What is Brugada syndrome?

Brugada Syndrome: Diagnosis and Management

Brugada syndrome is a genetic cardiac channelopathy characterized by distinctive ECG abnormalities (coved ST-segment elevation in right precordial leads) and a high risk of sudden cardiac death in individuals with structurally normal hearts, primarily affecting males in their third to fourth decade of life. 1

Clinical Characteristics

• Electrocardiographic Features:

  • Type 1 (diagnostic) pattern: Coved ST-segment elevation ≥2mm followed by negative T-wave in leads V1-V3 1
  • Type 2 and 3 (non-diagnostic) patterns: "Saddle-back" morphology with high takeoff ST-segment elevation 1
  • ECG changes may be dynamic and intermittent, requiring repeated ECGs 2

• Demographics:

  • Male predominance (>90% of diagnosed cases) 1
  • Most common in third and fourth decades of life 2
  • Can occur in children and neonates, though less common 2

• Genetic Basis:

  • Autosomal dominant inheritance pattern 2
  • Primary mutation in SCN5A gene (cardiac sodium channel) 2
  • Non-SCN5A loci have been reported but specific genes remain unidentified 2

Risk Factors and Triggers

• Fever is a significant trigger for arrhythmic events and cardiac arrest 2, 1
• Medications: Sodium channel blockers, vagotonic agents, tricyclic/tetracyclic antidepressants 3
• Male gender is a risk factor for sudden cardiac death 2
• Previous syncope increases risk of cardiac arrest 6-fold in patients with spontaneous ECG pattern 2
• Spontaneous Type 1 ECG pattern carries higher risk than drug-induced pattern 2

Diagnosis

1. ECG Assessment:

   • Examine right precordial leads (V1-V3) for characteristic patterns 1
   • If Type 1 pattern not clear but suspected:
     • Confirm correct lead placement
     • Repeat ECG if necessary
     • Perform high precordial lead ECG (V1 and V2 placed in 2nd or 3rd intercostal space) 1

2. Pharmacological Challenge:

   • Administration of sodium channel blockers (flecainide 2 mg/kg, ajmaline 1 mg/kg) can unmask ST segment elevation in concealed forms 2
   • Positive test: Development of Type 1 Brugada pattern

3. Differential Diagnosis:

   • Rule out conditions that may produce Brugada-like patterns:
     • Hyperkalemia
     • Cocaine use
     • Excessive alcohol intake 1

Risk Stratification

Risk stratification is crucial as implantable cardioverter-defibrillator (ICD) is the only proven effective therapy for preventing sudden death 1.

Highest Risk Patients:

• History of aborted cardiac arrest
• Documented ventricular tachycardia
• Syncope with spontaneous Type 1 ECG pattern 1

Moderate Risk Factors:

• Spontaneous Type 1 ECG without symptoms
• Male gender
• Family history of sudden cardiac death 2

Controversial Risk Assessment:

• Electrophysiological testing (EP) has conflicting evidence:
  • Some studies show high negative predictive value (93%) 2
  • Others report low accuracy in predicting cardiac arrest 2

Management

1. Implantable Cardioverter-Defibrillator (ICD):

   • Class I indication (should be performed) for:
     • Survivors of cardiac arrest
     • Patients with documented VT
     • Patients with syncope and spontaneous Type 1 ECG pattern 1

2. Pharmacological Therapy:

   • For electrical storm:
     • Isoproterenol (Class IIa recommendation) 2, 1
     • Quinidine (Class IIb recommendation) 2, 1
   • These medications work by:
     • Boosting calcium channel current (isoproterenol)
     • Inhibiting transient outward current (quinidine) 3

3. Preventive Measures:

   • Aggressive fever management with antipyretics 1
   • Avoidance of drugs that may induce or worsen Brugada ECG pattern 1
   • Regular clinical monitoring for development of spontaneous ST-segment elevation 2

4. Emerging Therapy:

   • Radiofrequency ablation of the right ventricular outflow tract epicardium may reduce arrhythmia vulnerability in selected patients 3

Follow-up and Family Screening

• Regular cardiac follow-up for all diagnosed patients 1
• Family screening recommended for first-degree relatives 1
• Family history alone should not be used to determine risk in affected individuals 2

Pitfalls to Avoid

• Do not assume asymptomatic individuals with characteristic ECG but no family history are at low risk 2
• Do not assume family members of an individual with SCD are necessarily at increased risk 2
• Do not rely solely on standard ECG if Brugada syndrome is suspected - use high precordial leads 1
• Do not underestimate the importance of fever management in these patients 2, 1

Brugada syndrome remains a challenging condition to diagnose and manage, but proper risk stratification and appropriate intervention can significantly reduce the risk of sudden cardiac death in affected individuals.