Temporal change of ventricular repolarization indices and index of cardioelectrophysiological balance (iCEB) during COVID-19 treatment including hydroxychloroquine at a tertiary referral hospital

Year 2022, , 7 - 12, 17.01.2022

Çaşıt Olgun Çelik , Orçun Çıftcı , Gaye Ulubay , Haldun Müderrisoğlu

https://doi.org/10.32322/jhsm.992586

Abstract

Aim: Hydroxychloroquine (HCQ) is widely administered to patients with confirmed or suspected COVID-19. It may increase the risk of cardiac arrhythmias associated with QT and QTc prolongation. This study aimed to assess the change in iCEB, a new marker of drug-induced arrhythmia, and other repolarization parameters in suspected COVID-19 patients treated with short-course HCQ.
Material and Method: This was a retrospective cross-sectional study including 40 patients hospitalized with suspected COVID-19 according to the CT findings and treated with HCQ. Serial assessments of the QT and QTc intervals and the calculation of the index of cardio-electrophysiological balance (iCEB) were performed using standard 12 lead electrocardiogram before hydroxychloroquine treatment, on the second day of HCQ treatment, and after the day of the last administered dose. 
Results: QT, QTcB, QTcF, iCEB, iCEBcB significantly increased on the second day of HCQ treatment compared to baseline (p=0.009, p=0.001, p=0.002, p=0.047, p=0.05, respectively). Similarly, QT, QTcB, QTcF, iCEBcB and iCEBcF were significantly higher on the fifth day compared to baseline (p=0.011, p=0.005, p=0.005, p=0.013, p=0.028, p=0.024 respectively). However, there were no differences between the second and the fifth days of treatment for any of the studied parameters.
Conclusions: QT, QTc, and iCEB significantly increased compared to baseline on the second day, and remained increased on the fifth day of treatment. The differences were attributed to the amount of loading dose and the duration of HCQ treatment. Our study suggests that, along with other ECG markers, iCEB can be used in COVID-19 patients treated with HCQ.

Keywords

COVID-19, QTc, iCEB, repolarization, Hydroxychloroquine

Project Number

KA20/227

References

• Siddiqi HK, Mehra MR. Covid-19 illness in native and immunosuppressed states: A clinical-therapeutic staging proposal. J Heart Lung Transplant 2020; 39: 405-7.
• Postema PG, Wilde AA. The measurement of the QT interval. Curr Cardiol Rev 2014; 10: 287-94.
• Laverty H, Benson C, Cartwright E, et al. How can we improve our understanding of cardiovascular safety liabilities to develop safer medicines? Br J Pharmacol 2011; 163: 675-93.
• Lu HR, Yan GX, Gallacher DJ. A new biomarker– index of cardiac electrophysiological balance (iCEB)–plays an important role in drug-induced cardiac arrhythmias: Beyond QT-prolongation and torsades de pointes (TdPs). J Pharmacol Toxicol Methods 2013; 68: 250-9.
• Robert E, Aya AG, dela Coussaye JE, et al. Dispersion-based reentry: Mechanism of initiation of ventricular tachycardia in isolated rabbit hearts. Am J Physiol 1999; 276: H413-H423.
• Robyns T, Lu HR, Gallacher DJ, et al. Evaluation of index of cardio-electrophysiological balance (iCEB) as a new biomarker for the identification of patients at increased arrhythmic risk. Ann Noninvasive Electrocardiol 2016; 21: 294-304.
• Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323: 1061-9.
• Liu K, Fang YY, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei province. Chin Med J (Engl) 2020; 133: 1025-31.
• 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: 1472-9.
• Chorin E, Wadhwani L, Magnani S, et al. QT interval prolongation and torsades de pointes in patients with COVID-19 treated with hydroxychloroquine/azithromycin. Hearth Rhythm 2020; 17: 1425-33.
• Saleh M, Gabriels J, Chang D, et al. The effect of chloroquine, hydroxychloroquine, and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection. Circ Arrhytm Electrophysiol 2020; 13: e008662.
• Santoro F, Monitillo F, Raimondo P, et al. QTc interval prolongation and life-threatening arrhythmias during hospitalization in patients with COVID-19. Results from a multi-center prospective registry. Clin Infect Dis 2020: ciaa1578.
• Angeli F, Spanevello A, De Ponti R, et al. Electrocardiographic features of patients with COVID-19 pneumonia. Eur J Intern Med 2020; 78: 101-6.
• Chorin E, Dai M, Shulman E, et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin. Nat Med 2020; 26: 808-9.
• Mahévas M, Tran VT, Roumier M, et al. Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data. BMJ 2020; 369: m1844.
• Sarma P, Kaur H, Kumar H, et al. Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: a systematic review and meta-analysis. J Med Virol 2020; 92: 776-85.
• Bignardi PB, Vengrus CS, Aquino BM, Neto AC. Use of hydroxychloroquine and chloroquine in patients with COVID-19: a meta-analysis of randomized clinical trials. Pathog Glob Health 2021; 115: 139-50.
• Abdulrahman A, Alsayed I, Almadhi M, et al. The efficacy and safety of hydroxychloroquine in patients with COVID-19: a multicenter national retrospective cohort. Infect Dis Ther 2021; 10: 439-55.
• Agstam S, Yadav A, Kumar-M P, Gupta A. Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis. Indian Pacing Electrophysiol J 2021; 21: 36-43.
• Mercuro NJ, Yen CF, Shim DJ, et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; 5: 1036-41.
• Drew BJ, Ackerman MJ, Funk M, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation 2010; 121: 1047-60.
• Roden DM, Harrington RA, Poppas A, Russo AM. Consideration for drug interactions on QTc in exploratory COVID-19 (Coronavirus Disease 2019) treatment. Circulation 2020; 141: e906-7.