Subject(s)
COVID-19 Drug Treatment , COVID-19/physiopathology , Hydroxychloroquine/adverse effects , Torsades de Pointes/chemically induced , Torsades de Pointes/physiopathology , Aged , Antimalarials/adverse effects , COVID-19/diagnosis , Electrocardiography/drug effects , Electrocardiography/methods , Humans , Hydroxychloroquine/blood , Male , Torsades de Pointes/diagnosisABSTRACT
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic. Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy. The incidence of torsade de pointes remains unknown. Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment. METHODS: Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study. A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest. RESULTS: The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin. Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5. There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced. CONCLUSIONS: The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy.
Subject(s)
Antiviral Agents/adverse effects , Azithromycin/adverse effects , COVID-19 Drug Treatment , Delivery of Health Care , Heart Conduction System/drug effects , Hydroxychloroquine/adverse effects , Torsades de Pointes/chemically induced , Action Potentials/drug effects , Adolescent , Adult , Aged , Antiviral Agents/administration & dosage , Azithromycin/administration & dosage , COVID-19/diagnosis , Cardiotoxicity , Female , Heart Conduction System/physiopathology , Heart Rate/drug effects , Hospitalization , Humans , Hydroxychloroquine/administration & dosage , Male , Middle Aged , New York , Patient Safety , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Torsades de Pointes/diagnosis , Torsades de Pointes/physiopathology , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K+ channel expression. METHODS: We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K+ channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time. RESULTS: In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K+ channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. CONCLUSIONS: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs. Graphic Abstract: A graphic abstract is available for this article.