Long QT syndrome

Related Terms

Andersen-Tawil syndrome, arrhythmia, CACNA1c, cardiac arrest, cardiac channelopathy, caveolin-3, congenital heart disease, congenital long QT syndrome, familial arrhythmia, familial heart disease, HERG, inherited heart disease, Jervell and Lange-Nielsen syndrome, JLN syndrome, KCNE1 gene, KCNE2 gene, KCNJ2 gene, KCNQ1 gene, long-QT syndrome, LQT1, LQT2, LQT3, LQT4, LQT5, LQT6, LQT7, LQT8, LQT9, LQT10, LQTS, Romano-Ward syndrome, SCN4B gene, SCN5A gene, sudden death, syncope, Timothy's syndrome, torsade de pointes, ventricular arrhythmia, ventricular tachyarrhythmia.

Background

Long QT syndrome (LQTS) is one of the leading causes of sudden cardiac death. It is a rare arrhythmia, or irregular heart rhythm. When the heart beats, the electrical impulses that cause it to contract must follow a precise pathway through the heart. Any interruption in these impulses can cause an arrhythmia. LQTS can be inherited or may be caused by blood electrolyte imbalances or drug use.
The hollow center of the heart is divided into four sections, called chambers. The two upper chambers in the heart are called atria. The two lower chambers in the heart are called ventricles. Normal heart rhythm is very regular, with minimal changes. Atrial contraction is always followed by ventricular contraction in the normal heart. Arrhythmias occur when this rhythm becomes irregular, too fast, too slow, or when the frequency of the atrial and ventricular beats are different.
LQTS is a heart rhythm disorder that may cause fast, chaotic heartbeats. This electrical disturbance can be seen on an electrocardiogram (ECG). Rapid heartbeats in LQTS may lead to fainting. In some cases, the heart's rhythm may beat so erratically that it can cause sudden death. People with LQTS may experience an arrhythmia called torsade de pointes, which is a very fast, abnormal heart rhythm. When this rhythm occurs, no blood is pumped out from the heart, and the brain quickly becomes deprived of oxygen. Torsade de pointes can lead to brain damage and ultimately death.
After a heartbeat, the heart's electrical system recharges itself in preparation for the next heartbeat. This is called repolarization. In LQTS, however, the heart takes longer than normal to recharge between beats. The QT interval is the time that it takes for depolarization and repolarization of the ventricles of the heart. In LQTS, the duration of repolarization is longer than normal.
Some people are born with a genetic mutation that puts them at risk for LQTS. There are many different types of inherited LQTS that are caused by different genetic mutations. LQTS may also be caused by use of certain drugs. There are more than 50 medications that may cause LQTS. Medical conditions, such as congenital heart defects, may also cause LQTS. Arrhythmias in individuals with LQTS are often associated with exercise or excitement.
Treatment for LQTS may include limiting physical activity, avoiding certain medications, or taking medications to prevent arrhythmia, such as beta-blockers. Some people with LQTS also need an implantable device, such as a pacemaker, to control the heart's rhythm and to prevent cardiac arrest.

Signs and symptoms

General: Long QT syndrome (LQTS) often goes undiagnosed or is misdiagnosed as a seizure disorder. Children, teenagers, and young adults with unexplained fainting, near-drowning or other accidents, unexplained seizures, or a history of cardiac arrest may have a genetic defect that causes LQTS. About half of the people with LQTS do not have any signs or symptoms. They may be aware of their condition only from results of an electrocardiogram (ECG) or because they have a family history of LQTS.
Symptoms of inherited LQTS may start during the first months of life or as late as middle age. Most LQTS-related deaths occur in people aged 11-30. Rarely, symptoms of LQTS occur during sleep or arousal from sleep. Usually, an affected person suddenly faints or passes out during exercise or when experiencing intense emotions, such as fear. There is usually no warning or sensation of feeling faint or dizzy. In 30% of cases where death results, the person appears quite fit and healthy and appears to have no symptoms at all before cardiac arrest.
Fainting (syncope): Fainting, or syncope, is a sudden loss of consciousness. It most often occurs when the blood pressure is too low (called hypotension) and the heart does not pump a normal supply of oxygen to the brain. Typically, a faint lasts only a few seconds or minutes and then the individual regains consciousness. A single fainting spell usually is not serious. It may be explained by factors such as stress, grief, overheating, dehydration, exhaustion, illness, or arrhythmias.
Seizures: If the heart continues to beat erratically, the brain becomes increasingly deprived of oxygen, which may lead to seizures. Some people with LQTS have been misdiagnosed as having a seizure disorder and have been incorrectly treated with antiepileptic medications.

