Troponin-I and left ventricular function in pediatric high-risk acute lymphoblastic leukemia after daunorubicin treatment
Abstract
Background Daunorubicin is a chemotherapy drug for leukemia treatment, but it can cause cardiotoxicity. When heart damage occurs, myocardial sarcomeres release troponin-I, which could potentially be useful as a cardiotoxicity biomarker.
Objective To assess for possible correlations between troponin-I and echocardiographic parameters of left ventricular function after administration of daunorubicin in children with high-risk acute lymphoblastic leukemia (ALL).
Methods This cross-sectional study on 37 children with high-risk ALL was performed from July 2017 to December 2018, in Padang, West Sumatera. The left ventricular systolic function parameters measured were ejection fraction (EF) and fractional shortening (FS); the left ventricular diastolic function parameter was E/A ratio. Troponin-I measurements and echocardiography were performed after daunorubicin treatment at the end of induction phase chemotherapy. Pearson’s correlation test was used to analyze for a correlation between troponin-I and echocardiographic parameters.
Results Subjects had a mean age of 6.27 (SD 4.43) years, and males comprised 56.8%. Subjects’ mean troponin-I concentration was 5.49 (SD 0.86) ng/mL, and mean EF, FS, and E/A values were 65 (SD 5) %, 36 (SD 4) %, and 1.52 (SD 0.56), respectively. Troponin-I was not significantly correlated with EF (r=0.062; P=0.715) or FS (r=0.309; P=0.172). However, there was a weak, significant negative correlation between troponin-I and E/A ratio
(r=-0.383; P=0.019).
Conclusion Troponin-I level has no significant correlations with the echocardiographic parameters of left ventricular systolic function. However, there is a weak significant negative correlation between troponin-I level and the left ventricular diastolic parameter of E/A ratio.
References
2. Lipshultz SE, Karnik R, Sambatakos P, Franco VI, Ross SM, Miller TL. Anthracycline-related cardiotoxicity in childhood cancer survivors. Curr Opin Cardiol. 2014;29:103-12. DOI: 10.1097/HCO.0000000000000034.
3. Volkova M, Russell R. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev. 2011;7:214-20. DOI: 10.2174/157340311799960645.
4. Corremans R, Adao R, DeKeulenaer GW, Leite-Moreira, Bras-Silva C. Update on pathophysiology and preventive strategies of anthracycline-induced cardiotoxicity. Clin Exp Pharmacol Physiol. 2019;46:204-15. DOI: 10.1111/1440-1681.13036.
5. Siahaan HI, Tobing TC, Rosdiana N, Lubis B. Dampak kardiotoksik obat kemoterapi golongan antrasiklin. Sari Pediatri. 2007;9:151-6. DOI: 10.14238/sp9.2.2007.151-6.
6. Shaikh AS, Saleem AF, Mohsin SS, Alam MM, Ahmed MA. Anthracycline-induced cardiotoxicity : Prospective cohort study from Pakistan. BMJ Open. 2013;3:e003663. DOI: 10.1111/1440-1681.13036.
7. Bu'Lock FA, Mott GM, Oakhill A, Martin EP. Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology. Br Heart J. 1995;73:340-50. DOI: 10.1136/hrt.73.4.340.
8. Salgado AA, Filho CDC, Reis CASS. The role of echocardiography in chemotherapy. Arq Bras Cardiol:imagem cardiovasc. 2014;27:18-23. DOI: 10.5935/2318-8219.20140004.
9. Oztarhan K, Guler S, Aktas B, Arslan M, Salsioglu Z, Aydogan G. The value of echocardiography versus cardiac troponin-I levels in the early detection of anthracycline cardiotoxicity in childhood acute leukemia: prospective evaluation of a 7-year-long clinical follow-up. Pediatr Hematol Oncol. 2011;28:380-94. DOI: 10.3109/08880018.2011.563772.
10. Cardinale D, Sandri MT. Role of biomarkers in chemotherapy-induced cardiotoxicity. Prog Cardiovasc Dis. 2010;53:121-9. DOI: 10.1016/j.pcad.2010.04.002.
