In the Wolff-Parkinson-White (WPW) syndrome, AV conduction occurs, partially or entirely, through an AV BT, which results in earlier activation (preexcitation) of the ventricles than if the impulse had traveled through the AVN.¹ In the setting of Lown-Ganong-Levine (LGL) syndrome, preexcitation purportedly occurs via atrio-Hisian BTs or, alternatively, no BT is present and enhanced AVN conduction accounts for the electrocardiographic (ECG) findings. The net effect is a short PR interval without delta wave or QRS prolongation. It is important to stress, however, that LGL is not a recognized syndrome with an anatomical basis, but only an ECG description, and the use of the term should be discouraged.^2,³ The so-called Mahaim variant of preexcitation does not typically result in a delta wave, because these pathways, which usually terminate in the conducting system or in the ventricular myocardium close to the conducting system, conduct slowly, and the AVN-HPS has adequate time to activate most of the ventricular muscle mass. Concealed AV BTs refer to AV BTs that do not manifest anterograde conduction and therefore do not result in ventricular preexcitation. Because they do not result in alteration of the QRS complex in the ECG, they cannot be detected by inspection of the surface ECG; they are called concealed. However, the concealed BT can conduct in a retrograde fashion, thereby creating a reentrant circuit with impulses traveling from the atrium to the AVN, HPS, ventricle, and then back to the atrium via the BT.

Pathophysiology

Wolff-Parkinson-White Syndrome

WPW pattern refers to the constellation of ECG abnormalities related to the presence of an AV BT (short PR interval, delta wave) in asymptomatic patients.¹ WPW syndrome refers to a WPW ECG pattern associated with tachyarrhythmias.

Because the AV BT typically conducts faster than the AVN, the onset of ventricular activation is earlier than if depolarization occurred only via the AVN, resulting in a shortened PR (P-delta) interval. Additionally, because the BT exhibits practically nondecremental conduction, the early activation (and P-delta interval) remains almost constant at all heart rates. Preexcited intraventricular conduction in WPW propagates from the insertion point of the AV BT in the ventricular myocardium via direct muscle-to-muscle conduction. This process is inherently slower than ventricular depolarization resulting from rapid HPS conduction. Thus, although the initial excitation of the ventricles (via the BT) occurs earlier, it is followed by slower activation of the ventricular myocardium than occurs normally. The net effect is that the QRS complex consists of fusion between the early ventricular activation caused by preexcitation with the later ventricular activation resulting from impulse propagation through the AVN and HPS to the ventricles. The initial part of ventricular activation resulting in the upstroke of the QRS complex is slurred because of slow muscle-to-muscle conduction; this is termed a delta wave. The more rapid the conduction along the BT in relation to the AVN, the greater the amount of myocardium depolarized via the BT, resulting in a more prominent or wider delta wave and increasing prolongation of the QRS complex duration.

Atrioventricular Bypass Tracts

The AV junctions are the areas of the heart where the atrial musculature connects to the annuli of the mitral and tricuspid valves. The AVN-HPS, which lies in the septal component of the AV junction, is the only normal electrical connection between the atria and the ventricles. The fibrous skeleton and AV valvular annuli act as an insulator to prevent electrical impulses from getting into the ventricles by any other route. The main function of the AVN is modulation of atrial impulse transmission to the ventricles, thereby coordinating atrial and ventricular contractions; it receives, slows down, and conveys atrial impulses to the ventricles.

AV BTs are aberrant muscle bundles that connect the atria to the ventricles outside of the normal AV conduction system. AV BTs are found most often in the parietal AV junctional areas, including the paraseptal areas. They breach the insulation provided by the fibrofatty tissues of the AV groove (sulcus tissue) and the hinge lines (fibrous annulus) of the valves. They are rarely found in the area of fibrous continuity between the aortic and mitral valves because in this area, there is usually a wide gap between the atrial myocardium and ventricular myocardium to accommodate the aortic outflow tract.^4,⁵ The remainder of the AV groove may be divided into quadrants consisting of the left free wall, right free wall, and posteroseptal and anteroseptal spaces. The distribution of BTs within these regions is not homogeneous—46% to 60% of BTs are found within the left free wall space; 25% are within the posteroseptal space; 13% to 21% of BTs are within the right free wall space; and 2% are within the right superoparaseptal (formerly called anteroseptal) space (Fig. 18-1).

FIGURE 18-1 Locations of atrioventricular bypass tracts (AV BTs) by anatomical region. Tricuspid and mitral valve annuli are depicted in a left anterior oblique view. Locations of the coronary sinus, AV node, and His bundle are shown. AV BTs may connect atrial to ventricular myocardium in any of the regions shown.

(From Miller JM, Zipes DP: Therapy for cardiac arrhythmias. In Libby P, Bonow R, Mann DL, Zipes DP, editors: Braunwald’s heart disease: a textbook of cardiovascular medicine, ed 8, Philadelphia, 2007, WB Saunders, pp 779-830.)

BTs are usually very thin muscular strands (rarely thicker than 1 to 2 mm) but can occasionally exist as broad bands of tissue. The AV BT can run in an oblique course rather than perpendicular to the transverse plane of the AV groove. As a result, the fibers can have an atrial insertion point that is transversely from less than one to several centimeters removed from the point of ventricular attachment.⁶ Some posteroseptal pathways insert into coronary sinus (CS) musculature rather than atrial myocardium and can be associated with the coronary venous system or diverticula from a CS branch vein.

Multiple AV BTs occur in 5% to 10% of patients. BTs are defined as multiple when they are separated by more than 1 to 3 cm. The most common combination of widely spaced multiple BTs is posteroseptal and right free wall BTs. The incidence of multiple BTs is particularly high in patients with antidromic atrioventricular reentrant tachycardia (AVRT) (50% to 75%), patients in whom AF resulted in ventricular fibrillation (VF), and patients with Ebstein anomaly.

Although the majority (approximately 60%) of AV BTs conduct both anterogradely and retrogradely (i.e., bidirectionally), some AV BTs are capable of propagating impulses in only one direction. BTs that conduct only in the anterograde direction are uncommon (<5%), often cross the right AV groove, and frequently possess decremental conduction properties.³ On the other hand, BTs that conduct only in the retrograde direction occur more frequently, accounting for 17% to 37% of all BTs. When the BT is capable of anterograde conduction, ventricular preexcitation is usually evident during normal sinus rhythm (NSR), and the BT is referred to as manifest. BTs capable of retrograde-only conduction are referred to as concealed.

Because working myocardial cells make up the vast majority of AV BTs, conduction over those BTs is mediated by the rapid inward sodium current, similar to normal His-Purkinje tissue and atrial and ventricular myocardium. Therefore, AV BTs have rather constant anterograde and retrograde conduction at all rates until the refractory period is reached, at which time conduction is completely blocked (nondecremental conduction). Thus, conduction over AV BTs usually behaves in an all-or-none fashion. In contrast, the AVN, which depends on the slow inward calcium current for generation and propagation of its action potential, exhibits what has been called decremental conduction, in which the conduction time of the impulse propagating through the AVN prolongs as the atrial cycle length (CL) shortens. Thus, AV conduction is more rapid through the AV BT than through the AVN, a difference that is increased at a fast heart rate. This difference has potentially great clinical importance. A primary function of the AVN is to limit the number of impulses conducted from the atria to the ventricles, which is particularly important during fast atrial rates (e.g., AF or atrial flutter [AFL]) when only a fraction of impulses are conducted to the ventricles, whereas the remainder are blocked in the AVN. However, in the presence of nondecrementally conducting AV BTs with short refractory periods, these arrhythmias can lead to very fast ventricular rates that can degenerate into VF.

Atrioventricular Reentry

AVRT is a macroreentrant tachycardia with an anatomically defined circuit that consists of two distinct pathways, the normal AV conduction system and an AV BT, linked by common proximal (atrial) and distal (ventricular) tissues. If sufficient differences in conduction time and refractoriness exist between the normal conduction system and the BT, a properly timed premature impulse of atrial or ventricular origin can initiate reentry. AVRTs are the most common (80%) tachycardias associated with the WPW syndrome. AVRT is divided into orthodromic and antidromic according to the direction of conduction in the AVN-HPS (Fig. 18-2). Orthodromic indicates normal direction (anterograde) of conduction over AVN-HPS during the AVRT.

FIGURE 18-2 Schematic representation of the reentrant circuit during orthodromic atrioventricular reentrant tachycardia (AVRT), antidromic AVRT, preexcited atrial tachycardia (AT), and preexcited atrioventricular nodal reentrant tachycardia (AVNRT) using a left-sided bypass tract (BT). HB = His bundle; LB = left bundle branch; RB = right bundle branch.

Orthodromic Atrioventricular Reentrant Tachycardia

In orthodromic AVRT, the AVN-HPS serves as the anterograde limb of the reentrant circuit (i.e., the pathway that conducts the impulse from the atria to the ventricles), whereas an AV BT serves as the retrograde limb (see Fig. 18-2). Approximately 50% of BTs participating in orthodromic AVRT are manifest (able to conduct bidirectionally) and 50% are concealed (able to conduct retrogradely only). Therefore, a WPW pattern may or may not be present on the surface ECG during NSR. When preexcitation is present, the delta wave seen during NSR is lost during orthodromic AVRT, because anterograde conduction during the tachycardia is not via the BT (i.e., the ventricle is not preexcited) but over the normal AV conduction system. Orthodromic AVRT accounts for approximately 95% of AVRTs and 35% of all paroxysmal supraventricular tachycardias (SVTs).

Antidromic Atrioventricular Reentrant Tachycardia

In antidromic AVRT, an AV BT serves as the anterograde limb of the reentrant circuit (see Fig. 18-2). Consequently, the QRS complex during antidromic AVRT is fully preexcited (i.e., the ventricles are activated totally by the BT with no contribution from the normal conduction system). The BT involved in the antidromic AVRT circuit must be capable of anterograde conduction and, therefore, preexcitation is typically observed during NSR. During classic antidromic AVRT, retrograde VA conduction occurs over the AVN-HPS. Other less frequent, nonclassic forms of antidromic AVRT can use a second BT as the retrograde limb of the reentrant circuit or a combination of one BT plus the AVN-HPS in either direction (Fig. 18-3). Antidromic AVRT occurs in 5% to 10% of patients with WPW syndrome. Susceptibility to antidromic AVRT appears to be facilitated by a distance of at least 4 cm between the BT and the normal AV conduction system. Consequently, most antidromic AVRTs use a lateral (right or left) BT as the anterograde route for conduction. Because posteroseptal BTs are in close proximity to the AVN, those BTs are less commonly part of antidromic AVRT if the other limb is the AVN and not a second free wall BT.³ Up to 50% to 75% of patients with spontaneous antidromic AVRT have multiple BTs (manifest or concealed), which may or may not be used as the retrograde limb during the tachycardia. Antidromic SVT is thus a subset of preexcited tachycardias.

FIGURE 18-3 The presence of multiple bypass tracts (BTs) is indicated by an eccentric atrial activation sequence during antidromic atrioventricular reentrant tachycardia using a right lateral BT anterogradely and a left lateral BT retrogradely. A = atrial electrogram; H = His bundle potential.

Permanent Junctional Reciprocating Tachycardia

Permanent junctional reciprocating tachycardia (PJRT) is an orthodromic AVRT mediated by a concealed, retrogradely conducting AV BT that has slow and decremental conduction properties. Conduction properties of this retrograde BT are slower than the anterograde conduction properties of the AVN and those of typical fast BTs found in patients with AVRT. The BT in PJRT is most often located in the posteroseptal region, although other portions of the AV groove can also harbor this unusual pathway. Because these BTs are almost always concealed and have slow conduction, all elements necessary for reentry are present at all times, and thus PJRT can be present much of the time (i.e., incessant), with only short interludes of sinus rhythm.

Other Arrhythmias Associated with Wolff-Parkinson-White Syndrome

Atrial tachycardia (AT), AFL, AF, and atrioventricular nodal reentrant tachycardia (AVNRT) can all coexist with a BT. In these preexcited tachycardias, the BT serves as a bystander route for ventricular or atrial activation, and is not required for the initiation or maintenance of the arrhythmia.

Atrioventricular Nodal Reentrant Tachycardia and Atrial Tachycardia

Physiology consistent with dual AVN physiology has been reported in 8% to 40% of patients with WPW syndrome, although spontaneous sustained AVNRT is less frequent. Both AVNRT and AT can use the bystander BT to transmit impulses to the ventricle (see Fig. 18-2). When AVNRT occurs in the WPW syndrome, the arrhythmia can be difficult to distinguish from AVRT without electrophysiological (EP) testing.

Atrial Fibrillation

Paroxysmal AF occurs in 50% of patients with WPW, and is the presenting arrhythmia in 20%. Chronic AF, however, is rare in these patients.³ Spontaneous AF is most common in patients with anterograde conduction through the BT. Patients with antidromic AVRT, multiple BTs, and BTs that have a short anterograde effective refractory period (ERP) are more liable to develop AF.³ In individuals with WPW, AF is often preceded by AVRT that degenerates into AF.

The frequency with which intermittent AF occurs in patients with the WPW syndrome is striking because of the low prevalence of coexisting structural heart disease, which is a major predisposing factor for AF in subjects without a BT. This observation suggests that the AV BT itself can be related to the genesis of AF.

The mechanisms by which AVRT precipitates AF are not well understood. The rapid atrial rate can cause disruption in atrial activation and reactivation, creating an electrophysiological substrate conducive to AF. The observation that most patients with BT and AF who undergo BT ablation are cured of both AVRT and AF is compatible with this hypothesis. Another possibility is that the complex geometry of networks of BTs predisposes to AF by fractionation of the activation wavefronts. Localized reentry has been recorded in some patients, using direct recordings of the activation of the BTs. Hemodynamic changes, atrial stretch caused by atrial contraction against closed AV valves during ventricular systole, can also play a role. Ablation of the BT can cure AF in more than 90% of patients; however, vulnerability to AF persists in up to 56%, and the response to atrial extrastimulation (AES) is also unaltered by ablation.

Atrial Flutter

AFL is the most common (60%) regular preexcited tachycardia in patients with WPW syndrome. AFL is caused by a reentrant circuit within the RA and therefore exists independently of the BT, and AFL does not have the same causal association to AV BTs as AF. In some patients with WPW syndrome who develop AFL, AVRT is the initiating event. This relationship can be mediated by contraction-excitation feedback into the atria during the AVRT.

AFL, like AF, can conduct anterogradely via a BT causing a preexcited tachycardia. Depending on the various refractory periods of the normal and pathological AV conduction pathways, AFL potentially can conduct 1:1 to the ventricles during a preexcited tachycardia, making the arrhythmia difficult to distinguish from ventricular tachycardia (VT; see Fig. 12-6).

Ventricular Fibrillation and Sudden Cardiac Death

The mechanism of sudden cardiac death (SCD) in most patients with WPW is likely the occurrence of AF with a very rapid ventricular rate that leads to VF. Although the frequency with which AF having rapid AV conduction via a BT degenerates into VF is unknown, the incidence of SCD in patients with WPW syndrome is rather low, ranging from 0% to 0.39% annually in several large case series. The trigger for AF in this population of patients (who usually are otherwise healthy individuals and are expected to have a low rate of AF) is generally an episode of SVT. In fact, most patients who have been resuscitated from VF secondary to preexcitation have previous history of AVRT, AF, or both (although in some patients, SCD may be the presenting symptom), and induction of SVT during EP testing is also predictive of clinical symptoms in some asymptomatic individuals.⁷^–¹¹

Several factors can help identify the patient with WPW who is at increased risk for VF, including symptomatic SVT, septal location of the BT, presence of multiple BTs, and male gender.⁸ Nonetheless, it is clear that the most important factor for the occurrence of VF in these patients is the ability of the BT to conduct rapidly to the ventricles. This is best measured by determining the shortest and average preexcited intervals during AF or alternatively by measuring the anterograde ERP of the BT. If the BT has a very short anterograde effective refractory period (ERP <250 milliseconds), a rapid ventricular response can occur with degeneration of the rhythm to VF. A short preexcited R-R interval during AF (≤220 milliseconds) appears to be a sensitive clinical marker for identifying patients at risk for SCD in children, although its positive predictive value in adults is only 19% to 38%.^9,^10,¹²

Drug therapy can be an additional determinant of the risk of VF in patients with preexcitation. As an example, intravenous verapamil can increase the ventricular response to AF and has resulted in VF in some patients. Several mechanisms are probably involved; hypotension produced by verapamil-induced vasodilation is followed by a sympathetic discharge that enhances BT conduction. Furthermore, verapamil slows AVN conduction directly and increases AVN refractoriness, resulting in less concealed penetration of the BT by normally conducted beats. Additionally, the increased rate, irregular rate, hypotension, and sympathetic discharge probably result in fractionation of the ventricular wavefront and VF. For these reasons, intravenous verapamil is contraindicated for the acute treatment of AF in patients with WPW. Other intravenous drugs that block the AVN also should be avoided, including beta blockers, adenosine, diltiazem, and digoxin. Both oral and intravenous digoxin has been associated with the degeneration of AF into VF in patients with preexcitation syndromes. Some of these patients had a history of previously benign AF. How digitalis might promote the development of VF is uncertain. One possible mechanism is that shortening of the atrial and BT ERP, plus increasing AVN block, results in decreased concealed retrograde penetration of the BT by normally conducted beats, thereby preventing its inactivation.

Intravenous adenosine, given appropriately to treat orthodromic AVRT, can also precipitate AF episodes. This is unusual and should not be viewed as a contraindication to adenosine use, but one should be prepared for emergency cardioversion before administering adenosine to SVT patients. Lidocaine, for reasons that are unclear, has also been associated with degeneration of AF into VF. It is occasionally used in patients with WPW who have a wide QRS complex tachycardia that might be misinterpreted as VT.

Ventricular Tachycardia

Coexisting VT is uncommon because patients with WPW syndrome infrequently have structural heart disease. Naturally, older patients are subject to coronary artery and other diseases that can cause VT.

Clinical Considerations

Epidemiology of Wolff-Parkinson-White Syndrome

Familial Wolff-Parkinson-White Syndrome

Among patients with the WPW syndrome, 3.4% have first-degree relatives with a preexcitation syndrome. A familial form of WPW has infrequently been reported and is usually inherited as an autosomal dominant trait. The genetic cause of a rare form of familial WPW syndrome has been described.^14,¹⁵ The clinical phenotype is characterized by the presence of preexcitation on the ECG; frequent SVTs, including AF; progressive conduction system disease; and cardiac hypertrophy. Patients typically present in late adolescence or the third decade with syncope or palpitations. Premature SCD occurred in 10% of patients. Paradoxically, by the fourth decade of life, progression to advanced sinus node dysfunction or AV block (with the loss of preexcitation) requiring pacemaker implantation was common. Approximately 80% of the patients older than 50 years had chronic AF. Causative mutations in the PRKAG2 gene were identified in these families. The PRKAG2 gene encodes the gamma-2 regulatory subunit of the adenosine monophosphate (AMP)–activated protein kinase, which is a key regulator of metabolic pathways, including glucose metabolism. The penetrance of the disease for WPW syndrome was complete, but the expression was variable. The described phenotype of this syndrome is similar to the autosomal recessive glycogen storage disease, Pompe disease. Given the function of the AMP-activated protein kinase and this similarity, the PRKAG2 syndrome is likely a cardiac-specific glycogenosis syndrome. This syndrome thus belongs to the group of genetic metabolic cardiomyopathies, rather than to the congenital primary arrhythmia syndromes.

Concealed Bypass Tracts

The true prevalence of concealed BTs is unknown because, unlike the situation with the WPW ECG pattern, these BTs are concealed on the surface ECG and are only expressed during AVRT; only symptomatic patients undergo EP testing. As noted, orthodromic AVRT accounts for approximately 95% of AVRTs and 35% of all paroxysmal SVTs, and 50% of the BTs that participate in orthodromic AVRT are concealed. SVTs using a concealed BT have no gender predilection and tend to occur more frequently in younger patients than in those with AVNRT; however, significant overlap exists. PJRT most often occurs in early childhood, although clinically asymptomatic patients presenting later in life are not uncommon.

Clinical Presentation

Most patients with preexcitation are asymptomatic and are discovered incidentally on an ECG obtained for unrelated reasons. When symptomatic arrhythmias occur in the WPW patient, the disorder is called the WPW syndrome. The two most common types of arrhythmias in the WPW syndrome are AVRT and AF. Patients with AVRT experience symptoms characteristic of paroxysmal SVT with sudden onset and termination, including rapid and regular palpitations, chest pain, dyspnea, presyncope, and rarely, syncope. Symptoms are usually mild and short-lived and terminate spontaneously or with vagal maneuvers. However, occasionally patients present with disabling symptoms, especially in the presence of structural heart disease. Of note, clinical symptoms are not usually helpful in differentiating AVRT from other forms of paroxysmal SVTs.

An AVRT that in general is well tolerated by the patient when additional heart disease is absent can deteriorate into AF. AF can be a life-threatening arrhythmia in the WPW syndrome if the BT has a short anterograde ERP, resulting in very fast ventricular rates, with possible deterioration into VF and SCD.

The incidence of SCD in patients with the WPW syndrome has been estimated to range from 0.15% to 0.39% over a 3- to 10-year follow-up. It is unusual for cardiac arrest to be the first symptomatic manifestation of WPW syndrome. Conversely, in about 50% of cardiac arrest cases in WPW patients, it is the first manifestation of WPW.

PJRT commonly presents as a frequently recurring or incessant tachycardia that is refractory to drug therapy and can lead to cardiomyopathy and congestive heart failure symptoms.

Initial Evaluation

History, physical examination, and 12-lead ECG constitute an appropriate initial evaluation. In patients with brief, self-terminating episodes of palpitations, an event recorder is the most effective way to obtain ECG documentation. Echocardiographic examination is often useful to exclude structural heart disease.

Several other noninvasive tests have been proposed as useful for evaluating symptomatic patients and risk-stratifying patients for SCD risk. However, the sensitivity and specificity of noninvasive testing have been shown to be limited. Invasive EP testing may be considered in patients with arrhythmias and those with a WPW ECG pattern when noninvasive testing does not lead to the conclusion that the anterograde ERP of the BT is relatively long.

EP testing can help risk-stratify asymptomatic patients with WPW pattern for developing symptoms and SCD secondary to preexcitation. As noted, inducibility of AVRT, a shorter BT ERP (<250 milliseconds), a shorter preexcited R-R interval during induced AF (<220 milliseconds), the presence of multiple pathways, and septal and right-sided pathway locations appear to identify a higher risk group.⁹^–¹¹ However, a strategy to perform an EP study for all asymptomatic patients with the WPW ECG pattern for the purpose of risk stratification is still controversial and not widely accepted.¹⁶

Methods for Evaluation of Bypass Tract Refractory Period

Demonstration of Intermittent Preexcitation

Observation of intermittent loss of the preexcitation pattern in a Holter monitor or serial ECGs is generally correlated with a long BT ERP and essentially ensures that the BT has a low “margin of safety” for conduction and hence is likely to block during AF, resulting in a slower ventricular response. Intermittent preexcitation, however, has to be distinguished from inapparent preexcitation (see later) and from a bigeminal ventricular rhythm with a long coupling interval.

