Electrophysiological Mechanism of Brugada Coved ST Elevations
The coved-type ST-segment elevation in Brugada syndrome results from transmural voltage gradients created by loss of the action potential dome specifically in right ventricular (RV) epicardium, while endocardium maintains normal repolarization—this heterogeneous repolarization generates the characteristic downsloping ST elevation and negative T-wave pattern. 1, 2
Primary Mechanism: Epicardial Action Potential Abnormalities
The fundamental electrophysiological disturbance involves a spike-and-dome configuration (deeply notched action potential) that develops in RV epicardium but not in endocardium 3. This creates the following cascade:
Transmural Dispersion of Repolarization
- Epicardial dome loss: In approximately 25% of cases linked to SCN5A mutations causing sodium channel dysfunction 1, the RV epicardial cells lose their action potential dome during phase 1
- Preserved endocardial repolarization: The endocardium maintains normal action potential morphology
- Voltage gradient formation: This disparity creates a transmural current flowing from endocardium to epicardium during early repolarization 3, 4
- ST elevation: The transmural voltage gradient manifests as the characteristic coved ST-segment elevation ≥2 mm in V1-V3 1
Molecular Basis
The genetic dysfunction primarily affects cardiac sodium channels (SCN5A gene mutations in ~20-30% of cases) 2, 5, resulting in:
- Decreased peak and persistent sodium current (INa)
- Increased closed-state inactivation
- Accelerated slow inactivation
- Delayed recovery from inactivation 6
This creates a reduced net depolarizing force that preferentially affects the RV outflow tract epicardium 7.
Secondary Mechanism: Conduction Abnormalities
Both depolarization and repolarization abnormalities contribute to the ECG pattern 7, 8:
RV Outflow Tract Conduction Delay
- Discontinuous transmural conduction: Propagation exhibits phase 0 block at the midmyocardial-to-epicardial transition 6
- Phase 2 conduction: Beyond the block region, excitation depends on L-type calcium current during the action potential dome ("phase 2 conduction") 6
- Delayed RV activation: This manifests as delayed onset of RV contraction relative to left ventricle, with the delay magnitude correlating with ST-segment elevation 7
- Peripheral fascicle involvement: The commonly associated S1-S2-S3 pattern reflects concomitant intraventricular conduction defects in peripheral right bundle branch fascicles distributing to the RV infundibulum 1
T-Wave Inversion Mechanism
The negative T-wave following the coved ST elevation results from:
- Prolongation of epicardial action potential duration by the spike-and-dome configuration
- Rapid reversal of transmural gradients during repolarization
- Late slow-upstroke action potentials at the subepicardium 3, 6
Arrhythmogenic Substrate
The heterogeneous loss of the epicardial dome creates:
- Marked dispersion of repolarization within epicardium and transmurally
- Phase 2 reentrant extrasystoles arising from these voltage gradients
- Trigger for VF: These reentrant beats can precipitate polymorphic VT/VF 4
Dynamic Nature and Modulating Factors
The ECG pattern is characteristically dynamic and can normalize transiently 1 because:
- Vagal tone enhancement: Increases ST elevation and arrhythmia risk 1
- Fever: Enhances the ST-segment elevation/J-wave 1
- Sympathetic stimulation: Isoproterenol can restore the epicardial dome, reducing ST elevation 4
- Sodium channel blockers: Unmask or enhance the Type 1 pattern by further reducing depolarizing current 1
Clinical Correlation
The downsloping morphology is pathognomonic: The coved pattern shows a ST/ST80 ratio >1 (where ST80 is measured 80 ms after J-point), distinguishing it from benign early repolarization in athletes which shows upsloping ST segments with ratios <1 1.
The electrophysiological mechanism explains why transient outward current (Ito) blockers like quinidine can be therapeutic—they restore the epicardial dome, normalize the ST segment, and prevent VT/VF 4.