Característica actual de los métodos para la determinación de troponinas cardíacas y su valor diagnóstico: minirrevisión

Aleksey Chaulin

doi:10.31053/1853.0605.v78.n4.32988

Autores

Aleksey Chaulin Samara State Medical University https://orcid.org/0000-0002-2712-0227

DOI:

https://doi.org/10.31053/1853.0605.v78.n4.32988

Palavras-chave:

hs-cTnI, hs-cTnT, métodos imunoquímicos de determinação, diagnóstico, infarto agudo do miocárdio, diagnóstico não invasivo

Resumo

A expansão e descoberta de novas possibilidades de diagnóstico para o uso de muitos biomarcadores de doenças cardiovasculares( DCV), incluindo isoformas cardioespecíficas de troponina (cTnI, cTnT), é devido à melhoria dos métodos laboratoriais para sua determinação. Ao longo de uma longa história da criação e melhoria de métodos imunoquímicos para a determinação de cTnI e cTnT, mudanças significativas foram observadas no conceito de biologia e seu valor diagnóstico como biomarcadores de DCV. Os métodos obsoletos de detecção de cTnI, cTnT, chamados de baixa e moderada sensibilidade, foram distinguidos por uma sensibilidade relativamente baixa, o que levou à confirmação tardia do diagnóstico de infarto agudo do miocárdio (IAM) e, portanto, esses métodos foram gradualmente substituídos por novos métodos de alta e moderada sensibilidade, como definições de métodos ultra-sensíveis (hs-cTnI, hs-cTnT). Com a introdução de hs-cTnI e hs-cTnT na prática clínica, a possibilidade de diagnóstico precoce e exclusão do IAM mediante a avaliação da cinética da concentração de hs-cTnI e hs-cTnT nas primeiras horas (0-1 hora, 0-2 horas, 0-3 horas) desde o momento em que o paciente entra em urgências. Além disso, algumas de nossas idéias sobre a biologia das troponinas cardíacas mudaram e surgiram novas oportunidades promissoras para uso em medicina. Este artigo discute as principais características analíticas dos métodos de detecção de hs-cTnI e hs-cTnT em comparação com métodos moderadamente sensíveis, e relata novos dados biológicos e algumas novas possibilidades de diagnóstico para o uso de hs-cTnI e hs-cTnT na prática clínica moderna.

Downloads

Os dados de download ainda não estão disponíveis.

Biografia do Autor

Aleksey Chaulin, Samara State Medical University

Samara State Medical University, student (2009-2017)
Samara State Medical University, postgraduate student (2017-2019)
Samara State Medical University, M.D., assistant of the department Histology and Embriology, Cardiology (2019-2021)
Samara Regional Cardiology Dispensary, M.D. (2017-2021) Russia. CAMPA.
Current research interests: Clinical Chemistry, Biochemistry, Biomedicine, Molecular biology, Laboratory Medicine, Cardiac troponins, hs-cTn,
acute myocardial infarction, heart failure, hypothyroidism

Referências

1. Chaulin AM, Duplyakov DV. [Biomarkers of acute myocardial infarction: diagnostic and prognostic value. Part 1.] Journal of Clinical Practice. 2020;11(3):75-84. doi:10.17816/clinpract34284 (Russian).

2. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Glob Heart. 2018 Dec;13(4):305-338. doi: 10.1016/j.gheart.2018.08.004.

3. Pasquale F, Syrris P, Kaski JP, Mogensen J, McKenna WJ, Elliott P. Long-term outcomes in hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene. Circ Cardiovasc Genet. 2012 Feb 1;5(1):10-7. doi: 10.1161/CIRCGENETICS.111.959973.

4. Duplyakov DV, Chaulin AM. [Mutations of heart troponines, associated with cardiomyopathies. Kardiologiya: novosti, mneniya, obuchenie] [Cardiology: News, Opinions, Training]. 2019;7(3):8–17. doi:10.24411/2309-1908-2019-13001. (Russian).

5. Sacks DB. Acute coronary ischemia: troponin I and T. Vasc Med. 1999;4(4):253–256. doi: 10.1177/1358836X9900400408.

6. Collinson PO. Troponin T or troponin I or CK-MB (or none?). Eur Heart J. 1998 Nov;19 Suppl N:N16-24. PMID: 9857934.

7. Park KC, Gaze DC, Collinson PO, Marber MS. Cardiac troponins: from myocardial infarction to chronic disease. Cardiovasc Res. 2017;113(14):1708-1718. doi:10.1093/cvr/cvx183

8. Messner B, Baum H, Fischer P, Quasthoff S, Neumeier D. Expression of messenger RNA of the cardiac isoforms of troponin T and I in myopathic skeletal muscle. Am J Clin Pathol. 2000 Oct;114(4):544-9. Erratum in: Am J Clin Pathol 2000 Dec;114(6):986.

