Effects of Short-Term Hydroxychloroquine Plus Moxifloxacin Therapy on Corrected QT Interval and Tp-e Interval in Patients With COVID-19

Abstract

Background Limited data are available regarding hydroxychloroquine (HCQ) and moxifloxacin (MOX) in patients with possible coronavirus disease 2019, (COVID-19). Both drugs may increase risk of malignant ventricular arrhythmias associated with prolongation of QT interval. Methods A total of 76 subjects with chest tomography findings compatible with COVID-19 pneumonia were enrolled in the study. Standard 12-lead electrocardiogram (ECG) was repeated on days 2 and 5 in patients receiving a combination of HCQ + MOX. Heart rate, QT interval, Tp-e interval, and Tp-e/QT ratio were measured. Results The mean age of the patients was 61.7 ± 14.8 years and 54% had hypertension. Compared to day 2, ECG on day 5 showed significant increases in QT interval (370.8 ± 32.5 vs. 381.0 ± 29.3, respectively, P = 0.001), corrected QT (QTc) interval (424 (403 - 436) vs. 442 (420 - 468), respectively, P < 0.001), Tp-e interval (60 (55 - 70) vs. 65 (57 - 75), respectively, P < 0.001), cTp-e interval (72.2 ± 12.9 vs. 75.4 ± 12.7, respectively, P < 0.001). Moreover, a slight decrease in Tp-e/QT ratio was observed (0.17 ± 0.03 vs. 0.17 ± 0.02, P = 0.030). QTc was > 500 ms in 5% of the patients, and 8% of patients had an increase in QTc interval > 60 ms. Tp-e/QT ratio was > 0.23 in 4% of patients. Five patients died due to pulmonary failure without evidence of ventricular arrhythmia. No ventricular arrhythmia events, including torsades de pointes (TdP), were observed. Conclusions HCQ + MOX combination therapy led to increases in QTc interval, Tp-e interval, and cTp-e interval. However, this therapy did not cause ventricular arrhythmia in the short-term observation.

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

“…Similarly, proarrhythmia has recently been reported in COVID-19 patients treated with Hydroxychloroquine plus Azithromycin therapy ( Anupama et al , 2020 ; Chorin et al , 2020 ; Mercuro et al , 2020 ). Likewise, polytherapy of Hydroxychloroquine and Moxifloxacin has been reported in patients with COVID-19 ( Afsin et al , 2020 ). Conversely, polytherapy of Azithromycin and Chloroquine has been shown not to be associated with arrhythmia liability in the anesthetized guinea pig model ( Fossa et al , 2007 ).…”

“…Consequently, Hydroxychloroquine has been promoted as a potential treatment of COVID-19. However, 4–61% of COVID-19 patients treated with Hydroxychloroquine and Chloroquine developed cardiotoxicity, primarily QT prolongation and Torsades de Pointes ( Afsin et al , 2020 ; Bernardini et al , 2020 ; Borba et al , 2020 ; Chorin et al , 2020 ; Hooks et al , 2020 ; Jankelson et al , 2020 ; Lalabekyan et al , 2020 ; Mercuro et al , 2020 ; Saleh et al , 2020 ; Szekely et al , 2020 ).…”

QT interval and repolarization dispersion changes during the administration of hydroxychloroquine/chloroquine with/without azithromycin in early COVID 19 pandemic: A prospective observational study from two academic hospitals in Indonesia

“…There is scarce evidence related to the effects of HCQ/CQ in Tp‐e interval changes in COVID‐19 patients. The underlying mechanism on how HCQ/CQ causes Tp‐e interval and Tp‐e/QT ratio increased, as observed in our study, has not been clearly elucidated 39 . There are several hypothesizes underly why we choose Tp‐e and Tp‐e/QT ratio in this study, as stated by Prenneret al (2016), the full repolarization of the M‐cell in the mid myocardial represents in the end of T wave; therefore, Tp‐e interval marks that the surface electrocardiogram corresponds to the dispersion of repolarization across the ventricular wall 26 .…”

“…The underlying mechanism on how HCQ/CQ causes Tp‐e interval and Tp‐e/QT ratio increased, as observed in our study, has not been clearly elucidated. 39 There are several hypothesizes underly why we choose Tp‐e and Tp‐e/QT ratio in this study, as stated by Prenneret al (2016), the full repolarization of the M‐cell in the mid myocardial represents in the end of T wave; therefore, Tp‐e interval marks that the surface electrocardiogram corresponds to the dispersion of repolarization across the ventricular wall. 26 The M‐cell itself has different electrophysiology properties compare with cells in the epicardium and endocardium, yet also has different response related to proarrhythmic drugs.…”

An Examination of COVID-19 Medications’ Effectiveness in Managing and Treating COVID-19 Patients: A Comparative Review

“…However, anti-bacterial drugs such as Fluoroquinolones, Levofloxacin, and Moxifloxacin have commonly been used on COVID-19 patients. Their use has been based on the understanding that with the viral infection under COVID-19, the patients’ immune is suppressed [ 46 , 47 ]. This exposes them to the risk of co-infection by bacterial infections.…”