Novel hs-cTnT Assay Doubles Early Myocardial Infarction Rule-Out

Key Takeaways

• The study-derived threshold below 13 ng/L was associated with more low-risk classification at presentation than the fifth-generation hs-cTnT approach.
• In external validation, 782 of 1721 patients, or 45.4%, were below 13 ng/L, with NPV 99.0% and sensitivity 97.8%.
• In the derivation cohort, the High-STEACS pathway categorized 569 of 918 patients as low risk and required fewer repeated troponin measurements in the study comparison, while prospective implementation studies are still needed.

In the derivation cohort, 601 of 987 patients, or 60.9%, were below that threshold, and the negative predictive value was 99.9%. The cohort included adults seen in emergency departments with possible non–ST-segment elevation myocardial infarction, and rule-out performance remained very high. Because the new assay uses different calibration, the sixth- and fifth-generation assays were not interchangeable, and the derived threshold classified more patients as low risk from the initial sample.

This Original Investigation was a prospective multicenter observational cohort study and a prespecified secondary analysis of POC-ET, with blinded adjudication and STARD reporting. Adults aged 18 years or older with possible non–ST-segment elevation myocardial infarction were enrolled in Scotland for derivation and in Czechia, Italy, Poland, Spain, and Switzerland for validation. The derivation cohort included 987 participants, and the validation cohort included 1721, enrolled from November 2022 through January 2025 and from 2014 through 2019, respectively. The primary outcome was type 1, 4b, or 4c myocardial infarction at index presentation, or subsequent type 1, 4b, or 4c myocardial infarction or cardiac death within 30 days. Data were analyzed from May to October 2025, and investigators selected the highest presentation threshold that met prespecified safety criteria for presentation testing.

With the fifth-generation comparator threshold below 5 ng/L, 271 of 987 patients, or 27.5%, were below threshold in the derivation cohort. Using the sixth-generation assay in that cohort, the High-STEACS pathway classified 569 of 918 patients, or 62.0%, as low risk and 349, or 38.0%, as high risk. Repeated troponin T measurements were required in 213 patients, or 23.2%, with the sixth-generation pathway versus 398, or 43.4%, with the fifth-generation assay. Investigators also evaluated hs-cTnI as a comparator assay, and the proposed pathway required fewer repeated troponin samples in the derivation cohort.

Validation in a separate multinational cohort supported the threshold, and the High-STEACS pathway retained high rule-out performance across a distinct case mix. The investigators noted that the sixth-generation and fifth-generation assays were not interchangeable because calibration differences shifted measured concentrations. The derivation cohort was predominantly White, only 13% presented within 2 hours of symptom onset, and event counts limited formal subgroup assessment. Precision around sensitivity was lower in female patients, and four female patients were incorrectly identified as low risk at presentation in validation. Authors concluded that prospective studies are needed to determine whether implementation reduces serial testing and facilitates earlier discharge.