What is Brugada syndrome?

From the Guidelines

Brugada syndrome is a rare genetic heart disorder that affects the heart's electrical system, causing abnormal heart rhythms that can lead to fainting, seizures, or sudden cardiac death, characterized by a specific electrocardiogram (ECG) pattern showing ST-segment elevation in the right precordial leads, and is typically diagnosed using ECG testing and medication challenge tests, with treatment focusing on preventing dangerous arrhythmias using implantable cardioverter-defibrillators (ICDs) and lifestyle modifications 1.

Key Characteristics of Brugada Syndrome

• Characterized by coved ST elevation in leads V1 or V2 positioned in the second, third, or fourth intercostal space either spontaneously or induced by administration of a sodium channel–blocking drug in the absence of other causes of ST elevation 1
• Associated with syncope or sudden cardiac arrest (SCA) due to ventricular fibrillation (VF), predominantly in young males, although it has been reported in all age groups 1
• The type 1 Brugada ECG with coved ST elevation in right precordial leads may be present spontaneously, during fever or vagotonic states, or after medication challenge with sodium channel blockers 1

Diagnosis and Treatment

• Diagnosis involves ECG testing, sometimes requiring medication challenge tests to reveal the characteristic pattern 1
• Treatment focuses on preventing dangerous arrhythmias, with implantable cardioverter-defibrillators (ICDs) being the primary treatment for high-risk patients 1
• Some patients may benefit from quinidine, a medication that can help stabilize heart rhythm 1
• Lifestyle modifications are also important, including avoiding certain medications, excessive alcohol, and fever-reducing measures during illness, as fever can trigger arrhythmias in Brugada patients 1

Prognosis and Management

• The yield of genetic testing in phenotype positive patients is approximately 20% to 30% in Brugada syndrome, with SCN5A variants accounting for most of this subset of genotype positive Brugada syndrome 1
• ICD implantation has been shown to reduce mortality in symptomatic patients with Brugada syndrome 1
• Ablation of abnormal areas of epicardial late activation in the RV can suppress recurrent VA as shown in a small number of patients 1

From the Research

Definition and Characteristics of Brugada Syndrome

• Brugada syndrome (BrS) is an inherited cardiac arrhythmia syndrome characterized by a distinct coved-type ST segment elevation in the right precordial leads 2, 3.
• It is associated with a high risk of sudden cardiac death in young adults, and less frequently in infants and children 2.
• The electrocardiographic manifestations of BrS are often concealed and may be unmasked or aggravated by various factors such as sodium channel blockers, fever, vagotonic agents, and certain antidepressants 2.

Diagnosis and Risk Stratification

• Diagnosis of BrS relies on the presence of a spontaneous or drug-induced coved-type ST segment elevation on an electrocardiogram (ECG) 3, 4.
• Risk assessment in patients with BrS is challenging, and various markers such as repolarization and conduction abnormalities are being investigated to predict the risk of life-threatening ventricular arrhythmic events 4.
• Programmed electrical stimulation and novel ECG parameters, such as QRS fragmentation, are also being studied for their predictive value in risk stratification 3.

Treatment and Management

• The first line of therapy for BrS is an implantable cardioverter-defibrillator (ICD), which is the most widely accepted approach to prevent sudden cardiac death 2, 3.
• Pharmacologic therapy, such as isoproterenol, cilostazol, and milrinone, can be used to abort electrical storms or as an adjunct or alternative to device therapy 2.
• Radiofrequency ablation of the right ventricular outflow tract epicardium has also been shown to be an effective option in reducing arrhythmia vulnerability and the electrocardiographic manifestation of the disease 2.
• Subcutaneous implantable cardioverter-defibrillators (S-ICDs) are an alternative to transvenous systems, with reduced risk of infection and complications, and may be eligible for patients with BrS after exercise stress testing 5.

Genetics and Molecular Mechanisms

• BrS is a genetically heterogeneous disorder, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation 6.
• The genetic basis of BrS is complex, with multiple common and rare genetic variants acting in concert to produce the BrS phenotype 3, 6.
• Recent advances in genetic and molecular mechanisms have improved our understanding of BrS, but further investigation is needed to elucidate the underlying electrophysiological mechanisms and to develop more targeted therapeutic interventions 6.