Treatment with hydroxychloroquine and azithromycin (HCQ/AZM) among patients hospitalized with COVID-19 was associated with increased corrected QT (QTc) interval while receiving the therapy, according to a study published Aug. 5 in JACC: Clinical Electrophysiology.

Thomas F. O'Connell, MD, et al., sought to assess the magnitude of QT prolongation and prevalence of serious arrhythmias in COVID-19 patients taking HCQ/AZM and determine whether there was an association between QT prolongation and adverse outcomes. The researchers looked at 415 hospitalized COVID-19 patients receiving HCQ/ACM. Baseline QTc intervals were calculated before therapy began and for the first five days of treatment. The study's primary endpoint was the magnitude of QTc prolongation and its associated factors. Secondary endpoints included incidents of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality.

The results show baseline QTc interval of 443 ± 25 msec (range, 365-539 msec). QTc progressively increased during HCQ/AZM therapy, with a maximum interval of 473 ± 40 msec (range, 372-693 msec). Compared with baseline, the magnitude of QTc prolongation was 30 ± 39 msec (range, 69-249 msec). After receiving HCQ/AZM, 87 patients (21%) had QTc intervals ≥500 msec. Factors associated with QTc prolongation included age of 65 years or older, history of heart failure (HF), body mass index ≥30 kg/m2, peak troponin levels >0.04 mg/ml, creatinine ≥1.5 mg/dL at admission, and concomitant use of medications with known risk of torsade de pointes. QTc changes over the duration of HCQ/AZM were assessed in 137 patients. In this subgroup, the average time to maximum QTc was 2.9 ± 1.4 days, and QTc progressively increased.

In terms of secondary outcomes, there were no primary high-grade ventricular arrhythmias during the study period. Of the 415 patients, 85 (21%) died during hospitalization, 32 of whom had pulseless electrical activity or bradycardia when resuscitation was initiated. The QTc interval changes were higher among patients who died during hospitalization vs. those who survived to discharge or termination of the study. Despite the association between QTc prolongation and mortality, age was the only independent predictor of mortality.

According to the researchers, the study demonstrates a significant and progressive increase in QTc in hospitalized COVID-19 patients treated with HCQ/AZM. Given this finding, the authors note that additional research on the prevalence of arrhythmias and mortality is needed if HCQ/AZM continues to be used as a treatment for COVID-19. "While the world waits for the results of larger trials, proposed systems to safely monitor the QTc will remain necessary and cannot be ruled out as an explanation for the results of this study," they write.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Novel Agents, Statins

Keywords: Torsades de Pointes, Ventricular Fibrillation, Azithromycin, Creatinine, Hydroxychloroquine, Bradycardia, Patient Discharge, Troponin, Prevalence, Body Mass Index, COVID-19, severe acute respiratory syndrome coronavirus 2, Arrhythmias, Cardiac, Long QT Syndrome, Hospitalization

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