Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.
Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.
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DOI：
10.3389/fcvm.2022.893681
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发表时间：
2022
影响因子：
3.6
通讯作者：
Boutjdir, Mohamed
中科院分区：
文献类型：
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作者：
Lazzerini, Pietro Enea;Accioli, Riccardo;Acampa, Maurizio;Zhang, Wen-Hui;Verrengia, Decoroso;Cartocci, Alessandra;Bacarelli, Maria Romana;Xin, Xiaofeng;Salvini, Viola;Chen, Ke-Su;Salvadori, Fabio;D'errico, Antonio;Bisogno, Stefania;Cevenini, Gabriele;Marzotti, Tommaso;Capecchi, Matteo;Laghi-Pasini, Franco;Chen, Long;Capecchi, Pier Leopoldo;Boutjdir, Mohamed
关键词：
心率校正QT间期（QTc）延长在2019年严重冠状病毒病（COVID-19）患者中普遍存在，并与不良预后相关。最近的证据表明，疾病特征的宿主免疫炎症反应，特别是白细胞介素-6 （IL-6）的增加，可能具有重要作用，可能通过对心脏电生理的直接影响。本研究旨在分析IL-6升高对重症COVID-19感染患者QTc的短期离散影响，并探讨其潜在机制。我们研究了以下机制：(1)COVID-19患者活动期和恢复期QTc持续时间及其与c反应蛋白（CRP）和IL-6水平的相关性；(2)在体内豚鼠模型中IL-6对QTc的急性影响；(3) IL-6对心室肌细胞的电生理作用。在活动期重症COVID-19伴IL-6水平升高的患者中，无论是否存在急性心肌损伤/应变及伴随的qt延长危险因素，QTc均显著延长，且与IL-6降低相关，且快速归一化。在体内豚鼠模型中直接给药IL-6可显著延长QTc持续时间。此外，与IL-6体外培养的心室肌细胞表现出明显的动作电位延长，以及对快速延迟整流钾电流（IKr）的显著抑制。我们首次证明，在严重的COVID-19中，全身炎症激活本身可以通过IL-6升高促进QTc延长，导致心室电重构。尽管是暂时的，但这种改变可能会在很大程度上导致COVID-19的心律失常事件和相关的不良结局。这些发现为目前针对COVID-19的抗炎治疗提供了进一步的理论依据，包括il -6靶向治疗。
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. 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. 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 (IKr). 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.
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DOI：
10.1007/s10840-021-01033-8
发表时间：
2022-03
期刊：
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing
影响因子：
--
作者：
Gulletta S;Della Bella P;Pannone L;Falasconi G;Cianfanelli L;Altizio S;Cinel E;Da Prat V;Napolano A;D'Angelo G;Brugliera L;Agricola E;Landoni G;Tresoldi M;Rovere PQ;Ciceri F;Zangrillo A;Vergara P
通讯作者：
Vergara P
影响因子：
5.7
作者：
Lazzerini, Pietro Enea;Laghi-Pasini, Franco;Capecchi, Pier Leopoldo
通讯作者：
Capecchi, Pier Leopoldo
影响因子：
2
作者：
Alsagaff MY;Oktaviono YH;Dharmadjati BB;Lefi A;Al-Farabi MJ;Gandi P;Marsudi BA;Azmi Y
通讯作者：
Azmi Y
影响因子：
2.8
作者：
Elsaid, Ossama;McCullough, Peter A.;Yoon, Anthony
通讯作者：
Yoon, Anthony
影响因子：
3.8
作者：
Hamlin, RL;Kijtawornrat, A;Hamlin, DM
通讯作者：
Hamlin, DM