Wolff-Parkinson-White Syndrome 

In 1930, Wolff, Parkinson, and White described a series of young patients who had a bundle branch block pattern on electrocardiography (ECG) findings, a short PR interval, and paroxysms of tachycardia.^[1] Case reports began appearing in the literature in the late 1930s and early 1940s, and the term Wolff-Parkinson-White (WPW) syndrome was coined in 1940.

Preexcitation was defined by Durrer et al in 1970 with the following statement, "Preexcitation exists, if in relation to atrial events, the whole or some part of the ventricular muscle is activated earlier by the impulse originating from the atrium than would be expected if the impulse reached the ventricles by way of the normal specific conduction system only."^[2]

WPW syndrome is currently defined as a congenital abnormality involving the presence of abnormal conductive tissue between the atria and the ventricles in association with supraventricular tachycardia (SVT). It involves preexcitation, which occurs because of conduction of an atrial impulse not by means of the normal conduction system, but via an extra atrioventricular (AV) muscular connection, termed an accessory pathway (AP), that bypasses the AV node.^{[3, 4]}

Classic ECG findings that are associated with WPW syndrome include the following:

• Presence of a short PR interval (< 120 ms)
• A wide QRS complex longer than 120 ms with a slurred onset of the QRS waveform producing a delta wave in the early part of QRS
• Secondary ST-T wave changes (see the image below)Classic Wolff-Parkinson-White electrocardiogram with short PR, QRS >120 ms, and delta wave.

Patients with WPW syndrome are potentially at an increased risk of dangerous ventricular arrhythmias due to extremely fast conduction across the bypass tract if they develop atrial flutter or atrial fibrillation (AF).

Some patients have a concealed bypass tract. Although they have an accessory AV connection, it lacks antegrade conduction; accordingly, these patients do not have the classic abnormalities of the surface ECG.

Only a small percentage of patients with WPW syndrome (< 1%) are at risk for sudden cardiac death (SCD). In patients who present with preexcited AF, cardiac electrophysiologic studies and radiofrequency (RF) catheter ablation may be curative. Other presentations include symptomatic SVT, which can also be cured by catheter ablation. Asymptomatic patients need periodic observation. The onset of cardiac arrhythmias, and possibly the sudden death risk, may be eliminated by prophylactic catheter ablation as well.^[5]

This review discusses the pathogenesis, clinical presentation, evaluation, and treatment of patients with WPW syndrome.

Go to Management of Acute Wolff-Parkinson-White Syndrome for complete information on this topic.

Accessory pathways or connections between the atrium and ventricle are the result of anomalous embryonic development of myocardial tissue bridging the fibrous tissues that separate the two chambers. This allows electrical conduction between the atria and ventricles at sites other than the AV node. Passage through APs circumvents the usual conduction delay between the atria and ventricles, which normally occurs at the AV node, and predisposes the patient to develop tachydysrhythmias.

Although dozens of locations for bypass tracts can exist in preexcitation, including atriofascicular, fasciculoventricular, nodofascicular, or nodoventricular, the most common bypass tract is an accessory atrioventricular (AV) pathway otherwise known as a Kent bundle. This is the anomaly seen in WPW syndrome. The primary feature that differentiates WPW syndrome from other AP-mediated supraventricular tachycardias (SVTs) is the ability of the AP to conduct in either an antegrade (ie, from atrium to ventricles) or a retrograde manner.

The presence of an AP allows a reentrant tachycardia circuit to be established. This reentrant mechanism is the typical cause of the SVT of which patients with preexcitation are at risk. The genesis of reentrant SVT involves the presence of dual conducting pathways between the atria and the ventricles^[6] :

• The natural AV nodal His-Purkinje tract
• One or more AV accessory tract(s) (ie, AV connection or AP, Kent fibers, Mahaim fibers)

These pathways usually exhibit different conduction properties and refractory periods that facilitate reentry. The effective refractory period (ERP, the time necessary for the electrical recovery needed to conduct the next impulse) of the accessory tract is often longer than that of the normal AV nodal His-Purkinje tract and requires time for conduction to recover before allowing reentry.

The degree of preexcitation on a surface ECG in a person with WPW pattern can be estimated by the width of the QRS and the length of the PR interval. A wider or more preexcited QRS with a short PR interval with absent or nearly absent isoelectric component reveals that most (or all) of the ventricular depolarization initiates through the AP insertion rather than through the AV node/His Purkinje system.

