Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes
Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes
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DOI：
10.1136/heartjnl-2016-311079
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发表时间：
2017-11-01
期刊：
影响因子：
5.7
通讯作者：
Capecchi, Pier Leopoldo
中科院分区：
文献类型：
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作者：
Lazzerini, Pietro Enea;Laghi-Pasini, Franco;Capecchi, Pier Leopoldo
目的越来越多的证据表明，全身炎症通过细胞因子介导的心肌细胞离子通道改变，是获得性长QT综合征（LQTS）的一个新的潜在原因。点扭转（TdP）是一种危及生命的多形性室性心动过速，发生在LQTS患者中，通常当多个延长qt的因素同时存在时。由于经典的危险因素不能完全解释许多患者的TdP事件，我们假设全身性炎症可能是目前被忽视的导致普通人群TdP发展的危险因素。方法连续招募40例TdP患者（TdP队列），比较c反应蛋白（CRP）和促炎因子(白细胞介素-6 （IL-6）、肿瘤坏死因子α （TNF - α)、白细胞介素-1 (IL-1)）与活动性类风湿关节炎（RA）患者、合并症患者及健康对照组的循环水平。另外46例不同炎症状况（急性感染，n=31；免疫介导性疾病，n=12；其他，n=3）和CRP升高的患者（炎症队列）被前瞻性纳入，并在活动性疾病期间和治疗后CRP降低bbb75 %后测量校正的QT （QTc）和细胞因子水平。结果：在TdP队列中，80%的患者CRP水平升高（中位数：类似于3mg /dL）， 40例患者中有18例可确定为炎症性疾病（急性感染，n=12；免疫介导性疾病，n=5；其他，n=1）。在这些受试者中，IL-6，但不包括TNFa和IL-1，比对照组高15-20倍，与RA患者相当。在炎症队列中，QTc延长是常见的（平均值：456.6 +/- 30.9 ms）， CRP降低与IL-6水平降低和QTc显著缩短（-22.3 ms）相关。结论该数据首次表明，在存在其他经典危险因素的情况下，通过IL-6水平升高引起的全身性炎症可能是一种新的qt延长危险因素，有助于TdP的发生。如果得到证实，这将为抗心律失常治疗开辟新的途径。
Objective 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.Methods 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 (TNF alpha), 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.Results In the TdP cohort, 80% of patients showed elevated CRP levels (median: similar to 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 TNFa and IL-1, was similar to 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).Conclusion 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.