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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Brugada disease, the last clinico-cardiologic entity described in the 20th century, initially called right bundle branch block syndrome with ST segment elevation from V1 to V2 or V3 and sudden cardiac death, is genetically determined in a dominant autosomal mode, and it affects the alpha subunit of the Na+ channel by alteration of chromosome 3 and mutation in the SCN5A gene. In clinical diagnosis the mentioned electrocardiographic pattern in a patient without structural heart disease and positivity in pharmacological tests are considered major criteria. As minor criteria, the following are considered: positive family history, presence of syncope with unknown origin, documented episode of VT/VF, inducibility in electrophysiologic study and positivity of genetic study. The long-standing technology of ECG, with more than a century of existence, remains as the supplementary method with highest value in diagnosis, and currently new electrocardiographic criteria are suggested, which indicate high risk of VF. Natural history indicates a somber diagnosis in symptomatic patients with a high index of arrhythmic SCD secondary to very fast polymorphic ventricular tachycardia bursts, which degenerate into VF. Asymptomatic individuals with only a Brugada-type electrocardiographic pattern have a low risk. The prognosis seems to depend more on clinical facts, since a positive electrophysiologic study has an accuracy of just around 50%. We propose that this entity should be promoted to the category of disease, since it has a characteristic set of signs and symptoms, and an identified genetic defect.
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PMID:Brugada disease: chronology of discovery and paternity. Preliminary observations and historical aspects. 1694 25

Brugada syndrome (BS) is an inherited cardiac disorder characterized by typical electrocardiographic patterns of ST segment elevation in the precordial leads, right bundle branch block, fast polymorphic ventricular tachycardia in patients without any structural heart disease, and a high risk of sudden cardiac death. The incidence of BS is high in male vs. female (i.e., 8-10/1: male/female). The disorder is caused by mutations in the SCN5A gene encoding Nav1.5, the cardiac sodium channel, which is the only gene in which mutations were found to cause the disease. Mutations in SCN5A associated with the BS phenotype usually result in a loss of channel function by a reduction in Na+ currents. We review the clinical aspects, risk stratification, and therapeutic management of this important syndrome.
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PMID:Clinical aspects and physiopathology of Brugada syndrome: review of current concepts. 1711 Oct 25

Brugada syndrome (BS) is an inherited cardiac disorder associated with a high risk of sudden cardiac death and is caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha-subunit (Na(v)1.5). The aim of this study was to identify the genetic cause of familial BS and characterize the electrophysiological properties of a novel SCN5A mutation (W1191X). Four families and one patient with BS were screened for SCN5A mutations by PCR and direct sequencing. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in tsA201 cells, and the sodium currents (I(Na)) were analyzed using the whole-cell patch-clamp technique. A novel mutation, W1191X, was identified in a family with BS. Expression of the WT or the mutant channel (Na(v)1.5/W1191X) co-transfected with the beta(1)-subunit in tsA201 cells resulted in a loss of function of Na(v)1.5 channels. While voltage-clamp recordings of the WT channel showed a distinct acceleration of Na(v)1.5 activation and fast inactivation kinetics, the Na(v)1.5/W1191X mutant failed to generate any currents. Co-expression of the WT channel and the mutant channel resulted in a 50% reduction in I(Na). No effect on activation and inactivation were observed with this heterozygous expression. The W1191X mutation is associated with BS and resulted in the loss of function of the cardiac sodium channel.
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PMID:A novel mutation in the SCN5A gene is associated with Brugada syndrome. 1714 Dec 78

The long QT syndrome type-3 (LQT3) is an inherited cardiac disorder caused by mutations in the sodium channel gene SCN5A. LQT3 has been associated with ventricular arrhythmias and sudden cardiac death, specially at low heart rates. Based on computer simulations and experimental investigations, analysis of the morphology of the Action Potential (AP) has shown that it undergoes early afterdepolarizations (EADs) and spontaneous discharges, which are thought to be the trigger for reentry like-activity. However, dynamic characteristics of cardiac tissue are also important factors of arrhythmia mechanisms. In this work, we propose a dynamical analysis of the LQT3 at cellular level. We use a detailed Markovian model of the DeltaKPQ mutation, which is associated with LQT3, and we study beat-to-beat AP Duration (APD) variations by using a long-term stimulation protocol. Compared to wild-type (WT) cells, DeltaKPQ mutant cells are found to develop APD alternans over a narrow range of stimulation frequencies. Moreover, the interval of frequency dependence of APD alternans is related to the degree of severity of the EADs present in the AP. In conclusion, dynamical analysis of paced cells is a useful approach to understand the mechanisms of rate dependent arrhythmias.
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PMID:Action potential alternans in LQT3 syndrome: a simulation study. 1800 37

The Brugada syndrome is an inherited arrhythmogenic and nonstructural heart disease that may cause syncope and sudden cardiac death (SCD). It is characterized by ST segment elevation in the right precordial leads (V1-V3) and male predominance. Mutation on SCN5A encoding the alpha-subunit of the sodium channel is seen in 20%-30% of patients with the syndrome. Because of low penetrance of gene mutation, clinical manifestations and prognosis can be variable in individuals. Therefore, asymptomatic population with Brugada-type electrocardiogram (ECG) exists in community and SCD risk stratification of the individual can be problematic. Although understanding of the cellular mechanism of the syndrome has advanced, there are conflicting data about its prevalence and prognosis. Population-based genetic epidemiology studies with longer follow-up periods may be able to elucidate clinical outcome of the syndrome, particularly asymptomatic patients.
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PMID:Brugada syndrome and Brugada-type electrocardiogram. 1843 88

