Brugada syndrome

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

Brugada syndrome is a genetic disease that is characterized by abnormal electrocardiogram (EKG) findings and an increased risk of sudden cardiac death in young adults, and occasionally in children and infants. Brugada syndrome is a condition that causes a disruption of the heart’s normal rhythm. Specifically, this disorder can lead to uncoordinated electrical activity in the heart’s lower chambers (ventricles), an abnormality called ventricular arrhythmia. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep.

Brugada syndorme was potentially first seen on EKG in survivors of cardiac arrest in 1989, but it was not until 1992 that the Brugada brothers recognized it as a distinct clinical entity which could cause sudden death by ventricular fibrillation.

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide.

Approximately 20% of persons with Brugada syndome have a mutation in the gene SCN5A. This gene encodes for the sodium ion channel. The mutation is inherited in an autosomal dominant pattern, and is more commonly seen in males. Brugada syndrome has also been shown to result from defects in a calcium channel.

Brugada syndrome should be differentiated from other cardiac disorders, electrolyte disturbances, and drug intoxication syndromes. The condition which most similarly presents to Brugada syndrome is arrhythmogenic right ventricular dysplasia, as they both cause sudden cardiac death in children. Brugada syndrome can be differentiated from arrhythmogenic right ventricular dysplasia by the genetic counterpart of SCN5A, the lack of structural abnormalities within the heart, the association with polymorphic ventricular tachycardia during sleep, and EKG changes that are enhanced by vagotonic agents.

Insofar as Brugada syndrome is a relatively newly recognized syndrome, its incidence and prevalence continues to increase. Brugada syndrome is quite common in Southeast Asia where it is endemic, and affects 500 out of every 100,000 individuals. It is the second leading cause of death after car accidents among young people in these countries. It has been estimated that Brugada syndrome accounts for 4% of all sudden cardiac deaths and 20% of sudden cardiac deaths among patients with structurally normal hearts. It is 8-10 times more common in men.

The EKG changes of Brugada syndrome can vary 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. During sleep, there is heightened vagal tone, and the pattern may be exacerbated at that time (as is the risk of sudden cardiac death at that time). The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever. The impact of exercise depends upon when the EKG is obtained: during exercise the ST segment elevation may decrease but may increase later after exercise when the body temperature has risen. Similar to early repolarization variant, when the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. While Brugada syndrome is often associated with polymorphic VT which may be self terminating, in the presence of autonomic imbalance, hypokalemia, fever or exacerbating drugs sustained ventricular fibrillation and sudden cardiac death may result.^[1]

Relatives of patients with Brugada syndrome can be screened for the syndrome by obtaining an EKG, although the diagnostic pattern may be concealed. Genetic testing can also be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.^[1] Unfortunately, despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis.

Brugada syndrome usually becomes apparent in adulthood, although it may present in infants and children as sudden cardiac death. The mean age of sudden death in patients with Brugada syndrome is 40 years old. The Brugada patient may develop atrial arrhythmias and abnormalities in atrial conduction, and these abnormalities are associated with inducibility of ventricular fibrillation. Implantation of a cardiac defibrillator AICD can improve prognosis for some.

The diagnosis of brugada syndrome is based upon electrocardiographic and clinical criteria. Only the Type I Brugada pattern qualifies as part of the diagnostic criteria for Brugada syndrome. Other rhythm abnormalities and family history are also taken into account when making the diagnosis of Brugada syndrome.

Patients with Brugada syndrome will sometimes have a family history of sudden cardiac death and a personal history of of arrhythmias. If patients are symptomatic they often have symptoms of syncope, seizures, agonal breathing, difficulty breathing, and patients may even present with sudden death. These symptoms most often come on either at rest or during sleep.

Insofar as Brugada syndrome is not associated with any structural heart disease, there are generally no abnormalities on physical examination. Vagal maneuvers such as carotid sinus massage may increase vagal tone and may unmask the presence of a Type I Brugada pattern. In a patient who has experienced recent symptoms such as syncope, it is important to check the temperature in so far as fever may trigger a self terminating or sustained episode of ventricular tachycardia / ventricular fibrillation. The presence of fever is also a target of antipyretic therapy.

