Brugada Syndrome 

Updated: Apr 03, 2020
Author: Jose M Dizon, MD; Chief Editor: Mikhael F El-Chami, MD 

Overview

Practice Essentials

Brugada syndrome is a disorder characterized by sudden death associated with one of several ECG patterns characterized by incomplete right bundle-branch block and ST-segment elevations in the anterior precordial leads. See the image below.

Three types of ST-segment elevation in Brugada syn Three types of ST-segment elevation in Brugada syndrome, as shown in the precordial leads on ECG in the same patient at different times. Left panel shows a type 1 ECG pattern with pronounced elevation of the J point (arrow), a coved-type ST segment, and an inverted T wave in V1 and V2. The middle panel illustrates a type 2 pattern with a saddleback ST-segment elevated by >1 mm. The right panel shows a type 3 pattern in which the ST segment is elevated < 1 mm. According to a consensus report (Antzelevitch, 2005), the type 1 ECG pattern is diagnostic of Brugada syndrome. Modified from Wilde, 2002. Image courtesy of Richard Nunez, MD, and EMedHome.com (http://www.emedhome.com/).

Signs and symptoms

Signs and symptoms in patients with Brugada syndrome may include the following:

  • Syncope and cardiac arrest: Most common clinical manifestations; in many cases, cardiac arrest occurs during sleep or rest

  • Nightmares or thrashing at night

  • Asymptomatic, but routine ECG shows ST-segment elevation in leads V1-V3

  • Associated atrial fibrillation (20%)[1]

  • Fever: Often reported to trigger or exacerbate clinical manifestations

The lack of a prodrome has been reported to be more common in patients with ventricular fibrillation documented as the cause of syncope in patients with Brugada syndrome.[2]

See Presentation for more detail.

Diagnosis

Most patients with Brugada syndrome have a normal physical examination. However, such an examination is necessary to exclude other potential cardiac causes of syncope or cardiac arrest in an otherwise healthy patient (eg, heart murmurs from hypertrophic cardiomyopathy or from a valvular or septal defect).

Testing

In patients with suspected Brugada syndrome, consider the following studies:

  • 12-lead ECG in all patients with syncope

  • Drug challenge with a sodium channel blocker in patients with syncope without an obvious cause

  • Electrophysiologic study to determine the inducibility of arrhythmias for risk stratification

Laboratory tests that may aid in the diagnosis of Brugada syndrome include the following:

  • Serum potassium and calcium levels: In patients presenting with ST-segment elevation in the right precordial leads

  • Potassium and calcium levels: ECG patterns in patients with hypercalcemia and hyperkalemia similar to that of Brugada syndrome

  • CK-MB and troponin levels: In patients with symptoms compatible with an acute coronary syndrome

  • Genetic testing for a mutation in SCN5A

Further testing may be indicated to exclude other diagnostic possibilities.

Imaging studies

Perform echocardiography and/or MRI, primarily to exclude arrhythmogenic right ventricular cardiomyopathy, as well as to assess for other potential causes of arrhythmias.

See Workup for more detail.

Management

To date, the only treatment that has proven effective in treating ventricular tachycardia and fibrillation and preventing sudden death in patients with Brugada syndrome is implantation of an automatic implantable cardiac defibrillator (ICD). Radiofrequency catheter ablation has been recently reported as an effective new treatment.[3, 4, 5, 6, 7]

No pharmacologic therapy has been proven to reduce the occurrence of ventricular arrhythmias or sudden death; however, theoretically, drugs that counteract the ionic current imbalance in Brugada syndrome could be used to treat it. For example, quinidine, which blocks the calcium-independent transient outward potassium current (Ito), has been shown to normalize the ECG pattern in patients with Brugada syndrome.[8] However, quinidine also blocks sodium (Na) currents, which could have contrary effects.

See Treatment and Medication for more detail.

Background

Brugada syndrome is a disorder characterized by sudden death associated with one of several electrocardiographic (ECG) patterns characterized by incomplete right bundle-branch block and ST elevations in the anterior precordial leads. See the image below.

Three types of ST-segment elevation in Brugada syn Three types of ST-segment elevation in Brugada syndrome, as shown in the precordial leads on ECG in the same patient at different times. Left panel shows a type 1 ECG pattern with pronounced elevation of the J point (arrow), a coved-type ST segment, and an inverted T wave in V1 and V2. The middle panel illustrates a type 2 pattern with a saddleback ST-segment elevated by >1 mm. The right panel shows a type 3 pattern in which the ST segment is elevated < 1 mm. According to a consensus report (Antzelevitch, 2005), the type 1 ECG pattern is diagnostic of Brugada syndrome. Modified from Wilde, 2002. Image courtesy of Richard Nunez, MD, and EMedHome.com (http://www.emedhome.com/).