A 51-year-old woman presented with an episode of syncope. Upon further review she was found to have a typical Brugada type pattern on her electrocardiogram. She did not have evidence for structural heart disease. At electrophysiological testing she was found to have marked infrahisian conduction disease and had easily inducible polymorphic ventricular tachycardia. She underwent implantation of a dual-chamber implantable cardioverter defibrillator (ICD) and family screening was recommended. Genetic analysis revealed a novel nonsense mutation in the gene encoding for the sodium channel (SCN5A). Five months after ICD implantation the patient had an episode of ventricular fibrillation documented on ICD interrogation. This case is unique as it is consistent with an overlap syndrome, namely both Brugada Syndrome and distal atrioventricular (AV) conduction disease secondary to a novel SCN5A mutation in a young female. This finding highlights the phenotypic heterogeneity of novel SCN5A mutations.
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PMID:Brugada syndrome with marked conduction disease: dual implications of a SCN5A mutation. 1843 84

Brugada syndrome (BrS) is a condition characterized by a distinct ST-segment elevation in the right precordial leads of the electrocardiogram and, clinically, by an increased risk of cardiac arrhythmia and sudden death. The condition predominantly exhibits an autosomal dominant pattern of inheritance with an average prevalence of 5:10,000 worldwide. Currently, more than 100 mutations in seven genes have been associated with BrS. Loss-of-function mutations in SCN5A, which encodes the alpha-subunit of the Na(v)1.5 sodium ion channel conducting the depolarizing I(Na) current, causes 15-20% of BrS cases. A few mutations have been described in GPD1L, which encodes glycerol-3-phosphate dehydrogenase-1 like protein; CACNA1C, which encodes the alpha-subunit of the Ca(v)1.2 ion channel conducting the depolarizing I(L,Ca) current; CACNB2, which encodes the stimulating beta2-subunit of the Ca(v)1.2 ion channel; SCN1B and SCN3B, which, in the heart, encodes beta-subunits of the Na(v)1.5 sodium ion channel, and KCNE3, which encodes the ancillary inhibitory beta-subunit of several potassium channels including the Kv4.3 ion channel conducting the repolarizing potassium I(to) current. BrS exhibits variable expressivity, reduced penetrance, and "mixed phenotypes," where families contain members with BrS as well as long QT syndrome, atrial fibrillation, short QT syndrome, conduction disease, or structural heart disease, have also been described.
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PMID:The genetic basis of Brugada syndrome: a mutation update. 1960 73

The Brugada syndrome is an inherited cardiac disorder initially described in 1992 by Pedro and Josep Brugada, with variable electrocardiographic features characteristic of right bundle-branch block, persistent ST-segment elevation in the precordial leads (VI-V3) at rest and sudden cardiac death. The genetic abnormalities that cause Brugada syndrome have been linked to mutations in the ion channel gene SCN5A which encodes for the alpha-subunit of the cardiac sodium channel. A consensus conference report published in 2002 described the diagnostic criteria for the Brugada syndrome and described the three distinct types of Brugada syndrome. In 2005, a second consensus report was published which described the risk stratification and approaches to therapy. Two specific types of ST-segment elevation, coved and saddleback, are observed in the Brugada syndrome, the former of which is reported to relate to a higher incidence of ventricular tachycardial ventricular fibrillation (VTNF) and sudden cardiac death.The objective of this paper is to review the genetics and the molecular biology behind the Brugada syndrome, the diagnostic criteria, including clinical and electrocardiographic characteristics, and current management.
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PMID:The Brugada syndrome. 2012 57

Brugada syndrome is characterized by the electrocardiographic (ECG) pattern of right bundle-branch block (RBBB) with a high take-off, coved ST-segment elevation in the precordial leads V1 to V3, and the risk of sudden cardiac death. Typically, there is no evidence of structural heart disease. In many cases, Brugada syndrome has been linked to a mutation of the gene SCN5A, which encodes for the fast cardiac sodium channel. In patients with the Brugada syndrome, pharmacologic sodium channel blockade can increase the degree of ST-segment elevation. Interestingly, even in patients with a normal baseline ECG and no clinical suggestion of the Brugada syndrome, toxic doses of class I antiarrhythmic agents as well as toxicities with several nonantiarrhythmic drugs that possess sodium channel blocking properties can induce the Brugada ECG abnormality. Specifically, the beta-receptor blocker propranolol, at high doses, binds to the cardiac sodium channels and inhibits sodium uptake. In this report, we describe a case of severe propranolol toxicity, which resulted in the Brugada ECG pattern in an otherwise healthy individual who had no clinical or ECG suggestion of the genetically determined Brugada syndrome.
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PMID:Brugada-pattern electrocardiogram in propranolol intoxication. 2015 10

Brugada syndrome is an inherited cardiac disorder associated with a specific electrocardiographic pattern, involving ST segment elevation in leads V1 to V3. When not spontaneously terminated, it can lead to ventricular fibrillation and sudden death. We present a case report of a young male whose brother suffered a sudden cardiac arrest while playing soccer. A novel mutation c.2678G>A was detected on the gene SCN5A through molecular diagnosis. The mutation was shown to be present in the individual, his daughter and his other brother. For patients with previous ventricular fibrillation and/or syncope, implantable cardiac device (ICD) is recommended. However, how can patients without symptoms but with a clear diagnosis prevent cardiac arrest?
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PMID:What can be done when asymptomatic patients discover they have Brugada syndrome? A case report of Brugada syndrome. 2038 Nov 79


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