Author: Kristina Lambrakis
Lambrakis, Kristina, 2025 Will Evolving the Universal Definition of Myocardial Infarction Improve Care and Outcomes?, Flinders University, College of Medicine and Public Health
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The definition, diagnosis and treatment of myocardial infarction (MI) reflects substantial advances in science, technology and clinical practice. Originally, it was a poorly understood and typically fatal condition. Early definitions were founded on observations post-event, based on the pattern of sequelae. With the advent of new technologies such as electrocardiograms and biochemical markers, diagnostic specificity was enhanced, providing opportunity to revolutionise MI care. With increased diagnostic capability came improved models of care and therapies, including coronary care units, reperfusion therapies and secondary prevention strategies.
Alongside, the need to define MI in a unified way arose, leading to the establishment of the Universal Definition of MI in 2007. This universal definition, which has evolved over years and is now in its fourth iteration, has sought to delineate MI into various diagnostic classifications. It denotes cardiac troponin as the cornerstone biomarker, with diagnostic criteria for all classifications primarily based on troponin results alongside evidence of acute myocardial ischemia.
Whilst troponin elevations were historically able to identify those who would benefit from coronary reperfusion (I.e. MI due to atherosclerotic plaque rupture or disruption), the advancements in troponin assays have now led to the development and the widespread adoption of highly sensitive troponin assays. Recognisably, increased sensitivity has come at the cost of specificity. As such, the challenge now faced in contemporary practice is that troponin can now be elevated for a variety of reasons not due to the presence of a coronary thrombus, and thus where the current evidence for MI treatment is unlikely to provide benefit.
The latest universal definition of MI has aimed to respond to this, by recognising troponin elevation due to alternative causes, thus teasing out classifications of myocardial injury and infarction further. However there are several challenges that persist including diagnostic ambiguity and complexity for classification and delineation in practice, vulnerability to inconsistency in its application as well as limited focus on prognostication.
Accordingly, this thesis aimed to evaluate whether the continued evolution of the universal definition of MI will improve care and outcomes. It explored the impacts of the introduction of high sensitivity troponin, as the key test underpinning the definition, as well as the clinical utility of the definition. Further it explored novel approaches to support its use in clinical practice, and both explored and proposed potential treatment strategies for key diagnostic classifications that currently lack an evidence-based to inform care. This has been undertaken through a review of the literature (chapter 1), a series of large-scale retrospective data analysis (chapters 2-6), a clinical trial design and protocol proposal (chapter 7) as well as a cluster-randomised trial (n= >14,000) (chapter 8).
The results of this thesis have demonstrated those with MI and injury experience poor outcomes and have evidence gaps in their care. One of the first key steps to improving care and outcomes is diagnostic classification, which remains challenging for the various types of MI and myocardial injury denoted by the Fourth Universal Definition of MI, even among cardiac experts. New technologies such as machine learning have potential to improve diagnostics and clinical decision making, however the continued evolution of the universal definition of MI in its current approach is unlikely to impact care and outcomes. Whilst there is some value in having a pathophysiological framework for understanding the mechanisms of troponin elevation, this approach has limited ability to instil action. Whilst novel technologies appear to have some potential to improve its clinical utility, the approach to the universal definition of MI likely requires re-imagining to truly impact and improve clinical care and outcomes.
Keywords: Myocardial Infarction, Myocardial Injury, Universal Definition, Artificial Intelligence, Clinical Decision Support, Diagnosis, Risk, Acute Coronary Syndromes, Troponin, High Sensitivity, Cardiac Care, Cardiac Outcomes
Subject: Cardiology thesis
Thesis type: Doctor of Philosophy
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Professor Derek Chew