9. Ricchiuti V, Apple FS. RNA expression of cardiac troponin T isoforms in diseased human skeletal muscle. Clin Chem. 1999 Dec;45(12):2129-35. Erratum in: Clin Chem 2000 Mar;46(3):437.

10. Wens SC, Schaaf GJ, Michels M, Kruijshaar ME, van Gestel TJ, In 't Groen S, Pijnenburg J, Dekkers DH, Demmers JA, Verdijk LB, Brusse E, van Schaik RH, van der Ploeg AT, van Doorn PA, Pijnappel WW. Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease. Circ Cardiovasc Genet. 2016 Feb;9(1):6-13. doi: 10.1161/CIRCGENETICS.115.001322.

11. Schmid J, Liesinger L, Birner-Gruenberger R, Stojakovic T, Scharnagl H, Dieplinger B, Asslaber M, Radl R, Beer M, Polacin M, Mair J, Szolar D, Berghold A, Quasthoff S, Binder JS, Rainer PP. Elevated Cardiac Troponin T in Patients With Skeletal Myopathies. J Am Coll Cardiol. 2018 Apr 10;71(14):1540-1549. doi:10.1016/j.jacc.2018.01.070.

12. Rusakov DY, Vologdina NN, Tulayeva ON. [The development of striated cardiac muscle tissue in the walls of the caval and pulmonary veins.] Journal of Anatomy and Histopathology. 2015;4(3):105-105. doi:10.18499/2225-7357-2015-4-3-105-105. (Russian).

13. Dhoot GK, Gell PG, Perry SV. The localization of the different forms of troponin I in skeletal and cardiac muscle cells. Exp Cell Res. 1978;117(2):357-70. doi:10.1016/0014-4827(78)90149-0.

14. Dhoot GK, Perry SV. Distribution of polymorphic forms of troponin components and tropomyosin in skeletal muscle. Nature. 1979 Apr 19;278(5706):714-8. doi:10.1038/278714a0.

15. Chaulin AM, Karslyan LS, Duplyakov DV. [Non-Coronarogenic Causes of Increased Cardiac Troponins in Clinical Practice]. Journal of Clinical Practice. 2019;10(4):81–93. doi:10.17816/clinpract16309. (Russian).

16. Chaulin AM, Abashina OE, Duplyakov DV. Pathophysiological mechanisms of cardiotoxicity in chemotherapeutic agents. Russian Open Medical Journal 2020; 9: e0305. doi: 10.15275/rusomj.2020.0305

17. Chaulin AM, Duplyakov DV. MicroRNAs in Atrial Fibrillation: Pathophysiological Aspects and Potential Biomarkers. International Journal of Biomedicine. 2020;10(3):198-205. doi: 10.21103/Article10(3)_RA3.

18. Wilhelm J, Hettwer S, Schuermann M, Bagger S, Gerhardt F, Mundt S, Muschik S, Zimmermann J, Amoury M, Ebelt H, Werdan K. Elevated troponin in septic patients in the emergency department: frequency, causes, and prognostic implications. Clin Res Cardiol. 2014 Jul;103(7):561-7. doi: 10.1007/s00392-014-0684-4.

19. Dubin RF, Li Y, He J, Jaar BG, Kallem R, Lash JP, Makos G, Rosas SE, Soliman EZ, Townsend RR, Yang W, Go AS, Keane M, Defilippi C, Mishra R, Wolf M, Shlipak MG; CRIC Study Investigators. Predictors of high sensitivity cardiac troponin T in chronic kidney disease patients: a cross-sectional study in the chronic renal insufficiency cohort (CRIC). BMC Nephrol. 2013 Oct 22;14:229. doi: 10.1186/1471-2369-14-229.

20. Zümrütdal A, Bakinen O, Uçan H, Atalay HV, Bodur H. Relationship between uremic myopathy and false-positive cardiac troponin T test. Nephron. 2000 Dec;86(4):522-3. doi: 10.1159/000045852.

21. Klinkenberg LJ, Wildi K, van der Linden N, Kouw IW, Niens M, Twerenbold R, Rubini Gimenez M, Puelacher C, Daniel Neuhaus J, Hillinger P, Nestelberger T, Boeddinghaus J, Grimm K, Sabti Z, Bons JA, van Suijlen JD, Tan FE, Ten Kate J, Bekers O, van Loon LJ, van Dieijen-Visser MP, Mueller C, Meex SJ. Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction. Clin Chem. 2016 Dec;62(12):1602-1611. doi: 10.1373/clinchem.2016.257485.

