Prospects for Precision Medicine in Acute Myocardial Infarction: Patient-Level Insights into Myocardial Injury and Repair

Abstract

Highlights: What Is Already Known and How This Shapes the Future Highly controlled experimental studies have illustrated the importance of ischaemia time in relation to myocyte necrosis in acute myocardial infarction. However, in humans, the situation is more complex and the relationship between clinical outcomes and ischaemia time is non-linear over a time window that is relevant to clinical presentation. Emerging techniques can characterise myocardia in individual patients, providing enhanced understanding of the heterogeneity of the response to ischemic injury. Assessments of microvascular function, including secondary changes such as intramyocardial haemorrhaging, should inform decision making regarding additional therapies. Early prediction of the nature and extent of myocardial recovery vs. irreversible injury would be useful for prognostic and therapeutic purposes in addition to guiding clinical pathways and safe resource allocation. Integrating knowledge of the status of the myocardium and the stages of activation of systemic responses should allow the development and application of therapies based on mechanistic characterisation of upstream signalling pathways and the downstream consequences of effector cells, e.g., of the innate immune system. The past decade has seen a marked expansion in the understanding of the pathobiology of acute myocardial infarction and the systemic inflammatory response that it elicits. At the same time, a portfolio of tools has emerged to characterise some of these processes in vivo. However, in clinical practice, key decision making still largely relies on assessment built around the timing of the onset of chest pain, features on electrocardiograms and measurements of plasma troponin. Better understanding the heterogeneity of myocardial injury and patient-level responses should provide new opportunities for diagnostic stratification to enable the delivery of more rational therapies. Characterisation of the myocardium using emerging imaging techniques such as the T1, T2 and T2* mapping techniques can provide enhanced assessments of myocardial statuses. Physiological measures, which include microcirculatory resistance and coronary flow reserve, have been shown to predict outcomes in AMI and can be used to inform treatment selection. Functionally informative blood biomarkers, including cellular transcriptomics; microRNAs; extracellular vesicle analyses and soluble markers, all give insights into the nature and timing of the innate immune response and its regulation in acute MI. The integration of these and other emerging tools will be key to developing a fuller understanding of the patient-level processes of myocardial injury and repair and should fuel new possibilities for rational therapeutic intervention.