QT interval and repolarization dispersion changes during the administration of hydroxychloroquine/chloroquine with/without azithromycin in early COVID 19 pandemic: A prospective observational study from two academic hospitals in Indonesia

Abstract

Background Hydroxychloroquine/chloroquine (HCQ/CQ) treatment for COVID‐19 was associated with QT interval prolongation and arrhythmia risks. This study aimed to investigate QTc interval and ventricular repolarization dispersion changes, as markers of arrhythmia risks, after HCQ/CQ administration with/without azithromycin (AZT) during COVID‐19 pandemic. Methods A prospective observational study was performed in two academic hospitals in Indonesia. Adult patients who received HCQ/CQ alone and HCQ/CQ + AZT concomitant treatments for COVID‐19 infection were enrolled. Baseline and post HCQ/CQ treatment electrocardiograms were obtained. Baseline and post HCQ/CQ treatment QT interval by Bazett (B‐QTc) and Fridericia (F‐QTc) formulas and ventricular repolarization dispersion indices by Tpeak‐Tend (Tp‐e) interval and Tpeak‐Tend/QT (Tp‐e/QT) ratio were calculated and analyzed. Results The study enrolled 55 (HCQ/CQ alone) and 77 subjects (HCQ/CQ + AZT concomitant). F‐QTc interval significantly lengthened in subjects with HCQ/CQ + AZT (mean difference 11.89 ms [P = .028]). The incidences of severe B‐QTc and F‐QTc lengthening were 13.1% and 12.3%, B‐QTc and F‐QTc prolongation were 25.4% and 12.3%, and severe B‐QTc and F‐QTc prolongation were 6.2% and 3.2%. Tp‐e interval lengthened significantly from baseline to posttreatment in HCQ/CQ alone and HCQ/CQ + AZT (mean difference 10.83 ms [P = .006] and 18.73 ms [P < .001], respectively). Tp‐e/QT ratio increased significantly from baseline to posttreatment in HCQ/CQ + AZT concomitant (mean difference 0.035 [P < .001]). No fatal arrhytmia occurred. Conclusions During COVID‐19 pandemic, HCQ/CQ + AZT concomitant treatment caused significant F‐QTc lengthening, significantly increased Tp‐e interval and increased Tp‐e/QT ratio. HCQ/CQ alone only caused significant increase of Tp‐e interval. Incidences of severe QTc lengthening and prolongation were low in both HCQ/CQ alone and HCQ/CQ + AZT concomitant.

Clinical and electrocardiographic characteristics in patients with fulminant myocarditis

“…These results may aid in early diagnosis in the clinical setting. Now, in the COVID‐19 era, 27 , 28 in the future, these findings, combined with BNP levels, will contribute to establishing a clinical scoring system.…”

Early Alterations of QTc in Patients with COVID-19 Treated with Hydroxychloroquine or Chloroquine in Libreville, Gabon

“…The median QTc observed at the CHUL could reflect a greater sensitivity of this population to treatment. Some authors showed that cardiac arrythmias in COVID-19 patients with severe or critical disease or with myocardial impact also involve QTc prolongation, while others found that QTc prolongation is rare during COVID-19 but drugs like HCQ and azithromycin are associated with a significant risk of QTc prolongation in SARS-CoV2 infected persons; this risk increases when azithromycin is associated with HCQ [ 23 , 24 , 25 ]. Additionally, COVID-19 patients were shown to be more susceptible to drug-induced QTc prolongation [ 23 , 24 , 25 ].…”

Uso de cloroquina, azitromicina e ivermectina durante a pandemia da COVID-19: Uma revisão integrativa

“…As concentrações sob o regime de dosagem atualmente recomendado estão abaixo da margem de segurança para efeitos colaterais, o que sugere que esses regimes de dosagem são geralmente seguros (Meo et al, 2020) Relatar as características biológicas, moleculares, farmacológicas e clínicas da cloroquina e hidroxicloroquina para o tratamento da COVID-19 Não foram encontradas evidências claras de benefícios da terapia com cloroquina para a infecção ambulatorial inicial ou para a profilaxia (Das et al, 2020) Avaliar Autores (Axfors et al, 2021;Das et al, 2020;Ferreira et al, 2023;Gumilang et al, 2021;Kashour et al, 2021;Meo et al, 2020;Nicol et al, 2020;Tleyjeh et al, 2021;Yao et al, 2021) Farmacocinética -Dose única: 155 mg de hidroxicloroquina e 300 mg ou 600 mg de cloroquina; Não se investigou: parâmetros de exposição, tempo para atingir a concentração sérica máxima e interação com alimentos na absorção; -Distribuição: concentrada nas hemácias, com ligação média a proteínas plasmáticas de 59% (30 a 50% para a hidroxicloroquina), além de baço, pulmões, rins e fígado; -Metabolização: hepática; -Eliminação: renal de 30 a 60 dias.…”