The impact of elevated cumulative anthracycline dose on cardiac repolarization changes in children with cancer: a prospective study

Purpose: We aimed to prospectively interpret the cardiac repolarization changes with 12-lead electrocardiography (ECG) in children with cancer who were treated with anthracycline drugs. Materials and methods: A total of 53 patients with cancer treated with anthracycline were enrolled in the study. During 6-month follow-up, standard 12-lead ECG was performed at basal, 1st, 4th, and 24th hours after the first dose of anthracycline treatment, at the time of 120 mg/m2 cumulative anthracycline dose and 240 mg/m2 of cumulative anthracycline dose in the same patients, respectively. P dispersion (PWd), QT dispersion (QTd), corrected QT dispersion (QTcd), Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio were obtained from 12-lead ECG. The patients were classified into three groups according to increasing cumulative anthracycline doses: Group 1: first dose (n=53), Group 2: 120 mg/m2 (n=53), Group 3: 240 mg/m2 (n=53). Results: The median age was 48 months (range 9-192 months). While PWd, QTd, QTcd, and Tp-e interval were significantly increased during first 24 hours of the first dose (p

Amaç: Antrasiklin kemoterapisi ile tedavi edilen kanserli çocuklarda kardiyak repolarizasyon değişikliklerini 12 derivasyonlu elektrokardiyografi (EKG) ile değerlendirmeyi amaçladık. Gereç ve yöntem: Antrasiklin ile tedavi edilen kanserli toplam 53 hasta çalışmaya dahil edildi. Bu hastalara 12 derivasyonlu EKG ile antrasiklin tedavisinin ilk dozu, 120 mg/m2 ve 240 mg/m2 kümülatif dozu sırasında her doz uygulamasının ilaç verilmeden hemen öncesinde ve ilaç verildikten sonraki 1., 4. ve 24. saatinde EKG’leri çekildi. Bu EKG’lerden P dispersiyonu (PWd), QT dispersiyonu (QTd), düzeltilmiş QT dispersiyonu (QTcd), Tp-e aralığı, Tp-e/QT ve Tp-e/QTc oranı hesaplandı. Hastalar artan kümülatif antrasiklin dozlarına göre üç gruba ayrıldı: Grup 1: ilk doz (n=53), Grup 2: 120 mg/m2 (n=53), Grup 3: 240 mg/m2 (n=53). Bulgular: Ortanca yaş 48 ay (aralık 9-192 ay) idi. İlk dozun ilk 24 saatinde PWd, QTd, QTcd ve Tp-e değişkenleri anlamlı olarak artış gösterdiği saptandı. (sırasıyla p

Kaynakça

1. Scholz Kreisel P, Kaatsch P, Spix C, et al. Second malignancies following childhood cancer treatment in Germany from 1980 to 2014 – a registry-based analysis. Dtsch Arztebl Int 2018;115:385-392. https:// doi.org/10.3238/arztebl.2018.0385

2. Armenian SH, Armstrong GT, Aune G, et al. Cardiovascular disease in survivors of childhood cancer: insights into epidemiology, pathophysiology, and prevention. J Clin Oncol 2018;36:2135-2144. https://doi.org/10.1200/JCO.2017.76.3920

3. Van der Pal HJ, van Dalen EC, van Delden E, et al. High risk of symptomatic cardiac events in childhood cancer survivors. J Clin Oncol 2012;30:1429-1437. https://doi.org/10.1200/JCO.2010.33.4730

4. Christensen PK, Gall MA, Major Pedersen A, et al. QTc interval length and QT dispersion as predictors of mortality in patients with non-insulin-dependent diabetes. Scand J Clin Lab Invest 2000;60:323-332. https://doi.org/10.1080/003655100750046486

5. Kors JA, Ritsema van Eck HJ, van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol 2008;41:575-580. https://doi. org/10.1016/j.jelectrocard.2008.07.030

6. Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008;41:567-574. https://doi.org/10.1016/j. jelectrocard.2008.07.016

7. Bieganowska K, Sawicka Parobczyk M, Bieganowski M, Piskorski J. Tpeak-tend interval in 12-lead electrocardiogram of healthy children and adolescents in childhood. Ann Noninvasive Electrocardiol 2013;18:344-351. https://doi: 10.1111/anec.12035

8. Kremer LC, van der Pal HJ, Offringa M, van Dalen EC, Voûte PA. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 2002;13:819-829. https://doi.org/10.1093/annonc/mdf167

