 ± 1 min (P = 0.124) and the procedure time were 67 ± 33

versus 46 ± 17 min (P = 0.026) in TRIPCI and TFIPCI, respectively. Crossover from radial to femoral access was required in one patient. TIMI 3 flows were achieved in all patients and there were no vascular complications, in hospital deaths, reinfarction or requirement for bypass surgery in either arm. Conclusion: Primary and rescue PCI can be performed with high success rates using radial access. Although radial access was associated with longer procedure time, this could be accounted for by the more complex lesions subset in the TRIPCI group. 373 Audit of Cypher Drug Eluting Stents for the Treatment of Ostial Coronary Stenoses—The Christchurch Experience Mark Nallaratnam* , Dougal McClean, Mark Richards, FCSANZ, John Elliott, FCSANZ, David Smyth Christchurch Hospital, Christchurch, New Zealand The presence of an ostial lesion involving a major epicardial artery is often considered an indication for coronary surgery due to the complexity associated with percutaneous coronary intervention. We audited the outcome of Cypher drug eluting stents for the treatment of ostial lesions. Methods: We retrospectively audited consecutive patients from 2003 till December 2005 who received a Cypher drug eluting stent for treatment of ostial stenosis. Major Clinical Adverse Events (MACE) was obtained by review of hospital notes and telephone follow up. Results: Thirty-one patients had 36 ostial lesions treated consisting of 27 de novo lesions and 7 in-stent restenosis (ISR). The patient’s age ranged from 34 to 83 years (mean age of 62 years). The site of the ostial lesion was left anterior descending (LAD) in 19 (53%), right coronary artery (RCA) in 10 (28%), left main 2 (5%), and left circumflex artery (LCX) in 5 (14%). Twenty-six percent of ostial LAD stenosis required a second Cypher stent inserted in circumflex/intermediate to prevent or treat plaque shift. Follow up was obtained in 91% of patients who had reached six-month post procedure. Twenty-nine percent have yet to reach six-month follow up.

Death

In-Hospital MACE

Six Month MACE

0

0

MI

0

0

TLRa

0

1

a

TLR (Target lesion revascularisation).

The one patient who had a repeat TLR with CABG had received a Cypher for ISR of a bare metal ostial stent. Conclusion: The use of Cypher Drug Eluting stent to treat ostial lesions is feasible. The immediate and short-term results are encouraging but further research and evaluation is required.

Abstracts

374 Treatment of Complex Bifurcations with Cypher Drug Eluting Stents Using the Crush Bifurcation Technique has Excellent Short and Medium Term Outcomes Mark Nallaratnam* , Dougal McClean, Mark Richards, FCSANZ, John Elliott, FCSANZ, David Smyth Christchurch Hospital, Christchurch, New Zealand Treatment of bifurcation lesions involving important side branches continues to be challenging for the interventional cardiologist. The Crush bifurcation technique is a new strategy using two drug eluting stents. Early reports have reported difficulty in rewiring the side branch, and problems with late stent thrombosis and restenosis of the side branch stent. We report our experience with complex bifurcation stenting using Cypher drug eluting stents in de novo bifurcation lesions. Methods: We retrospectively analysed, by hospital notes and telephone calls, consecutive de novo bifurcation lesions treated with Cypher Drug Eluting Stents from 2003 to Aug 2005. Patients were followed for a minimum of 6 months. Major Adverse Clinical Events (MACE) and Angina score were obtained. Results: There were a total of 45 bifurcation lesions treated in 42 patients. Site of bifurcation lesions were 67% LAD/Diagonal, 27% LCX/OM, 4% Left Main, 2% PDA/PLV. Techniques performed were 67% Crush, 24% Provisional stenting, 7% V stent, and 2% Modified T. All patients received aspirin longterm and clopidogrel for 6 months. 98% who had crush technique had final kissing balloons performed. At 6 months, 83% of patients had no angina, 12% Class 1 and 5% Class 2. In-Hospital MACE

Six Month MACE

Death

0

0

MI

1

0

TLRa

0

2

Late Stent Thrombosis

0

0

a

Target lesion revascularisation (TLR).

Conclusion: Complex bifurcation stenting with Cypher drug eluting stents using predominately the Crush Bifurcation technique has good short and medium term outcomes with patients remaining symptomatically well. We believe our excellent results are due to the importance of optimising stent/artery wall apposition by the use of final kissing balloons.

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375 Ostial LAD/LCx Lesions are Morphologically Complex and Invariably Involve Left Main Stem—A Salutary Lesson from Intravascular Ultrasound That May Impact Percutaneous Revascularisation Strategies Y. Malaiapan* , M. Leung, M. Zhang, S. Hope, S. Seneviretne, P.R. Antonis, I.T. Meredith, FCSANZ Monash Cardiovascular Research Centre, Monash University, Monash Medical Centre, Melbourne, Vic., Australia Background: Coronary angiography reflects luminal changes. Intravascular ultrasound (IVUS) shows the extent, burden and morphology of true atherosclerotic process. This is valuable for accurate assessment of ambiguous ostial lesions identified in coronary angiography. Methods: In 51 ambiguous left coronary ostial lesions detected on coronary angiography (39M, 22F, 65 ± 9 years), IVUS pullback (Boston Scientific Atlantis 40 Mhz probe) was performed across the ostial left anterior descending (LAD) or left circumflex (LCx) artery lesions into the left main stem (LMS). Minimum and maximum luminal diameter (MLD, max LD), lumen cross sectional area (CSA lumen), percent lumen cross sectional area (% CSA lumen), percent plaque burden (% plaque burden). Plaque morphology was assessed at 3–5 mm proximal to the distal end of LMS, the ostia and the proximal segments of LAD/LCx. Results: MLD of LMS and daughter vessels were 3.2 ± 0.6 and 2.5 ± 0.67, respectively. The % plaque burden in the LMS and daughter vessel were 49.4 ± 11.8% versus 56.29 ± 14.5%, respectively (P = 0.29). Total plaque length was 24.4 ± 7.7 mm with 7.10 ± 4.1 mm being in the LMS. CSA lumen of the LMS was 10.6 ± 17.3. The daughter vessels % CSA lumen was 63.8 ± 0.2. The LAD/LCx ostia were negatively remodeled (remodeling index 0.90 ± 0.24). There were more complex plaques in the ostia than in the proximal segment of the daughter vessels (50% versus 36%, P = 0.132). Calcific plaque comprised 26%, of which 75% were moderately calcified. Conclusion: Left coronary ostial lesions are morphologically complex and invariably involve LMS. This information can be used to appropriately strategize percutaneous interventions in this high-risk anatomic subset.

376 Percutaneous Closure of Ventricular Septal Defects Using the Amplatzer VSD Occluder Device A. McCann1 , D. Walters1 , FCSANZ, C. Aroney2 , FCSANZ, T.H. Goh1 , FCSANZ, Z. Hijazi1 1 The Department of Cardiology, The Prince Charles Hospital Brisbane; 2 The Holy Spirit Northside Hospital, Brisbane Qld., Australia

Percutaneous closure is emerging as an alternative to surgical closure in the treatment of ventricular septal defects in adults.

