Cardiac Arrest Risk During Acute Infections Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-Mediated Effects on Potassium Channel Expression
Cardiac Arrest Risk During Acute Infections Systemic Inflammation Directly Prolongs QTc Interval via Cytokine-Mediated Effects on Potassium Channel Expression
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DOI：
10.1161/circep.120.008627
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发表时间：
2020-08-01
影响因子：
8.4
通讯作者：
Capecchi, Pier Leopoldo
中科院分区：
文献类型：
--
作者：
Lazzerini, Pietro Enea;Acampa, Maurizio;Capecchi, Pier Leopoldo
工作背景：在急性感染期间，恶性室性心律失常的风险增加，部分原因是QTc延长的倾向更高。虽然一般认为QTc的变化几乎完全是由QT延长抗菌药物的伴随治疗引起的，但越来越多的人认识到炎性细胞因子对心室复极的直接影响。我们假设全身性炎症本身可以通过苦参碱介导的K（+）通道表达的变化显著延长急性感染期间的QTc。研究方法：我们评估了（1）不同类型急性感染患者在疾病活动期和缓解期QTc间期延长的频率及其与炎症标志物的相关性;（2）尖端扭转型室性心动过速患者队列中急性感染的患病率;（3）K（+）急性感染患者心室和外周血单个核细胞中通道mRNA水平及其随时间的变化。结果如下：在急性感染患者中，无论是否伴随QT延长抗生素治疗，QTc均显著延长，但与CRP（C反应蛋白）和细胞因子水平降低平行迅速恢复正常。在尖端扭转型室性心动过速队列中，伴随急性感染的发生率较高（30%），尽管这些病例中只有少数（25%）接受了延长QT的抗菌剂治疗。急性感染患者外周血单个核细胞KCNJ 2 K（+）通道表达与CRP、IL-1水平呈负相关，与心室肌细胞KCNJ 2 K（+）通道表达呈正相关。结论：在急性感染期间，全身性炎症迅速诱导麻黄碱介导的心室电重构和显著的QTc延长，无论伴随的抗菌治疗如何。虽然这些变化是短暂的，但可能会显著增加这些患者发生危及生命的室性心律失常的风险。将这些发现转移到当前的2019冠状病毒病（COVID-19）大流行中是及时和必要的，其中循环细胞因子和心律失常的数量增加被证明沿着几种QT延长药物的频繁伴随治疗。
Background: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K(+)channel expression. Methods: We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K(+)channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time. Results: In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K(+)channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. Conclusions: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs.