Brugada Syndrome

Brugada Syndrome (BrS) is a cardiac channelopathy, in which the heart muscle cells have altered electrical recovery after each beat due to genetic alterations in cardiac ionic channels. Patients may develop cardiac symptoms, like loss of consciousness, abnormally rapid heart rhythm (tachycardia) and even sudden cardiac death.

The syndrome is diagnosed by the recognition of a specific morphology of the electrocardiogram (EKG): a ‘coved-type’ (smooth, peaking) ST segment elevation of ≥2mm in precordial leads V1-V3 with inverted T waves and complete or incomplete right bundle branch block (electrical conduction delay to the right side of the heart). Another EKG pattern shows ‘saddle-back-type’ ST segment morphology (called type 2); individuals with this ECG type are considered “possibly affected by the disease” & need clinical evaluation.

These ECG abnormalities are often intermittent, and may come and go over time with different physical conditions. Fever may accentuate the pattern and also trigger arrhythmias.

Genetics of BrS

BrS has a genetic cause and is transmitted as autosomal dominant disease: the main gene associated with the disease is called SCN5A and controls the cardiac sodium current. Abnormalities (mutations) on this gene alter the electrical activity in the heart cells and cause the BrS. Only 25-30% of patients with BrS have a mutation on this gene and further research is needed to discover new genes that cause this syndrome. Currently, some 6 genes are linked to Brugada syndrome with the majority of mutations beginning to be investigated.

BrS Demographics

BrS is a cause of sudden, unexplained death in young adults. It is not known how many people have BrS in the U.S., some estimates say that about 1/1000 people in the population have this disease. The disease could be transmitted in equal proportion to male and females (autosomal) but symptoms manifest more often in males than females (ratio 8:1). The highest incidence of events is between 35-45 years of age, but also children and older adults may have symptoms.
Sudden death may be the first manifestation of BrS. BrS is treatable; with the correct diagnosis & appropriate precaution, most deaths are preventable, early diagnosis is very important.

New molecular & genetic techniques allow for the early detection of DNA defects underlying BrS and therefore genetic testing in combination with clinical evaluation contributes to the identification of patients & family members who are at risk for BrS.

Symptoms

Specifically, patients need to know the following:

  • The signs & symptoms of BrS
  • What to expect for proper evaluation
  • How to protect themselves & their families

The major symptom of BrS is sudden, temporary loss of consciousness (syncope). The serious events of BrS usually occur without warning. They often occur at rest or during sleep. A fever attack or an abundant meal could also trigger events. Why?

People with BrS are at risk of developing a specific type arrhythmia called “Polymorphic Ventricular Tachycardia.” This dangerous arrhythmia happens when an electrical impulse triggers a new heartbeat before the ventricles have fully recovered from the previous beat—usually at slower heart rates (at rest, sleeping, or after a big meal).   When this occurs, the heart muscle begins to quiver, and cannot contract effectively. Blood is not pumped out to the body and - most importantly - to the brain. If the brain is starved of blood and oxygen, the individual faints within seconds. If the heart does not return to a normal rhythm on its own, it may switch into a potentially lethal arrhythmia called ventricular fibrillation. Without immediate emergency treatment, death follows within minutes.
Fainting or syncope is the primary symptom—and may be the only warning sign of BrS. Only about 1/3 of patients exhibit symptoms, therefore, the lack of symptoms does not exclude a person or family from having BrS. As mentioned, BrS often goes undetected.

Also, people with BrS often have other, less dangerous, forms of fast heart rhythms: including atrial fibrillation, atrial flutter & supraventricular tachycardias. These are usually intermittent and can cause a fluttering sensation in the chest—called palpitations.

If there is a family history of unexplained syncope or sudden death, including a death in an otherwise healthy person or upon recognition of a BrS pattern on any EKG—you should seek further evaluation & refer family members for basic screening.

Evaluation

Typically, a consultation will last sixty to ninety minutes & will take place at the Heart Rhythm Center at the NYU Langone Medical Center. This will involve a thorough directed history, family history, & physical examination. Simple procedures are likely to be requested—primarily to further evaluate the EKG under different physiologic conditions (exercise, rest, on/off medications, etc.).

These may include:

  • An Electrocardiogram (EKG)
  • An Echocardiogram (ECHO)
  • A Holter Monitor (24-hour EKG monitor)
  • An exercise test (treadmill test)
  • A pharmacological challenge (procainamide test)
  • Genetic Testing (blood test)

A test using procainamide (and other antiarrhytmic drugs like ajmaline or flecainide) infusion is used in patients with type 2 or type 3 ECG to decide if they are or not affected by the syndrome. In most of the affected patients during infusion of one of the drugs the ECG will convert into a type 1.

Patients may also expect to receive genetic counseling to evaluate the full family history and to discuss the implications and value of genetic testing for risk stratification and family planning.

Once a family member is identified as carrier of a BrS mutation, it is extremely important that DNA of other family members is screened and mutations carriers undergo clinical evaluation. Patients are encouraged to bring to the visit records from prior work-up [hospital admit, EKG, treadmill stress test, Holter, etc.]

Some conditions may mimic the BrS pattern on EKG. These include: normal heart aging, electrolyte abnormalities, previous or acute heart attack, athletic heart muscle, & select medication effects —a careful evaluation with a cardiologist skilled in this field will assure the proper diagnosis.

Therapy

Currently, it is not possible to predict which person is destined to have symptoms. Preventive medical treatment in BrS is not possible because there are no antiarrhythmic drugs available of proven efficacy.

Treatment options for patients with BrS include symptom awareness & device therapy. Symptom awareness and lifestyle could be helpful to avoid potentially dangerous situations – including the recognition of syncope & palpitation, as well as prompt measures taken to decrease fever – a common exacerbating condition.

Device therapy (Implantable Cardioverter Defibrillator) is the only available therapy to prevent sudden death. In this picture, risk stratification by an expert team is extremely important in selecting those BrS patient who are at higher risk and will benefit from the device.

Overall, early recognition of BrS is important and a comprehensive evaluation by a specialized team of physicians with large experience in treating this uncommon disease is the key to the best outcome for both you & your family!

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