Abstract: BACKGROUND: Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain. METHODS: Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways. RESULTS: In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0%, who require further observation in the emergency department, respectively. CONCLUSIONS: CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.
Tags: *Acute Coronary Syndrome/diagnosis, *Myocardial Infarction/diagnosis, Abbott Diagnostics, outside the submitted work. Dr Koechlin received a research, algorithm. The other authors have reported no relationships relevant to the, and travel support from Medtronic, all outside the submitted work. Dr Lopez-Ayala, Biomarkers, Boeddinghaus, Doudesis, Lee, Bularga, Ferry, Tuck, Anand, and Gray are employees, Boehringer Ingelheim, Bayer, BMS, Idorsia, Novartis, Osler, Roche, and Sanofi,, contents of this article to disclose., Coulter, Bayer, Ortho Clinical Diagnostics, and Orion Pharma, outside the, Diagnostics, Ortho Clinical Diagnostics, Quidel Corporation, and Beckman Coulter,, Diagnostics, Siemens Healthineers, and Abbott Diagnostics, outside the submitted, Diagnostics, Siemens Healthineers, and LumiraDx. Dr Mueller has received research, Diagnostics, which had no role in the study design, data analysis, manuscript, Dr Nestelberger has received research support from the Swiss National Science, Edinburgh and honoraria or consultancy from Abbott Diagnostics, Roche, Female, Foundation (grant P400PM_191037/1), the Prof Dr Max Cloetta Foundation, the, Freiwillige Akademische Gesellschaft, as well as speaker honoraria from Roche, grant from the University of Basel, the Swiss Heart Foundation, the SAMW, and the, has received speaker honoraria or consultancy from Quidel, paid to the, Hospital Basel, as well as speaker or consulting honoraria from Siemens, Beckman, Humans, institution, outside the submitted work. Dr Lee has received honoraria from, Machine Learning, Male, Margarete und Walter Lichtenstein-Stiftung (grant 3MS1038), and the University, Middle Aged, myocardial infarction, of the University of Edinburgh, which has filed for a patent on the CoDE-ACS, Ortho Clinical Diagnostics, Quidel, Roche, Siemens, Singulex, and Sphingotec, as, outside of the submitted work. The cardiac troponin assay was donated by Abbott, preparation, or the decision to submit the manuscript for publication. Drs Mills,, submitted work. Dr Mills has received research grants to the University of, support from Abbott Diagnostics, Beckman Coulter, bioMerieux, Idorsia, Novartis,, the University of Queensland, Brisbane, Australia, and the University of Basel., Troponin, Troponin T.