Hypokalemia and hyperkalemia can both trigger either sustained or nonsustained episodes of ventricular tachycardia / ventricular fibrillation and serum electrolytes should therefore be checked. Both alcohol and cocaine intoxication can be associated with either sustained or nonsustained episodes of ventricular tachycardia/ventricular fibrillation and a toxicology screen should be ordered if there is a clinical suspicion. Likewise, tricyclic antidepressants can be associated with exacerbations of the syndrome, and levels of these agents should also be checked if there is a clinical suspicion.

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide. Type 1 Brugada syndrome may always be present on the EKG, or it may be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels such as ajmaline, flecainide) or it may be unmasked by various triggers or risk factors.

Insofar as Brugada syndrome is not associated with structural abnormalities of the heart, there are no associated abnormalities on the chest x-ray.

There is ongoing controversy as to whether there are structural abnormalities among patients with Brugada syndrome. There was one small study of 11 patients with Brugada syndrome that demonstrated a rapid swinging motion shifting towards the right ventricle of the basal segment of the intraventricular septum and early systole in 73% (8/11) of patients with Brugada syndrome. None of the control patients demonstrated this abnormality.^[2]

Patients who are inducible at the time electrophysiologic study have an eightfold increased risk of aborted sudden cardiac death compared with those patients who are not inducible.^[3] Some groups have advocated that programmed electrical stimulation (PES) be performed to induce ventricular fibrillation for risk assessment in Brugada patients ^[4][5] Other groups have not reproduced the predictive value of these tests,^[6][7] so the value of programmed electrical stimulation (PES) and inducibility remains controversial.

Despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis. Genetic testing can be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.^[1]

Implantation of a cardiac defibrillator is the only proven method of treatment in Brugada syndrome.Patients with aborted sudden cardiac death are at high risk for recurrence and should undergo AICD implantation, and do not require an electrophysiologic study to assess inducibility. Patients with symptoms (either syncope, seizures or nocturnal agonal respirations) should undergo implantation of a defibrillator if no other cause of their symptoms can be identified. Asymptomatic patients should undergo electrophysiologic testing, and if VT / VF can be induced, they should undergo implantation of an ICD. Asymptomatic patients who cannot be induced should followed-up closely. Patients who are asymptomatic with no family history of Brugada syndrome can be followed-up closely.

There are certain drugs that should be avoided in patients with Brugada syndrome. These drugs include ajmaline, flecainide, pilsicainide, procainamide, and propafenone. These drugs are all sodium blocking antiarrhythmics which are either in the IA class or IC class.

Drugs which are not contraindicated in Brugada syndrome, but which should be avoided, are amiodarone, cibenzoline, disopyramide, lidocaine, propanolol, and verapamil. These agents are all antiarrhythmics. Topical lidocaine used for anesthesia is thought to be safe when used in persons with Brugada syndrome.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

There are three electrocardiographic patterns associated with Brugada syndrome: Type I, Type II and Type III. The diagnosis of Brugada syndrome is based upon the presence of Type I EKG changes. Patients with Type II or Type III Brugada patterns can convert to a Type I Brugada pattern following the administration of sodium channel blockers such as ajmaline and flecainide. To be classified as having Brugada syndrome (not just the pattern), one or more of the following criteria must also be met:

• Family history of sudden cardiac death (SCD) (<45 years old)
• Documented ventricular fibrillation (VF)
• Polymorphic ventricular tachycardia
• Coved-type ECG changes in family members
• Inducibility of ventricular tachycardia (VT) with programmed electrical stimulation (PES)

The patient is also diagnosed as having Brugada syndrome when a Type 2 (saddleback pattern) or Type 3 ST-segment elevation is observed in more than one right precordial lead under baseline conditions that can be converted to the diagnostic Type 1 Brugada pattern following administration of a sodium channel blocker and the clinical criteria listed above are met as well.

