Background: The new high-sensitivity cardiac troponin (hs-cTn) T-Generation (gen) 6 assay has higher analytical sensitivity than the current hs-cTnT-gen5 assay, but its clinical performance is unknown.
Objectives: We aimed to assess the clinical performance and use-optimized cut-offs of the hs-cTnT-gen6 assay.
Methods: In this international, prospective, diagnostic multicenter study with central adjudication, adult patients presenting with suspected myocardial infarction (MI) to the emergency department (ED) were enrolled. hs-cTnT-gen6 and gen5 were measured at the same timepoints. The analytical and diagnostic performance of hs-cTnT-gen6 were compared to hs-cTnT-gen5, and assay-specific cut-offs for the ESC 0/1h- and 0/2h-algorithms were derived and internally and externally validated.
Results: Among 3,346 patients, MI was the final diagnosis in 616 (18.4%). The proportion of patients with concentrations above the upper reference limit and therefore myocardial injury was lower for hs-cTnT-gen6 (35.9%) than for hs-cTnT-gen5 (43.5%;P<0.001). Diagnostic accuracy at ED presentation, expressed as AUC, was 0.927 (95%CI:0.918-0.937) for hs-cTnT-gen6 and 0.931 (95% CI:0.921-0.940) for hs-cTnT-gen5. A gen6 cut-off <6 ng/L ruled out NSTEMI in 30% of patients with 100% sensitivity (95%CI:99.4-100%) irrespective of chest pain onset. A hs-cTnT-gen6 cutoff <8 ng/L at presentation (if chest pain onset was >3h) or <18 ng/L together with a 0/1h delta of <2 ng/L ruled out 56% with a sensitivity of 99.7% (95%CI,98.3-99.9). A hs-cTnT-gen6 concentration ≥112 ng/L or a 0/1h delta ≥10 ng/L ruled-in 20% with a specificity 93.4% (95%CI,92.0-94.6). A hs-cTnT-gen6 cutoff <8 ng/L at presentation (if chest pain onset was >3h) or <18 ng/L together with a 0/2h delta of <4 ng/L ruled out 51% with a sensitivity of 99.7% (95%CI,98.1-99.9). A hs-cTnT-gen6 concentration ≥112 ng/L or a 0/2h delta ≥15 ng/L ruled-in 24% with a specificity 92.7% (95%CI,90.8-94.2). Findings were consistent in sensitivity analyses as well as in the external validation cohort.
Conclusions: The novel hs-cTnT-gen6 assay demonstrated excellent and comparable diagnostic performance to the established hs-cTnT-gen5 assay with less patients identified as having myocardial injury. Use-optimized, assay-specific cut-offs for the ESC 0/1h- and 0/2h-algorithms provided very high sensitivity and high specificity.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Luca Koechlin, MD
Important Dates
Date of Release: May 5, 2026
Term of Approval/Date of CME/MOC Expiration: May 4, 2027