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Assessment of Early-Onset Chronic Progressive Anthracycline Cardiotoxicity in Children: Different Response Patterns of Right and Left Ventricles

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Abstract

We aimed to assess early-onset chronic progressive cardiotoxicity in the left and right ventricles with increasing cumulative anthracycline doses. We evaluated 72 patients within the first year after doxorubicin and/or daunorubicin treatment (median 1.3 months; range 0.3–11.5) and 31 healthy controls. Pretreatment and posttreatment QT interval analyzes were performed in 27 newly diagnosed patients. The echocardiographic data of all examinations of 72 patients were classified into three groups according to instant cumulative anthracycline doses: treatment group (TG)-I (≤120 mg/m2; n = 26), TG-II (120–240 mg/m2; n = 39), and TG-III (≥240 mg/m2; n = 40). Diastolic and systolic parameters were analyzed by conventional echocardiography and tissue Doppler imaging (TDI) and compared with those of healthy controls. The mean age for patients and controls was 8.2 ± 4.5 and 9.6 ± 4.2 years, respectively (p > 0.05). QTc dispersion significantly increased after anthracycline treatment (p = 0.02). TDI showed decreased E′ velocity (p < 0.001) and E′/A′ ratio (p < 0.001) at lateral tricuspid annulus segment in TG-I, and these findings continued in TG-II and -III. In addition, S′ velocity decreased in TG-I, -II, and -III at lateral mitral annulus (10.5 ± 2.6 cm/s, p < 0.05; 9.9 ± 2.2 cm/s, p < 0.001; and 10.1 ± 2.3 cm/s, p < 0.01, respectively). However, decrease in left-ventricular ejection fraction was statistically significant in TG-II and -III (p < 0.001). Although myocardial performance index was significantly increased in all treatment groups in both segments, it was primarily due to significant increases in isovolumic relaxation time at the lateral tricuspid annulus and isovolumic contraction time at the lateral mitral annulus. Abnormalities in diastolic function in right ventricle and systolic function in the left ventricle were observed even with a cumulative anthracycline dose <120 mg/m2 by TDI. In addition, anthracycline treatment led to an increase in QTc dispersion.

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References

  1. Ayhan SS, Özdemir K, Kayrak M, Bacaksiz A et al (2012) The evaluation of doxorubicin-induced cardiotoxicity: comparison of Doppler and tissue Doppler-derived myocardial performance index. Cardiol J 19:363–368

    Article  PubMed  Google Scholar 

  2. Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE (2007) Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Exp Opin Pharmacother 8:1039–1058

    Article  CAS  Google Scholar 

  3. Baysal T, Koksal Y, Oran B, Sen M et al (2010) Cardiac functions evaluated with tissue Doppler imaging in childhood cancers treated with anthracyclines. Pediatr Hematol Oncol 27:13–23

    Article  CAS  PubMed  Google Scholar 

  4. Chanan-Khan A, Srinivasan S, Czuczman M (2004) Prevention and management of cardiotoxicity from antineoplastic therapy. J Support Oncol 2:251–266

    PubMed  Google Scholar 

  5. Di Lisi D, Bonura F, Macaione F, Peritore A et al (2011) Chemotherapy-induced cardiotoxicity: role of the tissue Doppler in the early diagnosis of left ventricular dysfunction. Anticancer Drugs 22:468–472

    Article  PubMed  Google Scholar 

  6. Dodos F, Halbsguth T, Erdmann E, Hoppe UC (2008) Usefulness of myocardial performance index and biochemical markers for early detection of anthracycline-induced cardiotoxicity in adults. Clin Res Cardiol 97:318–326

    Article  PubMed  Google Scholar 

  7. Dorup I, Levitt G, Sullivan I, Sorensen K (2004) Prospective longitudinal assessment of late anthracycline cardiotoxicity after childhood cancer: the role of diastolic function. Heart 90:1214–1216

