Brugada syndrome

You don't need to be Editor-In-Chief to add or edit content to WikiDoc. You can begin to add to or edit text on this WikiDoc page by clicking on the edit button at the top of this page. Next enter or edit the information that you would like to appear here. Once you are done editing, scroll down and click the Save page button at the bottom of the page.

Brugada syndrome Classification and external resources
ECG findings of Brugada Syndrome
ICD-10	I42.8
ICD-9	746.89
OMIM	601144
DiseasesDB	31999
MeSH	D053840

Cardiology Network
Discuss Brugada syndrome further in the WikiDoc Cardiology Network
Adult Congenital
Biomarkers
Cardiac Rehabilitation
Congestive Heart Failure
CT Angiography
Echocardiography
Electrophysiology
Cardiology General
Genetics
Health Economics
Hypertension
Interventional Cardiology
MRI
Nuclear Cardiology
Peripheral Arterial Disease
Prevention
Public Policy
Pulmonary Embolism
Stable Angina
Valvular Heart Disease
Vascular Medicine

WikiDoc Resources for Brugada syndrome
Articles
Most recent articles on Brugada syndrome Most cited articles on Brugada syndrome Review articles on Brugada syndrome Articles on Brugada syndrome in N Eng J Med, Lancet, BMJ
Media
Powerpoint slides on Brugada syndrome Images of Brugada syndrome Photos of Brugada syndrome Podcasts & MP3s on Brugada syndrome Videos on Brugada syndrome
Evidence Based Medicine
Cochrane Collaboration on Brugada syndrome Bandolier on Brugada syndrome TRIP on Brugada syndrome
Clinical Trials
Ongoing Trials on Brugada syndrome at Clinical Trials.gov Trial results on Brugada syndrome Clinical Trials on Brugada syndrome at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Brugada syndrome NICE Guidance on Brugada syndrome NHS PRODIGY Guidance FDA on Brugada syndrome CDC on Brugada syndrome
Books
Books on Brugada syndrome
News
Brugada syndrome in the news Be alerted to news on Brugada syndrome News trends on Brugada syndrome
Commentary
Blogs on Brugada syndrome
Definitions
Definitions of Brugada syndrome
Patient Resources / Community
Patient resources on Brugada syndrome Discussion groups on Brugada syndrome Patient Handouts on Brugada syndrome Directions to Hospitals Treating Brugada syndrome Risk calculators and risk factors for Brugada syndrome
Healthcare Provider Resources
Symptoms of Brugada syndrome Causes & Risk Factors for Brugada syndrome Diagnostic studies for Brugada syndrome Treatment of Brugada syndrome
Continuing Medical Education (CME)
CME Programs on Brugada syndrome
International
Brugada syndrome en Espanol Brugada syndrome en Francais
Businness
Brugada syndrome in the Marketplace Patents on Brugada syndrome
Experimental / Informatics
List of terms related to Brugada syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Phone:617-525-6884

Please Join in Editing This Page and Apply to be an Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

The Brugada syndrome is a genetic disease that is characterised by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death in young adults, and occasionally in children and infants. It is also known as Sudden Unexpected Death Syndrome^[1] (SUDS), and is the most common cause of sudden death in young men without known underlying cardiac disease in Thailand and Laos^[1].

Although the ECG findings of Brugada syndrome were first reported^[1] among survivors of cardiac arrest in 1989, it was only in 1992 that the Brugada brothers^[1] recognized it as a distinct clinical entity, causing sudden death by causing ventricular fibrillation (a lethal arrhythmia) in the heart.

Epidemiology

The average age at the time of initial diagnosis or sudden death is 40 ± 22 years, with the youngest patient diagnosed at 2 days of age and the oldest at 84 years. The prevalence of the Brugada syndrome is estimated at 1–5 per 10,000 inhabitants worldwide. The frequency is lower in western countries and higher (≥5 per 10,000) in Southeast Asia.

