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。     

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.     

Vasospastic Angina with J‐Wave Pattern and Polymorphic Ventricular Tachycardia Effectively Treated with Quinidine

Background: Myocardial ischemia during coronary spasm may generate malignant ventricular arrhythmias. The J‐wave pattern was suggested to be a marker of a disorder associated with life‐threatening arrhythmias. Results: We report the case of a patient with vasospastic angina and J‐wave pattern in inferior and lateral leads associated with polymorphic ventricular tachycardia which was effectively treated only with quinidine—vasodilating drugs were not able to prevent the arrhythmia although they were effective in preventing ischemic events. Conclusion: The J‐wave pattern in inferolateral leads may be a sign of electrical vulnerability to lethal ventricular arrhythmia in patients suffering from vasospastic angina—quinidine can effectively prevent such arrhythmias in these patients.     

Idiopathic Ventricular Tachycardia and Fibrillation

Idiopathic Ventricular Tachycardia and Fibrillation. Important data have recently been added to our understanding of sustained ventricular tachyarrhythmias occurring in the absence of demonstrable heart disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic configuration and can be classified according to its site of origin as either right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several physiopathological types of monomorphic VT can be presently individualized, according to their mode of presentation, their relationship to adrenergic stress, or their response to various drugs. The long-term prognosis is usually good. Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less favorable prognosis. Idiopathic ventricular fibrillation may represent an underestimated cause of sudden cardiac death in ostensibly healthy patients. A high incidence of inducibility of sustained polymorphic VT with programmed ventricular stimulation has been found by our group, but not by others. Long-term prognosis on Class IA antiarrhythmic medications that are highly effective at electrophysiologic study appears excellentJfy Cardiovasc Electrophysiol, Vol. 4, pp. 356–368, June 1993 ).     

Implantable Cardioverter Defibrillator Therapy in Patients with Ischemic or Non-Ischemic Cardiomyopathy and Nonsustained Ventricular Tachycardia

BACKGROUND: Mortality benefit from implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) with non-sustained ventricular tachycardia (NS-VT) and inducible VT is well defined. Although NS-VT may suggest an increased risk of sudden cardiac death (SCD) in non-ischemic cardiomyopathy (NICM), the role of ICD therapy is unclear. This retrospective study compares follow-up data in these two groups after ICD implantation. METHODS: 153 consecutive patients with ICD implantation for NS-VT were analyzed. ICM patients received an ICD if they had inducible VT at electrophysiology study (EPS). NICM patients did not routinely undergo EPS before ICD implantation. RESULTS: There were 48 patients (33 males) in NICM group and 105 patients (89 males) in the ICM group. Baseline characteristics including mean ejection fraction (EF), distribution in various New York Heart Association (NYHA) classes, and the mean duration of follow up in the two groups were similar. 50% of the patients in the NICM group and 36% in the ICM group received appropriate therapies (p = 0.106). The mean number of appropriate therapies in the two groups were similar (23.3 +/- 56.7 and 22.5 +/- 59.5 respectively, p = NS). The percentage of patients with inappropriate therapies in the two groups were 27% and 23% respectively (p = NS). Patients in the NICM group received appropriate ICD discharges at a greater rate (p = 0.02). CONCLUSION: Patients undergoing ICD implantation for NICM and NS-VT receive appropriate ICD therapy at a greater rate than those implanted for ICM, NS-VT, and a positive EPS. Although these data do not prove survival benefit in NICM, they suggest a beneficial effect.     

Benefit of Pacing and Beta-Blockers in Idiopathic Repetitive Polymorphic Ventricular Tachycardia

An 18-year-old woman presented with recurrent exercise-induced syncopal episodes and severe systolic dysfunction. ECG monitoring disclosed repetitive polymorphic ventricular complexes, paroxysms of bidirectional ventricular tachycardia, and nonsustained bursts of slow polymorphic ventricular tachycardia that increased in length and rate during exercise. Ventricular arrhythmias were refractory to medical treatment, which included verapamil and beta-blockers. Addition of permanent atrial pacing to beta-blocker therapy suppressed the arrhythmias and reversed systolic impairment in the following months.     

