Abstract
Objectives
We evaluated the analytical performance characteristics and the biological equivalence of the Atellica TnIH assay.
Methods
Precision, detection capability, linearity, and sex specific 99th percentiles were determined de novo. Classification of patients relative to the 99th percentiles was used to assess biological equivalence.
Results
Analytical precision and detection capability of the Atellica TnIH assay is excellent with a limit of blank <1 ng/L and 62.5% of women and 93% of men had results above the limit of detection. The 99th percentiles (90% CI) in women were 49 ng/L (31–67) and 70 ng/L (48–121) in men. An asymmetrical distribution involving 5% of results was notable. Agreement was moderate (Kappa 0.58, 95% CI 0.53–0.63) with 20% of patients discordantly classified with Atellica TnIH below and Access hsTnI above the 99th percentiles. Serial results in 195 patients demonstrated good agreement (Kappa 0.84, 95% CI 0.77–0.90). Differences greater than the assay specific reference change values (z≥±1.96) occurred in 65% (95% CI 53–76%) of 99th percentile discordant patients compared to 2.7% (p<0.001) and 76% (p=0.17) of the concordant low and high cTnI groups respectively.
Conclusions
The 99th percentile discordant and the concordantly elevated groups are more alike with respect to their z≥±1.96 rates. This favours an overestimated Atellica TnIH 99th percentile as more likely, and we hypothesize that antibody interference resulting in asymmetric scatter of nearly 5% samples may be the underlying mechanism. Analytical accuracy and interferences in cardiac troponin assays should be investigated and resolved with high priority.
Funding source: Siemens Healthineers
-
Research funding: Reagents were provided at no cost by Siemens Healthineers. The funder played no role in the design, data collection, analysis, drafting or editing and the the decision to submit the manuscript.
-
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
-
Competing interests: Authors state no conflict of interest.
-
Informed consent: Not applicable.
-
Ethical approval: The local Institutional Review Board deemed the study exempt from review (Royal Brisbane and Women’s Hospital Ethical Committee LNR/2021/QRBW/74675).
References
1. Thygesen, K, Alpert, JS, Jaffe, A, Chaitman, BR, Bax, JJ, Morrow, DA, et al.. Fourth universal definition of myocardial infarction. Eur Heart J 2018;40:237–69. https://doi.org/10.5603/KP.2018.0203.Search in Google Scholar PubMed
2. Boeddinghaus, J, Twerenbold, R, Nestelberger, T, Badertscher, P, Wildi, K, Puelacher, C, et al.. Clinical validation of a novel high-sensitivity cardiac troponin I assay for early diagnosis of acute myocardial infarction. Clin Chem 2018;64:1347–60. https://doi.org/10.1373/clinchem.2018.286906.Search in Google Scholar PubMed
3. Greenslade, J, Cho, E, Van Hise, C, Hawkins, T, Parsonage, W, Ungerer, J, et al.. Evaluating rapid rule-out of acute myocardial infarction using a high-sensitivity cardiac troponin I assay at presentation. Clin Chem 2018;64:820–9. https://doi.org/10.1373/clinchem.2017.283887.Search in Google Scholar PubMed
4. Boeddinghaus, J, Nestelberger, T, Twerenbold, R, Koechlin, L, Meier, M, Troester, V, et al.. High-sensitivity cardiac troponin I assay for early diagnosis of acute myocardial infarction. Clin Chem 2019;65:893–904. https://doi.org/10.1373/clinchem.2018.300061.Search in Google Scholar PubMed
5. Chapman, AR, Fujisawa, T, Lee, KK, Andrews, JP, Anand, A, Sandeman, D, et al.. Novel high-sensitivity cardiac troponin I assay in patients with suspected acute coronary syndrome. Heart 2019;105:616–22. https://doi.org/10.1136/heartjnl-2018-314093.Search in Google Scholar PubMed PubMed Central
6. Nowak, RM, Christenson, RH, Jacobsen, G, McCord, J, Apple, FS, Singer, AJ, et al.. Performance of novel high-sensitivity cardiac troponin I assays for 0/1-hour and 0/2- to 3-hour evaluations for acute myocardial infarction: results from the HIGH-US Study. Ann Emerg Med 2020;76:1–13. https://doi.org/10.1016/j.annemergmed.2019.12.008.Search in Google Scholar PubMed
7. Bularga, A, Lee, KK, Stewart, S, Ferry, AV, Chapman, AR, Marshall, L, et al.. High-sensitivity troponin and the application of risk stratification thresholds in patients with suspected acute coronary syndrome. Circulation 2019;140:1557–68. https://doi.org/10.1161/circulationaha.119.042866.Search in Google Scholar
8. Christenson, RH, Duha, S, Apple, FS, Nowak, R, Peacock, WF, Limkakeng, AT, et al.. Pivotal findings for a high-sensitivity cardiac troponin assay: results of the HIGH-US study. Clin Biochem 2020;78:32–9. https://doi.org/10.1016/j.clinbiochem.2019.10.013.Search in Google Scholar PubMed
9. Wildi, K, Gimenez, MR, Twerenbold, R, Reichlin, T, Jaeger, CD, Heinzelmann, A, et al.. Misdiagnosis of myocardial infarction related to limitations of the current regulatory approach to define clinical decision values for cardiac troponin. Circulation 2015;131:2032–40. https://doi.org/10.1161/circulationaha.114.014129.Search in Google Scholar PubMed PubMed Central
