Early identification of patients at low risk of myocardial infarction (MI) in the emergency department (ED) can streamline care and reduce unnecessary admissions. A prospective multicenter cohort study published in the JAMA Cardiology derived and validated a risk-stratification threshold for a sixth-generation high-sensitivity cardiac troponin T (hs-cTnT) assay.

The derivation cohort included adults with possible non–ST-segment elevation MI recruited in Scotland between 2022 and 2025, while external validation was conducted across EDs in Czechia, Italy, Poland, Spain, and Switzerland using data from 2014 to 2019. Cardiac troponin concentrations were measured at presentation and serially using both fifth- and sixth-generation assays.

The primary endpoint was a composite of type 1, 4b, or 4c MI or cardiac death within 30 days.
In the derivation cohort (n=987; median age 59 years; 62% male), 82 patients (8.3%) met the primary endpoint. A threshold of <13 ng/L using the sixth-generation assay identified 61% of patients as low risk, achieving an NPV of 99.9% (95% credible interval [CrI] 99.7%–100%) and sensitivity of 99.4% (95% CrI 97.7%–100%).

Implementation within an early rule-out pathway increased low-risk classification compared with the fifth-generation assay (41.0% vs 17.4%; p<0.001). In the validation cohort (n=1,721), 45.4% were classified as low risk with the sixth-generation assay compared with 6.9% using the fifth-generation threshold (p<0.001), with NPV of 99.0% and sensitivity of 97.5%.

The sixth-generation hs-cTnT assay identified a substantially larger proportion of low-risk patients at presentation than the fifth-generation assay while maintaining high negative predictive value.