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Paradoxical blunting of the central pulse pressure response to exercise in patients with chronic kidney disease
S278
Heart, Lung and Circulation 2009;18S:S1–S286
Abstracts
ABSTRACTS
Conclusion: HA is a poorly recognized but important cause of PHBP in treated COA. Z-scores are important in identifying HA Interventional therapy of HA can resolve PHBP significantly by improving Z-scores (more so than gradients). doi:10.1016/j.hlc.2009.05.682 637 MECHANISMS OF AGE-RELATED BLOOD PRESSURE CHANGE IN A CROSS-SECTIONAL COHORT OF 1888 CARDIOLOGY OUTPATIENTS Mayooran Namasivayam 1,2, , Audrey Adji 1 , Michael F. O’Rourke 1,2 1 St.
Vincent’s Clinic, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia 2 University of New South Wales, Sydney, NSW, Australia Increasing aortic blood pressure contributes to rising morbidity and mortality with ageing. Haemodynamic consequences of aortic stiffening are responsible, but the relative importance of the incident and reflected pressure waves is debated. Aortic pressure waveforms were determined in 1888 cardiovascular outpatients (age 18–101 years) using a generalised transfer function applied to radially recorded waveforms obtained with applanation tonometry. Agerelated changes in the incident (P1) and reflected wave (AP) were observed, and their relative contribution to elevation in aortic systolic and pulse pressure per year of life was quantified using product of coefficient mediation analysis. Analyses were repeated after control for height, weight, heart rate and mean arterial pressure. AP increases across the entire lifespan in both genders. P1 appears to increase later in life in males compared to females. In males age <60, AP is the main factor elevating aortic systolic and pulse pressure. In females age <60, both AP and P1 are equivalent. In males and females age >60, both AP and P1 appear equivalent. The importance of the P1 and AP in the elevation of pulsatile aortic pressure appears to be affected by both age and gender in a clinical cohort. This finding is similar to our recently reported observations in a large healthy cohort, where irrespective of gender, AP was the dominant factor in subjects age <60, and both AP and P1 were equivalent at age >60. The importance of wave reflection in this clinical cohort may be underestimated, however, due to widespread use of vasodilator therapy. doi:10.1016/j.hlc.2009.05.683
638 MODELLING STUDY OF CHANGE IN AORTIC PRESSURE AND FLOW WAVEFORMS WITH AGE Audrey Adji 1,2, , Michael F. O’Rourke 2,3 , Alberto Avolio 1 1 Australian School of Advanced Medicine, Macquarie University, Sydney, Australia 2 St. Vincent’s Clinic, Sydney, Australia 3 University of New South Wales, Sydney; NSW, Australia
Non-invasive estimation of central aortic pressure has enabled interpretation of age-related changes in the pressure waveform. However, non-invasive recordings of aortic flow wave patterns have not been utilised to examine similar aging changes, although limited invasive and noninvasive recordings of aortic flow patterns have indicated changes due to altered ventricular function. The aim of this study was to determine changes in aortic flow in subjects in whom central aortic pressure is available, based on known age-related changes in aortic impedance. Aortic impedance values were obtained from studies in the literature for normal adults and calculated from central pressure and aortic flow for the elderly population. A parametric model was constructed by fitting impedance modulus and phase (as a function of frequency) with high order polynomials. Age-related functions were obtained for polynomial coefficients. Regression relations enabled the construction of age-related family of impedance curves, which were then applied to pressure waveforms in individual subjects to determine flow frequency components and to resynthesise flow waves. Impedance spectra were adequately described by 6th order polynomials over the physiological frequency and heart rate range and flow patterns were readily derived from Fourier decomposition of the central aortic pressure wave age-related model coefficients. Patterns also indicated changes in late systolic flow velocities occurring at age ranges with little change in systolic pressure augmentation. The study showed that the known age-related changes the ascending aortic impedance can be quantified by polynomials to enable acceptable non-invasive determination of aortic flow changes from the central aortic pressure wave. doi:10.1016/j.hlc.2009.05.684 639 PARADOXICAL BLUNTING OF THE CENTRAL PULSE PRESSURE RESPONSE TO EXERCISE IN PATIENTS WITH CHRONIC KIDNEY DISEASE E. Howden, D. Holland, J.S. Coombes, T.H. Marwick, J.E. Sharman The University of Queensland, Princess Alexandra Hospital, Brisbane, Australia Background: Patients with Stages 3 and 4 chronic kidney disease (CKD) have increased CV risk. We hypothesized that this may be mediated by increased arterial stiffness and exaggerated central blood pres-
Abstracts
Table 1.
