Commercial Quality Control Imprecision Estimates for High-Sensitivity Cardiac Troponin Deltas Used to Rule-in Myocardial Infarction with the ESC 0/1-Hour Algorithm

For high-sensitivity cardiac troponin (hs-cTn) assays a laboratory recommendation is to measure 3 levels of quality control (QC) materials with one concentration being between the limit of detection and the lowest sex-specific 99th-percentile concentration, another material with a concentration higher but close to the highest sex-specific 99th percentile concentration, with the third material having a concentration several-fold higher than the 99th-percentile concentration (1,). This joint recommendation from the AACC Academy and an IFCC task force further implores “that QC manufacturers produce materials that meet these recommendations for all cTn assays. Until they are available, laboratories should obtain QC materials that comply as closely as possible to the recommended concentrations.” (1,) However, for sites whose clinicians utilize the European Society of Cardiology (ESC) 0/1-hour algorithm, their respective clinical laboratories may find it challenging to obtain the most appropriate QC materials, as the stated hs-cTn cutoffs and their respective deltas are assay-dependent in the 0/1-hour algorithm (2, 3,). For example, focusing on the rule-in arm of the algorithm, the Abbott ARCHITECT hs-cTnI assay requires a 0 h hs-cTnI concentration ≥52 ng/L or a delta ≥6 ng/L over 1 hour whereas the most recent publication of this algorithm assessing the Ortho VITROS hs-cTnI assay requires a 0 h hs-cTnI concentration ≥40 ng/L or a delta ≥4 ng/L over 1 hour (2, 3,). Previous estimates on imprecision and total analytic error for hs-cTn assays have been derived from patient pool QC material and patient testing (1, 4). Accordingly, it is not known whether commercial QC will provide different precision estimates as compared to patient pool QC material for the assessment and laboratory monitoring of the ESC 0/1-hour algorithm. To this end, the Juravinski Hospital has been using patient pool QC materials that were prepared by obtaining an infectious free EDTA plasma pool with high cardiac troponin concentrations and spiking this material into leftover citrate phosphate dextrose plasma obtained from transfusion medicine to obtain 2 target concentrations. On material with a target concentration near 5 ng/L (normal) and the other material with a target concentration near 34 ng/L (male 99th percentile) for monitoring the Abbott ARCHITECT hs-cTnI assay from November 25, 2014 until October 8, 2019. From September 18, 2019 through to October 8, 2019, both the patient pool QC material (male 99th percentile QC n = 28) and the MAS OMNI CARDIO Control from Thermo Fisher (Lot no. OCRD2201LA; commercial control, n = 22) were tested with the imprecision being 2-fold higher than the commercial control compared to the patient pool QC over this time period (patient pool QC CV = 3.2% vs commercial control CV = 7.0%) (Table 1). From October 8 to October 24, 2019 when the commercial QC was used to monitor the Abbott ARCHITECT hs-cTnI assay, the imprecision estimates did not improve (CV = 7.5%). During this crossover period between QC materials, the commercial QC exhibited higher imprecision with drifts up to 2-SDs that would exceed 6 ng/L. Consequently, the increased variation of the commercial QC might necessitate the laboratory to set tighter quality control limits and interventions if clinicians or hospitals used the ESC 0/1-hour algorithm for patient management. Quality control material testing with different high-sensitivity cardiac troponin I assays and on different analyzers (Commercial QC is MAS OMNI CARDIO Control from Thermo Fisher Lot no. OCRD2201LA). Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (10.08.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 1 (10.14.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 2 (10.14.19 to 10.24.19) Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (10.08.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 1 (10.14.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 2 (10.14.19 to 10.24.19) Quality control material testing with different high-sensitivity cardiac troponin I assays and on different analyzers (Commercial QC is MAS OMNI CARDIO Control from Thermo Fisher Lot no. OCRD2201LA). Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (10.08.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 1 (10.14.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 2 (10.14.19 to 10.24.19) Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (09.18.19 to 10.08.19) Abbott hs-cTnI assay ARCHITECTi2000 (10.08.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 1 (10.14.19 to 10.24.19) Ortho hs-cTnI assay VITROS 7600 Analyzer 2 (10.14.19 to 10.24.19) To investigate whether this greater variation with a commercial QC material would be evident on a different hs-cTnI assay, the same commercial QC was also measured during this time frame on 2 VITROS 7600 analyzers (n = 20, with 2 measurements over 10 days between October 14 and October 24, 2019). On analyzer 1 (mean = 29.1 ng/L), the CV was 13.7%, and on analyzer 2 (mean = 28.1 ng/L), the CV was 9.3% (Table 1). With a delta of 4 ng/L stated in the ESC 0/1-hour algorithm for the Ortho hs-cTnI assay, the imprecision as demonstrated by the commercial QC may limit the ability of sites to utilize the ESC 0/1-hour algorithm. As more sophisticated approaches for ruling in and out myocardial infarction using different deltas are being proposed (5); the need for demonstrating and achieving appropriate precision for hs-cTn assays for use of these algorithms is important. Objective evidence produced by the clinical laboratory demonstrating the required precision is essential, and in this regard laboratory professionals may need to also consider the QC material itself as a source of variation if the imprecision estimates of the hs-cTn assay exceed those of algorithms used for early decision-making in the emergency setting. Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: None declared. Consultant or Advisory Role: P.A. Kavsak, Beckman, Roche, Siemens. Stock Ownership: None declared. Honoraria: P.A. Kavsak, Beckman, Roche, Siemens. Research Funding: P.A. Kavsak, Ortho Clinical Diagnostics. Expert Testimony: None declared. Patents: P.A. Kavsak, McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular biomarker field.

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