Rapid Exclusion of Acute Myocardial Injury and Infarction With a Single High-Sensitivity Cardiac Troponin T in the Emergency Department: A Multicenter United States Evaluation

Abstract

Background: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection (LoD) of 5 ng/L to exclude acute myocardial infarction. Per the United States (US) Food and Drug Administration (FDA), hs-cTnT can only report to the limit of quantitation (LoQ) of 6 ng/L, a threshold for which there is limited data. Our goal was to determine whether a single hs-cTnT below the LoQ of 6 ng/L is a safe strategy to identify patients at low-risk for acute myocardial injury and infarction. Methods: The efficacy (proportion identified as low-risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least one hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99 th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic electrocardiogram with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling-out acute myocardial infarction and safety (myocardial infarction or death at 30-days) were evaluated. Results: A total of 85,610 patients were evaluated in the CV Data Mart Biomarker cohort, amongst which 24,646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% vs. 20%, p<0.0001). 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% CI 98.6, 99.0) and sensitivity of 99.6% (95% CI 99.5, 99.6). In the adjudicated cohort, a nonischemic electrocardiogram with hs-cTnT<6 ng/L identified 33% of patients (610 of 1849) 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 myocardial infarction or death. Conclusions: A single hs-cTnT below the LoQ of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk

“…However, the sensitivities achieved for MI diagnostics and safety for both cohorts were very good: SEIGE, 98.9% and 99.3%; and SAMIE, 98.8% and 94.5%, respectively. Our findings for the novel whole-blood POC hs-cTnI assay are comparable to central laboratory hs-cTnI 9 and hs-cTnT 11 observations.…”

“…However, the sensitivities achieved for MI diagnostics and safety for both cohorts were very good: SEIGE, 98.9% and 99.3%; and SAMIE, 98.8% and 94.5%, respectively. Our findings for the novel whole-blood POC hs-cTnI assay are comparable to central laboratory hs-cTnI 9 and hs-cTnT 11 observations. Third, because of the variable rising kinetics of cTnI after acute MI in early presenters, 31 the lower sensitivities and NPVs for early rule-out were not as robust, and we suggest measuring a second sample to rule out MI in early presenters.…”

High-Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain

“…Recent US data confirm the safety of the use of a value at the LoQ (<6 ng/L) for the single sample rule out using the hs-cTnT assay. 56 We emphasize that there are robust clinical data for some hs-cTn assays suggesting that hs-cTn concentrations well above both the LoD and LoQ are of value in Limit of detection (LoD), limit of quantitation (LoQ), and 99th percentile upper reference limits according to the insert package information. Source: reference 10.…”

“…Recent US data confirm the safety of the use of a value at the LoQ (<6 ng/L) for the single sample rule out using the hs-cTnT assay. 56…”

Flexible and High-Throughput Photothermal Biosensors for Rapid Screening of Acute Myocardial Infarction Using Thermochromic Paper-Based Image Analysis

“…Within the last two decades, acute myocardial infarction (AMI) has become one of the major health risks for human beings. − Cardiac troponin I (cTnI) is a clear guide to the diagnosis of AMI based on serum or other body fluid biomarkers, mainly attributed to the fact that cTnI proteins exhibit a high specificity for injury in the surgical heart compared to creatine kinase-MB and fatty acid-binding proteins. , In addition, the gradual increase in cTnI levels in serum or other possible body fluids to the nanogram level a few days prior to the onset of actual acute symptoms provides actionable daily warning and early monitoring of AMI. , Currently, methods based on colorimetry, − fluorescent immunoassay, − and electrochemical testing , have been reported for sensitive testing of cTnI. However, it cannot be avoided that most methods require complex instrumentation and the involvement of well-trained personnel.…”