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Licensed Unlicensed Requires Authentication Published by De Gruyter August 26, 2020

Cardiotoxic effects and myocardial injury: the search for a more precise definition of drug cardiotoxicity

  • Daniela Maria Cardinale , Martina Zaninotto , Carlo Maria Cipolla , Claudio Passino , Mario Plebani ORCID logo and Aldo Clerico EMAIL logo

Abstract

Drug-induced cardiotoxicity is a major clinical problem; cardiotoxic drugs may induce both cardiac dysfunction and myocardial injury. Several recent studies reported that cardiac troponins measured with high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have some concerns about the standard definition of cardiotoxicity, in particular, regarding the early evaluation of chemotherapy cardiotoxicity in cancer patients. Several recent studies using the hs-cTn assay indicate that myocardial injury may precede by some months or years the diagnosis of heart failure (HF) based on the evaluation of left ventricular ejection fraction (LVEF). Accordingly, hs-cTn assay should considered to be a reliable laboratory test for the early detection of asymptomatic or subclinical cardiotoxic damage in patients undergoing cancer chemotherapy. In accordance with the Fourth Universal Definition of Myocardial Infarction and also taking into account the recent experimental and clinical evidences, the definition of drug-cardiotoxicity should be updated considering the early evaluation of myocardial injury by means of hs-cTn assay. It is conceivable that the combined use of hs-cTn assay and cardiac imaging techniques for the evaluation of cardiotoxicity will significantly increase both diagnostic sensitivity and specificity, and also better prevent chemotherapy-related left ventricular (LV) dysfunction and other adverse cardiac events. However, large randomized clinical trials are needed to evaluate the cost/benefit ratio of standardized protocols for the early detection of cardiotoxicity using hs-cTn assay in patients receiving chemotherapy for malignant diseases.


Corresponding author: Professor Aldo Clerico, MD, Laboratory of Cardiovascular Endocrinology and Cell Biology, Department of Laboratory Medicine, Fondazione CNR Toscana G. Monasterio, Scuola Superiore Sant’Anna, Via Trieste 41, Pisa, 56126, Italy, E-mail:

  1. Research funding: None declared.

  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.

References

1. Onakpoya, IJ, Heneghan, CJ, Aronson, JK. Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med 2016;14:10. https://doi.org/10.1186/s12916-016-0553-2.Search in Google Scholar PubMed PubMed Central

2. Ferdinandy, P, Baczkó, I, Bencsik, P, Giricz, Z, Görbe, A, Pacher, P, et al. Definition of hidden drug cardiotoxicity: paradigm change in cardiac safety testing and its clinical implications. Eur Heart J 2019;40:1771–7. https://doi.org/10.1093/eurheartj/ehy365.Search in Google Scholar PubMed PubMed Central

3. Chung, R, Ghosh, AK, Banerjee, A. Cardiotoxicity: precision medicine with imprecise definitions. Open Heart 2018;5:e000774. https://doi.org/10.1136/openhrt-2018-000774.Search in Google Scholar PubMed PubMed Central

4. Zamorano, JL, Lancellotti, P, Rodriguez Munoz, D, Aboyans, V, Asteggiano, R, Galderisi, M, et al.. ESC Scientific Document Group. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for practice guidelines. Eur Heart J 2016;37:2768–801. https://doi.org/10.1093/eurheartj/ehw211.Search in Google Scholar PubMed

5. Plana, JC, Galderisi, M, Barac, A, Ewer, MS, Ky, B, Scherrer-Crosbie, M, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imag 2014;15:1063–93. https://doi.org/10.1093/ehjci/jeu192.Search in Google Scholar PubMed PubMed Central

6. López-Fernández, T, Martín Garcıa, A, Santaballa Beltrán, A, Montero Luis, Á, García Sanz, R, Mazón Ramos, P, et al. Cardio-oncohematology in clinical practice. Position paper and recommendations. Rev Esp Cardiol 2017;70:474–86. https://doi.org/10.1016/j.rec.2016.12.041.Search in Google Scholar PubMed