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Eidem BW, Sapp BG, Suarez CR, Cetta F (2001) Usefulness of the myocardial performance index for early detection of anthracycline-induced cardiotoxicity in children. Am J Cardiol 87:1120–1122

    Article  CAS  PubMed  Google Scholar 

  9. Galetta F, Franzoni F, Cervetti G, Cecconi N et al (2005) Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients. Biomed Pharmacother 59:541–544

    Article  CAS  PubMed  Google Scholar 

  10. Gharib MI, Burnett AK (2002) Chemotherapy-induced cardiotoxicity: current practice and prospects of prophylaxis. Eur J Heart Fail 4:235–242

    Article  CAS  PubMed  Google Scholar 

  11. Hortobágyi GN (1997) Anthracyclines in the treatment of cancer. An overview. Drugs 54:1–7

    Article  PubMed  Google Scholar 

  12. Hudson MM, Rai SN, Nunez C, Merchant TE et al (2007) Noninvasive evaluation of late anthracycline cardiac toxicity in childhood cancer survivors. J Clin Oncol 25:3635–3643

    Article  CAS  PubMed  Google Scholar 

  13. Isaaz K, Thompson A, Ethevenot G, Cloez JL et al (1989) Doppler echocardiographic measurement of low velocity motion of the left ventricular posterior wall. Am J Cardiol 64:66–75

    Article  CAS  PubMed  Google Scholar 

  14. Kapusta L, Groot-Loonen J, Thijssen JM, DeGraaf R, Daniëls O (2003) Regional cardiac wall motion abnormalities during and shortly after anthracyclines therapy. Med Pediatr Oncol 41:426–435

    Article  PubMed  Google Scholar 

  15. Karakurt C, Koçak G, Ozgen U (2008) Evaluation of the left ventricular function with tissue tracking and tissue Doppler echocardiography in pediatric malignancy survivors after anthracycline therapy. Echocardiography 25:880–887

    Article  PubMed  Google Scholar 

  16. Kremer LC, van der Pal HJ, Offringa M, van Dalen EC, Voûte PA (2002) Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 13:819–829

    Article  CAS  PubMed  Google Scholar 

  17. Kulakowski P, Karczmarewicz S, Czepiel A, Makowska E et al (2001) QT interval dispersion in ventricular beats: a noninvasive marker of susceptibility to sustained ventricular arrhythmias. Pacing Clin Electrophysiol 24:352–357

    Article  CAS  PubMed  Google Scholar 

  18. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR et al (1991) Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 324:808–815

    Article  CAS  PubMed  Google Scholar 

  19. Lipshultz S, Alvarez J, Scully R (2008) Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart 94:525–533

    Article  CAS  PubMed  Google Scholar 

  20. Macfarlane PW, McLaughlin SC, Devine B, Yang TF (1994) Effects of age, sex, and race on ECG interval measurements. J Electrocardiol 27:14–19

    Article  PubMed  Google Scholar 

  21. Mertens A, Yasui Y, Neglia J, Potter J et al (2001) Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study. J Clin Oncol 19:3163–3172

    CAS  PubMed  Google Scholar 

  22. Nakamae H, Hino M, Akahori M, Terada Y et al (2004) Predictive value of QT dispersion for acute heart failure after autologous and allogeneic hematopoietic stem cell transplantation. Am J Hematol 76:1–7

    Article  PubMed  Google Scholar 

  23. Ocal B, Oguz D, Karademir S, Birgen D et al (2002) Myocardial performance index combining systolic and diastolic myocardial performance in doxorubicin-treated patients and its correlation to conventional echo/Doppler indices. Pediatr Cardiol 23:522–527

    Article  CAS  PubMed  Google Scholar 

  24. Oeffinger K, Mertens A, Sklar C, Kawashima T et al (2006) Chronic health conditions in adult survivors of childhood cancer. N Engl J Med 355:1572–1582

