Dataset Information

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 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.

SUBMITTER: Flint KM

PROVIDER: S-EPMC7261552 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Flint Kelsey M KM Shah Sanjiv J SJ Lewis Eldrin F EF Kao David P DP

ESC heart failure 20200311 3

<h4>Aims</h4>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).<h4>Methods and results</h4>We analysed 1767 patients in TOPCAT from the America ...[more]

PMID: 32160420

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Project description:BackgroundComorbidity-driven microvascular inflammation is posited as a unifying pathophysiologic mechanism for heart failure with preserved ejection fraction (HFpEF). Obesity is proinflammatory and common in HFpEF. We hypothesized that unique obesity-inflammation HFpEF phenotypes exist and are associated with differences in clinical features, fibrosis biomarkers, and functional performance.MethodsPatients (n=301) from 3 HFpEF clinical trials were studied. Unsupervised machine learning (hierarchical clustering) with obese status and 13 inflammatory biomarkers as input variables was performed. Associations of clusters with HFpEF severity and fibrosis biomarkers (PIIINP [procollagen III N-terminal peptide], CITP [C-telopeptide for type I collagen], IGFBP7 [insulin-like growth factor-binding protein-7], and GAL-3 [galectin-3]) were assessed.ResultsHierarchical clustering revealed 3 phenotypes: pan-inflammatory (n=129; 64% obese), noninflammatory (n=83; 55% obese), and obese high CRP (C-reactive protein; n=89; 98% obese). The pan-inflammatory phenotype had more comorbidities and heart failure hospitalizations; higher left atrial volume, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and fibrosis biomarkers; and lower glomerular filtration rate, peak oxygen consumption, 6-minute walk distance, and active hours/day (P<0.05 for all). The noninflammatory phenotype had the most favorable values for all measures. The obese high CRP phenotype resembled the noninflammatory phenotype except for isolated elevation of CRP and lower functional performance. Hierarchical cluster assignment was independent of CRP genotype combinations that alter CRP levels and more biologically plausible than other clustering approaches. Multiple traditional analytic techniques confirmed and extended the hierarchical clustering findings.ConclusionsUnique obesity-inflammation phenotypes exist in HFpEF and are associated with differences in comorbidity burden, HFpEF severity, and fibrosis. These data support comorbidity-driven microvascular inflammation as a pathophysiologic mechanism for many but not all HFpEF patients.

Project description:AimsThe Kansas City Cardiomyopathy Questionnaire (KCCQ) is a widely used patient-reported outcome measure in heart failure (HF). The KCCQ was validated in patients with HF with reduced ejection fraction (HFrEF), leaving knowledge gaps regarding its applicability in HF with preserved ejection fraction (HFpEF). This study addresses the psychometric properties of internal consistency and reliability, construct, and known-group validity of KCCQ in both HFrEF and HFpEF. We aimed to evaluate the psychometric properties of the KCCQ and their prognostic significance in HFpEF and HFrEF, within a large prospective multinational HF cohort.Methods and resultsWe examined the 23-item KCCQ in the prospective multinational ASIAN-HF study [4470 HFrEF (ejection fraction <40%); 921 HFpEF (ejection fraction ≥50%)]. Internal consistency (using Cronbach's alpha) showed high reliability in HFrEF and HFpeF: functional status score: 0.89 and 0.91 and clinical summary score: 0.89 and 0.90, respectively. Confirmatory factor analysis in HFrEF validated the five original domains of KCCQ (physical function, symptoms, self-efficacy, social limitation, and quality of life); in HFpEF, questions measuring physical function and social limitation had strong correlation (r = 0.66) and different domains emerged. We proposed an additional physical independence summary score, especially in HFpEF (comprising the original physical function and social limitation domains), which showed good internal consistency (α = 0.89) and has comparable receiver operating characteristic curve 0.766 ± 0.037 with the clinical summary score (receiver operating characteristic curve 0.774 ± 0.037), in predicting 1 year death and/or HF hospitalization.ConclusionsOur results confirmed the robustness of the KCCQ clinical summary score in HF regardless of ejection fraction group. In the assessment of physical capacity in HFpEF, our results suggest strong interaction with social limitation, and we propose a summary score comprising both components be used.

Dataset Information

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

Publications

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

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