What is Brugada syndrome?

Brugada Syndrome: Definition, Diagnosis, and Management

Brugada syndrome is a genetic cardiac channelopathy characterized by distinctive ECG abnormalities and an increased risk of sudden cardiac death due to ventricular fibrillation, occurring in structurally normal hearts. 1 This condition primarily affects young to middle-aged adults, with a predominance in males (more than 90% of diagnosed cases).

Clinical Characteristics

ECG Patterns

• Type 1 (diagnostic): Coved ST-segment elevation ≥2 mm followed by a negative T-wave in leads V1-V3 1
• Type 2 and 3 (non-diagnostic): "Saddle-back" morphology with high takeoff ST-segment elevation 1
• ECG patterns can be:
  • Spontaneous (worse prognosis)
  • Drug-induced with sodium channel blockers (flecainide, ajmaline, procainamide)
  • Intermittent and unmasked by fever 1, 2

Genetic Basis

• Autosomal dominant inheritance pattern
• Primarily linked to mutations in the SCN5A gene (cardiac sodium channel) in approximately 25% of cases 1
• Other ion channel gene mutations have been identified in some cases 3

Clinical Presentation

• Many patients are asymptomatic and diagnosed through family screening
• Symptomatic presentations include:
  • Syncope (especially during rest or sleep)
  • Aborted sudden cardiac death
  • Palpitations
• Cardiac events occur predominantly in the third and fourth decades of life 1
• Fever can acutely trigger cardiac arrest in Brugada syndrome 1

Risk Stratification

The following factors indicate higher risk for life-threatening arrhythmias:

1. Spontaneous Type 1 ECG pattern (not drug-induced) 1, 4
2. History of symptoms (syncope, aborted cardiac arrest) 1, 4
3. Male gender (though this doesn't appear to impact prognosis) 2

Patients with both spontaneous Type 1 ECG pattern and symptoms have the highest risk of cardiac events 4.

Diagnostic Approach

1. ECG evaluation:

   • Look for characteristic Type 1 pattern (coved ST elevation ≥2mm in V1-V3)
   • Use the "Corrado index" to differentiate from athlete's early repolarization: measure ST elevation at J-point (STJ) and 80ms after (ST80)
     • Brugada Type 1: STJ/ST80 ratio >1 (downsloping ST segment)
     • Early repolarization: STJ/ST80 ratio <1 (upsloping ST segment) 1

2. If pattern is unclear:

   • Confirm correct lead placement
   • Perform high precordial lead ECG (V1-V2 in 2nd or 3rd intercostal space) 1
   • Consider drug challenge with sodium channel blockers (flecainide, ajmaline) 1

3. Rule out Brugada phenocopy:

   • Check for conditions that can mimic Brugada pattern: electrolyte disturbances, myocardial infarction, mechanical compression 5

4. Genetic testing:

   • SCN5A mutation testing can help confirm diagnosis
   • Positive genetic testing in symptomatic patients indicates higher risk 4

Management

Management is based on risk stratification:

High-Risk Patients (Symptomatic)

• Implantable cardioverter-defibrillator (ICD) is the only proven effective therapy for preventing sudden death 1
• Indicated for:
  • Patients with aborted cardiac arrest
  • Patients with documented ventricular tachycardia
  • Patients with syncope and spontaneous Type 1 ECG pattern 1

Recurrent Arrhythmias

• Quinidine may be reasonable for treatment of electrical storm 1, 2
• Isoproterenol can be useful to treat electrical storm 1
• Epicardial ablation for patients with recurrent arrhythmias 2

Asymptomatic Patients

• Clinical monitoring for development of spontaneous ST-segment elevation 1
• Aggressive fever management (antipyretics) 4, 2
• Avoidance of drugs that may induce or worsen Brugada ECG pattern
• Electrophysiological testing may be considered for risk stratification in asymptomatic patients with spontaneous ST elevation 1

Special Considerations

• Fever management is crucial as fever can trigger arrhythmic events (27% of life-threatening arrhythmias in young patients) 4
• Family screening should be considered for first-degree relatives of affected individuals
• Pediatric patients with both symptoms at diagnosis and spontaneous Type 1 ECG pattern have shorter time to first life-threatening arrhythmic event 4

Common Pitfalls

1. Misdiagnosis: Failure to differentiate Brugada syndrome from Brugada phenocopy, which is reversible when underlying conditions are resolved 5

2. Incomplete evaluation: Not performing high precordial lead ECG or drug challenge when suspicious but non-diagnostic ECG patterns are present

3. Risk misclassification: Not recognizing that asymptomatic individuals with characteristic ECG but no family history may still be at risk 1

4. Overlooking triggers: Not advising patients about fever management and avoidance of certain medications