儿茶酚胺敏感性多形性室速与心肌复极异常

儿茶酚胺敏感性多形性室速(catecholaminergic polymorphic ventricular tachycardia,CPVT)是一种恶性化程度较高的家族遗传性心律失常性疾病,临床上主要表现为由运动或情绪激动诱发(肾上腺素介导)的双向性和/或多形性室速、晕厥和猝死。CPVT的致病基因主要为RyR2和CASQ2。RyR2通道功能障碍造成的钙释放异常是引发CPVT的主要病理基础。本文对CPVT患者发生心肌复极异常的机制进行了综述。研究表明,肾上腺素刺激可加剧CPVT患者心肌细胞钙瞬变的不规则性与交替性变化,引起心肌复极不规则、QT间期变异程度加深,从而导致恶性心律失常。     

儿茶酚胺敏感性多行性室性心动过速的研究进展

儿茶酚胺敏感性多形性室性心动过速(CPVT)是一种由心肌钙离子失调引起的罕见遗传性离子通道病,其特征是由交感肾上腺系统兴奋诱发的多形性室性心动过速,患者可表现为晕厥甚至心源性猝死。约56%的CPVT患者存在RyR2或CASQ2基因突变,该突变可导致心肌细胞肌质网的钙泄露,继而引起延迟后除极和触发冲动,但仍有近一半的患者病因未明。儿童、青少年进行体育锻炼或情绪激动时突发晕厥,应高度怀疑CPVT。β受体阻滞剂可有效减少室性心动过速的发作,既往有心脏骤停病史的患者,可置入心脏转复除颤器。目前的治疗方法还有交感神经节切除术、射频消融术等,基因治疗有可能成为未来的治疗方向。     

儿茶酚胺敏感性多形性室速的基因诊治进展

儿茶酚胺敏感性多形性室速(CPVT)是具有较高猝死风险的罕见单基因遗传病.已知多种CPVT基因突变可通过影响肌浆网钙通道蛋白RyR2的功能,破坏细胞内钙稳态,触发室性心律失常,而依靠腺相关病毒载体(AAVs)及CRISPR/Cas9技术进行基因层面的干预有望为CPVT的治疗提供新思路.本文就其遗传特征及基因干预等领域的研究现状作一总结.     

Lesson Fifty-nine Catecholaminergic Polymorphic Ventricular Tachycardia

<正>第59课儿茶酣胺源性多形性室性心动过速 与多形性室性心动过速(VT)或心室颤动相关的原发性电子病有长QT综合征、Brngada综合征、短偶联间期尖端扭转型室性心动过速、短QT综合征和儿茶酚胺源性多形性室性心动过速(CPVT)。CPVT是一种罕见的致心律失常疾病,特征表现为肾上腺素诱发的双向性和多形性VT。在欧洲该疾病发病率估计为1:10 000。1975年首次报道。关键特征包     

钠通道阻滞剂在儿茶酚胺敏感性多形性室性心动过速治疗中的应用

儿茶酚胺敏感性多形性室性心动过速（catecholaminergic polymorphic ventricular tachycardia, CPVT）是一种遗传性心律失常疾病,以运动或情绪激动（肾上腺素）诱发的双向型和（或）多形性室性心动过速为特征,多发生于无器质性心脏病、QT间期正常的青少年。     

儿童CPVT

正儿茶酚胺敏感性多形性室性心动过速(catecholaminergic polymorphic ventricular tachycardia,CPVT)是一种较少见的严重的原发性心脏电紊乱,多发生于无器质性心脏病、QT间期正常的儿童或青少年,以运动或情绪激动诱发双向性室性心动过速(bVT)或多形性室性心动过速(pVT)为特征,常伴发晕厥或猝死,是一种高度恶性的遗传性心律失常。在人群中的发病率约为1:10000。未经治疗的CPVT患者的病死率约为40%。CPVT易被误诊或诊断延迟。     

儿茶酚胺敏感性室性心动过速的植入式心律转复除颤器治疗

正儿茶酚胺敏感性多形性室性心动过速(catecholaminergic polymorphic ventricular tachy-cardia,CPVT)是一种高度恶性的遗传性心律失常疾病,以运动或情绪激动诱发的双向型和(或)多形性室性心动过速为特征,多发生于无器质性心脏病、QT间期正常的青少年。目前研究认为CPVT可分为常染色体显性遗传和隐性遗传两种形式,分别与编码心肌细胞肌浆网钙通道的RyR2基因和肌浆网内     

