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.     

iPSCs在心律失常疾病体外模型方面的研究进展

心律失常严重威胁人类健康,许多遗传性心律失常由基因突变引起。以患者的诱导型多能干细胞（iPSCs）源性的心肌细胞作为体外模型,可为研究心律失常的发病机制提供新的思路。本文主要对iPSCs源性诱导型心肌细胞的产生过程以及心律失常患者诱导iPSCs 心肌细胞在长QT综合征、儿茶酚胺依赖性室性心动过速、致心律失常性右室心肌病等疾病模型的研究进展进行了综述。     

Evaluation of suspected right ventricular pathology in the athlete

Rigorous training remodels the heart of elite endurance athletes to produce the phenotype of the "athlete's heart." This remodeling, which advantages cardiac performance, creates challenges in the diagnosis of cardiac disorders within this population. This is particularly so for right ventricular pathologies because of the limited number of studies documenting the impact of training on right ventricular remodeling. Although arrhythmogenic right ventricular cardiomyopathy is the focus of this review, several other pathologies that may mimic arrhythmogenic right ventricular cardiomyopathy, including right ventricular outflow tract tachycardia, Wolff-Parkinson-White syndrome, Brugada syndrome, pulmonary embolism, cardiac sarcoidosis, myocarditis, and right ventricular infarction, are also included. In particular, the electrocardiographic findings for each condition are highlighted because this is the most informative and easily accessible diagnostic clinical tool.     

Histologic abnormalities of the left ventricle in a patient with arrhythmogenic right ventricular dysplasia

Summary Right ventricular histologic abnormalities have been described in association with arrhythmogenic right ventricular dysplasia, but the cause of the disease is unknown. Identical abnormalities were noted in endomyocardial biopsy specimens from the right and left ventricles of a 20-year-old male patient with the clinical syndrome of arrhythmogenic right ventricular dysplasia. Left ventricular function was normal at rest and during bicycle exercise. Eighteen months previously, he had shown clinical and serologic evidence of mycoplasmal myocarditis. Arrhythmogenic right ventricular dysplasia may represent predominant involvement of the right ventricle in a generalized cardiomyopathic process, possibly as a consequence of healed myocarditis.     

PRKAG2 cardiac syndrome: familial ventricular preexcitation,conduction system disease,and cardiac hypertrophy

Genetic studies of families with inherited cardiac rhythm disturbances have established a molecular basis for ventricular arrhythmogenic disorders. Genes responsible for the long QT syndrome, Brugada syndrome, and polymorphic ventricular tachycardia have been identified. The elucidation of genetic defects responsible for more commonly occurring supraventricular rhythm disturbances have not been as forthcoming, with the exception of SCN5A mutations known to cause conduction system disease. Recently, we identified the genetic cause of a familial arrhythmogenic syndrome characterized by ventricular preexcitation and tachyarrhythmias (Wolff-Parkinson-White syndrome), progressive conduction system disease, and cardiac hypertrophy. The causative gene was shown to be the gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase. The role of AMP-activated protein kinase in the regulation of the glucose metabolic pathway in muscle suggests that genetic defects in PRKAG2 may induce a previously undescribed cardiac glycogenosis syndrome.     

Videoscopic Left Cardiac Sympathetic Denervation for Patients With Recurrent Ventricular Fibrillation/Malignant Ventricular Arrhythmia Syndromes Besides Congenital Long-QT Syndrome

Background- Treatment options for patients with recurrent ventricular arrhythmias refractory to pharmacotherapy and ablation are minimal. Although left cardiac sympathetic denervation (LCSD) is well established in long-QT syndrome, its role in non-long-QT syndrome arrhythmogenic channelopathies and cardiomyopathies is less clear. Here, we report our single-center experience in performing LCSD in this setting. Methods and Results- In this institutional review board-approved study, we retrospectively reviewed the electronic medical records of all patients (N=91) who had videoscopic LCSD at our institution from 2005 to 2011. Data were analyzed for the subset (n=27) who were denervated for an underlying diagnosis other than autosomal dominant or sporadic long-QT syndrome. The spectrum of arrhythmogenic disease included catecholaminergic polymorphic ventricular tachycardia (n=13), Jervell and Lange-Nielsen syndrome (n=5), idiopathic ventricular fibrillation (n=4), left ventricular noncompaction (n=2), hypertrophic cardiomyopathy (n=1), ischemic cardiomyopathy (n=1), and arrhythmogenic right ventricular cardiomyopathy (n=1). Five patients had LCSD because of high-risk assessment and β-blocker intolerance, none of whom had a sentinel breakthrough cardiac event at early follow-up. Among the remaining 22 previously symptomatic patients who had LCSD as secondary prevention, all had an attenuation in cardiac events, with 18 having no breakthrough cardiac events so far and 4 having experienced ≥1 post-LCSD breakthrough cardiac event. Conclusions- LCSD may represent a substrate-independent antifibrillatory treatment option for patients with life-threatening ventricular arrhythmia syndromes other than long-QT syndrome. The early follow-up seems promising, with a marked reduction in the frequency of cardiac events postdenervation.     

