Diastolic heart failure accounts for over 50% of heart failure cases in the population greater than 65 and is an important health care problem for older Americans. Our current research shows that elderly patients with diastolic heart failure have severe exercise intolerance and that this improves with exercise training. However, less than 30% of the improvement is attributable to increased cardiac output. This suggests a potential role for impaired peripheral vasoregulation by compromising muscle perfusion. Our pilot data suggest that in elderly diastolic heart failure patients endothelial dependent flow mediated arterial dilation (FMAD) is substantially impaired, correlates with exercise capacity, and is increased after exercise training. The primary aims of this study are to perform an initial cross-sectional comparison of 60 elderly diastolic heart failure patients (symptomatic heart failure, a normal LV ejection fraction and no significant coronary or valvular heart disease or pulmonary disease) with matched healthy normal subjects and then to enter the patients into a randomized, controlled, single blinded trial of aerobic exercise training in order to test the following specific hypotheses: 1. Elderly diastolic heart failure patients have decreased FMAD compared to age and gender matched healthy normal subjects. 2. Exercise intolerance in elderly diastolic heart failure patients is associated with decreased FMAD. 3. Exercise training in elderly heart failure patients will improve FMAD and exercise capacity. 4. Improvements in exercise capacity will correlate with improvements in FMAD. A secondary aim is to examine relationship between FMAD and other determinants of ventricular-vascular coupling. Principle measurements include brachial artery FMAD and indexes of carotid artery stiffness by high resolution ultrasound; pulse wave velocity by tonometry; maximal and submaximal oxygen consumption and ventilatory anerobic threshold by expired gas analysis, and cardiac volumes by digital echocardiography. This study will assess the contribution of endothelial dysfunction to exercise intolerance in diastolic heart failure using a physiologically rational, widely applicable intervention.

R01AG012257

1994-09-01

2002-06-30