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Brugada syndrome

Updated : May 29, 2024





Background

Brugada syndrome is a rare genetic heart disorder that affects the heart’s electrical system, leading to an increased risk of life-threatening heart rhythm abnormalities. It was first described by brothers Pedro and Josep Brugada in 1992. In Brugada syndrome, there is a specific abnormality in the sodium ion channels in the heart cells, which disrupts the normal flow of electrical signals.

This abnormality primarily affects the right ventricle, one of the heart’s chambers responsible for pumping blood to the lungs. The syndrome is often inherited in an autosomal dominant pattern, meaning a person has a 50% chance of inheriting the condition if one of their parents has it. However, in some cases, it can also occur sporadically without a family history.

The condition is often asymptomatic, meaning that individuals may have Brugada syndrome without experiencing any symptoms. However, in some cases, it can lead to abnormal heart rhythms, particularly ventricular tachycardia or ventricular fibrillation, which can cause fainting (syncope), cardiac arrest, or sudden death.

Epidemiology

Brugada syndrome is relatively rare, with an estimated prevalence ranging from 1 to 5 cases per 10,000 individuals in the general population. However, its prevalence can vary significantly across different populations and geographic regions. Brugada syndrome is more prevalent in certain ethnic groups, particularly individuals of Southeast Asian descent, such as people from Thailand, the Philippines, and Japan.

The syndrome is relatively more common in these populations than in individuals of European or African descent. Brugada syndrome can affect individuals of all ages, including children and adults. However, it is often diagnosed in young to middle-aged adults, with an average age of onset around 40 years. It is also more frequently observed in males than in females, with a male-to-female ratio ranging from 2:1 to 8:1.

Brugada syndrome is primarily inherited as an autosomal dominant trait, meaning that an affected individual has a 50% chance of passing the genetic mutation on to each of their children. Several genetic mutations have been associated with the syndrome, with the most common involving genes related to sodium ion channels in the heart.

Anatomy

Pathophysiology

The pathophysiology of Brugada syndrome involves abnormalities in the electrical system of the heart, specifically affecting the ventricles. It is primarily characterized by a disruption in the normal flow of sodium ions across the cardiac cell membrane, leading to an imbalance in the electrical currents responsible for generating the heart’s rhythm.

Brugada syndrome is predominantly caused by gene mutations encoding cardiac sodium channel proteins, particularly the SCN5A gene. These mutations result in altered sodium channel function, reducing sodium current during the early phase of the action potential. As a result, the depolarization of the cardiac cells in the right ventricular outflow tract is impaired, leading to an abnormal ECG pattern called the “Brugada pattern.”

The altered sodium channel function and subsequent disruption of the cardiac electrical activity can lead to various arrhythmias in individuals with Brugada syndrome. The most concerning arrhythmia associated with this condition is ventricular fibrillation (VF), which can cause sudden cardiac arrest. VF occurs due to the generation of reentrant electrical circuits within the ventricles, leading to chaotic and ineffective heart contractions.

The specific mechanisms contributing to the development of arrhythmias in Brugada syndrome are not fully understood. However, it is believed that the reduced sodium current in specific regions of the heart creates a substrate for the formation of these abnormal electrical circuits. Various factors, such as changes in autonomic tone, temperature, and electrolyte levels, can further modulate the likelihood of arrhythmias.

Etiology

The etiology of Brugada syndrome is primarily genetic, with most cases being inherited in an autosomal dominant manner. Mutations in specific genes involved in cardiac ion channels have been identified as the underlying cause of the syndrome. The most common gene associated with Brugada syndrome is SCN5A, which encodes the alpha subunit of the cardiac sodium channel.

Approximately 20% to 30% of individuals with Brugada syndrome have detectable mutations in the SCN5A gene. However, other genes are implicated in the syndrome, albeit less frequently. These include genes such as SCN1B, SCN2B, SCN3B, CACNA1C, CACNB2, and KCNE3, among others. Mutations in these genes can disrupt the normal function of ion channels involved in cardiac action potentials and contribute to the development of Brugada syndrome.

In addition to genetic factors, certain triggers and conditions can unmask or exacerbate the characteristic ECG abnormalities and arrhythmias in individuals with Brugada syndrome. These triggers include fever, medications (such as sodium channel blockers, tricyclic antidepressants, and antiarrhythmic drugs), alcohol consumption, and electrolyte imbalances. These factors can worsen the electrical abnormalities in the heart and increase the risk of arrhythmias.

Genetics

Prognostic Factors

Clinical History

Clinical History

Some individuals may remain completely asymptomatic throughout their lives and may only discover their condition incidentally during routine electrocardiogram (ECG) testing or after a family member is diagnosed with the syndrome. However, others may experience symptoms or potentially life-threatening events related to abnormal heart rhythms.

Syncope or fainting episodes are relatively common in individuals with Brugada syndrome. These episodes may occur due to arrhythmias, particularly ventricular tachycardia or ventricular fibrillation, which can lead to a sudden drop in blood pressure and loss of consciousness. The syncopal episodes are often unexplained, occurring without any obvious triggers or warning signs.

