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

backgroundThere 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.

methodsThis 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.

resultsAmong 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.

conclusionsThe 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.