Assessing Ability of Antiarrhythmic Agents to Produce Anterograde Block in Bypass Tracts

When, during NSR, the intravenous injection of ajmaline (1 mg/kg over 3 minutes) or procainamide (10 mg/kg over 5 minutes) results in complete block of the BT, a long anterograde ERP (>270 milliseconds) of the BT is likely. The shorter the BT ERP, the less likely it would be blocked by these drugs. Furthermore, the amount of ajmaline required to block conduction over the BT correlates with the duration of the anterograde ERP of the BT. However, the incidence of BT block in response to these drugs is low and, although the occurrence of block predicts a long ERP of the BT, failure to produce block does not necessarily suggest a short ERP. Moreover, pharmacological testing is carried out at rest and therefore does not indicate what effect the drug will have on the BT ERP during sympathetic stimulation, such as exercise, emotion, anxiety, and recreational drug use.^8,^17,¹⁸

Response of Preexcitation To Exercise

Demonstration of a sudden loss of preexcitation (indicated by abrupt loss of the delta wave associated with prolongation of the PR interval and normalization of the QRS) during exercise is consistent with block in the BT and is indicative of a long BT ERP (>300 milliseconds). This is a good predictor that the patient is not at risk for VF, even during sympathetic stimulation. However, the frequency of block in the BT during exercise is low (approximately 10%), and thus sensitivity of this test is poor.

Evaluation of Ventricular Response During Atrial Fibrillation

During spontaneous or induced AF, the propensity for rapid AV conduction can be judged by the interval between consecutively preexcited QRS complexes. A mean preexcited R-R interval of more than 250 milliseconds and a shortest preexcited R-R of more than 220 milliseconds predict low risk for SCD, with a negative predictive value of more than 95%; however, the positive predictive value is low (20%).

Response of Preexcitation to Transesophageal Atrial Stimulation

There is good correlation between the value of the anterograde ERP of the BT obtained during single-test programmed atrial stimulation and atrial pacing at increasing rates and the ventricular rate during AF. Programmed electrical stimulation of the atrium can be performed by the transesophageal route and the value of the anterograde ERP of the BT can be determined.

Electrophysiological Testing

Programmed atrial stimulation is used to evaluate the BT ERP. Because BT refractoriness shortens with decreasing pacing CL, the ERP should be determined at multiple pacing CLs (preferably ≤400 milliseconds). Additionally, atrial stimulation should be performed close to the BT atrial insertion site to obviate the effect of intraatrial conduction delay. Incremental rate atrial pacing is performed to determine the maximal rate at which 1:1 conduction over the BT occurs. Induction of AF should be performed to determine the average and the shortest R-R interval during preexcited AF. Atrial and ventricular stimulation is also performed to evaluate inducibility of AVRT as well as the number and location of BTs.

Principles of Management

Management of Asymptomatic Patients with Preexcitation

The role of EP testing and catheter ablation in asymptomatic patients with preexcitation is still controversial. Guidelines of the American College of Cardiology and European Society of Cardiology on the management of asymptomatic WPW patients suggest restricting catheter ablation of BTs to those in high-risk occupations (e.g., school bus drivers, police, and pilots) and professional athletes.¹⁹ Catheter ablation in asymptomatic preexcitation was classified as a class IIA indication with a B level of evidence. This means essentially that it is “reasonable” to offer ablation in selected patients but is not mandated in all patients. According to the North American Society of Pacing and Electrophysiology (NASPE; now the Heart Rhythm Society [HRS]) Expert Consensus Conference, asymptomatic WPW pattern on the ECG without recognized tachycardia is a class IIB indication for catheter ablation in children older than 5 years and a class III indication in younger children.²⁰

This approach has several justifications; one-third of asymptomatic individuals younger than 40 years when preexcitation was identified eventually developed symptoms, whereas no patients in whom preexcitation was first uncovered after the age of 40 years developed symptoms. Additionally, most patients with asymptomatic preexcitation have a good prognosis; cardiac arrest is rarely the first manifestation of the disorder. The positive predictive value of invasive EP testing is considered to be too low to justify routine use in asymptomatic patients.

Some studies, however, have questioned the approach discussed above.^8,^17,¹⁸ Those studies have shown that in the asymptomatic WPW population, a negative EP study with no AVRT or AF inducibility identifies subjects at very low risk for the development of spontaneous arrhythmias. Inducibility of sustained preexcited AF with a fast ventricular response, particularly in the presence of multiple BTs, may help select asymptomatic WPW subjects at definite risk for dying suddenly, and catheter ablation of the BT(s) appears to be required to prevent SCD. Because extensive studies have reported extremely rare complications from EP testing and radiofrequency (RF) ablation in experienced centers, it has been suggested that all asymptomatic patients with WPW pattern should undergo EP testing for risk stratification, and those with inducible AVRT or AF or who have a short BT ERP should be considered for catheter ablation of the BT, whereas patients who are noninducible and have a long BT ERP may be followed without treatment.⁸^–¹⁰ ²¹ This argument is further supported by the fact that assessment of the future VF risk in an asymptomatic patient with WPW is not easy. Noninvasive markers of lower risk such as intermittent loss of preexcitation, sudden loss of BT conduction on exercise stress testing, and loss of BT conduction after treatment with antiarrhythmic drugs are limited by inadequate sensitivity or specificity and the low incidence of future adverse events. With this approach, prophylactic ablation of BTs in high-risk subjects may be justified but is not an acceptable option for low-risk individuals. The physician involved needs to use special care and discretion in making the decision to proceed to ablation and must especially consider his or her own success and complication rates for ablation of the specific location of the BT identified.

