Effects of Hydroxychloroquine Treatment on QT Interval

Hooks, Matthew; Bart, Bradley; Vardeny, Orly; Westanmo, Anders; Adabag, Selçuk

BACKGROUND: Hydroxychloroquine (HCQ) has been promoted as a potential treatment for COVID-19 but there are safety concerns. OBJECTIVES: To determine the effect of HCQ treatment on QT interval METHODS: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. RESULTS: The patients were 64.0 (±10.9) years in age and 734 (90%) were men. The median dosage and duration of HCQ were 400mg daily and 1006 (471-2075) days, respectively. The mean on-treatment QTc was 430.9 (±31.8) msec. In total, 55 (7%) patients had QTc 470-500 msec and 12 (1.5%) had QTc >500msec. Chronic kidney disease (CKD), history of atrial fibrillation (AF) and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pre-treatment ECG, the mean QTc increased from 424.4 (±29.7) msec. to 432.0 (±32.3) msec (p<0.0001) during HCQ treatment. Of these, 23 (3.9%) patients had either prolongation of QTc >15% or an on-treatment QTc >500 msec. Over 5.97 (3.33-10.11) years of follow-up, 269 (33%) patients died. QTc >470 msec during HCQ treatment was associated with a greater mortality risk of (hazard ratio 1.78, 95% confidence interval 1.16-2.71; p=0.008) in univariable but not in multivariable analysis. CONCLUSION: Hydroxychloroquine is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF and heart failure, who may benefit from greater scrutiny.