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

Pedro Lopez-Ayala¹, Jasper Boeddinghaus¹, Luca Koechlin², Paolo Bima¹, Jonas Glaeser¹, Carlos C Spagnuolo¹, Luca Crisanti³, Oscar Miro⁴, Francisco Javier Martín-Sánchez⁵, Michael Christ⁶, Karin Wildi³, Simona Piazza³, Thomas Nestelberger¹, Maria Rubini Gimenez³, Juliane Gehrke³, Jude Formambuh³, Emel Kaplan³, Gabrielle Hure³, Tobias Breidthardt³, Evangelos Giannitsis⁷, Bertil Lindahl⁸, Michael Marber⁹, Felix Mahfoud³, Ivo Strebel¹⁰, Christian Mueller¹¹; APACE and TRAPID-AMI investigators

Collaborators, Affiliations

Collaborators

APACE and TRAPID-AMI investigators:
Desiree Wussler¹², Tobias Zimmermann¹², Dagmar I Keller¹³, Ksenija Slankamena¹³, Danielle M Gualandro¹², Andreas Buser¹⁴, Eliska Potlukova¹², Damian Kawecki¹⁵, Nicolas Geigy¹⁶, Katharina Rentsch¹⁷, Beata Morawiec¹⁵, Piotr Munzk¹⁵, Beatriz Lopez-Barbeito¹⁸, Gemma Martinez-Nadal¹⁸, Carolina Fuenzalida¹⁸, Sofia Calderón¹⁸, Esther Rodriguez Adrada¹⁹, Eva Ganovská²⁰, Jiri Parenica²⁰, Arnold von Eckardstein²¹, Isabel Campodarve²², Joachim Gea²², Roland Bingisser²³, Christian Nickel²³, James Mccord²⁴, Richard Nowak²⁵, Richard Body²⁶, Christopher R deFilippi²⁷, Robert H Christenson²⁸, Mauro Panteghini²⁹, Mario Plebani³⁰, Franck Verschuren³¹, John French³², Silvia Weiser³³, Tomas Jernberg³⁴, Aitor Alquézar-Arbé³⁵, Jordi Ordonez-Llanos³⁶, Tom Kaier³⁷

Affiliations

¹ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy.
² Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy; Department of Cardiac Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ GREAT network, Rome, Italy; Emergency Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁵ GREAT network, Rome, Italy; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
⁶ Department of Emergency Medicine, Luzerner Kantonsspital, Luzern, Switzerland.
⁷ Department of Medicine III, University Hospital Heidelberg, Heidelberg, Germany.
⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala, Sweden.
⁹ King's College London BHF Centre, Rayne Institute, St Thomas' Hospital, London, United Kingdom.
¹⁰ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy. Electronic address: ivo.strebel@usb.ch.
¹¹ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy. Electronic address: christian.mueller@usb.ch.
¹² Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland; GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland.
¹³ Department of Cardiology, University Hospital Brno, Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
¹⁴ Emergency Department, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland.
¹⁵ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Katowice, Poland.
¹⁶ Emergency Department, Kantonsspital Liestal, Switzerland.
¹⁷ Laboratory Medicine, University Hospital Basel, Switzerland.
¹⁸ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
¹⁹ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
²⁰ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Department of Cardiology, University Hospital Brno, Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
²¹ Department of Laboratory Medicine, University Hospital Zurich, Zurich, Switzerland.
²² Hospital del Mar, Barcelona, Spain.
²³ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland.
²⁴ Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, United States.
²⁵ Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan, United States.
²⁶ Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁷ Inova Heart and Vascular Institute, Falls Church, Virginia, United States.
²⁸ University of Maryland School of Medicine, Baltimore, Maryland, United States.
²⁹ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan Medical School, Milan, Italy.
³⁰ Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³¹ Department of Acute Medicine, Cliniques Universitaires St-Luc and Universite Catholique de Louvain, Brussels, Belgium.
³² Liverpool Hospital and University of New South Wales, Liverpool, NSW, Australia.
³³ Roche Diagnostics Germany, Penzberg, Germany.
³⁴ Department of Medicine, Karolinksa Institutet, Huddinge, Sweden.
³⁵ Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁶ Department of clinical biochemistry, Universitat Autonoma, Barcelona, Spain.
³⁷ Cardiology Department Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.

