Abstract
BACKGROUND: This study compared the diagnostic and prognostic performance of various non-ST-segment myocardial infarction (NSTEMI) rule-out protocols, incorporating cardiac myosin-binding protein C (cMyBP-C), high-sensitivity cardiac troponin T (hs-cTnT), and Copeptin, both individually and as part of dual-marker strategies (DMSs) against the European Society of Cardiology 0/1-hour and 0/3-hour algorithms. METHODS: We enrolled 1765 patients presenting to the emergency department with suspected NSTEMI. We evaluated biomarker algorithms including cMyBP-C (<10 ng/L, <2.3 ng/L), hs-cTnT (limit of blank [<3 ng/L], limit of detection [<5 ng/L], 99th percentile [≤14 ng/L]), and DMS combinations of copeptin (<10 pmol/L) with hs-cTnT, cMyBP-C with hs-cTnT, and copeptin with cMyBP-C. The European Society of Cardiology 0/1-hour and 0/3-hour algorithms were also tested. We calculated negative predictive values and sensitivities for NSTEMI rule-out and assessed effectiveness and prognostic performance based on cardiovascular events within 30 days and 1 year. RESULTS: The areas under the curve were 0.922 for hs-cTnT, 0.917 for cMyBP-C, and 0.624 for copeptin in diagnosing NSTEMI. DMS protocols showed negative predictive values of 99.1% to 100%, comparable with the European Society of Cardiology algorithms (99.3%-100%). Sensitivities for DMS ranged from 96.2% to 100%. All protocols had low rates of the combined end point of cardiovascular events within 30 days (0.0%-0.6%). CONCLUSIONS: The European Society of Cardiology 0/1-hour algorithm and DMS combining hs-cTnT with either cMyBP-C or copeptin provide highly reliable and safe protocols for NSTEMI rule-out. These DMS approaches offer promising alternatives to current standards, potentially improving clinical decision making and efficiency in emergency departments. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT06128317.