22. Chaulin AM, Duplyakova PD, Duplyakov DV. Circadian rhythms of cardiac troponins: mechanisms and clinical significance. Russian Journal of Cardiology. 2020;25:4061. doi:10.15829/1560-4071-2020-4061.

23. Chaulin AM, Duplyakov DV. [High-sensitivity cardiac troponins: circadian rhythms]. Cardiovascular Therapy and Prevention. 2021;20(1):2639. (Russian). doi:10.15829/1728-8800-2021-2639.

24. Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, Hollander J, Plebani M, Than M, Chan MH; International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem. 2015 Mar;48(4-5):201-3. doi: 10.1016/j.clinbiochem.2014.08.021.

25. Shah AS, Griffiths M, Lee KK, McAllister DA, Hunter AL, Ferry AV, Cruikshank A, Reid A, Stoddart M, Strachan F, Walker S, Collinson PO, Apple FS, Gray AJ, Fox KA, Newby DE, Mills NL. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 2015 Jan 21;350:g7873. doi: 10.1136/bmj.g7873. Erratum in: BMJ. 2015;350:h626. Erratum in: BMJ. 2016 Sep 06;354:i4840.

26. Gore MO, Seliger SL, Defilippi CR, Nambi V, Christenson RH, Hashim IA, Hoogeveen RC, Ayers CR, Sun W, McGuire DK, Ballantyne CM, de Lemos JA. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol. 2014 Apr 15;63(14):1441-8. doi: 10.1016/j.jacc.2013.12.032.

27. Trupp RJ, Albert G, Ziegler A. Sex-specific 99th percentiles derived from the AACC Universal Sample Bank for the Roche Gen 5 cTnT assay: Comorbidities and statistical methods influence derivation of reference limits. Clin Biochem. 2018 Feb;52:173. doi: 10.1016/j.clinbiochem.2017.11.003.

28. Aakre KM, Røraas T, Petersen PH, Svarstad E, Sellevoll H, Skadberg Ø, Sæle K, Sandberg S. Weekly and 90-minute biological variations in cardiac troponin T and cardiac troponin I in hemodialysis patients and healthy controls. Clin Chem. 2014 Jun;60(6):838-47. doi: 10.1373/clinchem.2013.216978.

29. van der Linden N, Cornelis T, Klinkenberg LJ, Kimenai DM, Hilderink JM, Litjens EJ, Kooman JP, Bekers O, van Dieijen-Visser MP, Meex SJ. Strong diurnal rhythm of troponin T, but not troponin I, in a patient with renal dysfunction. Int J Cardiol. 2016 Oct 15;221:287-8. doi: 10.1016/j.ijcard.2016.06.268.

30. Zenina OY, Makarova II, Ignatova YP, Aksenova AV. [Chronophysiology and chronopathology of cardiovascular system (Literature Review)]. Ekologiya cheloveka (Human Ecology). 2017;(1):25-33. doi: 10.33396/1728-0869-2017-1-25-33 (Russian).

31. Pervan, P, Svaguša, T, Prkačin, I, Savuk, A, Bakos, M, Perkov, S. Urine high sensitive Troponin I measuring in patients with hypertension. Signa Vitae - A Journal In Intensive Care And Emergency Medicine. 2017;13(Suppl3):62–64. doi: 10.22514/SV133.062017.13.

32. Chaulin AM, Karslyan LS, Bazyuk EV, Nurbaltaeva DA, Duplyakov DV. [Clinical and Diagnostic Value of Cardiac Markers in Human Biological Fluids]. Kardiologiia. 2019 Dec 11;59(11):66-75. Russian. doi: 10.18087/cardio.2019.11.n414.

33. Mirzaii-Dizgah I, Riahi E. Salivary high-sensitivity cardiac troponin T levels in patients with acute myocardial infarction. Oral Diseases. 2013;19(2):180-184. doi:10.1111/j.1601-0825.2012.01968.x.

34. Chaulin A.M., Duplyakova P.D., Bikbaeva G.R., Tukhbatova A.A., Grigorieva E.V., Duplyakov D.V. Concentration of high-sensitivity cardiac troponin I in the oral fluid in patients with acute myocardial infarction: a pilot study. Russian Journal of Cardiology. 2020;25(12):3814. doi:10.15829/1560-4071-2020-3814.

