A 28-year-old Southeast Asian male presents to the emergency department with a history of syncope during sleep. His 12-lead ECG shows the pattern marked **B** in the diagram — coved ST elevation in V2 with an inverted T wave. Genetic testing confirms a loss-of-function mutation in the SCN5A gene. Which of the following best explains the pathophysiological mechanism underlying this ECG finding?
A. Increased outward potassium current in the ventricular myocardium, prolonging the QT interval
B. Impaired calcium handling by the sarcoplasmic reticulum, leading to abnormal calcium cycling
C. Enhanced automaticity of the sinoatrial node due to increased beta-adrenergic sensitivity
D. Reduced inward sodium current during phase 0/1 of the action potential, creating heterogeneous repolarization across the right ventricular outflow tract
Explanation
Why "Reduced inward sodium current during phase 0/1 of the action potential, creating heterogeneous repolarization across the right ventricular outflow tract" is right
The coved ST elevation pattern marked B in V2 is the diagnostic Type 1 ECG finding of Brugada syndrome. This pattern is generated by loss-of-function mutations in SCN5A (chromosome 3p21), which encodes the cardiac sodium channel Nav1.5. The reduced inward sodium current (INa) during phase 0/1 of the action potential creates heterogeneous repolarization specifically across the right ventricular outflow tract (RVOT) epicardium. This heterogeneity generates the characteristic coved morphology with J-point elevation and downsloping ST segment followed by negative T wave, and creates a vulnerable substrate for phase 2 reentry leading to polymorphic VT/VF. This is the direct mechanistic explanation for the ECG pattern shown and the patient's syncope risk (HRS/EHRA/APHRS Inherited Primary Arrhythmia Syndromes Expert Consensus).
Why each distractor is wrong
Increased outward potassium current in the ventricular myocardium, prolonging the QT interval: This describes Long QT syndrome, not Brugada syndrome. While Brugada involves ion channel dysfunction, the primary defect is reduced inward sodium current, not increased outward potassium current. Long QT presents with prolonged QT interval and peaked T waves, not coved ST elevation.
Impaired calcium handling by the sarcoplasmic reticulum, leading to abnormal calcium cycling: This mechanism is characteristic of catecholaminergic polymorphic ventricular tachycardia (CPVT), which involves mutations in RYR2 or CASQ2 genes. Brugada syndrome is a sodium channelopathy, not a calcium-handling disorder. CPVT typically presents with bidirectional VT triggered by exercise or emotion, not the resting coved ST elevation seen here.
Enhanced automaticity of the sinoatrial node due to increased beta-adrenergic sensitivity: This does not explain the ECG pattern or the pathophysiology of Brugada syndrome. The disorder is not primarily a problem of abnormal automaticity but rather of heterogeneous repolarization and phase 2 reentry. Brugada events typically occur at rest or during sleep, not with increased sympathetic tone.
High-YieldNEET PG
Brugada syndrome = SCN5A loss-of-function → reduced INa → RVOT heterogeneous repolarization → coved ST elevation in V1-V3 + phase 2 reentry → VF/SCD in structurally normal hearts.
