MECHANISMS OF DIASTOLIC HEART FAILURE IN AGING

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DESCRIPTION: (From application) Congestive heart failure in the presence of normal or near normal left ventricular systolic function is referred to as diastolic heart failure. According to the applicant, it is thought that at least 50% of patients older than 65 years hospitalized with heart failure in 1995 (over 350,000 patients), had primary diastolic heart failure. Rates of re-hospitalization and costs associated with diastolic heart failure are equivalent to those of systolic heart failure, although mortality is lower. Despite its prevalence, the physiology of diastolic failure is poorly understood, the optimal diagnostic strategy has yet to be defined, and no therapy has been shown to lower the mortality of the disease. The research phase of this proposal, which is in four parts, will examine the roles of volume status, arterial stiffness, and myocardial relaxation in the pathophysiology of diastolic dysfunction in an elderly population. In Part 1, the effects of lowering intracardiac filling pressures on cardiac output will be measured in a group of patients with diastolic heart failure and age matched controls. Part 2 will determine the relationship between arterial stiffness and myocardial relaxation velocity in a similar group, using invasive measurements of intravascular pressures. In Part 3, hypertensive patients over age 65 years and age-matched controls will be studied using non- invasive measurements of pulsatile hemodynamics and myocardial relaxation validated in Part 2. The impact of vasodilators on these measurements will be tested in order to determine whether disparate pharmacological effects on arterial stiffness lead to different effects on myocardial relaxation. Using the results of these three studies, a treatment protocol will be designed which will allow development of a therapeutic plan individualized to the underlying physiological abnormalities in each patient with diastolic heart failure. The treatment protocol will target filling pressures, arterial impedance, and timing of reflected arterial pressure waves. This protocol will then be compared with standard care in a randomized fashion, in order to determine whether this strategy improves re-hospitalization rate, symptoms, quality of life, and exercise tolerance in patients with diastolic heart failure.