Diagnosis

General: The diagnosis of long QT syndrome (LQTS) is difficult, because 2.5% of the healthy population has a prolonged QT interval, and 10% of LQTS patients have a normal QT interval. Children, teenagers, and young adults with unexplained fainting, unexplained near-drowning or other accidents, unexplained seizures, or a history of cardiac arrest should be considered for diagnosis of LQTS.
LQTS diagnostic score: A doctor may diagnose LQTS using the LQTS diagnostic score. This score is based on several criteria, including measurements of cardiac electrical activity, incidence of fainting, deafness, a family history of LQTS, and other factors. A score of four or more points indicates a high probability of LQTS. A score of two or three points indicates an intermediate probability of LQTS. A score of one or fewer points indicates a low probability of LQTS.
Electrocardiogram (ECG/EKG): An electrocardiogram is a special recording machine that is attached to the legs, arms, and chest via 10 electrodes. An ECG measures and takes a picture of the electric signals that create heart rhythms. The data from an ECG can be analyzed by doctors for heart arrhythmias. In LQTS, the heart muscle takes longer than normal to repolarize (recharge between beats). An ECG measures electrical impulses as five distinct waves. Doctors label these five waves using the letters P, Q, R, S, and T. The waves labeled Q through T show electrical activity in the heart's lower chambers. The space between the start of the Q wave and the end of the T wave (i.e., the QT interval) corresponds to the time it takes for the heart to contract and then refill with blood before beginning the next contraction. Therefore, the QT interval refers to the length of time it takes cells in the heart's lower chambers to electrically discharge and then recharge. By measuring the QT interval, doctors can tell whether it occurs in a normal amount of time. If it takes longer than normal, it's called a prolonged QT interval. LQTS results from abnormalities in the heart's electrical recharging system, although the heart's structure is normal.
Echocardiogram: An echocardiogram is a special imaging machine with a microphone-like attachment that creates a videotaped image of the heart, including the heart's four chambers, valves, and movements. Results are analyzed by doctors to determine whether a patient has an arrhythmia.
Tilt table test: Tilt table testing is used to diagnose fainting or blackout spells by trying to reproduce the blackout episodes. A patient lies on a special table that is then tilted upright to about 60 degrees for a period of time, with continuous ECG recording and blood pressure monitoring.
Genetic testing: If LQTS is suspected, a 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 or defects in genes that are associated with LQTS. If genetic mutations are detected, a positive diagnosis is made. However, some forms of LQTS may not be detected through genetic testing.
Prenatal DNA testing: In a family with suspected LQTS, genetic testing can determine the defect in as many as 75% of subjects. Prenatal testing, including amniocentesis and chorionic villus sampling (CVS), may be performed to determine if a fetus has the disorder. Because there are serious risks associated with these tests, patients should discuss these procedures 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 week 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 genes associated with LQTS. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.
Holter monitoring: Holter monitoring detects irregular heart rhythms. Patients wear a Walkman-sized recording box attached to their chest by five adhesive electrode patches for 24-48 hours. Doctors analyze the results to determine if arrhythmia is present.
Exercise stress test: The exercise stress (treadmill) test enables doctors to record changes in the heart's electrical activity that may not occur at rest. As the individual exercises, the heart will need to pump more and more blood and oxygen to the body. The test can show if the blood supply is reduced in the arteries that supply the heart. It also helps doctors to understand the kind and level of exercise appropriate for a patient. The stress test is performed in an exercise laboratory (in a hospital or clinic) where the heart rate and blood pressure are recorded at rest. Sticky electrodes are attached to the chest, shoulders, and hips, and are connected to the ECG portion of the stress test machine.
The treadmill is started at a relatively slow warm-up speed. Gradually, the slope and speed are increased to simulate exercise stress. During the test, the doctor monitors the heart rate, blood pressure, changes in the ECG pattern, any irregular heart rhythm, and the individual's appearance and symptoms. The treadmill is stopped when the patient reaches 85% of the maximal heart rate predicted for the patient's age. If the patient is doing extremely well at peak exercise, however, the treadmill test may be continued further. The test may be stopped prior to achievement of the target heart rate if the patient develops significant chest discomfort, shortness of breath, dizziness, or unsteady gait, or if the ECG shows alarming changes or seriously irregular heartbeats. It may also be stopped if the blood pressure rises or falls beyond acceptable limits. The systolic blood pressure (the upper number in a blood pressure reading) may normally rise to 200 at peak exercise. At the same time, the diastolic blood pressure (the lower number in a blood pressure reading) remains unchanged or falls to a slight degree. Patients with hypertension or high blood pressure will show a rise of both systolic and diastolic readings; the diastolic reading may rise above 90-100.
Healthcare professionals recommend that patients not eat or drink for three hours prior to the exercise stress test. This reduces the likelihood of nausea that may accompany strenuous exercise after consuming a heavy meal. People with diabetes, especially those who use insulin, will need special instructions from the doctor's office regarding how to take their medications. It is also recommended that patients wear comfortable clothing and shoes that are suitable for exercise. An explanation of the test is provided and the patient is asked to sign a consent form. The risk of the stress portion of the test is very small and similar to what one would expect from any strenuous form of exercise such as jogging or running up a flight of stairs. As noted earlier, experienced healthcare professionals are in attendance to manage any rare complications such as sustained irregular heartbeats, unrelieved chest pain, or even a heart attack.