• There are three types of electrocardiogram patterns that are seen in Brugada syndrome; Type I, Type II, and Type III. Type I Brugada syndrome may always be present on the EKG, or it may be elicited by the administration of particular drugs (e.g., Class IC antiarrythmic drugs that blocks sodium channels such as ajmaline, flecainide) or it may be unmasked by various triggers or risk factors.^[1]

• Type I Brugada pattern is characterized by ST elevations in leads V₁-V₃ with a right bundle branch block (RBBB). A prolongation of the PR interval is also frequently seen. The EKG changes of Brugada syndrome can vary 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. The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever.^[2][3]
• 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.^[4]

• The three patterns of Brugada syndrome (Type I,II,III) are shown below:

The table below is from ECG pedia and is adapted from Wilde et al.^[5]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Brugada syndrome was potentially first seen on EKG in survivors of cardiac arrest in 1989, but it was not until 1992 that the Brugada brothers recognized it as a distinct clinical entity which could cause sudden death by ventricular fibrillation.

• Sudden unexplained death syndrome was first noted in 1977 by Hmong refugees in the US.^[1][2]
• The disease was again noted in Singapore, when a retrospective survey of records showed that 230 otherwise healthy Thai men died suddenly of unexplained causes between 1982 and 1990: publication of this data provoked a diplomatic incident.^[3]
• The condition appears to affect primarily young Hmong men from Laos (median age 33) and northeastern Thailand (where the population are mainly of Laotian descent).^[4][5]
• There is a strong hereditary component and the victims tend to die in their sleep. Survivors describe a feeling of intense fear and paralysis. There is a sensation of pressure in the chest, the presence of an alien being in the room and altered sensation.^[6]
• This phenomenon is well known among the Hmong people of Laos, who ascribe these deaths to a malign spirit, dab tsog (pronounced “da cho”), said to take the form of a jealous woman. Hmong men may even go to sleep dressed as women so as to avoid the attentions of this spirit.^[7]
• The Brugada brothers were the first to describe the characteristic ECG findings and link them to sudden death. Before that the characteristic ECG findings were often mistaken for a right ventricular myocardial infarction. In 1953 a publication by Oscher mentioned that despite being mistaken for right ventricular myocardial infarction, the ECG findings were not associated with myocardial ischemia.^[8]
• Although the ECG findings of Brugada syndrome were first reported among survivors of cardiac arrest in 1989, it was only in 1992 that the Brugada brothers recognized it as a distinct clinical entity, causing sudden death by causing ventricular fibrillation.^[9][10]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Approximately 20% of persons with Brugada syndrome have a mutation in the gene SCN5A. This gene encodes for the sodium ion channel. The mutation is inherited in an autosomal dominant pattern, and is more commonly seen in males. Brugada syndrome has also been shown to result from defects in a calcium channel.

• 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).^[1]
• 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.^[2][3]

• 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. ^[7]

• 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).^[8]

• 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.^{[9] [10] [11] [12] [13] [14] [15]}

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.^[16]
2. Glycerol-3-phosphate dehydrogenase (GPD1L) is associated with progressive conduction disease and low sensitivity to procainamide resulting from decreased sodium 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.^[17][18]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Brugada syndrome should be differentiated from other cardiac disorders, electrolyte disturbances, and drug intoxication syndromes. The condition which most similarly presents to Brugada syndrome is arrhythmogenic right ventricular dysplasia, as they both cause sudden cardiac death in children. Brugada syndrome can be differentiated from arrhythmogenic right ventricular dysplasia by the genetic counterpart of SCN5A, the lack of structural abnormalities within the heart, the association with polymorphic ventricular tachycardia during sleep, and EKG changes that are enhanced by vagotonic agents.

