| Autor: |
Pietro Enea Lazzerini, Riccardo Accioli, Maurizio Acampa, Wen-Hui Zhang, Decoroso Verrengia, Alessandra Cartocci, Maria Romana Bacarelli, Xiaofeng Xin, Viola Salvini, Ke-Su Chen, Fabio Salvadori, Antonio D’errico, Stefania Bisogno, Gabriele Cevenini, Tommaso Marzotti, Matteo Capecchi, Franco Laghi-Pasini, Long Chen, Pier Leopoldo Capecchi, Mohamed Boutjdir |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cardiovascular Medicine, Vol 9 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2297-055X |
| DOI: |
10.3389/fcvm.2022.893681 |
| Popis: |
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 (IKr).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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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