Complications

General: Prolonged QT intervals may never cause any problems in some patients. However, physical or emotional stress may cause the heart to beat in a dangerous rhythm if an individual is susceptible to prolonged QT intervals.
Fainting (syncope): Fainting, or syncope, is a sudden loss of consciousness. It most often occurs when the blood pressure is too low (called hypotension) and the heart does not pump enough oxygen-containing blood to the brain. Typically, a faint lasts only a few seconds or minutes and then the individual regains consciousness. Fainting is a common problem that affects one million people in the United States every year. About one-third of individuals will faint at least once during a lifetime. A single fainting spell usually is not serious. It may be explained by factors such as stress, grief, overheating, dehydration, exhaustion, illness, or arrhythmias.
Sudden cardiac death: Sudden cardiac death is the sudden loss of heart function in an individual who may or may not have diagnosed heart disease. In long QT syndrome (LQTS), life-threatening arrhythmias are responsible for sudden death.
Torsade de pointes: A prolonged QT interval may trigger a particular arrhythmia (irregular heart rhythm) called torsade de pointes, or twist of the points. In this condition, the heart's ventricles beat fast, making the waves on an electrocardiogram (ECG) monitor look twisted. When this arrhythmia occurs, less blood is pumped out from the heart, which can cause fainting. If an episode of torsade de pointes is short (less than one minute), the heart can correct itself seconds later. If an episode of torsade de pointes persists, however, it can lead to a life-threatening arrhythmia called ventricular fibrillation.
Ventricular fibrillation: In ventricular fibrillation, the ventricles beat so fast that the heart quivers and stops pumping blood. Unless the heart is shocked back into a normal rhythm by a device called a defibrillator, ventricular fibrillation can lead to brain damage and death. LQTS may explain some cases of sudden death in young people who otherwise appear healthy.

