Single test rule-out of acute myocardial infarction using the limit of detection of a new high-sensitivity troponin I assay

Abstract

ObjectivesTo determine the diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay in patients presenting to the Emergency Department (ED) with suspected acute coronary syndromes. Specifically, we evaluated the use of a single blood test at the time of arrival in the ED, using low hs-cTnI cut-offs. MethodsIn a prospective diagnostic test accuracy study at 14 centers, we included patients presenting to the ED with suspected ACS within 12 h of symptom onset. We drew blood for hs-cTnI (Siemens ADVIA Centaur, overall 99th percentile 47 ng/L, limit of quantification [LoQ] 2.50 ng/L) on arrival. Patients underwent serial cardiac troponin testing over 3–6 h. The primary outcome was an adjudicated diagnosis of acute myocardial infarction (AMI). We evaluated the incidence of major adverse cardiac events (MACE: death, AMI or revascularization) after 30 days. Test characteristics for hs-cTnI were calculated using previously reported cut-offs set at the LoQ and 5 ng/L. ResultsWe included 999 patients, including 131 (13.1%) with an adjudicated diagnosis of AMI. Compared to the LoQ (100.0% sensitivity [95% CI 95.9–100.0%]), 99.7% negative predictive value [NPV; 95% CI 97.6–100.0%]), a 5 ng/L cut-off had slightly lower sensitivity (99.2%; 95% CI 95.8–100.0%) and similar NPV (99.8%; 95% CI 98.6–100.0%) but would rule out more patients (28.6% at the LoQ vs 50.4% at 5 ng/L). MACE occurred in 2 (0.7%) patients with hs-cTnI below the LoQ and 7 (1.4%) patients with hs-cTnI < 5 ng/L. Accounting for time from symptom onset or ECG ischemia did not further improve sensitivity. ConclusionThe Siemens ADVIA Centaur hs-cTnI assay has high sensitivity and NPV to rule out AMI with a single blood test in the ED. At the LoQ cut-off a sensitivity > 99% can be achieved. At a 5 ng/L cut-off it may be possible to rule out AMI for over 50% patients.