Die Katheterablation als Notfalleingriff bei Intensivpatienten mit Rhythmusstörungen

Rescue ablation of tachyarrhythmias in intensive care medicine is not often indicated since antiarrhythmic drugs can often stabilize these serious conditions. However, in resuscitated patients with WPW syndrome, accessory pathway ablation is the therapy of first choice. Substrate mapping and ablation or modification in unmappable ventricular tachycardias with either incessant character or electrical storm in patients with ischemic cardiomyopathy is a bailout therapy with rather good results. Primary idiopathic ventricular fibrillation is rare but can be eliminated by focal ablation energy delivery within the distal Purkinje system.     

Noninvasive recognition of the parchment right ventricle (Uhl's anomaly arrhythmogenic right ventricular dysplasia) syndrome

The case of a 53-year-old man with right heart failure, selective enlargement of the right-sided cardiac chambers, and recurrent sustained ventricular tachycardia is presented. Echocardiographic, radionuclide ventriculographic, and angiographic studies were typical of the right ventricular abnormalities in Uhl's anomaly; electrocardiographic and electrophysiologic findings were those of arrhythmogenic right ventricular dysplasia. Features of this unusual cause of cardiac failure and ventricular arrhythmias in the adult are reviewed, and compared to previous reports of both Uhl's anomaly and arrhythmogenic right ventricular dysplasia. We postulate that these two syndromes are manifestations of a single, presumably congenital, pathophysiologic process—the “parchment right ventricle” syndrome.     

Is there an overlap between Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia?

The Brugada syndrome is a congenital syndrome displaying an autosomal dominant mode of transmission in patients with a structurally normal heart. The disease has been linked to mutations in SCN5A , a gene located on the short arm of chromosome 3 (p21-24) that encodes for the alpha subunit of the sodium channel. The syndrome is characterized by a dynamic ST-segment elevation (accentuated J wave) in leads V 1 to V 3 of the ECG followed by negative T wave. Right bundle-branch block of varying degrees is observed in some patients. The syndrome is associated with syncope and a relatively high incidence of sudden cardiac death secondary to the development of polymorphic ventricular tachycardia that may degenerate into ventricular fibrillation. An acquired form of the Brugada syndrome is also recognized, caused by a wide variety of drugs and conditions that alter the balance of currents active during the early phases of the action potential. Among patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia, there is a subpopulation with a clinical and electrocardiographic pattern similar to that of the Brugada syndrome. These cases of arrhythmogenic right ventricular cardiomyopathy/dysplasia are thought to represent an early or concealed form of the disease. This review examines the overlap between these 2 syndromes.     

Arrhythmogenic right ventricular cardiomyopathy with left ventricular involvement mimicking acute coronary syndrome - two case reports

We describe 2 patients with arrhythmogenic right ventricular cardiomyopathy (ARVD): 58 year-old female and 48 year-old man. Both patients presented with echocardiographic features typical for ARVD and impaired systolic left ventricular function. Both patients had symptoms resembling acute coronary syndrome and received cardioverter-defibrillator due to recurrent sustained ventricular tachycardia.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Brugada syndrome or ARVD (arrhythmogenic right ventricular dysplasia) or both? Significance and value of right precordial ECG changes

We report about a 20-year old patient suffering cardiopulmonary resuscitation due to ventricular fibrillation. We diagnosed Brugada syndrome after exclusion structural heart disease and a positive Ajmalin test and implanted an ICD. In that there is a 20-30% familiar disposition, it was necessary that all family members undergo a cardiac examination. It was found that one brother and one sister presented the beginning of a right ventricular dilatation and a fibrolipomatous area in the anterior wall segment of the right ventricle. This result is compatible with a "concealed" arrhythmogenic right ventricular dysplasia (ARVD). As a prognostic indication we decided to implant an ICD prophylactically. The case report demonstrates the value of familiar examination of patients with an unclear ventricular arrhythmogenic event.     

Atrial involvement in arrhythmogenic right ventricular dysplasia: primary or secondary? Description of a case of occult ventricular dysplasia with right atrial enlargement and exclusively sinoatrial arrhythmia

The atrial involvement in patients with arrhythmogenic right ventricular dysplasia is very rarely described. We here describe a patient with right atrial enlargement suffering from classical sinus and atrial electrical disease (tachycardia-bradycardia syndrome); the associated echo-angiographic aspects of the right ventricle are compatible, even in the absence of ventricular tachyarrhythmias, with a concealed form of right ventricular dysplasia. A common pathogenetic mechanism for the atrial and ventricular involvement is hypothetically considered.     

