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

Year 2021, Volume: 14 Issue: 2, 362 - 370, 01.04.2021
https://doi.org/10.31362/patd.815376

Abstract

Aim: 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 months follow-up, standard 12-lead ECG was performed at basal, 1st, 4th, and 24th hours after first dose of anthracycline treatment, at the time of 120mg/m2 cumulative anthracycline dose and 240mg/m2 of cumulative anthracycline dose in 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: Group1: first dose(n=53), Group2:120 mg/m2(n=53), Group3:240 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<0.001, p=0.005, p=0.041, p=0.016, respectively), Tp-e/QT and Tp-e/QTc ratios were significantly altered during first 24 hours of 120mg/m2 cumulative dose of anthracycline treatment(p<0.001). Any changes in 12-lead ECG were not significantly at 240mg/m2 cumulative dose. However, it was detected that all variables were affected according to each increased anthracycline cumulative dose despite it was not statistically significant.
Conclusions: ECG parameters such as PWd, QTd, QTcd, Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios are useful for detecting subclinical cardiac abnormality and acute anthracycline toxicity during both uses of single-dose anthracycline and increased anthracycline doses. These parameters may also predict arrhythmias in patients with cancer.

References

  • 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;115:385-92.
  • 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;36:2135-44.
  • 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;30:1429-37.
  • 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;60:323–32.
  • 5.Kors JA, Ritsema van Eck HJ, van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol 2008;41:575–80.
  • 6.Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008;41:567–74.
  • 7.Katarzyna B, Małgorzata S-P, Maciej B, et al. Tpeak-tend interval in 12-lead electrocardiogram of healthy children and adolescents in childhood. Ann Noninvasive Electrocardiol 2013;18:344–51.
  • 8.Kremer LC, van der Pal HJ, Offringa M, et al. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 2002;13:819-29.
  • 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:e123-36
  • 10.Dilaveris PE, Gialafos EJ, Sideris SK, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 1998;135:733–8.
  • 11.Bazett HC. An analysis of the time relations of electrocardiograms. Heart 1920;7:353–70
  • 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.
  • 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: 344–51.
  • 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.
  • 15.Kremer LC, Caron HN. Anthracycline cardiotoxicity in children. N Engl J Med 2004; 351: 120-1.
  • 16.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.
  • 17. Higham PD, Campell RW. QT dispersion. Br Heart J 1994; 71: 508-10.
  • 18.Tutar HE, Ocal B, İmamoglu A Atalay S et al. Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion. Heart. 1998; 80: 77-9
  • 19.Gulen H, Kazanci E, Mese T, Uzunkaya D, Erbay A, Tavli V, Vergin C. Cardiac functions by myocardial performance index and QT dispersion in survivors of childhood lymphoblastic leukaemia. Minerva Pediatr. 2007;59(2):107-13.
  • 20.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.
  • 21.Zhao X, Xie Z, Chu Y, Yang L, Xu W, Yang X, et al. Association between Tp-e/QT ratio and prognosis in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Clin Cardiol 2012;35(9):559-64.
  • 22.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.
  • 23.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.

Artan kümülatif antrasiklin dozunun kanserli çocuklarda kardiyak repolarizasyon değişikliklerine etkisi: prospektif bir çalışma

Year 2021, Volume: 14 Issue: 2, 362 - 370, 01.04.2021
https://doi.org/10.31362/patd.815376

