ESC 0/1h-algorithm using the updated, biotin-resistant high-sensitivity cardiac troponin T assay

Abstract

Abstract Background For rapid and safe triage of patients with suspected non-ST-elevation myocardial infarction (NSTEMI), the European Society of Cardiology (ESC) recommends the use of a 0/1h-algorithm based on high-sensitivity cardiac troponin (hs-cTn) T or I. Recently, multiple widely used immuno-assays including hs-cTnT have been reported to interfere with high biotin concentrations, potentially leading to false-negative results. To address this major concern, an updated, biotin-resistant hs-cTnT assays has been developed by the manufacturer to replace its previous version. Purpose We aimed to assess and compare the clinical performance of the updated, biotin-resistant hs-cTnT Elecsys assay when using the original ESC hs-cTnT 0/1h-algorithm. Methods In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department (ED), hs-cTnT was serially measured at ED presentation and after one hour with the original, biotin-sensitive (hs-cTnT-original) and the updated, biotin-resistant hs-cTnT (hs-cTnT-updated) assay. Patients presenting with STEMI were excluded. The final diagnosis was centrally adjudicated by two independent cardiologists using all available data including coronary angiography, echocardiography, follow-up data, and serial measurements of hs-cTn. We assessed the overall efficacy, rule-out safety and rule-in accuracy of the ESC hs-cTnT 0/1h-algorithm when using hs-cTnT-updated and compared it with the use of hs-cTnT-original. Results NSTEMI was the final diagnosis in 162 of 865 (19%) patients. The ESC 0/1h-algorithm using hs-cTnT-updated triaged 58% of patients towards "rule-out", 21% towards "rule-in", and 21% towards "observe" compared to 56%, 21% and 23% using hs-cTnT-original, respectively (Figure 1, p=ns). Only 6 patients were reclassified using hs-cTnT-updated. Safety of rule-out was very high using hs-cTnT-updated with a negative predictive value for NSTEMI of 100% (95% confidence interval (CI), 99.2-100%) and a sensitivity of 100% (95%CI, 97.7-100%) and was highly comparable to hs-cTnT-original (NPV 100% [95%CI 99.2-100], sensitivity 100% [95%CI, 97.7-100%], all p-values for comparison not significant). Of note, no NSTEMI-patient was missed by the ESC 0/1h-algorithm neither using hs-cTnT-updated nor original. Similarly, accuracy of rule-in was very high (positive predictive value 73.7% [95%CI, 66.8-79.6%], specificity 93.3% [95%CI, 91.2-94.9%]) and highly comparable to hs-cTnT-original (PPV 73.9% [95%CI 67.1-79.7%], specificity 93.2% [95%CI, 91.1-94.8%], all p-values for comparison not significant). Conclusions The safety and efficacy of the ESC 0/1h-algorithm using the novel updated, biotin-resistant hs-cTnT-assay is excellent and similar to the use of the original assay without the need to adjust the cutoffs to the new assay.Figure 1