Brugada Syndrome : What we know and what should we know ?

Brugada Syndrome

Prevalence of Brugada syndrome ECG is shown on the world map. Overall, type 1 and 2 Brugada ECG is more frequently observed in Asia than in Europe or the United States.

A,Fever-induced ST-segment elevation in a patient with BrS. B, ECG parameters at baseline and during fever were compared in 24 patients with BrS and 10 controls. Fever-elevated ST segment prolonged PR and QRS intervals in patients with BrS, whereas the PR interval shortened and the QRS interval or ST-segment amplitude did not change in the controls. *P<0.05 versus baseline. BrS indicates Brugada syndrome.

ECG abnormality diagnostic or suspected of Brugada syndrome. Type 1 ECG (coved-type ST-segment elevation) is the only diagnostic ECG in Brugada syndrome and is defined as a J-wave amplitude or an ST-segment elevation of ≥2 mm or 0.2 mV at its peak (followed by a negative T wave with little or no isoelectric separation). Type 2 ECG (saddle-back-type ST-segment elevation), defined as a J-wave amplitude of ≥2 mm, gives rise to a gradually descending ST-segment elevation (remaining ≥1 mm above the baseline) followed by a positive or biphasic T wave that results in a saddle-back configuration. Type 3 ECG is a right precordial ST-segment elevation (saddle-back type, coved type, or both) without meeting the aforementioned criteria.

A and B, Percentage of event rates (ventricular fibrillation or an appropriate implantable cardioverter-defibrillator discharge) in asymptomatic patients with spontaneous and drug-induced, respectively, type 1 BrS ECG during follow-up. The number of patients and follow-up periods are presented. Some of the follow-up periods are of the whole study population (including symptomatic cases). Event rates of the studies by Brugada et al (1998), Brugada et al (2003), and Delise et al (2011)include all asymptomatic patients (both spontaneous and drug-induced type 1 ECG) because the data were not available separately.

Right anterior oblique view of RV CARTO mapping. RV endocardial and epicardial signals recorded during electrophysiological study are shown. Electrograms shown are lead II and V2 of 12-lead ECG and bipolar (proximal, distal) and unipolar (proximal, distal) electrograms of the mapping catheter. Note that the fractionated electrogram is observed in the RV epicardium but not in the RV endocardium. RV indicates right ventricle. The figure is provided courtesy of Koonlawee Nademanee, MD.

What is Brugada Syndrome?

Brugada syndrome (BrS) is a recently identified disorder. Brugada syndrome is a rare but serious heart condition that affects the way electrical signals pass through the heart. It can cause the heart to beat dangerously fast. Spanish cardiologists Pedro Brugada and Joseph Brugada reported it as a distinct clinical syndrome in 1992.

Brugada syndrome (BrS) is a rare genetic heart disorder characterized by an abnormal electrocardiogram [ECG] due to ventricular arrhythmias. Brugada syndrome is characterized by the presence of ST-segment elevation in leads V₁ to V₃. The main symptom is irregular ventricular heartbeats (ventricular fibrillation) which may potentially result in sudden death without treatment.

Many people who have Brugada syndrome are apparently asymptomatic, have structurally normal hearts and are unaware of their condition. An electrocardiogram (ECG) test can help detect Brugada pattern in such people. The signs and symptoms usually develop in adulthood though the diagnosis may be made at an early age.

Brugada Syndrome – Facts and Figures

Studies indicate that Brugada syndrome is responsible for 4%-12% of unexpected sudden deaths and for up to 20% of all sudden deaths in apparently normal individuals with no previous heart conditions. The average age of persons afflicted with Brugada syndrome is 35-40 years.

According to the Centers for Disease Control (CDC) a high incidence of sudden cardiac death has been prevalent among immigrants of Asian ancestry. Also Southeast Asian countries such as Thailand, Japan and the Philippines have reported similar cases. Brugada syndrome has been found to be more prevalent among males.

Brugada syndrome is clinically related with sudden and unexpected death syndrome (SUDS), sudden unexpected nocturnal death syndrome (SUNDS) and sudden infant death syndrome (SIDS).

According to the National Institutes of Health it is estimated that 5 in 10,000 people worldwide are affected by the Brugada syndrome.

As awareness of Brugada syndrome increases among medical fraternity and public it can be expected that the number of identifiable cases worldwide will also increases.

What is the Genetics behind Brugada Syndrome?