PMID: 41222525
DOI: 10.1016/j.jacc.2025.09.008

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

Pedro Lopez-Ayala et al. J Am Coll Cardiol. 2025.

. 2025 Oct 13:S0735-1097(25)07767-8.

doi: 10.1016/j.jacc.2025.09.008. Online ahead of print.

Authors

Collaborators

APACE and TRAPID-AMI investigators:
Desiree Wussler¹², Tobias Zimmermann¹², Dagmar I Keller¹³, Ksenija Slankamena¹³, Danielle M Gualandro¹², Andreas Buser¹⁴, Eliska Potlukova¹², Damian Kawecki¹⁵, Nicolas Geigy¹⁶, Katharina Rentsch¹⁷, Beata Morawiec¹⁵, Piotr Munzk¹⁵, Beatriz Lopez-Barbeito¹⁸, Gemma Martinez-Nadal¹⁸, Carolina Fuenzalida¹⁸, Sofia Calderón¹⁸, Esther Rodriguez Adrada¹⁹, Eva Ganovská²⁰, Jiri Parenica²⁰, Arnold von Eckardstein²¹, Isabel Campodarve²², Joachim Gea²², Roland Bingisser²³, Christian Nickel²³, James Mccord²⁴, Richard Nowak²⁵, Richard Body²⁶, Christopher R deFilippi²⁷, Robert H Christenson²⁸, Mauro Panteghini²⁹, Mario Plebani³⁰, Franck Verschuren³¹, John French³², Silvia Weiser³³, Tomas Jernberg³⁴, Aitor Alquézar-Arbé³⁵, Jordi Ordonez-Llanos³⁶, Tom Kaier³⁷

Affiliations

¹ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy.
² Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy; Department of Cardiac Surgery, University Hospital Basel, University of Basel, Basel, Switzerland.
³ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland.
⁴ GREAT network, Rome, Italy; Emergency Department, Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁵ GREAT network, Rome, Italy; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
⁶ Department of Emergency Medicine, Luzerner Kantonsspital, Luzern, Switzerland.
⁷ Department of Medicine III, University Hospital Heidelberg, Heidelberg, Germany.
⁸ Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala, Sweden.
⁹ King's College London BHF Centre, Rayne Institute, St Thomas' Hospital, London, United Kingdom.
¹⁰ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy. Electronic address: ivo.strebel@usb.ch.
¹¹ Cardiovascular Research Institute Basel (CRIB) and Clinic of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Basel, Switzerland; GREAT network, Rome, Italy. Electronic address: christian.mueller@usb.ch.
¹² Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland; GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland.
¹³ Department of Cardiology, University Hospital Brno, Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
¹⁴ Emergency Department, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland.
¹⁵ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Katowice, Poland.
¹⁶ Emergency Department, Kantonsspital Liestal, Switzerland.
¹⁷ Laboratory Medicine, University Hospital Basel, Switzerland.
¹⁸ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain.
¹⁹ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, Hospital Clínico San Carlos, Madrid, Spain.
²⁰ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Department of Cardiology, University Hospital Brno, Brno, Czech Republic and Medical Faculty, Masaryk University, Brno, Czech Republic.
²¹ Department of Laboratory Medicine, University Hospital Zurich, Zurich, Switzerland.
²² Hospital del Mar, Barcelona, Spain.
²³ GREAT network, Rome, Italy; (c)Department of Cardiology, Inselspital, University of Bern, Switzerland; (d)Emergency Department, Kantonsspital Luzern, Switzerland; (e)Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland; Emergency Department, University Hospital Basel, Department of Clinical Research, University of Basel, Switzerland.
²⁴ Heart and Vascular Institute, Henry Ford Health System, Detroit, Michigan, United States.
²⁵ Department of Emergency Medicine, Henry Ford Health System, Detroit, Michigan, United States.
²⁶ Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
²⁷ Inova Heart and Vascular Institute, Falls Church, Virginia, United States.
²⁸ University of Maryland School of Medicine, Baltimore, Maryland, United States.
²⁹ Department of Biomedical and Clinical Sciences "Luigi Sacco", University of Milan Medical School, Milan, Italy.
³⁰ Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy.
³¹ Department of Acute Medicine, Cliniques Universitaires St-Luc and Universite Catholique de Louvain, Brussels, Belgium.
³² Liverpool Hospital and University of New South Wales, Liverpool, NSW, Australia.
³³ Roche Diagnostics Germany, Penzberg, Germany.
³⁴ Department of Medicine, Karolinksa Institutet, Huddinge, Sweden.
³⁵ Emergency Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
³⁶ Department of clinical biochemistry, Universitat Autonoma, Barcelona, Spain.
³⁷ Cardiology Department Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.

