SummaryBackground: Diastolic dysfunction is common in the elderly. Increased myocardial fibrosis, a major determinant of diastolic function, has been observed with advancing age. Spironolactone prevents age-related increases in myocardial fibrosis in old normotensive rats.Hypothesis: Spironolactone, via its antifibrotic activity, can improve diastolic function in the elderly with isolated diastolic dysfunction.Methods: The study was a prospective, double-blind, randomized, placebo-controlled trial. Thirty elderly subjects between 60 and 85 years of age with isolated diastolic dysfunction and no contraindications for spironolactone were randomized to 25 mg/day of spironolactone or placebo for 4 months. Mitral E/A and deceleration time, plasma levels of carboxy-terminal of procollagen type I (PICP), and brain natriuretic peptide (BNP) were measured at baseline and at the end of 4 months. Plasma level of potassium was also monitored to prevent clinically significant hyperkalemia.Results: There was no serious adverse event or clinically significant hyperkalemia in the spironolactone group. Compared with baseline values, spironolactone significantly improved mitral E/A ratio (0.71 ± 0.08 vs. 0.84 ± 0.19, p = 0.025) and deceleration time (285.5 ± 73.1 vs. 230.0 ± 54.7, p = 0.035). There were no significant differences in the magnitude

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