Analytical Bias in Troponin Assays Affects Rule-Out Rates More Than Diagnostic Sensitivity
This multicenter simulation study reveals that assay-specific analytical bias has a greater impact on the proportion of patients ruled out by 0/1-hour accelerated diagnostic protocols than on diagnostic sensitivity for myocardial infarction. Rule-out rates varied dramatically across bias scenarios (0-60% for hs-cTnT at 0h), suggesting that inter-laboratory analytical variability may explain much of the heterogeneity in reported ADP performance.
The original study
Analytical Error of Cardiac Troponin and Impact on the Performance of Accelerated Diagnostic Protocols in Patients with Acute Chest Pain.
- Authors
- Saeed N, Restan IZ, Steiro OT, Tjora HL, Langørgen J, Skadberg Ø, et al.
- Journal
- Clinical chemistry
- Type
- Journal Article, Multicenter Study, Observational Study
- PMID
- 41092105
Original abstract
BACKGROUND: This study simulates how assay-specific bias influences the diagnostic performance of 0/1-h accelerated diagnostic protocols (ADPs) for 3 different high-sensitivity cardiac troponin (hs-cTn) assays. METHODS: We included 1493 patients presenting with chest pain. hs-cTnT (Roche Diagnostics), hs-cTnI from Abbott Diagnostics (hs-cTnI-A), and Siemens Healthineers (hs-cTnI-S) were measured at admission. The absolute total error observed in a state-of-the-art EQA study were added to the admission concentrations, producing 6 new variables being adjusted for maximum possible bias (if analytical variation is 0) (+biasmean, +biasmax95%CI, +biasmin95%CI, -biasmean, -biasmax95%CI, -biasmin95%CI). The influence of this "worst-case scenario" bias was compared after calculating sensitivity, specificity, negative and positive predictive values, and rule-out proportion for 30-day myocardial infarction or death for the observed and bias-adjusted hs-cTn concentrations. RESULTS: For 0-h rule-out, hs-cTnI-S and hs-cTnT had a sensitivity of >99.0%, compared to 97.7% for hs-cTnI-A. After adding the bias, sensitivity was unchanged for hs-cTnI-S (99.5%), but lower for hs-cTnT (95.5%), and hs-cTnI-A (96.2%). For the 0-/1-h algorithm, adding bias reduced sensitivity to 95.5% for hs-cTnT, while both hs-cTnI algorithms were unchanged (100.0%). Rule-out proportions for 0 h ranged from 0% to 60.0% for hs-cTnT, 28.2%-62.7% for hs-cTnI-A, and 3.5%-35.5% for hs-cTnI-S. For the 0-/1-h algorithm, ranges were 57.7%-75.8% (hs-cTnT), 52.8%-67.5% (hs-cTnI-A), and 45.7%-61.2% (hs-cTnI-S). CONCLUSION: Analytical bias of hs-cTn assays affects the clinical rule-out rate of the 0/1-h ADPs more than the diagnostic sensitivity. Bias may have a greater influence on the proportion of patients requiring hospital admission and may contribute to the heterogeneity of the reported rule-out rates of current ADPs. ClinicalTrials.gov Registration Number: NCT02620202.