7. Varga, ZV, Ferdinandy, P, Liaudet, L, Pacher, P. Drug-induced mitochondrial dysfunction and cardiotoxicity. Am J Physiol Heart Circ Physiol 2015;309:H1453–67. https://doi.org/10.1152/ajpheart.00554.2015.Search in Google Scholar PubMed PubMed Central

8. Demonbreun, AR, McNally, EM. Plasma membrane repair in health and disease. Curr Top Membr 2016;77:67–96. https://doi.org/10.1016/bs.ctm.2015.10.006.Search in Google Scholar PubMed PubMed Central

9. Cooper, ST, McNeil, PL. Membrane repair: mechanisms and pathophysiology. Physiol Rev 2015;95:1205–440. https://doi.org/10.1152/physrev.00037.2014.Search in Google Scholar PubMed PubMed Central

10. Marjot, J, Kaier, TE, Martin, ED, Reji, SS, Copeland, O, Iqbal, M, et al. Quantifying the release of biomarkers of myocardial necrosis from cardiac myocytes and intact myocardium. Clin Chem 2017;63:990–6. https://doi.org/10.1373/clinchem.2016.264648.Search in Google Scholar PubMed PubMed Central

11. Mair, J, Lindahl, B, Hammarsten, O, Müller, C, Giannitsis, E, Huber, K, et al. How is cardiac troponin released from injured myocardium?. Eur Heart J Acute Cardiovasc Care 2018;7:553–60. https://doi.org/10.1177/2048872617748553.Search in Google Scholar PubMed

12. Takemura, G. Morphological aspects of apoptosis in heart diseases. J Cell Mol Med 2006;10:56–75. https://doi.org/10.1111/j.1582-4934.2006.tb00291.x.Search in Google Scholar PubMed PubMed Central

13. Takemura, G, Kanoh, M, Minatoguchi, S, Fujiwara, H. Cardiomyocyte apoptosis in the failing heart – a critical review from definition and classification of cell death. Int J Cardiol 2013;167:2373–86. https://doi.org/10.1016/j.ijcard.2013.01.163.Search in Google Scholar PubMed

14. Broughton, KM, Wang, BJ, Firouzi, F, Khalafalla, F, Dimmeler, S, Fernandez-Aviles, F, et al. Mechanisms of cardiac cell repair and regeneration. Circ Res 2018;122:1151–63. https://doi.org/10.1161/circresaha.117.312586.Search in Google Scholar PubMed PubMed Central

15. Cardinale, D, Colombo, A, Bacchiani, G, Tedeschi, I, Meroni, CA, Civelli, M, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 2015;133:1981–8. https://doi.org/10.1161/circulationaha.114.013777.Search in Google Scholar PubMed

16. Nicol, M, Baudet, M, Cohen-Solai, A. Subclinical left ventricular dysfunction chemotherapy. Card Fail Rev 2019;5:31–6. https://doi.org/10.15420/cfr.2018.25.1.Search in Google Scholar PubMed PubMed Central

17. Cardinale, D, Biasillo, G, Salvatici, M, Sandri, MT, Cipolla, CM. Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy. Expert Rev Mol Diagn 2017;17:245–56. https://doi.org/10.1080/14737159.2017.1283219.Search in Google Scholar PubMed

18. Cardinale, D, Ciceri, F, Latini, R, Franzosi, MG, Sandri, MT, CIvelli, M, Cucchi, G, et al. Anthracycline-induced cardiotoxicity: a multicenter randomised trial comparing two strategies for guiding prevention with enalapril: the International CardioOncology Society-one trial. Eur J Cancer 2018;94:126–37. https://doi.org/10.1016/j.ejca.2018.02.005.Search in Google Scholar PubMed

19. Thygesen, K, Alpert, JS, Jaffe, AS, Chaitman, BR, Bax, JJ, Morrow, DA, et al. Fourth universal definition of myocardial infarction. J Am Coll Cardiol 2018;72:2231–64. https://doi.org/10.1016/j.jacc.2018.08.1038.Search in Google Scholar PubMed

20. Wu, AHB, Christenson, RH, Greene, DN, Jaffe, AS, Kavsak, PA, Ordonez-Lianos, 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

