Effects of hydroxychloroquine and azithromycin use on ECG parameters due to COVID-19 in pediatric patient population
Abstract
Aim: Due to COVID-19 infection, the use of two drugs, hydroxychloroquine and azithromycin, with a high potential for arrhythmia, came to the fore in the pediatric patient group at the beginning of 2020, during the search for treatment. The aim is to reveal the synergistic arrhythmic effects of these two drugs in prolonging the QT interval on the ECG.
Materials and Methods: First of all, patients taking hydroxychloroquine were identified. Demographic data of these patients were recorded. In addition to hydroxychloroquine, azithromycin and other treatments they used were also recorded. Those with ECG data were selected. Transmyocardial repolarization parameters calculated by ECG were calculated retrospectively (QT, QTc, Tpe, Tpe/QT, Tpe/QTc). Then, laboratory findings and radiological imaging of these patients were recorded.
Results: Twenty-three pediatric patients who met the study criteria were identified. All of the patients were asymptomatic or mild disease. When initial and post-drug ECG parameters were compared; It was observed that the drugs did not have a significant arrhythmogenic effect on ECG parameters, especially QT interval and QTc.
Conclusion: Unlike the literature showing arrhythmic effects of these drugs in adult COVID-19 disease, hydroxychloroquine and azithromycin did not show such an effect in the pediatric population.
Keywords
Ethical Statement
Ethics committee approval was obtained with the decision of the Ethics Committee for Non-Interventional Procedures of Adıyaman University, dated and numbered 2020: 8/11. The study was conducted under the principles of the Declaration of Helsinki.
Supporting Institution
No person/organization is supporting this study financially.
Project Number
yok
References
- Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17(9):543-558. doi:10.1038/s41569-020-0413-9.
- Roden DM. Predicting drug-induced QT prolongation and torsades de pointes. J Physiol. 2016;9(November 2014):2459-2468. doi:10.1113/JP270526.
- Asensio E, Acunzo R, Uribe W, Saad EB, Sáenz LC. Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence. J Interv Card Electrophysiol. 2020;59(2):315-320. doi:10.1007/s10840-020-00765-3.
- Hormigo I, Silva TM, Laranjo S, et al. Protocol-based cardiotoxicity monitoring in hydroxychloroquine medicated COVID-19 pediatric patients. Revista Portuguesa de Cardiologia, 2020;41(2):155-163.
- Aksoy H, Wollina U. Angiotensin II receptors : Impact for COVID-19 severity. Dermatologic theraphy. 2020;9(July):1-6. doi:10.1111/dth.13989.
- Avcu G, Arslan A, Bal ZS, et al. Electrocardiographic changes in hospitalised children with COVID-19. Cardiol Young. 2023, 33(4), 525- 531. doi:10.1017/S1047951123000100.
- T.C. Sağlık Bakanlığı COVID-19 (SARS-CoV-2 Enfeksiyonu) Çocuk Hasta Yönetimi ve Tedavi Rehberi. Available from: https://covid19.saglik.gov.tr/Eklenti/38596/0/covid19rehbericocukhastayönetimi ve tedavi pdf.. (Accessed date: 30.05. 2021).
- Soysal A, Gönüllü E, Arslan H, et al. Comparison of clinical and laboratory features and treatment options of 237 symptomatic and asymptomatic children infected with SARS-CoV-2 in the early phase of the COVID-19 pandemic in Turkey. Japanese Journal of Infectious Diseases. 2021; 74(4): 273-279.
- Ece İ, Koçoğlu M, Kavurt AV, et al. Assessment of Cardiac Arrhythmic Risk in Children With Covid-19 Infection. Pediatr Cardiol. 2020;42(2):264-268. doi:10.1007/s00246-020-02474-0.
- Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai MC. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020;17(9):1472-1479. doi:10.1016/j.hrthm.2020.05.008.
- Chorin E, Dai M, Shulman E, et al. The QT interval in patients with SARS- CoV-2 infection treated with hydroxychloroquine/azithromycin. Nature medicine. 2020;16(6):808-809. doi: 10.1101/2020.04.02.20047050.
- Haeusler IL, Chan XHS, Guérin PJ, White NJ. The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review. BMC Med 2018;16:200).
- Wu CI, Postema PG, Arbelo E, et al. SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes. Heart Rhythm. 2020;17(9):1456-1462. doi:10.1016/j.hrthm.2020.03.024.