ABSTRACTS

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ABSTRACTS

Results: Eight patients with ventricular septal defects (VSD) underwent percutaneous closure using the Amplatzer VSD occluder device from 8/2003 to 12/2005 (mean age 48.8 range 26–82). Three patients underwent closure with an Amplatzer muscular occluder device (one patient failed surgical repair of post myocardial infarction VSD, one patient post AVR VSD and one patient VSD post alcohol septal ablation). The remainder of patients had isolated congenital perimembranous VSDs and underwent closure with the Amplatzer membranous VSD occluder device. All of the muscular cohort required intervention on the basis of cardiac failure and a significant shunt. Of the peri-membranous defects, 2 required intervention for endocarditis prophylaxis, 3 because of a significant shunt and left ventricular dilatation. Mean defect size was 7.1 mm (range 4–16 mm), device size was 9.75 mm (range 4–20 mm) and mean Qp:Qs was 1.9. In 3 of the 8 patients the defect was crossed retrograde from the aorta after failed antegrade approach. Procedural duration was 4.46 h (range 3.3–6.0) and average length of stay was 4 days. The device was successfully deployed in 7 of 8 (88%) patients. The procedure was abandoned in one patient who died shortly after the procedure who had dehiscence of a surgically repaired post infarction VSD. This patient was referred with cardiogenic shock and multi organ failure. No significant valvular dysfunction was observed post procedure. At a mean follow up of 7.5 months (range 2–21 months) all patients are asymptomatic with complete closure of the defect. One patient suffered intermittent hemolysis which resolved by 6 months. There have been no cases of post procedural complete atrioventricular block.

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BMS (n = 119)

DES (n = 96)

P

Age

62 ± 12

63 ± 12

NS

Gender (M:F)

96:23

73:23

NS

Diabetes

15

18

NS

History of smoking

58

64

NS

Hypertension

54

42

NS

Hypercholesterolaemia

64

64

NS

Procedural success (%)

96.6

91.7

NS

Clinical success (%)

88.2

88.5

NS

6.7

5.2

NS

Target lesion revasc. (%)

8.4

6.3

NS

Stent thrombosis (%)

2.5

2.1

NS

Deaths (%)

9.2

3.1

NS

In hospital

Deaths (%) Long-term

Conclusion: The use of DES compared with BMS in STEMI was not associated with an increase risk of adverse events in-hospital or over one to two years of follow-up. Particularly, there was no difference in the incidence of subacute or late stent thrombosis. Target lesion revascularisation was low in both groups. 378 Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Intervention in Acute Coronary Artery Lesions. Results of the PRACTICAL Trial

377 Long-Term Follow-Up of Patients with ST-Segment Elevation Acute Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention with Bare Metal versus Drug Eluting Stents

G. Yong1,* , J. Rankin1 , L. Ferguson1 , J. Thom1 , J. French2 , FCSANZ, D. Brieger3 , FCSANZ, D. Chew4 , FCSANZ, A. Whelan5 , FCSANZ, J. Eikelboom1

M.C.H. Leung* , M. Baldi, I.T. Meredith, FCSANZ

1 Royal Perth Hospital, Perth, WA, Australia; 2 Liverpool Hospi-

Monash Cardiovascular Research Centre, Monash Medical Centre, Monash University, Melbourne, Vic., Australia Introduction: There is a growing body of evidence that drug-eluting stents (DES) have a lower rate of restenosis than bare metal stents (BMS) in complex lesions. However, the safety and clinical efficacy of DES in treating ST-segment elevation myocardial infarction (STEMI) has not been validated. Method: We assessed the clinical characteristics, inhospital and one to two year outcomes (mean 732 ± 227 days) of 215 consecutive STEMI patients who had primary percutaneous coronary intervention with stent implantation at Monash Medical Centre between 2003 and 2004. Results: Baseline characteristics were similar between the two groups. Refer to table.

tal, Liverpool, NSW, Australia; 3 Concord General Repatriation Hospital, Concord, NSW, Australia; 4 Flinders Medical Centre, Bedford Park, SA, Australia; 5 Fremantle Hospital, Fremantle, WA, Australia Background: A 600 mg compared with 300 mg loading dose (LD) of clopidogrel achieves more rapid and complete inhibition of platelet aggregation and reduces the incidence of post-PCI myonecrosis in elective percutaneous coronary intervention (PCI). There are few data concerning higher clopidogrel LD in acute coronary syndrome (ACS) patients treated with early PCI. Method: In an Australian multi-centre trial, 256 clopidogrel-naive patients (mean age 63 years, 71% male) with high risk non-ST elevation ACS (92% elevated troponin or abnormal ECG) were randomised to receive a high (600 mg, n = 132) or standard (300 mg, n = 124) clopidogrel LD followed by coronary angiography and PCI (where appropriate) within 48 h. Optical platelet aggregometry (n = 200) was measured immediately prior to coronary angiography at 15.9 ± 10.6 h (mean ± S.D.)

following the LD. Those who underwent PCI contributed to the primary outcome of post-PCI myonecrosis, defined as a next-day Troponin I >5 times the upper limit of normal and greater than baseline. Findings: High dose compared with standard dose clopidogrel significantly reduced ADP-induced platelet aggregation (20 ␮mol/l ADP; 49.7% versus 55.7%, p = 0.01) but did not reduce the incidence of post-PCI myonecrosis (36.2% versus 38.0%, p = 0.83) in the 140 PCI patients (aspirin 100%, stent 97%, GP2b3a inhibitor 69%). There was no difference in 1-month clinical or bleeding outcomes. Conclusion: In this cohort of high-risk ACS patients, a 600 mg LD of clopidogrel provided greater suppression of platelet aggregation than a 300 mg LD but did not reduce the incidence of post-PCI myonecrosis. This may have been due to the high rate of concomitant GP2b3a inhibitor use. 379 Comparison of Outcomes in Percutaneous Coronary Interventions in Centres with “On-Site” Versus “Off-Site” Surgical Backup: Results from the Melbourne Interventional Group (MIG) Registry

Abstracts

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Table 1. Demographics Off-Site Backup (%) ACS STEMI NSTEMI Type B2-C lesions Rescue PCI GpIIb/IIIa inhibitor

66.9 20.9 25.7 41.2 0.9 29.0

On-Site Backup (%) 59.1 20.6 20.5 50.3 3.0 26.9

p Value <0.05 NS <0.001 <0.001 <0.01 NS

Table 2. Outcomes Off-Site Backup (%) Procedural success In-hospital Death Unplanned CABG 30-day MACE Bleeding

96.1 1.0 0.4 5.7 1.8

On-Site Backup (%) 95.5 1.6 1.0 7.4 1.0

p Value <0.05 NS NS NS NS

Conclusions: Despite off-site centres having more ACS patients, there was no difference in clinical outcomes. These data suggest that PCI can be safely performed in centres with off-site surgical back-up. 380 Effect of Intra-Coronary Metoprolol on Aortic and Coronary Vein B-Type Natriuretic Peptide (BNP) During Percutaneous Coronary Intervention

