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BACKGROUND There is no known effective therapy for patients with coronavirus disease 2019 . Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/ AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).OBJECTIVE The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.METHODS This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. RESULTSThe QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion.Extreme new QTc interval prolongation to .500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.CONCLUSION The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.

Limited data suggest that athletes may have a higher risk of developing atrial fibrillation (AF); however there has been no large prospective assessment of the relationship between vigorous exercise and AF. Logistic regression analyses stratified by time were utilized to assess the association between frequency of vigorous exercise and risk of developing AF among 16,921 apparently healthy men in the Physicians' Health Study. During 12 years of follow-up, 1,661 men reported developing AF. With increasing frequency of vigorous exercise (0, <1, 1−2, 3−4, 5−7 days per week), the multivariate relative risks for the full cohort were 1.0 (referent), 0.90, 1.09, 1.04, 1.20 (p=0.04). This risk was not significantly elevated when exercise habits were updated or in models excluding variables that may be in the biologic pathway through which exercise influences AF risk. In sub-group analyses, this elevated risk was observed only in men below age 50 [1.0, 0.94, 1.20, 1.05, 1.74 (p<0.01)] and joggers [1.0, 0.91, 1.03, 1.30, 1.53 (p<0.01)], where risks remained elevated in all analyses. In conclusion, frequency of vigorous exercise was associated with an increased risk of developing AF among young men and joggers. This risk diminished as the population aged and was offset by known beneficial effects of vigorous exercise on other AF risk factors. KeywordsAtrial fibrillation; exercise; arrhythmia Although vigorous exercise has numerous health benefits, case reports and limited data suggest that male elite athletes engaging in endurance exercise that enhances parasympathetic tone, particularly jogging, may be at higher risk for the development of atrial fibrillation (AF). 1,2, 3 There are limited data on the role of vigorous exercise in the development of AF among men participating in exercise at a less competitive level, where the known beneficial effects of exercise may counter balance this potential risk. We hypothesized that young men in whom parasympathetic tone is most pronounced may be at highest risk of developing AF. To further define the risks and benefits of exercise on AF risk, we prospectively examined the relationship between amount and type of vigorous exercise and subsequent development of AF among men in the Physicians' Health Study. MethodsThe methods of the Physicians' Health Study have been described in detail elsewhere. 4 The study complies with the Declaration of Helsinki, was approved by the Institutional Review Board of Brigham and Women's Hospital and the participants gave informed consent. Briefly, 22,071 male physicians 40 − 84 years old in 1982 with no history of myocardial infarction, stroke, transient ischemic attacks, or cancer were randomized to aspirin and/or beta-carotene using a double-blind, placebo-controlled, two-by-two factorial design. Information on health status, risk factors for cardiovascular disease and AF, along with dietary and lifestyle factors was collected via questionnaires. Participants who failed to complete the 3-year follow-up questionnaire regarding exercise habits (...