Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients with chronic heart failure

Objectives This study was designed to assess the effects of spironolactone (SP) on left ventricular (LV) function and exercise tolerance in patients with chronic heart failure (CHF). Background In severe heart failure (HF), SP improves survival, but the underlying mechanisms are not clear. Methods We randomized 106 outpatients with HF to SP (12.5 to 50 mg/day) (group 1) or control (group 2). Complete echocardiography and cardiopulmonary exercise testing were performed at baseline and 12 months after randomization. Results Left ventricular end-systolic volume at baseline and at follow-up was 188 ± 94 ml and 171 ± 97 ml in group 1 and 173 ± 71 ml and 168 ± 79 ml in group 2 (treatment group-by-time interaction, P = 0.03). Left ventricular ejection fraction at baseline and at follow-up was 33 ± 7% and 36 ± 9% in group 1 and 34 ± 7% and 34 ± 9% in group 2 (treatment group-by-time interaction, P = 0.02). At baseline, 9 patients in group 1 and 3 patients in group 2 had a restrictive mitral filling pattern, a marker of severe diastolic dysfunction; at follow-up, 3 patients in group 1 and no patient in group 2 improved their pattern. No patient in group 1 and 4 patients in group 2 worsened their pattern (chi-square, P = 0.02). Peak oxygen consumption increased significantly in patients treated with 50 mg of SP and decreased in group 2 (17.7 ± 5.2 vs. 18.5 ± 5.9 and 19.1 ± 5.6 vs. 17.9 ± 5.3, respectively; analysis of variance, P = 0.01). Conclusions Spironolactone improves LV volumes and function; furthermore, it improves exercise tolerance at the highest administered dose. Our data might explain the mortality reduction during aldosterone antagonism in patients with HF.