In the initial description of Brugada syndrome, the heart was reported to be structurally normal, but this concept has been challenged.[9] Subtle structural abnormalities in the right ventricular outflow tract have been reported.

Brugada syndrome is genetically determined and has an autosomal dominant pattern of transmission in about 50% of familial cases (see Etiology). The typical patient with Brugada syndrome is young, male, and otherwise healthy, with normal general medical and cardiovascular physical examinations.

Patients with Brugada syndrome are prone to develop ventricular tachyarrhythmias that may lead to syncope, cardiac arrest, or sudden cardiac death.[10, 11, 12] Infrahisian conduction delay and atrial fibrillation may also be manifestations of the syndrome.[13, 14]

About 5% of survivors of cardiac arrest have no clinically identified cardiac abnormality. About half of these cases are thought to be due to Brugada syndrome.[15]

At present, implantation of an automatic implantable cardiac defibrillator (ICD) is the only treatment proven effective in treating ventricular tachycardia and fibrillation and preventing sudden death in patients with Brugada syndrome (see Treatment).

Pathophysiology

Brugada syndrome is an example of a channelopathy, a disease caused by an alteration in the transmembrane ion currents that together constitute the cardiac action potential. Specifically, in 10-30% of cases, mutations in the SCN5A gene, which encodes the cardiac voltage-gated sodium channel Nav 1.5, have been found. These loss-of-function mutations reduce the sodium current (INa) available during the phases 0 (upstroke) and 1 (early repolarization) of the cardiac action potential.

This decrease in INa is thought to affect the right ventricular endocardium differently from the epicardium. Thus, it underlies both the Brugada ECG pattern and the clinical manifestations of the Brugada syndrome.

The exact mechanisms underlying the ECG alterations and arrhythmogenesis in Brugada syndrome are disputed.[16] The repolarization-defect theory is based on the fact that right ventricular epicardial cells display a more prominent notch in the action potential than endocardial cells. This is thought to be due to an increased contribution of the transient outward current (Ito) to the action potential waveform in that tissue.

A decrease in INa accentuates this difference, causing a voltage gradient during repolarization and the characteristic ST elevations on ECG. Research has provided human evidence for a repolarization gradient in patients with Brugada syndrome using simultaneous endocardial and epicardial unipolar recordings.[17] See the image below.

Schematics show the 3 types of action potentials i Schematics show the 3 types of action potentials in the right ventricle: endocardial (End), mid myocardial (M), and epicardial (Epi). A, Normal situation on V2 ECG generated by transmural voltage gradients during the depolarization and repolarization phases of the action potential. B-E, Different alterations of the epicardial action potential that produce the ECG changes observed in patients with Brugada syndrome. Adapted from Antzelevitch, 2005.

When the usual relative durations of repolarization are not altered, the T wave remains upright, causing a saddleback ECG pattern (type 2 or 3). When the alteration in repolarization is sufficient to cause a reversal of the normal gradient of repolarization, the T wave inverts, and the coved (type 1) ECG pattern is seen. In a similar way, a heterogeneous alteration in cardiac repolarization may predispose to the development of reentrant arrhythmias, termed phase 2 reentry, that can clinically cause ventricular tachycardia and ventricular fibrillation.[18]

An alternative hypothesis, the depolarization/conduction disorder model, proposes that the typical Brugada ECG findings can be explained by slow conduction and activation delays in the right ventricle (in particular in the right ventricular outflow tract).[16]

One study used ajmaline provocation to elicit a type 1 Brugada ECG pattern in 91 patients, and found that the repolarization abnormalities were concordant with the depolarization abnormalities and appeared to be secondary to the depolarization changes.[19] Using vectorcardiograms and body surface potential maps, investigators were able to show that depolarization abnormalities and conduction delay mapped to the right ventricle.

Etiology

The prototypical case of Brugada syndrome has been associated with alterations in the SCN5A gene, of which nearly 300 mutations have been described.[20] Mutations in other genes have been proposed to cause a variant of Brugada syndrome, including the genes coding for alpha1- and beta2b-subunits of the L-type calcium channel (CACNA1C and CACNB2), which are thought to cause a syndrome of precordial ST elevation, sudden death, and short QT interval.[21]

Mutations in the genes GPD1-L[22] and SCN1B[23] have been identified in a few familial cases. Cases in which a mutation in the SCN5A gene cannot be demonstrated may be due to mutations of these genes, due to other unidentified genes, or located in regions of the coding sequence or promoter region of SCN5A that are not routinely sequenced in lab tests.

