Brugada syndrome is an inherited channelopathy, characterized by large J-waves and coved ST elevation with associated T-wave inversion in leads V1-V3, that causes an increased risk of ventricular tachycardia (VT) and ventricular fibrillation (VF), leading to syncope and sudden death. Diagnosis is by ECG and often provocative electrodiagnostic testing and/or genetic testing. Treatment is with an implanted cardioverter-defibrillator. Family members should be screened.
(See also Overview of Arrhythmias and Overview of Channelopathies.)
Overall the incidence of Brugada syndrome is approximately 5 in 10,000 (1) but shows wide variation with ethnicity and, consequently geographical region, being highest is Southeast Asia (37 in 10,000), the Middle East (18/10,000), and the rest of Asia (17 in 10,000) and much lower in Europe (1/10,000) and North America (0.5/10,000) (1). The majority of patients with clinically apparent Brugada syndrome are male (85%) (1).
General reference
1. Vutthikraivit W, Rattanawong P, Putthapiban P, et al: Worldwide Prevalence of Brugada Syndrome: A Systematic Review and Meta-Analysis. Acta Cardiol Sin 34(3):267–277, 2018. doi: 0.6515/ACS.201805_34(3).20180302B
Pathophysiology of Brugada Syndrome
Brugada syndrome results from mutations that
Decrease inward sodium or calcium currents OR
Increase early outward potassium currents
These abnormalities lead to early loss of the action potential plateau, particularly in the epicardial cells of the right ventricular outflow tract that produce characteristic right precordial ECG changes and a propensity to ventricular tachyarrhythmias. Although different mutations have been reported, most are in the SCN5A gene, producing a loss-of-function of the inward sodium current (1).
Typically, patients have no structural heart disease. Nevertheless, relationships with other genetic and acquired structural heart diseases are increasingly being recognized, as are overlap syndromes with long QT syndrome type 3, with the early repolarization syndrome, and with arrhythmogenic right ventricular cardiomyopathy (ARVC).
Pathophysiology reference
1. Antzelevitch C, Yan GX, Ackerman MJ, et al: J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 13(10):e295–324, 2016. doi: 10.1016/j.hrthm.2016.05.024
Symptoms and Signs of Brugada Syndrome
In some patients, Brugada syndrome has no clinical expression. However, in many patients it leads to syncope or sudden cardiac death due to polymorphic ventricular tachycardia and ventricular fibrillation. Ventricular arrhythmias can cause sudden death during sleep. About 10% of patients develop atrial tachyarrhythmias, predominantly atrial fibrillation (1), and some even present with atrial fibrillation (2).
cocaine (3).
Symptoms and signs references
1. Giustetto C, Cerrato N, Gribaudo E, et al: Atrial fibrillation in a large population with Brugada electrocardiographic pattern: prevalence, management, and correlation with prognosis. Heart Rhythm 11(2):259–265, 2014. doi: 10.1016/j.hrthm.2013.10.043
2. Rodríguez-Mañero M, Namdar M, Sarkozy A, et al: Prevalence, clinical characteristics and management of atrial fibrillation in patients with Brugada syndrome. Am J Cardiol 111(3):362–367, 2013. doi:10.1016/j.amjcard.2012.10.012
3. Antzelevitch C, Yan GX, Ackerman MJ, et al: J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 13(10):e295–324, 2016. doi: 10.1016/j.hrthm.2016.05.024
Diagnosis of Brugada Syndrome
Electrocardiography (ECG)
Family history
Provocative testing to induce characteristic ECG changes
Genetic testing
Diagnosis should be considered in patients with unexplained cardiac arrest or syncope or a family history of such when the affected people do not have structural heart disease.
Initial diagnosis of Brugada syndrome is based on a characteristic ECG pattern, the type 1 Brugada ECG pattern (see figure Type 1 Brugada ECG Pattern). The type 1 Brugada ECG pattern has prominent ST elevation in V1 and V2 (sometimes involving V3) that causes the QRS complex in these leads to resemble right bundle branch block. The ST segment is coved and descends to an inverted T-wave. Only a spontaneous type 1 pattern is considered diagnostic for Brugada syndrome according to the Shanghai Brugada syndrome score (1).
