Why are Class I Antiarrhythmics (sodium channel blockers) contraindicated in Brugada syndrome?

Class I Antiarrhythmics in Brugada Syndrome: Contraindication Rationale

Class I antiarrhythmic drugs (sodium channel blockers) are contraindicated in Brugada syndrome because they can unmask or exacerbate the ECG pattern and precipitate life-threatening ventricular arrhythmias, potentially leading to sudden cardiac death. 1

Pathophysiological Mechanism

The contraindication of Class I antiarrhythmics in Brugada syndrome is based on their mechanism of action and the underlying pathophysiology of the syndrome:

1. Sodium Channel Dysfunction:

   • Brugada syndrome is primarily caused by mutations in the SCN5A gene that encodes the cardiac sodium channel alpha subunit
   • These mutations already reduce sodium current (INa) in cardiac cells 2
   • Class I antiarrhythmics further block sodium channels, exacerbating the existing sodium channel dysfunction

2. ECG Pattern Exacerbation:

   • Class I drugs can unmask or worsen the characteristic Brugada ECG pattern (ST-segment elevation in right precordial leads)
   • This effect is so reliable that sodium channel blockers (ajmaline, flecainide, procainamide) are actually used as provocative agents during diagnostic evaluation to reveal concealed Brugada patterns 3

3. Arrhythmia Precipitation:

   • The further reduction in sodium current can trigger ventricular fibrillation
   • This can occur even in patients with structurally normal hearts 3

Clinical Evidence and Guidelines

The European Society of Cardiology (ESC) guidelines explicitly state that:

• Avoidance of drugs that may induce ST-segment elevation in right precordial leads is a Class I recommendation for all patients with Brugada syndrome 3
• A comprehensive list of contraindicated medications is maintained at www.brugadadrugs.org 1

Risk Factors and Management

Certain situations increase the risk of arrhythmias when Class I drugs are administered:

• Fever: Can unmask Brugada ECG pattern and should be treated promptly with antipyretics 1
• Excessive alcohol intake: Should be avoided as it can trigger arrhythmias 1
• Large meals: Can precipitate arrhythmic events 3

Exceptions and Alternative Treatments

While Class I drugs are generally contraindicated, there are important exceptions:

1. Quinidine (Class IA):

   • Despite being a sodium channel blocker, quinidine has additional Ito (transient outward potassium current) blocking properties
   • It may be considered for specific situations:
     • Treatment of electrical storms 3
     • Management of recurrent ICD shocks 1
     • Treatment of supraventricular arrhythmias in Brugada patients 3

2. Isoproterenol:

   • Can be used to treat electrical storms in Brugada syndrome 1

Clinical Implications

• All patients diagnosed with Brugada syndrome must be educated about avoiding Class I antiarrhythmics
• Patients should check medication safety at www.brugadadrugs.org before taking any new drugs 1
• ICD implantation remains the gold standard therapy for high-risk patients with Brugada syndrome 3
• During diagnostic drug challenge tests with sodium channel blockers, the test should be terminated immediately if ventricular arrhythmias develop, marked QRS widening occurs, or a type 1 Brugada ECG pattern emerges 1

The contraindication of Class I antiarrhythmics in Brugada syndrome represents a critical safety consideration that can directly impact mortality and morbidity outcomes for these patients.