Many clinical situations have been reported to unmask or exacerbate the ECG pattern of Brugada syndrome. Examples are a febrile state, hyperkalemia, hypokalemia, hypercalcemia, alcohol or cocaine intoxication, and the use of certain medications, including sodium channel blockers, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, heterocyclic antidepressants, and a combination of glucose and insulin.[18]

Epidemiology

United States statistics

Because of its recent identification, the prevalence of Brugada syndrome is not well established. In a large university hospital on the West Coast of the United States, the prevalence of a Brugada ECG pattern among unselected, mainly white and Hispanic adults was 2 of 1348 patients (0.14%); in both cases, the ECG patterns were type 2.[24] The prevalence in Asian and other ethnic populations may be higher.

International statistics

The highest prevalence of Brugada syndrome is in Southeast Asia; the lowest is in North Africa.[25] In parts of Asia (eg, the Philippines, Thailand, Japan), Brugada syndrome seems to be the most common cause of natural death in men younger than 50 years. It is known as Lai Tai (Thailand), Bangungot (Philippines), and Pokkuri (Japan). In Northeast Thailand, the mortality rate from Lai Tai is approximately 30 cases per 100,000 population per year.[26]

Race-, sex-, and age-related demographics

Brugada syndrome is most common in people from Asia. The reason for this observation is not yet fully understood but may be due to an Asian-specific sequence in the promoter region of SCN5A.[27]

Brugada syndrome is 8-10 times more prevalent in men than in women, although the probability of having a mutated gene does not differ by sex. The penetrance of the mutation therefore appears to be much higher in men than in women.

Brugada syndrome most commonly affects otherwise healthy men aged 30-50 years, but affected patients aged 0-84 years have been reported. The mean age of patients who die suddenly is 41 years.[18]

Prognosis

Brugada syndrome is a cause of polymorphic ventricular tachycardia, which may degenerate into ventricular fibrillation and cause cardiac arrest. Prolonged hypoxia during cardiac arrest may leave patients with neurologic sequelae. Implantable cardioverters-defibrillators (ICDs) are often used to treat patients with Brugada syndrome, exposing them to complications related to device implantation and the potential for inappropriate shocks.

During a mean follow-up of 24 months, sudden cardiac death or ventricular fibrillation occurred in 8.2% of patients with Brugada syndrome. A history of syncope, a spontaneously abnormal ECG, and inducibility during programmed electrical stimulation (by one study) significantly increased this risk.[11]

Brugada syndrome may be a significant cause of death, aside from accidents, in men under 40. The true incidence is not known due to reporting biases. Although there is a strong population dependence, an estimated 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts are due to the syndrome. Those with the syndrome have a mean age of sudden death of 41 ±15 years.[28]

Patient Education

Educating the patient and his or her family members and coworkers about basic cardiopulmonary resuscitation (CPR) is important. Genetic counseling is reasonable if desired by the patient and family.

 

Presentation

History and Physical Examination

History

Syncope and cardiac arrest are the most common clinical manifestations leading to the diagnosis of Brugada syndrome. Nightmares or thrashing at night may occur. However, some patients remain asymptomatic, and the diagnosis of Brugada syndrome is suggested by a routine electrocardiogram (ECG) showing ST-segment elevation in leads V1 through V3.

A family history of sudden cardiac death is common, though not universal, as the syndrome can occur sporadically. In about 20% of patients, atrial fibrillation is an associated arrhythmia.[1]

The context of the cardiac event is important. In many cases, cardiac arrest occurs during sleep or rest. Cases occurring during physical activity are rare. Fever is often reported to trigger or exacerbate the clinical manifestations of Brugada syndrome.

A 2012 study suggested that the quality of symptoms prior to syncope can predict a benign or malignant cause in patients with Brugada syndrome. Specifically, the lack of a prodrome was more common in patients with ventricular fibrillation documented as the cause of syncope.[2]

Physical examination

The physical examination is usually normal in patients with Brugada syndrome. Nevertheless, physical examination is required to rule out other possible cardiac causes of syncope or cardiac arrest in an otherwise healthy patient (eg, heart murmurs from hypertrophic cardiomyopathy or from a valvular or septal defect).

 

DDx

Diagnostic Considerations

The differential diagnosis of cardiac arrest in an otherwise presumably healthy subject is varied, but it includes such entities as acute cardiac ischemia due to atherosclerosis or coronary anomaly, hypertrophic cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy (ARVC). Many of these entities can be differentiated on the basis of history and physical examination. Occasionally, however, there is overlap that requires special consideration.