H.B. Liew1,* , S. Duffy2 , FCSANZ, V. Pandeli1 , A. Teh1 , L. Roberts1 , D. Robynne1 , A. Ajani3,4 , FCSANZ, A. Brennan4 D. Clark5 , A. Meehan4 , C. Reid4 , FCSANZ, G. New1 , FCSANZ, on behalf of the Melbourne Interventional Group (MIG) Investigators

Dariusz Korczyk1,* , Seifedin El Jack1 , Mark Webster1 , Peter Ruygrok1 , FCSANZ, James Stewart1 , FCSANZ, Irene Zeng1 , Suwatchai Pornratanarangsi1 , Mark Richards2 , FCSANZ, Ralph Stewart1 , FCSANZ

1 Department

1 Cardiology Department, Auckland City Hospital; 2 Cardiology

of Cardiology, Box Hill Hospital; 2 Department of Cardiology, Alfred Hospital; 3 Department of Cardiology, Royal Melbourne Hospital; 4 NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia; 5 Department of Cardiology, Austin Hospital, Melbourne, Australia Background: Percutaneous coronary interventions (PCI) carries the risk of requiring “bailout” CABG. There is ongoing debate regarding the safety of performing PCI in centres without access to on-site cardiac surgery, where backup is provided off-site. Aim: To compare safety and efficacy of PCI performed between: centres with off-site (Group 1) versus on-site (Group 2) surgical backup. To identify factors that influence these outcomes. Methods: We used the MIG Registry to compare public hospitals where PCI were performed. Two thousand four hundred and twenty-nine PCIs were performed in 4 “off-site” centers (796 patients) and in 3 “on-site” (1633 patients). Patient characteristics, clinical, procedural details and outcomes were compared. Results: Group 1 had older patients, whereas a higher prevalence for dyslipidaemia, previous AMI and renal failure were noted in Group 2. There was no difference in diabetes, hypertension, or congestive heart failure. The strongest predictor for 30-day MACE was cardiogenic shock (OR 6.5, 95% CI 0.72–19.7, p < 0.001).

Department, Christchurch Hospital, New Zealand The acute effect of intra-coronary metoprolol on BNP in coronary venous blood during percutaneous coronary intervention (PCI) of LAD or RCA lesions was assessed in a randomised clinical trial. Thirty-three patients undergoing PCI 1–6 days after non ST elevation myocardial infarction were enrolled. Blood was sampled from the aorta and the anterior inter-ventricular vein/great cardiac vein junction (CV) which drains blood from the LAD (n = 23) but not RCA (n = 10) territory. Samples were obtained before and 60 s after intra-coronary metoprolol 5 mg or placebo, after the first balloon inflation, and at the end of the procedure. At baseline, BNP was higher in the CV than the aorta (43 ± 25 pmol/l versus 27 ± 12 pmol/l, p = 0.001), with no difference by treatment allocation or culprit vessel. CV BNP increased within 60 s of metoprolol but not placebo (50 ± 39 versus 39 ± 20, p = 0.03). At the end of the procedure aortic BNP had increased, compared to baseline, with metoprolol but not with placebo (p = 0.002). The aorta to CV gradient was unchanged from baseline in both groups; there was no difference by culprit vessel. Metoprolol infused into either the left or right coronary artery increases plasma BNP in the CV within 60 s.

ABSTRACTS

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ABSTRACTS

381 Percutaneous Coronary Revascularisation in a Centre with Off-Site Bypass Surgery- Single Centre Experience M. Govindan* , R. Ahmed, G. Eslick, S. Hallani, M. Patel, M.A. Fitzpatrick, D. Coulshed, FCSANZ, C. Fernandes, FCSANZ Cardiology Department, Nepean Hospital, Penrith NSW, Australia Several studies have demonstrated the safety of PCI in centres with off-site surgical back up. Nepean Hospital is a centre servicing a catchment area of 400,000 people in the Greater Western Region with the nearest cardiothoracic service being 40 km away. Methods: The angioplasty registry was reviewed from July 2004–July 2005. Primary endpoints assessed were target lesion revascularization (TLR), and major adverse cardiac event rates. Results: Three hundred and thirty-five patients underwent PCI and 513 lesions were treated. Average age was 63 ± 11 years. Mean follow up was 10 months. Indications for PCI included-non-ST elevation myocardial infarct (31%), ST-elevation myocardial infarction (14.3%), Unstable angina (19.5%), and stable coronary artery disease (35.2%). Thirty-five percent were types A lesions, 45% Type B and 20% Type C lesions. TLR was 4.7%. Fourteen cases of instent re-stenosis and two cases of subacute stent thrombosis were recorded. Procedural success rate was 98.2%. Of the six unsuccessful procedures, two were chronic occlusions, three were failure to cross the lesion and one occluded vein graft. IIb/IIIa glycoprotein inhibitors were required in 21% of cases. Intra-aortic balloon pump was used in 1.5% of cases. Nine percent of patients had a CK rise following their procedure. There were no transfers for emergency bypass surgery due to unsuccessful procedures and no procedure related deaths. Major groin complications requiring transfusion or surgical intervention occurred in 1.5% of cases. Conclusions: PCI is a safe and feasible option in centres without cardiothoracic surgery. With appropriate patient and lesion selection, good clinical outcomes can be achieved. 382 Systemic Inflammatory Response after PCI with Stenting Alice Y. Tiong1,2,* , Harry Lowe1,2 , S. Ben Freedman1,2 , FCSANZ, David Brieger1,2 , FCSANZ 1 University

of Sydney, Vascular Biology Laboratory, Anzac Research Institute; 2 Department of Cardiology, Concord Repatriation General Hospital, Concord, NSW, Australia Background: Early studies of percutaneous coronary intervention (PCI) showed that balloon angioplasty causes rapid neutrophil and platelet activation. We postulated that advances in endovascular stents and adjunctive pharmacotherapy are associated with less systemic neutrophil activation.

Heart, Lung and Circulation 2006;15S:S1–S167

Method: Aortic blood was sampled immediately pre and post-procedurally from 36 patient with stable angina (n = 28) and acute coronary syndromes (n = 8) undergoing stenting of native coronary arteries. All except 1 were pretreated with aspirin and clopidogrel; none received GpIIbIIIa antagonists. Results: Overall, Mac-1 expression (mean fluorescence) did not change significantly within 5–10 min of PCI compared to baseline (412 ± 34 versus 383 ± 31, p = ns). Subgroup analyses showed that Mac-1 was unchanged/downregulated in 23 patients (463 ± 41 versus 358 ± 39, p < 0.0001), and up-regulated, defined as ≥5% change, in 13 patients (321 ± 53 versus 433 ± 53, p = 0.005). There were no differences in clinical characteristics between the two groups. Patients with up-regulation in Mac-1 had longer lesions (13% versus 69%, p = 0.001 for lesions≥10 mm). In addition, they had greater total stent length (14.8 ± 0.9 versus 18.5 ± 1.7, p = 0.05); greater number of balloon inflations (2.4 ± 0.3 versus 3.9 ± 0.6, p = 0.01) with no difference in total ischemic time or pressure-time product; and trended towards longer fluoroscopy time (11.5 ± 1.1 versus 17.8 ± 4.3, p = 0.08). All who developed acute procedural complications also had up-regulation in Mac-1: ventricular arrhythmia (n = 1), acute chest pain and hypotension (n = 1) and increased troponin-T ≥5x upper limits of normal (n = 2). Conclusion: In current stent era, rapid systemic neutrophil activation is observed in only one-third patients undergoing PCI, is influenced by lesion morphology and procedural complexity, and occurred in all patients with acute procedural complications. 383 Comparison of In-Hours Versus Out-of-Hours Times to Primary PCI in Patients Presenting with STEMI W. Ahmar1,* , A. Ajani1 , FCSANZ, T. Quarin2 , M. Kennedy2 , B. Yan1 , L. Grigg1 1 Department

