Serum Concentrations of Matrix Metalloproteinase-1 and Procollagen Type I Carboxy Terminal Propeptide Discriminate Infarct-Like Myocarditis and Non-ST-Segment-Elevation Myocardial Infarction

Abstract

Background: Biomarkers simplifying the diagnostic workup by discriminating between non-ST-segment-elevation myocardial infarction (NSTEMI) and infarct-like myocarditis are an unmet clinical need.

Methods and results: A total of 105 subjects were categorized into groups as follows: ST-segment-elevation myocardial infarction (n=36), NSTEMI (n=22), infarct-like myocarditis (n=19), cardiomyopathy-like myocarditis (n=18), and healthy control (n=10). All subjects underwent cardiac magnetic resonance imaging, and serum concentrations of matrix metalloproteinase-1 (MMP-1) and procollagen type I carboxy terminal propeptide (PICP) were measured. Biomarker concentrations in subjects presenting with acute coronary syndrome and non-ST-segment-elevation, for example NSTEMI or infarct-like myocarditis, categorized as the non-ST-segment-elevation acute coronary syndrome-like cohort, were of particular interest for this study. Compared with healthy controls, subjects with myocarditis had higher serum concentrations of MMP-1 and PICP, while no difference was observed in individuals with myocardial infarction. In the non-ST-segment-elevation acute coronary syndrome-like cohort, MMP-1 concentrations discriminated infarct-like myocarditis and NSTEMI with an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI, 0.89-1.00), whereas high-sensitivity cardiac troponin T performed inferiorly (AUC, 0.74 [95% CI, 0.58-0.90]; P=0.012). Application of an optimal MMP-1 cutoff had 94.4% sensitivity (95% CI, 72.7%-99.9%) and 90.9% specificity (95% CI, 70.8%-98.9%) for the diagnosis of infarct-like myocarditis in this cohort. The AUC of PICP in this context was 0.82 (95% CI, 0.68-0.97). As assessed by likelihood ratio tests, incorporating MMP-1 or PICP with age and C-reactive protein into composite prediction models enhanced their diagnostic performance.

Conclusions: MMP-1 and PICP could potentially be useful biomarkers for differentiating between NSTEMI and infarct-like myocarditis in individuals with non-ST-segment-elevation acute coronary syndrome-like presentation, though further research is needed to validate their clinical applicability.

Keywords: NSTEMI; biomarker; cardiac troponin; matrix metalloproteinase‐1; procollagen type I carboxy terminal propeptide.

Figure 1. Study design and circulating levels of high‐sensitivity cardiac troponin T (hs‐cTnT), matrix metalloproteinase‐1 (MMP‐1), and procollagen type I carboxy terminal propeptide (PICP) in the 2 study cohorts.

A, Applying a strict definition for acute myocarditis distinguished 19 patients with infarct‐like myocarditis (IL‐myocarditis) from 18 patients with cardiomyopathy‐like myocarditis (CM‐myocarditis). The group of patients with myocardial infarction (MI) comprised 36 patients with ST‐segment–elevation MI (STEMI) and 22 patients with non–ST‐segment–elevation MI (NSTEMI). Since infarct‐like myocarditis and NSTEMI both clinically present non−ST‐segment‐elevation acute coronary syndrome (NSTE‐ACS)‐like, the comparison of these patients was of particular interest for this study. B through D, hs‐cTnT (B), MMP‐1 (C) and PICP (D) are shown for the complete study cohort (left panels), and for the cohort of patients presenting NSTE‐ACS‐like (right panels). Data are presented as dot plots combined with box plots presenting median±interquartile range. Reference concentrations (median±interquartile range) of the respective biomarkers in controls are shown as diaphanous bars in each panel.

Figure 2. Receiver operator characteristic (ROC) curves of matrix metalloproteinase‐1 (MMP‐1) and procollagen type I carboxy terminal propeptide (PICP) in the 2 study cohorts.

ROC curves and the dependent area under the ROC curve (AUC [95%CI]) are given for high‐sensitivity cardiac troponin T (hs‐cTnT), MMP‐1, and PICP. Analyses shown in (A) were performed in the complete study cohort, whereas those shown in (B) were performed in the refined study cohort of patients with non−ST‐segment−elevation acute coronary syndrome (NSTE‐ACS)‐like presentation. IL‐myocarditis indicates infarct‐like myocarditis; and NSTEMI, non–ST‐segment–elevation myocardial infarction.