Proteomics Identify Clinical Phenotypes and Predict Functional Outcomes in Heart Failure With Preserved Ejection Fraction: Insights From VITALITY-HFpEF

作者：Christopher R. deFilippi, Palak Shah, Sanjiv J. Shah, Wendimagegn Alemayehu, Carolyn S.P. Lam, Javed Butler, Lothar Roessig, Christopher M. O’Connor, Cynthia M. Westerhout, Paul W. Armstrong, for the VITALITY-HFpEF Study Group · 发表于：Circulation Heart Failure · 年份：2024 · DOI：10.1161/circheartfailure.124.011792 · 被引用次数：10 · 研究领域：Cardiovascular Function and Risk Factors、Cardiac Fibrosis and Remodeling、Heart Failure Treatment and Management

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome that may emerge from overlapping systemic processes associated with comorbidities. We assessed whether unique clusters of circulating proteins are associated with specific clinical characteristics and functional status at baseline and follow-up in a well-phenotyped cohort of patients with HFpEF. METHODS: We evaluated 368 proteins associated with cardiovascular disease and inflammation in prerandomization blood samples from 763 VITALITY-HFpEF (Vericiguat to Improve Physical Functioning in Daily Living Activities of Patients With HFpEF) participants who had a left ventricular ejection fraction ≥45% and a heart failure decompensation event within 6 months. Proteins were clustered, and their associations with clinical characteristics, baseline, and 24-week functional outcomes (Kansas City Cardiomyopathy Questionnaire Physical Limitation Score, 6-minute walk distance [6MWD], and Fried frailty phenotype) were estimated with linear regression. Elastic net regression was used to derive a proteomic summary composite to predict changes in 24-week functional outcomes. RESULTS: Four unique protein clusters were identified, containing 24, 66, 197, and 81 proteins. At baseline, 2 protein clusters with the hub proteins caspase-3 and Dickkopf-related protein 1 were associated with increased frailty, whereas the cluster with tumor necrosis factor receptor 1 as a hub protein was associated with lower...