scholarly journals Brugada syndrome: current concepts and genetic background

2021 ◽  
Vol 31 (1) ◽  
pp. 152-176
Author(s):  
Andrés Ricardo Pérez-Riera ◽  
Joseane Elza Tonussi Mendes ◽  
Fabiola Ferreira da Silva ◽  
Frank Yanowitz ◽  
Luiz Carlos de Abreu ◽  
...  
Keyword(s):  
Heart Disease ◽  
Brugada Syndrome ◽  
Connexin 43 ◽  
Large Scale ◽  
Rare Variants ◽  
Right Ventricular Outflow Tract ◽  
Structural Heart Disease ◽  
Sequencing Data ◽  
Increased Risk ◽  
The Right

Brugada syndrome (BrS) is a hereditary clinical-electrocardiographic arrhythmic entity with low worldwide prevalence. The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. The diagnosis is based on the presence of spontaneous or medicated ST elevation, characterized by boost of the J point and the ST segment ≥2 mm, of superior convexity "hollow type" (subtype 1A) or descending rectilinear model (subtype 1B). BrS is associated with an increased risk of syncope, palpitations, chest pain, convulsions, difficulty in breathing (nocturnal agonal breathing) and/or Sudden Cardiac Death (SCD) secondary to PVT/VF, unexplained cardiac arrest or documented PVT/VF or Paroxysmal atrial fibrillation (AF) in the absence of apparent macroscopic or structural heart disease, electrolyte disturbance, use of certain medications or coronary heart disease and fever. In less than three decades since the discovery of Brugada syndrome, the concept of Mendelian heredity has come undone. The enormous variants and mutations found mean that we are still far from being able to concretely clarify a genotype-phenotype relationship. There is no doubt that the entity is oligogenetic, associated with environmental factors, and that there are variants of uncertain significance, especially the rare variants of the SCN5A mutation, with European or Japanese ancestors, as well as a spontaneous type 1 or induced pattern, thanks to gnomAD (coalition) researchers who seek to aggregate and harmonize exome and genome sequencing data from a variety of large scale sequencing projects and make summary data available to the scientific community at large). Thus, we believe that this in depth analytical study of the countless mutations attributed to BrS may constitute a real cornerstone that will help to better understand this intriguing syndrome.

scholarly journals Rare GATA6 variants associated with risk of congenital heart disease phenotypes in 200,000 UK Biobank exomes

2021 ◽  
Author(s):  
Simon G Williams ◽  
Dominic Byrne ◽  
Bernard Keavney
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Rare Variants ◽  
Uk Biobank ◽  
Sequencing Data ◽  
Chd Risk ◽  
Increased Risk ◽  
Sequencing Studies ◽  
The Uk

Several genes have been associated with congenital heart disease (CHD) risk in previous GWAS and sequencing studies, but studies involving larger numbers of case samples remain needed to facilitate further understanding of what remains a complex and largely uncharacterised genetic etiology. Here we use whole exome sequencing data from 200,000 samples in the UK Biobank to assess ultra-rare and potentially pathogenic variation associated with increased risk of CHD. Our findings indicate that rare variants in GATA6, presumably with a lesser effect on gene function than those causing severe CHD phenotypes, or buffered by other genetic and environmental effects during development, are also associated with minor CHD conditions, specifically bicuspid aortic valve, the most common CHD condition.

scholarly journals Natural history of the electrical axis during the first four weeks of life

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Paerregaard ◽  
J Kock ◽  
C Pihl ◽  
A Pietersen ◽  
K.K Iversen ◽  
...  
Keyword(s):  
Heart Disease ◽  
Heart Diseases ◽  
Structural Heart Disease ◽  
Funding Source ◽  
Axis Deviation ◽  
General Population Study ◽  
Gestation Age ◽  
History Of ◽  
The Right ◽  
Heart Foundation

