Prolonged QT Syndrome

Definition

Prolonged QT syndrome, also known as long QT syndrome (LQTS), refers to a group of disorders that increase the risk for sudden death due to an abnormal heartbeat.

Description

Abnormal heartbeats (cardiac arrhythmias ) are a primary cause of sudden death, especially in the young population. In the United States, an estimated 1 in 300,000 individuals per year die suddenly due to irregular heart rhythms. One of the better understood causes of these arrhythmias is LQTS.

The QT of LQTS refers to an interval between two points (Q and T) on the common electrocardiogram (ECG, EKG) used to record the electrical activity of the heart. This electrical activity, in turn, is the result of small molecules (ions such as sodium and potassium) passing in and out of channels in the membranes surrounding heart cells. A prolonged QT interval indicates an abnormality in electrical activity that leads to irregularities in heart muscle contraction. One of these irregularities is a specific pattern of very rapid contractions (tachycardia) of the lower chambers of the heart called torsade de pointes, a type of ventricular tachycardia. The rapid contractions, which are not effective in pumping blood to the body, result in a decreased flow of oxygen-rich blood to the brain. This can result in a sudden loss of consciousness (syncope) and death.

Causes and symptoms

Both inherited and acquired forms of LQTS have been identified. Most acquired forms are thought to be due to certain drugs including adrenaline (epinephrine), several antihistamines and antibiotics, specific heart medications, diuretics, and others. It has been proposed, but not yet documented, that individuals who experience LQTS after using one of these medications, may actually have a genetic defect that increases their tendency to cardiac arrhythmias. Severe weight loss such as is associated with anorexia nervosa can also disrupt ion balances in the heart and result in prolongation of the QT interval.

Three inherited forms of LQTS have been described to date. Jervell and Lange-Neilsen syndrome, named for the physicians who described the condition in 1957, is associated with congenital deafness and is inherited as an autosomal recessive trait. Romano-Ward syndrome, the most common inherited form of LQTS, was first described in the 1960's. It is inherited in an autosomal dominant pattern and is not associated with other physical impairments such as deafness. In 1995, a third type of LQTS was reported in to occur in association with bilateral syndactyly. Little is known about the inheritance of this form, except that reported cases have been sporadic with no associated family history of LQTS.

As of early 2001, six different genes had been associated with the inherited forms of LQTS, and mutations in at least four of these genes had been reported in a number of affected individuals and families. The genes involved in LQTS play important roles in the formation of ion channels in the cell membrane, and, thus, mutations in these genes disrupt normal cardiac rhythms.

LQTS usually presents with symptoms that constitute a life-threatening emergency. Sudden loss of consciousness or cardiac arrest can be brought on by emotional or physical stress in young, otherwise healthy individuals, both female and male. Fright, anger, surprise, sudden awakening as a result of loud sounds (alarm clock, telephone), as well as physical activities, especially swimming, have all been reported to precipitate an episode of cardiac arrhythmia in susceptible individuals. Sudden death often occurs. Although the information is preliminary, recent research has also suggested that a small number of SIDS (sudden infant death syndrome ) cases may be due to mutations in one or more of the genes associated with LQTS.

Diagnosis

Problems exist in diagnosing LQTS. Although the method of diagnosis is the electrocardiogram, most young, healthy people do not routinely undergo this test, and, thus, their first, and possibly fatal, episode of LQTS comes without warning. In some cases, a nonfatal episode is mistakenly treated as a seizure, and, therefore, a follow-up assessment does not include an electrocardiogram. In addition, some cases of LQTS cannot be diagnosed by a routine electrocardiogram. That is, the QT interval is not found to be prolonged in routine testing. If LQTS is suspected either because of a previous episode of syncope or because of a family member with LQTS, an exercise electrocardiogram should be performed. In all instances where an individual is diagnosed with LQTS, family members should be thoroughly evaluated, and a detailed family history should be taken noting any individuals with episodes of sudden loss of consciousness and any cases of unexplained sudden death. Because many of the genes involved in LQTS have been identified, genetic testing can offer a more reliable means of diagnosis of other family members at risk. The first step in determining if this type of testing is appropriate in any particular situation is to consult a genetic counselor or medical geneticist.