The differential diagnosis of right precordial ST-segment elevation is as follows[18, 29] :

  • Atypical right bundle-branch block
  • Left ventricular hypertrophy
  • Early repolarization
  • Acute pericarditis
  • Acute myocardial ischemia or infarction
  • Prinzmetal angina
  • Pulmonary embolism
  • Dissecting aortic aneurysm
  • Mediastinal tumor or hemopericardium compressing the right ventricular outflow tract
  • Arrhythmogenic right ventricular dysplasia and/or cardiomyopathy
  • Various abnormalities of the central and autonomic nervous systems
  • Overdose of a heterocyclic antidepressant
  • Cocaine intoxication
  • Duchenne muscular dystrophy
  • Friedreich ataxia
  • Thiamine deficiency Hypercalcemia
  • Hyperkalemia
  • Hypothermia
  • Pectus excavatum
  • Effects of athletic training

Differential Diagnoses

 

Workup

Approach Considerations

Many patients with Brugada syndrome are young and otherwise healthy and may present with syncope. Patients with syncope should not be assumed to have a benign condition, and a 12-lead ECG should be performed.

A drug challenge with a sodium channel blocker should be considered in patients with syncope in whom no obvious cause is found. An experienced physician should interpret the ECGs, and an electrophysiologist should review them if possible.

Further testing may be indicated to exclude other diagnostic possibilities.

Laboratory Studies

Check serum potassium and calcium levels in patients presenting with ST-segment elevation in the right precordial leads. Both hypercalcemia and hyperkalemia may generate an ECG pattern similar to that of Brugada syndrome.

Laboratory markers, such as creatine kinase-MB (CK-MB) and troponin, should be checked in patients who have symptoms compatible with an acute coronary syndrome. Elevations indicate cardiac injury.

Genetic Testing

Patients with high likelihood of Brugada syndrome may be genetically tested for a mutation in SCN5A, which codes for the alpha subunit Nav 1.5 of the cardiac sodium channel. The results of this test support the clinical diagnosis and are important for the early identification of family members at potential risk. However, the yield of genetic testing remains relatively low at this time, with mutations in SCN5A found in only 11-28% of index cases.[20]

Echocardiography and MRI

Echocardiography and/or MRI should be performed, mainly to exclude arrhythmogenic right ventricular cardiomyopathy. However, these studies are also used to assess for other potential causes of arrhythmias, such as hypertrophic cardiomyopathy, unsuspected myocardial injury, myocarditis, or aberrant coronary origins.

Electrocardiography

Three ECG patterns have been described in Brugada syndrome[29] (see the image and table below). Placing the right precordial leads in the second intercostal space has been proposed to add sensitivity to the ECG diagnosis of Brugada syndrome.[30] Exercise stress testing may suppress ECG changes and arrhythmias.

Three types of ST-segment elevation in Brugada syn Three types of ST-segment elevation in Brugada syndrome, as shown in the precordial leads on ECG in the same patient at different times. Left panel shows a type 1 ECG pattern with pronounced elevation of the J point (arrow), a coved-type ST segment, and an inverted T wave in V1 and V2. The middle panel illustrates a type 2 pattern with a saddleback ST-segment elevated by >1 mm. The right panel shows a type 3 pattern in which the ST segment is elevated < 1 mm. According to a consensus report (Antzelevitch, 2005), the type 1 ECG pattern is diagnostic of Brugada syndrome. Modified from Wilde, 2002. Image courtesy of Richard Nunez, MD, and EMedHome.com (http://www.emedhome.com/).

Table. ECG Patterns in Brugada Syndrome (Open Table in a new window)

Characteristic

Type 1

Type 2

Type 3

J wave amplitude

≥2 mm

≥2 mm

≥2 mm

T wave

Negative

Positive or biphasic

Positive

ST-T configuration

Cove-type

Saddleback

Saddleback

ST segment, terminal portion

Gradually descending

Elevated by ≥1 mm

Elevated by < 1 mm

Recently, the QRS duration on 12-lead ECG has been suggested as a risk marker for vulnerability to dangerous arrhythmias.[31, 32] Inferolateral repolarization abnormalities have also been proposed to be a marker of risk.[33, 34]

Asymptomatic patients with a type 1 ECG pattern on routine ECG represent a difficult case. According to the latest consensus guidelines, a clinical electrophysiologist should evaluate patients in this situation.[18] Patients should be risk-stratified using the techniques described below, and a decision on implantable cardioverter-defibrillator (ICD) implantation should be made accordingly.

Signal-averaged ECG

Arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome may be difficult to differentiate in some cases. Late potentials on signal-averaged ECG may reveal the fibrofatty degeneration of the right ventricle seen in ARVC.

Challenge with sodium channel blockers

In some patients, the intravenous administration of drugs that block sodium channels may unmask or modify the ECG pattern, aiding in diagnosis and/or risk stratification in some individuals. Infuse flecainide 2 mg/kg (maximum 150 mg) over 10 minutes, procainamide 10 mg/kg over 10 minutes, ajmaline 1 mg/kg over 5 minutes, or pilsicainide 1 mg/kg over 10 minutes. This challenge should be performed with continuous cardiac monitoring and in a setting equipped for resuscitation.