Some individuals with Brugada syndrome may experience palpitations, abnormal or irregular heartbeats that can be felt as a racing, pounding, or fluttering sensation in the chest. Brugada syndrome often has a strong familial component. Therefore, a significant clinical history aspect is the presence of family members with the syndrome or a history of sudden unexplained deaths at a young age, particularly among male relatives. Family history can help identify at-risk individuals and may prompt further diagnostic testing and evaluation.

Physical Examination

Physical Examination

During a physical examination, the findings in individuals with Brugada syndrome are often normal. The condition primarily affects the electrical system of the heart, and many individuals with Brugada syndrome do not exhibit any physical signs or abnormalities on examination. The cardiovascular examination is typically normal in individuals with Brugada syndrome.

The heart sounds, including S1 and S2, are usually normal, and there may not be any murmurs or abnormal sounds. In some cases, there may be subtle neurological findings during the examination. This can include abnormal reflexes, such as brisk deep tendon reflexes, more commonly associated with Brugada syndrome type 2.

However, these neurological findings are absent in all individuals with the syndrome. Brugada syndrome has been associated with other conditions, such as atrial fibrillation, atrial flutter, and certain structural heart abnormalities (e.g., right bundle branch block). If these conditions are present, they may be detected during a thorough cardiovascular examination.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential Diagnoses

Atrial Fibrillation

Wolff-Parkinson-White syndrome

Sick Sinus Syndrome

QT prolongation

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The primary treatment for Brugada syndrome patients is the implantation of an implantable cardioverter-defibrillator (ICD). Current guidelines recommend ICD placement for individuals who have survived a cardiac arrest, those with Brugada ECG abnormalities and a history of syncope, and those who exhibit Brugada ECG patterns during drug challenge tests. Quinidine can be considered as an alternative treatment option.

However, there are conflicting study results regarding its efficacy compared to ICD placement. Quinidine can benefit Brugada syndrome patients with an ICD who experience multiple shocks or have contraindications for ICD placement. Another emerging therapy is radiofrequency ablation of the anterior part of the right ventricular outflow tract, which shows promise for improving outcomes in Brugada syndrome patients.

Treatment of asymptomatic individuals with Brugada ECG findings is more challenging. Personalized risk stratification is crucial to determine the appropriate management for these individuals, considering their risk factors. This requires a multidisciplinary approach and close and frequent follow-up to monitor their condition.

by Stage

by Modality

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Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

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References

Brugada syndrome

Updated : May 29, 2024




Brugada syndrome is a rare genetic heart disorder that affects the heart’s electrical system, leading to an increased risk of life-threatening heart rhythm abnormalities. It was first described by brothers Pedro and Josep Brugada in 1992. In Brugada syndrome, there is a specific abnormality in the sodium ion channels in the heart cells, which disrupts the normal flow of electrical signals.

This abnormality primarily affects the right ventricle, one of the heart’s chambers responsible for pumping blood to the lungs. The syndrome is often inherited in an autosomal dominant pattern, meaning a person has a 50% chance of inheriting the condition if one of their parents has it. However, in some cases, it can also occur sporadically without a family history.

The condition is often asymptomatic, meaning that individuals may have Brugada syndrome without experiencing any symptoms. However, in some cases, it can lead to abnormal heart rhythms, particularly ventricular tachycardia or ventricular fibrillation, which can cause fainting (syncope), cardiac arrest, or sudden death.

Brugada syndrome is relatively rare, with an estimated prevalence ranging from 1 to 5 cases per 10,000 individuals in the general population. However, its prevalence can vary significantly across different populations and geographic regions. Brugada syndrome is more prevalent in certain ethnic groups, particularly individuals of Southeast Asian descent, such as people from Thailand, the Philippines, and Japan.

The syndrome is relatively more common in these populations than in individuals of European or African descent. Brugada syndrome can affect individuals of all ages, including children and adults. However, it is often diagnosed in young to middle-aged adults, with an average age of onset around 40 years. It is also more frequently observed in males than in females, with a male-to-female ratio ranging from 2:1 to 8:1.

Brugada syndrome is primarily inherited as an autosomal dominant trait, meaning that an affected individual has a 50% chance of passing the genetic mutation on to each of their children. Several genetic mutations have been associated with the syndrome, with the most common involving genes related to sodium ion channels in the heart.

The pathophysiology of Brugada syndrome involves abnormalities in the electrical system of the heart, specifically affecting the ventricles. It is primarily characterized by a disruption in the normal flow of sodium ions across the cardiac cell membrane, leading to an imbalance in the electrical currents responsible for generating the heart’s rhythm.

Brugada syndrome is predominantly caused by gene mutations encoding cardiac sodium channel proteins, particularly the SCN5A gene. These mutations result in altered sodium channel function, reducing sodium current during the early phase of the action potential. As a result, the depolarization of the cardiac cells in the right ventricular outflow tract is impaired, leading to an abnormal ECG pattern called the “Brugada pattern.”