of Cardiology; 2 Emergency Department, Royal Melbourne Hospital, Melbourne, Australia ST-segment elevation myocardial infarction (STEMI) mandates rapid percutaneous coronary intervention (PCI) for optimal outcomes. The aim of this study was to evaluate delay times to primary PCI in a high volume PCI centre. Methods: We analysed consecutive patients (pts) presenting with STEMI (April-August 2005), and compared pts presenting In-hours [0700–1800 (Monday-Friday)] versus Out-of-hours (all other times). Results: Of the total STEMI cohort of 48 pts, 38 pts underwent primary PCI (mean age of 57.5 ± 10.2 years, 71% males). Of these, 19 pts (50%) had PCI performed In-hours. A breakdown of median times leading to the decision to perform PCI and subsequent treatment times are shown (Table). The median door to balloon time for primary PCI was significantly greater for Out-of-hours than In-hours pts (120 min versus 67 min, p < 0.01). The greatest time delay to PCI was from the PCI decision time to catheter laboratory arrival.

Time to Inform Cardiology (min)

In-Hours (n = 19) Out-ofHours (n = 19) Overall

10 (1–140) 9.5 (1–35)

10 (1–140)

Abstracts

Time to Cardiology PCI Decision (min)

Time from PCI Decision to Cath Lab Arrival (min)

Door-toSheath Time (min)

Door-toBalloon Time (min)

10 (2–25)

15 (3–85)

54 (38–225)

67 (47–240)

12.5 (1–65)

39 (5–155)

100 (63–165)

120 (75–172)

10 (1–55)

35 (5–60)

81 (38–225)

88 (47–240)

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385 The “New” Aortic Valvuloplasty Paul J. Klaassen2,* , Wesley R. Pedersen1 , Timothy D. Henry1 , Michael Mooney1 , Anil Poulose1 , Talia Pierce1 1 Abbott

Conclusions: Current ACC guideline recommendations for door-to-balloon times (90 min) were achieved during In-hours but were exceeded Out-of-hours. We have implemented changes to reduce the Out-of-hours time to PCI, including initiation of ‘Code-Heart’. 384 Intra-Coronary Versus Intravenous Abciximab for Acute Myocardial Infarction-Preliminary Results of a Prospective, Randomised Double Blinded Trial M. Rahman* , R. Huq, L. Ponnuthurai, M. Sebastian, FCSANZ, T. Yip, A. Black Department of Cardiology, The Geelong Hospital, Geelong, Vic., Australia Background: Abciximab is used in patients (Pts) with Acute Myocardial Infarction (AMI) undergoing percutaneous coronary intervention (PCI) to reduce major adverse cardiac events (MACE). Observational studies have suggested a favourable outcome with intra-coronary (IC) abciximab compared to intravenous (IV) route. This study aims to formally assess the safety and feasibility of IC versus IV abciximab in acute PCI, and to examine 30-day MACE. Patients and methods: Pts undergoing acute PCI (including rescue PCI for failed thrombolysis) were randomised in a blinded fashion to weight adjusted standard bolus dose of IV or IC abciximab, followed by the conventional 12-h IV infusion. To date, 23 Pts have been randomised, 13 IC and 12 IV. Mean age was 58 years, 20 Pts (87%) were males and four Pts (17%) were in cardiogenic shock. Initial flow was TIMI 0/1 in 17 Pts (70%). Results: One Pt in cardiogenic shock died prior to PCI. Successful PCI was performed in the remaining 22 Pts (100%). Four Pts (17%), two in each group had mild to moderate access site haematomas, no Pt required transfusion. None of the Pts needed target vessel revascularization (TVR), nor had recurrent angina, AMI or re-hospitalization for cardiac reasons at 30-day follow-up and overall MACE rate was 1/23 (4.3%). Conclusion: From this limited data, no significant difference between IC and IV abciximab has been observed. However, recruitment is ongoing and further results are awaited.

2 The

Northwestern Hospital, Minneapolis Heart Institute; University of Minnesota, USA

Background: Western population demographics will soon result in an epidemic of degenerative aortic stenosis. BAV currently practised in limited settings in isolated centres will be a critical component of the utilization of the new generation of balloon-deployed aortic valves now appearing in the literature. BAV itself is however probably an approach which should be more frequently applied than is currently the case. Just as with balloon angioplasty 2 decades ago, and now with left main stenting, interventional cardiologists will look to that patient population which is unsuitable for surgical treatment in our attempts to bring these therapies to clinical application in a group of innately high risk patients who wish to avail themselves of this opportunity—one which may in time become the mainstay approach. The Minneapolis Heart Institute at Abbott Northwestern Hospital and The University of Minnesota are currently amongst the highest volume centres for BAV with 83 performed between July 2003 and January 2006 at Abbott Northwestern alone. Findings: We examined the highest risk patients i.e. those over 90 years of age which included 26 of the above 83 patients. Twenty-two were performed antegrade and 4 retrograde. Three patients underwent simultaneous PCI. Procedural hospital mortality was 4%. There were only 2 cases of an increase in AR of more than 1 grade. Mean gradient reduction was 27 mmHg, and AVA reduction was 38%. Mean length of stay was 4 days. Conclusion: Aortic valvuloplasty is a surprisingly lower risk procedure than expected in nonagenarians when one considers their clinical baseline. Over the next decade, this population may well be the first group to benefit from post-dilatatory insertion of percutaneously inserted aortic valves as they have no surgical options, but BAV as a stand-alone palliative procedure, is probably currently underutilized. 386 Long-Term Outcome After PCI in Victorian Public Versus Private Hospitals: Impact of Restricted use of DrugEluting Stents in Public Hospitals G. Szto* , FCSANZ, A. Ajani, FCSANZ, D. Clark, D. Eccleston, FCSANZ, T. Walton, FCSANZ, S. Black, S. Duffy, FCSANZ, C. Reid, FCSANZ For MIG investigators, CCRE Therapeutics, Monash University, Melbourne, Vic., Australia Indications for use of drug-eluting stents (DES) in Victorian Public Hospitals (PUB) are limited to certain lesion/patient subsets, with no restriction in private hospitals (PVT). We sought to determine if this restriction results

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ABSTRACTS

in more favourable long-term outcomes in patients undergoing PCI at PVT. Methods: Prospective clinical data on 2092 patients were collated through a centralised metropolitan hospitals database and analysed. Results: DES use was twice as high in PVT versus PUB (45.3% versus 89.7%). Despite similar procedural success rates and higher DES stent use, the PVT patients ended up with proportionally similar MACE at 30-day and 1 year. The reason for this is unclear, further analysis will assist in understanding this discrepancy. Public Hospital (n = 2069)

