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).