TREATMENT OF HEART FAILURE IN OLDER HUMANS

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This proposal will identify the extent to which a medical intervention, therapy with a beta-adrenergic receptor antagonist, will enhance the functional independence of older humans with congestive heart failure (CHF). In addition, the effect of this intervention to modify sympathetic nervous system (SNS) function will be tested as a pathophysiologic mechanism which may contribute to the response to treatment. The initial step in this intervention development study will be to define the range of physiologic characteristics of SNS function in this population relative to older humans with normal myocardial systolic function. The first hypothesis to be tested is that compared to older humans with normal myocardial contractility, older humans with impaired myocardial contractility have a disproportionate increase in SNS activity in comparison to their reduction in beta-adrenergic receptor responsiveness. Two specific aims pertain to this hypothesis: Specific Aim 1: To characterize SNS function, the level of systemic SNS activity (SNSa) using compartmental analysis of 3/H-norepinephrine kinetics and cardiac and peripheral beta-adrenergic receptor function, in older humans with normal and impaired myocardial contractility. Specific Aim 2: To determine the association between myocardial contractile dysfunction and SNS function (e.g. level of SNSa and beta-adrenergic receptor responsiveness), functional measures of disability (e.g. VO/2max and treadmill exercise tolerance), and quality of life in older humans. The hypothesis to be tested in the intervention component of the proposal is the degree to which beta-adrenergic antagonist therapy suppresses SNS activity will predict the extent of improvements in myocardial contractile responsiveness and functional measures of disability and quality of life among older patients with impaired myocardial contractility. The related specific aim states: Specific Aim 3: To determine the effects of beta- antagonist therapy on myocardial contractility, SNS activity (SNSa), beta- receptor responsiveness, functional measures of disability and quality of life in older humans with myocardial dysfunction. The studies outlined in this proposal will determine the effect of beta- adrenergic antagonist therapy on physical performance, functional ability and quality of life in older humans with CHF. In addition, the pathophysiology which contributes to the response to treatment with respect to the role of SNS function in regulating myocardial contractility will also be determined.