Accelerated Junctional Rhythm and Nonalternans Repolarization Lability Precede Ventricular Tachycardia in Casq2−/− Mice

Repolarization Lability in Casq2?/? Mice . Background: Calsequestrin‐2 (CASQ2) is a Ca²⁺ buffering protein of myocardial sarcoplasmic reticulum. CASQ2 mutations underlie a form of catecholaminergic polymorphic ventricular tachycardia (CPVT). The CPVT phenotype is recapitulated in Casq2 ?/? mice. Repolarization lability (RL)—beat‐to‐beat variability in the T wave morphology—has been reported in long‐QT syndrome, but has not been evaluated in CPVT. Methods and Results: ECG from Casq2 ?/? mice was evaluated with respect to heart rate (HR) and RL changes prior to onset of ventricular tachycardia (VT) to gain insight into arrhythmogenesis in CPVT. Telemetry from unrestrained mice (3‐month‐old males, 5 animals of each genotype) and ECG before and after isoproterenol administration in anesthetized mice was analyzed. Average HR in sinus rhythm (SR), occurrence of nonsinus rhythm and RL were quantified. HR was slower in Casq2 ?/? animals. Accelerated junctional rhythm (JR) occurred more frequently in Casq2 ?/? mice and often preceded VT. In Casq2 ?/? mice, HR increased prior to VT onset, prior to onset of JR and on transition from JR to VT. RL increased during progression from SR to VT and after isoproterenol administration in Casq2 ?/?, but not in Casq2+/+ animals. Isoproterenol did not increase repolarization alternans in either genotype. Conclusions: Accelerated JR, likely caused by triggered activity in His/Purkinje system, occurs frequently in Casq2 ?/? mice. The absence of CASQ2 results in increased RL. The increase in HR and in RL precede onset of arrhythmias in this CPVT model. Nonalternans RL precedes ventricular arrhythmia in wider range of conditions than previously appreciated. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1355‐1363, December 2012)     

The Clinical Significance of Nonsustained Ventricular Tachycardia in Patients with Sustained Ventricular Tachyarrhythmias

Background: Nonsustained ventricular tachycardia (NSVT) predicts mortality in several disorders but its significance in patients with sustained ventricular tachyarrhythmias is unknown. We analyzed the clinical features and outcome associated with NSVT (>; 3 beats at >; 100 beats/min) recorded on a 48-hour Holter in the absence of antiarrhythmic drugs. Methods: Patients enrolled in the ESVEM trial (n = 486) were grouped according to the duration of the longest recorded episode of NSVT, and in the second analysis, according to frequency of recorded episodes. Assessments were on an intention-to-treat basis. Results: Patients without NSVT were more likely to have ischemic heart disease and had significantly lower frequencies of single and paired premature ventricular complexes (PVCs). There were no significant differences with respect to age, sex, presenting arrhythmia, years since last myocardial infarction, functional class, or present ejection fraction. The cumulative probabilities of arrhythmia recurrence and all-cause mortality at 4 years in patients without NSVT (60%± 7% and 32%± 6%, respectively) were not significantly different than those of patients with NSVT (63%± 3% and 41%± 3%, respectively). Cox regression models indicated that ejection fraction and functional class were significant predictors of outcome, but variables based on the presence, duration, and frequency of recorded episodes of NSVT were not. Conclusions: NSVT is common in patients with spontaneous and inducible sustained ventricular tachyarrhythmias and at least 10 PVCs/hour (ESVEM enrollment criteria), but is not a significant predictor of arrhythmia recurrence, sudden death, or all-cause mortality in patients with these characteristics.     