In patients with a normal baseline ECG, the results are positive when the drug generates a J wave with an absolute amplitude of 2 mm or more in leads V1, V2, and/or V3 with or without an RBBB. Administration of the drug should be stopped when the result is positive, when ventricular arrhythmia occurs, or when QRS widening of greater than 30% is observed.

Isoproterenol and sodium lactate may be effective as antidotes if the sodium channel blocker induces an arrhythmia, and the isoproterenol response may also have diagnostic use.

This drug test should not be performed in patients with a type 1 ECG pattern (see Table above) because it adds no new information.

In patients with the type 2 or 3 patterns, the drug challenge is recommended to clarify the diagnosis.[18] The sensitivity and specificity of drug challenge testing is not yet confirmed. A 2012 study examining patients with type 2 or 3 patterns showed that a positive drug challenge in symptomatic patients was associated with adverse events. However, asymptomatic patients with a similar result had a low event rate. This study suggests that a drug challenge may aid in risk stratification for symptomatic patients with a nondiagnostic ECG, but may not be justified in asymptomatic patients.[35]

Electrophysiologic Study

Some investigators use an electrophysiologic study (EPS) to determine the inducibility of arrhythmias, in an effort to risk-stratify patients with Brugada syndrome. However, the predictive value of this approach is debated. In 2001, Brugada showed that inducibility may be a good predictor of outcome.[36] However, in 2002, Priori reported a poor predictive value of invasive testing.[37] A subsequent study by Gehi concluded that EPS was not of use in guiding the management of patients with Brugada syndrome.[38]

More recently, investigators independently examining a large series of patients from Europe and Japan have failed to find any predictive value for EPS. In the large registry of Brugada syndrome patients from Europe, only symptoms and a spontaneous type 1 Brugada ECG pattern, but not EPS, were predictive of arrhythmic events.[39] In the smaller Japanese registry, only family history of sudden cardiac death at younger than 45 years and inferolateral early repolarization pattern on ECG predicted cardiac events.[34]

A study by Priori et al enrolled 308 patients with no history of cardiac arrest and a spontaneous or drug-induced type I ECG pattern.[40] Seventy eight of the patients had an ICD implanted prophylactically. EPS with a consistent stimulation protocol was performed on all patients; at a mean follow-up of 34 months, no differences were found in the incidence of appropriate ICD shocks or cardiac arrest between patients who were inducible and patients who were noninducible. Significant predictors of arrhythmia in this study included syncope and a spontaneous type I ECG pattern, a ventricular effective refractory period of less than 200 ms on EPS, and a fragmented QRS in the anterior precordial ECG leads.

Investigators from the United Kingdom examined a group of probands who suffered sudden arrhythmic death believed to be due to Brugada syndrome.[41] A retrospective review of risk factors determined that these patients would not have been considered high risk, calling into question the sensitivity of current risk factors (eg, symptoms, type I ECG pattern). However, few ECGs were available for examination in the probands with sudden death.

 

Treatment

Approach Considerations

To date, the only treatment that has proven effective in treating ventricular tachycardia and fibrillation and preventing sudden death in patients with Brugada syndrome is implantation of an automatic implantable cardiac defibrillator (ICD).[18] Radiofrequency catheter ablation has been recently reported as an effective new treatment.[3, 4, 5, 6, 7] No pharmacologic therapy has been proved to reduce the occurrence of ventricular arrhythmias or sudden death.

Placement of Implantable Cardioverter-Defibrillator

At present, implantation of an automatic implantable cardioverter-defibrillator (ICD) is the only treatment proved effective in treating ventricular tachycardia and fibrillation and preventing sudden death[18] in patients with Brugada syndrome. 

Indications for ICD implantation were published in the report of the Second Consensus Conference on Brugada syndrome.[28]  For patients at the two extremes of risk stratification, the decision to implant or not to implant an ICD is relatively straightforward.

Patients with Brugada syndrome and a history of cardiac arrest must be treated with an ICD. In contrast, asymptomatic patients with no family history of sudden cardiac death can be managed conservatively with close follow-up, and ICD implantation is not recommended. Patients with intermediate clinical characteristics present the greatest challenge. For details about risk stratification and indications for ICD implantation, readers are referred to the Second Consensus Conference report.[28]

Patients with syncope or cardiac arrest and suspected or diagnosed Brugada syndrome must be hospitalized. Continuous cardiac monitoring is necessary until definitive treatment (ie, ICD placement) can be provided.

