Proteomic-based biomarker discovery reveals panels of diagnostic biomarkers for early identification of heart failure subtypes

作者：Narainrit Karuna, Claire Tonry, Mark Ledwidge, Nadezhda Glezeva, Joe Gallagher, Kenneth McDonald, Chris Watson · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06563-7 · 被引用次数：5 · 研究领域：Heart Failure Treatment and Management、Cardiac Fibrosis and Remodeling、Cardiovascular Function and Risk Factors

BACKGROUND: Limited access to echocardiography can delay the diagnosis of suspected heart failure (HF), which in turn postpones the initiation of optimal guideline-directed medical therapy. Although natriuretic peptides like B-type natriuretic peptide (BNP) are valuable biomarkers for diagnosing and managing HF, the utility of combining BNP with other blood-based biomarkers to predict subtypes of new-onset HF remains underexplored. OBJECTIVES: This study sought to investigate and evaluate the diagnostic significance of adding blood-based biomarkers to BNP for identifying heart failure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), with the goal of enhancing diagnostic assays beyond BNP measurements. METHODS: We identified candidate blood protein biomarkers using untargeted proteomics workflows from a cohort of individuals recruited to the STOP-HF trial who were at risk of HF and subsequently developed either HFpEF or HFrEF over time ("HF progressors"; n = 40). Candidate biomarkers were verified in an independent cohort (n = 52) from a community-based rapid access HF diagnostic clinic. The biological processes associated with these proteins were assessed, and the diagnostic values of biomarker panels were evaluated using a machine learning approach. RESULTS: Within HF progressors, we identified 3 proteins associated with HFpEF development: vascular cell adhesion protein 1 (VCAM1), insulin-like growth factor 2 (IGF2), and inter-alpha-trypsin inhi...