Effects of mineralocorticoid receptor antagonists on left ventricular diastolic function, exercise capacity, and quality of life in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials

  • Hidekatsu FukutaEmail author
  • Toshihiko Goto
  • Kazuaki Wakami
  • Takeshi Kamiya
  • Nobuyuki Ohte
Original Article


Left ventricular (LV) diastolic dysfunction is associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and contributes importantly to exercise intolerance that results in a reduced quality of life (QOL) in HFpEF patients. Experimental studies have shown that aldosterone plays a role in the genesis of myocardial hypertrophy and fibrosis, thereby enhancing LV diastolic dysfunction, and that aldosterone antagonists (mineralocorticoid receptor antagonists [MRAs]) prevents myocardial hypertrophy and fibrosis. Although the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients have been examined in randomized clinical trials (RCTs), results are inconsistent due partly to limited power with small sample sizes. We aimed to conduct a meta-analysis of RCTs on the effects of MRAs on LV diastolic function, exercise capacity, and QOL in HFpEF patients. The search of electronic databases identified 6 studies including 755 HFpEF patients. In the pooled analysis, MRAs increased early diastolic mitral annular velocity (weighted mean difference [95% CI] = 0.455 [0.232–0.679] cm/s; Pfix < 0.001) and decreased the ratio of early diastolic mitral inflow to annular velocities (− 1.474 [− 2.073 to − 0.875]; Pfix < 0.001) compared with control. There was no significant difference in change of peak exercise oxygen uptake, 6-minute walking distance, or QOL questionnaire scores between MRA and control group. In conclusion, our meta-analysis showed that MRAs improved LV diastolic function in HFpEF patients. However, the observed improvement in LV diastolic function with the use of MRAs did not translate into improved exercise capacity or QOL in these patients.


Mineralocorticoid receptor antagonists Heart failure with preserved ejection fraction Diastolic function Exercise capacity Quality of life 



This paper is not funded by any external source.

Compliance with ethical standards

Conflict of interest

Dr. Ohte has received lecture fees from Takeda Pharmaceutical Co. Ltd., Daiichi Sankyo Co., Ltd, Bayer GA, AstraZeneca plc, and Boehringer Ingelheim and grant support from Takeda Pharmaceutical Co. Ltd., Bayer GA, Daiichi Sankyo Co., Ltd, MSD, Novartis International AG, Boehringer Ingelheim, Astellas Pharma Inc., and Otsuka Pharmaceutical Co., Ltd. No other disclosures were reported.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

380_2018_1279_MOESM1_ESM.tif (121 kb)
Forest plots showing the effects of mineralocorticoid receptor antagonists (MRAs) on systolic and diastolic blood pressure (mmHg). (TIFF 120 kb)
380_2018_1279_MOESM2_ESM.tif (91 kb)
Forest plots showing the effect of mineralocorticoid receptor antagonists (MRAs) on B-type natriuretic peptide (BNP) levels (pg/ml). (TIFF 90 kb)
380_2018_1279_MOESM3_ESM.docx (20 kb)
Supplementary material 3 (DOCX 20 kb)


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Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Core LaboratoryNagoya City University Graduate School of Medical SciencesNagoyaJapan
  2. 2.Department of Cardio-Renal Medicine and HypertensionNagoya City University Graduate School of Medical SciencesNagoyaJapan
  3. 3.Department of Medical InnovationNagoya City University Graduate School of Medical SciencesNagoyaJapan

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