Genetics and pathophysiology

Approximately 20% of the cases of Brugada syndrome have been shown to be associated with mutation(s) in the gene that encodes for the sodium ion channel in the cell membranes of the muscle cells of the heart (the myocytes). The gene, named SCN5A, is located on the short arm of the third chromosome (3p21). Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle. This results in transmural and epicardial dispersion of repolarization. The transmural dispersion underlies ST-segment elevation and the development of a vulnerable window across the ventricular wall, whereas the epicardial dispersion of repolarization facilitates the development of phase 2 reentry, which generates a phase 2 reentrant extrasystole that captures the vulnerable window to precipitate ventricular tachycardia and/or fibrillation that often results in sudden cardiac death. At present time however, all the reported patients died because of the disease and submitted to detailed necropsy study, have shown a structural right ventricular pathology underlying the syndrome.

Over 160 mutations in the SCN5A gene have been discovered to date, each having varying mechanisms and effects on function, thereby explaining the varying degrees of penetration and expression of this disorder. ^[1]

An example of one of the mechanisms in which a loss of function of the sodium channel occurs is a mutation in the gene that disrupts the sodium channel's ability to bind properly to ankyrin-G, an important protein mediating interaction between ion channels and cytoskeletal elements. Very recently a mutation in a second gene, Glycerol-3-phosphate dehydrogenase 1-like gene (GPD1L) has been shown to result in Brugada Syndrome in a large multigenerational family (London, 2006). This gene acts as an ion channel modulator in the heart, although the exact mechanism is not yet understood.

Recently Antzelevitch has identified mutations in the L-type calcium channel subunits (CACNA1C (A39V and G490R) and CACNB2 (S481L)) leading to ST elevation and a relatively short QT interval (below 360 msec).^[1]

This condition is inherited in an autosomal dominant pattern and is more common in males. In addition it has a higher prevalence in most Asian populations.^{[1] [1] [1] [1] [1] [1] [1]}

Electrocardiography

In some cases, the disease can be detected by observing characteristic patterns on an electrocardiogram, which may be present all the time, or might be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels and causing appearance of ECG abnormalities - ajmaline, flecainide) or resurface spontaneously due to as yet unclarified triggers. The pattern seen on the ECG is persistent ST elevations in the electrocardiographic leadsV₁-V₃ with a right bundle branch block (RBBB) appearance with or without the terminal S waves in the lateral leads that are associated with a typical RBBB. A prolongation of the PR interval (a conduction disturbance in the heart) is also frequently seen.The electrocardiogram can fluctuate over time, depending on the autonomic balance and the administration of antiarrhythmic drugs. Adrenergic stimulation decreases the ST segment elevation, while vagal stimulation worsens it. (There is a case report of a patient who died while shaving, presumed due to the vagal stimulation of the carotid sinus massage!) The administration of class Ia, Ic and III drugs increases the ST segment elevation, and also fever. Exercise decreases ST segment elevation in some patients but increases it in others (after exercise when the body temperature has risen). The changes in heart rate induced by atrial pacing are accompanied by changes in the degree of ST segment elevation. When the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. However, the contrary can also be observed.

Characteristics

• Characterized by a coved-type ST-segment elevation in the right precordial leads
• The Brugada ECG is often concealed, but can be unmasked or modulated by a number of drugs and pathophysiological states including sodium channel blockers, a febrile state, vagotonic agents, tricyclic antidepressants, as well as cocaine and Propranolol intoxication.

• Genetics

1. SCN5A is a gene that encodes the alpha sodium unit of the cardiac sodium channel. Mutations in SCN5A account for about 15-30% of Brugada syndrome cases. A negative genetic test for SCN5A does not exclude that SCN5A is causing the clinical syndrome because the genetic tests do not evaluate for mutations in promotors, cryptic splicing mutations, or gross rearrangements in the protein product.
2. Glycerol-3-phosphate dehydrogenase (GPD1L) is associated with progressive conduction disease and low sensitivity to procainamide resulting from decreased Isodium current. It has a relatively good prognosis.
3. CACNA1C (alpha subunit of L-type cardiac calcium channel) and CACNB2b (beta subunit of L-type cardiac calcium channel) is associated with a shortened QT interval and a combinatin Brugada/Short QT interval syndrome.