- Pastick KA, Okafor EC, Wang F, et al. Hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis. 2020;7(4):1-9. doi:10.1093/ofid/ofaa130.
- Mzayek F, Deng H, Mather FJ, et al. Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers. PLoS Clin Trials 2007; 2:e6.
- Lane, JCE, Weaver J, Kostka K, et al. "Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study." MedRxiv (2020).
- Arfaras-Melainis A, Tzoumas A, Kokkinidis DG, et al. Effect of hydroxychloroquine on qtc in patients diagnosed with covid-19: A systematic review and meta-analysis. J Cardiovasc Dev Dis. 2021;8(5):1-15. doi:10.3390/jcdd8050055
- Samuel S, Friedman RA, Sharma C, et al. Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR-positive SARS-CoV-2 infection, including drug-induced changes in the corrected QT interval. Heart Rhythm. 2020;17(11):1960-1966. doi:10.1016/j.hrthm.2020.06.033
- Tuncer T, Karaci M, Boga A, Durmaz H, Guven S. QT Interval Evaluation Associated with Use of Hydroxychloroquine with Combined Use of Azithromycin among Hospitalized Children Positive for COVID-19. Cardiol Young. 2019;30(10):1482-1485. doi:10.1017/S1047951120002425
- Parthasarathy P, Shaikh H, Ryan PMD, Mondal T. Does treatment with hydroxychloroquine or chloroquine lead to QTc prolongation in children? Prog Pediatr Cardiol. 2021;13:1-7. doi:10.1016/j.ppedcard.2021.101465
Pediatrik hasta popülasyonunda COVİD-19 sebebiyle hidroksiklorokin ve azitromisin kullanımın EKG parametreleri üzerine etkileri
Abstract
Amaç: COVID-19 enfeksiyonu nedeniyle, 2020 yılının başında tedavi arayışı sırasında aritmi potansiyeli yüksek hidroksiklorokin ve azitromisin isimli iki ilacın kullanımı pediatrik hasta grubunda gündeme geldi. Amaç bu iki ilacın EKG üzerinde QT intervalini uzatmadaki sinerjistik aritmik etkilerini ortaya koymaktır.
Gereç ve yöntem: Öncelikle hidroksiklorokin alan hastalar tespit edildi. Bu hastaların demografik verileri kaydedildi. Hidroksiklorokine ilaveten kullandıkları azitromisin ve diğer tedavileri de kayıt altına alındı. EKG verileri olanlar seçildi. EKG ile hesaplanan transmiyokardiyal repolarizasyon parametreleri retrospektif olarak (QT, QTc, Tpe Tpe/QT, Tpe/QTc) hesaplandı. Ardından bu hastaların laboratuvar bulguları ve radyolojik görüntülemeleri kaydedildi.
Bulgular: Çalışma kriterlerine uygun 23 pediatrik hasta tespit edildi. Hastaların tamamı asemptomatik ya da hafif hastalık tablosundaydı. Başlangıç ve ilaç sonrası EKG parametreleri karşılaştırıldığında; başta QT intervali ve QTc olmak üzere EKG parametreleri üzerine ilaçların belirgin bir aritmojenik etkisi olmadığı görüldü.
Sonuç: Erişkin COVİD-19 hastalığında bu ilaçların aritmik etkilerini gösteren literatüründen farklı olarak, hidroksiklorokin ve azitromisin böyle bir etkiyi pediatrik popülasyonda göstermediler.
Ethical Statement
Ethics committee approval was obtained with the decision of the Ethics Committee for Non-Interventional Procedures of Adıyaman University, dated and numbered 2020: 8/11. The study was conducted under the principles of the Declaration of Helsinki.
Supporting Institution
No person/organization is supporting this study financially.
Project Number
yok
References
- Nishiga M, Wang DW, Han Y, Lewis DB, Wu JC. COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives. Nat Rev Cardiol. 2020;17(9):543-558. doi:10.1038/s41569-020-0413-9.
- Roden DM. Predicting drug-induced QT prolongation and torsades de pointes. J Physiol. 2016;9(November 2014):2459-2468. doi:10.1113/JP270526.
- Asensio E, Acunzo R, Uribe W, Saad EB, Sáenz LC. Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence. J Interv Card Electrophysiol. 2020;59(2):315-320. doi:10.1007/s10840-020-00765-3.