Abstract Background The QRS axis represents the sum of the amplitudes and orientation of the ventricular depolarization. In newborns, the QRS axis is generally directed downward and to the right and left axis deviation (LAD) may be associated with heart disease. Accurate interpretation of abnormalities in the QRS axis may facilitate early diagnosis of heart diseases in newborns. Purpose To describe the evolution of the QRS axis during the first four weeks of life and provide updated, digitalized, normal values from healthy newborns. Methods Electrocardiograms from 12,317 newborns (age 0–28 days) included in a regional, prospective, general population study from 2016–2018 were analyzed. Electrocardiograms were obtained and analyzed with a computerized algorithm with manual validation. The algorithm calculated the QRS mean axis using the net amplitudes of three leads I, II, and III. The four main QRS axis classifications were: “adult normal” axis (+1° to +90°), left axis deviation (LAD, 0° to −90°), right axis deviation (RAD, +91° to +180°), and extreme axis deviation (EAD, +181° to +270°). Echocardiograms were performed according to standard guidelines. Only newborns with an echocardiography excluding structural heart disease were included. Results Electrocardiograms from 12,317 newborns with a median age at examination of 12 days (52% boys) were included. The median QRS axis was 119° at the ages 0–7 days and shifted leftwards to 102° at the ages 22–28 days (p<0.001). We found that girls had significant less pronounced right axis deviation than boys (111° vs 117°, p<0.001) and that increasing gestational age was associated with more pronounced right axis deviation (104° vs 116°, p<0.05). Infant size did not affect the axis (p>0.05). Only 0.5% had LAD (0° to −90°) and 1.1% had an axis within the interval +240° to +30° indicating that a QRS axis in this expanded interval is unusual in healthy newborns. Conclusion The QRS axis showed a gradual leftward-shift during the first four weeks of life and was affected by sex and gestation age but unaffected by infant size. LAD occurred in only 0.5% of the newborns. Our data serve as updated reference values, which may facilitate clinical handling of newborns. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): This work was supported by the Danish Children Heart Foundation, Snedkermester Sophus Jacobsen and wife Astrid Jacobsen's foundation (Grant 19-R112-A5248-26048), the Research Council at Herlev-Gentofte Hospital and Toyota-Fonden, Denmark.

scholarly journals Left Axis Deviation in Brugada Syndrome: Vectorcardiographic Evaluation during Ajmaline Provocation Testing Reveals Additional Depolarization Abnormalities

2021 ◽  
Vol 22 (2) ◽  
pp. 484
Author(s):  
Martijn H. van der Ree ◽  
Jeroen Vendrik ◽  
Jan A. Kors ◽  
Ahmad S. Amin ◽  
Arthur A. M. Wilde ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Brugada Syndrome ◽  
Right Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Conduction Delay ◽  
Channel Blockers ◽  
Axis Deviation ◽  
Provocation Testing ◽  
The Right

Patients with Brugada syndrome (BrS) can show a leftward deviation of the frontal QRS-axis upon provocation with sodium channel blockers. The cause of this axis change is unclear. In this study, we aimed to determine (1) the prevalence of this left axis deviation and (2) to evaluate its cause, using the insights that could be derived from vectorcardiograms. Hence, from a large cohort of patients who underwent ajmaline provocation testing (n = 1430), we selected patients in whom a type-1 BrS-ECG was evoked (n = 345). Depolarization and repolarization parameters were analyzed for reconstructed vectorcardiograms and were compared between patients with and without a >30° leftward axis shift. We found (1) that the prevalence of a left axis deviation during provocation testing was 18% and (2) that this left axis deviation was not explained by terminal conduction slowing in the right ventricular outflow tract (4th QRS-loop quartile: +17 ± 14 ms versus +13 ± 15 ms, nonsignificant) but was associated with a more proximal conduction slowing (1st QRS-loop quartile: +12[8;18] ms versus +8[4;12] ms, p < 0.001 and 3rd QRS-loop quartile: +12 ± 10 ms versus +5 ± 7 ms, p < 0.001). There was no important heterogeneity of the action potential morphology (no difference in the ventricular gradient), but a left axis deviation did result in a discordant repolarization (spatial QRS-T angle: 122[59;147]° versus 44[25;91]°, p < 0.001). Thus, although the development of the type-1 BrS-ECG is characterized by a terminal conduction delay in the right ventricle, BrS-patients with a left axis deviation upon sodium channel blocker provocation have an additional proximal conduction slowing, which is associated with a subsequent discordant repolarization. Whether this has implications for risk stratification is still undetermined.

Dormant conduction in the right ventricular outflow tract unmasked by adenosine in a patient with Brugada syndrome

2021 ◽  
Vol 32 (4) ◽  
pp. 1182-1186
Author(s):  
Tsukasa Kamakura ◽  
Josselin Duchateau ◽  
Frédéric Sacher ◽  
Pierre Jais ◽  
Michel Haïssaguerre ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Brugada Syndrome ◽  
Right Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Outflow Tract ◽  
Dormant Conduction ◽  
The Right

Antithrombotic Therapy in Patients Undergoing Transcatheter Interventions for Structural Heart Disease

Circulation ◽  
2021 ◽  
Vol 144 (16) ◽  
pp. 1323-1343
Author(s):  
Paolo Calabrò ◽  
Felice Gragnano ◽  
Giampaolo Niccoli ◽  
Rossella Marcucci ◽  
Marco Zimarino ◽  
...  
Keyword(s):  
Heart Disease ◽  
Antithrombotic Therapy ◽  
Structural Heart Disease ◽  
Current Evidence ◽  
Bleeding Complications ◽  
Tricuspid Valve Repair ◽  
Left Atrial Appendage Occlusion ◽  
Increased Risk ◽  
Valve Implantation ◽  
Transcatheter Interventions

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.

