Predictive factors for cardiac conduction abnormalities with hydroxychloroquine-containing combinations for COVID-19

• Published in: International journal of antimicrobial agents Vol. 56; no. 4; p. 106142
• Main Authors: Padilla, Sergio, Telenti, Guillermo, Guillén, Lucía, García, José A., García-Abellán, Javier, Ding, Carolina, Mora, Antonia, García-Pachón, Eduardo, Gutiérrez, Félix, Masiá, Mar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2020; Elsevier Ltd and International Society of Antimicrobial Chemotherapy
• Subjects: adults; age; Aged; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; arrhythmia; Azithromycin; Azithromycin - administration & dosage; Azithromycin - adverse effects; Betacoronavirus - drug effects; Betacoronavirus - immunology; Betacoronavirus - pathogenicity; Biomarkers - blood; blood serum; cohort studies; Coronavirus infections; Coronavirus Infections - diagnosis; Coronavirus Infections - drug therapy; Coronavirus Infections - physiopathology; Coronavirus Infections - virology; COVID-19; death; Disease Progression; Drug Combinations; Female; Humans; Hydroxychloroquine; Hydroxychloroquine - administration & dosage; Hydroxychloroquine - adverse effects; Infectious Disease; inflammation; Intensive Care Units; Long QT Syndrome - chemically induced; Long QT Syndrome - diagnosis; Long QT Syndrome - physiopathology; Lopinavir - administration & dosage; Lopinavir - adverse effects; Lopinavir/ritonavir; Lymphocytes - pathology; Lymphocytes - virology; Male; males; men; Middle Aged; monitoring; Neutrophils - pathology; Neutrophils - virology; Pandemics; patients; Pneumonia, Viral - diagnosis; Pneumonia, Viral - drug therapy; Pneumonia, Viral - physiopathology; Pneumonia, Viral - virology; prediction; Prognosis; Proportional Hazards Models; QT interval; regression analysis; Retrospective Studies; risk; Ritonavir - administration & dosage; Ritonavir - adverse effects; SARS-CoV-2; therapeutics; Treatment Outcome; Troponin; troponin I; Troponin I - blood; women; COVID-19; QT interval; Troponin; Hydroxychloroquine; Lopinavir/ritonavir; Azithromycin
• ISSN: 0924-8579; 1872-7913; 1872-7913
• DOI: 10.1016/j.ijantimicag.2020.106142

•Hydroxychloroquine (HCQ) has been widely used to treat COVID-19 worldwide even without good evidence of efficacy.•We analyzed the changes occurring in the QTc interval and their predictors in patients treated with HCQ-containing regimens for COVID-19.•Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher neutrophil-to-lymphocyte ratio, were major contributors to moderate-to-severe QTc prolongation requiring careful QTc interval monitoring.•In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed. This longitudinal, prospective cohort study aimed to assess risk of QTc interval prolongation and its predicting factors in subjects treated with combinations containing hydroxychloroquine (HCQ) for COVID-19. Moderate-to-severe QTc prolongation during therapy was defined as a QTc interval >470 ms in men or >480 ms in women. Patients were treated under strict cardiac supervision. A total of 105 adults were included [56% male; median (IQR) age 69 (57–79) years]. All patients received therapy with HCQ in combination with azithromycin (AZM), and 95 (90%) also with lopinavir/ritonavir (LPV/r). Concomitant medications classified as having risk of developing torsades de pointes (TdP) were simultaneously used in 81 patients (77%). Moderate-to-severe QTc prolongation was observed in 14 patients (13%), mostly at Days 3–5 from baseline, with 6 (6%) developing severe prolongation (>500 ms). There was no evidence of TdP arrhythmia or TdP-associated death. Adding LPV/r to HCQ+AZM did not significantly prolong the QTc interval. Multivariable Cox regression revealed that comedications with known risk of TdP (HR = 11.28, 95% CI 1.08–117.41), higher neutrophil-to-lymphocyte (NLR) ratio (HR = 1.10, 95% CI 1.03–1.18 per unit increase) and higher serum hs-cardiac troponin I (HR = 4.09, 95% CI 1.36–12.2 per unit increase) were major contributors to moderate-to-severe QTc prolongation. In this closely screened and monitored cohort, no complications derived from QTc prolongation were observed during pharmacological therapy containing HCQ for COVID-19. Evidence of myocardial injury with elevated troponin and strong inflammatory response, specifically higher NLR, are conditions requiring careful QTc interval monitoring.