Abstract
AimsCurrent non-invasive diagnostics for acute myocardial infarction (MI) identify myocardial necrosis rather than the primary cause and therapeutic target—plaque disruption and resultant thrombosis. The aim of this study was to identify changes specific to plaque disruption and pathological thrombosis that are distinct from acute myocardial necrosis.Methods and resultsWe quantified 1,032 plasma metabolites by mass spectrometry in 11 thrombotic MI, 12 non-thrombotic MI, and 15 stable coronary artery disease (CAD) subjects at two acute phase (time of catheterization [T0], six hours [T6]) and one quiescent (>3 months follow-up) time points. A statistical classifier was constructed utilizing baseline (T0) abundances of a parsimonious set of 17 qualifying metabolites. Qualifying metabolites were those that demonstrated a significant change between the quiescent phase and the acute phase and that were distinct from any change seen in non-thrombotic MI or stable CAD subjects. Classifier performance as estimated by 10-fold cross-validation was suggestive of high sensitivity and specificity for differentiating thrombotic from non-thrombotic MI and stable CAD subjects at presentation.Nineteen metabolites demonstrated an intra-subject change from time of acute thrombotic MI presentation to the quiescent state that was distinct from any change measured in both the non-thrombotic MI and stable CAD subjects undergoing cardiac catheterization over the same time course (false discovery rate <5%).ConclusionsWe have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state after MI, from acute non-thrombotic MI, and from stable CAD. Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI.
Highlights
Acute myocardial infarction (MI) remains a leading cause of death worldwide
We have identified a candidate metabolic signature that differentiates acute thrombotic MI from quiescent state after MI, from acute non-thrombotic MI, and from stable coronary artery disease (CAD)
Further validation of these metabolites is warranted given their potential as diagnostic biomarkers and novel therapeutic targets for the prevention or treatment of acute MI
Summary
Acute myocardial infarction (MI) remains a leading cause of death worldwide. plaque rupture and the ensuing coronary thrombosis are hallmarks of myocardial infarction (MI), many non-thrombotic causes of myocardial infarction / necrosis are known (i.e., demand ischemia, direct myocardial toxins, etc).[1]. While international guidelines recognize different types of MI, i.e., thrombotic (type 1) and non-thrombotic (type 2) MI, no diagnostic criteria exist for differentiating between these types of MI, which require different treatment strategies.[2] One recent study of all troponin tests ordered by treating physicians in a hospital system found 42% of troponin tests to be positive; 29% were secondary to non-thrombotic (type 2) etiologies compared with 13% from an acute thrombotic MI diagnosis.[3] Mortality was 59% at 3.2 years in the patients with non-thrombotic (type 2) troponin elevations.[3] while circulating levels of troponin are specific indicators of myocardial necrosis, the levels of these proteins often do not increase for several hours after the start of an acute MI.[4] current diagnostic criteria for acute MI are unable to delineate the cause of acute MI and often fail to confirm the diagnosis before the induction of irreversible myocardial necrosis, even with modern “super sensitive” cardiac troponin assays.[5]
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