Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes

Abstract Aims The aim of this study is to use six previously described heart failure with preserved ejection fraction (HFpEF) phenotypes to describe differences in (i) the biological response to spironolactone, (ii) clinical endpoints, and (iii) patient‐reported health status by HFpEF phenotype and...

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Main Authors: Kelsey M. Flint, Sanjiv J. Shah, Eldrin F. Lewis, David P. Kao
Format: Article
Language:English
Published: Wiley 2020-06-01
Series:ESC Heart Failure
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Online Access:https://doi.org/10.1002/ehf2.12660
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author Kelsey M. Flint
Sanjiv J. Shah
Eldrin F. Lewis
David P. Kao
author_facet Kelsey M. Flint
Sanjiv J. Shah
Eldrin F. Lewis
David P. Kao
author_sort Kelsey M. Flint
collection DOAJ
description Abstract Aims The aim of this study is to use six previously described heart failure with preserved ejection fraction (HFpEF) phenotypes to describe differences in (i) the biological response to spironolactone, (ii) clinical endpoints, and (iii) patient‐reported health status by HFpEF phenotype and treatment arm in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). Methods and results We analysed 1767 patients in TOPCAT from the Americas. Using 11 clinical variables, patients were classified according to six HFpEF phenotypes previously identified in the I‐PRESERVE and CHARM‐Preserved studies. Kansas City Cardiomyopathy Questionnaire (KCCQ) measured health status. All phenotypes showed increase in potassium with spironolactone, although only three phenotypes showed significant increase in creatinine, and two phenotypes showed significant decrease in systolic blood pressure. Rate of the TOPCAT primary outcome (cardiovascular death, aborted cardiac arrest, or heart failure hospitalization) differed by HFpEF phenotype (P < 0.001) but not by treatment arm within each HFpEF phenotype. Baseline KCCQ score differed by HFpEF phenotype (P < 0.001), although some phenotypes with poor health status had lower rates of the TOPCAT primary outcome, and some phenotypes with better health status had higher rates of the TOPCAT primary outcome. However, within 3/6 phenotypes, higher baseline KCCQ score was associated with lower risk of the TOPCAT primary outcome. Change in KCCQ scores at 4 and 12 months did not differ among HFpEF phenotypes overall or by treatment arm. Conclusions Complex, data‐driven HFpEF phenotypes differ according to biological response to spironolactone, baseline health status, and clinical endpoints. These differences may inform the design of targeted clinical trials focusing on improvement in outcomes most relevant for specific HFpEF phenotypes.
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spelling doaj-art-6d3cc44c9edd428c8a26f7571a5fb7762025-02-03T10:25:46ZengWileyESC Heart Failure2055-58222020-06-017381182410.1002/ehf2.12660Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypesKelsey M. Flint0Sanjiv J. Shah1Eldrin F. Lewis2David P. Kao3Division of Cardiology Rocky Mountain Regional VA Medical Center Cardiology (111), Building F2, Room 143 Aurora CO 80045 USADivision of Cardiology, Department of Medicine, Feinberg Cardiovascular Research Institute Northwestern University Feinberg School of Medicine Chicago IL USACardiovascular Division Brigham and Women's Hospital, Harvard Medical School Boston MA USADivision of Cardiology University of Colorado School of Medicine Aurora CO USAAbstract Aims The aim of this study is to use six previously described heart failure with preserved ejection fraction (HFpEF) phenotypes to describe differences in (i) the biological response to spironolactone, (ii) clinical endpoints, and (iii) patient‐reported health status by HFpEF phenotype and treatment arm in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). Methods and results We analysed 1767 patients in TOPCAT from the Americas. Using 11 clinical variables, patients were classified according to six HFpEF phenotypes previously identified in the I‐PRESERVE and CHARM‐Preserved studies. Kansas City Cardiomyopathy Questionnaire (KCCQ) measured health status. All phenotypes showed increase in potassium with spironolactone, although only three phenotypes showed significant increase in creatinine, and two phenotypes showed significant decrease in systolic blood pressure. Rate of the TOPCAT primary outcome (cardiovascular death, aborted cardiac arrest, or heart failure hospitalization) differed by HFpEF phenotype (P < 0.001) but not by treatment arm within each HFpEF phenotype. Baseline KCCQ score differed by HFpEF phenotype (P < 0.001), although some phenotypes with poor health status had lower rates of the TOPCAT primary outcome, and some phenotypes with better health status had higher rates of the TOPCAT primary outcome. However, within 3/6 phenotypes, higher baseline KCCQ score was associated with lower risk of the TOPCAT primary outcome. Change in KCCQ scores at 4 and 12 months did not differ among HFpEF phenotypes overall or by treatment arm. Conclusions Complex, data‐driven HFpEF phenotypes differ according to biological response to spironolactone, baseline health status, and clinical endpoints. These differences may inform the design of targeted clinical trials focusing on improvement in outcomes most relevant for specific HFpEF phenotypes.https://doi.org/10.1002/ehf2.12660HFpEFHealth statusMortalityHospitalizationHeart failure
spellingShingle Kelsey M. Flint
Sanjiv J. Shah
Eldrin F. Lewis
David P. Kao
Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes
ESC Heart Failure
HFpEF
Health status
Mortality
Hospitalization
Heart failure
title Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes
title_full Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes
title_fullStr Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes
title_full_unstemmed Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes
title_short Variation in clinical and patient‐reported outcomes among complex heart failure with preserved ejection fraction phenotypes
title_sort variation in clinical and patient reported outcomes among complex heart failure with preserved ejection fraction phenotypes
topic HFpEF
Health status
Mortality
Hospitalization
Heart failure
url https://doi.org/10.1002/ehf2.12660
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