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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 5  |  Issue : 1  |  Page : 31-34

Electrocardiographic characteristics of Nigerian children on anthracycline-based chemotherapy: A preliminary report


Department of Paediatrics, Aminu Kano Teaching Hospital, Kano, Nigeria

Date of Web Publication8-Mar-2017

Correspondence Address:
Dr. I D Peter
Department of Paediatrics, Aminu Kano Teaching Hospital, Kano
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/heartindia.heartindia_37_16

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  Abstract 

Background and Objective: Cardiotoxicity is one of the dose-limiting toxicities of anthracycline antibiotics, and electrophysiological abnormalities have been established. However, the existence of the established electrocardiographic abnormalities in pediatric cancer patients on chemotherapy is yet to be reported in Nigeria. This research seeks to characterize anthracycline cardiotoxicity in Nigerian children using electrocardiogram (ECG).
Materials and Methods: Seventeen children on anthracycline-based regimen for various malignancies in the Paediatric oncology ward of Aminu Kano Teaching Hospital Kano, Nigeria, were recruited for this cross-sectional study. Those with normal serum electrolytes had a bedside ECG after obtaining informed consent. Their QTc, QTc-dispersion, and ST segment morphology were studied and compared with reference ranges of apparently normal Nigerian children where applicable.
Results: There were 12 males (70.6%) and 5 females (29.4%) studied. The age range of the subjects was 2–7 years. Of the 17 subjects, only 3 were on daunorubicin-based regimen, while the rest were on doxorubicin-based regimen. The corrected QT was prolonged in 23.5% of the subjects; the QTc dispersion ranged from 20 to 126 for chest leads and 20–200 for limb leads. Whereas elevation of ST segment occurred in only one patient accounting for 5.9%, ST segment elevation, ST segment depression was present in 6 patients.
Conclusion: There are remarkable differences in the ECG characteristics of patients in this report who had anthracyclines when compared to apparently healthy children.

Keywords: Anthracycline, cardiotoxicity, daunorubicin, doxorubicin, electrocardiography


How to cite this article:
Peter I D, Aliyu I, Shehu U A, Ibrahim U A. Electrocardiographic characteristics of Nigerian children on anthracycline-based chemotherapy: A preliminary report. Heart India 2017;5:31-4

How to cite this URL:
Peter I D, Aliyu I, Shehu U A, Ibrahim U A. Electrocardiographic characteristics of Nigerian children on anthracycline-based chemotherapy: A preliminary report. Heart India [serial online] 2017 [cited 2020 Jul 15];5:31-4. Available from: http://www.heartindia.net/text.asp?2017/5/1/31/201741


  Introduction Top


Anthracycline antibiotics isolated from Streptomyces peucetius var. caesius are among the most widely used cytotoxic anticancer drugs, and they have remained a critical component of treatment for many pediatric malignancies because of their favorable therapeutic benefit.[1],[2] Cardiotoxicity is, however, one of its dose-limiting toxicities. The molecular mechanisms responsible for anthracycline cardiotoxicity remain poorly understood though one possible mechanism is the formation of reactive oxygen species and site-specific DNA damage.[3],[4] Anthracycline-induced cardiotoxicity could be acute or chronic.[5],[6],[7]

In Nigeria, Sule [8] reported death due to cardiac arrhythmias in three adult patients within 8 h of doxorubicin infusion. It is established that QTc interval prolongation is an electrocardiographic abnormality that portends the risk of severe arrhythmias including torsades de pointes and ventricular fibrillation.[9],[10],[11],[12] Studying Turkish children on anthracycline, Kocabas et al.[13] reported increased dispersion of QTc interval in 26% of them. However, there has been no report of this in Nigerian children. Therefore, this research is designed to establish the presence or absence of electrocardiogram (ECG) abnormalities in Nigerian children on anthracycline antibiotics. Considering the age, racial differences noted in ECG interpretation is the need to investigate the pattern of changes seen among our patients.


  Materials and Methods Top


This study was carried out at the Aminu Kano Teaching Hospital (AKTH), Kano. Eligible childhood cancer patients admitted to the pediatric oncology ward were recruited after due written informed parental consent and verbal assent from children aged 7 years and above.

Study design

This was a cross-sectional/descriptive study.

Study population

Pediatric cancer patients on admission in the pediatric oncology ward of AKTH, Kano who had received anthracycline-containing regimen at least 1 week.

Inclusion criteria

Children with confirmed diagnosis of malignancy and on an anthracycline-based regimen who had normal serum electrolytes.

Exclusion criteria

Children with preexisting acquired or congenital heart disease.

Ethical considerations

Informed consent was obtained from the parents/guardians and assent from study participants aged 7 years or older. Approval of the Ethics and Research Committee of the AKTH, Kano was obtained before commencement of this study.

