Key Facts

Brugada syndrome is a genetic cardiac channelopathy associated with a characteristic ECG pattern and a risk of ventricular fibrillation (VF) and sudden cardiac death (SCD), typically occurring at rest or during sleep. It is an important cause of sudden unexplained death, particularly in young men.

Epidemiology

• Prevalence: 1-5 per 10,000 worldwide; higher in Southeast Asia (up to 1 in 1,000)
• Male:female ratio 8-10:1 for clinical events (testosterone modulates ion channel expression)
• Mean age at diagnosis: 40 years
• Accounts for ~4% of all sudden cardiac deaths and ~20% of SCD in structurally normal hearts

Aetiology

• SCN5A (sodium channel gene) mutations identified in ~20-25%
• Multiple other genes identified (SCN1B, CACNA1C, CACNB2, KCNE3, etc.)
• Many cases are genetically unresolved
• Autosomal dominant with variable expressivity and incomplete penetrance

Pathophysiology

• Loss-of-function mutations in cardiac sodium channels (Nav1.5) reduce sodium current (INa)
• This creates transmural voltage gradient in the right ventricular outflow tract (RVOT) between epicardium and endocardium
• The gradient produces the characteristic coved ST elevation and predisposes to phase 2 re-entry, triggering VF
• Arrhythmias typically occur at rest or during sleep when vagal tone is high

Typical Presentation

• Syncope or cardiac arrest (VF), typically during rest or sleep
• Family history of sudden cardiac death (especially young males)
• Palpitations
• Nocturnal agonal respirations (witnessed by partner)

ECG Patterns

• Type 1 (diagnostic): ≥2 mm coved ST elevation in V1-V3, followed by negative T wave
• Type 2 (saddle-back): ≥2 mm ST elevation with ≥1 mm concave ST, positive or biphasic T wave — NOT diagnostic alone
• Type 3: <1 mm ST elevation — NOT diagnostic
• ECG pattern may be intermittent and provoked by sodium channel blockers, fever, or vagal activity

Triggers for Arrhythmia

• Fever (important — treat aggressively)
• Excessive alcohol
• Large meals (vagal stimulation)
• Sleep/rest
• Drugs: class I antiarrhythmics, TCAs, lithium, cocaine

Red Flags

• Aborted cardiac arrest
• Syncope with type 1 ECG pattern
• Family history of sudden death <45 years
• Type 1 pattern unmasked by fever

Bedside

• 12-lead ECG: with leads V1-V2 placed in 2nd and 3rd intercostal spaces (higher placement increases sensitivity)
• Serial ECGs (pattern may be intermittent)

Bloods

• U&Es: electrolyte abnormalities
• Temperature: fever can unmask pattern

Imaging

• Echocardiography: structurally normal heart (excludes structural causes of SCD)
• Cardiac MRI: exclude ARVC and subtle structural abnormalities

Special Tests

• Ajmaline provocation test: IV ajmaline 1mg/kg over 5 minutes — converts type 2/3 to type 1 in susceptible individuals (gold standard for diagnosis)
• Flecainide test: alternative to ajmaline
• Genetic testing: SCN5A and other genes; useful for family cascade screening
• EP study: role remains controversial; some centres use for risk stratification

Non-pharmacological

• Avoid triggers: treat fever aggressively (paracetamol, cooling), avoid excess alcohol, avoid drugs on Brugada list (www.brugadadrugs.org)
• Educate patient and family about triggers and warning signs
• Family screening: ECG screening of first-degree relatives; genetic cascade testing

Pharmacological

• Quinidine 300-600mg BD: only drug shown to suppress VF in Brugada syndrome
  • Used as adjunct to ICD, or when ICD is contraindicated/refused
  • Acts by blocking Ito current
• Isoprenaline infusion: for electrical storm with recurrent VF (acutely increases ICaL)
• Avoid: flecainide, propafenone, ajmaline (except for provocation test), TCAs, beta-blockers (controversial)

Surgical/Interventional

• ICD implantation: only proven treatment to prevent sudden cardiac death
  • Class I indication: survived cardiac arrest (secondary prevention)
  • Class IIa: spontaneous type 1 pattern with syncope
  • Risk of inappropriate shocks: ~20% over 5 years
• Catheter ablation of RVOT epicardium: emerging therapy; eliminates substrate in selected cases
  • Normalises ECG pattern in ~75%
  • May reduce ICD shocks

Referral Criteria

• All patients with suspected Brugada: referral to inherited cardiac conditions (ICC) service
• Survivors of cardiac arrest: urgent electrophysiology referral
• Family members: screening via ICC clinic
• Genetic counselling for affected families

• Annual rate of cardiac events in symptomatic patients (prior arrest/syncope): ~8-10% per year without ICD
• Asymptomatic with spontaneous type 1 pattern: ~0.5-1% annual event rate
• Asymptomatic with drug-induced type 1 only: very low risk (~0.1% per year)
• ICD effectively prevents SCD but has complications (inappropriate shocks, lead issues)
• Quinidine reduces arrhythmia burden but does not eliminate SCD risk
• Prognosis with ICD is excellent; life expectancy near-normal

Brugada ECG Types

Risk Stratification