What is the recommended management for Brugada syndrome, including indications for implantable cardioverter‑defibrillator placement and use of quinidine?

Brugada Syndrome Management

All patients with Brugada syndrome require strict lifestyle modifications, and ICD implantation is the definitive treatment for those with cardiac arrest, documented ventricular tachycardia, or spontaneous type 1 ECG with syncope, while quinidine serves as an alternative for ICD-ineligible patients or adjunctive therapy for electrical storms. 1

Diagnosis

Brugada syndrome is diagnosed by ST-segment elevation with type 1 morphology ≥2 mm in leads V1 and/or V2 (positioned in the 2nd, 3rd, or 4th intercostal space), occurring spontaneously or after sodium channel blocker challenge (ajmaline, flecainide, procainamide, or pilsicainide). 1, 2

• The type 1 pattern shows coved ST elevation followed by negative T waves in right precordial leads 1, 2
• This ECG pattern is often transient and variable—a single normal ECG does not exclude the diagnosis 2
• Provocative testing with sodium channel blockers should be terminated if ventricular arrhythmias develop, marked QRS widening occurs, or type 1 pattern appears 1, 2

Risk Stratification by Annual Arrhythmic Event Rates

The prognosis varies dramatically based on presentation 1, 2:

• Cardiac arrest survivors: 13.5% per year
• Patients with syncope: 3.2% per year
• Asymptomatic patients: 1% per year

Patients with spontaneous type 1 ECG pattern have significantly worse prognosis than those with drug-induced pattern only. 1, 2

Mandatory Lifestyle Modifications (Class I Recommendation for ALL Patients)

Every diagnosed patient must implement these changes regardless of symptom status: 1, 3, 2

• Avoid drugs that induce ST elevation (comprehensive list at www.brugadadrugs.org) including psychotropic medications, anesthetic agents, and sodium channel blockers 1, 3
• Avoid excessive alcohol intake and large meals (both act as vagal triggers that unmask type 1 pattern and precipitate ventricular fibrillation) 1, 2
• Aggressively treat any fever with antipyretics immediately (fever is a critical trigger for ventricular fibrillation and cardiac arrest) 1, 3, 2
• Avoid cocaine 1, 3

ICD Implantation Indications

Class I Recommendations (Definitive Indications)

ICD implantation is mandatory for: 1, 2

• Survivors of aborted cardiac arrest
• Documented spontaneous sustained ventricular tachycardia

Class IIa Recommendation (Should Be Considered)

ICD should be considered for patients with spontaneous type 1 ECG pattern AND history of syncope presumed due to ventricular arrhythmia. 1, 2

Class IIb Recommendation (May Be Considered)

• ICD may be considered for patients who develop ventricular fibrillation during programmed ventricular stimulation with 2-3 extrastimuli at two sites 1

Critical caveat: The prognostic value of programmed ventricular stimulation remains debated, with most studies failing to confirm positive or negative predictive value for cardiac events. 1

Quinidine Therapy

Indications for Quinidine (Class IIa Recommendation)

Quinidine should be considered for: 1, 4

• Patients who qualify for ICD but have contraindications or refuse the device
• Treatment of electrical storms (recurrent ventricular fibrillation)
• Patients requiring treatment for supraventricular arrhythmias
• Adjunctive therapy to reduce ICD shock burden

Quinidine Dosing

Standard dose: 324-648 mg every 8 hours (approximately 900-1900 mg daily total). 4

• Consider lower starting doses (300-400 mg daily) in elderly patients, those with renal impairment, or concerns about side effects 4
• Quinidine effectively prevents ventricular fibrillation induction in 88% of patients 5
• Long-term quinidine therapy (mean 56 months) showed no arrhythmic events in one prospective study, though 36% experienced side effects that resolved after discontinuation 5

Critical Drug Interactions

Avoid rifampicin (decreases quinidine levels), and monitor closely with digoxin, CYP2D6 substrates, and warfarin. 4

Contraindications include: severe diarrhea/GI intolerance and prolonged QT interval (though quinidine paradoxically treats Brugada, monitor carefully). 4

Acute Management of Electrical Storms

For recurrent ventricular fibrillation/electrical storms, use quinidine OR isoproterenol (Class IIa recommendation). 1

• Isoproterenol infusion combined with oral quinidine successfully suppresses ventricular tachyarrhythmias in electrical storms 6, 7
• This combination is particularly effective when early repolarization pattern is present on ECG 7

Catheter Ablation

Catheter ablation may be considered (Class IIb) for patients with electrical storms or repeated appropriate ICD shocks. 1

• Ablation targets abnormal epicardial late activation areas in the right ventricle 1
• Can eliminate spontaneous type 1 Brugada pattern in >75% of patients and markedly reduce ventricular tachycardia/fibrillation recurrences 1
• Experience and follow-up remain limited; ICD is still recommended for patients with syncope or cardiac arrest history even after ablation 1

Genetic Testing and Family Screening

Genetic testing yields positive results in only 20-30% of phenotype-positive patients, with SCN5A mutations accounting for most cases. 1, 3, 2

• A negative genetic test does NOT exclude Brugada syndrome—diagnosis remains primarily clinical and electrocardiographic 1, 3
• Genotype status does NOT correlate with risk of adverse events—risk stratification is based solely on symptoms and clinical findings 1, 2
• Genetic testing is useful for cascade screening of family members but does not influence individual prognosis or treatment decisions 1, 2
• Family screening with ECG and genetic counseling is recommended for first-degree relatives 3, 2

Common Pitfalls to Avoid

• Do not dismiss lifestyle modifications in asymptomatic patients—these are Class I recommendations for ALL diagnosed patients, not just symptomatic ones 1, 2
• Do not assume a single normal ECG excludes the diagnosis—the type 1 pattern is transient and requires serial ECGs or provocative testing 2
• Do not rely on genetic testing for risk stratification—clinical presentation (cardiac arrest, syncope, asymptomatic) determines management, not genotype 1, 2
• Do not focus solely on fever as a trigger—large meals and excessive alcohol are equally important modifiable risk factors 1, 2
• Asymptomatic patients with drug-induced pattern only have low risk and do not require ICD, but still need all lifestyle modifications 1, 2