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

Kelsey M Flint, Sanjiv J Shah, Eldrin F Lewis, David P Kao, Kelsey M Flint, Sanjiv J Shah, Eldrin F Lewis, David P Kao

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.

Trial registration: ClinicalTrials.gov NCT00094302.

Keywords: HFpEF; Health status; Heart failure; Hospitalization; Mortality.

Conflict of interest statement

None declared.

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1
Figure 1
Changes in (A) serum potassium, (B) serum creatinine, and (C) systolic blood pressure (SBP) by HFpEF phenotype and treatment arm.
Figure 2
Figure 2
A. Association of HFpEF phenotypes with time to Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) and I‐PRESERVE primary outcomes. All hazard ratios (HR) are calculated with Phenotype A chosen as the reference (i.e. HR 1.0). B. Association of the HFpEF phenotypes in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) with time to all‐cause, CV, HF, and non‐CV hospitalization. All hazard ratios (HR) are calculated with Phenotype A chosen as the reference (i.e. HR 1.0).
Figure 3
Figure 3
Baseline Kansas City Cardiomyopathy Questionnaire (KCCQ) score by heart failure with preserved ejection fraction (HFpEF) phenotype and primary outcome.

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