35. Chaulin AM, Duplyakov DV. Increased natriuretic peptides, not associated with heart failure. Russian Journal of Cardiology. 2020;25(12):4140. doi:10.15829/1560-4071-2020-4140.

36. Cummins B, Auckland ML, Cummins P. Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction. Am Heart J. 1987;113(6):1333‐1344. doi:10.1016/0002-8703(87)90645-4.

37. Venge P, Lindahl B. Cardiac troponin assay classification by both clinical and analytical performance characteristics: a study on outcome prediction. Clin Chem. 2013;59:976-981. doi: 10.1373/clinchem.2012.194928.

38. Katus HA, Looser S, Hallermayer K, Remppis A, Scheffold T, Borgya A, Essig U, Geuss U. Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem. 1992 Mar;38(3):386-93.

39. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined--a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000 Sep;36(3):959-69. doi: 10.1016/s0735-1097(00)00804-4. Erratum in: J Am Coll Cardiol 2001 Mar 1;37(3):973.

40. Hermsen D, Apple F, Garcia-Beltràn L, Jaffe A, Karon B, Lewandrowski E, Mühlbacher A, Müller R, Ordóñez J, Pagani F, Panteghini M, Plecko T, Jarausch J. Results from a multicenter evaluation of the 4th generation Elecsys Troponin T assay. Clin Lab. 2007;53(1-2):1-9.

41. Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG, Bergmann A, Potocki M, Noveanu M, Breidthardt T, Christ A, Boldanova T, Merki R, Schaub N, Bingisser R, Christ M, Mueller C. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009 Jun 30;54(1):60-8. doi: 10.1016/j.jacc.2009.01.076.

42. Mingels A, Jacobs L, Michielsen E, Swaanenburg J, Wodzig W, van Dieijen-Visser M. Reference population and marathon runner sera assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and I assays. Clin Chem. 2009 Jan;55(1):101-8. doi: 10.1373/clinchem.2008.106427.

43. Keller T, Zeller T, Ojeda F, Tzikas S, Lillpopp L, Sinning C, Wild P, Genth-Zotz S, Warnholtz A, Giannitsis E, Möckel M, Bickel C, Peetz D, Lackner K, Baldus S, Münzel T, Blankenberg S. Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction. JAMA. 2011 Dec 28;306(24):2684-93. doi: 10.1001/jama.2011.1896.

44. Adams JE 3rd, Bodor GS, Dávila-Román VG, Delmez JA, Apple FS, Ladenson JH, Jaffe AS. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation. 1993 Jul;88(1):101-6. doi: 10.1161/01.cir.88.1.101.

45. Apple FS. Counterpoint: Standardization of cardiac troponin I assays will not occur in my lifetime. Clin Chem. 2012;58(1):169‐71. doi:10.1373/clinchem.2011.166165.

46. Apple FS, Jaffe AS, Collinson P, Mockel M, Ordonez-Llanos J, Lindahl B, Hollander J, Plebani M, Than M, Chan MH; International Federation of Clinical Chemistry (IFCC) Task Force on Clinical Applications of Cardiac Bio-Markers. IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem. 2015 Mar;48(4-5):201-3. doi: 10.1016/j.clinbiochem.2014.08.021.

47. Anand A, Shah ASV, Beshiri A, Jaffe AS, Mills NL. Global Adoption of High-Sensitivity Cardiac Troponins and the Universal Definition of Myocardial Infarction. Clin Chem. 2019 Mar;65(3):484-489. doi: 10.1373/clinchem.2018.298059.

48. Armbruster DA, Pry T. Limit of blank, limit of detection and limit of quantitation. Clin Biochem Rev. 2008 Aug;29 Suppl 1(Suppl 1):S49-52.

49. Apple FS. A new season for cardiac troponin assays: it's time to keep a scorecard. Clin Chem. 2009 Jul;55(7):1303-6. doi: 10.1373/clinchem.2009.128363.

50. Collinson PO, Heung YM, Gaze D, Boa F, Senior R, Christenson R, Apple FS. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem. 2012 Jan;58(1):219-25. doi: 10.1373/clinchem.2011.171082.

51. Eggers KM, Apple FS, Lind L, Lindahl B. The applied statistical approach highly influences the 99th percentile of cardiac troponin I. Clin Biochem. 2016 Oct;49(15):1109-1112. doi: 10.1016/j.clinbiochem.2016.08.012.

52. Cervellin G, Mattiuzzi C, Bovo C, Lippi G. Diagnostic algorithms for acute coronary syndrome-is one better than another? Ann Transl Med. 2016 May;4(10):193. doi: 10.21037/atm.2016.05.16.