1). In such cases, the diagnosis of Brugada syndrome is considered possible. Application of clinical, family history, and genetic criteria is the required to establish the diagnosis (1).
The role of electrophysiologic testing is currently debated. Inducible ventricular tachycardia or ventricular fibrillation with programmed ventricular stimulation limited to 2 extra stimuli received a class IIa indication for patients who are asymptomatic with a spontaneous type 1 Brugada ECG pattern for risk stratification (2) but is not part of the Shanghai diagnostic scoring system (1). Genetic testing is usually recommended but has a yield of approximately 20% (3).
The diagnosis of Brugada syndrome includes considering, and ruling out, other disorders that produce similar cardiac findings, including hypothermia, hypocalcemia, right bundle branch block, arrhythmogenic right ventricular cardiomyopathy, acute pulmonary embolism, and left anterior descending coronary artery of conus branch of the right coronary artery occlusion (1).
Type 1 Brugada ECG Pattern
Prominent J-point elevation to a coved ST segment, leading to an inverted T-wave in leads V1 and V2. |
Diagnosis references
1. Antzelevitch C, Yan GX, Ackerman MJ, et al: J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 13(10):e295–324, 2016. doi: 10.1016/j.hrthm.2016.05.024
2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al: 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 138(13):e272–e391, 2018. doi: 10.1161/CIR.0000000000000549
3. Wilde AAM, Semsarian C, Márquez MF, et al: European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. J Arrhythm 38(4):491–553, 2022. doi: 10.1002/joa3.12717
Treatment of Brugada Syndrome
Implantable cardioverter-defibrillator
Screening of family members
Patients with a spontaneous or provoked type 1 Brugada syndrome ECG pattern and recent unexplained syncope, sustained VT, or cardiac arrest should typically have an implantable cardioverter-defibrillator (ICD) (1).
2). In patients refractory to such therapy, catheter ablation of the arrhythmogenic substrate may be considered (3).
Best treatment of Brugada syndrome in patients diagnosed based on ECG changes and family history but who do not have syncope or arrhythmia is unclear, although they do have increased risk of sudden death. Scoring systems have been developed to aid in determining if an ICD is appropriate therapy in such patients (4).
Treatment references
1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al: 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation 138(13):e272–e391, 2018. doi: 10.1161/CIR.0000000000000549
2. Brodie OT, Michowitz Y, Belhassen B: Pharmacological Therapy in Brugada Syndrome. Arrhythm Electrophysiol Rev 7(2):135–142, 2018. doi: 10.15420/aer.2018.21.2
3. Antzelevitch C, Yan GX, Ackerman MJ, et al: J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 13(10):e295–324, 2016. doi: 10.1016/j.hrthm.2016.05.024
4. Rattanawong P, Mattanapojanat N, Mead-Harvey C, et al: Predicting arrhythmic event score in Brugada syndrome: Worldwide pooled analysis with internal and external validation. Heart Rhythm 20:1358–1367, 2023. doi: 10.1002/joa3.12822
Prevention of Brugada Syndrome Arrhythmias
It is important to avoid factors that can trigger arrhythmias. Patients should monitor their temperature during infectious illness and take antipyretic therapy for fever. When possible, clinicians should stop any predisposing medications and prescribe alternatives. Patients should avoid substances, particularly cocaine and excessive alcohol, that are arrhythmogenic in Brugada syndrome (for an up-to-date list, see www.brugadadrugs.org).
Key Points
Brugada syndrome is a genetic disorder causing characteristic ECG changes and an increased risk of ventricular arrhythmias causing syncope and sometimes sudden cardiac death at a relatively young age.
Risk factors for symptomatic arrhythmias include fever and numerous medications and other substances (eg, alcohol, cocaine).
Diagnosis is by ECG, sometimes with provocative testing.
An implantable cardioverter-defibrillator may be required.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
www.brugadadrugs.org: Aims to provide up-to-date information on safe medication use in Brugada syndrome
