Alexander JF. Thurston, Yong Yong Tew, Pedro Lopez-Ayala, Luca Koechlin, Rachel O’Brien, Stephen Lynch, Jamie G. Cooper, T Fujisawa, Paolo Bima, M Mcdermott, Chris Tuck, Mizu Mizerska, Elizabeth Highton-Williamson, Fiona McCurrach, Matthew T.H. Lowry, D Doudesis, Atul Anand, Kuan Ken Lee, A S V Ferry, Andrew Chapman, David E. Newby, Jasper Boeddinghaus, Christian Mueller, Alasdair J. Gray, Nicholas L. Mills, POC-ET and APACE Investigators, Claire Cheyne, Shirley McDonald, Amanda Coutts, Onyinyechi Oziogu, Jennifer Noble, Ziwen Li, Daniel Perez Vicencio, Caelan Taggart, Ryan Wereski, Jennifer Blades, Salan Rowlands, Ross Campbell, Andrew Sorbie, Dorien Kimenai, Kirsten Wilson, Thomas Nestelberger, Desirée Wussler, Maria Rubini Gimenez, Jude Formambuh, Tobias Zimmerman, Danielle M Gualandro, Christian Puelacher, Jeanne du Fay de Lavallaz, Julia Reinhardt, Koray Durak, Beatriz López, Gemma Martinez-Nadal, Esther Rodríguez Adrada, Arnold von Eckardstein, Damian Kawecki, Piotr Muzyk, Nicolas Geigy, Eliška Potluková, Stephan Steuer, Angelika Hammerer-Lercher, Andreas Buser, Emel Kaplan, Òscar Miró, Michael Christ, Dagmar I Keller, F J Martin-Sanchez, Beata Morawiec, Jiri Parenica, Lourdes Herraiz Recuenco, Gabrielle Huré, Karin Wildi, Luca Crisanti, Carlos Spagnuolo, Jonas Glaeser, Catherine Caubergh, Katharina Rentsch, Ksenija Slankamenac, Ivo Strebel, Felix Mahfoud
Importance: In the emergency department, patients at low risk of myocardial infarction can be identified at presentation using a single cardiac troponin measurement with high-sensitivity assay. Objectives: To define a threshold to identify patients at low risk of myocardial infarction for the sixth-generation high-sensitivity cardiac troponin T (hs-cTnT) assay and to evaluate the impact of applying this in an early rule-out pathway. Design, Setting, and Participants: This was a prospective multicenter cohort study conducted from 2022 to 2025 (derivation cohort) and 2014 to 2019 (validation cohort). The setting included emergency departments at hospitals in Scotland (derivation cohort) and Czechia, Italy, Poland, Spain, and Switzerland (validation cohort). Participants included adults with possible non-ST-segment elevation myocardial infarction (both cohorts). Study data were analyzed from May to October 2025. Exposures: Cardiac troponin concentration measured at presentation and on serial samples using fifth-generation and novel sixth-generation hs-cTnT assays. Main Outcomes and Measures: Outcomes included the highest threshold at presentation with negative predictive value (NPV) greater than or equal to 99.5% and sensitivity greater than or equal to 99% for an adjudicated primary outcome of type 1, 4b, or 4c myocardial infarction or cardiac death at 30 days. Performance of an early rule-out pathway with the sixth-generation assay. Results: In total, 987 patients (median [IQR] age, 59 [50-70] years; 611 male [62%]) were recruited, with 82 (8.3%) meeting the primary outcome. At presentation, 601 patients (61%) had a cardiac troponin T concentration less than 13 ng/L using the sixth-generation hs-cTnT assay, with an NPV of 99.9% (95% credible interval [CrI], 99.7%-100%) and sensitivity of 99.4% (95% CrI, 97.7%-100%). More patients were identified as low risk at presentation in the early rule-out pathway when using the sixth-generation assay compared with fifth-generation assay (376 [41.0%] vs 160 [17.4%]; P < .001). In the external validation cohort, 782 of 1721 patients (45.4%) had a sixth-generation hs-cTnT measurement less than 13 ng/L at presentation with an NPV of 99.0% (95% Cr, 98.3%-99.6%) and sensitivity of 97.5% (95% Cr, 95.8%-99.0%), compared with 118 (6.9%) below the low risk-stratification threshold of the fifth-generation hs-cTnT assay (P < .001). Conclusions and Relevance: Results of this cohort study suggest that compared with the fifth-generation hs-cTnT assay, use of the sixth-generation assay with a risk-stratification threshold based on clinical performance could double identification of patients at low risk of myocardial infarction or cardiac death at presentation. Prospective studies are required to evaluate the impact of implementation on practice.