ABC | Volume 114, Nº6, June 2020

Viewpoint QT Interval Control to Prevent Torsades de Pointes during Use of Hydroxychloroquine and/or Azithromycin in Patients with COVID-19 Tan Chen Wu, 1 L uciana Sacilotto, 1 Francisco Carlos da Costa Darrieux, 1 Cristiano Faria Pisani, 1 Sissy Lara de Melo, 1 Denise Tessariol Hachul, 1 Mauricio Scanavacca 1 Universidade de São Paulo Faculdade de Medicina Hospital das Clínicas Instituto do Coração – Arritmia, 1 São Paulo, SP - Brazil Keywords Coronavirus/complications; COVID-19, Pandemics; Torsades Pointes; Tachycardia,Ventricular; Hydroxychloroquine/ therapeutic, use; Arrhythmias Mailing Address: Tan Chen Wu • Universidade de São Paulo Faculdade de Medicina Hospital das Clínicas Instituto do Coração – Arritmia - Av. Dr. Eneas de Carvalho Aguiar, 44. Postal Code 05403-000, São Paulo, SP – Brazil E-mail: tan_chen@bol.com.br, tanchen.cardio@gmail.com Manuscript received April 27, 2020, revised mansucript April 29, 2020, accepted April 29, 2020 DOI: https://doi.org/10.36660/abc.20200389 assessment before treatment and monitoring of the QTc interval during treatment are essential measures to preventing arrhythmic events. Giudicessi et al. 13 published an institutional guideline from the Mayo Clinic for safety of patients receiving HCQ and/or AZ. 13 The American College of Cardiology suggested controlling the QT interval and preventing ventricular arrhythmias in patients participating in the HQC/AZ protocol for treating COVID-19. 14 The Arrhythmia Center of the Heart Institute of the University of São Paulo formulated an institutional protocol in order to contribute to the conscious use of these medications during the COVID-19 outbreak. Definition The QT interval is the measurement of the duration from the beginning of the QRS complex to the end of the T wave, which is modulated by heart rate (Figure 1). When the interval is prolonged, it is associated with a greater risk of polymorphic ventricular arrhythmias and TdP (Figure 2). 15 Measurement of the QT interval should be corrected by heart rate (QTc); in the adult population, ≤ 440 ms is considered normal in men, and ≤ 460 ms is considered normal in women. 16 How to Measure the QTc Interval The QT interval can be measured either by the tangent method (Figure 3) or visually (when the end of the T wave is easy to define), preferably in leads DII or V5. 17 Heart rate correction can be done using Bazett’s formula, considering the RR interval preceding the measured QT interval (QTc = QT interval / square root of the RR interval). This formula is available on website calculators (QTc calculator) or in applications (for example, EP Mobile or MedCalX). Monitoring the QTc interval during treatment with HCQ/ AZ After evaluation of initial ECG, patients may be stratified by risk of developing TdP in the following manner: lower risk (green group), intermediate risk (blue group), intermediate to high risk (orange group), and high risk (red group). Monitoring after the start of treatment can be done by conventional 12-lead ECG, ECG with limb leads only, telemetry, or other remote devices in order to minimize the exposure of health professionals and equipment to the virus during this particular pandemic situation. We recommend that the frequency of electrocardiographic monitoring and Introduction In December 2019, the first cases of the novel coronavirus disease (COVID-19) were reported in Wuhan, China. 1 Since the pandemic designation in March 2020 by the World Health Organization (WHO), with intercontinental spread of the disease, we are intensely seeking for a safe and effective treatment. 2 In vitro studies have demonstrated some effect of chloroquine against the new coronavirus, 3 mediated by the glycosylation of SARS-CoV cell receptors and by increased endosomal pH, blocking cell invasion by the virus. 4 In addition to this antiviral activity, chloroquine, which is traditionally an immunomodulator, has shown to be promising for treatment of pneumonia that installs approximately one week after onset of symptoms. 5 Hydroxychloroquine (HCQ), which is derived from chloroquine, has similar therapeutic effects, with fewer adverse effects, and it is widely used in autoimmune diseases. The first clinical trials with HCQ for treatment of COVID-19 reinforced an apparent benefit and encouraged its approval for clinical studies by national and international regulatory institutions. 6-8 The macrolide azithromycin (AZ), due to a mechanism that is still unclear, has shown to be effective when initiated early in patients with severe respiratory infections. 9 Although these medications have an adequate safety profile in diverse clinical situations, both of them block the hERG potassium channel, which can prolong ventricular repolarization and cause torsades de pointes (TdP). 10,11 The subgroup of the population with the highest risk of potentially fatal events are patients with multiple comorbidities or patients in intensive care, who will be exposed to drug interactions and/or electrolyte disorders, in addition to patients with congenital long QT syndrome, who may need treatment (1:2000 individuals). 12 Risk 1061