ECG-Gated Multislice Computed Tomography To Assess Right Ventricular Function

The 10th Annual Scientific Meeting




HFSA

S19

061

063

Borderzone Myocardial Dyssynchrony Following Anteroapical Myocardial Infarction: A Real-Time Three-Dimensional Echocardiographic Study Liam P. Ryan1, Benjamin M. Jackson1, Landi M. Parish1, Martin G. St. John Sutton2, Theodore Plappert2, Joseph H. Gorman III1, Robert C. Gorman1; 1Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA; 2Department of Medicine, Division of Cardiology, University of Pennsylvania School of Medicine, Philadelphia, PA

Aldosterone Agonist Enhances Ventricular but Not Vascular Stiffness in an Aged Canine Model of Hypertensive Heart Disease Brian Shapiro1, Theophilus E. Owan1, Margaret M. Redfield1; 1Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN

Introduction: The hypocontractile but normally perfused borderzone myocardium (BZM) has been implicated in the pathogenesis of congestive heart failure following myocardial infarction (MI). Hypothesis: We used real-time three-dimensional echocardiography (rt-3DE) to test the hypothesis that BZM dysfunction is associated with delayed systolic activation of this region. Methods: Rt-3DE was performed in 9 Dorsett hybrid sheep at baseline, immediately following a moderately sized anteroapical myocardial infarction (MI) and at 10 weeks following MI. Manual endocardial tracing was performed using Tomtec software. The BZM was defined by the 6 segments adjacent to the dyskinetic infarcted myocardium. BZM end systolic delay (ESD) was defined as the average delay with respect to the first segment to reach its minimum segmental volume. BZM systolic dyssynchrony index (SDI) was defined as the standard deviation of ESDs for a given data set. In order to normalize the data for different heart rates, phase shift was expressed as a percentage of the cardiac cycle duration. Results: QRS widening did not occur in any experimental subject. A statistically significant (p ! 0.05) decrement in EF occurred between all measured time points. A statistically significant (p ! 0.001) increase in ESD occurred both immediately following infarction and at 10 weeks. A statistically significant (p ! 0.05) increase in SDI occurred at 10 weeks when compared to both baseline and post-infarction values. The magnitude of change was greatest during the interval between infarction and 10 weeks follow-up in all cases. Conclusions: Longitudinal increases in BZM hypokinesis and dyssynchrony were observed in the absence of QRS widening using rt-3DE during a 10 week interval in an ovine model of apical myocardial infarction. Rt-3DE may allow for echocardiographically guided BZM resynchronization in the future.

In aged canines, induction of hypertension by renal wrapping (rwHTN) is associated with hypertrophy, LV fibrosis and increased systolic and diastolic LV and effective arterial stiffness (elastance). Deoxycorticosterone acetate (DOCA), an aldosterone analog, promotes LV fibrosis. We hypothesized that administration of DOCA to aged dogs with rwHTN would accelerate increases in LV diastolic and systolic stiffness. Methods: Old dogs (n 5 22, age 8 to 12 years) underwent renal wrapping and were followed for 8 weeks. Dogs were randomized to receive DOCA (1 mg/kg IM) during weeks 6e8 (rwHTNþDOCA, n 5 11) or not (rwHTN). Dogs were anesthetized and instrumented for pressure volume analysis during preload reduction to characterize end systolic (ESPVR; ESP 5 slope*ESVþV0) and end diastolic (EDPVR; EDP 5 aeb*EDV) pressure volume relationships and effective arterial elastance (Ea). Aortic pressure, dimension and flow were also measured to characterize the aortic elastic modulus (EM), a measure of aortic stiffness. Results: See table. The rwHTNþDOCA dogs had increased diastolic (higher EDPVR-b and smaller EDV at a common EDP of 30 mmHg (EDV30)) and systolic (higher ESPVR-slope (Ees)) stiffness. Contractility was unchanged (similar preload recruitable stroke work (PRSW)). Aortic stiffness was not increased (similar aortic EM). While arterial pressures were higher in conscious rwHTNþDOCA vs rwHTN dogs (p 5 0.01), after the preload reducing effects of anesthesia and instrumentation, rwHTNþDOCA dogs had lower LV systolic pressure (p 5 0.02), a finding consistent with their higher Ees. Increased Ees without increases in vascular stiffness led to impaired ventricular vascular coupling (decrease in Ea/Ees ratio) in rwHTNþDOCA dogs. The LV mass/ EDV ratio was greater in rwHTNþDOCA dogs. Conclusions: DOCA administration in hypertensive heart disease worsens LV systolic and diastolic stiffening without changing arterial stiffness. We speculate this is due to increased LV fibrosis. rwHTN

