Incremental Value of Cardiac Myosin-Binding Protein C for the Early Diagnosis of Acute Myocardial Infarction - Lopez-Ayala, P.; Boeddinghaus, J.; Koechlin, L.; Bima, P.; Glaeser, J.; Spagnuolo, C. C.; Crisanti, L.; Miro, O.; Martin-Sanchez, F. J.; Christ, M.; Wildi, K.; Piazza, S.; et al. (J Am Coll Cardiol, 2025)
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).
Keywords: journalArticle; "Freiwillige Akademische Gesellschaft Basel," as well as speaker honoraria from; Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Idorsia, Novartis, Osler,; Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and; Beckman Coulter, Brahms, Idorsia, LSI Medience Corporation, Novartis, Ortho; Brahms, Idorsia, LSI Medience Corporation, Ortho Clinical Diagnostics, Quidel,; Coulter; Diagnostics, Quidel, Roche, Siemens, Singulex, and SphingoTec, outside the; Diagnostics, and Orion Pharma, outside the submitted work. Dr Mahfoud has; Division of Internal Medicine, the Swiss Academy of Medical Sciences, the; Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche; Foundation, the Margarete und Walter Lichtenstein-Stiftung (3MS1038), and the; Foundation, the Swiss Heart Foundation; Gottfried and Julia Bangerter-Rhyner Foundation, the Swiss National Science; Herzstiftung; National Science Foundation (P400PM_191037/1), the Prof Dr Max Cloetta; Queensland (PhD scholarship), the Wesley Medical Research Foundation, and the; Roche Diagnostics, Abbott, and Siemens, paid to the institution and outside the; Roche Diagnostics, Ortho Clinical Diagnostics, Quidel Corporation, and Beckman; Roche, Siemens, Singulex, and SpinChip Diagnostics. Dr Lopez-Ayala has received; Roche, and Sanofi, all paid to the institution. All other authors have reported; Sciences, and the Gottfried and Julia Bangerter-Rhyner Foundation, the; Scientific, Medtronic, Abbott, Beckman Coulter, Bayer, Ortho Clinical; Stiftung fur kardiovaskulare Forschung Basel, the University of Basel, Abbott,; Swiss Heart Foundation, University of Basel, the Swiss Academy of Medical; Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the; Terumo (all until May 2024). Dr Mueller has received research support from the; University Hospital Basel; University of Basel. Dr Nestelberger has received research support from the Swiss; and has received speaker honoraria from Quidel, Roche Diagnostics, and Polymedco; and has received speaker honoraria/consulting honoraria from; and has received speaker/consulting honoraria or; and has received travel support from Medtronic and Vascular Medical, all; and he has received; cMyC; disclose; from Ablative Solutions, Medtronic, and ReCor Medical; grants from the Swiss National Science Foundation, the Swiss Heart Foundation,; grants from the University of Basel, the University Hospital of Basel, the; has received honoraria from Siemens,; has received research; his employer (Saarland University) has received scientific support; in the last 36 months, all outside the submitted work. Dr Boeddinghaus is; myocardial infarction; outside the submitted work. Dr Koechlin has received a research grant from the; received research grants from Deutsche Gesellschaft fur Kardiologie, Deutsche; research grants from the Swiss Heart Foundation (FF20079, FF21103, and FF24149); research support from Edwards Lifesciences, Pronova Medical, Meril, Boston; speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca,; submitted work; submitted work. Dr Wildi has received research support from the University of; supported by an Edinburgh Doctoral College Scholarship; that they have no relationships relevant to the contents of this paper to; the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter,; troponin