Early Rule Out of Myocardial Infarction With a Novel High-Sensitivity Cardiac Troponin T Assay

ImportanceIn 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.ObjectivesTo 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 ParticipantsThis 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.ExposuresCardiac troponin concentration measured at presentation and on serial samples using fifth-generation and novel sixth-generation hs-cTnT assays.Main Outcomes and MeasuresOutcomes 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.ResultsIn 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 P Conclusions and RelevanceResults 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.