Abstract

Amaç: Antrasiklin kemoterapisi ile tedavi edilen kanserli çocuklarda kardiyak repolarizasyon değişikliklerini 12 derivasyonlu elektrokardiyografi (EKG) ile değerlendirmeyi amaçladık.
Gereç ve yöntem: Çalışmaya antrasiklin ile tedavi edilen kanserli toplam 53 hasta çalışmaya dahil edildi. Bu hastalara 12 derivasyonlu EKG ile antrasiklin tedavisinin ilk dozu, 120 mg/m2 kümülatif dozu ve 240 mg/m2 kümülatif dozu verilir ikenki her doz uygulaması sırasında ilaç verilmeden hemen önce, ilaç verildikten sonraki 1., 4. Ve 24. Saatteki 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 <0,001, p = 0,005, p = 0,041, p = 0,016). 120mg / m2 kümülatif antrasiklin tedavisinin ilk 24 saatinde ise Tp-e/QT and Tp-e/QTc oranları istatistiksel anlamlı olarak değişiklik gösterdi (p <0.001). 240 mg / m2 kümülatif antrasiklin dozunda ise herhangi bir anlamlı değişiklik saptanmadı. Ancak istatistiksel olarak anlamlı olmamakla birlikte, artan her antrasiklin kümülatif dozuna göre disperisyon değişkenlerinde uzama, Tp-e / QT ve Tp-e / QTc oranlarında ise azalma olduğu belirlendi.
Sonuç: PWd, QTd, QTcd, Tp-e aralığı, Tp-e / QT ve Tp-e / QTc oranları gibi EKG değişkenleri, hem tek doz antrasiklin hem de artan antrasiklin kullanımı sırasında subklinik kardiyak anormalliği ve akut antrasiklin toksisitesini saptamak için yararlı olduğunu saptadık. Bu parametreler değerlendirildiğinde kanserli hastalarda aritmileri de belirlemede önemli olacaktır.

References

  • 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;115:385-92.
  • 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;36:2135-44.
  • 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;30:1429-37.
  • 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;60:323–32.
  • 5.Kors JA, Ritsema van Eck HJ, van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol 2008;41:575–80.
  • 6.Gupta P, Patel C, Patel H, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008;41:567–74.
  • 7.Katarzyna B, Małgorzata S-P, Maciej B, et al. Tpeak-tend interval in 12-lead electrocardiogram of healthy children and adolescents in childhood. Ann Noninvasive Electrocardiol 2013;18:344–51.
  • 8.Kremer LC, van der Pal HJ, Offringa M, et al. Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review. Ann Oncol 2002;13:819-29.
  • 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:e123-36
  • 10.Dilaveris PE, Gialafos EJ, Sideris SK, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 1998;135:733–8.
  • 11.Bazett HC. An analysis of the time relations of electrocardiograms. Heart 1920;7:353–70
  • 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.
  • 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: 344–51.
  • 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.
  • 15.Kremer LC, Caron HN. Anthracycline cardiotoxicity in children. N Engl J Med 2004; 351: 120-1.
  • 16.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.
  • 17. Higham PD, Campell RW. QT dispersion. Br Heart J 1994; 71: 508-10.
  • 18.Tutar HE, Ocal B, İmamoglu A Atalay S et al. Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion. Heart. 1998; 80: 77-9
  • 19.Gulen H, Kazanci E, Mese T, Uzunkaya D, Erbay A, Tavli V, Vergin C. Cardiac functions by myocardial performance index and QT dispersion in survivors of childhood lymphoblastic leukaemia. Minerva Pediatr. 2007;59(2):107-13.
  • 20.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.
  • 21.Zhao X, Xie Z, Chu Y, Yang L, Xu W, Yang X, et al. Association between Tp-e/QT ratio and prognosis in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Clin Cardiol 2012;35(9):559-64.
  • 22.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.
  • 23.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.
There are 23 citations in total.

Details

Primary Language English
Subjects Oncology and Carcinogenesis
Journal Section Research Article
Authors

Sultan Aydin Köker 0000-0002-8801-7776

Yesim Oymak 0000-0002-6908-8309

Timur Meşe This is me 0000-0002-4433-3929

Murat Yılmazer This is me 0000-0003-0819-5829

Bengü Demirağ This is me 0000-0003-4399-0844

Rahmi Özdemir This is me 0000-0002-2775-166X

Tuba Hilkay Karapınar 0000-0002-4714-332X

Dilek İnce 0000-0002-7914-7886

Raziye Vergin 0000-0002-8594-9762

Publication Date April 1, 2021
Submission Date October 23, 2020
Acceptance Date January 18, 2021
Published in Issue Year 2021 Volume: 14 Issue: 2

Cite

AMA Aydin Köker S, Oymak Y, Meşe T, Yılmazer M, Demirağ B, Özdemir R, Karapınar TH, İnce D, Vergin R. The impact of elevated cumulative anthracycline dose on cardiac repolarization changes in children with cancer: a prospective study. Pam Med J. April 2021;14(2):362-370. doi:10.31362/patd.815376

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