Treatment

General: Treatment for long QT syndrome (LQTS) may involve lifestyle changes, medications, medical devices, and/or surgery. The goal of treatment is to prevent the heart from ever beating out of control.
Lifestyle changes: Physical activity, such as swimming, and stress-related emotions frequently trigger cardiac events in patients with LQTS. Strenuous exercise or contact sports; loud, startling noises; and stressful situations should be avoided by these individuals.
Torsade de pointes: Treatment for torsade de pointes includes the correction of electrolyte imbalances, if present, and stopping the use of any drugs that may induce this condition.
Drugs:
Arrhythmia (irregular heart rhythm) suppression involves the use of medications that prevent the underlying cause of the arrhythmias associated with LQTS. While medications will not cure LQTS, they can provide some protection against potentially fatal disruptions of the heart rhythm. Medications, such as beta-blockers, may need to be taken indefinitely.
Beta-blockers: Administration of beta-receptor blocking agents decreases the risk of stress-induced arrhythmias. Beta-blockers are the first choice in treating LQTS. Beta-blockers slow the heart rate by reducing the speed of the heart's contractions. Beta-blockers are used to treat other cardiac conditions, such as atrial fibrillation and atrial flutter. Individuals who have asthma and diabetes should not take these drugs. Examples of beta-blockers include atenolol (Tenormin?), metoprolol (Lopressor?, Toprol?, Toprol XL?), nadolol (Corgard?), and propranolol (Inderal?).
Sodium channel blockers: Sodium channel blockers slow the conduction of electrical impulses through the heart. These drugs are used to treat different types of abnormal heartbeats in order to maintain a normal heart rhythm. Side effects include potentially fatal arrhythmias, stomach upset, dizziness, light-headedness, tremor, urine retention, increased pressure in the eye in individuals with glaucoma, and dry mouth. Examples of sodium channel blockers include disopyramide (Norpace?), flecainide (Tambocor?), lidocaine (Xylocaine?), mexiletine (Mexitil?), moricizine (Ethmozine?), procainamide (Procan?, Procan SR?), propafenone (Rythmol?), quinidine (Quinidex?), and tocainide (Tonocard?).
Potassium: Potassium is a mineral that is found in the body. It is derived from the diet and is important for cardiac health. Potassium supplements may improve the heart's recharging system and may be helpful for people with certain forms of LQTS. If the potassium content in the blood rises, the action potential shortens. It is believed that increasing potassium concentration could minimize the occurrence of arrhythmias. Potassium supplements tend to work best in LQT2, because the HERG (human ether-a-go-go-related gene) potassium channel in the heart is especially sensitive to potassium concentration. However, this has not yet been proven.
Implantable devices:
Although drugs such as beta-blockers can effectively control nearly 90% of LQTS cases, some people need treatment with a pacemaker and implantable defibrillator.
Pacemaker: If symptom-producing arrhythmias do not have an identifiable and treatable cause, doctors often treat them with a pacemaker. A pacemaker is a small, battery-powered device that is usually implanted near the collarbone. A permanent pacemaker can be surgically placed into the chest through a small incision, while a temporary pacemaker can be worn outside the body and attached to the heart through a wire that is threaded through a neck vein. Temporary pacemakers are used only while an individual is in the hospital.
Implanting a permanent pacemaker is considered a minor surgical procedure. The procedure may take 1-2 hours to complete. The area where the pacemaker will be inserted will be numbed with an injection of an anesthetic such as lidocaine (Xylocaine?). The individual should not feel any pain during the procedure and should inform the doctor or staff if there is pain, so that more anesthetic medication may be given. One or more electrode-tipped wires are run from the pacemaker through the blood vessels to the inner heart. If the heart rate is too slow or if it stops, the pacemaker sends out electrical impulses that stimulate the heart to beat at a steady, proper rate. The more advanced pacemakers can monitor and pace either the atria, the ventricles, or both in proper sequence to maximize the amount of blood being pumped from the heart. The pacemaker's batteries may need to be changed every 5-10 years. The American Heart Association recommends that individuals with pacemakers limit their exposure to devices that may interfere with pulse generators such as cellular phones, CB radios, electric blankets, and microwaves.
After a pacemaker is implanted, the surgical wound may be somewhat painful and swollen for a few days. These symptoms can usually be controlled with medications, such as tramadol (Ultram?) or ibuprofen (Motrin?). The wound may also be red for a few days. If the area of redness enlarges, however, a doctor should be notified, due to the potential for a serious infection.
If there are no other problems, most individuals who have a permanent pacemaker surgically implanted can go home the next day. They can usually return to normal activities within six weeks. For several weeks after having a pacemaker implanted, the individual may be asked not to lift more than five pounds or to raise the affected arm higher than the shoulder.
Implantable cardioverter-defibrillator (ICD): An implantable cardioverter defibrillator, or ICD, is connected to leads that are 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. Because many individuals with LQTS experience long intervals of good health, the implantation of an ICD may not be appropriate in all patients. Whether or not an ICD is used should be discussed in detail with a qualified healthcare professional, such as a cardiologist.