• Abnormalities that can lead to ST-segment elevation in the right precordial leads include the following:^[1]
  • Acute myocardial ischemia or infarction
  • Acute myocarditis
  • Acute pericarditis
  • Acute pulmonary thromboemboli
  • Arrhythmogenic right ventricular dysplasia / cardiomyopathy (ARVD/C)^[2][3]
  • Cardioversion. Brugada-like ECG changes can be observed briefly after direct-current cardioversion. It is currently unclear if this is a sign that the patient is a gene carrier for Brugada syndrome.^[4][5][6]
  • Cocaine intoxication
  • Coronary spasm
  • Dissecting aortic aneurysm^[7]
  • Duchenne muscular dystrophy^[8]
  • Early repolarization
  • Friedreich ataxia
  • Heterocyclic antidepressant overdose
  • Hypercalcemia^[9][10]
  • Hyperkalemia^[11][12][13]
  • Hypothermia, can cause an Osborn wave on the ECG which can sometimes resemble Brugada syndrome^[14][15]
  • Left ventricular hypertrophy
  • Pectus excavatum^[16]
  • Prinzmetal’s angina^[17]
  • Mediastinal tumor compressing the right ventricular outflow tract (RVOT)
  • Right or left bundle-branch block (atypical)
  • Right ventricular infarction
  • Right ventricular ischemia
  • Right ventricular outflow tract compression due to a mediastinal tumoror hemopericardium^[18][19]
  • Thiamine deficiency^[20]
  • Various central and autonomic nervous system abnormalities
  • [Other conditions that can lead to ST-segment elevation in the right precordial leads]]
  • Early repolarization syndrome
  • Other normal variants (particularly in males)

Although both Brugada syndrome and arrhythmogenic right ventricular dysplasia are associated with sudden cardiac death in young patients, the two syndromes are fairly easy to distinguish electrocardiographically and clinically.^[21]

• There is only one gene associated with Brugada syndrome, namely the SCN5A gene, and there is no overlap of the genetic abnormalities associated with arrhythmogenic right ventricular dysplasia.

• While Brugada syndrome is not associated with structural abnormalities in the right ventricle, arrhythmogenic right ventricular dysplasia is associated with fibrofatty infiltration.

• Arrhythmogenic right ventricular dysplasia is associated with monomorphic ventricular tachycardia with a left bundle branch morphology and is precipitated by catecholamines or exercise. In contrast, Brugada syndrome is associated with polymorphic ventricular tachycardia and occurs predominantly during sleep or rest.

• The EKG abnormalities of Brugada syndrome are enhanced by vagotonic agents, beta-adrenergic blockers, and sodium channel blockers whereas the EKG changes of arrhythmogenic right ventricular dysplasia are constant and do not very with vagotonic agents, beta-adrenergic blockers, or sodium channel blockers.

Template:WH Template:WS CME Category::Cardiology

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

Insofar as Brugada syndrome is a relatively newly recognized syndrome, its incidence and prevalence continues to increase. Brugada syndrome is quite common in Southeast Asia where it is endemic, and affects 500 out of every 100,000 individuals. It is the second leading cause of death after car accidents among young people in these countries. It has been estimated that Brugada syndrome accounts for 4% of all sudden cardiac deaths and 20% of sudden cardiac deaths among patients with structurally normal hearts. It is 8-10 times more common in men.

• The prevalence of the Brugada syndrome is estimated at 50:100,000, largely depending on geographic location.^[1]

• The incidence of Brugada syndrome increases with age; the median age at diagnosis is 43 years.^[2][3]
• 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. Brugada syndrome usually becomes apparent in adulthood, although signs and symptoms, including sudden death, can occur any time from early infancy to old age. The mean age of sudden death is approximately 40 years. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep. Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.^[4]

• Brugada syndrome usually affects individuals of Asian ancestry, particularly in Japanese and Southeast Asian populations.^[5]
• Brugada syndrome is the most common cause of sudden death in young men without known underlying cardiac disease in Thailand and Laos.
• Among different Asian countries, different names have been given to SUDS: in the Phillipines it is called bangungut (to rise and moan in sleep) and in Thailand lai tai (death during sleep).^[6]

• Brugada syndrome affects men and women.^[7]
• Men are more commonly affected by Brugada syndrome than women. The men to women ratio is approximately 8 to 10 .^[8]

