Sudden unexplained nocturnal death syndrome

Related Terms

Arrhythmias, Brugada syndrome, CACNA1C, CACNB2, cardiac channelopathy, congenital heart disease, familial arrhythmias, familial heart disease, GPD1L, idiopathic ventricular fibrillation, inherited heart disease, long-QT syndrome, right bundle branch block, SCN5A, ST segment elevation, sudden cardiac death, sudden death syndrome, sudden unexplained nocturnal death syndrome, SUNDS, tachycardia, ventricular arrhythmias.

Background

Brugada syndrome, also known as sudden unexplained nocturnal death syndrome (SUNDS), is a rare heart disease characterized by irregular heartbeat. Other symptoms may include fainting, seizures, breathing problems, nightmares, disrupted sleep, and sudden death. These problems often occur when a person is either sleeping or at rest. There are four types of Brugada syndrome.
Brugada syndrome most often affects people in their thirties. However, symptoms can appear at any age. The average age of sudden death among people with Brugada syndrome is about 40 for all types of the disease.
Brugada syndrome can be classified as type 1, type 2, type 3, or type 4. Type 1, the most studied type, is sometimes caused by mutations or defects in the SCN5A gene. The SCN5A gene provides instructions for making the cardiac sodium channel, which is essential to the normal electrical functioning and rhythm of the heart. Only about one-third of people with Brugada syndrome have been identified as having a mutated copy of this gene. Most SCN5A mutations cause arrhythmias that produce channels that continue to operate late in the cardiac cycle when normal channels are silent; such late activity creates an environment for chaotic rhythms and sudden death. Some researchers believe that some cases of sudden infant death syndrome (SIDS) are also caused by a mutation in the SCN5A gene. In those individuals without a mutated SCN5A gene, the cause of type 1 Brugada syndrome is often unknown. In some cases, a nongenetic form of Brugada syndrome may be caused by certain drugs. Drugs used to treat some forms of arrhythmia (irregular heart beat), angina (chest pain), high blood pressure, and depression and other mental illnesses can cause an altered heart rhythm.
When Brugada syndrome is inherited, or passed down among family members, it follows an autosomal dominant pattern of inheritance. This means that only one copy of the defective gene is needed for the disease to occur.
The prevalence of the syndrome is unknown, but it is estimated to occur in about one in 2,000 people worldwide. Some researchers state that the prevalence of Brugada syndrome may be five in 1,000 in Caucasians worldwide and 14 in 1,000 in Japanese worldwide. Brugada syndrome is more common among people from Japan and Southeast Asia. Known as lai tai in Thailand, bangungut in the Philippines, and pokkuri in Japan, Brugada syndrome is the most common natural cause of death in men under 50 years of age in these countries. Brugada syndrome can affect both males and females. Although the probability of having a mutated gene does not differ by sex, Brugada syndrome is about 8-10 times more common in males. This discrepancy may be linked to testosterone, a male sex hormone.
Brugada syndrome has a very poor prognosis when left untreated. One-third of patients who have suffered from syncopal episodes or have been resuscitated from near sudden death develop ventricular tachycardia within two years. Ventricular tachycardia is a fast heart rhythm that originates in the heart's ventricles. Unfortunately, the prognosis is still poor in individuals who are asymptomatic and have a typical electrocardiogram. One-third of these individuals will display a first polymorphic ventricular tachycardia or ventricular fibrillation within two years of follow-up. The only available treatment is an implantable cardioverter-defibrillator, a device connected to leads positioned inside the heart or on its surface. These leads are used to deliver electrical shocks, sense the cardiac rhythm, and sometimes pace the heart. However, left untreated, the average age of sudden death among people with Brugada syndrome is about 40.