儿茶酚胺敏感性多形性室性心动过速的研究进展

儿茶酚胺敏感性多形性室性心动过速(CPVT)是一种原发性心脏电紊乱,可能是非器质性心脏病患者发生猝死的重要原因。少年及成人均可患病。异常的RyR2通道或CASQ2蛋白在交感兴奋的条件下诱发的延迟后除极可能是CPVT发生的机制。任何患者无论年龄大小,只要是交感神经系统兴奋诱发的双向或多形性室性心动过速,无器质性心脏病且QT间期正常,都应考虑CPVT的诊断。β受体阻滞剂可以控制大部分患者的心动过速发作。CPVT患者发生过心脏骤停为埋藏式心脏转复除颤器(ICD)治疗的Ⅰ类适应证。服用β受体阻滞剂时出现晕厥者为ICD治疗的Ⅱa类适应证。对于致病基因的携带者,特别是儿童,都应服用β受体阻滞剂进行一级预防。     

儿茶酚胺敏感多形性室性心动过速的临床与基因学研究进展

儿茶酚胺敏感多形性室性心动过速(catecholaminergic polymorphic ventricular tachycardia,CPVT)又称儿茶酚胺依赖型多形性或家族性多形性室性心动过速(VT),多发生于心脏结构及QT间期正常的儿童和年轻人,以运动或情绪激动时出现双向或多形性VT、导致晕厥和猝死为特征.CPVT为一种遗传性疾病,依据致病基因不同分为两种类型:(1)CPVT1:常染色体显性遗传,编码利罗丁受体2(ryanodine receptor 2,RyB2)基因突变所致;(2)CPVT2:常染色体隐性遗传,编码肌集钙蛋白2(calsequestrin2,CASQ2)基因突变所致.     

儿茶酚胺敏感性室性心动过速的遗传学和治疗学研究

儿茶酚胺敏感性室性心动过速(CPVT)是以双向或多形性室性心动过速为特征的遗传性心律失常,多发生于无结构性心脏病的青少年,呈明显的家族聚集性,有常染色体显性和隐性两种遗传形式。目前较成熟的治疗方法有β受体阻滞剂、植入埋藏式心脏转复除颤器、Ⅰ类抗心律失常药及交感神经消融术。随着对CPVT认识的深入,基因和干细胞研究及部分学者提出的迷走神经松弛和心房超速起搏等有望为CPVT治疗提供新的策略。     

Treatment of asymptomatic catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia is a rare genetic disorder caused by mutations in genes involved in the intracellular calcium homeostasis of cardiac cells. Affected patients typically present with life-threatening ventricular arrhythmias precipitated by emotional/physical stress. The diagnosis is based on the demonstration of polymorphic or bidirectional ventricular tachycardia associated with adrenergic stress. Genetic testing can be confirmatory in some patients. Treatment for catecholaminergic polymorphic ventricular tachycardia includes medical and surgical efforts to suppress the effects of epinephrine at the myocardial level and/or modulation of calcium homeostasis. Mortality is high when untreated and sudden cardiac death may be the first manifestation of the disease. First-degree relatives of a proband should be offered genetic testing if the causal mutation is known. If the family mutation is not known, relatives should be clinically evaluated with provocative testing. In the absence of rigorous trials, prophylactic treatment of the asymptomatic catecholaminergic polymorphic ventricular tachycardia patient appears to reduce morbidity and mortality.     

Catecholaminergic Polymorphic Ventricular Tachycardia from Bedside to Bench and Beyond

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a primary electrical myocardial disease characterized by exercise- and stress-related ventricular tachycardia manifested as syncope and sudden death. The disease has a heterogeneous genetic basis, with mutations in the cardiac Ryanodine Receptor channel (RyR2) gene accounting for an autosomal-dominant form (CPVT1) in approximately 50% and mutations in the cardiac calsequestrin gene (CASQ2) accounting for an autosomal-recessive form (CPVT2) in up to 2% of CPVT cases. Both RyR2 and calsequestrin are important participants in the cardiac cellular calcium homeostasis.We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling. The pathophysiology of cardiac arrhythmias related to myocyte calcium handling and the effects of different modulators are discussed.The putative derangements in myocyte calcium homeostasis responsible for CPVT, as well as the clinical manifestations and therapeutic options available, are described.     

Catecholaminergic Polymorphic Ventricular Tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly lethal form of inherited arrhythmogenic disease characterized by adrenergically mediated polymorphic ventricular tachycardia. The mutations in cardiac ryanodine receptor and calsequestrin genes are responsible for the autosomal dominant and recessive variants of CPVT, respectively. The clinical presentation encompasses exercise- or emotion-induced syncopal events and a distinctive pattern of reproducible, stress-related, bidirectional ventricular tachycardia in the absence of both structural heart disease and a prolonged QT interval. The mortality rate in untreated individuals is 30-50% by age 40. Clinical evaluation by exercise stress testing and holter monitoring and genetic screening can facilitate early diagnosis. beta-adrenergic blockers are the most effective pharmacological treatment in controlling arrhythmias in CPVT patients, yet about 30% of patients still experience cardiac arrhythmias and eventually require an implantable cardioverter defibrillator.     

Catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant form of arrhythmogenic disorder characterized by exercise- or emotional-induced polymorphic ventricular tachycardia in the absence of detectable structural heart disease. Because of the typical pattern of arrhythmias (bidirectional ventricular tachycardia and the occurrence and severity of arrhythmia correlated well with exercise workload) during exercise stress test, CPVT can be identified promptly. Molecular genetic screening of the genes encoding the cardiac ryanodine receptor and calsequestrin is critical to confirm uncertain diagnosis of CPVT. With the exception of beta-blockers, no pharmacologic therapy of proven effectiveness is available: although beta-blockers reduce the occurrence of ventricular tachycardia, 30% of patients treated with beta-blockers still experience cardiac arrhythmias and eventually require implantable cardioverter defibrillator implantation to prevent cardiac arrest.     

A novel mutation in FKBP12.6 binding region of the human cardiac ryanodine receptor gene (R2401H) in a Japanese patient with catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. The human cardiac ryanodine receptor gene (RyR2) was linked to CPVT. A 20-year-old male was referred to our hospital because of recurrent syncope after physical and emotional stress. Routine cardiac examinations including catheterization revealed no structural abnormality. Exercise on treadmill induced premature ventricular contraction in bigeminy and bidirectional ventricular tachycardia was induced during isoproterenol infusion. Beta-blocking drug was effective in suppressing the arrhythmias. We performed genetic screening by PCR-SSCP method followed by DNA sequencing, and a novel missense mutation R2401H in RyR2 located in FKBP12.6 binding region was identified. This mutation was not detected in 190 healthy controls. Since FKBP12.6 plays a critical role in Ca channel gating, the R2401H mutation can be expected to alter Ca-induced Ca release and E-C coupling resulting in CPVT. This is the first report of RyR2 mutation in CPVT patient from Asia including Japan.     

儿茶酚胺敏感性多形性室性心动过速

摘要：儿茶酚胺敏感性多形性室速(CPVT)是一种是好发于青少年的遗传性心律失常综合征,其核心是由肾上腺素所诱发的心律紊乱。其典型的临床特征是运动或情绪激动时诱发室性心动过速,常伴发晕厥,甚至发生猝死。对于既往有晕厥或室速发作的患者,应当坚持使用β-受体阻滞剂(Ⅰa类证据),CPVT患者发生过心脏骤停为埋藏式心脏转复除颤器(ICD)治疗的Ⅱa类适应证。     

Unusual clinical presentation in a family with catecholaminergic polymorphic ventricular tachycardia due to a G14876A ryanodine receptor gene mutation

A family was identified, of whom which 11 members were carriers of the G14876A ryanodine 2 receptor mutation. All but 1 were symptomatic at the time of the study. Exercise testing showed bidirectional or polymorphic arrhythmias in 4 patients, whereas in 5 patients, it showed monomorphic or rare minor polymorphic ventricular arrhythmias. Two young patients died suddenly at rest while asleep. This study demonstrates that arrhythmias occurring during exercise stress testing in patients affected by catecholaminergic polymorphic ventricular tachycardia (CPVT) could be minor even in very symptomatic patients. The diagnosis of CPVT must be considered in these patients with a familial history of typical CPVT.     

Disruption of calcium homeostasis and arrhythmogenesis induced by mutations in the cardiac ryanodine receptor and calsequestrin

Development of cardiac arrhythmias in several degenerative cardiac disorders such as heart failure is precipitated by abnormalities in intracellular calcium regulation. Recently, the identification of mutations in proteins responsible for the control of intracellular calcium has been associated with an inherited arrhythmogenic syndrome called catecholaminergic polymorphic ventricular tachycardia (CPVT). Here, we review the current knowledge about the molecular pathophysiology of CPVT and we discuss some potentially innovative strategies for controlling calcium-handling abnormalities in CPVT that may provide novel therapeutic options for affected patients.     

儿茶酚胺介导的多形性室速研究进展

儿茶酚胺介导的多形性室速是一种少见却严重的遗传性心律失常,表现为无器质性心脏病的个体在运动或激动时发生双向性、多形性室速导致发作性晕厥及进展为心室颤动导致猝死。心肌细胞肌浆网异常释放钙离子使细胞内钙离子超载引起的延迟后除极可能是儿茶酚胺介导的多形性室速发生的机制。目前已知的和儿茶酚胺介导的多形性室速相关的基因为常染色体显性遗传的RyR2（位于1q42.1-q43）和常染色体隐性遗传的CASQ2（位于1p13.3-p11）。治疗：β-阻断剂适用于所有临床症状的个体和可能有RyR2突变而没有心脏事件（晕厥）或运动试验诱发的室性心律失常等病史的个体。反复心脏骤停患者需植入式心律转复除颤器。每6至12个月随访以监测疗效。患者所有的一级亲属,都应予心脏评估。