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.     

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。     

Catecholaminergic polymorphic ventricular tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (VT) is a rare arrhythmogenic disease characterized by exercise- or stress-induced ventricular tachyarrhythmias, syncope, or sudden death, usually in the pediatric age group. Familial occurrence has been noted in about 30% of cases. Inheritance can be autosomal dominant or recessive, usually with high penetrance. The causative genes have been mapped to chromosome 1. Mutations of the cardiac ryanodine receptor gene (RyR2) have been identified in autosomal dominant pedigrees, while calsequestrin gene (CASQ2) mutations are seen in recessive cases. Ankyrin-B mutations may also be implicated in catecholaminergic polymorphic VT: mutations in this gene were previously linked to the long-QT 4 phenotype. Ventricular ectopy, bidirectional VT, and polymorphic VT occur in a predictable and progressive manner with increasing heart rate during exercise or isoproterenol infusion. Estimated mortality of untreated cases ranges from 30% to 50% before the age of 20-30 years according to family studies. Although beta-blocker therapy was considered to be effective in preventing clinical recurrence in the initial series, recent data show low efficacy. As there is a chance for sudden cardiac death if even a single dose of beta-blocker is missed, there is a trend toward implantation of defibrillators in more and more patients.     

Catecholaminergic polymorphic ventricular tachycardia,an update

Catecholaminergic polymorphic ventricular tachycardia is a rare devastating lethal inherited disorder or sporadic cardiac ion channelopathy characterized by unexplained syncopal episodes, and/or sudden cardiac death (SCD), aborted SCD (ASCD), or sudden cardiac arrest (SCA) observed in children, adolescents, and young adults without structural heart disease, consequence of adrenergically mediated arrhythmias: exercise‐induced, by acute emotional stress, atrial pacing, or β‐stimulant infusion, even when the electrocardiogram is normal. The entity is difficult to diagnose in the emergency department, given the range of presentations; thus, a familiarity with and high index of suspicion for this pathology are crucial. Furthermore, recognition of the characteristic findings and knowledge of the management of symptomatic patients are necessary, given the risk of arrhythmia recurrence and SCA. In this review, we will discuss the concept, epidemiology, genetic background, genetic subtypes, clinical presentation, electrocardiographic features, diagnosis criteria, differential diagnosis, and management.     

Catecholaminergic polymorphic ventricular tachycardia with associated sinus node dysfunction

An 11-year-old Nepalese male child presented with history of recurrent abrupt episodes of syncope for the last one year. There was no family history of sudden death at a young age in his family. ECG at base-line revealed an isorhythmic AV dissociation with a heart rate of 50 bpm and a normal QTc. Echocardiography of the heart was normal. His 24 hour holter study revealed frequent VPC's and episodes of polymorphic ventricular tachycardia. Exercise stress test provoked a polymorphic VT. On EP study, sinus node recovery time (SNRT) was prolonged and ventricular tachycardia (VT) was induced on Isoproterenol infusion. He was treated with a permanent pacemaker and beta-blocker.     

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.     

Catecholaminergic polymorphic ventricular tachycardia: electrocardiographic characteristics and optimal therapeutic strategies to prevent sudden death

Objective: To investigate the clinical outcome, ECG characteristics, and optimal treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), a malignant and rare ventricular tachycardia.     

Catecholaminergic polymorphic ventricular tachycardia. An important diagnosis in children with syncope and normal heart

Syncope in children is primarily related to vagal hyperreactivity, but ventricular tachycardia (VT) way rarely be seen. Catecholaminergic polymorphic VT is a rare entity that can occur in children without heart disease and with a normal QT interval, which may cause syncope and sudden cardiac death. In this report, we describe the clinical features, treatment, and clinical follow-up of three children with syncope associated with physical effort or emotion and catecholaminergic polymorphic VT. Symptoms were controlled with beta-blockers, but one patient died suddenly in the fourth year of follow-up. Despite the rare occurrence, catecholaminergic polymorphic VT is an important cause of syncope and sudden death in children with no identified heart disease and normal QT interval.     

Adenosine-induced non-sustained polymorphic ventricular tachycardia

Adenosine has become widely used because of its diagnostic andtherapeutic value in the emergency management of arrhythimias.it produces transient heart block by slowing conduction throughtile AV node and thus terminates supraventricular tachycardiasthat involve the atrioventricular node. Bradyarrhythmias ofshort duration are common side effects of the use of this drug.Premature atrial and ventricular beats have also been reported.The very short half-life and lack of serious adverse effectsgenerally lead to the consideration that adenosine is a safedrug. We describe a 56-year-old woman with a supra ventriculartachycardia. To terminate this rhythm disorder intravenous adenosinewas given. Interruption of tile supra ventricular tachycardiawas followed by non-sustained polymorphic ventricular tachycardia.     

表现为双向室性心动过速的儿茶酚胺敏感性多形室性心动过速一例

儿茶酚胺敏感的多形室性心动过速（catecholaminergic polymorphic ventricular tachycardia,CPVT）是一种恶性室性心律失常,最早由Leenhardt等[1]于1995年提出,指运动或儿茶酚胺在3个以上连续心搏可引起两种以上的室性心动过速（室速）形态,多为双向或多形室速[2];同时无电解质紊乱、药物或器质性心脏病等可导致多形室速/心室颤动（室颤）的因素存在.另外还应除外长QT综合征（LQTS）、Brugada综合征等原发性离子通道病.现有1例此病患者,兹报道如下.     

Autosomal recessive catecholamine-induced polymorphic ventricular tachycardia

Catecholamine-induced polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures or sudden death, in response to physical activity or emotional stress, and affects mainly young children with morphologically normal hearts. An autosomal recessive form of the disorder in seven families from a Bedouin tribe in the north of Israel was recently described by the authors, and the disease-causing gene was mapped to chromosome 1p13–1p21. Direct sequencing of calsequestrin 2 (CASQ2), a candidate gene from within the linkage interval, revealed a negatively charged aspartic acid change to a positively charged histidine at position 307 of the protein. CASQ2 serves as the major calcium reservoir within cardiac myocytes. This mutation occurs in a highly conserved residue of the protein. The implication of the calcium release cascade in this disease may lead to a better understanding of the pathophysiological events underlying ventricular tachycardia, and to the use of drugs directly involved in intracellular calcium control for the treatment of the PVT patients.     

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.     

Isolated noncompaction left ventricular myocardium and polymorphic ventricular tachycardia

A 57-year-old woman with syncope was admitted. She had a family history of sudden death: two brothers had died suddenly at the age of 47. Transesophageal echocardiography showed numerous prominent trabeculations and deep intertrabecular recesses in the anterior and lateroapical zones. Isotopic left ventricular ejection fraction was 46%. Cardiac catheterization showed coronary arteries with no angiographic lesions. A prominent trabecular zone and deep intertrabecular recesses were seen in the anterior wall on left ventriculography. Right ventriculography was normal. The diagnosis of isolated noncompaction left ventricular myocardium was established. Continuous 24-h electrocardiographic registry showed episodes of polymorphic ventricular tachycardia. Programmed ventricular stimulation performed at the right ventricular apex with up to three extrastimuli failed to induce ventricular arrhythmias. Treatment with beta blockers was initiated, but short runs of polymorphic ventricular tachycardia persisted. A dual-chamber automatic implantable defibrillator was implanted. We discuss the physiopathology of the arrhythmia. It appears that several factors could be responsible for the malignant arrhythmias in this entity.