Signs and symptoms

General: While several symptoms of Brugada syndrome have been described, sudden death may occur without any preexisting symptoms. Lack of symptoms should not be interpreted as absence of the disease. In some cases, fever was found to trigger symptoms of Brugada syndrome. In general, Brugada syndrome most often affects people in their thirties. However, symptoms can emerge at any age, and the average age of sudden death among people with Brugada syndrome is about 40.
Abnormal heart rhythm: The most common symptom of Brugada syndrome is arrhythmia (abnormal heart rhythm). These heartbeats are generally irregular and occur in the ventricles (lower chambers of the heart). During these episodes of ventricular arrhythmia, the pumping function of the heart is impaired. This impairment decreases blood flow to the brain and can cause fainting. It may also lead to ventricular fibrillation, chaotic, uncoordinated electrical activity that causes the heart to quiver and stop pumping blood. Sudden death usually follows unless the heart receives an immediate electrical shock from a defibrillator and returns to a normal rhythm.
Fainting: Fainting, which is called syncope when caused by a heart-related issue, may occur when blood flow to the brain is decreased as the result of abnormal electrical activity in the heart.
Other: Other symptoms may be caused by drugs used to treat arrhythmias in Brugada syndrome. These symptoms include sensations of pain, falling, or drowning. Nightmares causing thrashing of the body during sleep have also been reported.

Diagnosis

General: There are no specific diagnostic criteria for Brugada syndrome. Brugada syndrome typically affects men aged 30-50 years, but cases have been identified from birth to age 84. The average age of sudden death caused by Brugada syndrome is 40. It is not clear whether any of these diagnostic tools are specific to any type of Brugada syndrome, although it seems as if Brugada syndrome manifests as certain symptoms that may be brought about by different genetic mutations.
Physical exam: Although a physical exam will not lead directly to a diagnosis of Brugada syndrome, it is important to rule out other potential causes of symptoms, such as arrhythmia, which is abnormal electrical activity in the heart. In addition to a physical exam, a clinician should obtain a detailed drug history, because nongenetic forms of Brugada syndrome may be caused by use of certain drugs, such as those used to treat some forms of arrhythmia, angina (chest pain), high blood pressure, and depression and other mental illnesses. The genetic form of Brugada syndrome may be exacerbated by the use of these same drugs.
Electrocardiogram (ECG): A diagnosis of Brugada syndrome may be made after an electrocardiogram (ECG), which records the electrical activity of the heart. During an ECG, six small adhesive electrode pads are placed across the chest from the lower sternum (breastbone) to an area below the left armpit. Other pads will be placed on each of arm and leg. Insulated wires will connect each of these 10 pads to the ECG machine. Once these wires, called leads, are attached, the ECG records a few heartbeats on a single sheet of graph paper. Brugada syndrome is characterized by a distinctive ECG pattern with an elevated ST segment, which represents the period between the positive and negative charges of the heart cell's membrane, or J wave. The J wave is a deflection with a dome or hump configuration occurring at a certain point in an ECG. In the case of Brugada syndrome, this pattern occurs from the leads on the right side of the chest.
ECG alterations may fluctuate with body temperature, and ECG changes can be exacerbated by fever, use of certain drugs, such as sodium-channel blockers, and abnormal blood levels of glucose, insulin, potassium, and calcium. For these reasons, a diagnosis of Brugada syndrome cannot be based solely on an ECG. If Brugada syndrome is suspected but the ECG does not indicate the presence of the syndrome, certain drugs such as flecainide or procainamide, which are used to treat arrhythmic disorders, may be given to the patient to induce the characteristic ECG patterns and help in diagnosis. These drugs are administered prior to the ECG and work by blocking the sodium channel of the heart, resulting in a slowing of the conduction of the electrical impulse within the heart.
Genetic testing: If Brugada syndrome is suspected, a deoxyribonucleic acid (DNA) test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the SCN5A gene. If this defect is detected, a positive diagnosis may be made. However, a negative result generally does not rule out causal gene mutations, and because the genetic cause of the remaining cases of Brugada syndrome are still under investigation, diagnosis should not be based solely on genetic testing.
Prenatal DNA testing: If there is a family history of Brugada syndrome, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose Brugada syndrome. There are serious risks associated with these tests, and patients should discuss the potential health benefits and risks with a medical professional.
During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During CVS, a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutation in the SCN5A gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

General: Complications of Brugada syndrome occur from the abnormal activity of the heart. Complications may include fainting, seizures, breathing problems, nightmares, disruptive sleep, and sudden death. These problems often occur when a person is either sleeping or at rest.
Breathing problems: During an episode of ventricular arrhythmia, the individual may experience difficulty breathing.
Fainting: Fainting may occur during an episode of ventricular arrhythmia.
Seizures: An individual with Brugada syndrome may experience seizures as a result of the irregular heartbeats caused by ventricular arrhythmia.
Sudden death: Also caused by arrhythmias, sudden death often occurs when a person with Brugada syndrome is sleeping or at rest. The average age of sudden death caused by Brugada syndrome is 40, although it may occur from infancy into old age. Sudden death usually follows these episodes of ventricular arrhythmia unless the heart receives an immediate electrical shock from a defibrillator.
Other: Other symptoms that may be caused by arrhythmias in Brugada syndrome include nightmares, thrashing during sleep, and nerve problems. Improper function of the heart can cause decreased blood flow to the brain, ultimately resulting in brain damage.