Template:WH Template:WS CME Category::Cardiology

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

The EKG changes of Brugada syndrome can vary 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. During sleep, there is heightened vagal tone, and the pattern may be exacerbated at that time (as is the risk of sudden cardiac death at that time). The administration of class Ia, Ic and III drugs increases the ST segment elevation, as does fever. The impact of exercise depends upon when the EKG is obtained: during exercise the ST segment elevation may decrease but may increase later after exercise when the body temperature has risen. Similar to early repolarization variant, when the heart rate decreases, the ST segment elevation increases and when the heart rate increases the ST segment elevation decreases. While Brugada syndrome is often associated with polymorphic VT which may be self terminating, in the presence of autonomic imbalance, hypokalemia, fever or exacerbating drugs sustained ventricular fibrillation and sudden cardiac death may result.^[1]

The electrocardiographic findings of Brugada syndrome are often concealed, but can be unmasked or modulated by a number of drugs and pathophysiological states including (in alphabetical order):^[1]

• A combination of glucose and insulin. In Thailand large meals of glutinous sticky carbohydrate rich rice have been associated with sudden cardiac death.^[2][3]
  • Ajmaline (a diagnostic test agent)^[4]
  • α-adrenergic agonists^[5]
  • β-adrenergic blockers such as propranolol.^[6][5]
  • Calcium channel blockers

  • Diltiazem
  • Nifedipine
  • Verapamil

  • Carotid sinus massage
  • Cocaine^[7][8][9]
  • Dimenhydrinate
  • Family History: In large studies, a family history of sudden cardiac death among patients with Brugada syndrome does not appear to be a risk factor for sudden cardiac death in siblings.
  • Fever^[10].^{[11][12][13][14]} Hot baths and warm climates (such as that in Northeastern Thailand) may be precipitating factors for sudden cardiac death. It is for this reason that antipyretic agents are recommended to aggressively treat a fever in the patient with Brugada syndrome.
  • Flecainide^{[6][15][16][17]} (a diagnostic test agent)
  • Heat stroke^[18]
  • Hypercalcemia^[19][20]
  • Hyperkalemia^[21][22][23]
  • Hypokalemia.^[24] Hypokalemia in a patient with Brugada syndrome may trigger sustained ventricular fibrillation and sudden cardiac death. In northeastern Thailand where potassium deficiency is widespread, there is a higher incidence of sudden cardiac death than is observed in Bangkok where potassium levels in food are much higher.^[3]
  • Lithium. Administration of Lithium can result in EKG manifestations of the Brugada syndrome. ^[25][26]. Syncope and sudden cardiac death have been observed in these patients.^[27] The putative role of lithium has been suggested in so far as withdrawal of lithium results in either 1) normalization of the ECG or 2) conversion of the Brugada pattern to type 2 or 3. The appearance of Brugada type EKG patterns does not require toxic lithium levels.
  • Phenothiazines

  • Perphenazine
  • Cyamemazine

  • Potassium channel openers such as nicorandil.
  • Procainamide^{[6] [5]}(a diagnostic test agent)
  • Propranolol intoxication^[28]
  • Selective serotonin reuptake inhibitors

  • Fluoxetine

  • Shaving due to vagal stimulation^[29][30][31]
  • Sleep may exacerbate the electrocardiographic and clinical findings of brugada syndrome due to variations in the balance of sympathetic versus vagal tone, hormonal changes and other metabolic factors.^{[1][32][33][30]}
  • Sodium channel blockers^{[34][6][35][16]} (a diagnostic test agent)
  • Tetracyclic antidepressants^[36]

  • Maprotiline

  • Tricyclic antidepressants^{[37][38][36][8]}

  • Amitriptyline
  • Nortriptyline
  • Desipramine^[39]
  • Clomipramine

  • Vagotonic agents, heightened vagal tone and vagal maneuvers^[29][30][31]

• Less common risk factors in the development of [disease name] include:
  • [Risk factor 1]
  • [Risk factor 2]
  • [Risk factor 3]

In a study of 547 individuals who had confirmed Brugada syndrome who had no prior history of cardiac arrest, Brugada and associates identified the following correlates of future events:^[40]

Patients who are inducible at the time electrophysiologic study have an eightfold increased risk of aborted sudden cardiac death compared with those patients who are not inducible.^[41] Some groups have advocated that programmed electrical stimulation (PES) be performed to induce ventricular fibrillation for risk assessment in Brugada patients ^[42][43] Other groups have not reproduced the predictive value of these tests,^[44][45] so the value of programmed electrical stimulation (PES) and inducibility remains controversial.