Activity

Because regular physical activity may increase vagal tone, sport may eventually enhance the propensity of athletes with Brugada syndrome to have ventricular fibrillation and sudden cardiac death at rest or during recovery after exercise. Accordingly, Pelliccia et al recommended that patients with a definite diagnosis of Brugada syndrome be restricted from participation competitive sports.[42] However, no direct evidence supported this recommendation, and it was unclear whether asymptomatic carriers of SCN5A mutations should also be so restricted.

A scientific statement published in 2015 by the American Heart Association and the American College of Cardiology on athletic competition by persons with known or suspected cardiac channelopathies included the following recommendations related to Brugada syndrome[43] :

  • That a heart rhythm specialist or genetic cardiologist experienced in cardiac channelopathies conduct a thorough evaluation of an athlete in whom such a disorder has been diagnosed or is suspected
  • That asymptomatic athletes who are genotype-positive/phenotype-negative for long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization syndrome, short-QT syndrome, or idiopathic ventricular fibrillation be allowed to take part in all competitive sports if precautionary measures, such as the avoidance of drugs that exacerbate Brugada syndrome, are undertaken
  • That in an athlete with previously symptomatic or electrocardiographically evident Brugada syndrome, early repolarization syndrome, or short-QT syndrome, participation in competitive sports be considered if precautionary measures have been taken and disease-specific treatments are being administered and if the athlete has been asymptomatic on therapy for at least 3 months

Consultations

A board-certified cardiologist who specializes in cardiac arrhythmic disorders (ie, a clinical electrophysiologist) should evaluate patients with suspected Brugada syndrome. Consultation with a genetic counselor is indicated for genetic screening and counseling of patients and their relatives.

Long-Term Monitoring

A board-certified electrophysiologist should closely follow patients with Brugada syndrome. Taking a careful history is important, as not all syncope is necessarily arrhythmic in Brugada syndrome. For example, a clear prodrome suggesting vasovagal syncope does not suggest an adverse prognosis in an otherwise asymptomatic patient with a Brugada ECG pattern.

 

Guidelines

Guidelines Summary

Diagnosis

In its 2013 expert consensus statement on inherited primary arrhythmia syndromes, the Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society (HRS/EHRA/APHRS) recommended a diagnosis of  Brugada syndrome (BrS) when the following criteria are met[44] :

  • ST-segment elevation with type I morphology ≥2 mm in ≥1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space occurring either spontaneously or after provocative drug test with intravenous administration of Class I antiarrhythmic drugs
  • Type 2 or type 3 ST-segment elevation in ≥1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space when a provocative drug test with intravenous administration of class I antiarrhythmic drugs induces a type I ECG morphology

In 2015, the European Society of Cardiology (ESC) released guidelines for the management of ventricular arrhythmias and the prevention of sudden cardiac death (SCD) thatincluded the following specific recommendation for diagnosis of BrS.[45]

Class I (Level of evidence: C)

Brugada syndrome is diagnosed in patients with ST-segment elevation with type 1 morphology ≥2 mm in one or more leads among the right precordial leads V1 and/or V2 positioned in the second, third, or fourth intercostal space, occurring either spontaneously or after provocative drug test with intravenous administration of sodium channel blockers (such as ajmaline, flecainide, procainamide or pilsicainide).

Genetic testing

In 2011, the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) issued a joint expert consensus statement on genetic testing for channelopathies and cardiomyopathies with the following recommendations for BrS testing[46] :

  • Consider comprehensive or BrS1 (SCN5A) targeted genetic testing for individuals with strong clinical index of suspicion for BrS based on clinical history, family history, and expressed electrocardiographic phenotype (class IIa)
  • Mutation specific genetic testing for family members following identification of BrS mutation in an index case (class I)
  • Genetic testing is not indicated in the setting of an isolated type 2 or type 3 Brugada ECG pattern (class III)

Management and prevention of sudden cardiac death

The following is a summary of recommendation included in the 2015 ESC guidelines for management of of LQTS and preventions of SCD.[45]

Class I  (Level of evidence: C)

Lifestyle changes:

  • Avoidance of drugs that may induce ST-segment elevation in right precordial leads
  • Avoidance of excessive alcohol intake and large meals
  • Prompt treatment of any fever with antipyretic drugs.

ICD implantation in patients who are survivors of an aborted cardiac arrest and/or have documented spontaneous sustained ventricular tachycardia (VT).

Class IIa (Level of evidence: C)

Consider ICD in patients with a spontaneous diagnostic type I ECG pattern and history of syncope.

Consider quinidine or isoproterenol to treat electrical storms.

Consider quinidine for patients who qualify for an ICD but present a contraindication or refuse it and in patients who require treatment for supraventricular arrhythmias.