11. Muller-Bardorff M, Hallermayer K, Schroder A, Ebert C, Borgya A, Gerhardt W, et al. Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation. Clin Chem. 1997;43:458-66. DOI: 10.1093/clinchem/43.3.458
12. Bertinchant JP, Polge A, Juan JM, Oliva-Lauraire MC, Giuliana I, Marty-Double C, et al. Evaluation of cardiac troponin-I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings. Clin Chim Acta. 2003;329:39-51. DOI: 10.1016/s0009-8981(03)00013-5
13. Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109:3122–31. DOI: 10.1016/j.jacc.2009.02.050
14. 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. DOI: 10.1161/01.CIR.0000130926.51766.CC .
15. Unit Koordinasi Kerja Hematologi-Onkologi IDAI. Protokol pengobatan leukemia limpoblastik akut anak tahun 2013 (Indonesian Childhood ALL-2013 Protocol). Jakarta: UKK Hematologi-Onkologi IDAI 2013. p 1-29.
16. Katruka IA. Human cardiac troponin complex. Structure and functions. Biochemistry. 2013;78:1447-65. DOI: 10.1134/S0006297913130063
17. Mertens LL, Friedberg MK. Systolic ventricular function. In: Lai WW, Mertens LL, Cohen MS, Geva T, editors. Echocardiography in pediatric and congenital heart disease. Oxford: John Wiley&Sons Ltd; 2016. p. 96-131.
18. Park KM. Pediatric cardiology for practitioners. 5th ed. Philadelphia: Elsevier; 2008. p. 65-113.
19. Brunner M, Moeslinger T, Spieckerman PG. Echocardiography for teaching cardiac physiology in practical student courses. Am J Physiol. 1995;268:1-9. DOI: 10.1152/advances.1995.268.6.S2
20. Mertens LL, Friedberg MK. Echocardiographic assessment of cardiac dimensions, cardiac function and valve function. In: Allen HD, Driscoll DJ, Shaddy RE, Feltes TF, editors. Moss and Adam’s heart disease in infants, children and adolescents including the fetus and young adult. 8th ed. Philadelphia: Lippincott Williams & Wilkins;2012. p.172-206.
21. Sukardi R. Penatalaksanaan terkini gagal jantung pada anak. In: Putra ST, Djer MM, Roeslani RD, Endryarni B, Yuniar I, editors. Management of pediatric heart disease for practitioners: from early detection to intervention. Jakarta: Departemen Ilmu Kesehatan Anak FKUI-RSCM; 2000. p. 40-63.
22. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277–314. DOI: 10.1016/j.echo.2016.01.011
23. Kossaify A, Nasr A. Diastolic dysfunction and the new recommendations for echocardiographic assessment of left ventricular diastolic function: Summary of guidelines and novelties in diagnosis and grading. JDMS. 2019;35:317-25. DOI: 10.1177/8756479319836781.
24. Sari TT, Windiastuti E, Cempako GR, Devaera Y. Prognosis leukemia limfoblastik akut pada anak obes. Sari Pediatri. 2010;12:58-62. DOI: 10.14238/sp12.1.2010.58-62.
25. Wa’u DV, Mulatsih S, Murni IK. Profil jantung pasien akut limfoblastik leukemia anak yang mendapatkan terapi anthracycline. Indones J Cancer. 2017;11:15-20. DOI: 10.33371/ijoc.v11i1.496.
26. Wijayanti LP, Supriyadi E. Faktor prognostic dan kesintasan pasien leukemia limfoblastik akut anak di RSUP Dr. Sardjito, Yogyakarta, 2010-2015. Indones J Cancer. 2017;11:145-50. DOI: 10.33371/ijoc.v11i4.532.
27. Ariawati K, Windiastuti E, Gatot D. Toksisitas kemoterapi leukemia limfoblastik akut pada fase induksi dan profilaksis susunan saraf pusat dengan metotreksat 1 gram. Sari Pediatri. 2007;9:257-8. DOI: 10.14238/sp9.4.2007.252-8.
