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

Objective: 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.

Design: A large-scale cohort study with retrospective analysis of baseline and on-therapy QT interval corrected using Bazett and Fridericia formulas.

Setting: A multicentre study involving eight secondary and tertiary care hospitals of the Abu Dhabi Health Services Company (SEHA), United Arab Emirates.

Participants: 2014 patients consecutively admitted with PCR-confirmed SARS-CoV-2 infection between 1 March 2020 and 1 June 2020.

Interventions: 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.

Main outcome measures: Maximal QTc interval prolongation and its relationship to clinical severity, polymorphic ventricular tachycardia and sudden arrhythmic death while on treatment.

Results: 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).

Conclusions: 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.