Arrhythmic profile and 24-hour QT interval variability in COVID-19 patients treated with hydroxychloroquine and azithromycin

Background: Hydroxychloroquine and azithromycin combination therapy is often prescribed for coronavirus disease 2019 (COVID-19). Electrocardiographic (ECG) monitoring is warranted because both medications cause corrected QT-interval (QTc) prolongation. Whether QTc duration significantly varies during the day, potentially requiring multiple ECGs, remains to be established. Methods: We performed 12-lead ECGs and 12-lead 24-h Holter ECG monitoring in all patients aged <80 years admitted to our medical unit for COVID-19, in oral therapy with hydroxychloroquine (200 mg, twice daily) and azithromycin (500 mg, once daily) for at least 3 days. A group of healthy individuals matched for age and sex served as control. Results: Out of 126 patients, 22 (median age 64, 82% men) met the inclusion criteria. ECG after therapy showed longer QTc-interval than before therapy (450 vs 426 ms, p=.02). Four patients had a QTc >= 480 ms: they showed higher values of aspartate aminotransferase (52 vs 30 U/L, p=.03) and alanine aminotransferase (108 vs 33 U/L, p < .01) compared with those with QTc < 480 ms. At 24-h Holter ECGmonitoring, 1 COVID-19 patient and no control had >= 1 run of non-sustained ventricular tachycardia (p = .4). No patients showed "R on T" premature ventricular beats. Analysis of 24-h QTc dynamics revealed that COVID-19 patients had higher QTc values than controls, with no significant hourly variability. Conclusion: Therapy with hydroxychloroquine and azithromycin prolongs QTc interval in patients with COVID19, particularly in those with high levels of transaminases. Because QTc duration remains stable during the 24 h, multiple daily ECG are not recommendable. (C) 2020 Elsevier B.V. All rights reserved.