Integrative therapies

Note: Currently, there are limited scientific data on the use of integrative therapies for the treatment or prevention of long QT syndrome (LQTS). The therapies listed below have been studied for the prevention or treatment of arrhythmia and related conditions. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used instead of other proven therapies.
Good scientific evidence:
Magnesium: Intravenous magnesium has been reported to reduce the incidence of atrial fibrillation and cardiac arrhythmia. However, it was not found to affect to the length of hospitalization, incidence of myocardial infarction, or mortality.
Use cautiously in patients with bleeding disorders or in those taking anticoagulants or antiplatelet agents. Use cautiously in patients taking antidiabetic or antihypertensive agents. Use cautiously when magnesium sulfate is used topically for prolonged periods or repeatedly. Use cautiously with antibiotics. Use intravenous magnesium sulfate with extreme caution in patients with eclampsia. Avoid in patients with atrioventricular heart block. Avoid in patients with renal failure or severe renal disease. Avoid intravenous magnesium in women with toxemia during the first few hours of labor.
Unclear or conflicting scientific evidence:
Aconite: The toxic effects associated with aconitine (a poisonous alkaloid and the active principle of aconite) limit its ability to be used to treat arrhythmia. Additional research is needed in this area.
Aconite is highly toxic and is not safe for human consumption. Avoid with heart disease, irregular heartbeat, hemodynamic instability (abnormal blood flow), and gastrointestinal disorders (such as ulcers, reflux esophagitis, ulcerative colitis, spastic colitis, or diverticulosis). Use cautiously with diabetes or suicidal tendencies. Avoid if younger than 18 years old. Avoid if pregnant or breastfeeding.
Corydalis: Early evidence suggests certain compounds found in corydalis may be of benefit for arrhythmia. More studies are needed to confirm these findings.
Corydalis is generally considered safe. Avoid if allergic or sensitive to corydalis. Avoid if taking sedative or hypnotic drugs, drugs that treat abnormal heart rhythms (including bepridil), pain relievers, or anticancer drugs. Avoid if pregnant or breastfeeding.
L-carnitine: L-carnitine, or acetyl-L-carnitine, is an amino acid found in the body. L-carnitine has been reported to be beneficial in maintaining a healthy heart. Although preliminary results are promising, well-designed and reported clinical trials investigating the effect of L-carnitine on arrhythmia are lacking.
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 on hemodialysis. Use cautiously if taking anticoagulants (blood thinners), beta-blockers, or calcium channel blockers. Avoid if pregnant or breastfeeding.
Omega-3 fatty acids: There is evidence from multiple clinical studies supporting the intake of omega-3 fatty acid (also known as fish oil) supplements for a healthy heart. Fish oil supplements have been reported to lower triglycerides and reduce the risk of death, heart attack, and stroke in people with known heart disease. Fish oil may also slow the buildup of atherosclerotic plaques (hardening of the arteries) and lower blood pressure slightly. There is promising evidence that omega-3 fatty acids may decrease the risk of arrhythmias. Additional research is needed in this area before a firm conclusion can be reached.
Omega-3 fatty acids may increase the chances of bleeding, especially if the individual is taking blood-thinning medications, such as aspirin or warfarin (Coumadin?). It is important to choose fish and fish oils that are free of heavy metals such as mercury and lead. Avoid if allergic or hypersensitive to fish, nuts, omega-3 fatty acid products that come from fish or nuts, or linolenic acid. Use cautiously before surgery.
Traditional Chinese medicine: Traditional Chinese medicine (TCM) is a broad term encompassing many different methods and traditions of healing, such as acupuncture, herbal medicines, cupping, and moxibustion. They share a common heritage of technique or theory rooted in ancient Chinese philosophy (Taoism) and dating back over 5,000 years. TCM herb combinations have been used to stabilize arrhythmias 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. There have been reports of manufactured or processed Chinese herbal products being tainted with toxins or heavy metals or not containing the listed ingredients. Herbal products should be purchased from reliable sources. Avoid ma huang, which is the active ingredient in ephedra. Avoid ginseng if pregnant or breastfeeding.