In summary, the potential value of EP testing in identifying high-risk patients who may benefit from catheter ablation must be balanced against the approximately 2% risk of a major complication associated with catheter ablation.²² If RF catheter ablation were a totally risk-free procedure, one would logically advise such a procedure to the asymptomatic WPW patient with a short anterograde ERP. However, complications such as AV block, stroke, tamponade, and even death have been reported. It is not difficult to envision a small potential mortality benefit, if present, erased or eclipsed by a small complication rate if thousands of patients with BTs in various locations undergo ablation.¹⁶ Although complications of a diagnostic EP study are minor and non–life-threatening and are less common than those of catheter ablation, if routine EP testing of all asymptomatic WPW patients were considered, many patients would proceed immediately to RF ablation and, in others, there would be a strong temptation to ablate when catheters are in place (regardless of predicted SCD risk), especially given the fact that the criteria for ablation usually will not be black or white. This greatly increases the risk to the patient. Furthermore, invasive EP assessment has drawbacks, because no single factor has both a high sensitivity and specificity for identifying at-risk individuals. For example, a shortest preexcited R-R interval of less than 250 milliseconds during sustained induced AF is a very sensitive but not specific marker of the risk of VF in WPW patients, because approximately one-third of patients will have a shortest R-R interval of less than 250 milliseconds during induced AF. In fact, the addition of isoproterenol to the baseline study may shorten the ERP of the accessory pathway to levels of potential concern in the majority of individuals with WPW. In view of those considerations, prudence dictates that noninvasive testing with a Holter monitor and (if the Holter monitor does not show intermittent preexcitation) exercise testing should be considered before the EP study to identify the low-risk patient because of a long anterograde ERP of the BT.^21,²²

For the low-risk patient, it may be appropriate to pursue a strategy of follow-up with ECGs and reevaluation at selected intervals with a high degree of suspicion for new arrhythmia symptoms. This strategy is supported by recent prospective studies of asymptomatic patients with WPW pattern; although “potentially” life-threatening arrhythmias were observed during follow-up, no patients had actually died. This observation implies that patient education about the potential risks associated with preexcitation and about the symptoms of arrhythmias that should prompt them to seek attention can prove very important at reducing the risk of mortality without necessarily exposing the patient to the risks of catheter ablation.^10,¹⁶ It is also advisable to give the patient a copy of his or her ECG and a short note about the fact that the WPW pattern is present to prevent the misdiagnosis of myocardial infarction (MI) and to explain the basis of cardiac arrhythmias in case they develop later. Patients should also be encouraged to seek medical expertise whenever arrhythmia-related symptoms occur.

In patients not showing block in their BT during noninvasive studies, esophageal pacing may be performed to determine the anterograde ERP of the BT and the ability to induce sustained arrhythmias. This procedure is neither pleasant for patients nor often definitive, but if arrhythmias can be induced, the benefits and risk of an invasive investigation and catheter ablation should be based on individual considerations such as age, gender, occupation, and athletic involvement. This should be discussed with the patient or, in the case of a child, with the parents. Because knowledge about the success and complication rate at the EP center plays a major role in decision making, that information should be made available so that the appropriate place for invasive diagnosis and treatment can be selected. If an EP study is performed for risk stratification, the combination of inducible AVRT and a shortest preexcited R-R interval during AF of less than 250 milliseconds provides the most compelling indications for ablation. The key is a clear understanding by the patient of the relative merits of each strategy. The well-informed patient needs to choose between a very small risk of potentially life-threatening arrhythmia over a long period of time and a one-time small procedural risk associated with EP testing and catheter ablation. Certain patients such as athletes and those in higher risk occupations will generally choose ablation. Others, especially patients older than 30 years, may prefer the small risk of a conservative strategy.^10,^16,^21,²²

Management of Symptomatic Patients

Acute Management

Patients with AVRT are treated in a similar fashion as those with paroxysmal SVT. In patients with orthodromic and antidromic AVRT, drug treatment can be directed at the BT (ibutilide, procainamide, flecainide) or at the AVN (beta blockers, diltiazem, verapamil) because both are critical components of the tachycardia circuit. Adenosine should be used with caution because it can induce AF with a rapid ventricular rate in patients with preexcited tachycardias.¹⁹

AVN blocking drugs are ineffective in patients with antidromic AVRT who have anterograde conduction over one BT and retrograde conduction over a separate BT because the AVN is not involved in the circuit.¹⁹ Additionally, caution is advised against AVN blocking agents for the treatment of preexcited tachycardias occurring in patients with AT, AFL, or AF with a bystander BT. Antiarrhythmic drugs such as ibutilide, procainamide, or flecainide, which prevent rapid conduction through the bystander pathway, are preferable, even if they may not convert the atrial arrhythmia. When drug therapy fails or hemodynamic instability is present, electrical cardioversion should be considered.

Chronic Management

The NASPE policy statement on catheter ablation states that catheter ablation is considered first-line therapy (class I) and the treatment of choice for patients with the WPW syndrome—that is, patients with manifest preexcitation along with symptoms.²⁰ It is curative in more than 95% of patients and has a low complication rate. It also obviates the unwanted side effects of antiarrhythmic agents. For patients with preexcitation who are not candidates for ablation, antiarrhythmic drugs to block BT conduction should be used, such as sodium or potassium channel blockers.²³ However, there have been no controlled trials of pharmacological therapy in patients with AVRT, but small nonrandomized trials have reported the safety and efficacy of drug therapy. Despite the absence of data from clinical trials, chronic oral beta blocker therapy can be used for the treatment of patients with WPW syndrome, particularly if their BT has been demonstrated during EP testing to be incapable of rapid anterograde conduction. Verapamil, diltiazem, and digoxin, on the other hand, generally should not be used as the sole long-term therapy for patients with BT that might be capable of rapid conduction during AF.

Catheter ablation is also considered first-line therapy (class I) for patients with paroxysmal SVT involving a concealed BT. However, because concealed BTs are not associated with an increased risk of SCD in these patients, catheter ablation can be presented as one of a number of potential therapeutic approaches, including pharmacological therapy and clinical follow-up alone.¹⁹ When pharmacological therapy is selected for patients with concealed BTs, it is reasonable to consider a trial of beta blocker therapy, calcium channel blockers, or a class IC antiarrhythmic agent.

Electrocardiographic Features

Electrocardiography of Preexcitation

Anterogradely conducting AV BTs produce the classic WPW ECG pattern characterized by a fusion between conduction via the BT and the normal AVN-HPS: (1) short PR (P-delta) interval (<120 milliseconds); (2) slurred upstroke of the QRS (delta wave); and (3) wide QRS (>120 milliseconds) (Fig. 18-4).

