It has recently been recognized that diastolic dysfunction is a common cause of CHF, particularly among the elderly. Exercise intolerance is a prominent symptom of CHF and an important cause of disability. However in contrast to CHF due to systolic dysfunction, little information is available regarding the pathophysiology of exercise intolerance in patients with diastolic dysfunction. Our previous work suggests that exercise intolerance in patients with primary diastolic dysfunction may be due to markedly limited end diastolic volume response during exercise. Aerobic exercise training in healthy subjects results in increased end diastolic volume and several other modifications which might be expected to improve exercise tolerance in patients with diastolic dysfunction. Although an intervention that improves diastolic dysfunction and exercise intolerance could have a major impact on disability in the elderly, the effect of exercise training in these patients is unknown. Therefore the primary aim of this study will be to test the hypotheses that 1) elderly patients with primary diastolic dysfunction have exercise intolerance and this is associated with diminished ability to increase end-diastolic volume (LV distensibility), and 2)exercise training will improve exercise tolerance and LV distensibility. In a cross-sectional design, 50 patients equal to or more than age 65 with primary diastolic dysfunction (clinical symptoms and signs of CHF in the presence of a normal left ventricular ejection fraction and no clinical or echocardiographic evidence of significant coronary or valvular heart disease) will be compared with age and gender matched healthy subjects. The 50 patients will then enter a randomized, controlled, single blinded 16-week intervention trial of aerobic exercise training. Maximal oxygen consumption will be measured by expired gas analysis, and end diastolic volume and stroke volume will be measured by 2-dimensional echocardiography during rest, exercise and head-up tilt. Other measurements will include health related quality of life by self- administered surveys and assays for circulating norepinephrine, angiotensin-II, aldosterone, and atrial natriuretic factor. This study will address important fundamental questions regarding the mechanisms of exercise intolerance in elderly patients with heart failure and normal left ventricular ejection fractions, and will test a physiologically rational intervention to improve diastolic function, exercise tolerance and quality of life. This information has major implications for health care and disability in the elderly.
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