Watanabe Hiroshi, Knollmann Björn C
Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Electrocardiol. 2011 Nov-Dec;44(6):650-5. doi: 10.1016/j.jelectrocard.2011.07.025. Epub 2011 Aug 27.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. The diagnosis is made based on reproducible ventricular tachyarrhythmias including bidirectional VT and polymorphic VT during exercise testings. Two causative genes of CPVT have been identified: RYR2, encoding the cardiac ryanodine receptor (RyR2) Ca(2+) release channel, and CASQ2, encoding cardiac calsequestrin. A mutation in RYR2 or CASQ2 is identified in approximately 60% of patients with CPVT. Mutations in these two genes destabilize the RyR2 Ca(2+) release channel complex in sarcoplasmic reticulum and result in spontaneous Ca(2+) release through RyR2 channels leading to delayed after depolarization, triggered activity, and bidirectional/polymorphic VT. Implantable cardioverter defibrillators (ICDs) are recommended for prevention of sudden death in patients with CPVT.1. A.E. Epstein, J.P. DiMarco, K.A. Ellenbogen, et al., ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation. 2008;117:e350 However, painful shocks can trigger further adrenergic stress and arrhythmias, and deaths have occurred despite appropriate ICD shocks. Treatment with β-adrenergic blockers reduces arrhythmia burden and mortality, but is not completely effective. The beneficial effects of Ca(2+) channel blocker verapamil in combination with β-blocker have been reported, but the role of verapamil has not been well assessed. Because Ca(2+) leakage through ryanodine channel is a common mechanism of CPVT, ryanodine channel block may have a therapeutic effect. We discovered that flecainide directly inhibits RyR2 channels and prevent CPVT. Left cardiac sympathetic denervation may be an effective alternative treatment in combination with ICD, especially for patients whose arrhythmias are not controlled by drug therapies.
儿茶酚胺能多形性室性心动过速（CPVT）是一种遗传性心律失常综合征，其特征为在无结构性心脏病的情况下，由肾上腺素能应激诱发室性心动过速（VT），且心脏性猝死发生率高。诊断基于运动试验期间可重复出现的室性快速心律失常，包括双向VT和多形性VT。已确定CPVT的两个致病基因：编码心脏雷诺丁受体（RyR2）钙释放通道的RYR2，以及编码心脏肌钙蛋白的CASQ2。在约60%的CPVT患者中可检测到RYR2或CASQ2的突变。这两个基因的突变会破坏肌浆网中RyR2钙释放通道复合物的稳定性，导致通过RyR2通道的自发性钙释放，进而引发延迟后去极化、触发活动以及双向/多形性VT。推荐植入式心脏复律除颤器（ICD）用于预防CPVT患者的猝死。1. A.E. 爱泼斯坦、J.P. 迪马尔科、K.A. 埃伦博根等，《美国心脏病学会/美国心脏协会/心律学会2008年心脏节律异常器械治疗指南：美国心脏病学会/美国心脏协会实践指南工作组（修订ACC/AHA/NASPE 2002年心脏起搏器和抗心律失常器械植入指南更新的写作委员会）报告》：与美国胸外科协会和胸外科医师学会合作制定。《循环》。2008年；117：e350然而，疼痛性电击可引发进一步的肾上腺素能应激和心律失常，尽管ICD电击恰当，仍有死亡发生。β肾上腺素能阻滞剂治疗可减轻心律失常负担并降低死亡率，但并不完全有效。已有报道钙通道阻滞剂维拉帕米与β受体阻滞剂联合使用的有益效果，但维拉帕米的作用尚未得到充分评估。由于通过雷诺丁通道的钙泄漏是CPVT的常见机制，雷诺丁通道阻滞可能具有治疗作用。我们发现氟卡尼可直接抑制RyR2通道并预防CPVT。左心交感神经去神经支配可能是与ICD联合使用的一种有效替代治疗方法，尤其适用于心律失常未被药物治疗控制的患者。