Treatment

General: There is no cure for Brugada syndrome. Instead, treatment aims to reduce symptoms and prevent complications. Treatment guidelines for Brugada syndrome are specifically for patients who have experienced cardiac arrest, because asymptomatic patients typically do not receive medical care. When provided with an implantable defibrillator, total mortality in patients with Brugada syndrome has been 0% with up to 10 years of follow-up.
Artificial oxygen: The irregular heartbeat in Brugada syndrome may result in a lack of oxygen to the brain as a result of the heart's inability to pump blood through the body effectively. The first goal of treatment is to restore oxygen to the brain. The method of restoration depends on the cause of the hypoxia. For mild-to-moderate cases of hypoxia, removal of the cause may be sufficient. Inhaled oxygen may also be provided. In severe cases treatment may also involve life support and damage control measures.
Implantable cardioverter defibrillator: An implantable cardiac defibrillator (ICD) is currently the only treatment with proven efficacy to regulate electrical activity in the heart of individuals with Brugada syndrome. An ICD is connected to leads placed inside or on the surface of the heart. An ICD delivers electrical shocks, senses the rhythm of the heart, and may provide pacing for the heart. People with Brugada syndrome who have already experienced cardiac arrest should receive an ICD. Because many individuals with Brugada syndrome experience long intervals of good health, the implantation of an ICD may not be appropriate in all patients. It is typically reserved for those with recurring episodes of arrhythmia. Whether an ICD is used at all should be discussed in detail with a qualified healthcare professional.
Medications: There is limited evidence that drugs can improve the prognosis of people with Brugada syndrome. Quinidine may help regulate the electrical activity of the heart. While there is some evidence that quinidine decreases abnormal heart rhythms, use of this drug remains controversial. It tends to be used as an adjunct to other therapies in the most severely affected individuals with Brugada syndrome. The most common side effects are diarrhea, nausea, vomiting, heartburn, rash, fever, dizziness, and headache.
Restriction on activity: Because certain types of physical activity may predispose people with Brugada syndrome to abnormal heart rhythms, these individuals are advised not to participate in competitive sports.