However, the QRS width may vary, becoming narrower during more rapid heart rates. This is possible because catecholamines permit the AV node to contribute more (or entirely) to ventricular depolarization by enhancing AV node conduction.

Types of SVT include orthodromic tachycardia (down the AV nodal His-Purkinje system and retrograde conduction up an AP), orthodromic tachycardia with a concealed AP (retrograde conduction only), and antidromic tachycardia (down the AP and retrograde conduction up the His-Purkinje system and AV node). In patients with WPW in which the AP participates, 95% of SVT is due to orthodromic tachycardia and 5% is due to antidromic tachycardia.

Orthodromic tachycardia

When a premature ectopic atrial impulse advances towards the ventricle, it may block at the AP but conduct in down the normal AVN/His Purkinje pathway. The impulse then reenters the AP in a retrograde fashion to perpetuate a circus movement of the impulse. Such reentrant tachycardia is described as orthodromic. Premature ventricular contractions (PVCs) can also initiate orthodromic tachycardia.

In orthodromic tachycardia, the normal pathway is used for ventricular depolarization, and the AP is used for the retrograde conduction essential for reentry. On ECG findings, the delta wave is absent, the QRS complex is normal, and P waves are typically inverted in the inferior and lateral leads.

Orthodromic tachycardia with concealed accessory pathway

Some APs are unable to conduct in an antegrade fashion. These are called concealed APs (as in concealed WPW syndrome) because manifest preexcitation is considered to be a pattern visible on the usual surface ECG. They account for about 30% of all SVTs induced on EPS.

Although no evidence of the pathway is present during sinus rhythm (ie, no preexcitation), orthodromic tachycardias can occur. Orthodromic tachycardia may also occur when there are 2 or more accessory connections, and in that case, the retrograde conduction may occur through the AV node, through one of the accessory connections, or through both.

This type of SVT may be difficult to distinguish from the usual AV nodal reentrant tachycardia (AVNRT) on the standard surface ECG. If the heart rate is higher than 200 bpm with QRS alternans and a retrograde P wave visible in the ST segment (long R-P tachycardia) following the QRS complex, a concealed AP may be the diagnosis. This determination is most accurately made with EPS.

Antidromic tachycardia

Less commonly, a shorter refractory period in the AP may cause blockade of an ectopic atrial impulse in the normal pathway, with antegrade conduction down the AP and then retrograde reentry of the normal AV nodal pathway. This type of tachycardia is called antidromic tachycardia.

On ECG, the QRS is wide, reflecting an exaggeration of the delta wave during sinus rhythm (ie, wide-QRS tachycardia). Such tachycardias are difficult to differentiate from ventricular tachycardias and often have a slurred R wave upstroke with QRS duration longer than 160 ms.

Only about 5% of the tachycardias in patients who have WPW syndrome are antidromic tachycardias; the remaining 95% are orthodromic. Even when the AP conducts solely in a retrograde fashion, it can still participate in the reentrant circuit and produce an orthodromic AV reciprocating tachycardia with a narrow QRS morphology. The presence of an antidromic tachycardia should prompt a careful search for a second bypass tract.

Lown-Ganong-Levine syndrome

Another common preexcitation syndrome, Lown-Ganong-Levine (LGL) syndrome, also has an AP—the James fibers, which connect the atria serially to the His bundle. This leads to accelerated conduction to the ventricle without QRS widening, as the distal pathway remains the His Purkinje system. This pathway is not typically involved in re-entrant tachycardias, and is observed clinically.

APs are considered congenital phenomena that are related to a failure of insulating tissue maturation within the AV ring—even though their manifestations are often detected in later years, making them appear to be acquired.

Family studies, as well as recent molecular genetic investigations, indicate that WPW syndrome, along with associated preexcitation disorders, may have a genetic component. It may be inherited as a familial trait, with or without associated congenital heart defects (CHDs)^[7] ; 3.4% of those with WPW syndrome have first-degree relatives with preexcitation.

The familial form is usually inherited as a Mendelian autosomal dominant trait. Although rare, mitochondrial inheritance has also been described. The syndrome may also be inherited with other cardiac and noncardiac disorders, such as familial atrial septal defects, familial hypokalemic periodic paralysis, and tuberous sclerosis.