21. Franzini, M, Lorenzoni, V, Masotti, S, Prontera, C, Chiappino, D, Della Latta, D, et al. The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: a multicenter study in Italy. Clin Chim Acta 2015;438:376–81. https://doi.org/10.1016/j.cca.2014.09.010.Search in Google Scholar PubMed

22. Ndreu, R, Musetti, V, Masotti, S, Zaninotto, M, Prontera, C, Zucchelli, GC, et al. Evaluation of the cTnT immunoassay using quality control samples. Clin Chim Acta 2019;495:269–70. https://doi.org/10.1016/j.cca.2019.04.068.Search in Google Scholar PubMed

23. Caselli, C, Cangemi, G, Masotti, S, Ragusa, R, Gennai, I, Del Ry, S, et al. Plasma cardiac troponin I concentrations in healthy neonates, children and adolescents measured with a high sensitive immunoassay method: high sensitive troponin I in pediatric age. Clin Chim Acta 2016;458:68–71. https://doi.org/10.1016/j.cca.2016.04.029.Search in Google Scholar PubMed

24. Masotti, S, Prontera, C, Musetti, V, Storti, S, Ndreu, R, Zucchelli, GC, et al. Evaluation of analytical performance of a new high-sensitivity immunoassay for cardiac troponin I. Clin Chem Lab Med 2018;56:492–501. https://doi.org/10.1515/cclm-2017-0387.Search in Google Scholar PubMed

25. Musetti, V, Masotti, S, Prontera, C, Storti, S, Ndreu, N, Zucchelli, GC, et al. Evaluation of the analytical performance of a new ADVIA immunoassay using the Centaur XPT platform system for the measurement of cardiac troponin I. Clin Chem Lab Med 2018;56:e229–31. https://doi.org/10.1515/cclm-2018-0054.Search in Google Scholar PubMed

26. Clerico, A, Ripoli, A, Zaninotto, M, Masotti, S, Musetti, V, Ciaccio, M, et al. Head-to-head comparison of plasma cTnI concentration values measured with three high-sensitivity methods in a large Italian population of healthy volunteers and patients admitted to emergency department with acute coronary syndrome: a multi-center study. Clin Chim Acta 2019;496:25–34. https://doi.org/10.1016/j.cca.2019.06.012.Search in Google Scholar PubMed

27. Clerico, A, Zaninotto, M, Padoan, A, Masotti, S, Musetti, V, Prontera, C, et al. Evaluation of analytical performance of immunoassay methods for cardiac troponin I and T: from theory to practice. Adv Clin Chem 2019;93:239–62. https://doi.org/10.1016/bs.acc.2019.07.005.Search in Google Scholar PubMed

28. Giannoni, A, Giovannini, S, Clerico, A. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal?. Clin Chem Lab Med 2009;47:1167–77. https://doi.org/10.1515/cclm.2009.320.Search in Google Scholar PubMed

29. Clerico, A, Zaninotto, M, Ripoli, M, Masotti, S, Prontera, C, Passino, C, et al. The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology, and clinical implications. Clin Chem Lab Med 2017;55:1634–51. https://doi.org/10.1515/cclm-2016-0933.Search in Google Scholar PubMed

30. Bergmann, O, Zdunek, S, Felker, A, Salhpoor, M, Alkass, K, Bernard, S, et al. Dynamics of cell generation and turnover in the human heart. Cell 2015;161:1566–75. https://doi.org/10.1016/j.cell.2015.05.026.Search in Google Scholar PubMed

31. Sze, J, Mooney, J, Barzi, F, Hillis, GS, Chow, CK. Cardiac troponin and its relationship to cardiovascular outcomes in community populations. A systematic review and meta-analysis. Heart Lung Circ 2016;25:217–28. https://doi.org/10.1016/j.hlc.2015.09.001.Search in Google Scholar PubMed

32. van der Linden, N, Klinkenberg, LJ, Bekers, O, Loon, L, Dieijen-Visser, MP, Zeegers, MP, et al. Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population: a meta-analysis. Medicine 2016;95:e5703. https://doi.org/10.1097/md.0000000000005703.Search in Google Scholar PubMed PubMed Central