    Article  CAS  PubMed  Google Scholar 

  25. Orditura M, Sarubbi B, Devita F, Ducceschi V et al (1997) Prolonged corrected QT dispersion. Oncol Rep 4:1047–1050

    CAS  PubMed  Google Scholar 

  26. Paulus WJ, Tschöpe C, Sanderson JE, Rusconi C et al (2007) How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28:2539–2550

    Article  PubMed  Google Scholar 

  27. Ruggiero A, De Rosa G, Rizzo D, Leo A et al (2012) Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia. Int J Clin Oncol. doi:10.1007/s10147-012-0458-9

  28. Sarubbi B, Orditura M, Ducceschi V, De Vita F et al (1997) Ventricular repolarization time indexes following anthracycline treatment. Heart Vessels 12:262–266

    Article  CAS  PubMed  Google Scholar 

  29. Senju N, Ikeda S, Koga S, Miyahara Y et al (2007) The echocardiographic Tei-index reflects early myocardial damage induced by anthracyclines in patients with hematological malignancies. Heart Vessels 22:393–397

    Article  PubMed  Google Scholar 

  30. Shankar SM, Marina N, Hudson MM, Hodgson DC et al (2008) Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children’s Oncology Group. Pediatrics 121:e387–e396

    Article  PubMed  Google Scholar 

  31. Sorensen K, Levitt GA, Bull C, Dorup I, Sullivan ID (2003) Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study. Cancer 97:1991–1998

    Article  CAS  PubMed  Google Scholar 

  32. Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML (1991) Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 266:1672–1677

    Article  CAS  PubMed  Google Scholar 

  33. Steinherz LJ, Graham T, Hurwitz R, Sondheimer HM et al (1992) Guidelines for cardiac monitoring of children during and after anthracycline therapy: report of the Cardiology Committee of the Children’s Cancer Study Group. Pediatrics 89:942–949

    CAS  PubMed  Google Scholar 

  34. Trachtenberg BH, Landy DC, Franco VI, Henkel JM et al (2011) Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr Cardiol 32:342–353

    Article  PubMed  Google Scholar 

  35. van Dalen EC, van den Brug M, Caron HN, Kremer LC (2006) Anthracycline-induced cardiotoxicity: comparison of recommendations for monitoring cardiac function during therapy in paediatric oncology trials. Eur J Cancer 42:3199–3205

    Article  PubMed  Google Scholar 

  36. Vandecruys E, Mondelaers V, De Wolf D, Benoit Y, Suys B (2012) Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood. J Cancer Survivor 6:95–101

    Article  Google Scholar 

  37. Von Hoff DD, Layard MW, Basa P, Davis HL Jr et al (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717

    Article  Google Scholar 

  38. Yeung ST, Yoong C, Spink J, Galbraith A, Smith PJ (1991) Functional myocardial impairment in children treated with anthracyclines for cancer. Lancet 337:816–818

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pediatric Cardiology, Department of Pediatrics, Akdeniz University School of Medicine, Antalya, Turkey

    Abdullah Kocabaş, Fırat Kardelen, Halil Ertuğ & Gayaz Akçurin

  2. Department of Pediatrics, Akdeniz University School of Medicine, Antalya, Turkey

    Bilge Aldemir-Kocabaş

  3. Department of Biostatistics, Akdeniz University School of Medicine, Antalya, Turkey

    Özgür Tosun

  4. Division of Pediatric Hematology and Oncology, Akdeniz University School of Medicine, Antalya, Turkey

    Akif Yeşilipek & Volkan Hazar

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  1. Abdullah Kocabaş
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Correspondence to Abdullah Kocabaş.

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Kocabaş, A., Kardelen, F., Ertuğ, H. et al. Assessment of Early-Onset Chronic Progressive Anthracycline Cardiotoxicity in Children: Different Response Patterns of Right and Left Ventricles. Pediatr Cardiol 35, 82–88 (2014). https://doi.org/10.1007/s00246-013-0745-x

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