PMID: 41222525
DOI: 10.1016/j.jacc.2025.09.008

Abstract

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: cMyC; myocardial infarction; troponin.

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Conflict of interest statement

Funding Support and Author Disclosures The APACE study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Brahms, Idorsia, LSI Medience Corporation, Ortho Clinical Diagnostics, Quidel, Roche, Siemens, Singulex, and SpinChip Diagnostics. Dr Lopez-Ayala has received research grants from the Swiss Heart Foundation (FF20079, FF21103, and FF24149); and has received speaker honoraria from Quidel, Roche Diagnostics, and Polymedco in the last 36 months, all outside the submitted work. Dr Boeddinghaus is supported by an Edinburgh Doctoral College Scholarship; has received research grants from the University of Basel, the University Hospital of Basel, the Division of Internal Medicine, the Swiss Academy of Medical Sciences, the Gottfried and Julia Bangerter-Rhyner Foundation, the Swiss National Science Foundation, the Swiss Heart Foundation; has received honoraria from Siemens, Roche Diagnostics, Ortho Clinical Diagnostics, Quidel Corporation, and Beckman Coulter; and has received travel support from Medtronic and Vascular Medical, all outside the submitted work. Dr Koechlin has received a research grant from the Swiss Heart Foundation, University of Basel, the Swiss Academy of Medical Sciences, and the Gottfried and Julia Bangerter-Rhyner Foundation, the “Freiwillige Akademische Gesellschaft Basel,” as well as speaker honoraria from Roche Diagnostics, Abbott, and Siemens, paid to the institution and outside the submitted work. Dr Wildi has received research support from the University of Queensland (PhD scholarship), the Wesley Medical Research Foundation, and the University of Basel. Dr Nestelberger has received research support from the Swiss National Science Foundation (P400PM_191037/1), the Prof Dr Max Cloëtta Foundation, the Margarete und Walter Lichtenstein-Stiftung (3MS1038), and the University Hospital Basel; and has received speaker/consulting honoraria or research support from Edwards Lifesciences, Pronova Medical, Meril, Boston Scientific, Medtronic, Abbott, Beckman Coulter, Bayer, Ortho Clinical Diagnostics, and Orion Pharma, outside the submitted work. Dr Mahfoud has received research grants from Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung; his employer (Saarland University) has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical; and he has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo (all until May 2024). Dr Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the Stiftung für kardiovaskuläre Forschung Basel, the University of Basel, Abbott, Beckman Coulter, Brahms, Idorsia, LSI Medience Corporation, Novartis, Ortho Diagnostics, Quidel, Roche, Siemens, Singulex, and SphingoTec, outside the submitted work; and has received speaker honoraria/consulting honoraria from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Idorsia, Novartis, Osler, Roche, and Sanofi, all paid to the institution. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Associated data

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Medical

Research Materials