Class IIb (Level of evidence: C)

Consider ICD in patients who develop ventricular fibrillation during programmed ventricular stimulation with two or three extra stimuli at two sites.

Consider catheter ablation in patients with a history of electrical storms or repeated appropriate ICD shocks.

The 2013 HRS/EHRA/APHRS guidelines offer consistent recommendations. In additiona, the guidelines find ICD implantation is not indicated in asymptomatic BrS patients with a drug-induced type I ECG and on the basis of a family history of sudden cardiac death (SCD) alone.[44]

A scientific statement published in 2015 by the American Heart Association and the American College of Cardiology on athletic competition by persons with known or suspected cardiac channelopathies includes the following recommendations related to BrS[43] :

  • A heart rhythm specialist or genetic cardiologist experienced in cardiac channelopathies should conduct a thorough evaluation of an athlete in whom such a disorder has been diagnosed or is suspected (class I; level of evidence, C)
  • Symptomatic athletes with any suspected or diagnosed cardiac channelopathy should be restricted from all competitive sports until a comprehensive evaluation has been completed, the athlete and his or her family are well informed, a treatment program has been implemented, and the athlete has been asymptomatic on therapy for 3 months (class I; level of evidence, C)
  • Asymptomatic athletes who are genotype-positive/phenotype-negative for Brugada syndrome can be allowed to take part in all competitive sports if precautionary measures are taken, such as avoidance of drugs that exacerbate BrS, electrolyte/hydration replenishment and avoidance of dehydration, avoidance or treatment of hyperthermia from febrile illnesses or training-related heat exhaustion or heat stroke, possession of a personal automatic external defibrillator as part of the athlete’s personal sports safety gear, and establishment of an emergency action plan with the appropriate school or team officials (class IIa; level of evidence, C)
  • Competitive sports participation may be considered for an athlete with either previously symptomatic or electrocardiographically evident BrS, assuming appropriate precautionary measures and disease-specific treatments are in place and the athlete has been asymptomatic on treatment for at least 3 months (although treatment involving an implantable cardioverter-defibrillator is subject to additional recommendations) (class IIb; level of evidence, C)
 

Medication

Medication Summary

Theoretically, drugs that counteract the ionic current imbalance in Brugada syndrome could be used to treat it. For example, quinidine, which blocks the calcium-independent transient outward potassium current (Ito), has been shown to normalize the ECG pattern in patients with Brugada syndrome.[8] However, quinidine also blocks sodium (Na) currents, which could have contrary effects.

Tedisamil, a potent Ito blocker without strong Na channel effects, may be more effective than quinidine.[47] Isoproterenol, which boosts the L-type calcium current, can also counteract the ionic current imbalance.[47]

Thus far, no drug therapy for Brugada syndrome is recommended because clinical trials have failed to convincingly prove effectiveness.[28, 48, 49, 50] However, drugs such as isoproterenol can be used to treat VT storm. Quinidine can be used for patients who have recurrent appropriate ICD therapy.

A number of medications can unmask the Brugada pattern on ECG and potentially exacerbate the clinical manifestations of Brugada syndrome. The Web site BrugadaDrugs.org has been established to educate patients and professionals about these potentially dangerous medications.[51]

Antiarrhythmic Drugs

Class Summary

There is general consensus that certain drugs can be potentially antiarrhythmic in Brugada syndrome patients. However, there are no randomized clinical studies in Brugada syndrome patients. As such, only in the setting of long-term therapeutic treatment in an experienced medical center can practitioners consider the use of antiarrhythmics for high-risk patients. Currently, quinidine seems to be the treatment of choice for long-term therapy.

Quinidine

Quinidine maintains a normal heart rhythm following cardioversion of atrial fibrillation or flutter. It depresses myocardial excitability and conduction velocity. Prior to administration, control the ventricular rate and CHF (if present) with digoxin or calcium channel blockers.

 

Questions & Answers

Overview

What is Brugada syndrome (BrS)?

What are the signs and symptoms of Brugada syndrome (BrS)?

What is the significance of the lack of prodrome in Brugada syndrome (BrS)?

How is Brugada syndrome (BrS) diagnosed?

Which studies are used to diagnose Brugada syndrome (BrS)?

What is the role of lab testing in the diagnosis of Brugada syndrome (BrS)?

What is the role of echocardiography in the diagnosis of Brugada syndrome (BrS)?

What are the treatment options for Brugada syndrome (BrS)?

What is the role of pharmacologic therapy in the treatment of Brugada syndrome (BrS)?

What is Brugada syndrome (BrS)?

How is the heart affected in Brugada syndrome (BrS)?

What is the role of genetics in the etiology of Brugada syndrome (BrS)?

