Alternative Rule‐Out Cutoffs for a Novel High‐Sensitivity Cardiac Troponin I Assay in Patients With Suspected Myocardial Infarction

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.