S279
sure (BP) at an exercise intensity similar to daily life. Methods: Arterial stiffness (aortic pulse wave velocity [PWV], augmentation index [AIx]) and central BP were measured at rest and during moderate intensity bicycle ergometry in 38 patients with CKD (aged 59 ± 9 yrs) and 28 healthy controls (aged 53 ± 10 yrs). Central BP and arterial stiffness were estimated by applanation tonometry. Brachial BP was measured by mercury sphygmomanometer. Results: Compared with controls, resting aortic PWV, but not AIx, were significantly higher in CKD patients (Table 1), however, brachial systolic BP (SBP) was similar between groups (CKD, 130 ± 16 mmHg versus 124 ± 13 mmHg; P = 0.10). During exercise, peripheral SBP was not significantly different between groups (CKD, 172 ± 21 mmHg versus 176 ± 24 mmHg; P > 0.05) and neither were AIx, heart rate, brachial or central pulse pressure (P > 0.05 for all). Unexpectedly, the change in central pulse pressure from rest to exercise was significantly lower in CKD patients (6 ± 17% versus 23 ± 11%; P < 0.001). Moreover, aortic PWV was negatively correlated with the change in central pulse pressure from rest to exercise (r = −0.35; P = 0.01). Conclusion: Despite increased large artery stiffness and similar brachial BP, patients with CKD have a significantly reduced response in central pulse pressure during moderate intensity physical activity.
heart failure. To investigate feasibility, safety and blood pressure (BP) reduction, a first-in-man trial of renal sympathetic nerve ablation was conducted in patients with resistant hypertension (systolic BP ≥160 mmHg on ≥3 anti-hypertensive medications, including a diuretic). Methods: A percutaneous radiofrequency (RF) catheter (Symplicity® , Ardian, Inc.) was used to denervate renal sympathetics. Effectiveness of denervation was evaluated with renal noradrenaline spillover in a subgroup of patients. BP and safety data were assessed at baseline, 1, 3, 6, 9 and 12 months post-procedure. Renal angiography was performed before, immediately following and 14–30 days post-procedure. Renal Magnetic resonance angiogram (MRA) was performed 6 months postprocedure. Results: Fifty patients were enrolled at 5 Australian and European centres. The mean age was 58 ± 9 yrs, 44% female, 31% diabetic, and 22% had coronary artery disease. Baseline mean BP was 177/101 ± 20/15 mmHg, (mean 4.7 anti-hypertensive medications), eGFR 81 ± 23 mL/min/1.73 m2 . Median reduction in renal noradrenaline spillover was 49%. Post-procedure BPs were reduced by −14/−10, −21/−10, −22/−11, −24/−11 and −27/−17 mmHg at 1, 3, 6, 9 and 12 months, respectively. Among 5 anatomically ineligible patients, mean rise in BP was +3/−2, +2/+3, +14/+9, and +26/+17 mmHg at 1, 3, 6, and 9 months, respectively. One intra-procedural renal artery dissection occurred prior to RF energy delivery, without further sequelae. No other renovascular complications occurred. Conclusions: In patients with resistant hypertension, percutaneous renal sympathetic denervation results in significant and persistent reductions in BP, without significant adverse events.