9. Armenian SH, Hudson MM, Mulder RL, et al. Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 2015;16:123-136. https://doi.org/10.1016/S1470- 2045(14)70409-7

10. Dilaveris PE, Gialafos EJ, Sideris SK, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 1998;135:733-738. https://doi.org/10.1016/s0002- 8703(98)70030-4

11. Bazett HC. An analysis of the time relations of electrocardiograms. Heart 1920;7:353-370. https://doi. org/10.1111/j.1542-474X.1997.tb00325.x

12. Sap F, Karatas Z, Altin H, et al. Dispersion durations of P-wave and QT interval in children with congenital heart disease and pulmonary arterial hypertension. Pediatr Cardiol 2013;34:591-596. https://doi.org/10.1007/ s00246-012-0503-5

13. Bieganowska K, Sawicka Parobczyk M, Bieganowski M, et al. Tpeak -tend interval in 12-lead electrocardiogram of healthy children and adolescents tpeak -tend interval in childhood. Ann Noninvasive Electrocardiol 2013;18:344-351. https://doi.org/10.1111/anec.12035

14. Kılıcaslan F, Tokatli A, Ozdag F, et al. Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea. Pacing Clin Electrophysiol 2012;35:966-972. https://doi.org/10.1111/j.1540-8159.2012.03439.x

15. Lang RM, Badano LP, Mor Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015;28:14-39. https://doi. org/10.1016/j.echo.2014.10.003

16. Kremer LC, Caron HN. Anthracycline cardiotoxicity in children. N Engl J Med 2004;351:120-121. https://doi. org/10.1056/NEJMp048113

17. Outomuro D, Grana DR, Azzato F, Milei J. Adriamycine– induced myocardial toxicity: new solutions for an old problem? Int J Cardiol 2007;117:6-15. https://doi. org/10.1016/j.ijcard.2006.05.005

18. Higham PD, Campell RW. QT dispersion. Br Heart J 1994;71:508-510. https://doi.org/10.1136/hrt.71.6.508

19. Tutar HE, Ocal B, İmamoglu A, Atalay S. Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion. Heart 1998;80:77- 79. https://doi.org/10.1136/hrt.80.1.77

20. Gulen H, Kazanci E, Mese T, et al. Cardiac functions by myocardial performance index and QT dispersion in survivors of childhood lymphoblastic leukaemia. Minerva Pediatr 2007;59:107-113.

21. Tasolar H, Ballı M, Cetin M, Otlu YO, Altun B, Bayramoglu A. Effects of the coronary collateral circulation on the Tp-e interval and Tp-e/QT ratio in patients with stable coronary artery disease. Ann Noninvasive Electrocardiol 2015;20:53-61. https://doi. org/10.1111/anec.12173

22. Zhao X, Xie Z, Chu Y, et al. Association between Tp-e/QT ratio and prognosis in patients undergoing primary percutaneous coronary intervention for STsegment elevation myocardial infarction. Clin Cardiol 2012;35:559-564. https://doi.org/10.1002/clc.22022

23. Panikkath R, Reinier K, Uy Evanado A, et al. Prolonged Tpeak-toTend interval on the resting ECG is associated with increased risk of sudden cardiac death. Circ Arrhythm Electrophysiol 2011;4:441-447. https://doi. org/10.1161/CIRCEP.110.960658

24. Haarmark C, Hansen PR, Vedel Larsen E, et al. The prognostic value of the Tpeak–Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Electrocardiol 2009;42:555-560. https:// doi.org/10.1016/j.jelectrocard.2009.06.009

25. Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 1973;32:302-314. https:// doi.org/10.1002/1097-0142(197308)32:2<302::aidcncr2820320205>3.0.co;2-2

26. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003;97:2869-2879. https://doi.org/10.1002/ cncr.11407

27. Buzdar AU, Marcus C, Smith TL, Blumenschein GR. Early and delayed clinical cardiotoxicity of doxorubicin. Cancer 1985;55:2761-2765. https://doi. org/10.1002/1097-0142(19850615)55:12<2761::aidcncr2820551206>3.0.co;2-p

28. Steinherz LJ, Steinherz PG, Tan CT, Heller G, Murphy ML. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA 1991;266:1672-1677.

29. Cardinale D, Colombo A, Bacchiani G, et al. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation 2015;131:1981-1988. https://doi.org/10.1161/ CIRCULATIONAHA.114.013777

Kaynak Göster

  • ISSN: 1309-9833
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2008

365 79