Integrative therapies

Note: Currently there is limited scientific evidence on the use of integrative therapies for the treatment or prevention of Brugada syndrome. The therapies listed below have been studied for related conditions, such as arrhythmia. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.
Unclear or conflicting scientific evidence:
Aconite: Aconitum is a genus of flowering plant belonging to the Ranunculaceae (buttercup) family. Cured aconite preparations have a long history of use in Chinese medicine. Processed aconite has been used to treat heart failure and other heart diseases. However, the toxic effects associated with aconitine (a poisonous alkaloid and the active agent of aconite) limit its ability to be used to treat bradycardia, or slow heartbeat. Additional research is needed in this area to make a conclusion. Unprocessed aconite is highly toxic and is not safe for human consumption.
Corydalis: Corydalis is a genus of about 300 species of annual and perennial herbaceous flowering plants in the Fumariaceae family. Early evidence suggests that certain compounds found in Corydalis may help abnormal heart rhythms. More studies are needed to confirm these findings. Corydalis is generally considered safe and has been used since ancient times as part of traditional Chinese medicine (TCM) preparations. Avoid in individuals with known allergy or sensitivity to Corydalis. Individuals taking sedatives or hypnotics, drugs that treat abnormal heart rhythms (including bepridil), pain relievers, and anticancer drugs should use corydalis with caution.
L-carnitine: The main function of L-carnitine is to transfer long-chain fatty acids in the form of their acyl-carnitine esters across the inner mitochondrial membrane before beta-oxidation. In humans, L-carnitine is synthesized in the liver, kidney, and brain and actively transported to other areas of the body. For example, 98% of the total body L-carnitine is confined to the skeletal and cardiac muscle at concentrations approximately 70 times higher than those in the blood serum. Although preliminary results are promising, there is insufficient available evidence to recommend for or against use of L-carnitine for heart arrhythmia. Avoid with known allergy or hypersensitivity to carnitine. Use cautiously with peripheral vascular disease, hypertension (high blood pressure), alcohol-induced liver cirrhosis, and diabetes. Use cautiously in low-birthweight infants and individuals receiving hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.
Omega-3 fatty acids: Dietary sources of omega-3 fatty acids include fish oil and certain plant and nut oils. Fish oil contains both docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), while some nuts (e.g., English walnuts) and vegetable oils (e.g., canola, soybean, flaxseed, linseed, and olive) contain alpha-linolenic acid (ALA). There is promising evidence that omega-3 fatty acids may decrease the risk of cardiac arrhythmias. This is one proposed mechanism behind the reduced number of heart attacks in people who regularly ingest fish oil or EPA plus DHA. Additional research is needed in this area before a firm conclusion can be reached. People with allergy or hypersensitivity to fish should avoid fish oil or omega-3 fatty acid products derived from fish. Skin rash has been reported, but rarely. People with allergy or hypersensitivity to nuts should avoid alpha-linolenic acid or omega-3 fatty acid products derived from the types of nuts that cause a reaction. The U.S. Food and Drug Administration (FDA) classifies low intake of omega-3 fatty acids from fish as generally recognized as safe (GRAS).
Caution may be warranted in patients with diabetes, because of potential increases in blood sugar levels. Omega-3 fatty acids lower triglyceride levels but can actually increase (worsen) low-density lipoprotein (LDL, or "bad") cholesterol levels by a small amount. Fish flesh may contain methylmercury, and therefore caution is warranted in young children and pregnant or breastfeeding women. Omega-3 fatty acids may increase the risk of bleeding. There is little evidence of significant bleeding risk at lower doses. However, very large intakes of fish oil and omega-3 fatty acids may increase the risk of hemorrhagic (bleeding) stroke. High doses have also been associated with nosebleed and blood in the urine. Fish oils appear to decrease platelet aggregation and prolong bleeding time, increase fibrinolysis (breaking down of blood clots), and may reduce von Willebrand factor.
Traditional Chinese medicine (TCM): TCM herb combinations have been used to stabilize arrhythmia after viral myocarditis (inflammation of the heart). However, research designs have been weak, and more studies of better design are needed before recommendations can be made. Chinese herbs can be potent and may interact with other herbs, foods, or drugs. Consult a qualified healthcare professional before taking any TCM herbs. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metal, or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra and has been associated with heart rhythm abnormalities (e.g., arrhythmias, QT prolongation). Avoid ginseng if pregnant or breastfeeding.

Prevention

General: Because Brugada syndrome is an inherited condition, there is currently no known way to prevent the disorder. Avoiding drugs that cause or exacerbate Brugada syndrome may help relieve or prevent symptoms. In addition, careful monitoring of calcium and potassium blood levels may offset exacerbations in symptoms.
Relatives and coworkers of people with Brugada syndrome should be trained to perform cardiopulmonary resuscitation (CPR) in case of cardiac arrest.
Genetic testing and counseling: Individuals who have Brugada syndrome may meet with a genetic counselor to discuss the risks of having children with the disease. Individuals with a family history of Brugada syndrome, but who have not been diagnosed with the disorder themselves, may meet with a genetic counselor to determine whether they carry the defective SCN5A gene. People who have the defective SCN5A gene may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated risks of various tests, including preimplantation genetic diagnosis (PGD), amniocentesis, and chorionic villus sampling (CVS).
Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective SCN5A gene, and only the embryos that are not affected may be selected for implantation. Because Brugada syndrome can be detected in a fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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Causes