Treatment

A conventional treatment is the oral administration of beta-blockers, medications that decrease the input from the sympathetic nervous system to the heart. Although beta-blockers do not correct the abnormalities in the ion channels of the heart cells, they do appear to decrease the occurrence of cardiac arrhythmias. However, these medications are not helpful in all cases, and are actually contraindicated in some individuals. Potassium supplementation is also being explored as a treatment in certain cases. As the genetics of LQTS becomes better understood, it should be possible to tailor treatments that will be effective for each of the various gene mutations.

Alternative treatment

In some patients, severing of the sympathetic nerve to the heart has decreased the occurrence of arrhythmias. Pacemakers and defibrillators appear to hold promise as new forms of treatment. As devices of this type are developed that are smaller in size, they may come into more widespread use, either alone or in conjunction with specific medications.

Prognosis

LQTS is a life-long condition. Individuals who are not diagnosed and treated are at an increased risk of syncope and sudden death. Adequate treatment can decrease this risk. There is no cure. Individuals with one of the inherited forms of LQTS are at risk of passing the mutation and the disease to their offspring.

Prevention

The risk of cardiac arrhythmias due to acquired forms of LQTS can be decreased by avoiding the medications and situations that trigger episodes. At present there is no genetic therapy to correct the gene mutations present in the inherited forms of LQTS, but individuals who are known to have an inherited form may also be able to lessen the risk of a life-threatening episode by avoiding such environmental triggers and by taking the appropriate medications.

Resources

BOOKS

Keating, Mark T., and Sanguinetti, Michael C. "Familial Cardiac Arrhythmias." In The Metabolic & Molecular Bases of Inherited Disease, edited by C.R. Scriver, et al. New York: McGraw-Hill Press, April 2001.

PERIODICALS

Towbin, Jeffrey A., and Vatta, Matteo. "Molecular Biology and the Prolonged QT Syndromes" American Journal of Medicine 110 (April 2001): 385-398.

Vizgirda, Vida M. "The Genetic Basis for Cardiac Dysrhythmias and the Long QT Syndrome" J. Cardiovasc Nursing 13, no.4 (1999): 34-45.

ORGANIZATIONS

Sudden Arrhythimia Death Syndromes Foundation. 540 Arapeen Drive, Suite 207, Salt Lake City Utah, 84108, (800) STOP SAD, 〈http://www.sads.org〉 or 〈http://www.ihc.com/research/longqt.html〉.

OTHER

American Heart Association. 〈http://www.Americanheart.org/Heart_and_Stroke_A_Z_Guide/longqt.html〉.

NORD (National Organization for Rare Disorders, Inc.). 〈http://www.rarediseases.org〉.

KEY TERMS

Anorexia nervosa— A loss of appetite for food not explainable by local disease. It is thought to have a psychological basis.

Autosomal dominant— A pattern of inheritance in which only one of the two copies of an autosomal gene must be abnormal for a genetic condition or disease to occur. An autosomal gene is a gene that is located on one of the autosomes or non-sex chromosomes. A person with an autosomal dominant disorder has a 50% chance of passing it to each of their offspring.

Autosomal recessive— A pattern of inheritance in which both copies of an autosomal gene must be abnormal for a genetic condition or disease to occur. An autosomal gene is a gene that is located on one of the autosomes or non-sex chromosomes. When both parents have one abnormal copy of the same gene, they have a 25% chance with each pregnancy that their offspring will have the disorder.

Diuretic— An agent that increases the production of urine.

Electrocardiogram— A record of the electrical activity of the heart showing certain waves called P, Q, R, S, and T waves. The Q, R, S, T waves are associated with contraction of the ventricles, the lower two chambers of the heart.

Sympathetic nervous system— A division of the autonomic nervous sytem, the portion of the nervous system that controls involuntary bodily functions such as heart rate.

Syndactyly— A fusion of two or more toes or fingers.