Department of Cardiology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Eur J Heart Fail. 2011 Mar;13(3):264-70. doi: 10.1093/eurjhf/hfq198. Epub 2010 Nov 2.
Calcium channel plays an important role in the autoimmune pathogenesis of idiopathic dilated cardiomyopathy (DCM). Autoantibodies have emerged as a new upstream target of sudden death in DCM. We sought to validate the hypothesis that autoantibodies against l-type calcium channel (CC-AAbs) are arrhythmogenic and lead to sudden death in patients with DCM.
We investigated sudden death and ventricular arrhythmias in 80 patients with DCM in a prospective, case follow-up survey. During a follow-up of 32 (SD 8) months, CC-AAbs-positive patients not only had a higher incidence of ventricular tachycardia (VT) but also a higher incidence of sudden death than CC-AAbs-negative patients (for VT: 59.0 vs. 24.4%, P = 0.002 and for sudden death: 20.5 vs. 4.9%, P = 0.045). Further univariate and multivariate analyses showed that the occurrence of CC-AAbs was the strongest independent predictor for sudden death (odds ratio: 10.20, 95% confidence interval: 2.43-36.78, P = 0.0027). Experimental studies in ex vivo systems using affinity-purified CC-AAbs from patients demonstrated that CC-AAbs were able to induce VT by prolongation of action potential duration (APD) and triggered activity by early afterdepolarization (EAD).
Our results demonstrate for the first time to our knowledge that there is a high incidence of sudden death and VT in CC-AAbs-positive patients with DCM. Furthermore, experimental data from ex vivo systems suggest that CC-AAbs might induce VT by prolongation of APD and triggered activity by EAD.
钙通道在特发性扩张型心肌病（DCM）的自身免疫发病机制中发挥重要作用。自身抗体已成为 DCM 猝死的新上游靶点。我们试图验证这样一个假设，即针对 L 型钙通道（CC-AAbs）的自身抗体是致心律失常的，并导致 DCM 患者猝死。
我们在一项前瞻性病例随访研究中调查了 80 例 DCM 患者的猝死和室性心律失常。在 32（SD8）个月的随访期间，CC-AAbs 阳性患者不仅室性心动过速（VT）的发生率更高，而且猝死的发生率也高于 CC-AAbs 阴性患者（VT：59.0%比 24.4%，P=0.002；猝死：20.5%比 4.9%，P=0.045）。进一步的单变量和多变量分析表明，CC-AAbs 的发生是猝死的最强独立预测因素（优势比：10.20，95%置信区间：2.43-36.78，P=0.0027）。使用从患者中亲和纯化的 CC-AAbs 在离体系统中进行的实验研究表明，CC-AAbs 能够通过延长动作电位时程（APD）和早期后除极（EAD）诱发触发活动来诱发 VT。
我们的研究结果首次证明，在 CC-AAbs 阳性的 DCM 患者中，猝死和 VT 的发生率很高。此外，离体系统的实验数据表明，CC-AAbs 可能通过延长 APD 和 EAD 诱发的触发活动来诱发 VT。
