EXERCISE INTOLERANCE IN ELDERLY DIASTOLIC HEART FAILURE
Funded Grant
Overview
Affiliation
View All
Overview
description
Diastolic heart failure (DHF) accounts for about 50% of heart failure cases in the population equal to or > 65. However, few data are available regarding the pathophysiology and therapy of this disorder. We have shown that elderly patients with DHF have severe exercise intolerance and poor quality of life. Decreased aortic distensibility may be an important, modifiable contributor to exercise intolerance in elderly DHF patients. Aortic distensibility decreases with age, is related to exercise capacity, and is accelerated by hypertension, a common precursor to DHF. Furthermore, decreased aortic distensibility increases left ventricular (LV) load, stimulates LV hypertrophy, and impairs LV diastolic relaxation. Our pilot data suggest that elderly DHF patients have markedly decreased aortic distensibility and this correlates with their reduced exercise capacity. Angiotensin-II appears to be responsible for the changes in the aortic wall that cause decreased aortic distensibility. By blocking angiotensin-II, angiotensin-converting enzyme inhibition (ACEI) reverses these changes and improves aortic distensibility. We have recently shown that angiotensin-II antagonism improves exercise time and quality of life in patients with mild diastolic dysfunction. Enalapril provides long-acting ACEI and is available in generic formulations in March 2000. Thus, the primary aims of this study are to perform an initial crosssectional comparison of 70 elderly patients with diastolic heart failure and 30 age-matched normal subjects and then to randomize the 70 patients into a controlled, double-blind trial of ACEI to test the following specific hypotheses: 1. Elderly diastolic heart failure patients have decreased aortic distensibility compared to age and gender matched healthy normal subjects. 2. Exercise intolerance in elderly diastolic heart failure patients is associated with decreased aortic distensibility 3. ACEI in elderly heart failure patients will improve aortic distensibility, exercise tolerance, and quality of life. 4. Improvements in exercise tolerance will correlate with improvements in aortic distensibility. Principle measurements will include aortic distensibility and wall thickness by phase-contrast gradient-echo magnetic resonance imaging (MRI); maximal oxygen consumption and ventilatory anaerobic threshold by expired gas analysis; and quality of life by standardized questionnaires, and LV volumes and mass by MR1. This study will examine the role of decreased aortic distensibility in the pathophysiology of exercise intolerance in elderly patients with diastolic heart failure and determine whether aortic distensibility, exercise intolerance, and quality of life can be improved with the ACEI enalapril, which is well-tolerated in the elderly and is available in generic formulations.
