This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diastolic heart failure (DHF) accounts for the majority of heart failure cases in adults over 65 years of age. Exercise intolerance is the primary chronic symptom in this disorder and is associated with severly reduced quality of life. Evidence suggest that aldosterone excess may play an important role in the pathophysiology of exercise intolerance in elderly patients with DHF. Preliminary data show that serum aldosterone is increased in elderly patients with DHF. These patients have activation of the renin-angiotensin-aldosterone system. Aldosterone is a critical promoter of excess collagen deposition in the myocardial interstitium. The balance of collagen deposition/degradation in the myocardial extracellular matrix is a major determinant of left ventricular (LV) diastolic stiffness. With aging, this balance is altered in favor of deposition, and this is exacerbated by hypertension, a common precursor to DHF, resulting in interstitial fibrosis and increased LV diastolic stiffness. This is notable, because we have previously shown that exercise intolerance in DHF is related to limited Frank-Starling response during exercise, and that this is due to incresed diastolic LV stiffness. Based on this, we conducted a 4-month, open label pilot study of spironolactone in 10 elderly patients with isolated DHF. At follow-up, there were significant (p<0.05) improvements in exercise tolerance. While strongly supportive, these data require confirmation in an adequately powered, placebo-controlled study. This study is a randomized, double-blind, placebo-controlled trial evaluating spironolactone taken for 12 months in 72 patients, age 60 years or older with isolated diastolic heart failure.
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