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

Ambarish Pandey, Sushil Garg, Susan A Matulevicius, Amil M. Shah, Jalaj Garg, Mark H Drazner, Alpesh A Amin, Jarett D Berry, Thomas H. Marwick, Steven P Marso, James A de Lemos, Dharam J Kumbhani

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Abstract

Background--There 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 & Results--Randomized, 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.

Original languageEnglish (US)
Article numbere002137
JournalJournal of the American Heart Association
Volume4
Issue number10
DOIs
StatePublished - 2015

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Diastolic Heart Failure
Mineralocorticoid Receptor Antagonists
Meta-Analysis
Heart Failure
Left Ventricular Function
Fibrosis
Confidence Intervals
Blood Pressure
Peptides
Exercise Tolerance
Collagen Type II
Deceleration
Collagen Type I
Randomized Controlled Trials
Biomarkers
Therapeutics

Keywords

  • Diastolic dysfunction
  • Heart failure with preserved ejection fraction
  • Mineralocorticoid receptor antagonist

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{770a021904c84c12a476567166272e51,
title = "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 = "Background--There 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 & Results--Randomized, 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.",
keywords = "Diastolic dysfunction, Heart failure with preserved ejection fraction, Mineralocorticoid receptor antagonist",
author = "Ambarish Pandey and Sushil Garg and Matulevicius, {Susan A} and Shah, {Amil M.} and Jalaj Garg and Drazner, {Mark H} and Amin, {Alpesh A} and Berry, {Jarett D} and Marwick, {Thomas H.} and Marso, {Steven P} and {de Lemos}, {James A} and Kumbhani, {Dharam J}",
year = "2015",
doi = "10.1161/JAHA.115.002137",
language = "English (US)",
volume = "4",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Effect of mineralocorticoid receptor antagonists on cardiac structure and function in patients with diastolic dysfunction and heart failure with preserved ejection fraction

T2 - A meta-analysis and systematic review

AU - Pandey, Ambarish

AU - Garg, Sushil

AU - Matulevicius, Susan A

AU - Shah, Amil M.

AU - Garg, Jalaj

AU - Drazner, Mark H

AU - Amin, Alpesh A

AU - Berry, Jarett D

AU - Marwick, Thomas H.

AU - Marso, Steven P

AU - de Lemos, James A

AU - Kumbhani, Dharam J

PY - 2015

Y1 - 2015

N2 - Background--There 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 & Results--Randomized, 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.

AB - Background--There 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 & Results--Randomized, 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.

KW - Diastolic dysfunction

KW - Heart failure with preserved ejection fraction

KW - Mineralocorticoid receptor antagonist

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U2 - 10.1161/JAHA.115.002137

DO - 10.1161/JAHA.115.002137

M3 - Article

VL - 4

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

SN - 2047-9980

IS - 10

M1 - e002137

ER -