53. Sörensen NA, Neumann JT, Ojeda F, Schwemer T, Renné T, Schnabel RB, Zeller T, Karakas M, Blankenberg S, Westermann D. Challenging the 99th percentile: A lower troponin cutoff leads to low mortality of chest pain patients. Int J Cardiol. 2017 Apr 1;232:289-293. doi: 10.1016/j.ijcard.2016.12.167.

54. Lippi G, Bonfanti L, Dipalo M, Aloe R, Cervellin G. Clinical, organizational and economic analysis of high-sensitivity cardiac troponin testing in the emergency department. Ann Res Hosp 2017;1:44.

55. Pickering JW, Than MP, Cullen L, Aldous S, Ter Avest E, Body R, Carlton EW, Collinson P, Dupuy AM, Ekelund U, Eggers KM, Florkowski CM, Freund Y, George P, Goodacre S, Greenslade JH, Jaffe AS, Lord SJ, Mokhtari A, Mueller C, Munro A, Mustapha S, Parsonage W, Peacock WF, Pemberton C, Richards AM, Sanchis J, Staub LP, Troughton R, Twerenbold R, Wildi K, Young J. Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis. Ann Intern Med. 2017 May 16;166(10):715-724. doi: 10.7326/M16-2562. Epub 2017 Apr 18. Erratum in: Ann Intern Med. 2017 Oct 3;167(7):528.

56. Ferencik M, Mayrhofer T, Lu MT, Woodard PK, Truong QA, Peacock WF, Bamberg F, Sun BC, Fleg JL, Nagurney JT, Udelson JE, Koenig W, Januzzi JL, Hoffmann U. High-Sensitivity Cardiac Troponin I as a Gatekeeper for Coronary Computed Tomography Angiography and Stress Testing in Patients with Acute Chest Pain. Clin Chem. 2017 Nov;63(11):1724-1733. doi: 10.1373/clinchem.2017.275552.

57. Jaeger C, Wildi K, Twerenbold R, Reichlin T, Rubini Gimenez M, Neuhaus JD, Grimm K, Boeddinghaus J, Hillinger P, Nestelberger T, Singeisen H, Gugala M, Pretre G, Puelacher C, Wagener M, Honegger U, Schumacher C, Moreno Weidmann Z, Kreutzinger P, Krivoshei L, Freese M, Stelzig C, Dietsche S, Ernst S, Rentsch K, Osswald S, Mueller C. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am Heart J. 2016 Jan;171(1):92-102.e1-5. doi: 10.1016/j.ahj.2015.07.022.

58. Nestelberger T, Wildi K, Boeddinghaus J, Twerenbold R, Reichlin T, Giménez MR, Puelacher C, Jaeger C, Grimm K, Sabti Z, Hillinger P, Kozhuharov N, du Fay de Lavallaz J, Pinck F, Lopez B, Salgado E, Miró Ò, Bingisser R, Lohrmann J, Osswald S, Mueller C. Characterization of the observe zone of the ESC 2015 high-sensitivity cardiac troponin 0h/1h-algorithm for the early diagnosis of acute myocardial infarction. Int J Cardiol. 2016 Mar 15;207:238-45. doi: 10.1016/j.ijcard.2016.01.112.

59. Greenslade JH, Carlton EW, Van Hise C, Cho E, Hawkins T, Parsonage WA, Tate J, Ungerer J, Cullen L. Diagnostic Accuracy of a New High-Sensitivity Troponin I Assay and Five Accelerated Diagnostic Pathways for Ruling Out Acute Myocardial Infarction and Acute Coronary Syndrome. Ann Emerg Med. 2018 Apr;71(4):439-451.e3. doi: 10.1016/j.annemergmed.2017.10.030.

60. Garcia-Osuna A, Gaze D, Grau-Agramunt M, Morris T, Telha C, Bartolome A, Bishop JJ, Monsalve L, Livingston R, Estis J, Nolan N, Sandlund J, Ordonez-Llanos J. Ultrasensitive quantification of cardiac troponin I by a Single Molecule Counting method: analytical validation and biological features. Clin Chim Acta. 2018 Nov;486:224-231. doi: 10.1016/j.cca.2018.08.015.

61. Ifcc.org. 2021. High-Sensitivity* Cardiac Troponin I and T Assay Analytical Characteristics Designated by Manufacturer IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) v122019. [online] Disponible en: https://www.ifcc.org/media/478231/high-sensitivity-cardiac-troponin-i-and-t-assay-analytical-characteristics-designated-by-manufacturer-v122019.pdf> [Accedido el 25 October 2021].