QT interval and arrhythmic safety of hydroxychloroquine monotherapy in coronavirus disease 2019

• Main Authors: Arun R. Sridhar, MBBS, MPH, Neal A. Chatterjee, MD, MSc, Basil Saour, MD, Dan Nguyen, MD, Elizabeth A. Starnes, ARNP, Christine Johnston, MD, MPH, Margaret L. Green, MD, MPH, Gregory A. Roth, MD, Jeanne E. Poole, MD, FHRS
• Format: Article
• Language: English
• Published: Elsevier 2020-08-01
• Series: Heart Rhythm O2
• Subjects: Coronavirus; Electrocardiogram; Hydroxychloroquine; QT interval; Ventricular arrhythmia
• Online Access: http://www.sciencedirect.com/science/article/pii/S2666501820300751

Background: Observational studies have suggested increased arrhythmic and cardiovascular risk with the combination use of hydroxychloroquine (HCQ) and azithromycin in patients with coronavirus disease 2019 (COVID-19). Objective: The arrhythmic safety profile of HCQ monotherapy, which remains under investigation as a therapeutic and prophylactic agent in COVID-19, is less established and we sought to evaluate this. Methods: In 245 consecutive patients with COVID-19 admitted to the University of Washington hospital system between March 9, 2020, and May 10, 2020, we identified 111 treated with HCQ monotherapy. Patients treated with HCQ underwent a systematic arrhythmia and QT interval surveillance protocol including serial electrocardiograms (ECG) (baseline, following second HCQ dose). The primary endpoint was in-hospital sustained ventricular arrhythmia or arrhythmic cardiac arrest. Secondary endpoints included clinically significant QTc prolongation. Results: A total of 111 patients with COVID-19 underwent treatment with HCQ monotherapy (mean age 62 ± 16 years, 44 women [39%], serum creatinine 0.9 [interquartile range 0.4] mg/dL). There were no instances of sustained ventricular arrythmia or arrhythmic cardiac arrest. In 75 patients with serial ECGs, clinically significant corrected QT (QTc) prolongation was observed in a minority (n = 5 [7%]). In patients with serial ECGs, there was no significant change in the QTc interval in prespecified subgroups of interest, including those with prevalent cardiovascular disease or baseline use of renin-angiotensin-aldosterone axis inhibitors. Conclusions: In the context of a systematic monitoring protocol, HCQ monotherapy in hospitalized COVID-19 patients was not associated with malignant ventricular arrhythmia. A minority of patients demonstrated clinically significant QTc prolongation during HCQ therapy.