Peculiaridade dos pacientes com arritmias hereditárias na pandemia pela COVID-19 / Peculiar aspects of patients with Inherited arrhythmias during the COVID-19 pandemic

Resumo Desde dezembro de 2019, observamos o rápido avanço da síndrome respiratória aguda grave causada pelo coronavírus 2019 (SARS-CoV-2). O impacto da evolução clínica de uma infecção respiratória é pouco conhecido em pacientes portadores de arritmias hereditárias, devido à baixa prevalência dessas doenças. Os pacientes que apresentam quadros infecciosos podem exacerbar arritmias primárias ocultas ou bem controladas, por diversos fatores, tais como febre, distúrbios eletrolíticos, interações medicamentosas, estresse adrenérgico e, eventualmente, o próprio dano miocárdico do paciente séptico. O objetivo desta revisão é destacar os principais desafios que podemos encontrar durante a pandemia pela Covid 19, especificamente nos pacientes com arritmias hereditárias, com destaque para a síndrome do QT longo congênito (SQTL), a síndrome de Brugada (SBr), a taquicardia ventricular polimórfica catecolaminérgica (TVPC) e a cardiomiopatia arritmogênica do ventrículo direito.

Abstract Since December 2019 we have observed the rapid advance of the severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2). The impact of the clinical course of a respiratory infection is little known in patients with hereditary arrhythmias, due to the low prevalence of these diseases. Patients who present with infectious conditions may exacerbate hidden or well-controlled primary arrhythmias, due to several factors, such as fever, electrolyte disturbances, drug interactions, adrenergic stress and, eventually, the septic patient's own myocardial damage. The aim of this review is to highlight the main challenges we may encounter during the Covid 19 pandemic, specifically in patients with hereditary arrhythmias, with emphasis on the congenital long QT syndrome (LQTS), Brugada syndrome (SBr), ventricular tachycardia polymorphic catecholaminergic (CPVT) and arrhythmogenic right ventricular cardiomyopathy.

TECRL gene in catecholaminergic polymorphic ventricular tachycardia / 国际儿科学杂志

Catecholaminergic polymorphic ventricular tachycardia(CPVT)is a highly fatal inherited arrhythmia induced by emotional stress or exercise.It can be triggered by rapid polymorphism of ventricular tachycardia and ventricular fibrillation, and may lead to syncope or sudden death, with a poor prognosis.Genetic testing is one way to diagnose the disease.It has been found that the disease is related to abnormalities of RyR2, CASQ2, TECRL and other genes, whose mutations affect calcium homeostasis and lead to abnormal electrophysiological activity of the heart, leading to delayed depolar(DADs), and subsequently to malignant arrhythmia.This paper reviewes the mutation of the new pathogenic gene TECRL gene in catecholamine sensitive ventricular tachycardia, through the understanding and learning of the mutation gene reported in the previous literature, in order to further explore the pathogenesis of the disease, learn to deal with the occurrence of malignant arrhythmia, and promote the clinical precise treatment of the disease.

Ryanodine receptor 2 mutation: Not only catecholaminergic polymorphic ventricular tachycardia but also epileptiform discharges in electroencephalogram

@#Ca2+ leak via ryanodine receptor type 2 (RyR2) can cause potentially fatal arrhythmias, and RyR2 mutations have been shown in the aetiology of catecholaminergic polymorphic ventricular tachycardia. We report the case of a patient with catecholaminergic polymorphic ventricular tachycardia resulting from a RYR2 mutation who had not only typical electroencephalogram changes, but also epileptiform discharges in electroencephalogram. We believe the changes were closely related to the RYR2 mutation.