Prevention

General: People with long QT syndrome (LQTS) should seek medical treatment immediately for illnesses that could result in low blood potassium levels, such as conditions that cause vomiting and diarrhea. Friends, family, and colleagues of a patient with LQTS should be told about the condition and should be educated to immediately call emergency medical services if the person faints. They should also be trained to perform cardiopulmonary resuscitation (CPR) should the individual go into cardiac arrest. Patients with LQTS should be regularly followed by a cardiologist.
Genetic testing and counseling: Individuals who have LQTS may meet with genetic counselors to discuss the risks of having children with the disease. Individuals with family histories of LQTS but who have not been diagnosed with the disorder themselves may meet with genetic counselors to determine whether they carry a defective gene that is associated with LQTS. People who have genetic mutations that cause LQTS 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).
Medications: People who have LQTS should be careful about taking certain medications. Some medications, including certain appetite suppressants, decongestants, and common antibiotics, such as erythromycin, may trigger dangerous heart rhythms. Street drugs, such as cocaine and amphetamines, pose a serious risk for people with LQTS. People with LQTS should avoid stimulants, including medications found in over-the-counter cold and nasal congestion medications, such as pseudoephedrine and caffeine.
Stress reduction: Stress can increase blood pressure and the blood's tendency to clot. Managing stress can decrease the chances of developing the symptoms of LQTS.
Diet: It is important for all people, including those with LQTS, to consume a healthful diet. A heart-healthy diet should include five or more daily servings of fruits and vegetables, foods rich in soluble fiber (such as oatmeal and beans), foods rich in calcium (dairy products, spinach), soy products (such as tempeh, miso, tofu, and soy milk), and foods rich in omega-3 fatty acids (including cold-water fish, such as salmon, mackerel, and tuna). Pregnant women and women who plan to become pregnant in the next several years should limit their weekly intake of cold-water fish because of the potential for mercury contamination. The U.S. Food and Drug Administration (FDA) has announced that whole-grain barley and barley-containing products may feature a claim that they reduce the risk of coronary artery disease.

Author information

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

Bibliography

American Heart Association. .
Borchert B, Lawrenz T, Stellbrink C. Long and short QT syndrome. Herzschrittmacherther Elektrophysiol. 2006 Dec;17(4):205-10.
Collins KK, Van Hare GF. Advances in congenital long QT syndrome. Curr Opin Pediatr. 2006 Oct;18(5):497-502.
Heart Rhythm Society. .
Kannankeril PJ, Roden DM. Drug-induced long QT and torsade de pointes: recent advances. Curr Opin Cardiol. 2007 Jan;22(1):39-43.
Nader A, Massumi A, Cheng J, et al. Inherited arrhythmic disorders: long QT and Brugada syndromes. Tex Heart Inst J. 2007;34(1):67-75.
National Heart, Blood, and Lung Institute (NHLBI). .
Natural Standard: The Authority on Integrative Medicine. .
Vohra J. The Long QT Syndrome. Heart Lung Circ. 2007;16 Suppl 3:S5-12.