Brugada EKG

1. Type 1 ST segment elevation is diagnostic of Brugada syndrome and is characterized by a coved ST-segment elevation ≥2 mm (0.2 mV) followed by a negative T wave.
2. Type 2 ST-segment elevation has a saddleback appearance with a high take-off ST-segment elevation of ≥2 mm followed by a trough displaying ≥1 mm ST elevation followed by either a positive or biphasic T wave.
3. Type 3 ST-segment elevation has either a saddleback or coved appearance with an ST-segment elevation of <1 mm.

Diagnosis

• Diagnosed when a Type 1 ST-segment elevation is observed in more than one right precordial lead (V1-V3), in the presence or absence of sodium channel blocking agent, and in conjunction with one or more of the following:

1. Family history of SCD (<45 years old)
2. Documented VF
3. Polymorphic ventricular tachycardia
4. Coved-type ECGs in family members
5. Inducibility of VT with programmed electrical stimulation (PES)
6. Syncope
7. Nocturnal agonal respiration

• Diagnosis is also considered positive when a Type 2 (saddleback pattern) or Type 3 ST-segment elevation is observed in more than one right precordial lead under baseline conditions and can be converted to the diagnostic Type 1 pattern occurs upon exposure to sodium channel blocker.

Sodium Challenge

• Drugs that can be used
  • Ajmaline 1 mg/kg/5 min IV
  • Flecainide 2 mg/kg/10 min IV or 400 mg PO
  • Procainamide 10 mg/kg/10 min IV
  • Pilsicainide 1 mg/kg/10 min IV
• The sodium challenge should be terminated when

1. Diagnostic Type 1 ST-segment elevation or Brugada ECG, develops
2. ST segment in Type 2 increases by ≥2 mm
3. Premature ventricular beats or other arrhythmias develop
4. QRS widens to ≥130% of baseline

Arrhythmias

1. Polymorphic VT resembling a rapid Torsade de Pointes (TdP)
2. Monomorphic VT is observed infrequently
3. VT/VF often terminates spontaneously in patients with the Brugada syndrome which may explain why patients wake up at night after episodes of agonal respiration caused by the arrhythmia.

Risk Statification

• Patients with syncope and an abnormal Type 1 ECG are at higher risk
• Asymptomatic patients at risk can be identified
  • Presence of spontaneous Type 1 ST-segment elevation
  • Characteristics of the S wave
  • Presence of late potentials
  • Inducibility of VT/VF using PES.

Treatment

• Aborted sudden death are at high risk for recurrence and should receive an ICD
• VT storm has been successfully treated with Isoproterenol. The mechanism is thought to be augmenting the cardiac L type channel.
• Asymptomatic patients require risk stratification and clinical judegement to help guide therapy
• Quinidine (class IA sodium channel blocker) blocks the Ito current and is proven to suppress spontaneous VF
• Cilostazol (phosphodiesterase III inhibitor that increases inward L type calcium channel current and reported to suppress spontaneous VF
• Bepridil suppress spontaneous VF probably through blocking Ito current
• Medical therapy alone with the above agents is currently not evaluated in randomized trials and should not be used as loan therapy.

Treatment

The cause of death in Brugada syndrome is ventricular fibrillation.The episodes of syncope (fainting) and sudden death (aborted or not) are caused by fast polymorphic ventricular tachycardias or ventricular fibrillation. These arrhythmias appear with no warning. While there is no exact treatment modality that reliably and totally prevents ventricular fibrillation from occurring in this syndrome, treatment lies in termination of this lethal arrhythmia before it causes death. This is done via implantation of an implantable cardioverter-defibrillator (ICD), which continuously monitors the heart rhythm and will defibrillate an individual if ventricular fibrillation is noted. Some recently performed studies had evaluated the role of quinidine, a Class Ia antiarrythmic drug, for decreasing VF episodes occurring in this syndrome. Quinidine was found to decrease number of VF episodes and correcting spontaneous ECG changes, possibly via inhibiting Ito channels.^[1] Those with risk factors for coronary artery disease may require an angiogram before ICD implantation.

