Abstract

<h3>Objective</h3> 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. <h3>Design</h3> A large-scale cohort study with retrospective analysis of baseline and on-therapy QT interval corrected using Bazett and Fridericia formulas. <h3>Setting</h3> A multicentre study involving eight secondary and tertiary care hospitals of the Abu Dhabi Health Services Company (SEHA), United Arab Emirates. <h3>Participants</h3> 2014 patients consecutively admitted with PCR-confirmed SARS-CoV-2 infection between 1 March 2020 and 1 June 2020. <h3>Interventions</h3> 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. <h3>Main outcome measures</h3> Maximal QTc interval prolongation and its relationship to clinical severity, polymorphic ventricular tachycardia and sudden arrhythmic death while on treatment. <h3>Results</h3> The baseline QTc<sub>(Bazett)</sub> was 427.6±25.4 ms and the maximum QTc<sub>(Bazett)</sub> during treatment was 439.2±30.4 ms (p&lt;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&lt;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&lt;0.001). The overall in-hospital mortality was 3.97% and deceased patients had longer on-therapy QTc<sub>(Bazett)</sub> than survivors (459.8±21.4 ms vs 438.4±29.9 ms, p&lt;0.001). <h3>Conclusions</h3> 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.

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