Abstract 3876: High Incidence of Sudden Death in Dilated Cardiomyopathy With Arrhythmogenic Autoantibodies Against Calcium Channel
Objectives: We sought to validate the hypothesis that the novel autoantibodies against L-type calcium channel (CC-AAbs) were arrhythmogenic and led to sudden death in patients with dilated cardiomyopathy (DCM).
Methods: We investigated sudden death in 80 patients with DCM by a prospective, case follow-up survey and explored relationship between the CC-AAbs and ventricular arrhythmias. Electrophysiological experiments were performed to study the arrhythmogenic mechanism of CC-AAbs.
Results: The novel CC-AAbs were detected in patients with DCM and then divided into CC-AAbs positive (n=39) and negative (n=41) group. The CC-AAbs positive patients had a higher incidence of ventricular tachycardia (VT) than the negative ones (23/39,59.0% vs 10/41,24.4%, P=0.002), and the presence of CC-AAbs was the only independent predictor of VT (odds ratio: 8.65, 95% confidence interval: 2.51–26.33, P<0.0001) by multivariate logistic regression analysis. During a follow-up of 32 (SD 8) months, the incidence of sudden death was higher in the CC-AAbs positive patients than the negative ones (8/39,20.5% vs 2/41,4.9%, P=0.045), while the presence of CC-AAbs and left ventricular ejection fraction(LVEF)< 30% were independent predictors of sudden death, and the presence of CC-AAbs was the strongest one (see table⇓). VT generated by CC-AAbs perfusions in isolated rat heart model. CC-AAbs not only prolonged action potential duration (APD), but also induced early afterdepolarization (EAD) in rat ventricular myocytes. ICa-L and [Ca2+]i were significantly increased by CC-AAbs on human atrial myocytes, rat ventricular myocytes and Xenopus oocytes expressing human CaV1.2 channels.
Conclusions: For the first time, we found high incidence of sudden death in patients with CC-AAbs in DCM. The novel CC-AAbs could induce VT by prolongation of APD and triggered activity of EAD which resulted from enhancement of ICa-L and [Ca2+]i.