Methods
We conducted a retrospective analysis of consecutive symptomatic patients who were hospitalized for COVID-19 infection and received treatment with combination hydroxychloroquine/azithromycin. This study was approved by the Yale University School of Medicine Human Investigation Committee. Baseline 12-lead ECGs were obtained prior to initiation of therapy. Patients underwent continuous telemetry and the corrected QT interval (QTc) was measured by an electrophysiologist at baseline and then daily using Bazett’s formula. Independent variables of interest were those associated with QTc prolongation or disease severity (age, gender, baseline QTc, concurrent use of other high risk QT-prolonging medications, and laboratory markers of inflammation and infection (leukocytes, C-Reactive Protein), disease severity (Troponin T, D-Dimer), renal insufficiency (GFR < 60 ml/min) and hypokalemia (serum potassium). Definition of high-risk QTc medications was based on the classification by the Arizona Center for Education and Research on Therapeutics (AZCERT). The primary outcome was the development of significant QTc prolongation defined as increase in baseline QTc ≥60 ms and/or absolute QTc > 500 ms.6 Secondary outcomes included ventricular tachyarrhythmias (TdP, polymorphic VT or VF).
Demographic, clinical and laboratory characteristics were compared between patients who developed QTc prolongation compared to those who did not. Continuous variables are expressed as mean ± standard deviation (SD). Proportions were compared using the χ2 test. Continuous variables were compared using the t-test for normally distributed data or the Mann-Whitney U test if non-normal. Statistical significance was defined as p<0.05. Unadjusted odds ratios (OR) were calculated separately for each potential predictor of significant QT prolongation using univariable logistic regression. Significant predictors (p<0.05) from univariable analysis were then used as covariates in a multiple logistic regression model to calculate adjusted odds ratios (aOR).