ABSTRACT
Background and Aim: Experimental Hydroxychloroquine (HCQ)/Azithromycin (AZT) combination treatment is a widely accepted experimental treatment for COVID-19 and concerns stated about the potential lethal ventricular arrhythmias (VA). Corrected QT, Tpeak-Tend interval (Tp-e) and QT dispersion have been accepted as novel markers for the assessment of myocardial repolarization and VA. We aimed to evaluate the effects of HCQ±AZT treatment on ECG repolarization parameters among patients treated for COVID-19 and their association with the with poor prognos. Methods: All consecutive adult patients diagnosed with COVID-19 and hospitalized for treatment with HKK± AZT in participating centers were evaluated. Exclusion criteria: structural heart disease, Class I/III antiarrhythmic use, complete-bundle-branch-block, high-grade-AV-block, non-sinus rhythms and acute coronary syndrome in follow-up. Bazett qtc corrected tpte "Poor clinical outcome (PCO)" is defined as a combined definition for any of the following clinical features as in hospital death/>7 days of hospitalization/endotracheal entubation and/or ICU stay. Results: Of 312 cases, 296 patients (153 females, 56±21 years) were included for analysis. 136 patients also received AZT in addition to HCQ (46% of population, male%:female% 48.5:44 p=0.44). Mean follow up time was 8±5 days (Min-Max 1-35 days). In hospital death was observed in 14 patients (4.7%, 78±17 years) and all were due to multi-organ failure in intensive care unit. PCO occurred in 88 patients (29.7%, mean±SD 64±20 years which was significantly older, p<0.001). Female mortality rate=5.2% while male=4.2% non significant trend for females p=0.7. No lethal VA or any dysrhythmic death was observed in the follow up. QT/QTc intervals and QTdisp were significantly prolonged at the end of the treatment protocol with HCQ±AZT (mean±SD ms change from baseline to the end of the protocol in both sexes = QTc 422±30 to 431±32, p<0.001, QT dispersion-C median ± SEM ms 26±1.4 to 27±1.5 p=). 7.4% (17 cases) >50 ms Delta QTc and. TpTe, TpTe-c, QTd, QTdc and TpTe/QT parameters did not significantly prolong throughout the protocol. However, delta QTc was found to be correlated with and delta QTc >50 ms significantly predicts PCO [(OR 3.8 (95% CI 1.2-12) (p=0.02)]. Presence of prolonged long QT features on ECG at the end of the protocol (p=0.04) and QTdc >50 ms (p=0.04) were significantly associated with PCO. Conclusions: HCQ/AZT treatment prolongs QTc interval while seemingly exerting no profound effects on surface ECG repolarization parameters. This might be hypothesized as one of the reasons of observed low dysrhythmic events in our cohort of COVID-19 patients. More homogenous transmural repolarization prolongation without evident dispersion of repolarization on human myocardium obsrerved in our cohort with the HCQ use might be protective against the expected deleterious effects of ordinary QT prolonging drugs.