Effects of spironolactone treatment in elderly women with heart failure and preserved left ventricular ejection fraction

Background Although spironolactone has been shown to decrease morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction, its role in patients with heart failure and preserved left ventricular ejection fraction (HFpEF) is not well defined. In this study we investigated the mechanisms involved when elderly women with HFpEF are treated with spironolactone. Methods and Results Forty-eight women with HFpEF were enrolled in a randomized placebo-controlled trial and were assigned to 25 mg spironolactone daily (n = 24) or placebo (n = 24) for 6 months. Six-minute walk distance, clinical composite score, Doppler echocardiography, and biomarkers were determined at baseline and after 3 and 6 months of therapy. Six months of spironolactone treatment stabilized clinical symptoms, as demonstrated by significant worsening of the clinical composite score in the placebo group (P =.02). In addition, spironolactone treatment improved diastolic function by significantly increasing early diastolic tissue Doppler velocity of the lateral mitral annulus (lateral e′; P =.003) and significantly reducing the mitral peak E velocity to lateral e′ ratio (lateral E/e′; P =.0001). Finally, spironolactone favorably affected remodeling through a reduction in myocardial fibrosis measured by a reduction in type III procollagen levels (P =.035). Six-minute walk distance did not significantly improve with spironolactone treatment compared with placebo. Conclusions Spironolactone stabilizes functional capacity and symptoms and improves diastolic function, possibly through its ability to suppress type III procollagen synthesis.