FIGURE 18-4 Effect of atrial extrastimulation (AES) on preexcitation. A, Preexcitation is manifest during normal sinus rhythm (NSR) and atrial pacing associated with a short His bundle–ventricular (HV) interval (−11 milliseconds). AES produces decremental conduction over the atrioventricular node (AVN) (with prolonged atrial–His bundle [AH] interval) but not over the bypass tract (constant P-delta interval), increasing the degree of preexcitation with the His potential inscribed within the QRS (HV interval of −64 milliseconds). B, An earlier coupled AES produces more pronounced preexcitation and an HV interval of −93 milliseconds. C, A more premature AES produces full preexcitation with the HB activated retrogradely (H′), followed by ventriculoatrial conduction over the AVN and an echo beat (atrioventricular reentry).

The degree of preexcitation depends on several factors, including conduction time over the AVN-HPS, conduction time from the sinus node to the atrial insertion site of the BT (which depends on the distance, conduction, and refractoriness of the intervening atrial tissue), and conduction time through the BT (which depends on the length, thickness, and conduction properties of the BT).

Pharmacological and/or physiological maneuvers (e.g., carotid sinus massage, Valsalva maneuvers, adenosine, beta blockers) that alter AVN conduction can be used to alter the degree of preexcitation, thereby confirming the diagnosis of the presence of an AV BT.

The ECG pattern displayed by some patients with the WPW syndrome can simulate the pattern found in other cardiac conditions and can alter the pattern seen in the presence of other cardiac disease. A negative delta wave (presenting as a Q wave) can mimic an MI pattern. Conversely, a positive delta wave can mask the presence of a previous MI. Intermittent WPW can also be mistaken for frequent premature ventricular complexes (PVCs; Fig. 18-5). If the WPW pattern persists for several beats, the rhythm can be misdiagnosed as an accelerated idioventricular rhythm. The WPW pattern is occasionally seen on alternate beats and may suggest ventricular bigeminy. An alternating WPW and normal pattern can occasionally suggest electrical alternans. On the other hand, late-coupled PVCs (Fig. 18-6) and ventricular pacing (Fig. 18-7) with inapparent pacing artifacts can occasionally mimic ventricular preexcitation.

FIGURE 18-5 Preexcitation alternans. Surface ECG during sinus tachycardia demonstrating intermittent preexcitation in which a QRS complex manifesting a delta wave (red arrow) alternates with a normal QRS complex (blue arrow) (i.e., preexcitation alternans). Note the intermittent abrupt loss of delta wave associated with prolongation of the PR interval and the presence of a stable sinus rate, indicating that loss of preexcitation is secondary to anterograde block in the bypass tract (i.e., intermittent preexcitation) rather than enhanced atrioventricular nodal conduction.

FIGURE 18-6 Surface ECG of normal sinus rhythm with late-coupled premature ventricular complexes, which are inscribed shortly after the sinus P waves, resulting in a short PR interval and wide QRS complexes mimicking intermittent ventricular preexcitation. Note that the degree of widening of the QRS and the variability of the QRS morphology and the varying relationship to the preceding P waves all argue against ventricular preexcitation.

FIGURE 18-7 Surface ECG of normal sinus rhythm with atrial-tracking ventricular pacing. The QRS complexes are the result of fusion from ventricular pacing and conduction over the normal atrioventricular conduction axis, resulting in a pseudo-delta wave, mimicking a Wolff-Parkinson-White ECG pattern. The pacing artifacts are very small, but careful inspection reveals those artifacts most clearly in lead III.

Inapparent Versus Intermittent Preexcitation

Inapparent Preexcitation

With inapparent preexcitation, preexcitation is absent on the surface ECG despite the presence of an anterogradely conducting AV BT, because conduction over the AVN-HPS reaches the ventricle faster than that over the BT. In this setting, the PR interval is shorter than what the P-delta interval would be if preexcitation were present. Therefore, when preexcitation becomes inapparent, the PR interval becomes shorter, reflecting the now better AVN-HPS conduction.³

Inapparent preexcitation is usually caused by (1) enhanced AVN conduction, so that it is faster than conduction over the BT; (2) prolonged intraatrial conduction from the site of atrial stimulation to the atrial insertion site of BT (most often left lateral), favoring anterograde conduction over the AVN-HPS; and/or (3) prolonged conduction over the BT, so that it is slower than AVN-HPS conduction.

Intermittent Preexcitation

Intermittent preexcitation is defined as the presence and absence of preexcitation on the same tracing (Fig. 18-8). True intermittent preexcitation is characterized by an abrupt loss of the delta wave (independently of how fast or slow is AVN conduction), with prolongation (normalization) of the PR interval (reflecting the loss of the faster BT conduction, and the subsequent conduction over the slower AVN-HPS), and normalization of the QRS in the absence of any significant change in heart rate.

FIGURE 18-8 Intermittent preexcitation. Surface ECG leads II and V₁ and intracardiac recordings in a patient with Wolff-Parkinson-White syndrome and a right anterior bypass tract (BT). Note the intermittent abrupt loss of delta wave (stars) associated with prolongation of the PR interval and normalization of the His bundle–ventricular (HV) interval, despite the presence of a constant atrial–His bundle (AH) interval (atrioventricular node [AVN] conduction) and a stable sinus rate, indicating that loss of preexcitation is secondary to anterograde block in the BT (i.e., intermittent preexcitation) rather than enhanced AVN conduction.

Intermittent preexcitation is usually caused by (1) phase 3 (i.e., tachycardia-dependent) or phase 4 (i.e., bradycardia-dependent) block in the BT (see Chap. 10); (2) anterograde or retrograde concealed conduction produced by PVCs, premature atrial complexes (PACs), or atrial arrhythmias; (3) BTs with long ERP and the gap phenomenon in response to PACs; and/or (4) BTs with long ERP and supernormal conduction.

