scholarly journals Brugada Syndrome: Current Practices in Diagnosis, Prognosis, and Treatment

2017 ◽  
Vol 9 ◽  
Author(s):  
Muhammad Ali
Keyword(s):  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Loss Of Function ◽  
Bundle Branch Block ◽  
Effective Measure ◽  
Cardiac Sodium Channel ◽  
Class Iib ◽  
Current Practices

<p>Brugada syndrome (BrS) is a hereditable syndrome, first reported in 1992, characterized by right bundle branch block and an uncommon form of ST-T wave elevation in the V1 and V2 leads and associated with risk of sudden cardiac death (SCD) arising from polymorphic ventricular tachyarrhythmias. BrS is an autosomal dominant inherited condition; however, more than 50% of BrS cases may be sporadic. Approximately 20% to 25% of BrS cases originate from loss of function mutations in the SCN5A cardiac sodium channel.</p><p>The diagnosis of BrS is mainly based on electrocardiogram. SCD due to ventricular fibrillation can be the first clinical presentation of BrS. The insertion of an implantable cardioverter-defibrillator remains the only approved effective measure to prevent SCD in BrS patients. Risk stratification in BrS is still challenging. Because the role of electrophysiological study (EPS) for estimating prognosis in BrS patients has been controversial, but the expert consensus published in 2013 (Priori et al, 2013) considered the performance of EPS, class IIb. Future randomized studies focused on risk stratification and the value of radiofrequency ablation in BrS patients are needed.</p><p>This review provides a succinct general overview of BrS focusing on<strong> </strong>current practices in diagnosis, prognosis, and treatment.</p>

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

Clinical characteristics and long-term clinical course of patients with Brugada syndrome without previous cardiac arrest: a multiparametric risk stratification approach

EP Europace ◽  
2019 ◽  
Author(s):  
Konstantinos P Letsas ◽  
George Bazoukis ◽  
Michael Efremidis ◽  
Stamatis Georgopoulos ◽  
Panagiotis Korantzopoulos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Clinical Characteristics ◽  
Clinical Course ◽  
Electrophysiological Study ◽  
Rank Test ◽  
History Of ◽  
Event Rates

Abstract Aims Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS. Methods and results A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0–1 risk factor, 2–3 risk factors, and 4–5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients. Conclusions Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone.

Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: A prospective study

Heart Rhythm ◽  
2009 ◽  
Vol 6 (8) ◽  
pp. 1156-1162 ◽  
Author(s):  
Zhengrong Huang ◽  
Chinmay Patel ◽  
Weihua Li ◽  
Qiang Xie ◽  
Rong Wu ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Prospective Study ◽  
Brugada Syndrome ◽  
A Prospective Study

P95412 lead Holter monitoring in Brugada syndrome

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
P Carvalho ◽  
C Gravinese ◽  
A Previti ◽  
G P Varalda ◽  
L Montagna
Keyword(s):  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Right Ventricular Outflow Tract ◽  
Holter Monitoring ◽  
The Other ◽  
Drug Induced ◽  
Premature Ventricular Contractions ◽  
Bundle Branch Block ◽  
The Right

Abstract Background 12 lead-Holter monitoring is commonly used for the assessment  of type 1 Brugada repolarization"s burden. However, data considering the prevalence and morphology of premature ventricular contractions (PVC) in these patients is lacking. Purpose. We investigated the prevalence of PVCs in subjects with Brugada syndrome (BRs) phenotype during 24-hour 12 lead-Holter monitoring (12-L Holter), trying to identify their origin according to morphology.  Methods. From January 2013 to September 2018, a total of 156 patients with type 1 BRs phenotype (spontaneous or drug induced) were screened for PVCs. In these patients we placed the right precordial leads at the second (V1-V2) and the forth (V3-V4) intercostal spaces.  Results. 83 subjects (53%) displayed PVCs. Their mean age was 50 years (range 21-73) and 63 (76%) were male. 14 subjects (17%) had a spontaneous type 1 repolarization whereas 69 (83%) presented a drug induced type 1. One patient had implanted an ICD as secondary prevention after an aborted sudden cardiac death. The others were mostly asymptomatic as only five of them (6%) had history of suspected cardiac syncope. 17 subjects (20%) had performed an electrophysiological study, which resulted positive in 3 cases (4%). The population without PVCs had similar baseline characteristics. In 59 (71%) patients PVCs were monomorphic, in the other 29% we analyzed the prevalent morphology. PVCs were classified according to their morphology as follows (i) left bundle branch block (LBBB)/inferior axis suggesting an origin from the right ventricular outflow tract (RVOT), that was shown in 40 (48%) subjects; (ii) right bundle branch block (RBBB)/left axis suggesting an origin close to the posterior fascicle of the left bundle branch in 36 (43%). The other 7 patients presented several morphologies. According to their number during the 24-hour monitoring, PVCs were arbitrarily classified as follows: (i) 1-59,present in 62 patients (75%); (ii) 60-749, present in 16 patients (19%); (iii) 750-9000, present in 4 patients (5%); (iv) &gt;9000, in only one patient (1%).  Conclusions. In our population of subjects with BRs phenotype the prevalence of PCVs is similar to that of the general population. Their morphologies suggest an origin from the RVOT or close to the posterior fascicle of the left bundle branch.

