Background: High-sensitivity cardiac troponin (hs-cTn) T has been recently approved by the FDA to diagnose acute myocardial infarction (AMI) also in the United States (US). One uniform cut-off valus (19ng/L) has been recommended. However alternative sex-specific cut-offs have been also suggested (women 14ng/L, men 22ng/L). The values of these sex-specific values are higher as compared to the ones used outside the US.
Purpose and methods: We aim to explore the diagnostic reclassifications when using the FDA-approved sex-specific versus the FDA-approved uniform cut-offs for hs-cTnT in a large diagnostic multicentre study enrolling patients presenting with suspected MI to the ED. Patients presenting with ST-Segment-Elevation MI were excluded. The final diagnosis was centrally adjudicated by 2 independent cardiologists based on all available clinical information including serial measurements of hs-cTnT twice: once using the uniform cutoff value of 19ng/L and once using sex-specific cutoff values (women, 14ng/L; men, 22ng/L). The clinical impact of using sex-specific cut-offs was quantified by assessing diagnostic reclassifications when using sex-specific values. Duration of follow-up was 365 days.
Results: Among 4048 patients (1316 women and 2732 men), MI was diagnosed in 634 patients (15.7%, 168 women (12.8%) and 466 men (17.1%)) using the uniform cut-off value. Among these, concentrations of hs-cTnT were already greater or equal than the one overall cut-off value at ED presentation in 551 patients (sensitivity, 86.9% [95% CI, 84.0–89.4%], specificity (86.7% [95% CI, 85.5–87.8%]) with near-identical performance in women (sensitivity, 87.5% [95% CI, 81.5%-91.7%], specificity 87.7% [95% CI, 85.7%-89.6%]); and men (sensitivity, 86.7% [95% CI, 83.3%-89.7%], specificity 86.1% [95% CI, 84.7%-87.5%]).
After readjudication using sex-specific cut-offs, diagnostic reclassification occurred in 11 patients: 0.3% (95% CI, 0.1–0.5%) of all patients and 1.7% (95% CI, 0.9–3.0%) of patients with MI. In 4 women the diagnosis was upgraded from unstable angina (UA) to MI, and in 7 men the diagnosis was downgraded from MI to UA, overall resulting in 631 patients with a final adjudicated diagnosis of MI (versus 634 using the one overall cut-off (Figure). None of the reclassified patients died during 365-days follow-up. Among the 7 downgraded men 3 underwent PCI and 1 bypass grafting during the index admission. Among the 4 upgraded women, 3 underwent PCI.
Conclusion: Using the FDA-approved hs-cTnT cut-off values, the uniform 99th-percentile provides very high and near-identical sensitivity and specificity in women and men already at ED presentation. Sex-specific cut-off concentrations reclassify only a small percentage of patients. Accordingly, the uniform 99th-percentile should remain the standard of care also in the US.