Private Hospital (n = 523)

Age (years)

64.1 ± 11.9

67.4 ± 12.0

NS

Diabetes (%)

24.5

17.2

<0.01

DES use (%)

45.3

89.7

<0.01

Procedural success (%)

99.2

98.9

NS 0.17

P Value

30-day MACE (%)

5.4

7

1-year MACE (%)

13.6

20.5

0.08

1-year TVR (%)

7.1

8.5

NS

1-year mortality (%)

2.7

4.7

NS

Conclusion: Despite much higher use of DES in private hospitals, the 30-day and 1-year outcomes after PCI are no better. The reasons for this will be analysed. Paediatric Cardiology 387 Family History Determines Aortic Root Growth and Requirement for Surgery in Paediatric Marfan Subjects Marieke Bos1,2,* , Hee J. Park1 , Suzanna Vidmar1 , Jonathan Sterne1 , Martin Delatycki1 , Ravi Savirarayan1 , John Carlin1 , Robert Weintraub1 , FCSANZ 1 Royal 2 Beatrix

Children’s Hospital, Melbourne, Vic., Australia; Children’s Hospital, Groningen, The Netherlands

Background: The severity of cardiovascular involvement in Marfan syndrome varies considerably. This study examines the impact of family history on aortic root growth and outcomes. Methods: The study comprised all children with Marfan syndrome seen between 1973 and 1991, with at least one cardiac evaluation <20 years of age. Subjects were classified according to whether they had a severe family history (aortic dissection, early cardiac death or requirement for aortic root surgery), a mild family history, or no family history (sporadic group). Serial echocardiographic aortic root measurements were standardized as Z scores. Multilevel models were used to estimate the relationship between standardized aortic diameter and age, adjusting for the family history grouping. Results: There were 131 Marfan subjects seen with a mean (S.D.) age of 9.46 (5.22) years at first evaluation, and a mean follow-up duration of 8.11 (6.46) years. Seventy-two subjects had a positive family history, which was severe in 39 cases. Ninety-three of all study subjects were treated with a beta-blocker. The mean rate of increase in standardized

aortic diameter was higher in the severe family history and sporadic groups (0.158 year−1 , 95% CI 0.044–0.272 and 0.119 year−1 , 95% CI 0.043–0.195, respectively), compared to the mild family history group (0.001 year−1 , 95% CI −0.095 to 0.097). Compared to the sporadic group the hazard ratio for surgery in the mild group was 0.11 (95% CI 0.01–0.85) and 0.69 (95% CI 0.25–1.88) in the severe family history group (p = 0.04 log-rank). Conclusions: Paediatric Marfan subjects with sporadic disease or a severe family history manifest faster aortic root growth and are more likely to require aortic root surgery, compared to those with a family history of mild disease. 388 Outcome of Infant Following Prenatal Diagnosis of Major Cardiac Anormalies—1 Year Audit B.K. Yeu* , S. Menahem, FCSANZ, L. Fong, FCSANZ, P. Shekleton Paediatric Cardiology, Monash Medical Centre, Melbourne, Vic., Australia Aims: To evaluate the impact of an abnormal fetal cardiac scan on the outcome of newborn. Methods: All pregnancies where an abnormal fetal cardiac scan was considered, were reviewed to determine how it influenced the pregnancy, outcome of the fetuses, treatment and outcome of the newborn. Diagnoses were confirmed by neonatal echocardiography after the babies were delivered. In high risk fetuses, the delivery was planned with anticipation of interventions, if required. Results: Between January and November 2005, 95 abnormal fetal cardiac scans were carried out on 66 fetuses. Three opted for termination and two were successfully treated during the pregnancy for hydrops fetalis from tachyarrhythmia. One was induced for early delivery because of increasing cardiac size and deterioration of fetal well being. Nine needed prostaglandin infusion prior to surgery. Two required intensive care for associated malformations. There were nine survivors following often complex surgery, and two surgical deaths. Two newborns died prior to surgery because of severe tricuspid valve regurgitation, one with septicaemia, the surgery having been deferred. Conclusions: Early detection of fetal cardiac malformation offers the possibility of termination of pregnancy, ongoing antenatal care with planned site and timing of delivery, anticipatory post natal care for optimum outcomes.

389 Pregnancy with Complex Congenital Heart Disease – Good Maternal Outcomes but Frequent Fetal/Neonatal Complications Rahn Ilsar* , Lynne Pressley, Peter J. Robinson, FCSANZ, Richard E. Hawker, FCSANZ, David S. Celermajer, FCSANZ Royal Prince Alfred and Westmead Children’s Hospitals, Sydney, NSW, Australia Our congenital heart disease (CHD) program follows up several hundred adults with repaired lesions, several of whom have recently had pregnancy, mostly co-supervised by the adult CHD and high risk obstetric units. We studied the outcomes for mother and offspring in those with complex CHD (excluding simple lesions such as ASD, VSD and PDA). There were 29 pregnancies in 16 women (15 had had surgery for complex CHD, 2.6 ± 0.9 operations – and one had Eisenmenger VSD) between 1995–2005, at age 25 ± 4 years. Underlying CHDs included 6 tetralogy of Fallot or variants; 5 with TGA or variants and 3 with complex aortic coarctation. Prior to conception, 4 had significant RV systolic dysfunction (2 systemic, 2 subpulmonary), 3 had severe pulmonary hypertension (PHT) while 3 had severe pulmonary regurgitation (PR). Maternal complications included 5 with SVT and 4 cases of new or worsening heart failure but none had long-term sequelae and there were no maternal deaths. By contrast, 8 of 29 pregnancies (28%) did not result in a liveborn infant (6 spontaneous abortions in 1st trimester; 1 elective termination of pregnancy (TOP); one premature labour at 22 weeks with neonatal death) and a further 4 were complicated by prematurity (30 weeks, one case) or low birth weight at term (<2.5 kg, 3 cases). Seventeen liveborn infants were well with no evidence of CHD (59%). Conclusion: Even complex CHD is compatible with good maternal outcome in the setting of careful cardiac and obstetric management, however fetal outcomes are often poor.

Rehabilitation, Exercise and Prevention 390 A Single Centre Prospective Study of Percutaneous Coronary Intervention (PCI) with Off-Site Surgical Back-Up V. Pandeli* , M. Swale, B. Chou, A. Teh, C. Lim, L. Roberts, G. Proimos, FCSANZ, Y.M. Cheong, FCSANZ, C. Goods, M. Rowe, FCSANZ, D. Fernando, G. New, FCSANZ Department of Cardiology, Box Hill Hospital, Vic., Australia Background: Several studies have demonstrated the safety and efficacy of PCI with off-site surgical back-up. Box Hill Hospital (BHH) has such a program. Aims: To review the safety and ongoing efficacy of our PCI service in the setting of contemporary PCI management.