33. Hughes, MF, Ojeda, F, Saarela, O, Jørgensen, T, Zeller, T, Palosaari, T, et al. Association of repeatedly measured high-sensitivity-assayed troponin I with cardiovascular disease events in a general population from the MORGAM/BiomarCaRE Study. Clin Chem 2017;63:334–42. https://doi.org/10.1373/clinchem.2016.261172.Search in Google Scholar PubMed

34. Zellweger, MJ, Haaf, P, Maraun, M, Osterhues, HH, Keller, U, Müller-Brand, J, et al. Predictors and prognostic impact of silent coronary artery disease in asymptomatic high-risk patients with diabetes mellitus. Int J Cardiol 2017;244:37–42. https://doi.org/10.1016/j.ijcard.2017.05.069.Search in Google Scholar PubMed

35. Sigurdardottir, FD, Lynbakken, MN, Holmen, OL, Dalen, H, Hveem, K, Røsjø, H, et al. Relative prognostic value of cardiac troponin I and C-reactive protein in the general population (from the North-Trøndelag Health [HUNT] Study). Am J Cardiol 2018;121:949–55. https://doi.org/10.1016/j.amjcard.2018.01.004.Search in Google Scholar PubMed

36. Willeit, P, Welsh, P, Evans, JDW, Tschiderer, L, Boachie, C, Wouter Jukema, J, et al. High-sensitivity cardiac troponin concentration and risk of first-ever cardiovascular outcomes in 1,54,052 participants. J Am Coll Cardiol 2017;70:558–68. https://doi.org/10.1016/j.jacc.2017.05.062.Search in Google Scholar PubMed PubMed Central

37. Welsh, P, Preiss, D, Shah, ASV, McAllister, D, Briggs, A, Boachie, C, et al. Comparison between high-sensitivity cardiac troponin T and cardiac troponin I in a large general population cohort. Clin Chem 2018;64:1607–16. https://doi.org/10.1373/clinchem.2018.292086.Search in Google Scholar PubMed PubMed Central

38. Zhu, K, Knuiman, M, Divitini, M, Murray, K, Lim, EM, St John, A, et al. High-sensitivity cardiac troponin I and risk of cardiovascular disease in an Australian population-based cohort. Heart 2018;104:895–903. https://doi.org/10.1136/heartjnl-2017-312093.Search in Google Scholar PubMed

39. Passino, C, Aimo, A, Masotti, S, Musetti, V, Prontera, C, Emdin, M, et al. Cardiac troponins as biomarkers for cardiac disease. Biomark Med 2019;13:325–30. https://doi.org/10.2217/bmm-2019-0039.Search in Google Scholar PubMed

40. Eggers, KM, Venge, P, Lindahl, B, Lind, L. Cardiac troponin I levels measured with a high-sensitive assay increase over time and are strong predictors of mortality in an elderly population. J Am Coll Cardiol 2013;61:1906–13. https://doi.org/10.1016/j.jacc.2012.12.048.Search in Google Scholar PubMed

41. Aakre, KM, Røraas, T, Petersen, PH, Svarstad, E, Sellevoll, H, Skadberg, O, et al. Weekly and 90-minute biological variation in cardiac troponin T and cardiac troponin I in hemodialysis patients and healthy controls. Clin Chem 2014;60:838–47. https://doi.org/10.1373/clinchem.2013.216978.Search in Google Scholar PubMed

42. Corte, Z, Garcia, C, Venta, R. Biological variation of cardiac troponin T in patients with end-stage renal disease and in healthy individuals. Ann Clin Biochem 2015;52:53–60. https://doi.org/10.1177/0004563214545116.Search in Google Scholar PubMed

43. Vilela, EM, Bastos, JCC, Rodrigures, RP, Nunes, JPL. High-sensitivity troponin after running a systematic review. Neth J Med 2014;72:5–9.Search in Google Scholar

