The role of biomarkers across the care continuum in acute heart failure

Figures

• 

  Fig. 1. Pathophysiological domains of biomarkers in acute heart failure. This schematic highlights the principal biomarker domains in acute heart failure aligned with underlying biology. Fibrosis/remodeling (IGF1, IGFBP7, galectin-3, soluble ST2), inflammation/oxidative stress (hsCRP, IL-6, GDF15), and hemodynamic stress (BNP, NT-proBNP, MR-proANP) capture structural and functional cardiac stress. Myocardial injury is detected by high-sensitivity troponins, while neurohormonal activation is reflected by renin–aldosterone, copeptin, and chromogranin A. Kidney dysfunction (BUN, creatinine, CA-125, adrenomedullin) and emerging renal stress markers (NGAL, NAG, KIM-1, cystatin C) illustrate the cardio-renal axis. Omics and AI biomarkers represent the next frontier, integrating multi-omics and digital tools for precision phenotyping

• 

  Fig. 2. Proteolytic processing of ANP and BNP prohormones and assay-detectable biomarker fragments in acute heart failure. In atrial cardiomyocytes, pro-ANP is cleaved by the transmembrane serine protease corin to yield biologically active ANP (amino acids 99–126) and an N-terminal fragment. Because ANP is rapidly cleared, clinical assays instead measure the more stable mid-regional pro-ANP fragment (MR-proANP, amino acids 1–98). In ventricular cardiomyocytes, proBNP₁₋₁₀₈ is normally processed by the proprotein convertase furin (and/or corin) to generate biologically active BNP₁₋₃₂ (amino acids 77–108) and the N-terminal fragment NT-proBNP (amino acids 1–76). However, in advanced heart failure, O-linked glycosylation near the cleavage site (Thr71) may impair processing, resulting in secretion of intact proBNP₁₋₁₀₈. Because proBNP contains epitopes recognized by both BNP and NT-proBNP immunoassays, measured concentrations represent a composite of BNP, NT-proBNP, unprocessed proBNP, and truncated fragments such as BNP₃₋₃₂. This circulating molecular heterogeneity—and the overlapping assay targets—highlights the biological complexity of natriuretic peptides and underscores the importance of…

• 

  Fig. 3. Biomarkers across the clinical timeline in acute heart failure. The clinical significance of biomarkers in acute heart failure evolves with the phase of care. In the emergency and pre-hospital phase, natriuretic peptides and cardiac troponins support rapid diagnosis, triage, and initial risk stratification, with select emerging biomarkers potentially aiding diagnostic uncertainty. During hospitalization, biomarkers refine prognosis, inform congestion assessment, and help interpret renal function changes. In the predischarge phase, persistently elevated biomarker concentrations or insufficient natriuretic peptide decline identify patients at high early post-discharge risk. During post-discharge follow-up, biomarker trajectories further characterize ongoing myocardial stress, fibrotic signaling, and long-term prognosis, supporting individualized follow-up strategies