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Methods: We report our database of all patients who attended BHH or were transferred from referral hospitals from 1st July 2002 until 31st December 2005 who underwent a PCI. Results: One thousand five hundred and twenty patients underwent Primary, Emergent or Elective angioplasty during this period. Seventy-four percent were male with the average age 63 ± 12 years. Eight percent of the patients were over 80 years and 20% were diabetics. Procedure success was 96%. Table 1. 30-Day Outcomes Outcome Recurrent-MI TVR Death Death excl. cardiogenic shock MACE total MACE excl. cardiogenic shock

Primary (n = 367)

Emergent (n = 639)

Elective (n = 514)

Total (n = 1520)

2 (0.5%) 6 (1.6%) 25 (6.8%) 12 (3.3%)

6 (1%) 3 (0.5%) 9 (1.4%) 8 (1.3%)

2 (0.4%) 0 1 (0.2%) 0

10 (0.7%) 9 (0.6%) 35 (2.3%) 20 (1.3%)

33 (9%) 19 (5.2%)

18 (2.8%) 17 (2.6%)

3 (0.6%) 3 (0.6%)

54 (3.6%) 39 (2.6%)

Conclusions: PCI can be performed in centres with off-site surgery provided they comply with the CSANZ guidelines. This large and local registry confirms that such a program is not only safe and efficacious but is also a practical and economical option for the community where patients avoid inter-hospital transfer for primary or emergent procedures and potentially long waiting times for elective intervention.

391 Are there Gender Differences in Quality of Life Outcomes of Cardiac Rehabilitation in Post Myocardial Infarction Patients? R.P. Zecchin* , Y.Y. Chai, J. Hungerford, G. Lindsay, S. Manners, M. Owen, J. Thelander, A.R. Denniss, FCSANZ Cardiac Education and Assessment Program (CEAP), Westmead Hospital, Sydney, NSW, Australia Cardiac rehabilitation (CR) aim is to promote recovery and enhance quality of life (QOL) in post myocardial infarction (AMI) patients. This study was designed to evaluate the differences in QOL data between males (M) and females (F) who had a recent AMI. Methods: All AMI patients (n = 721) who entered our CR program, from July 2000 to December 2005, were given a generic QOL (SF-36) and Depression, Anxiety, and Stress (DASS21 ) questionnaires. Results: A 39% (249 M and 34 F) completion rate of both surveys was observed. No difference in the site of the AMI were seen but M had more ST elevation AMI (67%: F 50%; p = 0.001). There were no differences in age, days from AMI to CR entry, left ventricular function, and past medical history but M had greater exercise capacity (8.56 ± 2.45: F 6.21 ± 1.49 METS; p > 0.001). In the SF-36, M only had a significantly higher score in the Physical Functioning

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domain at both CR entry and exit (p = 0.007 and p = 0.04, respectively), but lower scores than F in the Bodily Pain domain (M 62.02: F 74.65; p = 0.02) only at CR entry. M and F achieved similar scores to the Australian norms at CR exit. There were no differences in the DASS21 scores at CR entry and exit, and in the reduction of the depression, anxiety and stress symptomatology at CR exit between M and F (both > 50%). Conclusions: This study demonstrates very little difference in QOL for both M and F AMI patients at CR entry and exit except for Physical Functioning. This study results differs greatly from the cardiothoracic surgical population in CR. A need for closer observation of the F AMI population is still required due to the small number of respondents to the surveys in this study. 392 Gender Differences in Quality of Life Outcomes of Cardiac Rehabilitation in Cardiothoracic Surgical Patients R.P. Zecchin* , Y.Y. Chai, J. Hungerford, G. Lindsay, S. Manners, M. Owen, J. Thelander, A.R. Denniss, FCSANZ Cardiac Education and Assessment Program (CEAP), Westmead Hospital, Sydney, NSW, Australia Cardiac rehabilitation (CR) aim is to promote recovery and enhance quality of life (QOL) in cardiothoracic surgical patients (CTSx) patients. This study was designed to evaluate the differences in QOL between males (M) and females (F) who underwent a CTSX procedure. Methods: All CTSx patients (n = 771) who entered our CR program, from July 2000 to December 2005, were given a generic QOL (SF-36) and Depression, Anxiety, and Stress (DASS21 ) questionnaires to be completed. Results: A 54% (341 M and 71 F) completion rate of both surveys was observed. The types of CTSx were similar to both groups except F had more lone valve replacements then M (p = 0.04). There were no differences in age, days from surgery to entry into CR, risk factors, medication use, and past medical history. Differences were seen in prior myocardial infarctions (M 37%: F 14%; p > 0.001) and exercise capacity (M 7.74 ± 2.20: F 5.94 ± 1.74 METS; p = 0.001. M had higher scores in the SF-36 for the Physical Functioning, Vitality, and Mental Health domains at both entry and exit points (all p < 0.01). The Bodily Pain domain was the only difference at the exit point (M 79.37: F 72.28; p = 0.02) from the entry point. Both M and F achieved similar scores to the Australian norms (ABS 1995) at the CR exit. The DASS21 scores showed that F had higher anxiety levels at entry and exit then the M and a higher level of stress levels at the exit point. The reduction of the depression, anxiety and stress symptomatology at the exit point was greater in the M population than the F (60%: 35%; p < 0.001). Conclusions: This study demonstrates significant differences in QOL for both M and F CTSx patients at CR entry and exit points. Greater emphasis on the psychosocial needs of F is recommended for all CR programs.

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393 General Practitioners and Cardiologists Differ in their Approach to Statin Therapy in a Patient with Recent Myocardial Infarction Nikhil Sapre* , Stewart Mann, FCSANZ, C. Raina Elley Wellington School of Medicine, Wellington, New Zealand Aim: We wished to assess how General Practitioners (GPs) and Cardiologists (Cs) perceive and communicate the benefits of statin therapy and how they recommend starting therapy in a patient following myocardial infarction (MI). Methods: We interviewed 20 GPs and 22 Cs to determine treatment policies and ways of expressing its benefits to a post-MI patient with moderate dyslipidaemia. We asked what drug and dosage they would recommend. Main results: Twelve GPs would start either diet alone or a low dose (10–20 mg/day) of (funded) simvastatin whereas 19 Cs would commence 40 mg/day immediately. Most (19) GPs used total cholesterol as a target whereas Cs (18) focused on LDLc and pursuing more aggressive target levels vigorously. All but one C would justify therapy to the patient by citing a reduced chance of major adverse cardiovascular events (MACE), 12 quoting an estimate of relative risk reduction (RRR); 18 GPs also cited this but only three ventured a RRR estimate. All but two in each group felt the patient could expect a longer life with therapy, nine GPs and one C estimating a gain of >5 years. Eighteen Cs estimated a RRR for MACE (range 10–50%, median 40%), GPs were less likely to define this and only 50% of them estimated an absolute risk reduction (ARR) over 5 years. Estimates of ARR from each group varied widely from 0–5% to >20%. Conclusion: There were major disparities between the two groups of clinicians in perception and policy and overestimation of effect of treatment on life expectancy.

