Abstract

Objective: Anthracyclines which are the main drug of chemotherapy protocols had cardiotoxicity as the most frequent and well-known side effect. We aimed to evaluate prospectively the heart rate variability with 24-hour Holter electrocardiography (ECG) in children with cancer who treated with anthracycline drugs.

Material and Methods: The 24-hour Holter ECG monitoring was performed at the baseline, at time of 120 mg/m2 and ≥240 mg/m2 of cumulative anthracycline dose in patients with cancer who treated with anthracycline. The time-domain and frequency-domain measurements of heart rate variability (HRV) were obtained. The patients were classified into three groups as Group1:at baseline (n=54), Group 2:≥120mg/m2 (n=54), Group 3:≥240mg/m2 (n=54).

Results: The median age was 48 months (range 9-192 months). All types of cancer were 38 patients (70.4%) of acute leukemia, two patients (3.8%) of T lymphoblastic lymphoma, and 14patients (25.8%) of other childhood cancer who treated with anthracycline. However, all heart rate variability parameters were decreased after each increased cumulative anthracycline dose, especially time-domain parameters such as nSDNN index, rMSSD, pNN50, frequency parameters such as LF, HF, and Total power were significantly altered among Group1 and Group 3. LF/HF ratio was also statistically significantly increased in Group 3. According the heart rate parameters, the mean average heart rate, mean minimum heart rate and mean RR were statistically significantly prolonged from Group1 to Group 3.

Conclusion: Heart rate variability parameters are a noninvasive technique to demonstrate cardiac autonomic neural dysfunction and early myocardial injury. The 24-hour Holter ECG may be used for detecting early cardiac dysautonomia effect during anthracycline treatment with each elevated 120mg/m2 anthracycline of cumulative dose.

Keywords: Cumulative anthracycline, heart rate variability, cardiotoxicity

References

  1. Lipshultz SE, Alvarez JA, Scully RE. Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart 2008;94:525–33.
  2. Van Dalen EC, van der Pal HJ, Kok WE, Caron HN, Kremer LC. Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow up study. Eur J Cancer 2006;42:3191–8.
  3. Sorensen K, Levitt G, Bull C, Chessells J, Sullivan I. Anthracycline dose in childhood acute lymphoblastic leukemia: issues of early survival versus late cardiotoxicity. J Clin Oncol 1997;15:61–8.
  4. Lipshultz SE, Colan SD, Gelber RD, Perez Atayde AR, Sallan SE, Sanders SP. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med 1991;324:808–15.
  5. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 2003;97:2869–79.
  6. Zimetbaum PJ, Josephson ME. The evolving role of ambulatory arrhythmia monitoring in general clinical practice. Ann Intern Med 1999;130:848-56.
  7. Joshi AK, Kowey PR, Prystowsky EN, Benditt DG, Cannom DS, Pratt CM, et al. First experience with a Mobile Cardiac Outpatient Telemetry (MCOT) system for the diagnosis and management of cardiac arrhythmia. Am J Cardiol 2005;95:878-81.
  8. Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, et al. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ 2009;339:b4606.
  9. Karacan M, Ceviz N, Olgun H. Heart rate variability in children with acute rheumatic fever. Cardiol Young 2012;22:285-92.
  10. Task Force of The European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability-standards of measurement, physiological interpretation, and clinical use. Eur Heart J 1996;17:354–81.
  11. Stachowiak P, Milchert-Leszczyńska M, Falco M, Wojtarowicz A, Kaliszczak R, Safranow K, et al. Heart rate variability during and after chemotherapy with anthracycline in patients with breast cancer. Kardiol Pol 2018;76:914-6.
  12. Makikallio TH, Huikuri HV, Makikalliob A, Sourander LB, Mitrani RD, Castellanos A, et al. Prediction of sudden cardiac death by fractal analysis of heart rate variability in elderly subjects. J Am Coll Cardiol 2001;37:1395–402.
  13. Kim K, Chae J, Lee S. The role of heart rate variability in advanced non-small-cell lung cancer patients. J Palliat Care 2015;31:103–8.
  14. Singh N, Mironov D, Armstrong PW, Ross AM, Langer A. Heart Rate Variability Assessment Early After Acute Myocardial Infarction Pathophysiological and Prognostic Correlates. Circulation 1996;93:1388–95.
  15. Goldenberg I, Goldkorn R, Shlomo N, Einhorn M, Levitan J, Kuperstein R, et al. Heart Rate Variability for Risk Assessment of Myocardial Ischemia in Patients Without Known Coronary Artery Disease: The HRV-DETECT (Heart Rate Variability for the Detection of Myocardial Ischemia) Study. J Am Heart Asso 2019;8:e014540.
  16. Zamorano J, Lancellotti P, Muñoz D, Aboyans V, Asteggiano R, Galderisi M, et al. Stanowisko ESC dotyczące toksycznego wpływuleczenia onkologicznego na układ sercowo-naczyniowy w 2016 roku, opracowane pod auspicjami Komisji ESC do spraw Wytycznych Postępowania [Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines]. Kardiol Pol 2016;74:1193–233.
  17. Asensio-López MC, Soler F, Sánchez-Más J, Figal DP, Belda FF, Lax A. Early oxidative damage induced by doxorubicin: Source of production, protection by GKT137831 and effect on Ca(2+) transporters in HL-1 cardiomyocytes. Arch Biochem Biophys 2016;594:26–36.
  18. Poręba M, Poręba R, Gać P, Zubkiewicz LU, Pilecki W, Piotrowicz E, et al. Heart rate variability and heart rate turbulence in patients with hematologic malignancies subjected to high-dose chemotherapy in the course of hematopoietic stem cell transplantation. Ann Noninvasive Electrocardiol 2014;19:157–65

Copyright and license

Copyright © 2021 The Author(s). This is an open access article distributed under the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited.

How to cite

1.
Aydin Köker S, Demirağ B, Meşe T, Yılmazer M, Oymak Y, Özdemir R, et al. Assessment of Heart Rate Variability in Children with Cancer after Elevated Cumulative Anthracycline Dose: A Prospective Study. Turk J Pediatr Dis [Internet]. 2021 May 25 [cited 2025 Aug. 23];15(3):216-21. Available from: https://turkjpediatrdis.org/article/view/790