062 Real-Time Three-Dimensional Echocardiography To Quantify Remodeling after Infarction in Ovine Heart Failure Models Liam P. Ryan1, Hirotsugu Hamamoto1, Benjamin M. Jackson1, Landi M. Parish1, Martin G. St. John Sutton2, Theodore Plappert2, Joseph H. Gorman III1, Robert C. Gorman1; 1Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia, PA; 2Department of Medicine, Division of Cardiology, University of Pennsylvania School of Medicine, Philadelphia, PA Introduction: Magnetic resonance imaging (MRI) has been the gold-standard for the assessment of ventricular size and geometry. However, MRI is expensive, time and labor intensive, not universally available and often requires transport of human and animal subjects to remote areas of the hospital. In addition, MRI currently does not allow assessment of valvular structure and function. Hypothesis: Real-time three-dimensional echocardiography (rt-3DE) overcomes many of the limitations associated with MRI. While rt-3DE volumetric analysis has been validated in human subjects, cardiac geometry differs in many experimental animal species raising concern regarding the adequacy of volume averaging algorithms incorporated into both the two-dimensional echocardiography (2DE) and rt-3DE analysis software. Methods: Rt-3DE, 2DE and MRI were performed in 9 Dorsett hybrid sheep at baseline and at 10 weeks following apical MI. End-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were calculated independently at each time point by means of rt-3DE, 2DE and MRI. Results: Statistically significant (p ! 0.01) increases in both EDV and ESV and decreased in EF occurred as determined by all three modalities. Correlation between EDV, ESV and EF as determined by rt-3DE and MRI was excellent with R equal to 0.99. 0.99 and 0.98 respectively. Correlation between EDV, ESV and EF as determined by means of 2DE and MRI was also acceptable with R equal to 0.83, 0.87 and 0.84 respectively. Conclusions: Left ventricular volumes as determined by rt-3DE are nearly identical to those determined by MRI. Those determined by 2DE are also very similar. Both echocardiographic techniques are accurate in a well-established ovine model of CHF which has become an increasingly prominent platform for heart failure research. Left Ventricular Volumes and EF Before and After Apical MI

EDV (mm3) 3DE MRI 2DE ESV (mm3) 3DE MRI 2DE EF (%) 3DE MRI 2DE

Basline

10 Weeks Post-MI

53.0 55.3 69.0

149.6 149.0 156.1

22.1 24.3 37.3

123.1 122.0 126.9

58.5 56.1 46.0

18.8 18.9 19.1

EM (dyne/cm2) EDPVR-b EDPVR-a EDV at EDP 5 30 (ml) ESPVR-slope (Ees, mmHg/ml) PRSW (erg*cm-3*103) Ea/Ees LV mass/BW (g/Kg) LV mass/EDV (g/ml)

