Brugada syndrome BrS is a genetic disorder in which the electrical activity within the heart is abnormal. About a quarter of those with Brugada syndrome have a family member who also has the condition. There is no cure for Brugada syndrome. The condition affects between 1 and 30 per 10, people. 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. If a dangerous heart rhythm does not stop by itself and is left untreated, the person may have a fatal cardiac arrest.
|Published (Last):||1 November 2005|
|PDF File Size:||17.71 Mb|
|ePub File Size:||6.14 Mb|
|Price:||Free* [*Free Regsitration Required]|
Brugada syndrome BrS is a genetic disorder in which the electrical activity within the heart is abnormal. About a quarter of those with Brugada syndrome have a family member who also has the condition.
There is no cure for Brugada syndrome. The condition affects between 1 and 30 per 10, people. 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.
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. 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. The individual cells of the heart communicate with each other with electrical signals, and these electrical signals are disrupted in those with Brugada syndrome. As a genetic condition , the syndrome is ultimately caused by changes to a person's 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.
The ECG pattern can also be seen following excessive use of alcohol or cocaine. Brugada syndrome is inherited in an autosomal dominant manner, meaning that only one copy of the defective gene is needed to produce the syndrome. However, a person diagnosed with the condition may be the first in their family to have Brugada syndrome if it has arisen as a new mutation. Mutations in SCN5A associated with Brugada syndrome generally cause the flow of sodium ions to decrease.
However, the genetics of Brugada syndrome are complex, and it is likely that the condition results from the interactions of many genes. Because of these complex interactions, some members of a family who carry a particular mutation may show evidence of Brugada syndrome while other carrying the same mutation may not, referred to as variable penetrance. Several other genes have been identified in association with Brugada syndrome.
Another gene associated with this condition is RRAD. Some mutations associated with Brugada syndrome can also cause other heart conditions. Those who show more than one cardiac conditions at the same time caused by a single mutation are described as having an ' overlap syndrome '. An example of an overlap syndrome is Brugada and long QT syndrome LQT3 caused by a mutation in SCN5A that reduces the peak sodium current but simultaneously leaves a persistent current leak.
The abnormal heart rhythms seen in those with Brugada syndrome are typically dangerous arrhythmias such as ventricular fibrillation or polymorphic ventricular tachycardia, but those with BrS are also more likely to experience rapid heart rates due to less dangerous arrhythmias such as AV nodal re-entrant tachycardia  and abnormally slow heart rhythms such as sinus node dysfunction. Some argue that the main reason these arrhythmias arise is due to abnormally slow electrical conduction in areas of the heart, specifically the right ventricle.
The sodium current is a major contributor to the characteristic flow of electrical charge across the membrane of heart muscle cells that occurs with each heartbeat known as the action potential.
I Na causes the initial rapid upstroke of the action potential phase 0 , and decreasing the early peak current, as occurs in BrS-associated genetic variants, leads to slowing of the electrical conduction through the heart muscle.
Given the right circumstances, this wavebreak can allow the waves of electricity to perform a U-turn within the muscle, travelling in the reverse direction before beginning to rapidly circle around a point, referred to as re-entry, and causing an abnormal heart rhythm.
Others suggest that the main cause of arrhythmias is a difference in the electrical properties between the inside endocardium and outside epicardium of the heart known as the repolarisation hypothesis. The action potential in cells from the epicardium shows a prominent notch after the initial spike due to a transient inward current. This notch is far less evident in cells from the endocardium, and the difference between the endocardium and epicardium are most clearly seen in the right ventricle.
In those with Brugada syndrome, these differences are increased, creating a brief period within each cardiac cycle when current flows from the endocardium to the epicardium creating the characteristic ECG pattern. The differences in electrical properties between the epi- and endocardium are described as a 'transmural dispersion of repolarisation" which if large enough can lead to electrical impulses becoming blocked in some regions but not others.
Once again, this wavebreak can allow the waves of electricity which usually travel in only one direction to instead begin circling around a point as a re-entrant circuit, causing an arrhythmia. A further factor promoting arrhythmias in Brugada syndrome is changes to the structure of the heart. As Brugada syndrome can be caused by mutation in many different genes, it is possible that different mechanisms may be responsible for the arrhythmias seen in different patients.