44. Skadberg, Ø, Kleiven, Ø, Bjørkavoll-Bergseth, M, Meilberg, T, Bergseth, R, Selvåg, J, et al. Highly increased troponin I levels following high-intensity endurance cycling may detect subclinical coronary artery disease in presumably healthy leisure sport cyclists: the North Sea Race Endurance Exercise Study (NEEDED) 2013. Eur J Prev Cardiol 2017;24:885–94. https://doi.org/10.1177/2047487317693130.Search in Google Scholar PubMed

45. Aengevaeren, VL, Hopman, MTE, Thompson, PD, Bakker, EA, George, KP, Thijssen, DHJ, et al. Exercise-induced cardiac troponin I increase and incident mortality and cardiovascular events. Circulation 2019;140:804–14. https://doi.org/10.1161/circulationaha.119.041627.Search in Google Scholar

46. Skadberg, O, Kleiven, O, Orn, S, Bjørkavoll-Bergseth, MF, Melberg, TH, Omland, T, et al. The cardiac troponin response following physical exercise in relation to biomarker criteria for acute myocardial infarction; the North Sea Race Endurance Exercise Study (NEDEED) 2013. Clin Chim Acta 2018;479:155–9. https://doi.org/10.1016/j.cca.2018.01.033.Search in Google Scholar PubMed

47. Cardinale, D, Sandri, MT, Colombo, A, Colombo, N, Boeri, M, Lamantia, G, et al. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 2004;109:2749–54. https://doi.org/10.1161/01.cir.0000130926.51766.cc.Search in Google Scholar

48. Cardinale, D, Colombo, A, Sandri, MT, Lamantia, G, Colombo, N, Civelli, M, et al. Prevention of high-dose chemotherapy–induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 2006;114:2474–81. https://doi.org/10.1161/circulationaha.106.635144.Search in Google Scholar

49. Cao, L, Zhu, W, Wagar, EA, Meng, QH. Biomarkers for monitoring chemotherapy-induced cardiotoxicity. Crit Rev Clin Lab Sci 2017;54:87–101. https://doi.org/10.1080/10408363.2016.1261270.Search in Google Scholar PubMed

50. Gülgün, M, Fidancı, K, Genç, FA, Kesik, V. Natriuretic peptide and cardiac troponin levels in doxorubicin-induced cardiotoxicity. Anatol J Cardiol 2016;16:299.10.14744/AnatolJCardiol.2016.7001Search in Google Scholar

51. Kitayama, H, Kondo, T, Sugiyama, J, Kurimoto, K, Nisghino, Y, Kawada, M, et al. High-sensitive troponin T assay can predict anthracyclineand trastuzumab-induced cardiotoxicity in breast cancer patients. Breast Cancer 2017;24:774–82. https://doi.org/10.1007/s12282-017-0778-8.Search in Google Scholar PubMed

52. Jones, M, O’Gorman, P, Kelly, C, Mahon, N, Fitzgibbon, MC. High-sensitive cardiac troponin-I facilitates timely detection of subclinical anthracycline-mediated cardiac injury. Ann Clin Biochem 2017;54:149–57. https://doi.org/10.1177/0004563216650464.Search in Google Scholar PubMed

53. Michel, L, Rassaf, T, Totzeck, M. Biomarkers for the detection of apparent and subclinical cancer therapy-related cardiotoxicity. J Thorac Dis 2018;10(35 Suppl):S4282–95. https://doi.org/10.21037/jtd.2018.08.15.Search in Google Scholar PubMed PubMed Central

54. Riddell, E, Lenihan, D. The role of cardiac biomarkers in cardio-oncology. Curr Probl Cancer 2018;42:375–85. https://doi.org/10.1016/j.currproblcancer.2018.06.012.Search in Google Scholar PubMed

55. Sarocchi, M, Grossi, F, Arboscello, E, Bellodi, A, Genova, C, Del Bello, MG, et al. Serial troponin for early detection of Nivolumab cardiotoxicity in advanced non-small cell lung cancer patients. Oncologist 2018;23:936–42. https://doi.org/10.1634/theoncologist.2017-0452.Search in Google Scholar PubMed PubMed Central

