Abstract
Rapid diagnosis of acute myocardial infarction (AMI) is crucial for optimal patient management. Accurate diagnosis and time of onset of an acute event can influence treatment plans, such as percutaneous coronary intervention (PCI). PCI is most beneficial within 3 hours of AMI onset. MicroRNAs (miRNAs) are promising biomarkers, with potential of early AMI diagnosis, since they are released before cell death and subsequent release of larger molecules [e.g., cardiac troponins (cTn)], and have greater sensitivity and stability in plasma versus cTn regardless of timing of AMI onset. However, miRNA-based AMI diagnosis can result in false positives due to miRNA content overlap between AMI and stable coronary artery disease (CAD). Accordingly, we explored the possibility of using a miRNA profile, rather than a single miRNA, to distinguish between CAD and AMI, as well as different stages following AMI onset. First we screened a library of 800 miRNA using plasma samples from 4 patient cohorts; no known CAD, CAD, ST-segment elevation myocardial infarction (STEMI) and STEMI followed by PCI, using Nanostring miRNA profiling technology. From this screening, based on machine learning SCAD and Lasso algorithms, we identified 9 biomarkers (miR-200b, miR-543, miR-331, miR-3605, miR-301a, miR-18a, miR-423, miR-142, and miR-132) that were differentially expressed in CAD, STEMI and STEMI-PCI and explored them to identify a miRNA profile for rapid and accurate AMI diagnosis. These 9 miRNAs were selected as the most frequently identified targets by SCAD and Lasso, as indicated in the "drum-plot" model in the machine learning approach. We used age-matched patient samples to validate selected 9 miRNA biomarkers using a multiplexed ion-exchange membrane-based miRNA sensor platform, which measures specific miRNAs, and cTn as a control, simultaneously as a point-of-care device. Findings from this study will inform timely and accurate diagnosis of AMI and its stages, which are essential for effective management and optimal patient outcomes.