BACKGROUND: Changes in the cardiovascular system with age may predispose older persons to development of heart failure with preserved ejection fraction. Vascular stiffening, aortic pressure augmentation, and ventricular-vascular coupling have been implicated. We explored the potential for acute reductions in late systolic pressure augmentation to impact left ventricular relaxation in older persons without heart failure. METHODS:Sixteen older persons free of known cardiovascular disease with the exception of hypertension had noninvasive tonometry and cardiac ultrasound to evaluatecentral augmentation index (AI) and diastolic function at baseline and after randomized, blinded administration of intravenous B-type natriuretic peptide (BNP) and hydralazine in a crossover design. RESULTS: AI was significantly reduced after BNP (11.4±8.9 to -0.2±14.7%; P = 0.02) and nonsignificantly reduced after hydralazine (14.7±8.4% to 11.5±8.8%; P = 0.39). With decreased AI during BNP, a trend toward worsened myocardial relaxation by tissue Doppler imaging occurred (E' velocity pre- and post-BNP: 10.0±2.5 and 8.8±2.0cm/s, respectively; P = 0.06). There was a significant fall in stroke volume with BNP (68.5±18.3 to 60.9±18.1ml; P = 0.02), suggesting that changes in preload overwhelmed effects of afterload reduction on ventricular performance. With hydralazine, neither relaxation nor stroke volume changed. CONCLUSIONS: Acute changes in late systolic aortic pressure augmentation do not necessarily lead to improved systolic or diastolic function in older people. Preload may be a more important determinant of cardiac performance than afterload in older people with compensated ventricular function. The potential for changes in preload to impair rather than enhance left ventricular systolic and diastolic function in older people warrants further study. CLINICAL TRIALS REGISTRATION: This study is registered at clinicaltrials.gov as NCT00204984.
RCT Entities:
BACKGROUND: Changes in the cardiovascular system with age may predispose older persons to development of heart failure with preserved ejection fraction. Vascular stiffening, aortic pressure augmentation, and ventricular-vascular coupling have been implicated. We explored the potential for acute reductions in late systolic pressure augmentation to impact left ventricular relaxation in older persons without heart failure. METHODS: Sixteen older persons free of known cardiovascular disease with the exception of hypertension had noninvasive tonometry and cardiac ultrasound to evaluate central augmentation index (AI) and diastolic function at baseline and after randomized, blinded administration of intravenous B-type natriuretic peptide (BNP) and hydralazine in a crossover design. RESULTS: AI was significantly reduced after BNP (11.4±8.9 to -0.2±14.7%; P = 0.02) and nonsignificantly reduced after hydralazine (14.7±8.4% to 11.5±8.8%; P = 0.39). With decreased AI during BNP, a trend toward worsened myocardial relaxation by tissue Doppler imaging occurred (E' velocity pre- and post-BNP: 10.0±2.5 and 8.8±2.0cm/s, respectively; P = 0.06). There was a significant fall in stroke volume with BNP (68.5±18.3 to 60.9±18.1ml; P = 0.02), suggesting that changes in preload overwhelmed effects of afterload reduction on ventricular performance. With hydralazine, neither relaxation nor stroke volume changed. CONCLUSIONS: Acute changes in late systolic aortic pressure augmentation do not necessarily lead to improved systolic or diastolic function in older people. Preload may be a more important determinant of cardiac performance than afterload in older people with compensated ventricular function. The potential for changes in preload to impair rather than enhance left ventricular systolic and diastolic function in older people warrants further study. CLINICAL TRIALS REGISTRATION: This study is registered at clinicaltrials.gov as NCT00204984.
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