56. Simões, R, Silva, LM, Cruz, ALVM, Fraga, VG, de Paula Sabino, A, Gomes, KB. Troponin as a cardiotoxicity marker in breast cancer patients receiving anthracycline-based chemotherapy: a narrative review. Biomed Pharmacother 2018;107:989–96. https://doi.org/10.1016/j.biopha.2018.08.035.Search in Google Scholar PubMed

57. Li, J, Chang, HM, Banchs, J, Araujo, DM, Hassan, SA, Wagar, EA, et al. Detection of subclinical cardiotoxicity in sarcoma patients receiving continuous doxorubicin infusion or pre-treatment with dexrazoxane before bolus doxorubicin. Cardio-Oncology 2020;6:1. https://doi.org/10.1186/s40959-019-0056-3.Search in Google Scholar PubMed PubMed Central

58. Cardinale, D, Colombo, A, Lamantia, G, Colombo, N, Civelli, M, De Giacomi, G, et al. Anthracycline-induced cardiomyopathy. Clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 2010;55:213–20. https://doi.org/10.1016/j.jacc.2009.03.095.Search in Google Scholar PubMed

59. Cardinale, D, Fabiano, I, Cipolla, CM. Cardiotoxicity of anthracyclines. Front Cardiovasc Med 2020;7:26. https://doi.org/10.3389/fcvm.2020.00026.Search in Google Scholar PubMed PubMed Central

60. Cappetta, D, Rossi, F, Piegari, E, Quaini, F, Berrino, L, Urbanek, K, et al. Doxorubicin targets multiple players: a new view of an old problem. Pharmacol Res 2018;27:4–14. https://doi.org/10.1016/j.phrs.2017.03.016.Search in Google Scholar PubMed

61. Segura, AM, Frazier, OH, Buja, LM. Fibrosis and heart failure. Heart Fail Rev 2014;19:173–85. https://doi.org/10.1007/s10741-012-9365-4.Search in Google Scholar PubMed

62. Passino, C, Barison, A, Vergaro, G, Gabutti, A, Borrelli, C, Emdin, M, et al. Markers of fibrosis, inflammation, and remodeling pathways in heart failure. Clin Chim Acta 2015;443:29–38. https://doi.org/10.1016/j.cca.2014.09.006.Search in Google Scholar PubMed

63. Lippi, G, Plebani, M. Personalized medicine: moving from simple theory to daily practice. Clin Chem Lab Med 2015;53:959–60. https://doi.org/10.1515/cclm-2015-0291.Search in Google Scholar PubMed

64. Schwaederle, M, Zhao, M, Lee, JJ, Lazar, V, Leyland-Jones, B, Schilsky, RL, et al. Association of biomarker-based treatment strategies with response rates and progression-free survival in refractory malignant neoplasms: a meta-analysis. JAMA Oncol 2016;2:1452–9. https://doi.org/10.1001/jamaoncol.2016.2129.Search in Google Scholar PubMed

65. NIH, Office of Cancer Survivors, Division of Cancer Controls & Population Science. Statistics, graphs and definitions. Available from: https://cancercontrol.cancer.gov/ocs/statistics/index.html [Last Updated 8 Nov 2019].Search in Google Scholar

66. European Observatory on Health System and Policies. European Commission. State of health in the EU. Italy: Country health profile; 2019:1–23 pp. Available from: https://ec.europa.eu/health/sites/health/files/state/docs/2019_chp_it_english.Search in Google Scholar

67. O’Brien, PJ. Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology 2008;245:206–18.10.1016/j.tox.2007.12.006Search in Google Scholar PubMed

68. Clerico, A, Cardinale, DM, Zaninotto, M, Aspromonte, N, Sandri, MT, Passino, C, et al. High-sensitivity cardiac troponin I and T methods for the early detection of myocardial injury in patients on chemotherapy 2020 May 22. Available from: /j/cclm.ahead-of-print/cclm-2020-0362/cclm-2020-0362.xml, https://doi.org/10.1515/cclm-2020-0362 [Epub ahead of print].Search in Google Scholar PubMed

Received: 2020-04-23
Accepted: 2020-08-06
Published Online: 2020-08-26
Published in Print: 2021-01-26

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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