Clinicians have long recognized the association of WPW syndrome with autosomal dominant familial hypertrophic cardiomyopathy. However, only comparatively recently was a genetic substrate linking hypertrophic cardiomyopathy to WPW syndrome and skeletal myopathy described.^[8]

Patients with mutations in the gamma 2 subunit of adenosine monophosphate (AMP)-activated protein kinase (PRKAG2) develop cardiomyopathy characterized by ventricular hypertrophy, WPW syndrome, AV block, and progressive degenerative conduction system disease. The mutation is believed to produce disruption of the annulus fibrosus by accumulation of glycogen within myocytes, which causes preexcitation. This is thought to be the case in Pompe disease, Danon disease, and other glycogen-storage diseases.

Infantile Pompe disease or glycogen-storage disease type II is a fatal genetic muscle disorder that is caused by deficiency of acid alpha-glucosidase (GAA). These patients have a shortened PR interval, large left ventricular (LV) voltages, and an increased QT dispersion (QTd).

Mutations in the lysosome-associated membrane protein 2 (LAMP2), which cause accumulation of cardiac glycogen, are thought to be the etiology of a significant number of hypertrophic cardiomyopathies in children, especially when skeletal myopathy, WPW syndrome, or both are present.

For example, Danon disease is an X-linked lysosomal cardioskeletal myopathy; males are more often and more severely affected than females. It is caused by mutations in the LAMP2 that produce proximal muscle weakness and mild atrophy, left ventricle hypertrophy, WPW syndrome, and mental retardation.

Patients with the Ebstein anomaly may develop WPW syndrome. They frequently have multiple accessory bypass tracts, mostly on the right, in the posterior part of the septum or the posterolateral wall of the right ventricle. The orthodromic reciprocating tachycardia in such patients often exhibits right bundle-branch block (RBBB) and a long ventriculoatrial (VA) interval.

Preexcitation can be surgically created, as in certain types of Bjork modifications of the Fontan procedure, if atrial tissue is flapped onto and sutured to ventricular tissue. Certain tumors of the AV ring, such as rhabdomyomas, may also cause preexcitation.

United States statistics

The prevalence of ventricular preexcitation is thought to be 0.1-0.3%, or 1 to 3 per 1000 people in the general population. Estimates of arrhythmia incidence in patients with preexcitation vary widely, ranging from 12% to 80% in several surveys.

The incidence of preexcitation and WPW syndrome ranges from 0.1 to 3 cases per 1000 population (average, 1.5 cases per 1000 population) in otherwise healthy persons. This includes only patients with manifest preexcitation (delta wave evident on surface 12-lead ECG). About 60-70% of these individuals have no other evidence of heart disease. Approximately 4 newly diagnosed cases of WPW syndrome per 100,000 population occur each year.

In a review of ECG findings from 22,500 healthy aviation personnel, 0.25% exhibited findings consistent with the WPW pattern, with a 1.8% reported incidence of tachycardia.

The location of the APs, in descending order of frequency, is (1) 53%, the left free wall, (2) 36%, posteroseptal, (3) 8%, right free wall, and (4) 3%, anteroseptal. The presence of concealed APs accounts for approximately 30% of patients with apparent SVT referred for EPS. These patients do not have true WPW syndrome because no delta wave is present, but they do have the potential for orthodromic tachycardia.

Approximately 80% of patients with WPW syndrome have a reciprocating tachycardia, 15-30% will develop AF, and 5% have atrial flutter. Ventricular tachycardia is uncommon. Patients with mitral valve prolapse have an association with WPW, but the mechanism is unclear.

International statistics

Worldwide, the incidence and prevalence of WPW syndrome parallel those seen in the United States.

Age-related differences in incidence

WPW syndrome is found in persons of all ages. Most patients with WPW syndrome present during infancy. However, a second peak of presentation is noted in school-aged children and in adolescents. This interesting bimodal age distribution is due to permanent or transitory loss of preexcitation during infancy in some patients and during late adolescence in others.

The prevalence of WPW syndrome decreases with age as a consequence of apparent attenuation of conduction speed in the AP. About one fourth of patients lose preexcitation over a 10-year period, probably as a result of fibrotic changes at the site of insertion of the accessory bypass tract with loss of electrical conduction properties between cardiac chambers. Cases have been described in which ECG evidence of preexcitation disappears completely. One tenth of patients with concealed APs lose retrograde conduction over 10 years.

In asymptomatic patients, antegrade conduction across the accessory pathway (AP) may spontaneously disappear with advancing age (one fourth of patients lose antegrade bypass tract conduction over 10 years).