Basic and clinical insights in catecholaminergic (familial) polymorphic ventricular tachycardia

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

Genes related to catecholaminergic polymorphic ventricular tachycardia / 国际儿科学杂志

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a kind of common hereditary arrhythmia syndrome in adolescents.Its core is arrhythmia induced by adrenaline,and the root underlying cause of the arrhythmia is rapid ventricular tachycardia (bidirectional or polymorphic).The CPVT patient often has no obvious clinical manifestations,and almost normal in examinations,which may lead to missed diagnosis and misdiagnosis.Gene detection may be a classical and reliable diagnostic method.It has been found that mutation genes related to CPVT include Ryanodine receptor 2,Calsequestrin 2,and their mutations affect calcium homeostasis,causing electrophysiological abnormalities of cardiomyocytes,overloading calcium ions in cardiomyocytes,leading to the delayed depolarization of cardiomyocytes and further induction of ventricular arrhythmias.In this review,we summarize the mutations of ryanodine receptor 2,calsequestrin 2 and other possible genes related to CPVT,which is helpful for clinical precise treatment and exploration of the molecular mechanism of CPVT.

Thoracoscopic Left Cardiac Sympathetic Denervation for a Patient with Catecholaminergic Polymorphic Ventricular Tachycardia and Recurrent Implantable Cardioverter-Defibrillator Shocks

A patient presented with loss of consciousness and conversion. During an exercise test, catecholaminergic polymorphic ventricular tachycardia (CPVT) resulted in cardiac arrest. He started taking medication (a beta-blocker and flecainide) and an implantable cardioverter defibrillator (ICD) was inserted, but the ventricular tachycardia did not resolve. Left cardiac sympathetic denervation (LCSD) was then performed under general anesthesia, and the patient was discharged on the second postoperative day without complications. One month after the operation, no shock had been administered by the ICD, and an exercise stress test did not induce ventricular tachycardia. Although beta-blockers are the gold standard of therapy in patients with CPVT, thoracoscopic LCSD is safe and can be an effective alternative treatment option for patients with intractable CPVT.

Muerte súbita cardiaca en el corazón estructuralmente normal: una actualización / Sudden cardiac death in individuals with normal hearts: an update

La muerte súbita (MS) es un evento trágico que representa un grave problema de salud. Se estima que causa cerca de 4-5 millones de decesos por año en todo el mundo. La MS se define como la muerte ocurrida en el lapso de 1 h en una persona sin signos previos de fatalidad; puede denominarse «recuperada¼, cuando el paciente afectado sobrevive al episodio potencialmente fatal ya sea por reanimación cardiopulmonar o desfibrilación efectiva. Las canalopatías arritmogénicas son alteraciones funcionales de los canales iónicos del corazón, generalmente condicionados por mutaciones en los genes que los codifican y dan lugar a diversos tipos de arritmias que pueden culminar en MS, el deceso ocurre normalmente antes de los 40 años y el corazón en estudio de autopsia suele ser estructuralmente normal. En la presente revisión presentamos las principales causas de MS en el contexto del corazón estructuralmente normal y discutimos el abordaje que se debe dar a los pacientes y familiares de víctimas que han experimentado éste trágico evento.

Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1 h after the onset of symptoms in a person without previous signs of fatality. It can be named «recovered SD¼ when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event.

Taquicardia ventricular polimórfica catecolaminérgica / Catecholaminergic polymorphic ventricular tachycardia

