Brugada Syndrome

Brugada syndrome (BrS) is a genetic condition that results in abnormal electrical activity within the heart, increasing the risk of sudden cardiac death. Those affected may have episodes of passing out. The abnormal heart rhythm often occur when a person is at rest and may be triggered by a fever.

The condition is often inherited from a person’s parent with about a quarter of people having a family history. Some cases may be due to a new mutation or certain medications. The most commonly involved gene is SCN5A which creates the cardiac sodium channel. Diagnosis is typically by electrocardiogram (ECG), however, the abnormalities may not be consistently present. Medications such as ajmaline may be used to reveal the ECG changes. Similar ECG patterns may be seen in certain electrolyte disturbances or when the blood supply to the heart has been reduced.

There is no cure for Brugada syndrome. Those at higher risk of sudden cardiac death may be treated using an implantable cardioverter defibrillator (ICD). In those without symptoms the risk of death is much lower, and how to treat this group is less clear. Isoproterenol may be used in the short term for those who have frequent life-threatening abnormal heart rhythms, while quinidine may be used longer term. Testing people’s family members may be recommended.

The condition affects between 1 and 30 per 10,000 people. It is more common in males than females and in those of Asian descent. The onset of symptoms is usually in adulthood. It is named after the Spanish cardiologists Pedro and Josep Brugada who described the condition in 1992. Their brother Ramon Brugada was the first to describe one potential genetic cause in 1998.

Signs and symptoms
While many of those with Brugada syndrome do not have any symptoms, Brugada syndrome may cause fainting or sudden cardiac death due to serious abnormal heart rhythms such as ventricular fibrillation or polymorphic ventricular tachycardia. Blackouts may be caused by brief abnormal heart rhythms that revert to a normal rhythm spontaneously. If a dangerous heart rhythm does not stop by itself and is left untreated, the person may have a fatal cardiac arrest. However, blackouts can occur in those with Brugada syndrome despite a normal heart rhythm due to a sudden drop in blood pressure, known as vasovagal syncope.

The abnormal heart rhythms seen in Brugada syndrome often occur at rest, following a heavy meal, or even during sleep. These situations are linked to periods when the vagus nerve is activated, referred to as periods of high vagal tone. Abnormal heart rhythms may also occur during fever or following excessive alcohol. Certain medications may also worsen the tendency to abnormal heart rhythms in patients with Brugada syndrome and should be avoided by these patients.

Causes
The individual cells of the heart communicate with each other with electrical signals, and these electrical signals are disturbed in those with Brugada syndrome. As a genetic condition, the syndrome is ultimately caused by changes to a persons DNA, known as genetic mutations. The first mutations described in association with Brugada syndrome were in a gene responsible for a protein or ion channel that controls the flow of sodium ions through the cell membrane of heart muscle cells – the cardiac sodium channel. Many of the genetic mutations that have subsequently been described in association with Brugada syndrome influence the sodium current in some way, or affect other ionic currents.

A long list of factors that can generate a Brugada ECG pattern have been described, including certain medications, electrolyte disturbances such as a decrease in the levels of potassium in the blood, and a reduction in blood supply to key areas of the heart, specifically the right ventricular outflow tract. Drugs that have been implicated include antiarrhythmic medications such as flecainide, verapamil and propranolol, antidepressants such as amitryptiline, and drugs that enhance vagal tone such as acetylcholine. The ECG pattern can also be seen following excessive use of alcohol or cocaine.

Treatment
The main aim when treating people with Brugada syndrome is to reduce the risk of sudden death due to serious abnormal heart rhythms such as ventricular fibrillation or polymorphic ventricular tachycardia. While some with this condition are at high risk of serious heart rhythm disturbances, others are at much lower risk, meaning that some may require more intensive treatment than others. In addition to treating the person who has Brugada syndrome, it is often important to investigate members of their immediate family to see if they too carry the condition.

Lifestyle
The first line of treatment, suitable for all people with Brugada syndrome regardless of their risk of arrhythmias, is lifestyle advice. People should be advised to recognise and avoid things that may increase the risk of serious arrhythmias. These include avoiding excessive alcohol consumption, avoiding certain medications (a list of which can be found on the BrugadaDrugs.org website), and treating fever promptly with paracetamol. Although the abnormal heart rhythms seen in Brugada syndrome are generally more likely to occur at rest or even during sleep, some people with Brugada syndrome experience arrhythmias during strenuous exercise. Some physicians may therefore advise people with Brugada syndrome that while gentle exercise is helpful, very strenuous exercise should be avoided.

Implantable defibrillator
In people felt to be at higher risk of sudden cardiac death, an implantable cardioverter-defibrillator (ICD) may be recommended. These small devices implanted under the skin continuously monitor the heart rhythm. If the device detects a potentially life-threatening arrhythmia it can give the heart a small electric shock, stunning the heart back into a normal rhythm. An ICD can also function as a pacemaker, preventing abnormally slow heart rates that can also occur in people with Brugada syndrome.

Implanting an ICD is a relatively low-risk procedure and is frequently performed as a day case under local anaesthetic. However, complications such as infection, bleeding or unnecessary shocks can occur, which can sometimes be serious. Because of the small risk associated with implanting an ICD, as well as the cost of the devices, ICDs are not recommended for all people with Brugada syndrome but are instead reserved for people deemed at higher risk of sudden cardiac death.

Medication
Quinidine is an antiarrhythmic drug that may reduce the chance of serious abnormal heart rhythms occurring in some people with Brugada syndrome. It is most frequently used in people with Brugada syndrome who have an ICD and have experienced several episodes of life-threatening arrhythmias, but may also be used in people at high risk of arrhythmias but in whom an ICD is not appropriate.

Isoprenaline, a drug that has similarities with adrenaline, can be used in an emergency for people with Brugada syndrome who are having frequent repeated life-threatening arrhythmias, known as an “electrical storm”. This drug must be given as a continuous infusion into a vein and therefore is not suitable for long-term use.

Catheter ablation
A further treatment option for people with Brugada syndrome is radiofrequency catheter ablation. In this procedure, wires are passed through a vein in the leg into the heart, or through a small hole underneath the sternum. These wires are used to find the area of the heart responsible for initiating the arrhythmias. The tip of one of these wires is used to make a series of tiny burns, intentionally damaging the area of abnormal heart muscle that has been causing the problem. Current recommendations suggest that this treatment should be reserved for those with Brugada syndrome who have had repeated shocks from an ICD.

Epidemiology
Between 1 and 30 per 10,000 people are affected by Brugada syndrome. Although those affected are born with the condition, symptoms are only rarely seen in childhood and the first symptoms are usually seen in adulthood. While the rare cases seen in childhood are equally likely to be male or female, in adulthood the condition is more frequently seen in males than females, potentially due to the higher testosterone levels found in men.

Brugada syndrome is more common in people of Asian descent and is the most common cause of sudden death in young men without known underlying cardiac disease in Thailand and Laos. In these countries Sudden Unexpected Nocturnal Death Syndrome (SUNDS), likely in many cases to be due to Brugada syndrome, may be known as Lai Tai (Thailand), Banungut (Phillipines), or Pokkuri (Japan). Type 1 Brugada ECG patterns are seen more frequently in Asian populations (0%–0.36%) than those in Europe (0%–0.25%) and the United States (0.03%). Similarly, Type 2 and Type 3 ECG patterns are more prevalent in Asia (0.12%–2.23%) than in Europe (0.0%–0.6%) or the United States (0.02%).

Leave a Reply