Causes

General: Long QT syndrome (LQTS) can be inherited or it can be acquired. In some cases, LQTS is congenital (present at birth). Generally, these cases are inherited, or passed down among family members. Most cases of LQTS, however, are acquired causes. They can be divided into two main categories: those due to disturbances in blood electrolytes and those due to various drugs. There are also some other causes of QT prolongation, such as anorexia nervosa, underactive thyroid, HIV infection, and heart attack.
Inherited:
Several different genetic mutations may cause LQTS. Genetic LQTS can arise from a mutation in one of several genes. These mutations tend to prolong the duration of the ventricular action potential, resulting in a lengthening of the QT interval.
Autosomal dominant inheritance: Some forms of LQTS are inherited, or passed down among family members, in an autosomal dominant pattern of inheritance. This means that only one copy of the defective gene is needed for the disease to manifest. 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.
Autosomal recessive inheritance: When LQTS is inherited in an autosomal recessive manner, two mutated alleles (one from each parent) of a single gene must be inherited for a person to develop the disorder. A person who has only one mutated allele does not experience symptoms and is called a carrier. If one parent is a carrier, there is a 50% chance with each birth that the child will also be a carrier and a 0% chance that the child will inherit the disease. If both parents are carriers, there is a 25% chance with each birth that the child will inherit the disease and a 50% chance that each child will be a carrier.
Acquired:
Electrolyte disorders: Individuals with low potassium, magnesium, or calcium blood levels may be susceptible to prolonged QT intervals. People with the eating disorder anorexia nervosa are prone to electrolyte disorders.
Drug-induced: In adults, LQTS may be triggered by certain medications, including antibiotics, antifungals, antidepressants, antihistamines, antipsychotics, cholesterol-lowering drugs, diabetes medications, and diuretics. In addition, drugs used to treat irregular heart rhythm, angina or heart-related chest pain, high blood pressure, depression, and other mental illness may trigger LQTS. Genetic mutations may make a person more susceptible to drug-induced LQTS.
The following drugs should not be taken by anyone who is at risk for LQTS: arsenic trioxide (Trisenox?), bepridil (Vascor?), chlorpromazine (Thorazine?), cisapride (Propulsid?), clarithromycin (Biaxin?), disopyramide (Norpace?), dofetilide (Tikosyn?), dolasetron (Anzemet?), droperidol (Inapsine?), erythromycin (E.E.S.?, Erythrocin?), felbamate (Felbatol?), fluoxetine (Prozac?, Sarafem?), foscarnet (Foscavir?), fosphenytoin (Cerebyx?), gatifloxacin (Tequin?), halofantrine (Halfan?), haloperidol (Haldol?), ibutilide (Corvert?), indapamide (Lozol?), isradipine (DynaCirc?), levofloxacin (Levaquin?), levomethadyl (Orlaam?), mesoridazine (Serentil?), moexipril/HCTZ (Uniretic?), moxifloxacin (Avelox?), naratriptan (Amerge?), nicardipine (Cardene?), octreotide (Sandostatin?), paroxetine (Paxil?), pentamidine (NebuPent?, Pentam?), pimozide (Orap?), procainamide (Procan?, Pronestyl?), quetiapine (Seroquel?), quinidine (Cardioquin?, Quinaglute?), risperidone (Risperdal?), salmeterol (Serevent?), sertraline (Zoloft?), sotalol (Betapace?), sparfloxacin (Zagam?), sumatriptan (Imitrex?), tacrolimus (Prograf?), tamoxifen (Nolvadex?), thioridazine (Mellaril?), tizanidine (Zanaflex?), venlafaxine (Effexor?), ziprasidone(Geodon?), and zolmitriptan (Zomig?).

Risk factors

Long QT syndrome (LQTS) affects about one in 7,000 people. The risk of death from LQTS is higher in males than in females until 10 years of age, when the risk becomes equal. People taking medications known to cause prolonged QT intervals are at risk for developing LQTS.
Potassium, magnesium, and calcium are all important minerals for the health of the heart's electrical system. People with low potassium, magnesium, or calcium blood levels, such as those with the eating disorder anorexia nervosa, may be susceptible to prolonged QT intervals.
There have been reports of a link between sudden infant death syndrome (SIDS) and LQTS. About 10-15% of babies with SIDS have a genetic defect for LQTS.
LQTS often goes undiagnosed or is misdiagnosed as a seizure disorder, such as epilepsy. However, researchers believe that LQTS may be responsible for some otherwise unexplained deaths in children and young adults. For example, an unexplained drowning of a young person may be the first clue to inherited LQTS in a family. Children, teenagers, and young adults with unexplained fainting, unexplained near-drownings or other accidents, seizures, or a history of LQTS or cardiac arrest may have genetic defects that could cause LQTS.

