Recent advances in biomarkers for cardiac fibrosis

Myocardial fibrosis significantly contributes to the progression of cardiovascular diseases, ultimately leading to heart failure. Early, non-invasive diagnosis is essential for improving patient outcomes. This article reviews recent qualitative research on myocardial fibrosis biomarkers from 2022 to 2026, focusing on descriptive integration of clinical observational evidence without conducting a unified quantitative comparison of diagnostic efficacy. Initially, the article outlines the pathophysiological background of myocardial fibrosis, emphasizing both canonical TGF-β/Smad and non-canonical signaling pathways (MAPK, PI3K/Akt, Rho-like GTPase) that drive fibrotic remodeling. It further analyzes the interactions and feedback loops among core fibrogenic signaling pathways, providing a basis for interpreting dynamic changes in biomarker levels over time. The review examines current research progress, potential clinical applications, and limitations associated with circulating protein biomarkers, cardiac magnetic resonance imaging biomarkers, and emerging multi-omics molecular biomarkers. It distinguishes between biomarkers that indicate irreversible scar tissue and those that detect active, reversible fibrotic processes, clarifying their suitability for early disease detection and monitoring established disease. Furthermore, the article addresses the mechanisms of exosomal miRNA and protein packaging in activated cardiac fibroblasts and their release into peripheral circulation, elucidating the cellular origin and function of these circulating biomarkers. It also discusses the impact of post-translational modifications, such as glycosylation and phosphorylation, on biomarker stability, assay performance, and functional activity, offering insights for assay optimization and result interpretation. The review critically examines the correlation between circulating biomarkers and invasive endomyocardial biopsy-based histopathological fibrosis quantification, the diagnostic gold standard, and analyzes sources of heterogeneity in existing validation studies. It elaborates on molecular mechanisms, detection technologies, clinical validation results, and the practical value of these biomarkers in patient risk stratification, treatment response monitoring, and prognosis prediction. Specifically, it summarizes changes in circulating and imaging biomarkers following interventions like renin-angiotensin-aldosterone system inhibitors, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter 2 inhibitors. The article analyzes evidence on the temporal relationship between biomarker trajectories and cardiac functional improvements. Finally, the article explores strategies for multi-biomarker combined evaluation, proposing a framework for panel design that considers biomarker weighting, cross-class combination, redundancy reduction, and cost-performance balance. It discusses future directions for clinical translational research, aiming to provide a theoretical reference and novel perspectives for the comprehensive assessment and precise management of myocardial fibrosis.