See also

• Cardiac action potential
• Genetics
• Ion channel
• Tambocor

References

External links

• GeneReviews: Brugada syndrome
• Algado et al: http://www.medspain.com/ant/n13_jun00/Brugada.htm
• Behr: http://www.c-r-y.org.uk/long_qt_syndrome.htm
• The Ramon Brugada Senior Foundation
• http://digilander.libero.it/martini_syndrome/

v • d • e Electrocardiography
Overview	History of the EKG • EKG interpretation basics • Normal sinus rhythm
EKG Complexes	P wave • QRS complex • ST Segment • T wave • U wave Osborn wave • H wave • K wave • Delta wave NSSTW changes
EKG Intervals	PR Interval • QRS Interval • ST Interval • QT Interval
Conduction System & Bradycardia	Cardiac pacemaker • SA node • AV node• Bundle of His • Purkinje fibers • Sinus bradycardia • First Degree AV Block • Second Degree AV Block • Complete or Third-Degree AV Block • Concealed conduction • AV Junctional Rhythms • LBBB • LAHB • LPHB • RBBB • Trifascicular block
Atrial Arrhythmias	Sinus tachycardia • Premature Atrial Contractions (PACs) • Ectopic Atrial Rhythm • Paroxysmal Atrial Tachycardia (PAT) • Paroxysmal Atrial Tachycardia (PAT) with Block • Multifocal Atrial Tachycardia (MAT) • Atrial Flutter • Atrial Fibrillation • Wandering atrial pacemaker
Ventricular Arrhythmias	Differential Diagnosis of Tachycardia with a Wide QRS Complex • Accelerated Idioventricular Rhythm • Ventricular Parasystole • Premature Ventricular Contractions (PVCs) • Ventricular tachycardia • Ventricular Fibrillation • Sudden cardiac death
EKG Abnormalities in Disease States	Hypertrophy & Dilatation • Right atrial enlargement • Left atrial enlargement • Biatrial enlargement • Left Ventricular Hypertrophy • Right Ventricular Hypertrophy • Biventricular Hypertrophy • Acute myocardial infarction • NSTEMI • STEMI • Right ventricular myocardial infarction • Atrial infarction Pre-excitation Syndromes • Wolff-Parkinson-White Syndrome • Lown Ganong Levine Syndrome • Mahaim Type Preexcitation Cardiomyopathies • Arrhythmogenic Right Ventricular Dysplasia • Dilated Cardiomyopathy • Hypertrophic Cardiomyopathy Drug Effects on the EKG • Adenosine • β-blockers • Digitalis • Quinidine • Procainamide • Disopyramide • Lidocaine • Tocainide and Mexiletine • Phenytoin • Encainide, Flecainide and Propafenone • Amiodarone • Bretylium • Ca Channel Blockers • Phenothiazines • Tricyclic Antidepressants • Lithium Congenital Heart Disease • Dextrocardia • Atrial Septal Defect • Ventricular Septal Defect • Tetralogy of Fallot • Conjoined Twins or Siamese Twins Electrolyte Disturbances • Hyperkalemia • Hypokalemia • Hypercalcemia • Hypocalcemia • Nonspecific Changes Other Heart Diseases • Pericarditis • Myocarditis • Tamponade • Heart Transplantation • Sick Sinus Syndrome • Long QT Syndrome Inherited Disease • Brugada Syndrome Systemic Diseases • CNS Disease • Cardiac Tumors Heart Transplantation • EKG Changes in patient with Heart Transplantation Exogenous Effects • Hypothermia • Chest Trauma • Insect Bites • Electric Injuries
Technical Issues and Potential Errors in Interpretation	Artifacts • Lead Placement Errors • The EKG in a Patient with a Pacemaker

