What is Brugada Syndrome?
Brugada syndrome is an inherited cardiac channelopathy characterized by a distinctive ECG pattern of ST-segment elevation in the right precordial leads (V1-V3) that predisposes patients to life-threatening ventricular arrhythmias and sudden cardiac death, despite having a structurally normal heart. 1
Core Pathophysiology
Brugada syndrome is a primary electrical disease caused by dysfunction of cardiac ion channels, most commonly involving mutations in the SCN5A gene encoding the cardiac sodium channel (NaV1.5), though this accounts for only 20-30% of cases. 1, 2
The condition represents a channelopathy without structural heart abnormalities, distinguishing it from other causes of sudden cardiac death. 1
The disease is transmitted in an autosomal dominant pattern with incomplete penetrance, though recent evidence suggests more complex inheritance mechanisms may be involved. 1, 3
Diagnostic ECG Features
The hallmark ECG finding is a type 1 Brugada pattern: coved ST-segment elevation ≥2 mm in one or more right precordial leads (V1-V2), followed by a negative T-wave. 2, 4
The ECG pattern is characteristically intermittent and dynamic, not continuously present—it may appear spontaneously, during fever, in vagotonic states, or only after sodium channel blocker challenge (ajmaline, flecainide, procainamide). 2, 1
High electrode positioning in the second and third intercostal spaces improves detection of the type 1 pattern. 2
A single normal ECG does not exclude the diagnosis due to the fluctuating nature of the pattern. 2
Clinical Presentation and Demographics
Cardiac events occur predominantly in males (>90% of affected individuals) in their third and fourth decades of life, though presentation can range from neonates to the elderly. 1
Sudden cardiac death typically occurs at rest or during sleep, caused by rapid polymorphic ventricular tachycardia or ventricular fibrillation. 1
Clinical manifestations include syncope, cardiac arrest, or the condition may be entirely asymptomatic and discovered incidentally. 1
Critical Risk Factors and Triggers
Fever is a major precipitating factor that can acutely predispose to cardiac arrest and unmask the ECG pattern—aggressive antipyretic treatment is essential. 1, 5
Spontaneous type 1 ECG pattern carries significantly worse prognosis than drug-induced patterns. 1, 5
Patients with syncope and spontaneous type 1 ST-elevation have a 6-fold higher risk of cardiac arrest compared to asymptomatic patients with spontaneous ECG pattern. 1, 2
Annual arrhythmic event rates vary dramatically: 13.5% in cardiac arrest survivors, 3.2% in patients with syncope, and 1% in asymptomatic patients. 2, 5
Risk Stratification Challenges
Family history does not predict cardiac events among family members—asymptomatic individuals with characteristic ECG but no family history are not necessarily at low risk, and relatives of sudden death victims should not be assumed at increased risk. 1
The role of electrophysiological testing remains controversial: some data show high negative predictive value (93%) but low positive predictive value (23%), while other studies demonstrate poor accuracy in predicting cardiac arrest. 1
Specific SCN5A mutations do not identify higher-risk subsets. 1
Management Principles
Implantable cardioverter-defibrillator (ICD) is the only proven therapy to prevent sudden cardiac death and is recommended for cardiac arrest survivors and those with documented sustained ventricular tachycardia. 1, 2, 5
ICD should be considered for patients with spontaneous type 1 ECG pattern AND history of syncope. 2, 5
Lifestyle modifications are essential for all patients: avoid drugs that induce ST-elevation, avoid excessive alcohol and large meals, and aggressively treat fever with antipyretics. 2, 5
Quinidine is recommended for patients with recurrent ICD shocks, those who refuse or have contraindications to ICD, or as alternative therapy. 2, 5
Catheter ablation of the right ventricular outflow tract may prevent electrical storms in patients with recurring episodes. 5
Common Clinical Pitfalls
Do not assume asymptomatic patients with only drug-induced patterns require chronic therapy—they have low risk and observation is appropriate. 2
Do not rely on a single normal ECG to exclude the diagnosis—serial ECGs are essential given the fluctuating pattern. 2
Do not assume genetic testing influences prognosis or treatment decisions—it is useful for cascade screening of relatives but does not guide individual management. 2
Avoid medications that can unmask or worsen the condition, including certain psychotropic agents, anesthetic agents, and cocaine. 2