hs-cTnTA sixth-generation high-sensitivity cardiac troponin T (hs-cTnT) assay could enable clinicians to safely rule out myocardial infarction in more than twice as many patients with a single blood test, potentially reducing hospital admissions and emergency department (ED) challenges, according to a multinational cohort study.

Chest pain and related symptoms account for a substantial proportion of ED visits worldwide, yet fewer than 10% of these patients ultimately have a myocardial infarction. Current diagnostic pathways often require serial blood testing and prolonged observation, contributing to ED overcrowding and increased healthcare costs.

Researchers from the UK and Europe evaluated whether a newly developed sixth-generation hs-cTnT assay could improve the rapid assessment of patients presenting to EDs with suspected myocardial infarction.

Published in the journal JAMA Cardiology, the study included a prospective derivation cohort of 987 adults presenting with suspected non-ST-segment elevation myocardial infarction at hospitals in Scotland between 2022 and 2025. An independent validation cohort comprised 1,721 patients from hospitals in Switzerland, Spain, Italy, Poland and Czechia.

The primary outcome was myocardial infarction or cardiac death within 30 days of presentation.

Among the Scottish cohort, 82 patients (8.3%) experienced the primary outcome. Researchers compared results from the novel sixth-generation assay with those from the currently used fifth-generation hs-cTnT assay and established a risk-stratification threshold of < 13 ng/L for the new assay.

At this threshold, 60.9% (n=601) were classified as low risk at presentation. The assay achieved a negative predictive value (NPV) of 99.9% and a sensitivity of 99.4% for myocardial infarction or cardiac death within 30 days.

Improved performance of the sixth-generation hs-cTnT assay

The principal advantage of the sixth-generation hs-cTnT assay was its ability to identify substantially more low-risk patients while maintaining comparable safety performance.

Using the current fifth-generation assay, only 27.5% of patients fell below the accepted rule-out threshold. In contrast, 60.9% were below the new sixth-generation threshold.

When incorporated into the established High-STEACS early rule-out pathway, the difference was even more pronounced. In the derivation cohort, 41.0% of patients could be ruled out immediately after the first blood test using the sixth-generation assay, compared with 17.4% using the current-generation test.

The pathway also reduced the need for repeat blood sampling. Only 23.2% of patients required additional troponin testing with the sixth-generation assay, compared with 43.4% using the existing assay.

The improved performance was replicated in the independent validation cohort. Among 1,721 patients, 45.4% had troponin concentrations below the new sixth-generation threshold, compared with 6.9% below the traditional fifth-generation threshold. The assay maintained a sensitivity of 97.8% and an NPV of 99.0% for the primary outcome.

When applied within the High-STEACS pathway, 30.1% of patients could be classified as low risk after a single test, while overall pathway sensitivity remained 97.5% and NPV 99.0%.

Potential impact on ED cardiac care

According to the authors, the enhanced analytical precision of the sixth-generation hs-cTnT assay enabled clinicians to use a clinically derived risk threshold rather than relying on the assay’s lower limit of detection, which had constrained earlier rule-out strategies.

The study also found that one in five patients classified as having myocardial injury by the current assay would be reclassified as not having myocardial injury using the new assay. Very few of these patients subsequently experienced cardiovascular events.

The authors suggested this finding could reduce unnecessary investigations and hospital admissions, although implementation studies are still required.

However, they cautioned that the study was not powered to provide highly precise estimates of sensitivity and that the cohort was predominantly White, limiting generalisability. Women accounted for 38% of participants, and further work is planned to assess whether sex-specific thresholds could improve performance.

The authors emphasised that prospective implementation studies are needed before widespread adoption to determine whether use of the sixth-generation assay translates into shorter hospital stays, fewer repeat tests and improved efficiency in routine clinical practice.

Reference
Thurston AJF, Tew YY, Lopez-Ayala P. Early Rule Out of Myocardial Infarction With a Novel High-Sensitivity Cardiac Troponin T Assay. JAMA Cardiol 2026;11(6):583–92.