Andrew DeFilippis, MD

Increasingly sensitive tests for myocardial injury (e.g., troponin) have resulted in the identification of an increasing number of patients with previously undetected acute MI, primarily one etiologically distinct sub-type: type 2 MI (oxygen supply-demand mismatch not secondary to plaque disruption coronary thrombosis), as opposed to the more traditionally recognized type 1 MI (plaque disruption resulting in coronary thrombosis). 

Despite the greater prevalence, mortality, and distinct pathobiology, no prospective cohorts have identified type 2 MI as defined by international consensus.  We hypothesize that the incidence of etiologically distinct types of MI (type 1 and 2) will differ.  Furthermore, we hypothesize that the baseline risk factors that put individuals at risk for future acute myocardial injury events will differ significantly by event type with risk factors reflective of plaque morphology and thrombogenicity most closely associated with future type 1 MI events, while measures of myocardial vulnerability will be most closely associated with type 2 MI and acute non-ischemic myocardial injury.  We propose evaluating this hypothesis by adjudicating all clinical events of suspected myocardial injury in the Multi-Ethnic Study of Atherosclerosis (MESA) as MI Type 1-5, acute non-ischemic myocardial injury, or chronic non-ischemic myocardial injury, as defined by the Fourth Universal Definition of Myocardial Infarction.  Despite the frequency of myocardial injury, international consensus on the multiple types of myocardial injury, including subtypes of myocardial infarction (MI), diagnosing the etiology of an individual myocardial injury event remains a challenge for individual patients and the health care system.  While the cardiac troponin test is very sensitive and specific for detecting myocardial injury, it provides only limited information of the etiology of the myocardial injury which may be secondary to several distinct mechanisms resulting in several categories of myocardial injury (several distinct diagnoses) that necessitate different, timely, therapeutic intervention.

Development of a non-invasive, readily available, and safe test to identify and differentiate the types of myocardial injury, including acute myocardial infarction subtypes will radically alter clinical practice. Such a classifier (diagnostic) will allow for earlier, etiologically informed treatment of specific MI subtypes, resulting in the minimization of ischemic injury and limiting pharmacological and procedural interventions (and associated side effects) to only those likely to benefit. This diagnostic advance would be expected to improve the efficacy, safety, and effectiveness of treatment for over 6 million Americans presenting with signs and/or symptoms of suspected acute myocardial infarction each year.  Our laboratory has developed a unique cohort that has been phenotyped as acute thrombotic (type 1) MI, acute non-thrombotic myocardial injury (including type 2 MI) and stable coronary artery disease.   We are leveraging multiple omics platforms and calorimetry to identify perturbations specific to these acute diagnoses and testing the use of these biomarkers for the early identification and differentiation of the different myocardial injury types.