期刊
FRONTIERS IN CARDIOVASCULAR MEDICINE
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2022.893681
关键词
QTc interval; systemic inflammation; interleukin-6; guinea pig model; ventricular electrical remodelling; action potential duration; I-Kr current; COVID-19
资金
- Bando Ricerca COVID-19 Toscana -2021
- Progetto PRECARVID
- Biomedical Laboratory Research & Development Service of Veterans Affairs Office of Research Development [W81XWH-21-1-0424]
- U.S. Department of Defense [I01 BX002137]
This study investigates the short-term impact of IL-6 elevation on QTc in patients with severe COVID-19 and explores the underlying mechanisms. The findings demonstrate that IL-6 elevation can promote QTc prolongation through ventricular electric remodeling. These findings highlight the importance of anti-inflammatory treatment in COVID-19.
BackgroundHeart 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. MethodsWe 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. ResultsIn 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). ConclusionFor 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.
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