Clinical Research in Cardiology

, Volume 108, Issue 9, pp 1000–1008 | Cite as

Doxorubicin treatments induce significant changes on the cardiac autonomic nervous system in childhood acute lymphoblastic leukemia long-term survivors

  • Maxime CaruEmail author
  • Denis Corbin
  • Delphine Périé
  • Valérie Lemay
  • Jacques Delfrate
  • Simon Drouin
  • Laurence Bertout
  • Maja Krajinovic
  • Caroline Laverdière
  • Gregor Andelfinger
  • Daniel Sinnett
  • Daniel Curnier
Original Paper



Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the effects of the treatments on the cardiac autonomic nervous system.

Methods and results

A total of 203 cALL survivors were included in our analyses and were classified into 3 categories based on the prognostic risk group: standard risk, high risk with and without dexrazoxane. A 24-h Holter monitoring was performed to study the cardiac autonomic nervous system. The frequency domain heart rate variability (HRV) was used to validate the cardiac autonomic nervous system modifications. Other analyses were performed using linear HRV indexes in the time domain and non-linear indexes. A frequency domain HRV parameters analysis revealed significant differences on an overall time-period of 24 h. A repeated measures ANOVA indicated a group-effect for the low frequency (p = 0.029), high frequency (p = 0.03) and LF/HF ratio (p = 0.029). Significant differences in the time domain and in the non-linear power spectral density HRV parameters were also observed.


Anti-cancer treatments induced significant changes in the cardiac autonomic nervous system. The HRV was sensitive enough to detect cardiac autonomic nervous system alterations depending on the cALL risk category. Protection strategies (i.e., dexrazoxane treatments), which were used to counter the adverse effects of doxorubicin, could prevent changes observed in the cardiac autonomic nervous system.


Acute lymphoblastic leukemia Cardiac autonomic nervous system Heart rate variability Doxorubicin treatments Electrophysiology 



This work was supported by the Institute of Cancer Research (ICR) of the Canadian Institutes of Health Research (CIHR), in collaboration with C17 Council, Canadian Cancer Society (CCS), Cancer Research Society (CRS), Garron Family Cancer Centre at the Hospital for Sick Children, Ontario Institute for Cancer Research (OICR) and Pediatric Oncology Group of Ontario (POGO) (grant number: TCF 118694). This research was also supported in part by PhD study grants from Cole Foundation, Fonds de Recherche du Québec—Santé (FRQS), Sainte-Justine University Hospital Center Foundation and Foundation of Stars. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We appreciate the invaluable assistance of Ariane Levesque (McGill University) for her review of the article in the English language.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Maxime Caru
    • 1
    • 2
    • 3
    • 4
    Email author
  • Denis Corbin
    • 1
  • Delphine Périé
    • 4
  • Valérie Lemay
    • 1
    • 4
  • Jacques Delfrate
    • 4
  • Simon Drouin
    • 4
  • Laurence Bertout
    • 4
  • Maja Krajinovic
    • 4
    • 5
  • Caroline Laverdière
    • 4
    • 5
  • Gregor Andelfinger
    • 4
    • 5
  • Daniel Sinnett
    • 4
    • 5
  • Daniel Curnier
    • 1
    • 4
  1. 1.Laboratoire de Physiopathologie de l’EXercice (LPEX), Département de KinésiologieUniversité de Montréal, CEPSUM, 2100MontrealCanada
  2. 2.Department of PsychologyUniversity of Paris NanterreNanterreFrance
  3. 3.Laboratoire EA 4430-Clinique Psychanalyse Developpement (CliPsyD)University of Paris NanterreNanterreFrance
  4. 4.Sainte-Justine University Health Center, Research CenterMontrealCanada
  5. 5.Department of PediatricsUniversity of MontrealMontrealCanada

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