Brugada Syndrome

Brugada syndrome is an inherited channelopathy causing a characteristic coved ST elevation in the right precordial leads and an increased risk of polymorphic VT and sudden cardiac death in structurally normal hearts.

Prevalence about 1 in 2000 (higher in Southeast Asia, where it is called sudden unexplained nocturnal death syndrome); men account for 80%, with symptoms in the third to fifth decade.

Genetics: SCN5A loss of function variants in 20 to 30% (autosomal dominant, incomplete penetrance); polygenic contributions.

Mechanism: transmural voltage gradient from reduced sodium current and delayed right ventricular outflow tract depolarisation or repolarisation heterogeneity.

Events occur at rest or during sleep; triggers: fever, vagotonic states, large meals, alcohol, cocaine, sodium channel blockers, tricyclic antidepressants, lithium, some anaesthetics, hypokalaemia, hyperkalaemia.

Annual event rate: 0.5% asymptomatic, 1.5 to 2% prior syncope, 7 to 13% after aborted sudden death.

• Frequently asymptomatic.
• Syncope (often arrhythmic), nocturnal agonal respiration, palpitations, cardiac arrest.
• Atrial fibrillation in 10 to 20%.
• Family history of sudden death under 45 years.

• Type 1 Brugada ECG pattern: coved ST elevation of 2 mm or more followed by negative T wave in at least one right precordial lead (V1 or V2, placed at standard or 2nd to 3rd intercostal spaces), spontaneous or induced by sodium channel blocker challenge.
• Diagnostic criterion (2013 and Shanghai score): type 1 pattern in the absence of other causes; or with a positive family history, arrhythmia or syncope.
• Provocation: ajmaline 1 mg/kg IV over 5 to 10 minutes (or flecainide 2 mg/kg, procainamide 10 mg/kg) with continuous ECG and resuscitation equipment; positive if type 1 develops. Fever may unmask the pattern.
• Genetic testing (SCN5A) and cascade family screening.
• Electrophysiology study is controversial (inducibility of VF for risk).
• Exclude mimics: acute ischaemia, ARVC, pulmonary embolism, hyperkalaemia, early repolarisation, right bundle branch block.
• Holter and signal averaged ECG (fragmented QRS, late potentials).

Lifestyle and trigger avoidance (all patients)

• Treat fever promptly with paracetamol 1 g (and cooling).
• Avoid drugs that unmask or aggravate the Brugada pattern (BrugadaDrugs.org list): class I antiarrhythmics, psychotropics such as amitriptyline and lithium, bupivacaine in high doses, propofol infusion, cocaine, excess alcohol.
• Correct electrolyte disturbances.
• Avoid large meals and excessive alcohol.

Device therapy

• ICD for survivors of cardiac arrest or documented sustained VT (class I), and for patients with spontaneous type 1 pattern and syncope likely arrhythmic. Subcutaneous ICD preferred in young patients without pacing need.
• Asymptomatic with spontaneous type 1 pattern: risk stratify (family history, electrophysiology study, fragmented QRS); ICD usually not indicated.

Medical

• Quinidine 300 to 600 mg twice daily (hydroquinidine) for recurrent ICD shocks, arrhythmic storm or ICD refusal; gastrointestinal side effects and thrombocytopenia limit use.
• Isoproterenol infusion 1 to 3 micrograms/min for electrical storm.
• Cilostazol, bepridil as alternatives in some settings.

Catheter ablation

Epicardial ablation of the right ventricular outflow tract substrate for recurrent VF storms and ICD shocks (reduces recurrence in 80 to 90%).

Family and counselling

• Screen first degree relatives with ECG (including high precordial leads) and ajmaline challenge when appropriate. Children with fever need antipyretic management.
• Driving and sport restrictions are individualised.
• Genetic counselling.