BACKGROUND: Rapid rule-out strategies using highsensitivity cardiac troponin assays are largely supported by studies performed outside the US in selected cohorts of patients with chest pain that are atypical of US practice, and focused exclusively on ruling out acute myocardial infarction (AMI), rather than acute myocardial injury, which is more common and associated with a poor prognosis. METHODS: Prospective, observational study of consecutive patients presenting to emergency departments [derivation (n = 1647) and validation (n = 2198) cohorts], where high-sensitivity cardiac troponin I (hs-cTnI) was measured on clinical indication. The negative predictive value (NPV) and diagnostic sensitivity of an hs-cTnI concentration <limit of detection (LoD) at presentation was determined for acute myocardial injury and for AMI or cardiac death at 30 days. RESULTS: In patients with hs-cTnI concentrations<99th percentile at presentation, acute myocardial injury occurred in 8.3% and 11.0% in the derivation and validation cohorts, respectively. In the derivation cohort, 27% had hs-cTnI < LoD, with NPV and diagnostic sensitivity for acute myocardial injury of 99.1% (95% CI, 97.7-99.8) and 99.0% (97.5-99.7) and an NPV for AMI or cardiac death at 30 days of 99.6% (98.4-100). In the validation cohort, 22% had hs-cTnI <LoD, with an NPV and diagnostic sensitivity for acute myocardial injury of 98.8% (97.9-99.7) and 99.3% (98.7-99.8) and an NPV for AMI or cardiac death at 30 days of 99.1% (98.2-99.8). CONCLUSIONS: A single hs-cTnI concentration <LoD rules out acute myocardial injury, regardless of etiology, with an excellent NPV and diagnostic sensitivity, and identifies patients at minimal risk of AMI or cardiac death at 30 days. ClinicalTrials.gov Identifier: NCT02060760
Bibliographical noteFunding Information:
Derivation cohort (Minneapolis, MN) partially funded through a grant from Abbott Diagnostics, who had no role in the design and conduction of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and the Minneapolis Medical Research Foundation. Validation cohort (Edinburgh, UK) funded by the British Heart Foundation (SP/12/10/29922 and PG/15/51/31596), and Senior Clinical Research Fellowship (FS/16/14/32023); F.S. Apple, Abbott Diagnostics to the institution; and research through Minneapolis Medical Research Foundation (MMRF) (not salaried), Abbott Diagnostics, Roche Diagnostics, Siemens Healthcare, Alere, Ortho-Clinical Diagnostics, Beckman Coulter, Trinity, Nanomix, and Becton Dickinson. Dr. Fred S. Apple had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
© 2016 American Association for Clinical Chemistry.