scholarly journals P1594Risk stratification in Brugada syndrome: The role of electrophysiological study

EP Europace ◽  
2017 ◽  
Vol 19 (suppl_3) ◽  
pp. iii340-iii340
Author(s):  
I. Silveira ◽  
C. Roque ◽  
R. B Santos ◽  
MJ. Sousa ◽  
M. Trepa ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Electrophysiological Study

Clinical aspects and physiopathology of Brugada syndrome: review of current concepts

2006 ◽  
Vol 84 (8-9) ◽  
pp. 795-802 ◽  
Author(s):  
E. Herbert ◽  
M. Chahine
Keyword(s):  
Brugada Syndrome ◽  
Structural Heart Disease ◽  
Polymorphic Ventricular Tachycardia ◽  
Clinical Aspects ◽  
Gene Encoding ◽  
Bundle Branch Block ◽  
St Segment Elevation ◽  
Disease Mutations ◽  
St Segment ◽  
Cardiac Sodium Channel

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.

scholarly journals Brugada syndrome masked by complete left bundle branch block. A clinical and functional study of its association with the p.1449Y>H SCN5A variant.

2021 ◽  
Author(s):  
Eduardo Arana-Rueda ◽  
Rosa Pezzotti ◽  
Alonso Pedrote ◽  
Juan Acosta ◽  
Manuel Frutos-López ◽  
...  
Keyword(s):  
Left Bundle Branch Block ◽  
Brugada Syndrome ◽  
Functional Study ◽  
Loss Of Function ◽  
Bundle Branch Block ◽  
Conduction Disturbances ◽  
Disease Penetrance ◽  
Functional Consequences ◽  
Patch Clamp Electrophysiology ◽  
Scn5a Gene

SCN5A gene variants are associated with both Brugada syndrome and conduction disturbances, sometimes expressing an overlapping phenotype. Functional consequences of SCN5A variants assessed by patch clamp electrophysiology are particularly beneficial for a correct pathogenic classification and are related to disease penetrance and severity. Here, we identify a novel SCN5A loss of function variant, p.1449Y>H, which presented with high penetrance and complete left bundle branch block, totally masking the typical findings on the electrocardiogram. We highlight the possibility of this overlap combination that makes impossible an electrocardiographic diagnosis and, through a functional analysis, associate the p.1449Y>H variant to SCN5A pathogenicity.

scholarly journals Targeting the Microtubule EB1-CLASP2 Complex Modulates Na V 1.5 at Intercalated Discs

2021 ◽  
Author(s):  
Gerard A Marchal ◽  
Mariam Jouni ◽  
David Y Chiang ◽  
Marta Pérez-Hernández Duran ◽  
Svitlana Podliesna ◽  
...  
Keyword(s):  
Sodium Current ◽  
Induced Pluripotent Stem Cell ◽  
Loss Of Function ◽  
Whole Cell ◽  
Intercalated Discs ◽  
Cardiac Sodium Channel ◽  
Optical Reconstruction ◽  
Induced Pluripotent ◽  
And Function