Genetic testing in the management of inherited arrhythmia syndromes

Although the first gene responsible for long QT syndrome was described more than a decade ago, only now has the genetic testing become readily available to clinicians treating patients with inherited arrhythmia syndromes. Recognition of these syndromes, including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular cardiomyopathy, is important for both internists and cardiologists. The potential for malignant ventricular arrhythmias and sudden cardiac death makes integration of clinical and genetic information critical for managing these patients. Although the presence of variable penetrance and genotype-phenotype correlations can limit the effectiveness of widespread genetic screening, directed genetic testing can be very helpful in confirming diagnosis, delineating prognosis, and identifying high-risk individuals.     

16. Folge: Ventrikuläre Elektrodenlage

This case illustrates how the ventricular lead position can be defined exactly if different fluoroscopic views and a 12 lead ECG are available.     

急性心脏事件体表心电图预警

心脏性猝死(SCD)严重威胁人类的健康,体表心电图的某些改变可对SCD危险因素进行分层和预测。这些改变包括室性早搏、室性心动过速、心室颤动或心室扑动、电风暴(ES)、极速心房颤动(AF)、病态窦房结综合征(SSS)、急性ST段偏移、急性缺血性J波、ST-T动态演变、坏死性Q波突然消退、特征性T波、恶性早期复极综合征及Brugada波。Epsilon波提示致心律失常性右心室发育不良。窄而深的Q波警示年轻人肥厚型梗阻性心肌病。     

Molecular genetics of cardiac arrhythmias

INTRODUCTION: Recent progress in molecular biology led to the identification of the genes involved in various cardiac arrhythmias causing syncope and sudden death in young people. EXEGESIS: This article briefly describes the clinical features and the genes associated with the congenital long QT syndrome, the short QT syndrome, Brugada's syndrome, catecholaminergic polymorphic ventricular tachycardias and arrhythmogenic right ventricular dysplasia. CONCLUSION: Identification of genetic variations that cause cardiac tachyarrhythmias can help to identify at risk-patients and to propose clinical follow-up and preventive therapy. Further studies are needed to discover other cardiac genetic disorders and to understand cellular mechanisms involved in these diseases.     

Tako-Tsubo-Kardiomyopathie: Differentialdiagnose des akuten Koronarsyndroms

We report on a 71-year-old female, who was admitted to the emergency department because of acute chest pain. Due to similar symptoms the previous day an acute coronary syndrome had been ruled out non-invasively by ECG and laboratory tests. Acute physical or emotional stressful events were negated by the patient. The ECG showed newly diagnosed inverted T waves in the precordial leads. The lab showed a minimal release of myocardial enzymes and proteins. Echocardiographically apical hypokinesia was observed. Coronary angiography revealed no significant occlusion and showed left ventricular apical ballooning. Due to the symptoms resembling acute myocardial infarction, the absence of obstructive coronary disease and the typical left ventricular apical ballooning we assume that the patient had Tako-Tsubo cardiomyopathy.     

Left dominant arrhythmogenic cardiomyopathy: A morbid association of ventricular arrhythmias and unexplained infero-lateral T-wave inversion

Left-dominant arrhythmogenic cardiomyopathy is a subtype of arrhythmogenic right ventricular cardiomyopathy characterized by early predominant left ventricular involvement. Α 34-year-old man presented with palpitations and a history of frequent ventricular extrasystoles of both LBBB and RBBB configuration. Cardiac workup revealed repolarization abnormalities at infero-lateral leads in the absence of diagnostic structural/functional alterations or obstructive coronary artery disease. Six months later he died suddenly. Histopathology was diagnostic for arrhythmogenic right ventricular cardiomyopathy affecting predominantly the left ventricle at subepicardial/midwall myocardial layers. Thus, ventricular arrhythmias accompanied by unexplained infero-lateral T-wave inversion should warn of a possible morbid association underlying left-dominant arrhythmogenic cardiomyopathy.     

The right ventricular outflow tract in patients with suspected arrhythmogenic right ventricular cardiomyopathy referred for cardiac magnetic resonance imaging.

OBJECTIVES: To determine if right ventricular outflow tract dilatation occurs in patients with a clinical suspicion of arrhythmogenic right ventricular dysplasia. METHODS: Fifty patients referred to us with a clinical suspicion of arrhythmogenic right ventricular dysplasia underwent cardiac magnetic resonance imaging. The area of the right ventricular outflow tract was estimated in 29 patients. RESULTS: Out of the 29 subjects, eight had cardiac magnetic resonance findings suggestive of arrhythmogenic right ventricular dysplasia. The mean area of the right ventricular outflow tract in these eight patients was significantly larger compared to normal controls without cardiac pathology. CONCLUSION: The right ventricular outflow tract was enlarged in patients with cardiac magnetic resonance findings suggestive of arrhythmogenic right ventricular dysplasia. Routine assessment of this parameter should be considered in cardiac magnetic resonance imaging studies.