A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction
Thomas E Kaier, Raphael Twerenbold, Pedro López‐Ayala, Thomas Nestelberger, Jasper Boeddinghaus, Bashir Alaour, Iris-Martina Huber, Yuan Zhi, Luca Koechlin, Desirée Wussler, Karin Wildi, Samyut Shrestha, Ivo Strebel, Òscar Miró, Javier Martín‐Sánchez, Michael Christ, Damian Kawecki, Dagmar I. Keller, María Rubini Giménez, Michael Marber, Christian Mueller, APACE Investigators, Michael Freese, Paul David Ratmann, Alexandra Prepoudis, Danielle Menosi 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 Rodríguez Adrada, Piotr Muzyk, Beata Morawiec, Jiří Pařenica, Eva Ganovská, Jens Lohrmann, Andreas Buser, Arnold von Eckardstein, Roland Bingisser, Christian H. 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.