Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation

Frontiers in Cardiovascular Medicine

article

Pietro Enea Lazzerini¹  Riccardo Accioli¹  Maurizio Acampa²  Wen-Hui Zhang³  Decoroso Verrengia¹  Alessandra Cartocci⁵  Maria Romana Bacarelli¹  Xiaofeng Xin⁶  Viola Salvini¹  Ke-Su Chen⁷  Fabio Salvadori¹  Antonio D’errico¹  Stefania Bisogno¹  Gabriele Cevenini⁵  Tommaso Marzotti¹  Matteo Capecchi¹  Franco Laghi-Pasini¹  Long Chen³  Pier Leopoldo Capecchi¹  Mohamed Boutjdir⁸ 

[1] Department of Medical Sciences, Surgery and Neurosciences, University of Siena;Stroke Unit, University Hospital of Siena;National Standard Laboratory of Pharmacology for Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine;Department of Pharmacy, Maanshan People’s Hospital;Department of Medical Biotechnologies, University of Siena;Department of Respiration, Affiliated Jinling Hospital School of Medicine, Nanjing University;School of Medicine, Nanjing University;VA New York Harbor Healthcare System;SUNY Downstate Health Sciences University;NYU School of Medicine

关键词: QTc interval;    systemic inflammation;    interleukin-6;    guinea pig model;    ventricular electrical remodelling;    action potential duration;    I Kr current;    COVID-19;   

DOI  :  10.3389/fcvm.2022.893681

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Background Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms. Methods We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro . Results In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (I Kr ). Conclusion For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

【 授权许可】

CC BY