Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 16, 2022

Analytical and clinical performance evaluation of a new high-sensitivity cardiac troponin I assay

Shuo Yang, Qian Zhang, Boxin Yang, Zijing Li, Wenyuan Sun and Liyan Cui

Abstract

Objectives

To validate the analytical performance and diagnostic accuracy for non-ST-segment elevation myocardial infarction (NSTEMI) with a new high-sensitivity cardiac troponin I (hs-cTnI) assay on the automated light-initiated chemiluminescent assay (LiCA®) platform.

Methods

Comprehensive analytical validations were performed, and the 99th percentile upper reference limit (URL) from apparently healthy individuals were established. We evaluated the diagnostic performance of the assay for NSTEMI.

Results

The limit of quantitation (LoQ) were 1.9 ng/L (20% CV) and 5.1 ng/L (10% CV). The sex-specific 99th percentile URLs were 17.6 ng/L (4.2% CV) for men (age 20–79y) and 14.2 ng/L (4.9% CV) for women (age 19–89y) in serum, 14.4 ng/L (4.9% CV) for men (age 19–88y) and 12.9 ng/L (5.2% CV) for women (age 19–87y) in plasma, respectively. Detection rates in healthy individuals were from 98.7 to 99.1%. The correlation coefficient and median bias between LiCA and Architect were 0.985 and 0.1% (−2.0–2.9%) in full analytical range of serum specimens. In lower range (<100 ng/L), LiCA had an overall positive bias 6.7% (−1.6–13.3%), R=0.949. At the specific medical decision levels (15.2, 26.2 and 64.0 ng/L), assay difference was estimated to be <10%. No significant differences on AUC, sensitivity and specificity, NPV and PPV were found between LiCA and Architect for the diagnosis of NSTEMI.

Conclusions

LiCA hs-cTnI is a precise, highly sensitive and specific assay that meets the requirement of a 3rd generation (level 4) high-sensitivity method. The diagnostic accuracy of LiCA assay for NSTEMI is comparable to the established Architect hs-cTnI assay.


Corresponding author: Liyan Cui, MD, Department of Laboratory Medicine, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, P.R. China, Phone: 86 10 82267612, E-mail:

Funding source: National Major Science and Technology Projects of China

Award Identifier / Grant number: 2017ZX09304012-005

  1. Research funding: This work was funded by National Major Science and Technology Projects of China (No. 2017ZX09304012-005). The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulation, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the Ethics Committee of Peking University Third Hospital (M2021347).

  6. Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

1. Thygesen, K, Alpert, JS, Jaffe, AS, Chaitman, BR, Bax, JJ, Morrow, DA, et al.. Fourth universal definition of myocardial infarction (2018). Circulation 2018;138:e618–51. https://doi.org/10.1161/CIR.0000000000000617.Search in Google Scholar

2. Collet, JP, Thiele, H, Barbato, E, Barthelemy, O, Bauersachs, J, Bhatt, DL, et al.. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289–367. https://doi.org/10.1093/eurheartj/ehaa575.Search in Google Scholar

3. Puymirat, E, Simon, T, Cayla, G, Cottin, Y, Elbaz, M, Coste, P, et al.. Acute myocardial infarction: changes in patient characteristics, management, and 6-month outcomes over a period of 20 years in the FAST-MI program (French registry of acute ST-elevation or non-ST-elevation myocardial infarction) 1995 to 2015. Circulation 2017;136:1908–19. https://doi.org/10.1161/circulationaha.117.030798.Search in Google Scholar

4. Braunwald, E, Morrow, DA. Unstable angina: is it time for a requiem? Circulation 2013;127:2452–7. https://doi.org/10.1161/circulationaha.113.001258.Search in Google Scholar

5. Shah, ASV, Anand, A, Strachan, FE, Ferry, AV, Lee, KK, Chapman, AR, et al.. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial. Lancet 2018;392:919–28. https://doi.org/10.1016/S0140-6736(18)31923-8.Search in Google Scholar

6. Wu, AHB, Christenson, RH, Greene, DN, Jaffe, AS, Kavsak, PA, Ordonez-Llanos, J, et al.. Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the academy of the American Association for Clinical Chemistry and the task force on clinical applications of cardiac bio-markers of the international federation of clinical chemistry and laboratory medicine. Clin Chem 2018;64:645–55. https://doi.org/10.1373/clinchem.2017.277186.Search in Google Scholar PubMed