Nonsustained Ventricular Tachycardia

Nonsustained ventricular tachycardia (VT) has been an intimidating diagnosis for many physicians because its presence, in general, portends an increased risk of sudden death. The management and approach has been quite diverse and inconsistent in part due to the absence of a large body of literature. There have been major developments, however, over the last two decades in better understanding the mechanism of VPCs and ventricular tachycardia as well as adopting a more systematic approach to diagnosis and management. With the publication of the results of CAST I and II, there has been a movement away from empiric treatment of asymptomatic VPCs and nonsustained VT, and an emphasis on risk stratification on the basis of the underlying heart disease. Coronary artery disease, by far, is the most common etiology for heart disease in the United States, but there are numerous other conditions such as hypertrophic and dilated cardiomyopathies, as well as right ventricular dysplasia and “normal heart” ventricular tachycardias that require a tailored approach. Noninvasive and invasive methods of risk stratification, such as measurement of heart rate variability and signal-averaged ECG's, as well as electrophysiologic testing, respectively, have enabled us to identify “high risk” patients that may benefit from therapy whether it be antiarrhythmics or implantable defibrillators. Recent and on-going prospective trials such as the CAMIAT, EMIAT, GESICA, MADIT, MUSTT, and CABG-PATCH will hopefully further our knowledge base and make the management of VPCs and nonsustained VT a more uniform process.     

Bradycardia-Induced Polymorphic Ventricular Tachycardia After Atrioventricular Junction Ablation for Sinus Tachycardia-Induced Cardiomyopathy

Bradycardia-Induced Polymorphic VT. In a patient with severe left ventricular dysfunction resulting from chronic nonparoxysmal sinus tachycardia, rate control and improvement in left ventricular function were achieved with atrioventricular junction ablation and ventricular pacemaker implantation. Within 12 hours after the ablation procedure, several episodes of polymorphic ventricular tachycardia that may have been triggered by the abruptly decreased heart rate occurred. Recurrence of polymorphic ventricular tachycardia was prevented by an increase in pacing rate.     

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.     

Management of Ventricular Tachycardia in Heart Failure

Ventricular tachyarrhythmias are common in patients with congestive heart failure. The clinical presentation ranges from an asymptomatic incidental electrocardiographic finding to palpitations, syncope, and sudden cardiac death. Although implantable cardioverter defibrillators successfully prevent sudden cardiac death associated with ventricular fibrillation and ventricular tachycardia, recurrent implantable cardioverter defibrillators shocks remain a clinical management challenge. In this review, we discuss management strategies of ventricular tachycardia in congestive heart failure, including drug therapy, radiofrequency catheter ablation (RFCA), and recent RFCA advances.     

Mode of Onset of Malignant Ventricular Arrhythmias in Idiopathic Ventricular Fibrillation

Mode of Onset of Idiopathic VF. Introduction : The mode of onset of malignant ventricular arrhythmias (ventricular tachycardia [VT] or ventricular fibrillation [VF] has been well described in patients with organic heart disease and in patients with the long QT syndromes. Less is known about the mode of onset of VF in patients with out-of-hospital VF who have no evidence of organic heart disease or identifiable etiology.
Methods and Results : We reviewed the ECGs of all our patients with Idiopathic VF. Documentation of the onset of spontaneous arrhythmias was available for 22 VK episodes in 9 patients (6 men and 3 women; age 41 ± 16 years). In all instances, spontaneous VF followed a rapid polymorphic VT, which was initiated by premature ventricular complexes (PVCs) with very short coupling intervals. The PVC initiating VF had a coupling interval of 302 ± 52 msec and a prematurity index of 0.4 ± 0.07. These PVCs occurred within 40 msec of the peak of the preceding T wave. Pause-dependent arrhythmias were never observed.
Concltision : Cardiac arrest among patients with idiopathic VF has a very distinctive mode of onset. Documentation of a polymorphic VT that is not pause dependent is of diagnostic value.     

Inherited Arrhythmia Syndromes: Applying the Molecular Biology and Genetic to the Clinical Management

Thanks to the contribution of molecular genetics, the genetic bases, the pathogenesis and genotype–phenotype correlation of diseases such as the Long QT syndrome, the Brugada Syndrome, the Progessive cardiac conduction defect (Lenegre disease), the Catecholaminergic Polymorphic Ventricular Tachycardia and Andersen Syndrome have been progressively unveiled and show an extremely high degree of genetic heterogeneity. The evidences supporting this concept are outlined with a particular emphasis on the growing complexity of the molecular pathways that may lead to arrhythmias and sudden death, in term of the relationships between genetic defect(s) and genotype(s) as well as gene-to gene interactions. The current knowledge is reviewed, focusing on the evidence that a single clinical phenotype may be caused by different genetic substrates and, conversely, a single gene may cause very different phenotypes acting through different pathways.