Department of Medical Sciences, Surgery and Neurosciences (P.E.L., F.L.-P., F.F., F.V., M.N., S.B., B.G., N.M., A. D'Errico, P.L.C.), University Hospital of Siena, Italy.
Stroke Unit (M.A.), University Hospital of Siena, Italy.
Circ Arrhythm Electrophysiol. 2020 Aug;13(8):e008627. doi: 10.1161/CIRCEP.120.008627. Epub 2020 Jul 13.
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.
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.
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.
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. Graphic Abstract: A graphic abstract is available for this article.
在急性感染期间，恶性室性心律失常的风险增加，部分原因是发生 QTc 延长的倾向增加。虽然人们普遍认为 QTc 改变几乎完全是由于同时使用延长 QT 的抗生素所致，但炎症细胞因子对心室复极的直接作用正日益受到关注。我们假设，全身炎症本身可通过细胞因子介导的 K 通道表达变化，在急性感染期间显著延长 QTc。
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 延长的频率及其与炎症标志物的关系；（2）连续发生尖端扭转型室性心动过速患者队列中急性感染的发生率；（3）急性感染患者心室和外周血单个核细胞中 K 通道 mRNA 水平及其随时间变化的关系。
在急性感染患者中，无论是否同时使用延长 QT 的抗生素治疗，无论是否同时使用延长 QT 的抗生素治疗，QTc 均显著延长，但与 CRP（C 反应蛋白）和细胞因子水平降低呈平行快速正常化。同样，在尖端扭转型室性心动过速患者队列中，急性感染的发生率很高（30%），尽管只有少数（25%）此类病例接受了延长 QT 的抗生素治疗。外周血单个核细胞中 KCNJ2 K 通道表达与心室中表达强烈相关，与急性感染患者的 CRP 和白细胞介素（IL）-1 变化呈负相关。
在急性感染期间，全身炎症迅速引起细胞因子介导的心室电重构和显著的 QTc 延长，无论是否同时使用抗生素治疗。尽管这些变化是短暂的，但它们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。及时将这些发现应用于当前的 2019 年冠状病毒病（COVID-19）大流行是适时且必要的，在大流行中，循环细胞因子的数量增加，以及经常同时使用几种延长 QT 的药物治疗，都与心脏心律失常有关。
