A practical approach for the validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a North American city

Abstract

ObjectivesDespite several publications on the analytical performance of high-sensitivity cardiac troponin (hs-cTn) assays, there has been little information on how laboratories should validate and implement these assays into clinical service. Our study provides a practical approach for the validation and implementation of a hs-cTn assay across a large North American City.Design and methodsValidation for the Abbott ARCHITECT hs-cTnI assay (across 5 analyzers) consisted of verification of limit of blank (LoB), precision (i.e., coefficient of variation; CV) testing at the reported limit of detection (LoD) and within and outside the 99th percentile, linearity testing, cTnI versus hs-cTnI patient comparison within and between analyzers (Passing and Bablok and non-parametric analyses). Education, clinical communications, and memorandums were issued in advance to inform all staff across the city as well as a selected reminder the day before live-date to important users. All hospitals switched to the hs-cTnI assay concurrently (the contemporary cTnI assay removed) with laboratory staff instructed to repeat samples previously measured with the contemporary cTnI assay with the hs-cTnI assay only by physician request.ResultsAcross the 5 analyzers and 6 reagent packs the overall LoB was 0.6 ng/L (n=60) with a CV of 33% at an overall mean of 1.2 ng/L (n=60; reported LoD=1.0 ng/L), with linearity demonstrated from 45,005 ng/L to 1.1 ng/L. Precision testing with a normal patient-pool QC material (mean range across 5 analyzers was 3.9–4.4 ng/L) yielded a range of CVs from 7% to 10% (within-run) and CVs from 7% to 18% (between-run) with the high patient-pool QC material (mean range across 5 analyzers was 29.6–36.3 ng/L) yielding a range of CVs from 2% to 5% (within-run) and CVs from 4% to 8% (between-run). There was agreement between hs-cTnI versus cTnI with the patient samples (slope ranges: 0.89–1.03; intercept ranges: 1.9–3.8 ng/L), however, the median CV on patient samples <100 ng/L across the analyzers was 5.6% for hs-cTnI versus 18.7% for the contemporary assay (p<0.001). Following the switch to hs-cTnI testing, no requests for repeat measurements were received.ConclusionsValidation and implementation of hs-cTnI testing across multiple sites requires collaboration within the laboratories and between hospital laboratories and clinical staff.

Acceptable Analytical Variation May Exceed High-Sensitivity Cardiac Troponin I Cutoffs in Early Rule-Out and Rule-In Acute Myocardial Infarction Algorithms

“…To rule in acute myocardial infarction, the 2-h algorithm proposes a change of 15 ng/L in hs-cTnI concentrations, which does appear to exceed our analytical variation for concentrations Ͻ64 ng/L, as corroborated by the high patient-pool QC data and our previous study (4 ). Interesting, though, is the cutoff of Ն64 ng/L to rule in, which is at least 2 times higher than the published 99th percentile and would most likely be different for laboratories using heparin plasma, because that matrix yields higher results than serum (used in 2-h protocol) or EDTA plasma (used at HHS), especially for concentrations Ͼ60 ng/L (5 ).…”

“…Clinically, we report hs-cTnI results in whole numbers while keeping an extra significant digit for QC monitoring (4 ). It is noteworthy that a change of 3 ng/L at hscTnI concentrations Յ6 ng/L would be within the acceptable analytical variation of the assay in our hospital network.…”

Clinical chemistry score versus high-sensitivity cardiac troponin I and T tests alone to identify patients at low or high risk for myocardial infarction or death at presentation to the emergency department

“…19,[26][27][28][29][30][31][32] Importantly, these concentrations can be monitored by laboratories via different quality assurance procedures, which will mitigate misclassification of patients owing to unacceptable analytical variation. 5,38 The CCS was reproducible across different sample types (ethylenediaminetetraacetic acid plasma, lithium heparin plasma and serum), and under different storage and preanalytical conditions, which should be reassuring to physicians and clinical laboratories, because hs-cTn measurements alone can be affected by different blood collection tubes and preanalytical interferences.…”

“…The cut-offs used for each test were based on accepted normal levels and low-risk clinical cut points, with values of eGFR of 90 mL/min/1.73 m 2 or more, glucose of less than 5.6 mmol/L, hs-cTnI of less than 4 ng/L and of hs-cTnT less than 8 ng/L used to identify patients at low risk (i.e., abnormal value 1 point and normal 0 points). 13,[25][26][27] For hs-cTn, 2 additional cut points were selected based on analytical variation, population and health outcome studies, [26][27][28][29][30][31][32] to have a final CCS range of 0-5 points (i.e., sum of the points for the results for glucose, eGFR and hs-cTn obtained from the patient's blood work at presentation to the emergency department; Supplemental Table 1, Appendix 3, available at www.cmaj.ca/ lookup/suppl/doi:10.1503/cmaj.180144/-/DC1).…”

Adopting ‘ng/L’ as the units for high-sensitivity cardiac troponin assays and commitment by the entire health-care team could be the key for adopting recommendations

“…During the transition from the sensitive cTnI assay to the hscTnI assay, we changed the units to ng/L, maintained the 99th percentile cut-off, recommended a 3 h time interval between measurements, and this time obtained prior agreement and commitment from the clinical services for this transition. 7 In the six months following the implementation of hs-cTnI testing, the median time interval between the first and second sample for hscTnI measurements (n ¼ 5479 pairs) in the ED was significantly shorter, at 3.7 h vs. 7.2 h; P < 0.001 by MannWhitney U test.…”