0.71 0.053 1.31 79 4.83 79 1.81 5.6 2.9

6 6 6 6 6 6 6 6 6

0.05 0.009 0.42 6 0.81 4 0.35 0.3 0.3

rwHTNþDOCA

p

6 6 6 6 6 6 6 6 6

0.91 0.02 0.27 0.007 0.047 0.97 0.01 0.66 0.048

0.69 0.105 0.70 56 13.19 79 0.76 5.8 4.2

0.14 0.018 0.32 5 5.93 6 0.15 0.3 0.6

064 ECG-Gated Multislice Computed Tomography To Assess Right Ventricular Function Marc A. Simon1, Christopher Deible2, Navin Rajagopalan1, Shobhit Madan2, Orly Goitein2, Angel Lopez-Candales1, Michael Mathier1, Joan Lacomis2; 1 Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA; 2Department of Radiology, University of Pittsburgh, Pittsburgh, PA Background: Assessment of right ventricular (RV) function is essential for management of heart failure (HF) and pulmonary hypertension (PH). Standard methods to evaluate RV function are limited to 2D echocardiography (echo) and right heart catheterization (RHC). Objective: To develop an ECG-gated CT protocol to provide 3D anatomical and functional data of the RV. Methods: A total of 17 pts (age 51 6 11, 7 males, mean PA pressure range 17e79 mmHg) underwent RHC, 2D echo with RV fractional area change (FAC) calculated from the apical 4-chamber view and ECGgated multislice CT of the chest with IV contrast timed to opacify the RV. RV CT protocol obtained on GE Lightspeed 16 (n 5 13) or VCT 64 slice (n 5 4) scanners: initial test bolus of IV contrast to time for peak pulmonary artery (PA), pulmonary vein (PV) and ascending aortic (AA) enhancement; then, after injection of scanning bolus, ECG-gated, single breath hold, helical acquisition with 0.63 mm (64-slice) or 1.25 mm (16-slice) collimation through the chest. Scans were reconstructed in 20 phases (5e95% R-R q 5%). RV EDV, ESV, EF were obtained utilizing GE ADW 5.2 software after manual endocardial tracings. Results: RV CT protocol was successful in all pts, regardless of heart rate. RV EF calculated by CT correlated well with RV FAC calculated by 2D echo (figure, R2 5 0.589, p 5 0.0003) and with cardiac index from RHC (R2 5 0.612, p 5 0.0002). RV FAC by echo was O0.35 in 7 pts and !0.35 in 10 (mean 0.51 6 0.12 vs. 0.20 6 0.05, p ! 0.0005). Transit time of IV contrast to PA, to PV, and from PA to PV was significantly shorter in RV FAC O0.35 pts (13 6 2 sec vs. 17 6 3 sec, p 5 0.02; 17 6 3 sec vs. 26 6 3 sec, p ! 0.0005; 9 6 3 sec vs. 4 6 1 sec, p 5 0.001). Conclusions: ECG-gated multislice CT is

S20 Journal of Cardiac Failure Vol. 12 No. 6 Suppl. 2006 a technically feasible method to assess RV function. RV EF calculated by CT correlates well with RV FAC calculated by echo and cardiac index measured by RHC. Transit time of IV contrast through the pulmonary circuit by the RV CT protocol distinguishes normal from abnormal RV function.

