Impact of discordance in cardiac troponin T versus I on the performance of triage pathways for myocardial infarction

Abstract Background Biological, analytical, and regulatory differences between high-sensitivity cardiac troponin T (hs-cTnT) and hs-cTnI could lead to an underestimation of the performance of a hs-cTnT-based triage-algorithm if evaluated against a hs-cTnI-based reference standard, and vice versa. Unfortunately, the impact of hs-cTnT/hs-cTnI-discordance on diagnostic performance measures is largely unknown. Methods We quantified the impact of hs-cTnT/hs-cTnI-discordance on the diagnostic performance of the three most widely used and guideline recommended hs-cTnT/I-based triage algorithms for patients presenting with symptoms suggestive of myocardial infarction (MI): the ESC 0/1h-algorithm, the ESC 0/2h-algorithm and the High-STEACS pathway. For the central adjudication of the final diagnosis (reference standard), two independent cardiologists had access to all available clinical information and applied the 4th universal definition of MI, one time with serial hs-cTnT-Elecsys measurements (gold standard T) and a second time with serial hs-cTnI-Architect measurements (gold standard I). The primary diagnostic endpoint for the rule-out of NSTEMI was sensitivity, while for rule-in of NSTEMI specificity. Results Among 7728 eligible patients, the final diagnosis was NSTEMI in 1463 patients (18.9%). Of these, NSTEMI was diagnosed with only one of the two adjudication methods (either gold standard T or I) in 167 (11.4%) patients. When the three hs-cTnT-based early-triage algorithms were evaluated using gold standard T and gold standard I, sensitivity was very high and comparable. In contrast, when the three hs-cTnI-based early-triage algorithms were evaluated using gold standard T and gold standard I, sensitivity was again very high, but consistently lower when using gold standard T as compared to gold standard I. The difference in sensitivity was 1.1% (95%CI, 0.6–1.7) for ESC hs-cTnI-0/1h (Table 1A), 1.0% (95% CI, 0.5—1.6) for ESC hs-cTnI-0/2h (Table 1B), and 2.6% (95%CI, 1.7—3.5) for High-STEACS (Table 2). The differences observed in specificity mirrored those for sensitivity, i.e. always lower specificity when using the other hs-cTnT/I-assay for adjudication. Conclusion The impact of hs-cTnT/hs-cTnI-discordance on the diagnostic performance of hs-cTnT/I-based triage algorithms is modest, but large enough to result in a fallacious underestimation of the rule-out safety when evaluating hs-cTnI-based strategies using a hs-cTnT-based reference standard.