doi:10.1016/j.hlc.2009.05.685
doi:10.1016/j.hlc.2009.05.686
640 PERCUTANEOUS RENAL SYMPATHETIC DENERVATION FOR TREATMENT OF RESISTANT HYPERTENSION
641 PREDICTIVE VALUE OF CAROTID AUGMENTATION INDEX AND ARTERIAL STIFFNESS ON LEFT VENTRICULAR MASS IN HEALTHY SUBJECTS
Parameter
CKD
Controls
P-value
Aortic PWV (m/s) Resting AIx (%) Exercise AIx (%)
10.4 ± 1.0 25 ± 10 7 ± 12
7.5 ± 0.3 20 ± 13 8 ± 14
<0.001 >0.05 >0.05
R. Whitbourn 1 , H. Krum 2,7 , M. Schlaich 3 , P.A. Sobotka 4,5 , J. Sadowski 6 , K. Bartus 6 , B. Kapelak 6 , A. Walton 7 , H. Sievert 8 , S. Thambar 9 , W.T. Abraham 5 , M. Esler 3 1 St.
Vincent’s Hospital, Melbourne, Australia 2 Centre of Cardiovascular Research & Education in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia 3 Baker IDI Heart & Diabetes Institute, Melbourne, Australia 4 Ardian, Inc., Palo Alto, CA, USA 5 The Ohio State University, Columbus, OH, USA 6 Jagiellonian University, Krakow, Poland 7 Alfred Hospital, Melbourne, Australia 8 CardioVascular Center Frankfurt, Frankfurt, Germany 9 John Hunter Hospital, Newcastle, Australia Background: Renal sympathetic activity is associated with systemic hypertension, chronic renal disease and
J. Otton, F. Ali, C.S. Hayward St. Vincent’s Hospital, Sydney, Australia Background: Late systolic augmentation of the central pressure waveform contributes to the after load experienced by the left ventricle. The ratio of the augmented central arterial pressure to pulse pressure (augmentation index/AIx) has been proposed as a predictor of both left ventricular hypertrophy and cardiovascular risk. Methods: We analysed registry data of 702 healthy volunteers with normal cardiac function, aged 18–81 years, who had measurement of AIx by carotid applanation tonometry and left ventricular mass and function determined by transthoracic echocardiography. Results: In univariate analysis AIx contributed weakly to left ventricular mass (LVM, r2 = 0.01, p < 0.02). How-
ABSTRACTS
Heart, Lung and Circulation 2009;18S:S1–S286
Heart, Lung and Circulation 2009;18S:S1–S286
Abstracts
ABSTRACTS
Conclusion: HA is a poorly recognized but important cause of PHBP in treated COA. Z-scores are important in identifying HA Interventional therapy of HA can resolve PHBP significantly by improving Z-scores (more so than gradients). doi:10.1016/j.hlc.2009.05.682 637 MECHANISMS OF AGE-RELATED BLOOD PRESSURE CHANGE IN A CROSS-SECTIONAL COHORT OF 1888 CARDIOLOGY OUTPATIENTS Mayooran Namasivayam 1,2, , Audrey Adji 1 , Michael F. O’Rourke 1,2 1 St.
Vincent’s Clinic, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia 2 University of New South Wales, Sydney, NSW, Australia Increasing aortic blood pressure contributes to rising morbidity and mortality with ageing. Haemodynamic consequences of aortic stiffening are responsible, but the relative importance of the incident and reflected pressure waves is debated. Aortic pressure waveforms were determined in 1888 cardiovascular outpatients (age 18–101 years) using a generalised transfer function applied to radially recorded waveforms obtained with applanation tonometry. Agerelated changes in the incident (P1) and reflected wave (AP) were observed, and their relative contribution to elevation in aortic systolic and pulse pressure per year of life was quantified using product of coefficient mediation analysis. Analyses were repeated after control for height, weight, heart rate and mean arterial pressure. AP increases across the entire lifespan in both genders. P1 appears to increase later in life in males compared to females. In males age <60, AP is the main factor elevating aortic systolic and pulse pressure. In females age <60, both AP and P1 are equivalent. In males and females age >60, both AP and P1 appear equivalent. The importance of the P1 and AP in the elevation of pulsatile aortic pressure appears to be affected by both age and gender in a clinical cohort. This finding is similar to our recently reported observations in a large healthy cohort, where irrespective of gender, AP was the dominant factor in subjects age <60, and both AP and P1 were equivalent at age >60. The importance of wave reflection in this clinical cohort may be underestimated, however, due to widespread use of vasodilator therapy. doi:10.1016/j.hlc.2009.05.683