Genetic mutation: Brugada syndrome type 1 is sometimes caused by mutations or defects in the SCN5A gene. The SCN5A gene provides instructions for making a cardiac sodium channel, a protein essential to the normal electrical functioning and rhythm of the heart. The sodium channel normally transports positively charged sodium ions into heart muscle cells. This type of ion channel plays a critical role in maintaining the heart's normal rhythm. Mutations in the SCN5A gene alter the structure or function of the channel, which reduces the flow of sodium ions into cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Brugada syndrome. Only about one-third of people with Brugada syndrome have been identified as having a mutated copy of this gene.
Brugada syndrome type 2 is caused by a mutation in the GPD1L gene. This mutation decreases the expression of the sodium channel on the cell surface, resulting in reduced inward sodium current and abnormal heart function.
Brugada syndrome type 3 is caused by a mutation in the CACNA1C gene. This gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium ions into cells, play a key role in the cell's ability to generate and transmit electrical signals.
Brugada syndrome type 4 is caused by a mutation in the CACNB2 gene, a subunit of the L-type cardiac calcium channel. A mutation in this gene can lead to a shorter-than-normal QT interval, resulting in a faster heart rate.
The genetic cause or causes of the remaining cases of Brugada syndrome are still under investigation.
Autosomal dominant inheritance: When Brugada syndrome is inherited, or passed down among family members, it follows an autosomal dominant pattern of inheritance. This means that only one copy of the defective gene is needed for the disease to occur. Individuals receive two copies of most genes, one from the mother and one from the father. If one parent has the disorder, there is a 50% chance that his or her child will have the disorder. If both parents have the disorder, there is a 75% chance that their child will have the disorder. It has been estimated that approximately 60% of individuals with sudden death and the typical electrocardiogram of Brugada syndrome have a family history of sudden death or have family members with the same electrocardiographic abnormalities.
Random occurrence: In some cases, Brugada syndrome occurs in an individual with no family history of the disease. This is caused by a spontaneous genetic mutation in the sperm or egg cells or in the developing embryo. People who acquire Brugada syndrome as the result of a spontaneous mutation may be able to pass on the syndrome to their children.
Other: In rare cases, Brugada syndrome has been caused by abnormally low potassium levels or abnormally high calcium levels in the blood.

Risk factors

Brugada syndrome is sometimes caused by mutations or defects in the SCN5A gene. The SCN5A gene provides instructions for making the cardiac sodium channel, a protein essential to the normal electrical functioning and rhythm of the heart. Only about one-third of people with Brugada syndrome have been identified as having a mutated copy of this gene. The major risk factor for this cause of Brugada syndrome is a family history. When Brugada syndrome is inherited, or passed down among family members, it follows an autosomal dominant pattern of inheritance. This means that only one copy of the defective gene is needed for the disease to occur.
In those individuals without a mutated SCN5A gene, the cause of Brugada syndrome is often unknown. It may be caused by a spontaneous mutation in the gene or by certain drugs that affect heart rhythm, such as those used to treat some forms of arrhythmia (irregular heart beat), angina (chest pain), high blood pressure, and depression and other mental illnesses.
The prevalence of the syndrome is unknown, but it is estimated to occur in about one in 2,000 people worldwide. Some researchers state that the prevalence of Brugada syndrome may be five in 1,000 in Caucasians worldwide and 14 in 1,000 in Japanese worldwide. Brugada syndrome is more common among people from Japan and Southeast Asia. Known as lai tai in Thailand, bangungut in the Philippines, and pokkuri in Japan, Brugada syndrome is the most common natural cause of death in men under 50 years of age in these countries.
Although the probability of having a mutated gene does not differ by sex, Brugada syndrome is about 8-10 times more common in males. This discrepancy may be linked to testosterone, a male sex hormone.

Types of the disease

General/Brugada syndrome type 1: Because Brugada syndrome type 1 (usually referred to simply as Brugada syndrome) is the most common, it is the focus of most of the available information on this disorder. Brugada syndrome type 1 is sometimes caused by mutations or defects in the SCN5A gene. The SCN5A gene provides instructions for making a cardiac sodium channel, a protein essential to the normal electrical functioning and rhythm of the heart.
Brugada syndrome type 2: Brugada syndrome type 2 is caused by a mutation in the GPD1L gene. A mutation in this genedecreases the expression of the sodium channel on the cell surface that is produced by the SCN5A gene, resulting in reduced inward sodium current and abnormal heart function.
Brugada syndrome type 3: Brugada syndrome type 3 is caused by a mutation in the CACNA1C gene. This gene belongs to a family of genes that provide instructions for making calcium channels. These channels, which transport positively charged calcium atoms (ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals.
Brugada syndrome type 4: Brugada syndrome type 4 is caused by a mutation in the CACNB2 gene, which is a subunit of the L-type cardiac calcium channel. A mutation in this gene can lead to a shorter-than-normal QT interval, resulting in a faster heart rate.