Alternative Rule-Out Cutoffs for a Novel High-Sensitivity Cardiac Troponin I Assay in Patients With Suspected Myocardial Infarction - Durak, K.; Lopez-Ayala, P.; Koechlin, L.; Boeddinghaus, J.; De Vita, F.; Kaplan, E.; Herraiz-Recuenco, L.; Miro, O.; Christ, M.; Keller, D. I.; Martin-Sanchez, J. F.; Morawiec, B.; et al. (J Am Heart Assoc, 2026)
BACKGROUND: There is major uncertainty among physicians on how to best use the novel hs-cTnI (high sensitivity-cardiac troponin I)-VITROS assay, as the limit of quantification (2 ng/L), applied by the US Food and Drug Administration and other regulators, is higher than the limit of detection (1 ng/L)-based rule-out cutoffs from recent pilot studies for 0/1-hour and 0/2-hour algorithms. METHODS: This prospective, multicenter study aimed to derive and validate higher limit of quantification-based assay-specific cutoffs for safe and efficient rule-out of myocardial infarction among adult patients presenting with acute chest discomfort to the emergency department. Final diagnoses of myocardial infarction were centrally adjudicated by 2 independent cardiologists, blinded to hs-cTnI-VITROS concentrations. RESULTS: Among 2931 eligible patients, 467 (16%) were diagnosed with myocardial infarction. In the derivation cohort (n=1466), a cutoff </=2 ng/L at presentation in patients with chest pain onset >3 hours (direct rule-out) and </=2 ng/L in combination with a 1-hour absolute change of </=1 ng/L ruled out 51% of patients, with a sensitivity of 99.1% (96.9%-99.8%). Predefined rule-in thresholds (0 hour-value >/=40 ng/L [direct rule-in] or an absolute change within 1 hour of >/=4 ng/L) identified 16.9% of patients, with a specificity of 95.9% (94.7%-96.9%). Very high sensitivity and specificity were confirmed in the validation cohort (n=1465). Comparable findings were observed for the alternative 0/2-hour algorithm with </=2 ng/L as the rule-out threshold. CONCLUSIONS: The alternative 0/1-hour and 0/2-hour algorithms using limit of quantification-based rule-out cutoffs of </=2 ng/L with the hs-cTnI-VITROS assay demonstrated very high safety and efficacy in suspected myocardial infarction. REGISTRATION: URL: https://www.clinicaltrials.gov/; Identifier: NCT00470587.
Keywords: journalArticle; *Myocardial Infarction/diagnosis/blood; *Troponin I/blood; Aged; Algorithms; Biomarkers/blood; Female; Humans; Male; Middle Aged; Nstemi; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Time Factors; biomarkers; chest pain; myocardial infarction