- Hormigo I, Silva TM, Laranjo S, et al. Protocol-based cardiotoxicity monitoring in hydroxychloroquine medicated COVID-19 pediatric patients. Revista Portuguesa de Cardiologia, 2020;41(2):155-163.
- Aksoy H, Wollina U. Angiotensin II receptors : Impact for COVID-19 severity. Dermatologic theraphy. 2020;9(July):1-6. doi:10.1111/dth.13989.
- Avcu G, Arslan A, Bal ZS, et al. Electrocardiographic changes in hospitalised children with COVID-19. Cardiol Young. 2023, 33(4), 525- 531. doi:10.1017/S1047951123000100.
- T.C. Sağlık Bakanlığı COVID-19 (SARS-CoV-2 Enfeksiyonu) Çocuk Hasta Yönetimi ve Tedavi Rehberi. Available from: https://covid19.saglik.gov.tr/Eklenti/38596/0/covid19rehbericocukhastayönetimi ve tedavi pdf.. (Accessed date: 30.05. 2021).
- Soysal A, Gönüllü E, Arslan H, et al. Comparison of clinical and laboratory features and treatment options of 237 symptomatic and asymptomatic children infected with SARS-CoV-2 in the early phase of the COVID-19 pandemic in Turkey. Japanese Journal of Infectious Diseases. 2021; 74(4): 273-279.
- Ece İ, Koçoğlu M, Kavurt AV, et al. Assessment of Cardiac Arrhythmic Risk in Children With Covid-19 Infection. Pediatr Cardiol. 2020;42(2):264-268. doi:10.1007/s00246-020-02474-0.
- Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai MC. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020;17(9):1472-1479. doi:10.1016/j.hrthm.2020.05.008.
- Chorin E, Dai M, Shulman E, et al. The QT interval in patients with SARS- CoV-2 infection treated with hydroxychloroquine/azithromycin. Nature medicine. 2020;16(6):808-809. doi: 10.1101/2020.04.02.20047050.
- Haeusler IL, Chan XHS, Guérin PJ, White NJ. The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: a systematic review. BMC Med 2018;16:200).
- Wu CI, Postema PG, Arbelo E, et al. SARS-CoV-2, COVID-19, and inherited arrhythmia syndromes. Heart Rhythm. 2020;17(9):1456-1462. doi:10.1016/j.hrthm.2020.03.024.
- Pastick KA, Okafor EC, Wang F, et al. Hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis. 2020;7(4):1-9. doi:10.1093/ofid/ofaa130.
- Mzayek F, Deng H, Mather FJ, et al. Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers. PLoS Clin Trials 2007; 2:e6.
- Lane, JCE, Weaver J, Kostka K, et al. "Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study." MedRxiv (2020).
- Arfaras-Melainis A, Tzoumas A, Kokkinidis DG, et al. Effect of hydroxychloroquine on qtc in patients diagnosed with covid-19: A systematic review and meta-analysis. J Cardiovasc Dev Dis. 2021;8(5):1-15. doi:10.3390/jcdd8050055
- Samuel S, Friedman RA, Sharma C, et al. Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR-positive SARS-CoV-2 infection, including drug-induced changes in the corrected QT interval. Heart Rhythm. 2020;17(11):1960-1966. doi:10.1016/j.hrthm.2020.06.033
- Tuncer T, Karaci M, Boga A, Durmaz H, Guven S. QT Interval Evaluation Associated with Use of Hydroxychloroquine with Combined Use of Azithromycin among Hospitalized Children Positive for COVID-19. Cardiol Young. 2019;30(10):1482-1485. doi:10.1017/S1047951120002425
- Parthasarathy P, Shaikh H, Ryan PMD, Mondal T. Does treatment with hydroxychloroquine or chloroquine lead to QTc prolongation in children? Prog Pediatr Cardiol. 2021;13:1-7. doi:10.1016/j.ppedcard.2021.101465
Details
| Primary Language | English |
|---|---|
| Subjects | Pediatric Infectious Diseases, Pediatric Cardiology |
| Journal Section | Research Article |
| Authors | |
| Project Number | yok |
| Publication Date | December 31, 2023 |
| Submission Date | June 12, 2023 |
| Acceptance Date | October 17, 2023 |
| Published in Issue | Year 2023 Volume: 9 Issue: 3 |
