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CLINICAL STUDY: HEART FAILURE

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

^* Dipartimento di Scienze Biomediche e Chirurgiche, Sezione di Cardiologia Università degli Studi di Verona, Verona, Italy

Manuscript received January 22, 2002; revised manuscript received March 8, 2002, accepted April 17, 2002.

^* Reprint requests and correspondence: Dr. Mariantonietta Cicoira, Divisione Clinicizzata di Cardiologia Ospedale Civile Maggiore, P. le Stefani, 1-37126 Verona, Italy.
mariantonietta.cicoira{at}univr.it

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.

Abbreviations and Acronyms   ACE   angiotensin-converting enzyme   ANOVA   analysis of variance   CHF   chronic heart failure   E/A   E-wave/A-wave ratio   HF   heart failure   LV   left ventricular   LVEF   left ventricular ejection fraction   NYHA   New York Heart Association   RALES   Randomized ALdactone Evaluation Study   RMFP   restrictive mitral filling pattern   SP   spironolactone   VE   minute ventilation   VCO2   carbon dioxide production   VO2   oxygen consumption

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