28. Dolci A, Dominici R, Cardinale D, Sandri MT, Panteghini M. Biochemical markers for prediction of chemotherapy induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol. 2008;130:688-95. DOI: 10.1309/AJCPB66LRIIVMQDR.
29. Shafi A, Siddiqui N, Imtiaz S, Sajid MUD. Left ventricular systolic dysfunction predicted by early troponin-I release after anthracycline based chemotherapy in breast cancer patients. J Ayub Med Coll Abbottabad. 2017;29:266-9.
30. Raj S, Franco VI, Lipshultz SE. Anthracycline-induced cardiotoxicity: a review of pathophysiology, diagnosis and treatment. Curr Treat Options Cardiovasc Med. 2014;16:315. DOI: 10.1007/s11936-014-0315-4.
31. Bertinchant JP, Polge A, Juan JM, Oliva-Lauraire MC, Giuliani I, Marty-Double C, et al. Evaluation of cardiac troponin-I and T levels as markers of myocardial damage in doxorubicine-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings. Clin Chim Acta. 2003;329:39-51. DOI: 10.1016/S0009-8981(03)00013-5.
32. Handojo K, Sjakti HA, Yanuarso PB, Akib AAP. Fungsi sistolik dan diastolic jantung pada pasien anak dengan osteosarcoma yang mendapat terapi doksorubicin di RS Cipto Mangunkusumo. Sari Pediatri. 2014;16:149-56. DOI: 10.14238/sp16.3.2014.149-56.
33. Rahman MA. Fungsi sistolik dan diastolik ventrikel kiri pada anak dengan leukemia limfoblastik akut pasca terapi daunorubicin. Sari Pediatri. 2005;7:160-8. DOI: 10.14238/sp7.3.2005.160-8.
34. Mele D, Nardozza M, Spallarossa P, Frassoldati A, Tocchetti CG, Cadeddu C, et al. Current views on anthracycline cardiotoxicity. Heart Fail Rev. 2016;21:621-34. DOI: 10.1007/s10741-016-9564-5.
35. Sandri MT, Cardinale D, Zorzino L, Passerini R, Lentati P, Martinoni A, et al. Minor increases in plasma troponin-I predict decreased left ventricular ejection fraction after high-dose chemotherapy. Clin Chem. 2003;49:248-52. DOI: 10.1373/49.2.248.
36. Leandro J, Dyck J, Poppe D, Shore R, Airhart C, Greenburg M, et al. Cardiac dysfunction late after cardiotoxic therapy for childhood cancer. Am J Cardiol. 1994;74:1152-6. DOI: 10.1016/0002-9149(94)90470-7.
37. Cardinale D, Sandri MT, Martinoni A, Tricca A, Civelli M, Lamantia G, et al. Left ventricular dysfunction predicted by early troponin-I release after high-dose chemotherapy. J Am Coll Cardiol. 2000;36:517-22. DOI: 10.1016/S0735-1097(00)00748-8.
38. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM, Schaffer EM, Schwartz RG, et al. Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Children Cancer Study Group. Pediatrics. 1992;89:942-9. PMID: 1579408.
39. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22:107-33. DOI: 10.1016/j.echo.2016.01.011.
40. Hutchison S. Principles of echocardiography and intracardiac echocardiography. Philadelphia: Elsevier Saunders; 2012. p.253-69.
41. Schmitt K, Tulzer G, Merl M, Aichhorn A, Grillenberger A, Wiesinger G, et al. Early detection of doxorubicin and daunorubicin cardiotoxicity by echocardiography: diastolic versus systolic parameters. Eur J Pediatr. 1995;154:201-4. DOI: 10.1007/BF01954271.
42. Dorup I, Levitt G, Sullivan I, Sorensen K. Prospective longitudinal assessment of late anthracycline cardiotoxicity after childhood cancer: the role of diastolic function. Heart. 2004;90:1214-6. DOI: 10.1136/hrt.2003.027516.
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Accepted 2021-03-16
Published 2021-03-16