La taquicardia ventricular polimórfica catecolaminérgica es una canalopatía caracterizada por la inducción de arritmias ventriculares polimórficas en presencia de catecolaminas. Deberá sospecharse en todo paciente joven, en especial niño o adolescente, que presente síncopes relacionados con el ejercicio físico o el estrés emocional, que no tenga cardiopatía estructural y que su electrocardiograma muestre un intervalo QT normal. Es poco frecuente, pero importante por el riesgo elevado de muerte súbita, que en ocasiones puede ser el debut. Las arritmias ventriculares son polimórficas o bidireccionales, fácilmente inducibles con el ejercicio físico y con infusión de isuprel, tienen un umbral predecible y una complejidad progresiva. Los antecedentes patológicos familiares de muerte súbita se observan entre el 30 y 40 pociento de los pacientes. Se han identificado 2 mutaciones genéticas causantes de la entidad (receptores de rianodina 2, con herencia autosómica dominante y calsecuestrina 2, con herencia autosómica reseciva); pero solo entre 50-55 porciento de los enfermos se ha testado una mutación causal. Las mutaciones condicionan la fuga de Ca2+ del retículo sarcoplásmico que favorece el origen de posdespolarizaciones tardías, las que inducirán la actividad ectópica ventricular. Los Ô-bloqueadores son el tratamiento de elección. El desfibrilador automático implantable está indicado en los pacientes recuperados de un evento de muerte súbita y en los sintomáticos a pesar del tratamiento farmacológico. La denervación simpática cardíaca izquierda, el verapamilo, la flecainida y la propafenona, son opciones alternativas en los sintomáticos a pesar del uso de β-bloqueadores

Catecholaminergic polymorphic ventricular tachycardia is a channelopathy characterized by the induction of polymorphic ventricular arrhythmias in the presence of catecholamines. It should be suspected in any young patient, especially a child or adolescent, presenting with syncope associated with physical exercise or emotional stress, with no structural heart disease and an ECG showing a normal QT interval. It is a rare disease, its importance lying in the high risk of sudden death, which may sometimes be its debut. Ventricular arrhythmias may be polymorphic or bidirectional. They are highly inducible by physical exercise and Isuprel infusion, their threshold is predictable and their complexity progressive. A family history of sudden death is reported in 30 to 40 percent of patients. Two genetic mutations have been identified as causes of the condition (ryanodine receptor 2 with autosomal dominant inheritance and calsequestrin 2, with autosomal recessive inheritance). However, a causal mutation has been found in only 50-55 percent of patients. Mutations influence sarcoplasmic reticulum Ca 2+ leak, facilitating the appearance of late post-depolarisations, which will in turn induce ventricular ectopic activity. Beta-blockers are the treatment of choice. The automatic implantable defibrillator is indicated in patients recovered from a sudden death event and in those who remain symptomatic despite medical therapy. Left cardiac sympathetic denervation, verapamil, flecainide and propafenone are alternative options for patients who remain symptomatic despite the use of beta-blockers

Catecholaminergic Polymorphic Ventricular Tachycardia in Children

PURPOSE: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is the disease entity of adrenergic dependent, potentially lethal tachyarrhythmia in a child with no structural heart disease, which manifest itself as a syncope or sudden death. The objective of this study is to present our experiences on this important, although rare, disease. METHODS: Retrospective analysis of 5 patients with episodes of syncope related to exercise, who were referred to our hospital from January 1985 to December 1998. RESULTS: All patients were male and the mean age at the time of the first syncopal episode was 5.1+/-3.2 years (range 1.3 to 10 years). There were no structural cardiac abnormalities in clinical and laboratory evaluations. In all, polymorphic ventricular tachycardia showing the characteristic pattern of CPVT in which, as the heart became stimulated adrenergically, isolated ventricular premature beats appeared, increased with rate, became polymorphic, finally formed burst with bidirectional salvoes and disappeared in resting state was induced during exercise test and/or isoproterenol infusion test. During the mean follow up period of 3.75+/-3.1 years (range 1 month to 7.3 years), one died suddenly. In this case, low dose of beta-blocker was administered because of associated sinus bradycardia resulting in incomplete control of the syncopal episodes. The other 4 cases were alive and asymptomatic by means of adequate modification of beta-blocker dosage and method of administration. CONCLUSIONS: This study emphasizes that CPVT is an important, although rare, cause of exercise related syncope in children and can be diagnosed by means of exercise test and/or isoproterenol infusion. beta-blockers were very effective in all cases, even though increasing amount of beta-blocker was frequently necessary to control ventricular arrhythmia in some cases.