Cardiology

Background 

Brugada syndrome is a genetic cardiac channelopathy characterized by ST-segment elevation in the right precordial leads (V1–V3) and an increased risk of ventricular fibrillation (VF) and sudden cardiac death (SCD), often in young, otherwise healthy individuals. It arises from abnormal sodium channel function, particularly involving the SCN5A gene. 

II) Classification/Types

By ECG Pattern: 

• Type 1 (Diagnostic): Coved-type ST-segment elevation ≥2 mm followed by negative T wave in ≥1 right precordial lead (V1–V2), either spontaneously or after sodium channel blockade. 

• Type 2: Saddle-back ST elevation ≥2 mm with upright or biphasic T wave. 

• Type 3: Coved or saddle-back ST elevation <2 mm; considered nondiagnostic. 

By Clinical Presentation: 

• Asymptomatic Brugada pattern (ECG changes without symptoms) 

• Brugada syndrome (ECG changes + history of syncope, VF, or SCD) 

Pathophysiology 

Brugada syndrome results from a loss-of-function mutation in the cardiac sodium channel gene (SCN5A in ~20–30% of cases), leading to reduced inward sodium current during phase 0 of the action potential. This creates transmural dispersion of repolarization, particularly in the right ventricular outflow tract (RVOT), predisposing to reentrant ventricular arrhythmias. 

Epidemiology 

• Prevalence: ~0.05%–0.1% globally; higher in Southeast Asian populations. 

• Male-to-female ratio: ~8:1. 

• Typical age of presentation: 30–50 years. 

• Major cause of sudden cardiac death in young adults, especially males in their sleep. 

Etiology 

I) Causes

• Inherited mutations (e.g., SCN5A, SCN10A, CACNA1C, others) 

• Idiopathic (in ~70% of patients, no mutation is identified) 

II) Risk Factors

• Family history of sudden cardiac death 

• Febrile states (fever exacerbates ST elevation and arrhythmia risk) 

• Certain drugs (e.g., Class IC antiarrhythmics, tricyclic antidepressants, cocaine, lithium) 

• Electrolyte imbalances (e.g., hyperkalemia, hypercalcemia) 

• Male sex 

• Sleep/rest states (increased vagal tone) 

Clinical Presentation 

I) History (Symptoms)

• Syncope (often nocturnal or postprandial) 

• Palpitations or chest discomfort 

• Sudden cardiac arrest (especially during sleep or rest) 

• Family history of unexplained sudden death 

II) Physical Exam (Signs)

• Typically normal 

• May show signs of bradycardia or irregular rhythm during episodes 

• No structural heart abnormalities on exam 

Differential Diagnosis (DDx) 

• Right bundle branch block (RBBB) 

• Early repolarization 

• Arrhythmogenic right ventricular cardiomyopathy (ARVC) 

• Acute pericarditis 

• Myocardial infarction (especially anterior) 

• Electrolyte disturbances 

• Long QT or Short QT syndrome 

Diagnostic Tests 

Initial Work-Up 

12-lead ECG (spontaneous or drug-induced): 

• Type 1 Brugada pattern in V1–V2 (placed in 2nd or 3rd intercostal space) 

• Pseudo-RBBB pattern 

• ST elevation followed by T-wave inversion 

Ambulatory Monitoring: 

• Detect intermittent Type 1 ECG pattern or arrhythmias 

Echocardiogram: 

• Usually normal; rules out structural heart disease 

Advanced Testing 

Sodium Channel Blocker Challenge (e.g., Ajmaline, Flecainide): 

• Induces diagnostic Type 1 pattern in borderline cases 

• Performed in a monitored setting due to arrhythmia risk 

Electrophysiology Study (EPS): 

• Not routinely required 

• May be used for risk stratification (e.g., inducibility of VF) 

Genetic Testing: 

• Confirms SCN5A mutation 

• Useful for screening first-degree relatives 

Treatment 

I) Acute Management

• Ventricular Fibrillation/Tachycardia: Immediate defibrillation 

• Avoid sodium channel blockers and QT-prolonging drugs 

• Fever management: Aggressive antipyretic therapy 

II) Chronic Management

• Implantable Cardioverter-Defibrillator (ICD): 

• Indicated for patients with history of cardiac arrest, syncope with documented arrhythmias, or spontaneous Type 1 ECG + inducible VF 

• Quinidine: 

• Considered in patients with recurrent arrhythmias or who are ICD-ineligible 

• Isoproterenol infusion: 

• Used in electrical storm (recurrent VF episodes) 

Medications 

Device Therapy 

• Implantable Cardioverter-Defibrillator (ICD): 

• Mainstay of therapy for secondary prevention 

• Also for primary prevention in selected high-risk individuals 

• Catheter ablation: 

• For patients with frequent ICD shocks or localized arrhythmogenic substrate in RVOT 

Patient Education, Screening, Vaccines 

Education: 

• Avoid trigger medications (maintain updated list) 

• Treat fevers promptly 

• Recognize warning signs (syncope, palpitations) 

• Encourage family screening and genetic counseling 

Screening/Prevention: 

• ECG screening in first-degree relatives 

• Consider EPS or genetic testing for family members with suspicious symptoms 

Vaccinations: 

• Routine immunizations encouraged 

• Manage fever aggressively post-vaccination to avoid arrhythmia triggers 

Consults/Referrals 

• Cardiology/Electrophysiology: For diagnosis and ICD evaluation 

• Genetics: For mutation testing and family counseling 

• Emergency Medicine: For management of arrhythmias or cardiac arrest 

• Neurology: If syncope work-up includes neurologic differential 

Follow-Up 

Short-Term 

• Device check after ICD implantation 

• Monitor for recurrent syncope or arrhythmia symptoms 

• Family member evaluation and testing 

Long-Term 

• Regular ICD checks 

• Avoidance of trigger substances and prompt fever treatment 

• Periodic reassessment of risk profile and family history 

Prognosis 

• Excellent with ICD placement in high-risk patients 

• Mortality rate significantly reduced with appropriate therapy 

• Risk of SCD persists without intervention, especially in those with spontaneous Type 1 ECG pattern 

• Many individuals with Brugada pattern (asymptomatic) remain event-free but require periodic reassessment