Evaluation of the diagnostic performance of current and next-generation assays for cardiac troponin I in the BWH-TIMI ED Chest Pain Study

摘要

Background: Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (Tnl) assay with 10-100-times greater sensitivity than current commercial assays. Methods: Among patients with non-traumatic chest pain enrolled in the BWH-TIMI ED Chest Pain Study, we measured Tnl (n=381) at baseline, 4-6 h, and 12-24 h with an investigational assay (S-Tnl; Singulex, detection-limit 0.0002 ug/l, 99th percentile 0.009 ug/l) and a contemporary sensitive assay (Tnl-Ultra; Siemens, detection-limit 0.006 ug/l, 99th percentile 0.04 ug/l). Final diagnosis was adjudicated using all diagnostic data and local hospital-based cardiac Tnl (Siemens), blinded to investigational cardiac Tn. Results: The adjudicated diagnosis was myocardial infarction (Ml) in 96 patients, unstable angina in 41, and acute non-coronary cardiovascular conditions in 50 patients. Baseline S-Tnl was highly sensitive for Ml (97%, 95% Cl 91-99%) with specificity 81 % (95% Cl 76-86%) and positive predictive value 63% (95% Cl 55-71%). The negative predictive value with S-Tnl was 99% (95% Cl 96-100%). S-Tnl had better diagnostic accuracy than the local assay (area under the curve 0.976 vs. 0.916, p=0.003). Among 20 patients with negative baseline Tnl and diagnosis of Ml, 19 had elevated baseline S-Tnl. Compared to Tnl-Ultra, S-Tnl trended toward higher sensitivity (97 vs. 94%, p=NS) but did not differ significantly in negative predictive value (99 vs. 98%) or area under the curve (p=0.29). Conclusion: Current and investigational Tn assays substantially increased clinical sensitivity and improved diagnostic accuracy for Ml, despite a decline in specificity. A contemporary sensitive assay delivered similar overall accuracy to the investigational test, suggesting that we have reached a point of maximum diagnostic return with increasing analytical sensitivity.