Arrhythmogenic autoantibodies against calcium channel lead to sudden death in idiopathic dilated cardiomyopathy.
OBJECTIVE
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Cardiology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hua
H
Xiao
Min
M
Wang
Yimei
Y
Du
Jing
J
Yuan
Xiang
X
Cheng
Zhijian
Z
Chen
Anruo
A
Zou
Fen
F
Wei
Guanghong
G
Zhao
Yu-Hua
YH
Liao
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000276:immunology; D001323:Autoantibodies; D020746:Calcium Channels, L-Type / Q000276:immunology*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000276:immunology / Q000401:mortality / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000276:immunology
D001323:Autoantibodies; D020746:Calcium Channels, L-Type