Beyond troponin: emerging biomarker strategies to differentiate type 1 from type 2 myocardial infarction

The widespread adoption of high-sensitivity cardiac troponin (hs-cTn) assays has markedly improved the detection of myocardial injury, but at the cost of reduced specificity for atherothrombotic type 1 myocardial infarction (T1MI). Therefore, troponin-positive presentations increasingly reflect heterogeneous conditions, including supply-demand mismatch-related type 2 myocardial infarction (T2MI) and acute or chronic non-ischemic myocardial injury, creating major diagnostic and therapeutic challenges in time-sensitive clinical pathways. Because the current distinction between T1MI and T2MI largely relies on clinical context and expert adjudication, there is growing interest in circulating biomarkers that could refine etiologic classification, support early triage decisions, and improve risk stratification. In this narrative review, we synthesize contemporary evidence on established and emerging biomarker strategies aimed at discriminating T1MI from T2MI, including troponin kinetics and ratios, cardiac myosin-binding protein C, biomarkers of hemodynamic and neurohormonal stress (e.g., copeptin, natriuretic peptides, MR-proANP), markers of endothelial and microvascular dysfunction (e.g., MR-proADM, CT-proET1, GDF-15), biomarkers of plaque activation, thrombosis, and proteomic/metabolomic signatures. Overall, single biomarkers provide only modest separation between T1MI and T2MI, whereas performance improves when biomarkers are integrated into multivariable clinical models or pragmatic multimarker combinations that capture the biological contrast between focal coronary injury and systemic stress. We conclude by proposing a practical framework for clinico-biomolecular phenotyping and highlighting the key requirements for clinical translation linked to actionable management pathways. Future studies should prioritize head-to-head comparisons in rigorously adjudicated cohorts and evaluate whether biomarker-guided pathways can safely reduce unnecessary invasive coronary angiography while preserving timely reperfusion in patients with atherothrombotic T1MI.