Changes in QTc interval after hydroxychloroquine therapy in patients with COVID-19 infection: a large, retrospective, multicentre cohort study.

Abstract

To evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths. A large-scale cohort study with retrospective analysis of baseline and on-therapy QT interval corrected using Bazett and Fridericia formulas. A multicentre study involving eight secondary and tertiary care hospitals of the Abu Dhabi Health Services Company (SEHA), United Arab Emirates. 2014 patients consecutively admitted with PCR-confirmed SARS-CoV-2 infection between 1 March 2020 and 1 June 2020. Treatment with hydroxychloroquine alone or in combination with azithromycin for at least 24 hours and with a baseline ECG and at least one ECG after 24 hours of therapy. Maximal QTc interval prolongation and its relationship to clinical severity, polymorphic ventricular tachycardia and sudden arrhythmic death while on treatment. The baseline QTc_(Bazett) was 427.6±25.4 ms and the maximum QTc_(Bazett) during treatment was 439.2±30.4 ms (p<0.001). Severe QTc prolongation (QTc ≥500 ms) was observed in 1.7%-3.3% of patients (Fridericia and Bazett, respectively). There were no cases of polymorphic ventricular arrhythmia or hydroxychloroquine-related arrhythmic death. QTc prolongation was more pronounced in combination therapy compared with hydroxychloroquine alone (22.2 ms vs 11.0 ms, p<0.001) and in patients with higher COVID-19 clinical severity (asymptomatic: 428.4±25.4 ms, severe COVID-19 infection: 452.7±35.7 ms, p<0.001). The overall in-hospital mortality was 3.97% and deceased patients had longer on-therapy QTc_(Bazett) than survivors (459.8±21.4 ms vs 438.4±29.9 ms, p<0.001). The incidence of severe QTc prolongation with hydroxychloroquine was low and not associated with ventricular arrhythmia. The safety concerns surrounding the use of hydroxychloroquine may have been overestimated; however, caution should be exercised when using hydroxychloroquine in patients with risk factors for QT prolongation.