Genetics and mechanism
Brugada syndrome is most often associated with loss-of-function in the cardiac sodium channel (SCN5A, ~20–30% of cases). The result is heterogeneous loss of the action-potential dome in the right ventricular outflow tract epicardium, creating transmural and epicardial dispersion of repolarization — the substrate for phase 2 reentry and polymorphic VT/VF. Events cluster at rest, during sleep, and with fever, when vagal tone is high and sodium current is further reduced.
ECG patterns
- Type 1 (diagnostic) — coved ST elevation ≥2 mm with a gradually descending ST segment into an inverted T wave, in ≥1 right precordial lead.
- Type 2 — saddleback morphology; suggestive only. Pursue with higher leads and, if appropriate, provocation.
- High right precordial leads (V1–V2 placed in the 2nd or 3rd intercostal space) markedly improve sensitivity.
The pattern is dynamic — it can be transiently present, so a single normal ECG does not exclude the diagnosis.
Provocation and unmasking
- Fever — the most clinically important provoker; obtain an ECG in any suspected patient who is febrile.
- Sodium-channel blocker challenge — IV ajmaline, procainamide, or flecainide to unmask type 1 in a patient with a non-diagnostic baseline and a compatible history/family history. Perform with monitoring and resuscitation readiness; a positive test converts type 2 to type 1.
Risk stratification
- Highest risk: aborted cardiac arrest, or spontaneous type 1 with arrhythmic syncope
- Intermediate: spontaneous type 1 without symptoms — individualized
- Lower: drug-induced type 1 in an asymptomatic patient without family history
- The role of EP study with programmed stimulation for risk stratification remains debated and is used selectively, not routinely
Management
- ICD — the only therapy proven to prevent sudden death; indicated for cardiac-arrest survivors and high-risk symptomatic patients. The subcutaneous ICD is often attractive (young patients, no pacing need) — confirm S-ICD screening, since the Brugada ECG can challenge sensing.
- Quinidine — reduces recurrent VF; used for electrical storm, as an adjunct, or when an ICD is declined/contraindicated.
- Isoproterenol — acute therapy for electrical storm (augments calcium current, restores the epicardial dome).
- Lifestyle: prompt fever treatment, avoid provoking drugs (brugadadrugs.org), moderate alcohol, avoid large nocturnal meals.
- Family screening: clinical ± genetic cascade screening of first-degree relatives.