Wolff-Parkinson-White (WPW) syndrome is a rare congenital heart disorder involving irregularities in the electrical system of the heart. In individuals with WPW syndrome, an abnormal alternate electrical pathway (accessory pathway), exists between the atrium and the ventricle, resulting in abnormal heartbeat rhythms (arrhythmias) and faster than normal heartbeats (tachycardia).
The normal heart has four chambers. The two upper chambers are the atria and the two lower chambers are the ventricles. Within the right atrium of a normal heart is a natural pacemaker that initiates and controls the heartbeat. The electrical stimulus travels from the pacemaker (sinoatrial or SA node) to the ventricles along a specific pathway consisting of conducting tissue and known as the AV (atrioventricular) node. The extra electrical pathway in individuals with WPW syndrome bypasses the normal route and causes the ventricles to beat earlier than normal (preexcitation) and can allow electrical impulses to be conducted in both directions (i.e., from the atria to the ventricles and from the ventricles to the atria).
The symptoms associated with WPW syndrome vary greatly from case to case. Some individuals may not have any abnormal heartbeats or associated symptoms (asymptomatic). Although the disorder is present at birth (congenital), symptoms may not become apparent until adolescent or early adulthood.
Individuals with WPW syndrome may exhibit one or more irregular heartbeats especially episodes of abnormally fast heartbeats that originate above the ventricles (supraventricular tachycardias). These episodes often begin and stop abruptly and may last a few minutes to a few hours. The frequency of episodes varies from case to case. Some individuals may experience episodes every week, others may only have a few sporadic episodes.
A variety of symptoms may occur during these episodes including palpitations, difficulty breathing (dyspnea), light-headedness, chest pain, decreased exercise tolerance, anxiety, and dizziness. In some cases, affected individuals may lose consciousness (syncope).
Some individuals with WPW syndrome may experience an atrial flutter, in which the atrium beats regularly at an extremely rapid rate or atrial fibrillation, in which there is rapid, irregular twitching of the muscular wall. In extremely rare cases, affected individuals may develop ventricular fibrillation, a serious condition in which in which the heart’s normal electrical activity becomes disordered resulting in uncoordinated heartbeats and malfunction of the main pumping chambers of the heart (ventricles). Although rare in WPW syndrome, ventricular fibrillation can potentially result in cardiac arrest and sudden death.
Most cases of WPW syndrome occur randomly in the general population for no apparent reason (sporadically) and do not run in families. Some cases of WPW syndrome run in families and may be inherited as an autosomal dominant trait.
Genetic diseases are determined by two genes, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
No specific genetic mutation has been identified in individuals with isolated WPW syndrome and the exact role genetics plays in the development of WPW syndrome is not fully understood. However, a rare autosomal dominant disorder known as familial Wolff-Parkinson-White syndrome has been linked to chromosome 7. Investigators have determined that mutations of the gamma-2 regulatory subunit of AMP-activated protein kinase (PRKAG2) gene located on the long arm (q) of chromosome 7 (7q36) cause this disorder, which comprises the features of WPW syndrome, progressive conduction block, and overgrowth of a portion of the heart (cardiac hypertrophy).
Some researchers believe that familial WPW syndrome is a glycogen storage disorder, a group of disorders in which stored glycogen, which is normally broken down (metabolized) into glucose to supply energy, accumulates in various organs of the body. WPW syndrome is known to occur as part of other glycogen storage disorders, specifically Pompe disease or Danon disease.
Approximately 7 to 20 percent of individuals with WPW syndrome have a congenital heart defect, such as Ebstein’s anomaly, a condition in which the tricuspid valve is malformed. The tricuspid valve connects the right atrium to the right ventricle.
The symptoms of WPW syndrome result from the presence of an alternate electrical pathway. The normal heart has one conduction pathway (the Bundle of His) along which electrical impulses are transmitted from the small chambers of the heart (the atria) to the large chambers (the ventricles). These electrical impulses induce the muscles of the atria and then the ventricles, to contract and relax, pumping blood throughout the body. Individuals with WPW syndrome have a second abnormal conduction pathway, the Bundle of Kent, which sends extra electrical impulses from the muscles of the atria to those of the ventricles. These extra electrical impulses bypass the normal route and disrupt the normal rhythm of heartbeats and generate irregularities, usually exceptionally rapid heartbeats known as “atrial flutter, atrial fibrillation, or paroxysmal supraventricular tachycardia.” The exact cause of alternate pathways is unknown.
WPW syndrome is often present at birth (congenital), but may not be detected until adolescence or later. Peak incidence has been reported in individuals between 30 and 40 years old in otherwise healthy adults. Some reports suggest that WPW syndrome occurs in males more often than females. The disorder’s estimated prevalence is .1-3.1 per 1,000 people in the United States.
A diagnosis of WPW syndrome is suspected based upon a thorough clinical evaluation, a detailed patient history and a variety of specialized tests. Such tests might include an electrocardiogram (ECG), Holter monitor, and electrophysiology study. An electrocardiogram records the heart's electrical impulses and may reveal abnormal electrical patterns. A Holter monitor is a portable device designed to continuously monitor the electrical activity of the heart. A Holter monitor is usually worn for 24 hours. During electrophysiology study, a thin tube (catheter) is inserted into a blood vessel and threaded to the heart where it measures electrical activity. Each of these specialized tests can detect abnormal heart rhythms associated with WPW syndrome.