Brugada syndrome predominantly has a genetic cause. Each child of an affected individual has a 50% chance of inheriting the genetic variation as an autosomal dominant.

The primary gene associated with Brugada syndrome is located on chromosome 3 and is known as the SCN5A gene. Approximately 15%-30% of individuals with Brugada syndrome have a SCN5A gene mutation

SCN5A gene is responsible for the production of a protein that allows movement of sodium ions into cardiac muscle cells. Abnormalities in the SCN5A gene cause a disturbed functioning of this sodium channel. This results in a reduction of sodium into the heart cells leading to an abnormal heart rhythm that can lead to sudden death.

More than 250 mutations have been reported in the following 18 different genes (SCN5A, SCN1B, SCN2B, SCN3B, SCN10A, ABCC9, GPD1L, CACNA1C, CACNB2, CACNA2D1, KCND3, KCNE3, KCNE1L KCNE5, KCNJ8, HCN4, RANGRF, SLMAP, and TRPM4). These genes encode for sodium, potassium, and calcium channels or proteins associated with these channels. These genes have varying mechanisms and expressions associated with Brugada Syndrome.

Despite the identification of these genes, 65%–70% of clinically diagnosed cases remain without an identifiable genetic cause.

What are the Causes of Brugada syndrome?

Genetics: Brugada syndrome is mostly inherited as an autosomal dominant. It is caused mainly by mutations in the SCN5A gene which induces a disturbed functioning of sodium channels or proteins that regulate them. Dysfunction of the sodium channels leads to local conduction blockages in the heart.

Structural abnormalities in the heart such as right ventricular dilation, fibrous and fatty replacement of tissues of the right ventricle, and fibrotic disruption of the right bundle branch.

Diffused or localized right ventricular inflammation [myocarditis] due to Coxsackie, Epstein-Barr virus and Parvovirus.

Effects of as sodium blocking drugs such as Ajmaline, Ethacizin, and Flecainide.

Usage of drugs such as Cocaine and Ergonovine (a medication used to cause contractions of the uterus to treat heavy vaginal bleeding after childbirth).

What are the Signs & Symptoms of Brugada syndrome?

• Fainting or loss of consciousness
• Irregular and fast heartbeats (arrhythmias)
• Palpitations (being aware of one’s heart beating)
• Seizures
• Difficulty in breathing
• ST segment elevation in ECG, either spontaneously present or induced with sodium channel-blocker drug.

How do You Diagnose Brugada Syndrome?

• Electrocardiogram (ECG) is used to detect irregularities in the heart's rhythm and structure. Type 1 ECG (Coved ST segment elevation >2mm followed by an inverted T wave) in more than one right precordial lead (V1-V3) with or without administration of a sodium channel blocker is potentially diagnostic. This is also referred to as Brugada sign.
• This ECG abnormality must be associated with one of the following clinical criteria to confirm the diagnosis:
• Presence of ventricular fibrillation (VF) or ventricular tachycardia (VT).
• Family history of sudden cardiac death at <45 years.
• Coved type ECGs in family members.
• Inducibility of ventricular tachycardia with electrical stimulation or drugs.
• Syncope or fainting
• Electrocardiogram (ECG) with specific sodium channel blockers that provoke characteristic ECG features of Brugada syndrome.
• Electrophysiology (EP) test todetect the electrical signals running through the heart. A catheter is passed through a vein in the groin up to the heart. Electrodes are then passed through this catheter to different points in the heart. These help in mapping out irregular heartbeats.
• Genetic testing is used to confirm the diagnosis but only about 30-35% of affected individuals have an identifiable gene mutation after a comprehensive genetic test. Sequence analysis of the SCN5A gene is the first step because nearly 25% of mutations in this gene are the most common cause of Brugada syndrome.

How do You Treat Brugada Syndrome?

• Implantable cardioverter defibrillator (ICD) is a tiny device used in individuals who are at a high risk of ventricular fibrillation. The ICD detects the abnormal heartbeat and delivers an electrical impulse to the heart restoring a normal rhythm.ICDis recommended for people who are at high risk such as serious rhythm disturbances, recurrent fainting spells, and history of sudden cardiac arrest.
• Antiarrhythmic drugs such as Isoproterenol which are used during ventricular arrhythmias and electrical storms.

How do You Prevent Brugada Syndrome?

• By using a medical device called an implantable cardioverter defibrillator
• Avoiding sodium channel blockers medications such as Ajmaline, Ethacizin, and Flecainide
• Genetic counseling and prenatal testing of family members of affected persons.