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Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved
Frank Edelmann1, Rolf Wachter, Albrecht G Schmidt
1Department of Cardiology and Pneumology, Heart Center, University of Göttingen, Göttingen, Germany.
Insights
Spironolactone improved diastolic function in patients with heart failure with preserved ejection fraction (HFpEF) but did not improve exercise capacity or symptoms. Further research is needed to determine the clinical significance of these diastolic improvements in HFpEF.
Area of Science:
- Cardiology
- Internal Medicine
Background:
- Diastolic heart failure, or heart failure with preserved ejection fraction (HFpEF), is prevalent and lacks targeted therapies.
- Aldosterone may play a role in the progression of HFpEF.
Purpose of the Study:
- To evaluate the long-term efficacy and safety of aldosterone receptor blockade with spironolactone in HFpEF patients.
- To determine if spironolactone improves diastolic function and exercise capacity compared to placebo.
Main Methods:
- The Aldo-DHF trial was a randomized, double-blind, placebo-controlled study involving 422 HFpEF patients.
- Participants received either 25 mg of spironolactone or placebo daily for 12 months.
- Primary endpoints included changes in diastolic function (E/e') and maximal exercise capacity (peak VO2).
Main Results:
- Spironolactone significantly improved diastolic function (E/e') compared to placebo.
- No significant difference was observed in maximal exercise capacity (peak VO2).
- Spironolactone led to reverse cardiac remodeling and improved neuroendocrine markers but did not improve symptoms or quality of life.
Conclusions:
- Long-term aldosterone receptor blockade with spironolactone improves left ventricular diastolic function in HFpEF.
- It does not enhance maximal exercise capacity, patient-reported symptoms, or quality of life.
- The clinical relevance of improved diastolic function requires further investigation in larger cohorts.
Importance:
Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression.
Objective:
To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction.
Design And Setting:
The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction.
Intervention:
Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up.
Main Outcome Measures:
The equally ranked co-primary end points were changes in diastolic function (E/e') on echocardiography and maximal exercise capacity (peak VO2) on cardiopulmonary exercise testing, both measured at 12 months.
Results:
Diastolic function (E/e') decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, -1.5; 95% CI, -2.0 to -0.9; P < .001). Peak VO2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, -0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, -6 g/m2; 95% CI, -10 to-1 g/m2; P = .009) and improved neuroendocrine activation (N-terminal pro-brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (-15 m; 95% CI, -27 to -2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P < .001) and decreased estimated glomerular filtration rate (-5 mL/min/1.73 m2; 95% CI, -8 to -3 mL/min/1.73 m2; P < .001) without affecting hospitalizations.
Conclusions And Relevance:
In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations.
Trial Registration:
clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31.
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