Types of the disease

Acquired long QT syndrome: More than 50 medications, many of them common, can lengthen the QT interval in otherwise healthy people. Use of these drugs may cause a form of long QT syndrome (LQTS) known as drug-induced or acquired LQTS. Medications that can lengthen the QT interval and upset heart rhythm include certain antibiotics, antidepressants, antifungals, antihistamines, antipsychotics, diuretics, heart medications, cholesterol-lowering drugs, and diabetes medications. People who develop drug-induced LQTS may also have some subtle genetic defects in their hearts that make them more susceptible to disruptions in heart rhythm caused by using these drugs.
Inherited long QT syndrome: At least 12 genes associated with LQTS have been identified thus far, and hundreds of mutations within these genes have been identified. Mutations in three of these genes account for about 75% of LQTS.
Romano-Ward syndrome: Romano-Ward syndrome is a form of inherited LQTS that follows an autosomal dominant pattern of inheritance. Romano-Ward syndrome affects about one in 2,500 people.
Jervell and Lange-Nielsen syndrome: Jervell and Lange-Nielsen syndrome (JLNS) is a form of inherited LQTS that follows an autosomal recessive pattern of inheritance. JLNS is associated with deafness that is congenital (present at birth). It is caused by defects in the KCNE1 and KCNQ1 genes. Symptoms of this rare form of LQTS usually occur earlier in life and are more severe than in Romano-Ward syndrome. JLNS is generally suspected in children who are born deaf and who have inherited LQTS.
LQT1: LQT1 is the most common type of LQTS. In LQT1, the KCNQ1 gene is defective. This gene provides instructions for making the potassium channel in the heart. Mutations to the KCNQ1 gene can be inherited in an autosomal dominant or an autosomal recessive manner, even within the same family. People with this type of LQTS have high rates of fainting but a lower risk of sudden death than other forms. Jervell and Lange-Nielsen syndrome is one form of LQT1.
LQT2: LQT2 is the second-most common form of LQTS. This type most likely involves mutations of the HERG gene, which is partially responsible for the time that it takes to complete one heartbeat and therefore the length of the QT interval.
LQT3: LQT3 is caused by mutations in the gene that provides instructions for making part of the sodium channel in the heart (SCN5A). A large number of mutations have been characterized as leading to LQT3. Mutations in SCN5A can also cause Brugada syndrome, which causes unexpected cardiac death; cardiac conduction disease, which causes heart failure due to a blocked heart; and dilated cardiomyopathy, which causes a weakened and enlarged heart.
LQT5: LQT5 is an uncommon form of the disease that follows an autosomal dominant pattern of inheritance. LQT5 is caused by mutations in the KCNE1 gene, which provides instructions for making a component of the heart potassium channel. It can lead to JLNS.
LQT6: LQT6 is an uncommon form of the disease that follows an autosomal dominant pattern of inheritance. It involves mutations in the KCNE2 gene, which provides instructions for making a component of the heart potassium channel.
LQT7: LQT7, which is also called Andersen-Tawil syndrome, is an autosomal dominant form of LQTS that is associated with skeletal deformities and paralysis. LQT7 is caused by a mutation in the KCNJ2 gene, which provides instructions for making a component of the heart potassium channel.
LQT8: LQT8, which is also called Timothy's syndrome, is caused by mutations in the calcium channel gene CACNA1c. Patients with Timothy's syndrome have many clinical manifestations including congenital heart disease, autism, syndactyly (fusion of the fingers or toes), and immune deficiency.
LQT9: LQT9 is caused by mutations in the membrane structural protein caveolin-3, which is important in the heart sodium channel. Similar to LQT3, these particular mutations increase late sodium currents and impair cardiac repolarization.
LQT10: LQT10 is caused by a defect in the SCN4B gene. The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current. Thus far, only one mutation in one patient has been found for this type of LQTS.