From CK-MB to MicroRNAs: Evolving Biomarker Strategies for Early Diagnosis of Myocardial Infarction

Abstract

Myocardial infarction (MI) remains a major cause of morbidity and mortality worldwide, and accurate early diagnosis is
critical to improving clinical outcomes. High-sensitivity cardiac troponins (hs-cTn) are the current gold standard biomarkers
due to their excellent sensitivity, yet they have limitations including delayed elevation in very early infarction and reduced
specificity in patients with renal dysfunction or non-ischemic myocardial injury. This systematic review evaluated the
diagnostic performance of traditional biomarkers (CK, CK-MB, myoglobin, hs-cTn) and emerging molecular approaches
including circulating microRNAs (miRNAs) and multi-marker strategies. Seven studies and one meta-analysis were
included, encompassing over 23,000 patients. Classical biomarkers such as CK and CK-MB demonstrated limited sensitivity
but retained niche value in peri-procedural MI due to higher specificity, with CK-MB achieving up to 96% specificity.
High-sensitivity troponins provided superior early detection with sensitivities approaching 90% but showed reduced
positive predictive value in unselected emergency department populations. Circulating miRNAs, particularly miR-499 and
miR-133a, achieved pooled sensitivities and specificities around 0.88, highlighting their potential for ultra-early MI detection.
Furthermore, computational models like the ARTEMIS algorithm integrating hs-cTn with clinical variables achieved AUCs
of 0.92–0.98, surpassing traditional threshold-based diagnostics and enabling personalized probability-based assessment.
Overall, the findings suggest that while hs-cTn remains the primary diagnostic biomarker, combining it with molecular
markers and advanced computational models can improve early diagnosis, specificity, and clinical decision-making in
myocardial infarction.