638 MODELLING STUDY OF CHANGE IN AORTIC PRESSURE AND FLOW WAVEFORMS WITH AGE Audrey Adji 1,2, , Michael F. O’Rourke 2,3 , Alberto Avolio 1 1 Australian School of Advanced Medicine, Macquarie University, Sydney, Australia 2 St. Vincent’s Clinic, Sydney, Australia 3 University of New South Wales, Sydney; NSW, Australia
Non-invasive estimation of central aortic pressure has enabled interpretation of age-related changes in the pressure waveform. However, non-invasive recordings of aortic flow wave patterns have not been utilised to examine similar aging changes, although limited invasive and noninvasive recordings of aortic flow patterns have indicated changes due to altered ventricular function. The aim of this study was to determine changes in aortic flow in subjects in whom central aortic pressure is available, based on known age-related changes in aortic impedance. Aortic impedance values were obtained from studies in the literature for normal adults and calculated from central pressure and aortic flow for the elderly population. A parametric model was constructed by fitting impedance modulus and phase (as a function of frequency) with high order polynomials. Age-related functions were obtained for polynomial coefficients. Regression relations enabled the construction of age-related family of impedance curves, which were then applied to pressure waveforms in individual subjects to determine flow frequency components and to resynthesise flow waves. Impedance spectra were adequately described by 6th order polynomials over the physiological frequency and heart rate range and flow patterns were readily derived from Fourier decomposition of the central aortic pressure wave age-related model coefficients. Patterns also indicated changes in late systolic flow velocities occurring at age ranges with little change in systolic pressure augmentation. The study showed that the known age-related changes the ascending aortic impedance can be quantified by polynomials to enable acceptable non-invasive determination of aortic flow changes from the central aortic pressure wave. doi:10.1016/j.hlc.2009.05.684 639 PARADOXICAL BLUNTING OF THE CENTRAL PULSE PRESSURE RESPONSE TO EXERCISE IN PATIENTS WITH CHRONIC KIDNEY DISEASE E. Howden, D. Holland, J.S. Coombes, T.H. Marwick, J.E. Sharman The University of Queensland, Princess Alexandra Hospital, Brisbane, Australia Background: Patients with Stages 3 and 4 chronic kidney disease (CKD) have increased CV risk. We hypothesized that this may be mediated by increased arterial stiffness and exaggerated central blood pres-
Abstracts
Table 1.
S279
sure (BP) at an exercise intensity similar to daily life. Methods: Arterial stiffness (aortic pulse wave velocity [PWV], augmentation index [AIx]) and central BP were measured at rest and during moderate intensity bicycle ergometry in 38 patients with CKD (aged 59 ± 9 yrs) and 28 healthy controls (aged 53 ± 10 yrs). Central BP and arterial stiffness were estimated by applanation tonometry. Brachial BP was measured by mercury sphygmomanometer. Results: Compared with controls, resting aortic PWV, but not AIx, were significantly higher in CKD patients (Table 1), however, brachial systolic BP (SBP) was similar between groups (CKD, 130 ± 16 mmHg versus 124 ± 13 mmHg; P = 0.10). During exercise, peripheral SBP was not significantly different between groups (CKD, 172 ± 21 mmHg versus 176 ± 24 mmHg; P > 0.05) and neither were AIx, heart rate, brachial or central pulse pressure (P > 0.05 for all). Unexpectedly, the change in central pulse pressure from rest to exercise was significantly lower in CKD patients (6 ± 17% versus 23 ± 11%; P < 0.001). Moreover, aortic PWV was negatively correlated with the change in central pulse pressure from rest to exercise (r = −0.35; P = 0.01). Conclusion: Despite increased large artery stiffness and similar brachial BP, patients with CKD have a significantly reduced response in central pulse pressure during moderate intensity physical activity.
