Clinical meaning
Brugada syndrome is an inherited cardiac channelopathy caused predominantly by loss-of-function mutations in the SCN5A gene, which encodes the alpha subunit of the cardiac sodium channel (Nav1.5). Over 300 mutations have been identified, all resulting in reduced sodium current (INa) during phase 0 of the ventricular action potential.
At the cellular level, the normal ventricular action potential relies on a precise balance between inward depolarizing currents (INa and ICa,L) and outward repolarizing currents (Ito, IKr, IKs). In the right ventricular epicardium, the transient outward potassium current (Ito) is particularly prominent. When sodium channel function is impaired (reduced INa), the unopposed Ito creates a transmural voltage gradient between the epicardium and endocardium during phase 1 of the action potential. This gradient manifests on the surface ECG as the characteristic ST-segment elevation in leads V1-V3.
The loss of the action potential dome (phase 2) in some epicardial cells but not others creates heterogeneous repolarization. Adjacent cells with and without the dome develop phase 2 reentry: current flows from cells that maintained the dome to cells that lost it, triggering premature ventricular complexes that can degenerate into polymorphic ventricular tachycardia and ventricular fibrillation.
Brugada ECG patterns are classified into three types: Type 1 (diagnostic) shows coved ST elevation ≥2 mm followed by a negative T wave in V1-V3. Type 2 shows saddleback ST elevation ≥2 mm with positive or biphasic T wave. Type 3 shows either coved or saddleback morphology with <1 mm ST elevation. Only Type 1 is diagnostic; Types 2 and 3 require provocative testing with sodium channel blockers (ajmaline, procainamide, or flecainide) to unmask a Type 1 pattern.