What are the clinical manifestations of Brugada syndrome (BrS)?

How is ventricular tachycardia managed in Brugada syndrome (BrS)?

What is the pathophysiology of Brugada syndrome (BrS)?

What is the repolarization-defect therapy of the pathogenesis of Brugada syndrome (BrS)?

Which readings on electrocardiogram (ECG) are characteristic of Brugada syndrome (BrS)?

What is depolarization/conduction disorder model of Brugada syndrome (BrS)?

What is the role of ajmaline provocation in the pathogenesis of Brugada syndrome (BrS)?

What is the role of genetics in Brugada syndrome (BrS)?

Which clinical situations may unmask or exacerbate the electrocardiogram (ECG) pattern of Brugada syndrome (BrS)?

What is the prevalence of Brugada syndrome (BrS) in the US?

What is the global prevalence of Brugada syndrome (BrS)?

What are the racial predilections for Brugada syndrome (BrS)?

How does the prevalence of Brugada syndrome (BrS) vary by sex?

How does the prevalence of Brugada syndrome (BrS) vary by age?

What is the prognosis of Brugada syndrome (BrS)?

What are the risk factors for sudden cardiac death in patients with Brugada syndrome (BrS)?

What is the incidence of cardiac death in patients with Brugada syndrome (BrS)?

What is included in the patient education information for Brugada syndrome (BrS)?

Presentation

What are the signs and symptoms of Brugada syndrome (BrS)?

What is a common finding in the history of patients with Brugada syndrome (BrS)?

When do most cardiac events of Brugada syndrome (BrS) occur?

What is the significance of a lack of prodrome in Brugada syndrome (BrS)?

What is the purpose of physical exam in the evaluation of Brugada syndrome (BrS)?

DDX

What is included in the differential diagnoses of cardiac arrest in Brugada syndrome (BrS)?

What is included in differential diagnoses of right precordial ST-segment elevation in Brugada syndrome (BrS)?

What are the differential diagnoses for Brugada Syndrome?

Workup

How should syncope be evaluated in suspected Brugada syndrome (BrS)?

Which lab studies are performed for the diagnosis of Brugada syndrome (BrS)?

What is the role of genetic testing in the diagnosis of Brugada syndrome (BrS)?

What is the role of echocardiography and/or MRI in the diagnosis of Brugada syndrome (BrS)?

Which electrocardiogram (ECG) patterns have been described in Brugada syndrome (BrS)?

What does the QRS duration on the 12-lead electrocardiogram (ECG) suggest in the evaluation of Brugada syndrome (BrS)?

When should an electrophysiologist be consulted in the diagnosis of Brugada syndrome (BrS)?

How are arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome (BrS) differentiated?

What is the role of sodium channel blockers in the workup of Brugada syndrome (BrS)?

What is the purpose of an electrophysiologic study (EPS) in the diagnosis of Brugada syndrome (BrS)?

What is the efficacy of electrophysiologic study (EPS) for the diagnosis of Brugada syndrome (BrS)?

Treatment

What are the treatment options for Brugada syndrome (BrS)?

What are the indications for implantable cardioverter-defibrillator (ICD) implantation in the treatment of Brugada syndrome (BrS)?

What are the treatment options for asymptomatic Brugada syndrome (BrS)?

When is hospitalization indicated for the treatment of Brugada syndrome (BrS)?

What are the activity restrictions for patients with Brugada syndrome (BrS)?

What are the AHA/ACC activity recommendations for patients with Brugada syndrome (BrS)?

Which specialists should be consulted in the diagnosis and management of Brugada syndrome (BrS)?

What is included in the long-term monitoring of patients with Brugada syndrome (BrS)?

Guidelines

What are the HRS/EHRA/ARHRS diagnostic criteria for Brugada syndrome (BrS)?

Which organization released treatment guidelines for ventricular arrhythmias and the prevention of sudden cardiac death (SCD) in patients with Brugada syndrome (BrS)?

What is the ESC diagnostic criteria for Brugada syndrome (BrS)?

What are the HRS/EHRA guidelines for genetic testing in Brugada syndrome (BrS)?

What are the ESC recommendations for lifestyle changes to manage Brugada syndrome (BrS) and prevent sudden cardiac death?

What are the ESC guidelines class IIa level recommendations for the treatment of Brugada syndrome (BrS)?

What are the ESC guidelines class IIb level recommendations for the treatment of Brugada syndrome (BrS)?

What are the AHA/ACC guidelines for athletic competition for patients with Brugada syndrome (BrS)?

Medications

Which medications are used in the treatment of Brugada syndrome (BrS)?

Which medications in the drug class Antiarrhythmic Drugs are used in the treatment of Brugada Syndrome?