Brugada syndrome is diagnosed by identifying characteristic patterns on an electrocardiogram. There may be evidence of a slowing of electrical conduction within the heart, as shown by a prolonged PR interval. These patterns may be present all the time, but may appear only in response to particular drugs see below , when the person has a fever , during exercise, or as a result of other triggers.
The ECG pattern may become more obvious by performing an ECG in which some of the electrodes are placed in different positions from usual. Three forms of the Brugada ECG pattern have been described . According to current recommendations, only a Type 1 ECG pattern, occurring either spontaneously or in response to medication, can be used to confirm the diagnosis of Brugada syndrome as Type 2 and 3 patterns are not infrequently seen in persons without the disease.
Some medications, particularly antiarrhythmic drugs that block the cardiac sodium current I Na, can reveal a Type 1 Brugada pattern in susceptible people. These drugs can be used to help make a diagnosis in those suspected of having Brugada syndrome e.
Genetic testing can be helpful to identify patients with Brugada syndrome, most commonly in family members of a person with Brugada syndrome, but sometimes performed in a person who has died suddenly and unexpectedly. In family members who all carry a particular genetic variant associated with Brugada syndrome, some family members may show evidence of Brugada syndrome on their ECGs while others may not.
To further complicate matters, many frequently occurring variations in the SCN5A gene do not cause any problems, and therefore genetic variants are sometimes identified in persons with Brugada syndrome that are not truly causing the disease. Invasive electrophysiological studies , in which wires are passed through a vein to stimulate and record electrical signals from the heart, can sometimes be used to assess the risk of a person with Brugada syndrome experiencing dangerous abnormal heart rhythms.
Type 1 Brugada ECG pattern note non-standard lead position, V 5 is placed one intercostal space above V 1 and V 6 is placed one intercostal space above V 2. 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.
The first line of treatment, suitable for all people with Brugada syndrome regardless of their risk of arrhythmias, is lifestyle advice. These include avoiding excessive alcohol consumption, avoiding certain medications,  and treating fever promptly with paracetamol. Some physicians may therefore advise people with Brugada syndrome that while gentle exercise is helpful, very strenuous exercise should be avoided.
In people felt to be at higher risk of sudden cardiac death, an implantable cardioverter-defibrillator ICD may be recommended. 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.
Implanting an ICD is a relatively low-risk procedure and is frequently performed as a day case under local anaesthetic. Quinidine is an antiarrhythmic drug that may reduce the chance of serious abnormal heart rhythms occurring in some people with Brugada syndrome.
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". A further treatment option for people with Brugada syndrome is radiofrequency catheter ablation. 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. Between 1 and 30 per 10, people are affected by Brugada syndrome. While the rare cases seen in childhood are equally likely to be male or female, in adulthood symptoms occur more frequently 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 males without known underlying cardiac disease in Thailand and Laos.
Local names vary — in the Philippines the condition has been known as Bangungut meaning "a scream followed by sudden death during sleep",  while in Thailand it was known as Lai Tai , and in Japan Pokkuri. Brugada syndrome is named after the Spanish cardiologists Josep and Pedro Brugada who described the condition in ,  although the association between the characteristic ECG pattern and sudden cardiac death had been reported in From Wikipedia, the free encyclopedia. Genetics Home Reference.
March Archived from the original on 28 October Retrieved 28 October European Journal of Internal Medicine. Archived from the original on 11 February Archived from the original on 17 October Genetics in Medicine. Current Problems in Cardiology. Electrical diseases of the heart. Basic foundations and primary electrical diseases. London: Springer. December Heart Rhythm. A multicenter report". Journal of the American College of Cardiology. Journal of Cardiology.
January Human Mutation. European Heart Journal. International Journal of Molecular Sciences. Frontiers in Physiology. Journal of Molecular and Cellular Cardiology. Circulation: Arrhythmia and Electrophysiology. Current Opinion in Cardiology. February Frontiers in Cardiovascular Medicine.
International Journal of Sports Medicine.
The journal, published since , is the official publication of the Spanish Society of Cardiology and founder of the REC Publications journal family. Articles are published in both English an Spanish in its electronic edition. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years. CiteScore measures average citations received per document published. Read more. SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact.
All works go through a rigorous selection process. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years. CiteScore measures average citations received per document published. Read more. SRJ is a prestige metric based on the idea that not all citations are the same.