Novel Biomarker Strategies Refine Diagnosis of Type 1 vs. Type 2 Myocardial Infarction

The widespread use of high-sensitivity cardiac troponin (hs-cTn) assays has enhanced detection of myocardial injury, but at the cost of reduced specificity for atherothrombotic type 1 myocardial infarction (T1MI). This leads to diagnostic challenges, as troponin-positive cases often include supply-demand mismatch-related type 2 myocardial infarction (T2MI) or non-ischemic injury. Current differentiation relies heavily on clinical context, creating a critical need for circulating biomarkers that can refine etiologic classification, support early triage, and improve risk stratification in time-sensitive clinical pathways.

This narrative review synthesized contemporary evidence on established and emerging biomarker strategies for discriminating T1MI from T2MI. Researchers evaluated the utility of troponin kinetics and ratios, cardiac myosin-binding protein C, and markers of haemodynamic/neurohormonal stress (e.g., copeptin, natriuretic peptides, MR-proANP). Also covered were biomarkers of endothelial and microvascular dysfunction (e.g., MR-proADM, CT-proET1, GDF-15), markers of plaque activation, thrombosis, and proteomic/metabolomic signatures. The review aimed to propose a practical framework for clinic-biomolecular phenotyping.

The review found that single biomarkers generally provide only modest separation between T1MI and T2MI. However, diagnostic performance significantly improves when these biomarkers are integrated into multivariable clinical models or pragmatic multimarker combinations. These multimarker approaches effectively capture the biological contrast between focal coronary injury (T1MI) and systemic stress (T2MI), leading to more refined etiologic classification. The synthesis highlighted the utility of troponin kinetics and ratios, cardiac myosin-binding protein C, and neurohormonal markers like copeptin and natriuretic peptides in improving diagnostic accuracy. Furthermore, markers of endothelial dysfunction such as MR-proADM and GDF-15 show promise in distinguishing the underlying pathophysiology. The review concludes by proposing a framework for clinic-biomolecular phenotyping, emphasizing the need for actionable management pathways. > 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.