065 The Metabolic Syndrome in Patients with Heart Failure with Normal Ejection Fraction Rajesh K. C. Vindhya1, Raja Wajahat1, Inna Titova1, Rose Cohen1, Mathew S. Maurer1; 1The Clinical Cardiovascular Research Laboratory for the Elderly, Columbia University College of Physicians & Surgeons, New York, NY Background: The metabolic syndrome (MetSyn) is characterized by a group of metabolic risk factors. Subjects with heart failure and a normal ejection fraction (HFNEF) constitute a heterogenous group of patients many of whom have concomitant co-morbid conditions that could cause or contribute to the heart failure syndrome. Accordingly, we sought to evaluate the prevalence of the metabolic syndrome in a cohort of subjects with HFNEF and compare cardiovascular phenotype stratified by the presence or absence of the metabolic syndrome. Methods: Metabolic syndrome was defined by three or more of the following conditions: 1) Diabetes Mellitus 2) Hypertension 3) Obesity (BMIO 30) 4) TriglyceridesO 150 and/or 5) HDL! 40. Subjects underwent freehand three-dimensional echocardiography (3DE) to evaluate LV volumes and mass, with these variables being combined with either cuff pressure of central aortic pressure, which were derived by tonometric analyses of radial waveforms (Sphygmocor System, AtCor Medical, Sydney, Australia) to derive non-invasive estimates of ventricular vascular properties. Results: Among 46 Subjects (age 71 6 12 years, 80% women) with HFNEF, 28 (61%) met criteria for the metabolic syndrome. There was no difference in age, gender nor race between HFNEF subjects with or with the MetSyn. Cardiac structure, function and arterial properties between cohorts did not differ (see table below) Conclusions: There is a high prevalence of the metabolic syndrome in elderly subjects with HFNEF. However, cardiovascular phenotype does not differ based on the presence of the metabolic syndrome. Further studies defining the mechanistic interaction of these two syndromes are warranted.

Parameter LV Size LVIDd (cm) LVIDs (cm) EDV (ml) ESV (ml) Myocardial Characteristics PWT (cm) LV Mass (g) RWT (cm) EDV/Mass Ratio End systolic Stress (gm/cm2) LV Function Ejection Fraction (%) Stroke Volume (ml) Cardiac Output (L/min) Arterial Properties PP (mm Hg) PP/SV (mm Hg/ml) Ea (mmHg/ml)

HFNEF þ Metabolic HFNEF without Metabolic (n 5 28) (n 5 18) 4.62 3.14 119.5 56.2

6 6 6 6

0.6 0.75 28.2 15.2

4.67 3.33 116.4 55.6

6 6 6 6

0.5 0.5 32.8 16.4

0.38 175 0.59 0.70 115

6 6 6 6 6

0.18 37 0.19 0.19 49

0.34 175 0.54 0.68 146

6 6 6 6 6

0.2 59 0.17 0.13 55

0.53 6 0.05 63.3 6 15.6 4.2 6 1.4

0.52 6 0.03 60.6 6 17.8 4.0 6 1.3

68 6 17 1.1 6 0.3 2.1 6 0.4

70 6 22 1.3 6 0.6 2.3 6 0.7

066 Increased Lung Ventilation during Exercise in Patients with Neurocardiogenic Syncope Kenneth C. Beck1, Kira Q. Stolen1, Timothy E. Meyer1, Stacia A. Merkel1; 1Clinical Applied Research, Guidant Corporation, Saint Paul, MN Abnormal physiological interactions between the cardiac and pulmonary systems can lead to abnormalities in response to exercise. To investigate abnormal responses to exercise in a patient population being treated for bradycardia, we report here data from patients enrolled in the Limiting Chronotropic Incompetence for Pacemaker Recipients (LIFE) study. Methods: Patients signed written informed consent approved by the local study center review board. Of 1532 patients enrolled, a subset of 122 underwent cardiopulmonary exercise testing (CPX) at 4 centers with CPX capability. The subset of 122 patients was not otherwise selected. After excluding tests with technical errors or obvious submaximal exercise efforts (peak Borg scale 15 or less, peak respiratory exchange ratio of !0.8 or O1.3), patterns of response to CPX testing were analyzed in 109 pts tested 30 days after implant of a Guidant INSIGNIA pacemaker. We tested for differences in response among patients with 3 categories of reasons for receiving the pacemaker device: 2nd-3rd Degree heart block (HB, N 5 21), Sinus node dysfunction (SND, N 5 77) and Neurocardiogenic syncope/Carotid Sinus Syndrome (NS/CSS, N 5 11). For this evaluation, patients were programmed to DDD with lower rate limit set at 60 BPM and rate adaptive pacing turned off. Results: Ninety four percent of the patients were NYHA I & II. Mean peak oxygen consumption (VO2pk) was 18.5 þ/ 6.4 ml/min/kg. The table shows that VO2pk was not different among HB, SND and NS/CSS groups, even after correcting for age, although the VO2pk tended to be lower and the slope of ventilation to carbon dioxide production (VE/VCO2) was highest in the NS/CSS group compared to the other groups. There was a significant negative correlation between VO2pk and VE/VCO2 slope (r 5 0.24,P 5 0.01). Conclusion: The pattern of high VE/VCO2 slope and VO2pk in range of NYHA class II & III in the NS/CSS group is consistent with heart failure patients, though clinical diagnostic information was not available in this study. Future studies are warranted to evaluate possible predictors of ventilatory response and if either rate adaptive pacing or CRT therapy may affect this response. CPX Data by implant diagnosis HB Age BMI VO2pk VE/VCO2 slope

