Makindo Medical Notes

Related Subjects: |Brugada Syndrome |Long QT syndrome (LQTS) Acquired |Long QT syndrome (LQTS) Congenital |Torsades de Pointes |Ventricular Fibrillation |Ventricular Tachycardia |Resuscitation - Adult Tachycardia Algorithm |Automatic Implantable Cardioverter Defibrillator (AICD)

Brugada syndrome is a potentially life-threatening condition, and the only known effective treatment is an implantable cardioverter-defibrillator (ICD) for preventing sudden cardiac death.

About

• Definition: Brugada syndrome is a genetic channelopathy characterized by specific ECG changes and an increased risk of sudden cardiac death due to malignant arrhythmias.
• Incidence: Affects 1-6 per 1000 people, predominantly Southeast Asian men, with an 8-fold higher incidence in men compared to women.
• Discovery: The syndrome was first described in 1992 by Spanish cardiologists Pedro and Josep Brugada, with genetic research contributions from their brother Ramon.

ECG/EKG

Genetics

• Key Genes: The most commonly implicated gene is SCN5A, encoding the sodium channel NaV1.5 in the heart.
• Other associated genes include CACNA1C, CACNB2, and SCN10A, though mutations in these are less frequent.
• Inheritance: Typically inherited in an autosomal dominant pattern with variable expression.

Aetiology and Pathophysiology

• Brugada syndrome involves a reduction in the inward sodium current during phase 0 of the cardiac action potential.
• This sodium channel dysfunction causes an imbalance of ion currents, particularly during the repolarization phase, leading to arrhythmias.
• The right ventricular outflow tract (RVOT) is particularly affected, contributing to the characteristic ECG changes.
• About 30% of cases have loss-of-function mutations in the SCN5A gene (located on chromosome 3).

Types of Brugada Syndrome

• Type 1: Classic "coved-type" ST-segment elevation > 2 mm in the right precordial leads (V1-V3) with a negative T wave.
• Type 2/3: "Saddleback" ST-segment elevation, which is less specific and may require provocation testing for confirmation.

Clinical Presentation

• Sudden Cardiac Arrest: Often the first presentation, particularly during sleep or rest.
• Syncope: Episodes of unexplained fainting, often triggered by fever, stress, or physical exertion.
• Nocturnal Agonal Respirations: May be reported by family members in cases of sudden nocturnal death syndrome (SUNDS).
• Asymptomatic: Many individuals are asymptomatic and diagnosed through family screening or incidental ECG findings.

Investigations

• ECG: Characteristic ST-segment elevation in leads V1-V3, often with a right bundle branch block pattern. QT interval is usually normal. Polymorphic VT and VF can be seen.
• Provocation Testing: Sodium channel blockers (e.g., ajmaline, flecainide) can unmask Type 1 ECG changes, but should only be performed in a controlled environment.
• Genetic Testing: Testing for SCN5A mutations can confirm the diagnosis and is useful for family screening.
• Imaging: Echocardiography, cardiac MRI, and other structural tests are typically normal, as Brugada syndrome affects the electrical function, not the heart's structure.
• Holter Monitor: Prolonged monitoring may capture episodes of VT or VF, especially in patients with syncope or palpitations.

Risk Factors for Sudden Cardiac Death (SCD)

Management

• Implantable Cardioverter-Defibrillator (ICD):
  • The primary and most effective treatment for preventing sudden cardiac death.
  • Recommended for patients with a history of cardiac arrest, syncope, or documented ventricular arrhythmias.
• Lifestyle Modifications:
  • Avoid fever, as it can precipitate arrhythmias—use antipyretics promptly for infections.
  • Avoid medications known to exacerbate Brugada syndrome (e.g., certain antiarrhythmics, TCAs, antipsychotics).
  • Limit excessive alcohol intake and avoid recreational drugs like cocaine.
• Drug Therapy:
  • Quinidine: May reduce the risk of ventricular arrhythmias in patients with recurrent ICD shocks.
  • Other antiarrhythmics are generally not recommended for routine management of Brugada syndrome.
• Catheter Ablation:
  • Considered for patients with frequent VT/VF episodes who are not adequately controlled with medication or who have recurrent ICD shocks.
  • Focuses on ablating the arrhythmogenic substrate in the right ventricular outflow tract (RVOT).

References

• Safe Drugs in Brugada Syndrome
• AHA/ACC/HRS Guidelines on the Management of Patients with Brugada Syndrome