Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta‐Analysis and Systematic Review

Abstract

BackgroundThere has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF). However, a comprehensive evaluation of MRA effects on left ventricular (LV) structure and function in these patients is lacking. In this meta‐analysis, we evaluated the effects of MRAs on LV structure and function among patients with diastolic dysfunction or HFPEF.Methods & ResultsRandomized, controlled clinical trials evaluating the efficacy of MRAs in patients with diastolic dysfunction or HFPEF were included. The primary outcome was change in E/e’, a specific measure of diastolic function. Secondary outcomes included changes in other measures of diastolic function, LV structure, surrogate markers for myocardial fibrosis (carboxy‐terminal peptide of procollagen type I [PICP] and amino‐terminal peptide of pro‐collagen type‐II [PIIINP]), blood pressure, and exercise tolerance. In the pooled analysis, MRA use was associated with significant reduction in E/e’ (weighted mean difference [WMD] [95% confidence interval {CI}]: −1.68 [−2.03 to −1.33]; P<0.0001) and deceleration time (WMD [95% CI]: −12.0 ms [−23.3 to −0.7]; P=0.04) as compared with control, suggesting and improvement in diastolic function. Furthermore, blood pressure and levels of PIIINP and PICP were also significantly reduced with MRA therapy with no significant change in LV mass or dimensions.Conclusion MRA therapy in patients with asymptomatic diastolic dysfunction or HFPEF is associated with significant improvement in diastolic function and markers of cardiac fibrosis without a significant change in LV mass or dimensions.

Biomarker‐based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo‐DHF trial

“…Previous clinical studies demonstrate that spironolactone reduces the circulating serum levels of PICP in asymptomatic patients with LVDD . This study reports for the first time that spironolactone treatment is associated with a reduction in serum PICP in patients with HFpEF.…”

Tailoring mineralocorticoid receptor antagonist therapy in heart failure patients: are we moving towards a personalized approach?

“…Despite potential LS improvement in patients randomized to spironolactone, this treatment was not associated with significant differences in measures of LV mass or dimensions in the 239 patients with echocardiographic follow‐up at 12–18 months after randomization . A meta‐analysis of MRA trials in HFpEF found a potential association with diastolic improvement in patients treated with MRAs as assessed by E/E′, deceleration time and E/A ratio, and, in addition, cardiac collagen markers were significantly reduced with MRA therapy …”

Insuficiencia cardíaca con función preservada. Revisión del tema y comunicación de la experiencia española

“…De forma global, revisando distintos metaanálisis, se podría decir que los AA no demuestran reducción de mortalidad, aunque sí reducen hospitaliza-ciones, aportan mejoría en calidad de vida y mejoran parámetros de disfunción diastólica (38,39) .…”