Sample size

Our calculated sample size is 19 subjects based on the reported 26% anthracycline-induced cardiotoxicity reported by Kocabas et al.[13] All eligible subjects were consecutively recruited to attain the sample size. The study was conducted over the 12-month duration, between June 2015 and May 2016.

Data collection/presentation

A portable heated stylus direct writing AT-2 Swiss made electrocardiograph (Schiller AG CARDIOVIT CH6341) with a frequency of 150 Hz and sampling frequency of 1000 Hz, with speeds of 25 mm/s and 50 mm/s, and three levels of sensitivity at 5, 10, and 20 mm/mV was used for this study. Unipolar, bipolar limb leads, and chest leads with European color coding system was used. All measurements and interpretations were done manually by the authors. To obtain heart-rate corrected values for QT interval (QTc interval), we used the Bazett's formula: QTc = QT/√RR.[14] Their QTc, QTc-dispersion, and ST segment morphology were studied. These were compared with established local normative values reported by Kolawole and Omokhodion.[15],[16] Dispersion of the QT and QTc intervals were defined as the difference between the maximum and minimum QT and QTc intervals occurring in any of the 12 leads (QT-d and QTc-d).[17] ST segment elevation or depression of more than 1 mm in the limb leads and more than 2 mm in the precordial leads was considered significant.[18] Simple percentages were used to present data.


  Results Top


A total of 17 patients met the inclusion criteria and were studied, making a response rate of 89.5%. The age range of patients was 2–7 years, and there were 12 males (70.6%) and 5 females (29.4%). Only 3 of 17 patients were on daunorubicin-based regimen; others received doxorubicin-based regimen. Age-dependent corrected QT interval was prolonged in 23.5% of cases when compared with those of healthy Nigerian children. The dispersion of QT and QTc ranged 40–240 and 60–300 respectively as shown in [Table 1].
Table 1: QT (digit above) and heart-rate corrected QT intervals (digit below) with their dispersions

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Elevation of ST segment occurred in V5 of only one patient accounting for 5.9% [Figure 1] whereas, ST segment depression [Figure 2] was variably present in all leads except aVR and aVL in 6 patients. ST segment depression per lead; V1 (11.8%), V2 (5.9%), V3 (23.5%), V4 (5.9%), V5 (17.6%), V6 (5.9%), I (5.9%), II (5.9%), III (5.9%), aVR (0%), aVL (0%), aVF (5.9%).
Figure 1: ST segment elevation in V5

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Figure 2: ST segment depression V1, V3, V4

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  Discussion Top


We found that anthracycline-based chemotherapy in Nigerian childhood cancer patients is associated with changes in electrical activity of the myocardium. Although none of the subjects studied had clinically detected arrhythmia, age-dependent QTc interval prolongation above local normative values occurred in 23.5% of our patients, and this portend a risk for development of malignant ventricular arrhythmias and sudden cardiac death. Horacek et al.,[19] in Czech Republic, however, studied adult cancer patients on anthracycline and reported a lower prevalence of QTc interval prolongation of 11.5% and 15.4% after their first and last cycles of therapy, respectively. Apart from possible age-related differences which may account for this slight dissimilarity, the type of anthracycline agent used by their patients (idarubicin, daunorubicin, or mitoxantrone) which is unlike ours' (basically doxorubicine, with only three of them on daunorubicin) may have affected the QTc slightly differently. More so, theirs was a cohort study, while we did a simple cross-sectional study with a mixed population of patients at various studies of chemotherapy.

The dispersion of QT interval was increased in all (100%) of our study population when compared with the first pediatric QT dispersion normative values published.[10] Our finding is in far excess of the 27% increase in QTc dispersion among Turkish pediatric cancer patients reported by Kocabas et al.[13] possibly reflecting a significant racial ECG affectation by anthracycline. QT dispersion reflects spatial differences in myocardial repolarization time.[11] It is known that grossly abnormal values outside the range of measurement error potentially have practical value by pointing to a grossly abnormal repolarization.[20]

We also found the elevation of ST segment in only one patient accounting for 5.9% and ST segment depression was present in 6 patients (35%). From work done by Hesseling et al.,[21] ST segment depression occurred in the inferolateral leads of 2.2% of cancer patients on anthracycline therapy. This was far less than what we found, possibly because they studied long-term survivors post anthracycline-based chemotherapy, while we studied those who were still on treatment with the possibility of more immediate cardiac affectation. The isolated V5 ST segment elevation may not be of much clinical significance; maybe it is a variation from normal, however, emphasis of ST segment changes in our study was that of ST segment depression. Dazzi et al.[6] in Switzerland demonstrated the typical microscopic findings of myocardial fibrosis and perinuclear vacuolisated myocytes in 5 patients with anthracycline-induced acute onset cardiotoxicity and these changes account for the ST segment changes observed.


  Conclusion Top


Nigerian childhood cancer patients on anthracycline-based regime have significant QTc and ST segment abnormalities reflecting the risk for fatal arrhythmias and evidence of myocardial damage.