In patients with abnormal ECG findings indicative of WPW syndrome, the frequency of SVT paroxysms increases from 10% in people aged 20-39 years to 36% in people older than 60 years.^[9] Overall, about 50% of patients with WPW develop tachyarrhythmias.

Sex-related differences in incidence

WPW pattern appears to affect the 2 sexes equally; however, WPW syndrome has been found to be more frequent in males. One study documented a male-to-female ratio of approximately 2:1. Another reported 1.4 cases of WPW syndrome per 1000 men and 0.9 cases per 1000. A third study found a 3.5-fold higher prevalence of WPW syndrome in men.

Race-related differences in incidence

No clear racial predilection appears to exist.

Once identified and appropriately treated, WPW syndrome is associated with an excellent prognosis, including the potential for permanent cure through RF catheter ablation.

Asymptomatic patients with only preexcitation on ECG generally have a very good prognosis. Many develop symptomatic arrhythmias over time, which can be prevented with prophylactic EPS and RF catheter ablation. Patients with a family history of SCD or significant symptoms of tachyarrhythmias or cardiac arrest have worse prognoses. However, once definitive therapy is performed, including curative ablation, the prognosis is once again excellent.

Noninvasive risk stratification can be useful if abrupt loss of preexcitation occurs with exercise or procainamide infusion.

Mortality in WPW syndrome is rare and is related to SCD. The incidence of SCD in WPW syndrome is approximately 1 in 100 symptomatic cases when followed for up to 15 years. Although relatively uncommon, SCD may be the initial presentation in as many as 4.5% of cases.

Even in patients with asymptomatic WPW, the risk of SCD is increased above that of the general population. Medical therapy with agents such as digoxin may increase this risk if the patient has AF or atrial flutter. The risk in asymptomatic patients is low and can be reduced further with prophylactic catheter ablation of the accessory pathway (EPS and RF ablation).

Other factors that appear to influence the risk of SCD are the presence of multiple bypass tracts, short AP refractory periods (< 240 ms), AF and atrial flutter, or a family history of premature sudden death. SCD is unusual without preceding symptoms.

The cause of SCD in WPW syndrome is rapid conduction of AF to the ventricles via the AP, resulting in ventricular fibrillation (VF). AF develops in one fifth to one third of patients with WPW syndrome; the reasons for this and the effects of AP ablation on its development are unclear.

However, 1 study hypothesized that 2 mechanisms are involved in the pathogenesis of AF in patients with WPW syndrome: one is related to the AP that predisposes the atria to fibrillation, and the other is independent from the AP and is related to increased atrial vulnerability present in these individuals.^[10]

According to the literature, risk factors for the development of AF in the setting of WPW syndrome include advancing age (2 peak ages for AF occurrence are recognized, one at 30 years and the other at 50 years), male gender, and prior history of syncope.^[11]

Certain factors increase the likelihood of VF, including rapidly conducting APs and multiple pathways.^[12] Cases have also been reported in association with esophageal studies, digoxin, and verapamil. A few reports document spontaneous VF in WPW syndrome, and SVT may degenerate into AF, thus leading to VF^[13] ; however, both scenarios are rare in pediatric patients.

Morbidity may be related to rapid near syncopal or syncopal arrhythmias. Even when syncope is absent, the arrhythmia episodes may be highly symptomatic. In most patients, the SVT is well tolerated and is not life threatening. However, the potential for syncope, hemodynamically compromising rhythms, or sudden death may prevent patients with WPW syndrome from participating in competitive sports or hazardous occupations until the substrate is definitively addressed and cured by a catheter ablation procedure.

Patient education is of paramount importance in patients with WPW syndrome. This is especially true in asymptomatic young patients who have been told of their abnormal ECG results. Periodic follow-up care of such patients is necessary, along with thoughtful discussions of consideration for EPS and prophylactic catheter ablation.

Urge patients to carry a sample ECG in sinus rhythm and a medical identification bracelet in case of cardiac arrest.

Educate patients who are being treated with drug therapy thoroughly regarding the disease and the type of medications they are taking. Such patients must be taught the following:

• How to recognize disease recurrence
• How to perform vagal maneuvers, when needed
• To keep their follow-up appointments
• To identify the adverse effects of antiarrhythmic drugs
• To avoid competitive sports
• To learn about ablative options and the indications for ablation

Patients with WPW syndrome should also educate their family members, and their siblings should be screened for preexcitation with 12-lead ECG.

For patient education resources, see the Heart Center, as well as Supraventricular Tachycardia.