The altered sodium channel function and subsequent disruption of the cardiac electrical activity can lead to various arrhythmias in individuals with Brugada syndrome. The most concerning arrhythmia associated with this condition is ventricular fibrillation (VF), which can cause sudden cardiac arrest. VF occurs due to the generation of reentrant electrical circuits within the ventricles, leading to chaotic and ineffective heart contractions.

The specific mechanisms contributing to the development of arrhythmias in Brugada syndrome are not fully understood. However, it is believed that the reduced sodium current in specific regions of the heart creates a substrate for the formation of these abnormal electrical circuits. Various factors, such as changes in autonomic tone, temperature, and electrolyte levels, can further modulate the likelihood of arrhythmias.

The etiology of Brugada syndrome is primarily genetic, with most cases being inherited in an autosomal dominant manner. Mutations in specific genes involved in cardiac ion channels have been identified as the underlying cause of the syndrome. The most common gene associated with Brugada syndrome is SCN5A, which encodes the alpha subunit of the cardiac sodium channel.

Approximately 20% to 30% of individuals with Brugada syndrome have detectable mutations in the SCN5A gene. However, other genes are implicated in the syndrome, albeit less frequently. These include genes such as SCN1B, SCN2B, SCN3B, CACNA1C, CACNB2, and KCNE3, among others. Mutations in these genes can disrupt the normal function of ion channels involved in cardiac action potentials and contribute to the development of Brugada syndrome.

In addition to genetic factors, certain triggers and conditions can unmask or exacerbate the characteristic ECG abnormalities and arrhythmias in individuals with Brugada syndrome. These triggers include fever, medications (such as sodium channel blockers, tricyclic antidepressants, and antiarrhythmic drugs), alcohol consumption, and electrolyte imbalances. These factors can worsen the electrical abnormalities in the heart and increase the risk of arrhythmias.

Clinical History

Some individuals may remain completely asymptomatic throughout their lives and may only discover their condition incidentally during routine electrocardiogram (ECG) testing or after a family member is diagnosed with the syndrome. However, others may experience symptoms or potentially life-threatening events related to abnormal heart rhythms.

Syncope or fainting episodes are relatively common in individuals with Brugada syndrome. These episodes may occur due to arrhythmias, particularly ventricular tachycardia or ventricular fibrillation, which can lead to a sudden drop in blood pressure and loss of consciousness. The syncopal episodes are often unexplained, occurring without any obvious triggers or warning signs.

Some individuals with Brugada syndrome may experience palpitations, abnormal or irregular heartbeats that can be felt as a racing, pounding, or fluttering sensation in the chest. Brugada syndrome often has a strong familial component. Therefore, a significant clinical history aspect is the presence of family members with the syndrome or a history of sudden unexplained deaths at a young age, particularly among male relatives. Family history can help identify at-risk individuals and may prompt further diagnostic testing and evaluation.

Physical Examination

During a physical examination, the findings in individuals with Brugada syndrome are often normal. The condition primarily affects the electrical system of the heart, and many individuals with Brugada syndrome do not exhibit any physical signs or abnormalities on examination. The cardiovascular examination is typically normal in individuals with Brugada syndrome.

The heart sounds, including S1 and S2, are usually normal, and there may not be any murmurs or abnormal sounds. In some cases, there may be subtle neurological findings during the examination. This can include abnormal reflexes, such as brisk deep tendon reflexes, more commonly associated with Brugada syndrome type 2.

However, these neurological findings are absent in all individuals with the syndrome. Brugada syndrome has been associated with other conditions, such as atrial fibrillation, atrial flutter, and certain structural heart abnormalities (e.g., right bundle branch block). If these conditions are present, they may be detected during a thorough cardiovascular examination.

Differential Diagnoses

Atrial Fibrillation

Wolff-Parkinson-White syndrome

Sick Sinus Syndrome

QT prolongation

The primary treatment for Brugada syndrome patients is the implantation of an implantable cardioverter-defibrillator (ICD). Current guidelines recommend ICD placement for individuals who have survived a cardiac arrest, those with Brugada ECG abnormalities and a history of syncope, and those who exhibit Brugada ECG patterns during drug challenge tests. Quinidine can be considered as an alternative treatment option.

However, there are conflicting study results regarding its efficacy compared to ICD placement. Quinidine can benefit Brugada syndrome patients with an ICD who experience multiple shocks or have contraindications for ICD placement. Another emerging therapy is radiofrequency ablation of the anterior part of the right ventricular outflow tract, which shows promise for improving outcomes in Brugada syndrome patients.

Treatment of asymptomatic individuals with Brugada ECG findings is more challenging. Personalized risk stratification is crucial to determine the appropriate management for these individuals, considering their risk factors. This requires a multidisciplinary approach and close and frequent follow-up to monitor their condition.