What is Brugada syndrome?
Brugada syndrome is an ECG irregularity with a high incidence of sudden death in patients with structurally normal hearts.
First described in 1992 by the Brugada brothers, the disease has since seen an exponential increase in the number of reported cases. The mean age of sudden death is 41 years, and the age at diagnosis ranges from 2 days to 84 years.
High incidence in Southeast Asia, where it had previously been described as sudden unexplained nocturnal death syndrome (SUNDS).
- Sudden unexplained nocturnal death syndrome
- Pokkuri death syndrome
Causes of Brugada syndrome
Brugada syndrome can be caused by changes in one of several genes. The most frequently mutated gene in this condition is SCN5A, which is altered in about 30 percent of affected people. This gene provides instructions for creating a sodium channel, which normally carries positively charged sodium atoms (ions) to the cells of the heart muscle. This type of ion channel plays a fundamental role in maintaining the normal rhythm of the heart. Mutations in the SCN5A gene alter the structure or function of the channel, reducing the flow of sodium ions into cells. A disturbance in ion transport alters the way the heartbeats, leading to the abnormal heart rhythm characteristic of Pokkuri death syndrome.
Mutations in additional genes can also cause Brugada syndrome. Together, these other genetic changes account for less than 2 percent of cases of the condition. Some of the extra genes involved in Pokkuri death syndrome provide orders for making proteins that ensure the correct location or function of sodium channels in heart muscle cells. Proteins produced by other genes involved in the disease form or help regulate ion channels that carry calcium or potassium to or from heart muscle cells. As with sodium channels, the proper flow of ions through the calcium and potassium channels in the heart muscle helps maintain a regular heart rate. Mutations in these genes interrupt the flow of ions, affecting the normal rhythm of the heart.
In affected people without a recognized genetic mutation, the cause of Pokkuri death syndrome is often unknown. In some cases, certain medications can cause a non-genetic (acquired) form of the disorder. Medications that can induce a disturbed heart rhythm include medications used to treat some forms of arrhythmia, a condition called angina (which causes chest pain), high blood pressure, depression, and other mental illnesses. Abnormally high blood levels of calcium (hypercalcemia) or potassium (hyperkalemia), as well as remarkably low levels of potassium (hypokalemia), have also been associated with acquired Pokkuri death syndrome. In addition to causing a non-genetic form of this disorder, these factors can trigger symptoms in people with an underlying mutation in SCN5A or another gene.
Risk factors for Brugada syndrome include:
- Family history of Brugada syndrome: This condition is often passed down from parent to child (hereditary). If other family members have had Brugada syndrome, you are also at higher risk for it.
- Being a man: Men are diagnosed with Brugada syndrome more often than women.
- Race: Brugada syndrome happens more regularly in Asians than in other races.
- Fever: Fever does not cause Brugada syndrome, but it can irritate the heart and lead to fainting or sudden cardiac arrest in someone with Brugada syndrome, especially children.
Who is at risk for Brugada syndrome?
People who are most at risk for the disorder are those of Asian descent, particularly those of Japanese and Southeast Asian descent. It occurs 8 to 10 times more frequently in men than in women. Researchers believe that the male hormone testosterone may contribute to the difference between the genders.
Symptoms of Brugada syndrome
Symptoms that can occur with Brugada syndrome include:
- Sudden death or cardiac arrest
Diagnosis of Brugada syndrome
The diagnosis of Brugada syndrome is based on a thorough clinical evaluation, a complete family and medical history that may include a family history of sudden cardiac death and a specialized test known as an electrocardiogram (ECG or EKG) that records the electrical activity of the heart. and it can reveal abnormal electrical patterns. Doctors may use specific drugs (sodium channel blockers) that cause the characteristic EKG features of Brugada syndrome.
Molecular genetics (DNA) testing is available for mutations in all genes to confirm the diagnosis, but only about 30-35% of affected persons have an identifiable gene mutation after a full genetic test. Sequence analysis of the SCN5A gene is the first step in making a molecular genetic diagnosis because mutations in this gene are the most shared cause of Brugada syndrome (nearly 25%).
Clinical tests and preparation
An electrocardiogram is recommended to determine the extent of the disease in those affected. An electrophysiological study can be used to assess the risk of sudden cardiac death.
Treatment for Brugada syndrome
The main goal of treating people with Brugada syndrome is to reduce the risk of sudden death due to severe abnormal heart rhythms, such as ventricular fibrillation or polymorphic ventricular tachycardia. While some with this condition are at high risk for 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 with Brugada syndrome, it is often important to investigate members of their immediate family to see if they, too, have the condition.
The first line of treatment, suitable for all people with Brugada syndrome regardless of their risk for arrhythmias, is lifestyle counseling. People should be warned to recognize and avoid things that can increase the risk of serious arrhythmias. These include avoiding excessive alcohol consumption, avoiding certain medications, and treating fever quickly with acetaminophen. Though 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 knowledge arrhythmias during strenuous exercise. Therefore, some doctors may advise people with Brugada syndrome that while gentle exercise is helpful, very strenuous exercise should be avoided.
In people who are considered to be at increased risk for sudden cardiac death, an implantable cardioverter-defibrillator (ICD) may be recommended. These small devices implanted under the skin continuously monitor the heart rate. If the device detects a life-threatening arrhythmia, it can give the heart a small electrical shock, stunning it back to 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.
Implantation of an ICD is a relatively low-risk procedure and is often performed as a day case under local anesthesia. However, complications such as infection, bleeding, or unnecessary shock can occur and can sometimes be serious. Because of the small risk associated with the implantation of an ICD, as well as the cost of the devices, ICDs are not recommended for all people with Brugada syndrome but are reserved for people who are considered to have an increased risk of sudden cardiac death.
Quinidine is an antiarrhythmic drug that can reduce the chance of severe abnormal heart rhythms in some people with Brugada syndrome. It is used most often in people with Brugada syndrome who have an ICD and have experienced several episodes of life-threatening arrhythmias, but it can also be used in people at high risk for arrhythmias but in whom an ICD is not appropriate.
Isoprenaline, a drug that has similarities to adrenaline, can be used in an emergency for people with Brugada syndrome who have frequent and repeated life-threatening arrhythmias, known as “electrical storms.” This medicine must be given as a continuous infusion into a vein and is therefore not suitable for long-term use.
Another treatment option for folks with Brugada syndrome is radiofrequency catheter ablation. In this process, wires are passed through a vein in the leg to the heart, or through a small hole under the breastbone. These leads are used to find the area of the heart responsible for initiating arrhythmias. The tip of one of these leads is used to make a series of small burns that intentionally damage the area of the 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 discharges from an ICD.
Complications of Brugada syndrome require emergency medical attention. They include:
- Sudden cardiac arrest if not treated right away, this sudden loss of heart function, breathing, and consciousness, which often occurs while you sleep, is fatal. With prompt and proper medical care, it is possible to survive.
- If you have Brugada syndrome and pass out, seek emergency medical attention.
If someone in your family has Brugada syndrome, genetic testing can be done to find out if you have or are at risk for the condition.