A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction

Thomas E Kaier, Raphael Twerenbold, Pedro Lopez-Ayala, Thomas Nestelberger, Jasper Boeddinghaus, Bashir Alaour, Iris-Martina Huber, Yuan Zhi, Luca Koechlin, Desiree Wussler, Karin Wildi, Samyut Shrestha, Ivo Strebel, Oscar Miro, Javier F Martín-Sánchez, Michael Christ, Damien Kawecki, Dagmar I Keller, Maria Rubini Gimenez, Michael Marber, Christian Mueller, APACE Investigators, Michael Freese, Paul David Ratmann, Alexandra Prepoudis, Danielle M Gualandro, Nicolas Geigy, Tobias Reichlin, Katharina Rentsch, Mario Maier, Valentina Troester, Juliane Gehrke, Tania Coscia, Noemi Glarner, Hadrien Schoepfer, Michael Buechi, Joan Walter, Ana Yufera Sanchez, Christian Puelacher, Jeanne du Fay de Lavallaz, Alessandra Sanzione, Ibrahim Schäfer, Petra Hillinger, Beatriz López, Esther Rodriguez Adrada, Piotr Muzyk, Beata Morawiec, Jiri Parenica, Eva Ganovská, Jens Lohrmann, Andreas Buser, Arnold von Eckardstein, Roland Bingisser, Christian Nickel, Thomas E Kaier, Raphael Twerenbold, Pedro Lopez-Ayala, Thomas Nestelberger, Jasper Boeddinghaus, Bashir Alaour, Iris-Martina Huber, Yuan Zhi, Luca Koechlin, Desiree Wussler, Karin Wildi, Samyut Shrestha, Ivo Strebel, Oscar Miro, Javier F Martín-Sánchez, Michael Christ, Damien Kawecki, Dagmar I Keller, Maria Rubini Gimenez, Michael Marber, Christian Mueller, APACE Investigators, Michael Freese, Paul David Ratmann, Alexandra Prepoudis, Danielle M Gualandro, Nicolas Geigy, Tobias Reichlin, Katharina Rentsch, Mario Maier, Valentina Troester, Juliane Gehrke, Tania Coscia, Noemi Glarner, Hadrien Schoepfer, Michael Buechi, Joan Walter, Ana Yufera Sanchez, Christian Puelacher, Jeanne du Fay de Lavallaz, Alessandra Sanzione, Ibrahim Schäfer, Petra Hillinger, Beatriz López, Esther Rodriguez Adrada, Piotr Muzyk, Beata Morawiec, Jiri Parenica, Eva Ganovská, Jens Lohrmann, Andreas Buser, Arnold von Eckardstein, Roland Bingisser, Christian Nickel

Abstract

Aims: Cardiac myosin-binding protein C (cMyC) demonstrated high diagnostic accuracy for the early detection of non-ST-elevation myocardial infarction (NSTEMI). Its dynamic release kinetics may enable a 0/1h-decision algorithm that is even more effective than the ESC hs-cTnT/I 0/1 h rule-in/rule-out algorithm.

Methods and results: In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department, cMyC was measured at presentation and after 1 h in a blinded fashion. Modelled on the ESC hs-cTnT/I 0/1h-algorithms, we derived a 0/1h-cMyC-algorithm. Final diagnosis of NSTEMI was centrally adjudicated according to the 4th Universal Definition of Myocardial Infarction. Among 1495 patients, the prevalence of NSTEMI was 17%. The optimal derived 0/1h-algorithm ruled-out NSTEMI with cMyC 0 h concentration below 10 ng/L (irrespective of chest pain onset) or 0 h cMyC concentrations below 18 ng/L and 0/1 h increase <4 ng/L. Rule-in occurred with 0 h cMyC concentrations of at least 140 ng/L or 0/1 h increase ≥15 ng/L. In the validation cohort (n = 663), the 0/1h-cMyC-algorithm classified 347 patients (52.3%) as 'rule-out', 122 (18.4%) as 'rule-in', and 194 (29.3%) as 'observe'. Negative predictive value for NSTEMI was 99.6% [95% confidence interval (CI) 98.9-100%]; positive predictive value 71.1% (95% CI 63.1-79%). Direct comparison with the ESC hs-cTnT/I 0/1h-algorithms demonstrated comparable safety and even higher triage efficacy using the 0h-sample alone (48.1% vs. 21.2% for ESC hs-cTnT-0/1 h and 29.9% for ESC hs-cTnI-0/1 h; P < 0.001).

Conclusion: The cMyC 0/1h-algorithm provided excellent safety and identified a greater proportion of patients suitable for direct rule-out or rule-in based on a single measurement than the ESC 0/1h-algorithm using hs-cTnT/I.

Trial registration: ClinicalTrials.gov number, NCT00470587.

Keywords: APACE; Cardiac myosin-binding protein C; Myocardial infarction; Troponin I; Troponin T; cMyC.

© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Comparison of cMyC and ESC hs-TnT/I 0/1h-algorithms: direct comparison of patient distribution in the validation cohort according to the cMyC 0/1h-algorithm and the ESC hs-cTnT/I 0/1h-algorithms. Final clinical adjudication of NSTEMI included hs-cTnT.
Figure 2
Figure 2
Dual-marker strategy: Concept outlining how the 0h cMyC concentration could be employed as a triage-booster when integrated into the established ESC 0/1h-algorithm.
Figure 3
Figure 3
Mortality plot: cumulative event plot for the cMyC 0/1h-algorithm, with statistical comparison of event curves at 30 and 365 days with the log-rank tests; table displays number-at-risk and absolute number of events.

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