Some individuals with WPW syndrome may be clinically "silent" meaning that they have no symptoms associated with the disorder including no abnormal findings on various heart tests.
The treatment of Wolff-Parkinson-White syndrome may include observation without specific intervention, the use of various medications, and a surgical procedure known as catheter (radiofrequency) ablation.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as the type of arrhythmia present; the frequency; the type and severity of associated symptoms; risk of cardiac arrest; an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.
In some individuals without symptoms (asymptomatic cases) no therapy may be necessary. Regular, follow-up visits are necessary to monitor heart function.
Various medications can be used to control episodes of arrhythmias in some individuals with WPW syndrome. Such medications, known as antiarrhythmics, include adenosine, procainamide, sotalol, flecainide, ibutilide, and amiodarone. Calcium channel blockers such as verapamil may also be used. Certain medications such as verapamil may increase the risk of ventricular fibrillation and should be used with caution.
The heart drug, digoxin, is contraindicated in adults with WPW syndrome. However, it is sometimes used for prophylaxis treatment of infants with WPW syndrome who do not have ventricular preexcitation.
In some cases, medications may not be sufficient to control episodes of abnormal heartbeats or individuals may not be able to tolerate the medicine. A surgical procedure known as catheter ablation may be used in such cases. This procedure may also be used in individuals who are at high risk of developing cardiac arrest and sudden death including some asymptomatic individuals.
During a catheter ablation, a small thin tube (catheter) is inserted into the heart and guided to the abnormal pathway where high-frequency electrical energy is used to destroy (ablate) the tissue making up the abnormal pathway. This form of therapy has an extremely high success rate and may end the need of medications in many individuals.
In the past, open heart surgery had been used to treat individuals with WPW syndrome. Because of the success of the less invasive procedure, catheter (radiofrequency) ablation, open heart surgery is rarely performed for individuals with WPW syndrome.
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Behrman RE, Kliegman RM, Jenson HB. Eds. Nelson Textbook of Pediatrics. 17th ed. Elsevier Saunders. Philadelphia, PA; 2005:1559-61.
Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison’s Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:1350-1.
Foster V, Alexander RW, O’Rourke RA, et al. Eds. Hurst’s The Heart. 11thed. McGraw-Hill Companies. New York, NY; 2004:855-870.
Light PE. Familial Wolff-Parkinson-White syndrome: a disease of glycogen storage or ion channel dysfunction? J Cardiovasc Electrophysiol. 2006;17:S158-61.
Ehtisham J, Watkins H. Is Wolff-Parkinson-White syndrome a genetic disease? J Cardiovasc Electrophysiol. 2005;16:1258-62.
Sidhu JS, Rajawat YS, Tapan GR, et al., Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome. Circulation. 2005;111:21-9.
Redfearn DP, Krahn AD, Skanes AC, Yee R, Klein GJ. Use of medications in Wolff-Parkinson-White syndrome. Expert Opin Pharmacother. 2005;6:955-63.
Huang D, Yamauchi K, Inden Y, et al., Use of artificial neural network to localize accessory pathways of Wolff-Parkinson-White syndrome with 12-lead electrocardiogram. Med Inform Internet Med. 2005;30:277-86.
Pappone C, Manguso F, Santinelli R, et al., Radiofrequency ablation in children with asymptomatic Wolff-Parkinson-White syndrome. N Engl J Med. 2004;351:1197-205.
Milliez P, Slama R. Wolff-Parkinson-White syndrome. Rev Pract. 2004;54:1747-53.
Arad M, Benson D, Perez-Atayde AR, et al., Constituively activate AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest. 2002;109:357-62.
Gollob MH, Green MS, Tang MSL, et al., Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med. 2001;344:1823-31.
MacRae CA, Ghaisas N, Kass S, et al., Familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome maps to a locus on chromosome 7q3. J Clin Invest. 1995;96:1216-20.
FROM THE INTERNET
The Cleveland Clinic. Wolff-Parkinson-White syndrome (WPW). April 2001. Available at: http://www.clevelandclinic.org/heartcenter/pub/guide/disease/electric/wpw.htm Accessed On: June 29, 2006.
Hemingway TJ. Wolff-Parkinson-White syndrome. Emedicine Journal, June 14 2006. Available at: http://www.emedicine.com/emerg/topic644.htm Accessed on: June 29, 2006.
Singh VN. Wolff-Parkinson-White syndrome. Emedicine Journal, October 28, 2004. Available at: http://www.emedicine.com/med/topic2417.htm Accessed on: June 29, 2006.
Bouvagnet P. Wolff-Parkinson-White syndrome. Orphanet encyclopedia, March 2002. Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=907 Accessed on: April 4, 2006.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:194200; Last Update:10/08/2004. Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=194200 Accessed on: June 30, 2006.
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