Undetectable concentrations of an FDA-approved high-sensitivity cardiac Troponin T assay to rule out acute myocardial infarction at emergency department arrival

Abstract

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 were, 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 3-200ng/L.

Results

7130 patients met inclusion criteria. AMI incidence at 7-, 30- and 90 days was 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. The limit of detection of the assay (5ng/L) ruled out AMI in 33.6% of patients with 99.8% sensitivity and 99.95% negative predictive value for 7-day AMI. The limit of quantification (the 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% negative predictive value. The sensitivity of the cutoffs of <3, <5 and <6 ng/L for 7-day MACE was 99.6%, 97.4% and 96.6%, respectively. The NPV of the cutoffs of <3, <5 and <6 ng/L for 7-day MACE was 99.8%, 99.5% and 99.4%, respectively.A secondary analysis was performed in a subgroup of 3549 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; 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 sensitivity of cutoffs of <3, <5 and <6 ng/L for 7-day MACE was 99.8%, 97.4% and 96.6%, respectively. In this higher-risk subgroup, the NPV of cutoffs of <3, <5 and <6 ng/L for 7-day MACE was 99.7%, 98.5% and 98.4%, respectively.

Conclusions

When used in real-world clinical practice conditions, hsTnT concentrations < 6 ng/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 negative predictive value. The sensitivity for MACE is unacceptably low, thus a single-troponin rule-out strategy should only be used in the context of a structured risk evaluation.

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