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.