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This review critically synthesizes the current biomarker landscape and proposes an integrative framework to address the significant translational gaps between biomarker science and clinical practice. We conducted a comprehensive critical review, analyzing established and emerging biomarkers, including cardiac troponins, natriuretic peptides, and inflammatory and fibrotic markers, within the context of biological confounders, etiology-specific challenges, and clinical implementation barriers. Through thematic synthesis, we developed the novel C.A.L.I.B.R.A.T.E. framework to structure biomarker integration. While high-sensitivity assays have improved detection, they reveal chronic elevations in conditions like renal dysfunction, aging, and heart failure, reducing specificity and complicating acute diagnosis. Emerging biomarkers (eg, sST2, galectin-3) offer prognostic insight but lack therapeutic guidance and specificity. Etiology-specific puzzles (eg, myocarditis, COVID-19, MINOCA) highlight the limitations of isolated biomarker interpretation. The C.A.L.I.B.R.A.T.E. framework addresses these gaps by integrating Clinical context, Assay characteristics, Likelihood, Injury mechanism, Biomarker profiles, Rule-out\/in thresholds, Adjunctive tests, Time kinetics, and Etiologies &amp; comorbidities. The future of myocardial injury management depends on shifting from isolated biomarker measurement to integrated, algorithm-driven interpretation. The C.A.L.I.B.R.A.T.E. framework provides a structured pathway for personalized diagnostic reasoning, bridging the translational chasm and advancing precision cardiology through context-dependent, multi-modal data synthesis.<\/jats:p>","DOI":"10.1177\/11795468261454738","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T09:00:53Z","timestamp":1781168453000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward Precision in Myocardial Injury Management: A Critical Synthesis and the C.A.L.I.B.R.A.T.E. 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