7. Apple, FS, Jaffe, AS, Collinson, P, Mockel, M, Ordonez-Llanos, J, Lindahl, B, et al.. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem 2015;48:201–3. https://doi.org/10.1016/j.clinbiochem.2014.08.021.Search in Google Scholar PubMed

8. Apple, FS. A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem 2009;55:1303–6. https://doi.org/10.1373/clinchem.2009.128363.Search in Google Scholar PubMed

9. Giannitsis, E, Kurz, K, Hallermayer, K, Jarausch, J, Jaffe, AS, Katus, HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 2010;56:254–61. https://doi.org/10.1373/clinchem.2009.132654.Search in Google Scholar PubMed

10. 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

11. Apple, FS, Wu, AHB, Sandoval, Y, Sexter, A, Love, SA, Myers, G, et al.. Sex-specific 99th percentile upper reference limits for high sensitivity cardiac troponin assays derived using a universal sample bank. Clin Chem 2020;66:434–44. https://doi.org/10.1093/clinchem/hvz029.Search in Google Scholar PubMed

12. Ullman, EF, Kirakossian, H, Switchenko, AC, Ishkanian, J, Ericson, M, Wartchow, CA, et al.. Luminescent oxygen channeling assay (LOCI): sensitive, broadly applicable homogeneous immunoassay method. Clin Chem 1996;42:1518–26. https://doi.org/10.1093/clinchem/42.9.1518.Search in Google Scholar

13. CLSI. User verification of precision and estimation of bias; approved guideline-third edition. CLSI document EP15-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.Search in Google Scholar

14. CLSI. Evaluation of the linearity of quantitative measurement procedures: a statistical approach; approved guideline. CLSI document EP6-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2003.Search in Google Scholar

15. CLSI. Evaluation of detection capability for clinical laboratory measurement procedures; approved guideline-second edition. CLSI document EP17-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2012.Search in Google Scholar

16. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline-third edition. CLSI document C28-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2010.Search in Google Scholar

17. CLSI. Method comparison and bias estimation using patient samples; approved guideline-second edition. CLSI document EP9-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2002.Search in Google Scholar

18. Roffi, M, Patrono, C, Collet, JP, Mueller, C, Valgimigli, M, Andreotti, F, et al.. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2016;37:267–315. https://doi.org/10.1093/eurheartj/ehv320.Search in Google Scholar PubMed

19. DeLong, ER, DeLong, DM, Clarke-Pearson, DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988;44:837–45. https://doi.org/10.2307/2531595.Search in Google Scholar

20. Thygesen, K, Mair, J, Giannitsis, E, Mueller, C, Lindahl, B, Blankenberg, S, et al.. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012;33:2252–7. https://doi.org/10.1093/eurheartj/ehs154.Search in Google Scholar PubMed

21. Yang, S, Yang, R, Zhang, S, Liu, D, Zhou, J, Wang, T, et al.. Clinical diagnostic performance of light-initiated chemiluminescent assay compared with the Architect chemiluminescence immunoassay for detection of HCV antibody. J Clin Lab Anal 2019;33:e22928. https://doi.org/10.1002/jcla.22928.Search in Google Scholar PubMed PubMed Central

22. Zhang, Y, Liang, Y, Feng, L, Cui, L. Diagnostic performance of 14-3-3eta and anti-carbamylated protein antibodies in Rheumatoid Arthritis in Han population of Northern China. Clin Chim Acta 2020;502:102–10. https://doi.org/10.1016/j.cca.2019.12.011.Search in Google Scholar PubMed

23. Li, J, Li, S, Huang, L, Cui, Y, She, T, Bian, Y, et al.. A light-initiated chemiluminescent assay for rapid quantitation of allergen-specific IgG4 in clinical samples. Clin Chim Acta 2019;489:83–8. https://doi.org/10.1016/j.cca.2018.11.036.Search in Google Scholar PubMed

24. Bevins, NJ, Hubbard, JA, Fitzgerald, RL, Kelner, MJ. A dilution method to mitigate biotin interference in cardiac troponin T testing. J Appl Lab Med 2019;4:415–21. https://doi.org/10.1373/jalm.2018.028589.Search in Google Scholar PubMed

