Lazzerini Pietro Enea, Laghi-Pasini Franco, Bertolozzi Iacopo, Morozzi Gabriella, Lorenzini Sauro, Simpatico Antonella, Selvi Enrico, Bacarelli Maria Romana, Finizola Francesco, Vanni Francesca, Lazaro Deana, Aromolaran Ademuyiwa, El Sherif Nabil, Boutjdir Mohamed, Capecchi Pier Leopoldo
Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
Cardiology Intensive Therapy Unit, Department of Internal Medicine, Hospital of Carrara, Carrara, Italy.
Heart. 2017 Nov;103(22):1821-1829. doi: 10.1136/heartjnl-2016-311079. Epub 2017 May 10.
Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population.
Forty consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), interleukin-1 (IL-1)) were compared with patients with active rheumatoid arthritis (RA), comorbidity or healthy controls. An additional 46 patients with different inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12; others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled, and corrected QT (QTc) and cytokine levels were measured during active disease and after a CRP decrease of >75% subsequent to therapy.
In the TdP cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a definite inflammatory disease identifiable in 18/40 cases (acute infections, n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but not TNFα and IL-1, was ~15-20 times higher than in controls, and comparable to RA patients. In the inflammatory cohort, where QTc prolongation was common (mean values: 456.6±30.9 ms), CRP reduction was associated with IL-6 level decrease and significant QTc shortening (-22.3 ms).
The data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy.
越来越多的证据表明，全身炎症是获得性长QT综合征（LQTS）的一个新的潜在病因，通过细胞因子介导的心肌细胞离子通道变化起作用。尖端扭转型室速（TdP）是LQTS患者中发生的一种危及生命的多形性室性心动过速，通常在多种QT延长因素同时存在时出现。由于经典危险因素无法完全解释许多患者的TdP事件，我们推测全身炎症可能是普通人群中导致TdP发生的一个目前被忽视的危险因素。
连续纳入40例发生TdP的患者（TdP队列），并将其C反应蛋白（CRP）和促炎细胞因子（白细胞介素-6（IL-6）、肿瘤坏死因子α（TNFα）、白细胞介素-1（IL-1））的循环水平与活动性类风湿关节炎（RA）患者、合并症患者或健康对照进行比较。另外前瞻性纳入46例患有不同炎症性疾病（急性感染，n=31；免疫介导疾病，n=12；其他，n=3）且CRP升高的患者（炎症队列），在疾病活动期以及治疗后CRP下降>75%后测量校正QT（QTc）和细胞因子水平。
在TdP队列中，80%的患者CRP水平升高（中位数：约3mg/dL），18/40例患者可确定患有明确的炎症性疾病（急性感染，n=12；免疫介导疾病，n=5；其他，n=1）。在这些患者中，IL-6而非TNFα和IL-1比对照组高约15 - 20倍，与RA患者相当。在炎症队列中，QTc延长很常见（平均值：456.6±30.9毫秒），CRP降低与IL-6水平下降及显著的QTc缩短（-22.3毫秒）相关。
这些数据首次表明，在存在其他经典危险因素的情况下因IL-6水平升高导致的全身炎症可能是导致TdP发生的一个新的QT延长危险因素。如果得到证实，这可能为抗心律失常治疗开辟新途径。
