Brugada syndrome

Introduction

Brugada syndrome is a genetic disorder that is characterized by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death. It is named after the Spanish cardiologists Pedro and Josep Brugada who first described the condition in 1992. The syndrome is typically inherited in an autosomal dominant pattern and is associated with mutations in the SCN5A gene, which encodes the cardiac sodium channel.

Clinical Presentation

Brugada syndrome often presents with syncope, nocturnal agonal respiration, or sudden cardiac death, particularly in young adults. The characteristic ECG findings include coved-type ST-segment elevation in the right precordial leads (V1-V3). These ECG abnormalities may be transient and can be unmasked or exacerbated by fever, certain medications, or electrolyte imbalances.

Pathophysiology

The pathophysiology of Brugada syndrome involves abnormalities in the sodium channels of the heart, which affect the action potential and lead to arrhythmias. The most common genetic mutation associated with Brugada syndrome is found in the SCN5A gene, which encodes the alpha subunit of the cardiac sodium channel (Nav1.5). This mutation leads to a loss of function of the sodium channel, resulting in reduced sodium current during the action potential.

Diagnosis

The diagnosis of Brugada syndrome is primarily based on ECG findings and clinical criteria. The ECG pattern can be classified into three types:

Type 1: Coved-type ST-segment elevation ≥2 mm in ≥1 right precordial lead (V1-V3) followed by a negative T wave.
Type 2: Saddle-back ST-segment elevation ≥2 mm in ≥1 right precordial lead (V1-V3) followed by a positive or biphasic T wave.
Type 3: Either coved-type or saddle-back ST-segment elevation <2 mm in ≥1 right precordial lead (V1-V3).

Genetic Testing

Genetic testing can confirm the diagnosis of Brugada syndrome by identifying mutations in the SCN5A gene or other associated genes. However, not all patients with Brugada syndrome will have identifiable genetic mutations, and the absence of a mutation does not exclude the diagnosis.

Management

Management of Brugada syndrome focuses on preventing sudden cardiac death. This may involve lifestyle modifications, pharmacological therapy, and device implantation. Key strategies include:

Avoiding medications that can exacerbate the ECG abnormalities or provoke arrhythmias.
Treating fever promptly to prevent ECG changes.
Implantable cardioverter-defibrillator (ICD) placement in patients with a history of syncope, documented ventricular arrhythmias, or family history of sudden cardiac death.

Prognosis

The prognosis of Brugada syndrome varies depending on the presence of symptoms and risk factors. Asymptomatic individuals with Brugada syndrome generally have a lower risk of sudden cardiac death compared to symptomatic individuals. Regular follow-up and risk stratification are essential for managing patients with Brugada syndrome.

Epidemiology

Brugada syndrome is more prevalent in Southeast Asian populations, particularly in Thailand, the Philippines, and Japan. It is estimated to affect 1 in 2,000 people worldwide, with a higher incidence in males compared to females.

Research and Future Directions

Ongoing research in Brugada syndrome aims to better understand the genetic basis, pathophysiology, and optimal management strategies. Advances in genetic testing and molecular biology may lead to improved diagnostic tools and targeted therapies for patients with Brugada syndrome.