Incremental Value of Cardiac Myosin-Binding Protein C for the Early Diagnosis of Acute Myocardial Infarction

Background: Cardiac myosin-binding protein C (cMyC) is a cardiac-specific sarcomeric protein with faster release kinetics compared with those of high-sensitivity cardiac troponin (hs-cTn). Objectives: The aim of this study was to compare the diagnostic performance of cMyC, measured with a novel prototype automated immunoassay, with high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) for the early diagnosis of non–ST-segment elevation myocardial infarction (NSTEMI). Furthermore, we derived a single blood draw dual-biomarker strategy combining hs-cTn and cMyC and compared it with the hs-cTnT/I–only strategy endorsed by the European Society of Cardiology. Methods: This was a secondary analysis from an international prospective study recruiting adult patients presenting to the emergency department (ED) with suspected NSTEMI. cMyC, hs-cTnT, and hs-cTnI concentrations were measured upon ED presentation. Final diagnoses were centrally adjudicated by 2 independent cardiologists blinded to cMyC values. To compare the single- and dual-biomarker strategy, safety (defined as the sensitivity and negative predictive value for ruling out index NSTEMI) and triage efficacy (defined as the proportion of patients triaged to either rule-out or rule-in) were assessed. The diagnostic endpoint was index NSTEMI. The prognostic endpoint was 30-day, 1-year, and 5-year cardiovascular death or MI. Findings were externally validated in an independent international cohort. Results: Among 4,735 eligible patients, 854 (18%) were diagnosed with NSTEMI. The discrimination for NSTEMI at presentation was higher for cMyC (area under the curve [AUC]: 0.943; 95% CI: 0.936-0.95) than for hs-cTnT (AUC: 0.936; 95% CI: 0.929-0.944; P = 0.008). Differences were mainly driven by patients with chest pain onset ≤3 hours (AUC of 0.939 [95% CI: 0.928-0.951] vs 0.921 [95% CI: 0.907-0.936], respectively; P < 0.001). The dual-biomarker strategy increased overall triage efficacy from 26.8% (hs-cTnT only) to 60.0% (hs-cTnT and cMyC), without compromising safety during the index visit. Despite identifying up to 3 times more patients for rule-out, the dual-biomarker strategy showed comparable cumulative incidences of cardiovascular death or myocardial infarction at 30 days, 1 year, and 5 years. Similar results were observed with hs-cTnI and in the external validation cohort. Conclusions: CMyC adds significant incremental value to hs-cTn values in the early diagnosis of NSTEMI, improving diagnostic discrimination and enabling more patients to be safely and immediately ruled out for NSTEMI. The single blood draw dual-biomarker strategy is particularly attractive in busy ED settings due to its simplicity and quick time-to-decision. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587)