Rationale: Loss-of-function of the cardiac sodium channel Na V 1.5 causes conduction slowing and arrhythmias. Na V 1.5 is differentially distributed within subcellular domains of cardiomyocytes, with sodium current (I Na ) being enriched at the intercalated discs (ID). Various pathophysiological conditions associated with lethal arrhythmias display ID-specific I Na reduction, but the mechanisms underlying microdomain-specific targeting of Na V 1.5 remain largely unknown. Objective: To investigate the role of the microtubule (MT) plus-end tracking proteins end binding protein 1 (EB1) and CLIP-associated protein 2 (CLASP2) in mediating Na V 1.5 trafficking and subcellular distribution in cardiomyocytes. Methods and Results: EB1 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) resulted in enhanced whole-cell I Na , increased action potential (AP) upstroke velocity (V max ), and enhanced Na V 1.5 localization at the plasma membrane as detected by multi-color stochastic optical reconstruction microscopy (STORM). Fluorescence recovery after photobleaching (FRAP) experiments in HEK293A cells demonstrated that EB1 overexpression promoted Na V 1.5 forward trafficking. Knockout of MAPRE1 in hiPSC-CMs led to reduced whole-cell I Na , decreased V max and AP duration (APD) prolongation. Similarly, acute knockout of the MAPRE1 homolog in zebrafish (mapre1b) resulted in decreased ventricular conduction velocity and V max as well as increased APD. STORM imaging and macropatch I Na measurements showed that subacute treatment (2-3 hours) with SB216763 (SB2), a GSK3β inhibitor known to modulate CLASP2-EB1 interaction, reduced GSK3β localization and increased Na V 1.5 and I Na preferentially at the ID region of wild type murine ventricular cardiomyocytes. By contrast, SB2 did not affect whole cell I Na or Na V 1.5 localization in cardiomyocytes from Clasp2-deficient mice, uncovering the crucial role of CLASP2 in SB2-mediated modulation of NaV1.5 at the ID. Conclusions: Our findings demonstrate the modulatory effect of the MT plus-end tracking protein EB1 on Na V 1.5 trafficking and function, and identify the EB1-CLASP2 complex as a target for preferential modulation of I Na within the ID region of cardiomyocytes.

Genome-wide association study identifies 18 new susceptibility variants loci associated with Brugada Syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Barc ◽  
R Trados ◽  
C Glinge ◽  
F Simonet ◽  
D Chiang ◽  
...  
Keyword(s):  
Association Study ◽  
Brugada Syndrome ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Public Institution ◽  
Genome Wide Association ◽  
Funding Source ◽  
Genome Wide ◽  
Cardiac Sodium Channel

Abstract   The Brugada Syndrome (BrS) is characterized by ST-segment elevation in the right precordial leads and is associated with an increased risk of sudden cardiac death. The disorder was initially described as a monogenic primary cardiac electrical disease. However, mutations in SCN5A, encoding the cardiac sodium channel (NaV1.5), which is the major gene associated with the disorder are found in only around 20% of cases and are associated with low penetrance. Furthermore many cases did not display familial aggregation. Based on a previous GWAS conducted on 312 BrS patients and the discovery of the unexpected strong effect of 3 common variants, we proposed that the BrS may comprise a more complex inheritance model. We conducted a genome-wide association study on 2820 individuals with BrS and 10001 ancestry-matched controls to uncover additional genetic loci that modulate susceptibility to BrS, to characterize further the BrS genetic architecture and to uncover new molecular mechanisms. We identified 21 susceptibility variants that passed the genome-wide statistical significance threshold (P&lt;5.10–8), of which 18 were novel. Eight were located at the SCN5A-SCN10A locus, illustrating the central role of NaV1.5 in the disease. Interestingly, 9 occur in the vicinity of genes known to play a crucial role in cardiac development (HEY2, TBX20, GATA4, ZFPM2, WT1, TBX5, IRX3, IRX5) and / or control cardiac ion channel expression. Of note, 2 others signals occurred in the vicinity of microtubule / cytoskeleton associated proteins (MAPRE2 and MYO18B). Through studies in zebrafish and in human iPSC-derived cardiomyocytes, we demonstrate a role of MAPRE2 on NaV1.5 function. We identified 18 new susceptibility variants associated with BrS and uncovered a new pathophysiological molecular mechanism underlying BrS susceptibility. We provided further support for a complex genetic architecture underlying susceptibility for the disorder. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): H2020 - Marie Sklodowska Curie IF grant, Rising star grant from the Pays de la Loire regional council

Sign in / Sign up

Export Citation Format

Share Document