Biomarkers for differential diagnosis of myocarditis, acute coronary syndrome, and sepsis-induced cardiomyopathy

Backgrounds Diagnosing acute myocardial injury remains a significant challenge in contemporary cardiovascular and critical care medicine. Myocarditis, acute coronary syndrome (ACS), and sepsis-induced cardiomyopathy (SICM) frequently present with overlapping features, chest pain, elevated cardiac biomarkers, and electrocardiographic abnormalities, yet require divergent management, making rapid and accurate etiological diagnosis essential for optimal patient outcomes. Methods This narrative review synthesizes current evidence on the pathophysiology and biomarker signatures of myocarditis, ACS, and SICM, and examines how these signatures can be integrated into a practical diagnostic approach for the emergency department and intensive care unit. Results High-sensitivity cardiac troponin (hs-cTn) remains the central biomarker of acute myocardial injury, but its kinetics differ across the three conditions. A steep rise and fall in ACS, a sustained moderate elevation in myocarditis, and a gradual, severity-parallel course in sepsis. Among complementary biomarkers, C-reactive protein lacks specificity, whereas procalcitonin supports the recognition of bacterial sepsis in SICM, and natriuretic peptides reflect myocardial wall stress, disproportionately elevated relative to troponin in SICM. Emerging molecular biomarkers, circulating microRNAs (like miR-4763-3p and miR-155) and extracellular matrix remodeling markers, show promise for distinguishing inflammatory from ischemic myocardial injury, but remain investigational owing to the lack of standardized assays and practical constraints on acute bedside use. Therefore diagnosis rests on an integrated, multimodal assessment. Conclusion The differential diagnosis of acute myocardial injury requires a systematic, biomarker-centered multimodal approach. Future research should prioritize the prospective validation of multi-biomarker panels and the development of rapid non-invasive tools to reduce reliance on emergency coronary angiography.