Undetectable Concentrations of a Food and Drug Administration-approved High-sensitivity Cardiac Troponin T Assay to Rule Out Acute Myocardial Infarction at Emergency Department Arrival

Background: The objective of this study was to quantify the sensitivity of very low concentrations of high-sensitivity cardiac troponin T (hsTnT) at ED arrival for acute myocardial infarction (AMI) in a large cohort of chest pain patients evaluated in real-world clinical practice. Methods: This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs, excluding those with ST-elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes were AMI at 7, 30, and 90 days. Secondary outcomes included major adverse cardiac events (MACE; all-cause mortality, AMI, and revascularization) and the individual MACE components. Test characteristics were calculated for hsTnT values from 3 to 200ng/L . Results: A total of 7,130 patients met inclusion criteria. AMI incidences at 7, 30, and 90 days were 5.8, 6.0, and 6.2%. When the hsTnT assay was performed at ED arrival, the limit of blank of the assay (3ng/L) ruled out 7-day AMI in 15.5% of patients with 100% sensitivity and negative predictive value (NPV). The limit of detection of the assay (5ng/L) ruled out AMI in 33.6% of patients with 99.8% sensitivity and 99.95% NPV for 7-day AMI. The limit of quantification (the Food and Drug Administration [FDA]-approved cutoff for lower the reportable limit) of 6ng/L ruled out AMI in 42.2% of patients with 99.8% sensitivity and 99.95% NPV. The sensitivities of the cutoffs of <3, <5, and <6ng/L for 7-day MACE were 99.6, 97.4, and 96.6%, respectively. The NPVs of the cutoffs of <3, <5, and <6ng/L for 7-day MACE were 99.8, 99.5, and 99.4%, respectively. A secondary analysis was performed in a subgroup of 3,549 higher-risk patients who underwent serial troponin testing. In this subgroup, a cutoff of 3ng/L ruled out 7-day AMI in 9.6% of patients with 100% sensitivity and NPV, a cutoff of 5ng/L ruled out 7-day AMI in 23.3% of patients with 99.7% sensitivity and 99.9% NPV, and a cutoff of 6ng/L ruled out 7-day AMI in 29.8% of patients with 99.7 and 99.9% NPV. In the higher-risk subgroup, the sensitivities of cutoffs of <3, <5, and <6ng/L for 7-day MACE were 99.8, 97.4, and 96.6%, respectively. In this higher-risk subgroup, the NPV of cutoffs of <3, <5, and <6ng/L for 7-day MACE were 99.7, 98.5, and 98.4%, respectively. Conclusions; When used in real-world clinical practice conditions, hsTnT concentrations<6ng/L (below the lower reportable limit for an FDA-approved assay) at the time of ED arrival can rule out AMI with very high sensitivity and NPV. The sensitivity for MACE is unacceptably low, and thus a single-troponin rule-out strategy should only be used in the context of a structured risk evaluation.