What is Brugada syndrome?

What is Brugada Syndrome?

Brugada syndrome is an inherited cardiac channelopathy characterized by ST-segment elevation in the right precordial leads (V1-V3) on ECG and a high risk of sudden cardiac death from ventricular arrhythmias in individuals with structurally normal hearts. 1

Core Pathophysiology

Primary Electrical Disease Without Structural Abnormality

• Brugada syndrome represents a primary channelopathy where the heart muscle itself is structurally normal, but the electrical system is fundamentally abnormal 1
• The underlying defect involves dysfunction of cardiac ion channels, most commonly affecting sodium channels 1
• This electrical abnormality creates a substrate for life-threatening ventricular arrhythmias including polymorphic ventricular tachycardia and ventricular fibrillation 1

Genetic Basis and Inheritance

Autosomal Dominant Inheritance Pattern

• The syndrome follows an autosomal dominant inheritance pattern with incomplete penetrance 1
• The cardiac sodium channel gene (SCN5A) is the primary identified genetic cause, though it accounts for only 20-30% of cases 2
• More than 90% of affected individuals with diagnostic ECG findings are male, indicating significant gender-based phenotypic expression 1

Characteristic ECG Pattern

Diagnostic Type 1 Brugada Pattern

• The hallmark ECG finding shows coved ST-segment elevation ≥2 mm in leads V1 and/or V2, with negative T-waves 2
• J-point elevation typically occurs in right precordial leads V1 to V3, sometimes accompanied by right bundle branch block morphology 1
• This ECG pattern is characteristically intermittent and can fluctuate between normal and abnormal over time 2
• The pattern may be present spontaneously or only after provocation with sodium channel blockers (ajmaline, flecainide, procainamide) 1, 2
• High electrode positioning in the second and third intercostal spaces improves detection sensitivity 2

Clinical Presentation and Age of Onset

Typical Presentation in Young to Middle-Aged Adults

• Cardiac events (syncope or cardiac arrest) occur predominantly in the third and fourth decades of life 1
• Males are disproportionately affected, representing over 90% of diagnosed cases 1
• Presentation can range from completely asymptomatic (discovered on screening) to sudden cardiac arrest 3
• Arrhythmic events characteristically occur at rest or during sleep 4
• Neonatal and childhood presentations have been reported but are less common 1

Critical Triggers and Precipitants

Fever as a Major Arrhythmic Trigger

• Fever can acutely precipitate cardiac arrest in Brugada syndrome and must be aggressively treated with antipyretics 1, 2
• Fever accounts for 27% of life-threatening arrhythmic events in pediatric patients 3
• Vagotonic states can unmask or trigger the type 1 ECG pattern 2
• Certain medications (psychotropic agents, anesthetic agents, cocaine) and excessive alcohol intake can induce dangerous ST-segment elevation 2

Risk Stratification for Sudden Death

Spontaneous ECG Pattern Indicates Higher Risk

• Patients with spontaneous type 1 Brugada ECG pattern have significantly worse prognosis than those with only drug-induced patterns 1, 2
• Patients with syncope AND spontaneous ST-segment elevation have a 6-fold higher risk of cardiac arrest compared to asymptomatic patients with spontaneous pattern 1, 2
• Annual arrhythmic event rates vary dramatically: 13.5% per year in cardiac arrest survivors, 3.2% per year with syncope history, and 1% per year in asymptomatic patients 2
• Asymptomatic patients with only drug-induced patterns have low risk and do not require chronic therapy 2

Family History and Genetic Counseling Considerations

Family History Does Not Predict Individual Risk

• There are no data showing that family history of sudden death predicts cardiac events among other family members with Brugada syndrome 1
• Asymptomatic individuals with characteristic ECG but no family history are NOT necessarily at low risk 1
• Family members of someone who died from Brugada syndrome should not be assumed to be at increased risk themselves 1
• First-degree relatives should undergo screening, but their risk must be assessed independently based on their own ECG findings and symptoms 2

Primary Prevention Strategy

ICD as the Only Proven Preventive Measure

• Implantable cardioverter-defibrillator (ICD) implantation is the only prophylactic measure proven to prevent sudden cardiac death in Brugada syndrome 1
• ICD is recommended (Class I) for survivors of cardiac arrest or those with documented spontaneous sustained ventricular tachycardia 2
• ICD should be considered (Class IIa) for patients with spontaneous type 1 ECG AND history of syncope 2
• In pediatric populations, ICD complications occur in 41% of cases, necessitating careful risk-benefit assessment 3

Common Clinical Pitfalls

Critical Diagnostic and Management Errors to Avoid

• Do not rely on a single normal ECG to exclude Brugada syndrome—serial ECGs are essential because the pattern fluctuates 2
• Do not assume asymptomatic patients with drug-induced patterns only are at high risk—they have low event rates 2
• Do not fail to educate patients about fever management—aggressive antipyretic use is critical 2, 3
• Do not assume family history predicts individual risk—each patient requires independent assessment 1
• The role of electrophysiological testing remains controversial with low positive predictive value (23%) but high negative predictive value (93%) 1

Alternative Management Options

Pharmacological and Ablation Strategies

• Quinidine should be considered for patients who qualify for ICD but have contraindications, refuse it, or experience recurrent ICD shocks 2
• Isoproterenol can be useful to treat electrical storm 1
• Hydroquinidine has shown efficacy in small series, with 8 of 11 treated pediatric patients remaining asymptomatic 3
• Epicardial ablation of right ventricular outflow tract substrate is used for patients with recurrent arrhythmias 4

Lifestyle Modifications

Essential Risk Reduction Measures

• Avoid drugs that induce ST-segment elevation (sodium channel blockers, certain psychotropic and anesthetic agents) 2
• Avoid excessive alcohol intake and large meals 2
• Promptly treat any fever with antipyretic drugs—this is a critical intervention 2, 3
• Patients should be educated about arrhythmia triggers and warning symptoms 2