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Long-term, dose-dependent effects of spironolactone on left ventricular function and exercise tolerance in patients
Mariantonietta Cicoira1, Luisa Zanolla, Andrea Rossi
1Dipartimento di Scienze Biomediche e Chirurgiche, Sezione di Cardiologia Università degli Studi di Verona, P. Le Stefani, I-37126 Verona, Italy. mariantoinetta.cicoira@univr.it
Insights
Spironolactone (SP) improves left ventricular (LV) function and exercise capacity in chronic heart failure (CHF) patients. The highest SP dose significantly enhanced peak oxygen consumption, potentially explaining survival benefits.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Spironolactone (SP) is known to improve survival in severe heart failure (HF).
- The precise mechanisms behind SP's benefits in HF remain unclear.
- Understanding these mechanisms is crucial for optimizing HF treatment.
Purpose of the Study:
- To evaluate the impact of spironolactone on left ventricular (LV) function.
- To assess the effects of spironolactone on exercise tolerance in chronic heart failure (CHF) patients.
- To explore potential mechanisms for SP's survival benefits in HF.
Main Methods:
- 106 outpatients with HF were randomized to receive either spironolactone (12.5-50 mg/day) or a control.
- Complete echocardiography and cardiopulmonary exercise testing were performed at baseline and 12-month follow-up.
- Analysis focused on changes in LV volumes, ejection fraction, diastolic function, and peak oxygen consumption.
Main Results:
- Spironolactone treatment led to significant improvements in LV end-systolic volume (p = 0.03) and ejection fraction (p = 0.02).
- A significant reduction in restrictive mitral filling patterns, indicative of diastolic dysfunction, was observed in the SP group (p = 0.02).
- Peak oxygen consumption increased significantly in patients receiving 50 mg of SP, unlike the control group (p = 0.01).
Conclusions:
- Spironolactone effectively improves left ventricular volumes and systolic function in CHF patients.
- The drug enhances exercise tolerance, particularly at higher doses.
- These findings provide insights into the mechanisms underlying mortality reduction observed with aldosterone antagonism in 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.