heart failure. To investigate feasibility, safety and blood pressure (BP) reduction, a first-in-man trial of renal sympathetic nerve ablation was conducted in patients with resistant hypertension (systolic BP ≥160 mmHg on ≥3 anti-hypertensive medications, including a diuretic). Methods: A percutaneous radiofrequency (RF) catheter (Symplicity® , Ardian, Inc.) was used to denervate renal sympathetics. Effectiveness of denervation was evaluated with renal noradrenaline spillover in a subgroup of patients. BP and safety data were assessed at baseline, 1, 3, 6, 9 and 12 months post-procedure. Renal angiography was performed before, immediately following and 14–30 days post-procedure. Renal Magnetic resonance angiogram (MRA) was performed 6 months postprocedure. Results: Fifty patients were enrolled at 5 Australian and European centres. The mean age was 58 ± 9 yrs, 44% female, 31% diabetic, and 22% had coronary artery disease. Baseline mean BP was 177/101 ± 20/15 mmHg, (mean 4.7 anti-hypertensive medications), eGFR 81 ± 23 mL/min/1.73 m2 . Median reduction in renal noradrenaline spillover was 49%. Post-procedure BPs were reduced by −14/−10, −21/−10, −22/−11, −24/−11 and −27/−17 mmHg at 1, 3, 6, 9 and 12 months, respectively. Among 5 anatomically ineligible patients, mean rise in BP was +3/−2, +2/+3, +14/+9, and +26/+17 mmHg at 1, 3, 6, and 9 months, respectively. One intra-procedural renal artery dissection occurred prior to RF energy delivery, without further sequelae. No other renovascular complications occurred. Conclusions: In patients with resistant hypertension, percutaneous renal sympathetic denervation results in significant and persistent reductions in BP, without significant adverse events.
doi:10.1016/j.hlc.2009.05.685
doi:10.1016/j.hlc.2009.05.686
640 PERCUTANEOUS RENAL SYMPATHETIC DENERVATION FOR TREATMENT OF RESISTANT HYPERTENSION
641 PREDICTIVE VALUE OF CAROTID AUGMENTATION INDEX AND ARTERIAL STIFFNESS ON LEFT VENTRICULAR MASS IN HEALTHY SUBJECTS
Parameter
CKD
Controls
P-value
Aortic PWV (m/s) Resting AIx (%) Exercise AIx (%)
10.4 ± 1.0 25 ± 10 7 ± 12
7.5 ± 0.3 20 ± 13 8 ± 14
<0.001 >0.05 >0.05
R. Whitbourn 1 , H. Krum 2,7 , M. Schlaich 3 , P.A. Sobotka 4,5 , J. Sadowski 6 , K. Bartus 6 , B. Kapelak 6 , A. Walton 7 , H. Sievert 8 , S. Thambar 9 , W.T. Abraham 5 , M. Esler 3 1 St.
Vincent’s Hospital, Melbourne, Australia 2 Centre of Cardiovascular Research & Education in Therapeutics, Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia 3 Baker IDI Heart & Diabetes Institute, Melbourne, Australia 4 Ardian, Inc., Palo Alto, CA, USA 5 The Ohio State University, Columbus, OH, USA 6 Jagiellonian University, Krakow, Poland 7 Alfred Hospital, Melbourne, Australia 8 CardioVascular Center Frankfurt, Frankfurt, Germany 9 John Hunter Hospital, Newcastle, Australia Background: Renal sympathetic activity is associated with systemic hypertension, chronic renal disease and
J. Otton, F. Ali, C.S. Hayward St. Vincent’s Hospital, Sydney, Australia Background: Late systolic augmentation of the central pressure waveform contributes to the after load experienced by the left ventricle. The ratio of the augmented central arterial pressure to pulse pressure (augmentation index/AIx) has been proposed as a predictor of both left ventricular hypertrophy and cardiovascular risk. Methods: We analysed registry data of 702 healthy volunteers with normal cardiac function, aged 18–81 years, who had measurement of AIx by carotid applanation tonometry and left ventricular mass and function determined by transthoracic echocardiography. Results: In univariate analysis AIx contributed weakly to left ventricular mass (LVM, r2 = 0.01, p < 0.02). How-
ABSTRACTS
Heart, Lung and Circulation 2009;18S:S1–S286