Sustained and non-sustained ventricular tachycardia and no associated heart disease (idiopathic ventricular tachycardia)

ESC CardioMed ◽  
2018 ◽  
pp. 2288-2293
Author(s):  
Victor Bazan ◽  
Enrique Rodriguez-Font ◽  
Francis E. Marchlinski
Keyword(s):  
Heart Disease ◽  
Ventricular Tachycardia ◽  
Drug Therapy ◽  
Catheter Ablation ◽  
Beta Blockers ◽  
Young Patients ◽  
Structural Heart Disease ◽  
Holter Monitoring ◽  
Severe Arrhythmia ◽  
The Right

Around 10% of ventricular arrhythmias (VA) occur in the absence of underlying structural heart disease. These so-called ‘idiopathic’ VAs usually have a benign clinical course. Only rarely do these “benign” arrhythmias trigger polymorphic ventricular tachycardia (PVT) and idiopathic ventricular fibrillation (VF). Due to their focal origin and to the absence of underlying myocardial scar, the 12-lead ECG very precisely establishes the right (RV) or left (LV) ventricular site of origin of the arrhythmia and can help regionalizing the origin of VT for ablation. A 12-lead ECG obtained during the baseline rhythm and 24-hour ECG Holter monitoring are indicated in order to identify structural or electrical disorders leading to PVT/VF and to determine the VA burden. The most frequent origin of idiopathic VAs is the RV outflow tract (OT). Other origins include the LVOT, the LV fascicles (fascicular VTs), the LV and RV papillary muscles, the crux cordis, the mitral and tricuspid annuli and the RV moderator band. Recognizing the typical anatomic sites of origin combined with a 12 lead ECG assessment facilitates localization.  Antiarrhythmic drug therapy (including use of beta-blockers) or catheter ablation may be indicated to suppress or eliminate idiopathic VAs, particularly upon severe arrhythmia-related symptoms or if the arrhythmia burden is high and ‘tachycardia’-induced cardiomyopathy is suspected. Catheter ablation is frequently preferred to prevent lifelong drug therapy in young patients.

scholarly journals Early Response after Catheter Ablation of the Epicardial Substrate in a Patient with Brugada Syndrome Can Be Predicted by High Precordial Leads

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Yae Min Park ◽  
Mi Sook Cha ◽  
Hanul Choi ◽  
Woong Chol Kang ◽  
Seung Hwan Han ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Brugada Syndrome ◽  
Low Voltage ◽  
Early Stage ◽  
Right Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Early Response ◽  
Intercostal Space ◽  
The Right ◽  
Fourth Intercostal Space

A 52-year-old male with Brugada syndrome presented with repeated and appropriate shock from an implantable cardioverter defibrillator (ICD). Catheter ablation for substrate elimination targeting low-voltage, complex, and fractionated electrocardiograms and late potentials in the epicardial right ventricular outflow tract was successfully performed. Brugada phenotype in the right precordial leads from the third intercostal space disappeared in the early stage after catheter ablation and that from the standard fourth intercostal space disappeared later. He remained free from ventricular fibrillation over the next fourteen months. We suggest that this novel ablation strategy is effective in Brugada syndrome patients with ICD, and early response after catheter ablation can be predicted by high precordial leads.

scholarly journals Discovery of a Symptomatic Left Anomalous Coronary Artery from the Opposite Sinus and Postoperative Considerations

2009 ◽  
Vol 2009 ◽  
pp. 1-3 ◽  
Author(s):  
Ahmad Slim ◽  
John Thurlow ◽  
Jennifer Blevins ◽  
Shaun Martinho ◽  
Brian Markelz
Keyword(s):  
Coronary Artery ◽  
Right Ventricular Outflow Tract ◽  
Rare Condition ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Outflow Tract ◽  
Anomalous Origin ◽  
Complex Anatomy ◽  
Increased Risk ◽  
The Right

This is the case of an 18 year old active duty soldier with symptoms of exertional chest pressure and syncope who was found to have anomalous origin of the left main coronary artery (LMCA) from the right coronary cusp (RCC) traveling partially between the great vessels before taking a septal approach between the left ventricular outflow tract (LVOT) and the right ventricular outflow tract (RVOT). Anomalous origin of coronary arteries is a rare condition that carries an increased risk of angina, myocardial ischemia, and sudden cardiac death (SCD). Surgical treatment of such anomalies with both high and lower risk features can be challenging, and traditional benefit from surgical correction may not be achieved due to complex anatomy. As evident by our patient, this rare condition even though benign from sudden death standpoint could be debilitating despite best efforts and available resources.

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