25. Mzougui, S, Favresse, J, Soleimani, R, Fillee, C, Gruson, D. Biotin interference: evaluation of a new generation of electrochemiluminescent immunoassays for high-sensitive troponin T and thyroid-stimulating hormone testing. Clin Chem Lab Med 2020;58:2037–45. https://doi.org/10.1515/cclm-2020-0214.Search in Google Scholar PubMed

26. Kavsak, PA, Edge, T, Roy, C, Malinowski, P, Bamford, K, Clark, L, et al.. Analytical assessment of ortho clinical diagnostics high-sensitivity cardiac troponin I assay. Clin Chem Lab Med 2020;59:749–55. https://doi.org/10.1515/cclm-2020-1115.Search in Google Scholar

27. Pagani, F, Stefini, F, Chapelle, JP, Lefevre, G, Graine, H, Luthe, H, et al.. Multicenter evaluation of analytical performance of the Liaison troponin I assay. Clin Biochem 2004;37:750–7. https://doi.org/10.1016/j.clinbiochem.2004.04.003.Search in Google Scholar

28. Farmakis, D, Mueller, C, Apple, FS. High-sensitivity cardiac troponin assays for cardiovascular risk stratification in the general population. Eur Heart J 2020;41:4050–6. https://doi.org/10.1093/eurheartj/ehaa083.Search in Google Scholar

29. Shah, AS, Anand, A, Sandoval, Y, Lee, KK, Smith, SW, Adamson, PD, et al.. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet 2015;386:2481–8. https://doi.org/10.1016/s0140-6736(15)00391-8.Search in Google Scholar

30. Favresse, J, Bayart, JL, Gruson, D, Bernardini, S, Clerico, A, Perrone, M. The underestimated issue of non-reproducible cardiac troponin I and T results: case series and systematic review of the literature. Clin Chem Lab Med 2021;59:1201–11. https://doi.org/10.1515/cclm-2020-1564.Search in Google Scholar PubMed

31. Pretorius, CJ, Dimeski, G, O’Rourke, PK, Marquart, L, Tyack, SA, Wilgen, U, et al.. Outliers as a cause of false cardiac troponin results: investigating the robustness of 4 contemporary assays. Clin Chem 2011;57:710–8. https://doi.org/10.1373/clinchem.2010.159830.Search in Google Scholar PubMed

32. Ryan, JB, Southby, SJ, Stuart, LA, Mackay, R, Florkowski, CM, George, PM. Comparison of cardiac TnI outliers using a contemporary and a high-sensitivity assay on the Abbott Architect platform. Ann Clin Biochem 2014;51:507–11. https://doi.org/10.1177/0004563214534637.Search in Google Scholar PubMed

33. Dimeski, G, Coogan, M, Jones, B, Brown, N. Is the new Beckman AccuTnI+3 assay capable of producing false-positive troponin I results? Clin Chem Lab Med 2015;53:e101–3. https://doi.org/10.1515/cclm-2014-0616.Search in Google Scholar PubMed

34. Warner, JV, Marshall, GA. High incidence of macrotroponin I with a high-sensitivity troponin I assay. Clin Chem Lab Med 2016;54:1821–9. https://doi.org/10.1515/cclm-2015-1276.Search in Google Scholar PubMed

35. Krintus, M, Panteghini, M. Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays. Clin Chem Lab Med 2020;58:1773–83. https://doi.org/10.1515/cclm-2020-0017.Search in Google Scholar PubMed

36. Apple, FS. Counterpoint: standardization of cardiac troponin I assays will not occur in my lifetime. Clin Chem 2012;58:169–71. https://doi.org/10.1373/clinchem.2011.166165.Search in Google Scholar PubMed

37. Gore, MO, Seliger, SL, Defilippi, CR, Nambi, V, Christenson, RH, Hashim, IA, et al.. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol 2014;63:1441–8. https://doi.org/10.1016/j.jacc.2013.12.032.Search in Google Scholar PubMed PubMed Central


Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2021-1136).


Received: 2021-10-25
Accepted: 2022-05-02
Published Online: 2022-05-16
Published in Print: 2022-07-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Scroll Up Arrow