394 The Translation of Specialist Nurse-Led Multidisciplinary Services for Heart Failure from Clinical Trials to Clinical Practice: Outcomes of the South East Sydney Area Health Service (SESAHS) Chronic Care Collaborative in Heart Failure J. McVeigh* , K. Bardsley, J. Newton, L. Soars, G. Paull, on behalf of the SESAHS Heart Failure Implementation Committee South Eastern Sydney Area Health Services, Sydney, Australia Specialist nurse-led multidisciplinary care services (MCS) have been shown in randomised, controlled trials to reduce hospitalisation rates, improve quality of life and possibly survival in patients with heart failure. The aim of this study was to report the characteristics and outcomes of HF patients referred to 5 MCS that were established in 1999 across the South Eastern Sydney Area Health Service (SESAHS). Over a period of 6 years to December 2005, 2287 patients have been referred to these services. The average age of referred patients was 77 ± 13 years, with 69%

of patients aged 75 or older. One third of patients lived alone, 29% were from a non-English speaking background and 62% were considered to be at high risk for readmission. For patients referred to MCS, influenza and pneumococcal vaccination rates were 72% and 63%, respectively. ACE inhibitors and beta-blockers were prescribed in 72% and 78% of patients, respectively. Total admissions, total bed days (TBD) and average length of stay (ALOS) for CHF across SESAHS have reduced by 13%, 16% and 5%, respectively, due mainly to an 18% reduction in unplanned admissions. Conclusions: As expected, the majority of HF patients referred to MCS are elderly and many are socially isolated. In spite of this, high rates of evidenced based drug therapy and sustained reductions in hospitalisations for HF were achieved. These findings suggest that the benefits of MCS demonstrated in randomised clinical trials can be readily translated to the broader HF population. 395 Beneficial Effects of a Short Duration of Aerobic Training in Patients with Left Ventricular Systolic Dysfunction and Congestive Heart Failure are Maintained Over 6 Months after Cessation of Training Alison Daniel* , Arnold Ng, Christine Allman, Mark Newman, FCSANZ, Sidney T. Lo, FCSANZ, K.S. Edward Chow, FCSANZ, Andrew P. Hopkins, FCSANZ, Dominic Y. Leung, FCSANZ Department of Cardiology, Liverpool Hospital, Sydney, NSW, Australia We have previously shown that a short course of exercise training led to reverse remodelling in patients with left ventricular (LV) systolic dysfunction. Whether these beneficial effects are maintained after cessation of training is unclear. Methods: Sixteen patients (aged 61 ± 11 years, 14 men) with LV dysfunction (ejection fraction [EF], 32 ± 13%) underwent exercise echocardiography with expired gas analysis before and after low intensity, aerobic training 3 times/week for 6 weeks and again after 6 months without further supervised training. Results: Exercise training resulted in improvement in exercise duration (5.2 ± 2.5 min versus 7.1 ± 2.6 min, p < 0.001) and respiratory exchange ratio (RER. 1.17 ± 0.14 versus 1.26 ± 0.15, p = 0.049). This occurred despite absence of significant increases in VO2 max (17.3 ± 3.7 ml/kg/min versus 18 ± 4.6 ml/kg/min). Training led to a significant decrease in LV end systolic volume (ESV, 106.1 ± 40.9 ml versus 97 ± 42.9 ml, p = 0.004) with a non-significant increase in LVEF (32 ± 12.9% versus 35.1 ± 11.8%, p = 0.22). There was no change in B-type Natriuretic peptides or indices of systolic or diastolic function measured with Tissue Doppler with training. Without further training at 6 months, the improvements with the initial short duration of training are maintained (exercise duration 8.1 ± 1.8 min, RER 1.24 ± 0.1, LVESV 81 ± 32 ml, all p = NS compared with their values at 6 weeks).

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Conclusions: A 6-week course of low intensity exercise training led to reverse remodelling of the LV and improvement in exercise capacity. These occurred without significant improvements in LV systolic or diastolic function or vasopeptide levels. These beneficial effects are maintained at 6 months despite the cessation of training. 396 A Controlled Exercise Training Trial in Patients with Diastolic Dysfunction Neil Smart* , PhD, Carrie Ritchie, PhD, Brian Haluska, MS, Thomas H. Marwick, MD, PhD, FACC, FCSANZ University of Queensland, Brisbane, Qld., Australia Background: Exercise training (ExT) improves functional capacity in systolic heart failure, but the role of ExT in diastolic dysfunction (DD) is unclear. Methods: Twenty-four DD patients were randomized to ExT or normal treatment. ExT was completed in 15 patients (8 men, 63 ± 4 years, LVEF 55 ± 9%) 9 DD patients undertook usual treatment (7 men, 58 ± 8 years, LVEF 57 ± 7%). Peak VO2 , quality of life QOL; Minnesota Living with Heart Failure [MLWHF] and Hare-Davis [HD] questionnaires) and echo measures (EF, systolic [Sm] and diastolic tissue velocity [Em] and filling pressure [E/E ]) were performed at baseline and 16 weeks ExT. Results: Both groups showed similar baseline VO2 (13.2 ± 5.8 ml/kg/min versus 16.4 ± 4.2 ml/kg/min, p = 0.16), Sm (5.2 ± 1.2 cm/s versus 6.0 ± 0.9 cm/s, p = 0.10) and E/E (21.6 ± 12 versus 11.2 ± 10, p = 0.12) but different Em (3.7 ± 3.8 cm/s versus 6.6 ± 1.6 cm/s, p = 0.04). Baseline MLWHF and HD scores were similar in both groups, change in the total (p = 0.01) and emotional (p = 0.006) dimensions of MLWHF and HD (p = 0.05) scores were significantly improved at 12 weeks in ExT patients. After ExT, the increment in peak VO2 was greater in ExT (27%) versus control group (3%) (p = 0.02). Conclusions: In patients with exercise limitation attributed to DD, the improvement in peak VO2 and QOL with ExT is similar to those with SD, but unrelated to changes in diastolic function. 397 Cardiovascular Risk and Risk Factor Management in Gout: An Analysis Using Guideline Based Electronic Clinical Decision Support K. Colvine* , A. Kerr, A. McLachlan, P. Gow, S. Kumar, J. Ly, C. Wiltshire, N. Dalbeth Departments of Rheumatology and Cardiology, Middlemore Hospital, Auckland, New Zealand Aims: To assess cardiovascular disease (CVD) risk in patients with gout, and whether this risk is appropriately managed, using PREDICTTM CVD/DM decision support software, an electronic translation of the the NZGG Guidelines (2003) for the Assessment and Management of Cardiovascular Risk and the Guidelines for the Management of Type 2 Diabetes.

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Methods: We studied 100 consecutive patients referred to the rheumatology service for management of gout. Fasting lipids and glucose were obtained. CVD risk factor and management data were collected. PREDICTTM CVD/DM was used to calculate Framingham five-year CVD risk, and to analyse current management against guideline recommended management. Results: Fifty-nine (59%) patients had a high (≥15%) or very high (≥20%) five year CVD risk, including thirty (30%) with pre-existing ischaemic CVD. The prevalence of the metabolic syndrome using the NZGG/ATPIII definition was 86%. For those at high or very high risk of CVD, target systolic blood pressure (130 mmHg) was exceeded in 66%, target LDL-cholesterol (2.5 mmol/L) was exceeded in 49%, target HDL-cholesterol (1 mmol/L) was not achieved in 44%, and 19% continued to smoke. For diabetics, target HbA1c (7.0%) was exceeded in 61%. Using the NZGG guidelines, 55% of eligible patients missed appropriate therapy with aspirin, 30% beta-blockers, 40% statins and 30% ACE inhibitors. Conclusions: Patients with gout referred to secondary care are at high risk for CVD, have a high burden of modifiable risk factors, and are sub-optimally managed. Implementation of CVD screening and management programs in these patients should have high therapeutic yield.

