Myocardial Fibrosis in Cardiovascular Disease: An Integrative Biomarker-Imaging Framework Linking Molecular...

Background: Myocardial fibrosis (MF) is a dynamic remodeling process characterized by excessive extracellular matrix (ECM) deposition, fibroblast activation, and dysregulated matrix turnover. Although initially reparative, persistent fibrotic remodeling promotes myocardial stiffening, electrical instability, and progressive cardiac dysfunction across diverse cardiovascular diseases. Circulating biomarkers reflecting collagen synthesis, degradation, proteolytic regulation, and inflammatory activation have emerged as potential tools for assessing fibrotic activity and risk stratification. Methods: This targeted narrative review was based on manually guided searches of PubMed and Scopus, supplemented by citation chaining and inclusion of landmark mechanistic and translational studies. Publications addressing myocardial extracellular matrix remodeling, circulating fibrosis-related biomarkers and imaging-derived fibrosis phenotypes were selected for qualitative synthesis. Results: Myocardial fibrosis reflects interconnected inflammatory, neurohormonal, oxidative, and extracellular matrix remodeling pathways. Among circulating biomarkers, C-terminal propeptide of procollagen type I (PICP) showed the most consistent association with myocardial collagen burden and adverse outcomes, whereas carboxy-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), galectin-3, osteopontin, soluble suppression of tumorigenicity 2 (sST2), and natriuretic peptides provided more context-dependent signals. Standalone interpretation remains limited by restricted cardiac specificity, renal dysfunction, systemic inflammation, assay heterogeneity, and lack of standardized thresholds. Integration with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE), T1 mapping, and extracellular volume (ECV) may improve biological and structural phenotyping. Conclusions: Circulating biomarkers capture complementary dimensions of myocardial remodeling but cannot replace structural imaging. We propose an updated, hypothesis-generating biomarker-imaging framework integrating inflammatory activation, collagen turnover, matrix quality, hemodynamic stress, and structural imaging to support phenotypic stratification and future validation of antifibrotic strategies.