The presence of a spontaneous abnormal Type I pattern of ST segment elevation is associated with a 7.7 fold increased risk of in arrhythmic event during a patient’s lifetime compared with those patients who only develop a Type I pattern following sodium blocker infusion.^[46]

Male gender is associate with the 5.5 fold increased risk of sudden cardiac death.^[47]

A family history of the disease is not associated with a higher risk of sudden death compared with sporadic occurrence of the disease.^[48]

In another study, Brugada has reported that the symptoms of the patient may aid in risk stratification:^[49]

• Brugada syndrome patients who present with aborted sudden cardiac death are at particularly high risk of recurrence with an incidence of 69% at 54 months of follow-up in the Brugada series.
• Brugada syndrome patients with syncope and Type 1 ST elevation pattern have a 19% risk of recurrence at 26 months.
• Brugada syndrome patients who are asymptomatic have an 8% risk of cardiac events over the same time period.

Genetic testing does not identify patients at high risk of sudden cardiac death and does not aid in risk stratification.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Screening for Brugada syndrome is recommended. Relatives of patients with Brugada syndrome can be screened for the syndrome by obtaining an EKG, although the diagnostic pattern may be concealed. Genetic testing can also be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.

• Screening for Brugada syndrome is recommended. Relatives of patients with Brugada syndrome can be screened for the syndrome by obtaining an EKG, although the diagnostic pattern may be concealed. Genetic testing can also be used to support the diagnosis of Brugada syndrome and to detect relatives at risk.^[1][2]
• Unfortunately, despite the association of the Brugada syndrome with the SCN5A genotype, there is unfortunately no association between the results of genetic testing and clinical prognosis.

Template:WH Template:WS CME Category::Cardiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Brugada syndrome usually becomes apparent in adulthood, although it may present in infants and children as sudden cardiac death. The mean age of sudden death in patients with Brugada syndrome is 40 years old. The Brugada patient may develop atrial arrhythmias and abnormalities in atrial conduction, and these abnormalities are associated with inducibility of ventricular fibrillation. Implantation of a cardiac defibrillator AICD can improve prognosis for some.

Brugada syndrome usually becomes apparent in adulthood, although signs and symptoms, including sudden death, can occur any time from early infancy to old age. The mean age of sudden death is approximately 40 years. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep. Sudden unexplained nocturnal death syndrome (SUNDS) is a condition characterized by unexpected cardiac arrest in young adults, usually at night during sleep. This condition was originally described in Southeast Asian populations, where it is a major cause of death. Researchers have determined that SUNDS and Brugada syndrome are the same disorder.

Patients with Brugada syndrome frequently develop or are born with supraventricular tachycardias:^[1]

• Supraventricular tachycardia: 20% of Brugada patients
• Atrial fibrillation: 10% – 20% of Brugada patients
• Atrioventricular (AV) nodal reentrant tachycardia
• Wolff-Parkinson-White syndrome^[2]

Disturbances of atrial conduction and sinus node function have also been reported:

• Prolonged sinus node recovery time and sinoatrial conduction time ^[3]
• Slowed atrial conduction^[4]
• Atrial standstill^[4]

The appearance of atrial arrhythmias and impaired atrial conduction are remarkable in so far as these findings are associated with inducibility of ventricular fibrillation.^[5] Indeed those patients who undergo implantation of a defibrillator (AICD) have twice the incidence of atrial arrhythmias (27% versus 13%)(p<0.05).

The following arrhythmias may occur in the patient with Brugada syndrome:

• Polymorphic VT resembling a rapid Torsade de Pointes (TdP) as shown below:

• Common complications of Brugada syndrome include:
  • Monomorphic VT is observed infrequently
  • 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.^[6]

• Patients who are symptomatic with unexplained syncope, ventricular tachycardia or aborted sudden cardiac death may have a symptom recurrence risk of 2% to 10% per year. In these patients an AICD implant is advisable.^[7]
  

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