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.     

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     

Lesson Fifty- nine Catecholaminergic Polymorphic Ventricular Tachycardia

The primary electric disorders responsible for polymorphie ventrieular taehyeardia （VT） or ventricular fibrillation are long-QT syndrome, Brugada syndrome, the short-coupled variant of torsades dR pointes, short-QT syndrome, and eateeholaminergie polymorphie VT （CPVT）. CPVT is a rare arrhythmogenic disorder characterized by adrenergie-indueed bidirectional and polymorphic VT. The prevalence of the disease is esti- mated to be 1：10 000 in Europe. T     

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。     

New Family With Catecholaminergic Polymorphic Ventricular Tachycardia Linked to the Triadin Gene

We describe a new family with cathecholaminergic polymorphic ventricular tachycardia (CPVT) linked to the Triadin gene. This is the second report of such a CPVT of autosomal recessive inheritance. Using an NGS panel including 42 genes involved in cardiac sudden death, 2 heterozygous pathogenic mutations (c.613C> T/p.Gln205* and c.22 + 29 A>G) were identified in the Triadin gene in 2 sibs who experienced early severe arrhythmias without evidence of CPVT diagnosis at first cardiac evaluation. However, significant arrhythmias occurred after catecholaminergic stimulation. Each of the TRDN mutations was inherited from a healthy parent. In this family, genetic studies permit confirmation of the CPVT diagnosis in the 2 affected sibs and permit the early diagnosis of the third asymptomatic child. It also helped guide the therapeutic strategy in this family.     

儿茶酚胺敏感性室性心动过速诊治新进展

临床研究表明儿茶酚胺敏感性室性心动过速（catecholaminergic polymorphic ventricular tachycardia,CPVT）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、多形性室性心动过速（室速）导致发作性晕厥;当这些心律失常自行停止时,可自发性恢复;另一些情况下,室速转为心室颤动（室颤）,若未及时心肺复苏可导致猝死。     

Guidelines for the diagnosis and management of Catecholaminergic Polymorphic Ventricular Tachycardia

BACKGROUND: Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is an inherited arrhythmia syndrome, characterised by polymorphic ventricular tachycardia induced by adrenergic stress. CPVT can be caused by mutations the cardiac ryanodine receptor gene (RYR2) or mutations in the cardiac calsequestrin gene CASQ2. Structural heart disease is usually absent and the baseline ECG is usually normal. Patients with CPVT often present with exercise- or emotion induced syncope, the first presentation can also be sudden cardiac death. MANAGEMENT: Besides removal of triggers treatment with beta blockers is currently a class I indication in clinically diagnosed patients. Beta blockage should be titrated up to an effective level. The addition of flecainide seems to be a promising approach in patients where arrhythmias are not completely suppressed by beta blockers. A cardioverter-defibrillator (ICD) or left cervical sympathetic denervation might be considered under special circumstances. Genetic counselling is recommended and all first degree relatives should be properly evaluated.     

Precision Medicine in Catecholaminergic Polymorphic Ventricular Tachycardia: JACC Focus Seminar 5/5

In this final of a 5-part Focus Seminar series on precision medicine, we focus on catecholaminergic polymorphic ventricular tachycardia (CPVT). This focus on CPVT allows us to take a “deep dive” and explore the full extent of the precision medicine opportunities for a single cardiovascular condition at a level that was not possible in the preceding articles. As a new paradigm presented in this article, it has become clear that CPVT can occur as either a typical or atypical form. Although there is a degree of overlap between the typical and atypical forms, it is notable that they arise due to different underlying genetic changes, likely exhibiting differing mechanisms of action, and presenting with different phenotypic features. The recognition of these differing forms of CPVT and their different etiologies and mechanisms is an important step toward implementing rapidly emerging precision medicine approaches that will tailor novel therapies to specific gene defects.     

Prevention of Ventricular Arrhythmia and Calcium Dysregulation in a Catecholaminergic Polymorphic Ventricular Tachycardia Mouse Model Carrying Calsequestrin‐2 Mutation

Arrhythmia Prevention in CPVT . Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmic syndrome caused by mutations in genes encoding the calcium‐regulation proteins cardiac ryanodine receptor (RyR2) or calsequestrin‐2 (CASQ2). Mechanistic studies indicate that CPVT is mediated by diastolic Ca²⁺ overload and increased Ca²⁺ leak through the RyR2 channel, implying that treatment targeting these defects might be efficacious in CPVT. Method and results: CPVT mouse models that lack CASQ2 were treated with Ca²⁺‐channel inhibitors, β‐adrenergic inhibitors, or Mg²⁺. Treatment effects on ventricular arrhythmia, sarcoplasmic reticulum (SR) protein expression and Ca²⁺ transients of isolated myocytes were assessed. Each study agent reduced the frequency of stress‐induced ventricular arrhythmia in mutant mice. The Ca²⁺ channel blocker verapamil was most efficacious and completely prevented arrhythmia in 85% of mice. Verapamil significantly increased the SR Ca²⁺ content in mutant myocytes, diminished diastolic Ca²⁺ overload, increased systolic Ca²⁺ amplitude, and prevented Ca²⁺ oscillations in stressed mutant myocytes. Conclusions: Ca²⁺ channel inhibition by verapamil rectified abnormal calcium handling in CPVT myocytes and prevented ventricular arrhythmias. Verapamil‐induced partial normalization of SR Ca²⁺ content in mutant myocytes implicates CASQ2 as modulator of RyR2 activity, rather than or in addition to, Ca²⁺ buffer protein. Agents such as verapamil that attenuate cardiomyocyte calcium overload are appropriate for assessing clinical efficacy in human CPVT . (J Cardiovasc Electrophysiol, Vol. 22, pp. 316‐324, March 2011)     

A De Novo Novel Cardiac Ryanodine Mutation (Ser4155Tyr) Associated with Catecholaminergic Polymorphic Ventricular Tachycardia

We describe the case of a 14‐year‐old girl with a history of syncopal episodes triggered by stress or exercise. Catecholaminergic polymorphic ventricular tachycardia was diagnosed with the aid of an implantable loop recorder. The genetic testing of the patient and her family revealed a de novo novel missense mutation (Ser4155Tyr) in the exon 90 of the ryanodine receptor gene. This mutation affects a highly conserved residue (S4155) and results to replacement of serine (S) with tyrosine (Y) leading to change in physical and chemical properties. The girl was treated with an implantable defibrillator, metoprolol and flecainide. Over 1 year of follow‐up she had no recurrence of ventricular tachycardia.     

Ten-Year Follow-Up of Cardiac Sympathectomy in a Young Woman with Catecholaminergic Polymorphic Ventricular Tachycardia and an Implantable Cardioverter Defibrillator

Current recommendations for therapy of catecholaminergic ventricular tachycardia (CPVT) include beta blockade and implantable cardioverter defibrillators (ICDs). Patients may experience recurrent arrhythmias, ICD shocks and, rarely, sudden death despite optimal medical therapy. We report a young woman with CPVT who received frequent ICD shocks despite beta blockade, who subsequently underwent cardiac sympathectomy with a dramatic reduction in shocks over 10 years of follow-up.     

多形性室性心动过速的临床特征与处理

总结分析 11例多形性室性心动过速 (室速 )的临床 ,心电图特征及治疗。伴发于QT间期延长7例 ,其中获得性 5例 ,先天性 2例 ;伴发于QT间期正常 4例 ,3例与冠心病有关 ,1例伴发于极短联律间距。指出对不同类型多形性室速应仔细鉴别 ,区别对待