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。     

其它遗传性心律失常的诊断及治疗

<正>1儿茶酚胺敏感性多形性室速儿茶酚胺敏感性多形性室速(CPVT)是一种高度恶性遗传性心律失常疾病,以运动或情绪激动(肾上腺素)诱发的双向性或多形性室速或猝死为特征,发生于无器质性心脏病,QT间期正常的青少年。1.1儿茶酚胺敏感性多形性室速临床表现儿茶酚胺敏感性多形性室速(CPVT)是Coumel等在1978年首次描述的以体力活动或情绪激动诱发的多形性室性心律失常和晕厥、静息心电图和心脏结构正常为特征的     

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2例报告

儿茶酚胺敏感性室性心动过速(室速)又称儿茶酚胺敏感性多形性室速(CPVT),是一种家族遗传性离子通道病,也是导致年轻人心脏性晕厥及猝死的常见疾病之一。由于CPVT发病多为青少年,     

双向性室性心动过速

1922年,Schwensen首次报道1例洋地黄中毒患者伴有双向性室性心动过速(bidirectional ventriculartachycardia)。因此,双向性室速的概念并不陌生,近年来发现双向性室速也是家族遗传性儿茶酚胺敏感性室速(CPVT)患者的特征性心电图表现。[心电图特点]“双向性室速”这一心电学术语     

双向性室性心动过速(30)

1922年,Schwensen首次报道1例洋地黄中毒患者伴有双向性室性心动过速(bidirectional ventricular tachycardia).因此,双向性室速的概念并不陌生,近年来发现双向性室速也是家族遗传性儿茶酚胺敏感性室速(CPVT)患者的特征性心电图表现.     

儿茶酚胺敏感性多形性室性心动过速的诊断

<正>儿茶酚胺敏感性室性心动过速(Catecholaminergic polymorphic ventricular tachycardia,CPVT)是一种少见的遗传性恶性心律失常。以运动或情绪激动诱发的双向性或多形性室速为特征,不伴结构性心脏病和QT间期延长[1],严重者可进一步发展为室颤而引起晕厥甚至猝死,是青少年发生心源性猝死的重要病因之一[2]。目前已经确定与CPVT有关的突变基因有RyR2~([3])和CASQ2~([4]),RyR2和CASQ2基因的突变使RyR2通道蛋白出现异常,引起心肌细胞肌质网持续     

儿茶酚胺诱发的多形性室性心动过速：心电图特征及预防猝死的最佳方案

儿茶酚胺诱发的多形性室性心动过速 (CPVT)是运动或静滴儿茶酚胺时发生的两种以上形态的室性心动过速。CPVT不存在电解质紊乱、药物治疗及原发性心脏疾病等诱因 ,且无长QT及Brugada综合征等原发性电生理紊乱。目前对CPVT的预后 ,临床及心电图特征尚未完全明确 ,本文对有关问题进行了探讨。方法 :对 2 9例符合CPVT诊断标准的患者分别在控制期及发作期进行了完整体表心电图记录。患者均经心血管专科医师体检 ,并完成X胸片及UCG检查。CPVT来源位置由束支阻滞类型及QRS电轴判定。结果 :2 9例患者 (男 13 ,女 16)平均年龄 10 .3± 6.…     

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。     

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.     

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基因特异性管理

儿茶酚胺敏感性多形性室性心动过速(catecholaminergic polymorphic ventricular tachycardia，CPVT)是一种罕见的遗传性疾病，与基因突变导致的心肌细胞内钙稳态的失衡有关，运动或情绪激动可诱发致命性的室性心律失常。CPVT的诊断基于肾上腺素引起的双向性或多形性室性心动过速，部分患者通过基因检测确诊。在治疗上可通过内、外科方法，抑制或阻断肾上腺素对心肌钙稳态的影响。未正规治疗的患者死亡率高，且猝死常为首发症状。文章阐述CPVT的遗传学新发现及其对临床管理的影响，同时阐述基因检测的局限性和级联筛查的最佳应用。     

Cardiac Calsequestrin: The New Kid on the Block in Arrhythmias

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited disease characterized by physical or emotional stress-induced ventricular arrhythmias in the absence of any structural heart disease or QT prolongation. Thus far, mutations in genes encoding the sarcoplasmic reticulum Ca²⁺ release channel (RYR2) and the sarcoplasmic reticulum Ca²⁺ binding protein cardiac calsequestrin (CASQ2) have been identified in CPVT patients. Here, we review the role of cardiac calsequestrin in health and disease, with a particular focus on how calsequestrin deficiency can cause arrhythmia susceptibility. Clinical implications and a promising new drug therapy for CPVT are discussed.     

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)     

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。     

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遗传性心律失常是指具有家族聚集倾向、临床上易于出现室性心动过速、心室颤动及猝死等表现的遗传性心脏疾病,可伴或不伴心脏结构的改变。对遗传性心律失常患者进行基因检测能够协助诊断及治疗。目前已有多种方法用于致病基因的检测,不同方法各有其优缺点及适用范围。对于单基因遗传性疾病,可应用单核苷酸多态性(SNP)等遗传标记对致病基因进行精细定位,对候选基因进行测序从而明确致病基因;对于多基因遗传病可通过连锁分析定位易感基因位点并通过群体关联研究缩小候选基因的范围。高通量测序和基因芯片的出现为致病基因检测提供了广阔的发展空间。     

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.     

Human cardiac ryanodine receptor mutations in ion channel disorders in Japan

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergic induced bidirectional or polymorphic ventricular tachycardias. Some of CPVT families were reported to be associated with cardiac ryanodine receptor gene (RyR2) mutations. However, association between RyR2 and other arrhythmogenic disorders is not clarified. In this study, we analyzed 83 Japanese patients including patients with long-QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, arrhythmogenic right ventricular cardiomyopathy and CPVT. Genetic screening of RyR2 revealed 3 distinct mutations among 4 families with CPVT (75% of incidence). However, no mutation was found in other groups. This is the first report to demonstrate prevalence of RyR2 mutations in various arrhythmogenic disorders in Japan. RyR2 mutations were detected frequently in CPVT but not in other diseases.     

Mechanism underlying catecholaminergic polymorphic ventricular tachycardia and approaches to therapy

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) Ca²⁺ 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 Ca²⁺ release channel complex in sarcoplasmic reticulum and result in spontaneous Ca²⁺ 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 Ca²⁺ channel blocker verapamil in combination with β-blocker have been reported, but the role of verapamil has not been well assessed. Because Ca²⁺ 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.