65 29 18.8 26.3

6 6 6 6

SND 18 6 5.9 5.9*

70 28 18.9 30.1

6 6 6 6

NS/CSS 14 6 6.7 6.9

76 28 14.9 33.7

6 6 6 6

9 3 4.7 8.7*

Mean 6 SD; *indicates significant group comparisons, P ! 0.01. BMI: Body Mass index, kg/M2.

067 Invasive Characterization of Hemodynamic Events during Diastasis in Patients with Structural Heart Disease Wissam A. Jaber1, Carolyn S. P. Lam1, Lieng H. Ling2, Jae K. Oh1, Rick A. Nishimura1; 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN; 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore Introduction: Diastasis, the period of diastole between early and late filling, is often assumed to be quiescent, with balance between left atrial and left ventricular pressures (LAP, LVP). However, imbalance may occur in abnormal ventricles with prolonged LV relaxation extending into mid-diastole or continued LA inflow from the pulmonary veins in volume-overloaded states. Indeed forward flow during diastasis has been recorded on Doppler echo (mitral L wave). Studies have suggested that this mid-diastolic flow represents severely abnormal diastolic function and portends greater heart failure risk. This has never been characterized invasively. Methods: Subjects were adults undergoing cardiac catheterization, left ventriculography and Doppler echo for assessment of dyspnea. Significant valvular heart disease was excluded. Cardiac pressures were measured using micromanometer catheters and volumes determined by ventriculography. LA and LV compliance were estimated by dividing stroke volume (SV) by rise in systolic LAP and diastolic LVP respectively. The time constant of LV relaxation (t) was derived by the method of Weiss, and the time from onset of diastole to completion of relaxation was estimated as 3.5*t. Results: Twenty-one patients (43% male; age 49 6 17) were included. All had cardiomyopathy (hypertrophic 41%, hypertensive 36%, restrictive 14%, dilated 9%). Doppler mid-diastolic flow was present in 9 (43%, Gp I) and absent in 12 (Gp II). Gp I had higher mean LAP (25 6 7 vs 15 6 8 mmHg, p ! 0.01), peak systolic LAP (45 6 14 vs 25 6 16 mmHg, p 5 0.02) and end-diastolic LVP (27 6 9 vs 16 6 5 mmHg, p ! 0.01) compared to Gp II. t was similar between groups (56 6 12 vs 56 6 22 ms, p 5 0.92). LV end-diastolic volume was higher in Gp I than Gp II (165 6 39 vs 121 6 25 ml, p ! 0.01), as was SV (108 6 27 vs 81 6 23 ml, p 5 0.03). There was no difference in EF (66 6 11 vs 68 6 15%, p 5 0.68) or LV compliance (p 5 0.33). LA compliance was lower in Gp I (5.6 6 2 vs 11.3 6 6.3 ml/mmHg, p 5 0.03). In Gp I, relaxation had ended before onset of mid-diastolic flow (time from aortic valve closure 190 6 63 vs 200 6 60 ms respectively).