Recommendation

Regular electrocardiographic monitoring for cancer patients on anthracycline is recommended.

Area of further studies

Individual differences in QTc affectation by the various anthracycline agents could be studied to assess which is least cardiotoxic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Harake D, Franco VI, Henkel JM, Miller TL, Lipshultz SE. Cardiotoxicity in childhood cancer survivors: Strategies for prevention and management. Future Cardiol 2012;8:647-70.  Back to cited text no. 1
    
2.
Puma N, Ruggiero A, Ridola V. Anthracycline-related cardiotoxicity: Risk factors and therapeutic options in childhood cancers. Signa Vitae 2008;3:30-4.  Back to cited text no. 2
    
3.
Sterba M, Popelová O, Lenco J, Fucíková A, Brcáková E, Mazurová Y, et al. Proteomic insights into chronic anthracycline cardiotoxicity. J Mol Cell Cardiol 2011;50:849-62.  Back to cited text no. 3
    
4.
Sterba M, Popelová O, Vávrová A, Jirkovský E, Kovaríková P, Geršl V, et al. Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection. Antioxid Redox Signal 2013;18:899-929.  Back to cited text no. 4
    
5.
Schimmel KJ, Richel DJ, van den Brink RB, Guchelaar HJ. Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev 2004;30:181-91.  Back to cited text no. 5
    
6.
Dazzi H, Kaufmann K, Follath F. Anthracycline-induced acute cardiotoxicity in adults treated for leukaemia. Analysis of the clinico-pathological aspects of documented acute anthracycline-induced cardiotoxicity in patients treated for acute leukaemia at the University Hospital of Zürich, Switzerland, between 1990 and 1996. Ann Oncol 2001;12:963-6.  Back to cited text no. 6
    
7.
Krischer JP, Epstein S, Cuthbertson DD, Goorin AM, Epstein ML, Lipshultz SE. Clinical cardiotoxicity following anthracycline treatment for childhood cancer: The Pediatric Oncology Group experience. J Clin Oncol 1997;15:1544-52.  Back to cited text no. 7
    
8.
Sule EA. Doxorubicin associated deaths in two hospitals in Niger Delta. Cont J Trop Med 2011;5:1-4.  Back to cited text no. 8
    
9.
Day CP, McComb JM, Campbell RW. QT dispersion: An indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990;63:342-4.  Back to cited text no. 9
    
10.
Tutar HE, Ocal B, Imamoglu A, Atalay S. Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion. Heart 1998;80:77-9.  Back to cited text no. 10
    
11.
Day CP, McComb JM, Campbell RW. QT dispersion in sinus beats and ventricular extrasystoles in normal hearts. Br Heart J 1992;67:39-41.  Back to cited text no. 11
    
12.
Zabel M, Portnoy S, Franz MR. Electrocardiographic indexes of dispersion of ventricular repolarization: An isolated heart validation study. J Am Coll Cardiol 1995;25:746-52.  Back to cited text no. 12
    
13.
Kocabas A, Kardelen F, Ertug H, Aldemir-Kocabas B, Tosun Ö, Yesilipek A, et al. Assessment of early-onset chronic progressive anthracycline cardiotoxicity in children: Different response patterns of right and left ventricles. Pediatr Cardiol 2014;35:82-8.  Back to cited text no. 13
    
14.
Bazett JC. An analysis of time relations of electrocardiograms. Heart 1920;7:353-67.  Back to cited text no. 14
    
15.
Kolawole AJ, Omokhodion SI. Normal limits for pediatric electrocardiogram in Ilorin, Nigeria. Niger J Cardiol 2014;11:112-23.  Back to cited text no. 15
    
16.
Sadoh WE. Electrocardiographic reference values for Nigerian children. Nig J Cardiol 2014;11:65.  Back to cited text no. 16
  [Full text]  
17.
Statters DJ, Malik M, Ward DE, Camm AJ. QT dispersion: Problems of methodology and clinical significance. J Cardiovasc Electrophysiol 1994;5:672-85.  Back to cited text no. 17
    
18.
Park MK. Electrocardiography. In: Park MK, editor. Pediatric Cardiology for Practitioners. 5th ed. Philadelphia: Mosby Elsevier; 2008.  Back to cited text no. 18
    
19.
Horacek JM, Jakl M, Horackova J, Pudil R, Jebavy L, Maly J. Assessment of anthracycline-induced cardiotoxicity with electrocardiography. Exp Oncol 2009;31:115-7.  Back to cited text no. 19
    
20.
Malik M, Batchvarov VN. Measurement, interpretation and clinical potential of QT dispersion. J Am Coll Cardiol 2000;36:1749-66.  Back to cited text no. 20
    
21.
Hesseling PB, Kalis NN, Wessels G. The effect of anthracyclines on myocardial function in 50 long-term survivors of childhood cancer. S Air Med J 1999;89:C25-8.  Back to cited text no. 21
    


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