Rapid Exclusion of Acute Myocardial Injury and MI With hs-cTnT

Quick Takes

  • While several guidelines recommend the use of a single high-sensitivity troponin T level below the limit of detection (LoD) to exclude MI, this concentration threshold is not available for use in the United States, as the FDA requires the use of limit of quantitation (LoQ). The LoQ is the lowest detectable value with an imprecision of ≤20%.
  • This is a retrospective observational study examining the efficacy of hs-cTnT <6 ng/L (LoQ) in ruling out myocardial injury in two cohorts.
  • The negative predictive value of hs-cTnT <6 ng/L for myocardial injury was 98.8% (95% CI, 98.6, 99.0). Combining hs-cTnT <6 ng/L with a nonischemic ECG resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for 30-day MI or death.

Study Questions:

Is a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of quantitation (LoQ) of 6 ng/L a safe strategy to identify patients at low risk for acute myocardial injury and infarction?


This study examined the efficacy of hs-cTnT <6 ng/L in identifying patients at low risk of acute myocardial injury. The authors first leveraged a large multicenter biomarker cohort (CV Data Mart Biomarker Cohort)—which includes 85,610 patients presenting at any of the Mayo Clinic emergency departments and in whom at least one hs-cTnT measurement was obtained within 12 hours of presentation. The primary outcome was acute myocardial injury, defined as any subsequent hs-cTnT increase above the 99th percentile during the first 24 hours. Findings were validated in a separate cohort, the ACTION (MAyo Southwest WisConsin 5th Gen Troponin T ImplementatiON) study, a retrospective observational study in which hs-cTnT and electrocardiogram (ECG) data were collected in 1,979 patients. The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in this to evaluate the diagnostic performance for ruling-out acute myocardial infarction (AMI) and safety (MI or death at 30 days).


The mean age was 63 (± 18) years and women represented 50% of the CV Data Mart Biomarker cohort. A total of 24,646 (29%) had a baseline hs-cTnT <6 ng/L, of whom 49 (0.2%) had a diagnosis of AMI and 19 (0.1%) died. Those with hs-cTnT <6 ng/L were more likely to be younger and be women compared to those with detectable hs-cTnT. Among 11,962 patients with baseline hs-cTnT <6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% confidence interval [CI], 98.6, 99.0) and sensitivity of 99.6% (95% CI, 99.5, 99.6).

In the ACTION cohort (n = 1,979), the incidence of AMI (including both type 1 and 2 MIs) was 7.1% (n = 141). Overall, 624 (32%) patients had a baseline hs-cTnT <6 ng/L. A nonischemic ECG with hs-cTnT <6 ng/L identified 33% of patients (610 of 1,849 with ECGs) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for 30-day MI or death. Findings did not differ based on time of presentation (early vs. late) or the presence of chest pain.


A single hs-cTnT below the LoQ of 6 ng/L may be safe in identifying patients at very low risk for acute myocardial injury and infarction.


The latest AHA/ACC clinical practice guidelines recommend the use of a single hs-cTn below the limit of detection (LoD) to exclude myocardial injury. The Food and Drug Administration (FDA), however, has imposed the use of LoQ, which is the lowest measurable concentration with an imprecision of ≤20%. Few studies have examined the safety of using the LoQ threshold in excluding myocardial injury. The LoD has typically been <5 ng/L, while the LoQ is <6 ng/L. This study, while retrospective, provides findings supportive of the use of LoQ and consistent with that of major clinical trials, which evaluated the use of LoD. In the study, less than half of patients underwent serial testing of hs-cTnT, despite an institutional 0/2-hour testing protocol, raising the concern of selection bias. Given the nonsystematic measuring of hs-cTnT, the context of measurement becomes key; with the conclusion being: an hs-cTnT <6 ng/L can safely exclude acute myocardial injury in the right context. Troponin testing should support, and never supplant, clinical judgment.

Clinical Topics: Acute Coronary Syndromes, Prevention, ACS and Cardiac Biomarkers

Keywords: Acute Coronary Syndrome, Biomarkers, Chest Pain, Diagnostic Tests, Routine, Electrocardiography, Emergency Service, Hospital, Myocardial Infarction, Risk Assessment, Secondary Prevention, Troponin T

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