10. Kavsak, PA, Mondoux, SE, Martin, J, Hewitt, MK, Clark, L, Caruso, N, et al.. Disagreement between cardiac troponin tests yielding a higher incidence of myocardial injury in the emergency setting. J Cardiovasc Dev Dis 2021;8:31. https://doi.org/10.3390/jcdd8030031.Search in Google Scholar PubMed PubMed Central
11. Karády, J, Mayrhofer, T, Ferencik, M, Nagurney, JT, Udelson, JE, Kammerlander, AA, et al.. Discordance of high-sensitivity troponin assays in patients with suspected acute coronary syndromes. J Am Coll Cardiol 2021;77:1487–99. https://doi.org/10.1016/j.jacc.2021.01.046.Search in Google Scholar PubMed PubMed Central
12. Ungerer, JPJ, Marquart, L, O’Rourke, PK, Wilgen, U, Pretorius, CJ. Concordance, variance, and outliers in 4 contemporary cardiac troponin assays: implications for harmonization. Clin Chem 2012;58:274–83. https://doi.org/10.1373/clinchem.2011.175059.Search in Google Scholar PubMed
13. Pretorius, CJ, Tate, JR, Wilgen, U, Cullen, L, Ungerer, JPJ. A critical evaluation of the Beckman Coulter access hsTnI: analytical performance, reference interval and concordance. Clin Biochem 2018;55:49–55. https://doi.org/10.1016/j.clinbiochem.2018.03.003.Search in Google Scholar PubMed
14. CLSI. Evaluation of detection capability for clinical laboratory measurement procedures; approved guideline, 2nd ed. CLSI Document EP17-A2. Wayne PA: Clinical and Laboratory Standards Institute; 2012.Search in Google Scholar
15. CLSI. User verification of precision and estimation of bias; approved guideline, 3rd ed. CLSI Document EP15-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.Search in Google Scholar
16. CLSI. Evaluation of the linearity of quantitative measurement procedures: a statistical approach; approved guideline CLSI Document EP06-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2003.Search in Google Scholar
17. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline, 3rd ed. CLSI Document C28-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.Search in Google Scholar
18. Pretorius, CJ, Wilgen, U, Ungerer, JPJ. Serial cardiac troponin differences measured on four contemporary analyzers: relative differences, actual differences and reference change values compared. Clin Chim Acta 2012;413:1789–91. https://doi.org/10.1016/j.cca.2012.07.001.Search in Google Scholar PubMed
19. Pretorius, CJ, Cullen, L, Parsonage, WA, Greenslade, JH, Tate, JR, Wilgen, U, et al.. Towards a consistent definition of a significant delta troponin with z-scores: a way out of chaos? Eur Heart J Acute Cardiovasc Care 2014;3:149–57. https://doi.org/10.1177/2048872613517084.Search in Google Scholar PubMed
20. Clerico, A, Ripoli, A, Masotti, S, Musetti, V, Aloe, R, Dipalo, M, et al.. Evaluation of 99th percentile and reference change values of a high-sensitivity cTnI method: a multicenter study. Clin Chim Acta 2019;493:156–61. https://doi.org/10.1016/j.cca.2019.02.029.Search in Google Scholar PubMed
21. Aw, TC, Huang, W, Le, TT, Pua, CJ, Ang, B, Phua, SK, et al.. High-sensitivity cardiac troponins in cardio-healthy subjects: a cardiovascular magnetic resonance imaging study. Sci Rep 2018;8:15409. https://doi.org/10.1038/s41598-018-33850-9.Search in Google Scholar PubMed PubMed Central
22. Fitzgerald, RL, Hollander, JE, Peacock, WF, Limkakeng, AT, Breitenbeck, N, Rivers, EJ, et al.. The 99th percentile upper reference limit for the 5th generation cardiac troponin T assay in the United States. Clin Chim Acta 2020;504:172–9. https://doi.org/10.1016/j.cca.2020.01.027.Search in Google Scholar PubMed
23. Petersen, PH, Stöckl, D, Blaabjerg, O, Pedersen, B, Birkemose, E, Thienpont, L, et al.. Graphical interpretation of analytical data from comparison of a field method with a reference method by use of difference plots. Clin Chem 1997;43:2039–46. https://doi.org/10.1093/clinchem/43.11.2039.Search in Google Scholar
24. Kavsak, PA, Roy, C, Malinowski, P, Mark, C, Scott, T, Clark, L, et al.. Macrocomplexes and discordant high-sensitivity cardiac troponin concentrations. Ann Clin Biochem 2018;55:500–4. https://doi.org/10.1177/0004563217734883.Search in Google Scholar PubMed
25. Lam, L, Aspin, L, Heron, RC, Ha, L, Kyle, C. Discrepancy between cardiac troponin assays due to endogenous antibodies. Clin Chem 2020;66:445–54. https://doi.org/10.1093/clinchem/hvz032.Search in Google Scholar PubMed
26. Kavsak, PA, Worster, A, Hill Jaffe, AS. Evaluation of the Siemens ADVIA Centaur high-sensitivity cardiac troponin I assay in serum. Clin Chim Acta 2018;487:216–21. https://doi.org/10.1016/j.cca.2018.10.012.Search in Google Scholar PubMed
27. Árnadóttir, Á, Pedersen, S, Hasselbalch, RB, Goetze, JP, Friis-Hansen, LJ, Bloch-Münster, A, et al.. Temporal release of high-sensitivity cardiac troponin T and I and copeptin after brief induced coronary artery balloon occlusion in humans. Circulation 2021;143:1095–104.10.1161/CIRCULATIONAHA.120.046574Search in Google Scholar PubMed
Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-0991).
© 2021 Walter de Gruyter GmbH, Berlin/Boston
