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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...

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Main Authors: Lopez-Ayala, Pedro (Author) , Boeddinghaus, Jasper (Author) , Koechlin, Luca (Author) , Bima, Paolo (Author) , Glaeser, Jonas (Author) , Spagnuolo, Carlos C. (Author) , Crisanti, Luca (Author) , Miro, Oscar (Author) , Martín-Sánchez, Francisco Javier (Author) , Christ, Michael (Author) , Wildi, Karin (Author) , Piazza, Simona (Author) , Nestelberger, Thomas (Author) , Gimenez, Maria Rubini (Author) , Gehrke, Juliane (Author) , Formambuh, Jude (Author) , Kaplan, Emel (Author) , Hure, Gabrielle (Author) , Breidthardt, Tobias (Author) , Giannitsis, Evangelos (Author) , Lindahl, Bertil (Author) , Marber, Michael (Author) , Mahfoud, Felix (Author) , Strebel, Ivo (Author) , Mueller, Christian (Author)
Format: Article (Journal)
Language:English
Published: December 23/30, 2025
In: Journal of the American College of Cardiology
Year: 2025, Volume: 86, Issue: 25, Pages: 2616-2632
ISSN:1558-3597
DOI:10.1016/j.jacc.2025.09.008
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jacc.2025.09.008
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0735109725077678
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Author Notes:Pedro Lopez-Ayala, MD; Jasper Boeddinghaus, MD; Luca Koechlin, MD; Paolo Bima, MD; Jonas Glaeser, MD; Carlos C. Spagnuolo, MD; Luca Crisanti, MD; Oscar Miro, MD, PhD; Francisco Javier Martín-Sánchez, MD; Michael Christ, MD; Karin Wildi, MD, PhD; Simona Piazza, BSc; Thomas Nestelberger, MD; Maria Rubini Gimenez, MD; Juliane Gehrke, MD; Jude Formambuh, MD; Emel Kaplan, MD, PhD; Gabrielle Hure, MSc; Tobias Breidthardt, MD; Evangelos Giannitsis, MD; Bertil Lindahl, MD; Michael Marber, MD, PhD; Felix Mahfoud, MD; Ivo Strebel, PhD; Christian Mueller, MD; the APACE and TRAPID-AMI investigators
Description
Summary: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)
Item Description:Gesehen am 30.03.2026
Physical Description:Online Resource
ISSN:1558-3597
DOI:10.1016/j.jacc.2025.09.008

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