v • d • e WikiDoc Research Resources for Brugada syndrome (Click show to right to view)
Articles on Brugada syndrome	Most recent articles on Brugada syndrome • Most cited articles on Brugada syndrome • Review articles on Brugada syndrome • Articles on Brugada syndrome in N Eng J Med, Lancet, BMJ
Media (Slides, Video, Images, MP3) on Brugada syndrome	Powerpoint slides on Brugada syndrome • Images of Brugada syndrome • Photos of Brugada syndrome • Podcasts & MP3s on Brugada syndrome • Videos on Brugada syndrome
Evidence Based Medicine Regarding Brugada syndrome	Cochrane Collaboration on Brugada syndrome • Bandolier on Brugada syndrome • TRIP on Brugada syndrome
Cost Effectiveness of Brugada syndrome	Cost Effectiveness of Brugada syndrome
Clinical Trials Involving Brugada syndrome	Ongoing Trials on Brugada syndrome at Clinical Trials.gov • Trial results on Brugada syndrome • Clinical Trials on Brugada syndrome at Google
Guidelines / Policies / Government Resources (FDA/CDC) Regarding Brugada syndrome	US National Guidelines Clearinghouse on Brugada syndrome • NICE Guidance on Brugada syndrome • NHS PRODIGY Guidance • FDA on Brugada syndrome • CDC on Brugada syndrome
Textbook Information on Brugada syndrome	Books and Textbook Information on Brugada syndrome
Pharmacology Resources on Brugada syndrome	Dosing of Brugada syndrome • Drug interactions with Brugada syndrome • Side effects of Brugada syndrome • Allergic reactions to Brugada syndrome • Overdose information on Brugada syndrome • Carcinogenicity information on Brugada syndrome • Brugada syndrome in pregnancy • Pharmacokinetics of Brugada syndrome •
Genetics, Pharmacogenomics, and Proteinomics of Brugada syndrome	Genetics of Brugada syndrome • Pharmacogenomics of Brugada syndrome • Proteomics of Brugada syndrome
Newstories on Brugada syndrome	Brugada syndrome in the news • Be alerted to news on Brugada syndrome • News trends on Brugada syndrome
Commentary on Brugada syndrome	Blogs on Brugada syndrome
Patient Resources on Brugada syndrome	Patient resources on Brugada syndrome • Discussion groups on Brugada syndrome • Patient Handouts on Brugada syndrome • Directions to Hospitals Treating Brugada syndrome • Risk calculators and risk factors for Brugada syndrome
Healthcare Provider Resources on Brugada syndrome	Symptoms of Brugada syndrome • Causes & Risk Factors for Brugada syndrome • Diagnostic studies for Brugada syndrome • Treatment of Brugada syndrome
Continuing Medical Education (CME) Programs on Brugada syndrome	CME Programs on Brugada syndrome
International Resources on Brugada syndrome	Brugada syndrome en Espanol • Brugada syndrome en Francais
Business Resources on Brugada syndrome	Brugada syndrome in the Marketplace • Patents on Brugada syndrome
Informatics Resources on Brugada syndrome	List of terms related to Brugada syndrome

de:Brugada-Syndromfr:Syndrome de Brugada it:Sindrome di Brugada he:תסמונת ברוגדה ja:ブルガダ症候群fi:Brugadan oireyhtymä

WikiDoc Help Menu Quick Start.. Get Started Here! How to Login How to Search Pages How to Start a New Page How to Edit a Page Cheat Sheet Editing basics Learning Basic Formatting How to make Links in WikiDoc & to External Sites How to Make Lists How to Ignoring Formatting Adding References or Footnotes to Articles Tracking Changes You Have Made How to Put an Article Into a Category When Multiple Topics Should Go To The Same Page (MI, Acute MI, AMI) Using Redirection Advanced editing How to Make Tables How to Insert Images and Other Media How to Add Video Help:How to Make Columns Web Colors How To Make Templates How to Move Pages Inserting Dynamic Dates and Times Inserting WikiDoc Statistics Editing the Table of Contents Communicating your edits Let others know what you changed: The importance of Edit Summaries Minor Edits Edit Conflicts Help Videos You Can Watch Getting Started Video

Acknowledgement and Attribution Regarding Sources of Content

Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .