Diagnostic validation of a novel high-sensitivity cardiac troponin T assay

Background High-sensitivity cardiac troponin assays are integral to evaluating suspected myocardial infarction (MI) and form the cornerstone of the ESC 0/1h-hour diagnostic algorithm. Recently, a novel high-sensitivity cardiac troponin T assay (TnT hs Gen 6 assay) has been developed, but independent data on its diagnostic and prognostic performance remains limited. Purpose This study aims to determine the diagnostic and prognostic performance of the newly developed TnT hs Gen 6 assay using an ESC 0/1h-hour algorithm and to assess its prognostic value for 1-year overall mortality and major adverse cardiac events (MACE). Methods In a prospective cohort of patients presenting to the emergency department with suspected non-ST-elevation MI, diagnostic discrimination of TnT hs Gen 6 measured at time of presentation and after 1 hour was tested using area under the curve (AUC) analyses. Diagnostic performance was assessed using priorly derived cut-off concentrations according to the ESC 0/1h algorithm-approach. Head-to-head comparisons between the new TnT hs Gen 6 assay and established assays were performed. Prognostic performance of TnT hs Gen 6 for 1-year overall mortality and major adverse cardiac events (MACE) was analyzed using Cox regressions adjusted for age, sex, smoking status, arterial hypertension, hypercholesterinemia, diabetes mellitus, and history of coronary artery disease (CAD). Results Among 1,415 patients (mean age 64 years and 64.2% male), MI was diagnosed in 12.1%. The novel TnT hs Gen 6 assay demonstrated excellent discrimination with an AUC of 0.87 (95% CI 0.84,0.90) on admission and 0.91 (95% CI 0.89,0.93) after 1 hour. Using a 0h cut-off <8ng/L or <18 ng/L and Δ 0/1h of <2 ng/L enabled rule-out in 54.3% (95% CI 51.7%, 57.0%) with a NPV of 99.5% (95% CI 98.7%, 99.9%); sensitivity was 97.7% (95% CI 94.1%, 99.4%). For rule-in, a 0h cut-off ≥112 ng/L or a Δ 0/1h ≥10 ng/L yielded a PPV of 58.5% (95% CI 51.9%, 64.9%) and specificity of 92.2% (95% CI 90.6%, 93.6%) with rule-in of 16.5% (95% CI 14.6%, 18.6%). In the rule-out group, overall mortality at one year was extremely low with 0.9% compared with 7.1% in the observe group and 12.0% in the rule-in group (p<0.001). Irrespective of triage category and adjusted for age, sex, and cardiovascular risk factors, TnT hs Gen 6 concentrations were independently associated with 1-year overall mortality (hazard ratio 1.39 [95% CI 1.28,1.51) and MACE (hazard ratio 1.22 [95% CI 1.15,1.29]). Conclusions The novel TnT hs Gen 6 assay demonstrates high safety and diagnostic accuracy for rapid rule-out and rule-in of MI and offers valuable prognostic information regarding 1-year overall mortality and MACE. These findings support its clinical utility for both diagnosis and risk stratification in patients with suspected MI.Graphical Abstract TnT hs Gen 6