398 Modular Guided Self-Choice Achieved Equivalent Risk Factor Level and Prevalence to Standard Cardiac Rehabilitation Following Acute Coronary Syndrome (ACS) J. Redfern1,* , E. Ellis1 , T. Briffa2 , S.B. Freedman1,3 , FCSANZ 1 University 3 Department

of Sydney NSW; 2 Curtin University WA; of Cardiology Concord Hospital NSW, Australia

Poor participation in time-limited, centre-based rehabilitation among low-risk patients is unlikely to deliver significant secondary prevention following ACS. The objective of this study was to compare a modular guided self-choice approach to secondary prevention (MSP) with standard cardiac rehabilitation (SCR) over three months. Volunteer ACS survivors who were eligible for but declined rehabilitation were allocated to MSP (n = 72) and compared with a contemporary group attending rehabilitation (n = 64). Coronary risk factors and LIPID score were assessed at baseline and three months. For most risk factors, baseline prevalence was significantly higher in MSP than SCR. By three months, the mean level and prevalence for all risk factors did not differ between the groups due to significant reductions in TC, LDL, number of risk factors and prevalence of physical inactivity and overweight in the MSP group. At three months, there was no significant reduction in level or prevalence for risk factor in the SCR group.

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Modular Secondary Prevention (MSP) Risk Factor (RF)

Baseline

Cardiac Rehabilitation (SCR)

3 months

Baseline

3 months

4.8 ± 0.1*

4.1 ± 0.1‡

TC >4 mmol/L

77%*

58%†

53%

44%

LDL (mmol/L)

2.7 ± 0.1

2.1 ± 0.1‡

2.3 ± 2.0

2.0 ± 0.1

TC (mmol/L)

4.3 ± 0.1

4.0 ± 0.1

SBP (mmHg)

137 ± 2.1

133 ± 2.6

136 ± 2.6

136 ± 2.9

Median number RF (IQR)

3.0 (3.0–3.0)

2.0 (1.0–3.0)

1.0 (1.0–2.0)

2.0 (1.0–3.0)

Physically Inactive

82%**

25%‡

23%

24%

BMI ≥30 kg/m2

45%

28%‡

32%

27%

Depressed – CDS ≥90

20%*

25%

5%

19%†

Smokers

14%*

7%

1%

1%

4 or more risk factors

24%**

14%

2%

17%†

LIPID score ≥5

49%*

38%

22%

31%

**

† p < 0.05, ‡ p < 0.01 for MSP or SCR 3 months versus baseline, * p < 0.05, p < 0.01 for MSP versus SCR baseline.

ACS survivors, at higher baseline risk, attending individualised modular secondary prevention achieve risk factor equivalence to the select group in cardiac rehabilitation after three months. More ACS survivors may achieve effective secondary prevention when offered an alternative to standard rehabilitation.

399 Effectiveness of Exercise on Emerging Risk Factors for Cardiovascular Disease M.A. Neaverson1,* , Bermingham2

Bridget

Abell1 ,

Margaret

1 Heart Disease Prevention Centre, Noosaville; 2 Dept of Biomed-

ical Science, University of Sydney, Australia A number of emerging risk factors for atherosclerosis have been identified which may further improve risk analysis. Recently, we have demonstrated a significant correlation between highly atherogenic small dense LDL particles and triglyceride/HDL ratio (p = 0.0001). Additionally, fibrinogen, C-reactive protein, homocysteine and lipoprotein a may be equally important, or more so, than traditional cardiovascular risk factors. Research however about the effectiveness of exercise at reducing such parameters is scarce. Method: The effect of eighteen 30-min sessions of exercise on these risk factors was studied in 270 male and female subjects undertaking a cardiac exercise programme for either primary or secondary prevention of cardiovascular disease. Results: Following training patients experienced: • A significant 7% decrease in fibrinogen levels (3.34 ± 1.94 to 3.12 ± 079 g/L, p = 0.012). • A significant reduction in triglyceride: HDL cholesterol ratio of 16% (2.05 ± 1.87 to 1.73 ± 1.26, p = 0.016). • A highly significant reduction in HsC-reactive protein of 29%, irrespective of statin use (3.6 ± 2.7 to 2.5 ± 2.0 g/L, p = 0.001).

These benefits were even more marked in patients in the high-risk categories for each variable with highly significant reductions in: • Plasma fibrinogen (12%, p < 0.0001) • Triglyceride/HDL ratio (26%, p = 0.0004) • HsCRP (37%, p < 0.0001) Conclusions: A unique, simple and time-effective form of exercise is able to positively impact some of the emerging risk factors for cardiovascular disease. More importantly those patients at the highest levels of risk experienced the greatest benefits. These findings may help establish such exercise programmes as a vital element in the prevention and treatment of cardiovascular disease. 400 The SHIPEM Registry. Outcomes of Shipping Infarcts for Primary Angioplasty in Eastern Melbourne L. Roberts* , V. Pandeli, M. Swale, B. Chou, A. Teh, C. Lim, C. Goods, FCSANZ, M. Rowe, FCSANZ, G. Proimos, FCSANZ, Y.M. Cheong, FCSANZ, D. Fernando, P. Archer, G. Thompson, A. Maclean, D. Leech, G. New, FCSANZ Box Hill Hospital, Box Hill, Victoria, Australia Background: Several studies have demonstrated superior 30-day patient outcomes for STEMI patients who are transferred from nearby hospitals (<3 h) for angioplasty (PCI) versus onsite thrombolysis. Aim: To present our local experience on the safety and efficacy of transferring STEMI patients for primary PCI from nearby hospitals without PCI facilities in Eastern Melbourne.

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Table. Outcomes Outcomes 30 Day Death Death Excl. Cardiogenic Shock MI (CK >2x ULN) TVR MACE Total MACE Excl. Cardiogenic Shock

SHIPEM (n = 132) 6 (4.5%) 1 (0.8%) 1 (0.8%) 1 (0.8%) 8 (6%) 3 (2.3%)

Method: We prospectively collected data from STEMI patients who were transferred to BHH from 1st July 2002 until 31st December 2005. Mean door-to-balloon times were within the 3-h timeframe. Results: One hundred and thirty two patients were transferred for Primary (81%), Facilitated or Rescue PCI. Mean age ± S.D. was 61 ± 13 years. Seventy-two percent were male. Fifty-one percent were anterior STEMIs. Five percent (n = 7) had anatomy not suitable for PCI and 4 of these patients were transferred for CABG. One hundred and forty six lesions were treated in 128 procedures. Procedural success rate was 95%. No patients required emergency CABG for PCI complication. Conclusion: The transferring of patients from nearby referral hospitals for primary PCI is safe with acceptable door to balloon times and 30 day MACE rates. The feasibility and safety of transferring STEMI patients for primary PCI is suitable for hospitals able to provide treatment within acceptable timeframe and clinical outcomes. Cardiogenic shock remains a poor prognostic factor for survival.

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