Intermittent preexcitation is generally a reliable sign that the AV BT has a relatively long anterograde ERP and is not capable of excessively rapid impulse conduction, such as during AF. Maneuvers that slow AVN conduction (e.g., carotid sinus massage, AVN blockers) would unmask inapparent preexcitation but would not affect intermittent preexcitation.

Preexcitation alternans is a form of intermittent preexcitation in which a QRS complex manifesting a delta wave alternates with a normal QRS complex (see Fig. 18-5). Concertina preexcitation is another form of intermittent preexcitation in which the PR intervals and QRS complex durations show a cyclic pattern; that is, preexcitation becomes progressively more prominent over a number of QRS complex cycles followed by a gradual diminution in the degree of preexcitation over several QRS cycles, despite a fairly constant heart rate.

Differentiation between intermittent preexcitation and inapparent preexcitation on an ECG showing QRS complexes with and without preexcitation can be achieved by comparing the P-delta interval during preexcitation and the PR interval when preexcitation is absent. Loss of preexcitation associated with a PR interval longer than the P-delta interval is consistent with intermittent preexcitation (see Fig. 18-8), whereas loss of preexcitation associated with a PR interval shorter than the P-delta interval is consistent with inapparent preexcitation.

Supraventricular Tachycardias Associated with Wolff-Parkinson-White Syndrome

Orthodromic Atrioventricular Reentrant Tachycardia

The ECG during orthodromic AVRT shows P waves inscribed within the ST-T wave segment with an RP interval that is usually less than half of the tachycardia R-R interval (i.e., RP interval < PR interval) (Fig. 18-9). The RP interval remains constant, regardless of the tachycardia CL, because it reflects the nondecremental conduction over the BT. QRS morphology during orthodromic AVRT is generally normal and not preexcited, even when preexcitation is present during NSR (Fig. 18-10). Functional bundle branch block (BBB) can be observed frequently during orthodromic AVRT (see Fig. 18-9). The presence of BBB during SVT in a young person (<40 years) should raise the suspicion of orthodromic AVRT incorporating a BT ipsilateral to the blocked bundle, because the longer conduction time through the involved ventricle engendered by the BBB facilitates orthodromic reentry by enabling all portions of the circuit enough time to recover excitability from the prior cycle. This is particularly true with left bundle branch block (LBBB), which is very uncommon in younger patients.

FIGURE 18-9 Surface ECG of orthodromic atrioventricular reentrant tachycardia (AVRT) using a concealed superoparaseptal bypass tract (BT). Note the P waves (arrows) inscribed within the ST-T wave segment (short RP interval). Ischemic-appearing ST segment depression is also observed. Functional right bundle branch block occurs in the right side of the tracing, with prolongation of the RP (ventriculoatrial [VA]) interval, suggesting that retrograde VA conduction during the supraventricular tachycardia is mediated by a right-sided BT. The dashed lines denote the QRS onset and P wave onset.

FIGURE 18-10 Surface ECG of multiple supraventricular arrhythmias in a patient with a bidirectional left posteroseptal bypass tract (BT). Ventricular preexcitation is evident during normal sinus rhythm (NSR). Atrial flutter with 2:1 atrioventricular (AV) conduction over the BT results in a wide complex tachycardia. The narrow complex tachycardia represents orthodromic atrioventricular reentrant tachycardia (AVRT) using the BT as the retrograde limb of the reentrant circuit. Atrial fibrillation results in an irregularly irregular rhythm with “clumping” of the preexcited (wide) and normal QRS complexes.

Orthodromic AVRT tends to be a rapid tachycardia, with rates ranging from 150 to more than 250 beats/min. A beat-to-beat oscillation in QRS amplitude (QRS alternans) is present in up to 38% of cases and is most commonly seen when the rate is very rapid. The mechanism for QRS alternans is not clear but can partly result from oscillations in the relative refractory period of the distal portions of the HPS.

Ischemic-appearing ST segment depression also can occur during orthodromic AVRT, even in young individuals who are unlikely to have coronary artery disease. An association has been observed between repolarization changes (ST segment depression or T wave inversion) and the underlying mechanism of the tachycardia, because such changes are more common in orthodromic AVRT than AVNRT (57% versus 25%). Several factors can contribute to ST segment depression in these arrhythmias, including changes in autonomic tone, intraventricular conduction disturbances, a longer ventricular-atrial (VA) interval, and a retrograde P wave of longer duration that overlaps into the ST segment. The location of the ST segment changes can vary with the location of the BT; ST segment depression in leads V₃ to V₆ is almost invariably seen with a left lateral BT, whereas ST segment depression and a negative T wave in the inferior leads is associated with a posteroseptal or posterior BT. A negative or notched T wave in leads V₂ or V₃ with a positive retrograde P wave in at least two inferior leads suggests an anteroseptal BT. However, ST segment depression occurring during orthodromic AVRT in an older patient mandates consideration of possible coexisting ischemic heart disease.

Antidromic Atrioventricular Reentrant Tachycardia

Antidromic AVRT is characterized by a wide (fully preexcited) QRS complex, usually regular R-R intervals, and ventricular rates of up to 250 beats/min. The width of the preexcited QRS complex and the amplitude of the ST-T wave segment usually obscure the retrograde P wave on the surface ECG. When the P waves can be identified, they are inscribed within the ST-T wave segment with an RP interval that may be more than half of the tachycardia R-R interval because retrograde conduction occurs slowly via the AVN-HPS. The PR (P-delta) interval remains constant, regardless of the tachycardia CL, because it reflects nondecremental conduction over the BT.

Permanent Junctional Reciprocating Tachycardia

PJRT tends to be incessant, stopping and starting spontaneously every few beats without initiating PACs or PVCs. The heart rate is usually between 120 and 200 beats/min and the QRS duration is generally normal. Slow retrograde conduction over the BT causes the RP interval during PJRT to be long, usually more than half of the tachycardia R-R interval (Fig. 18-11). The P waves resulting from retrograde conduction are easily seen on the ECG and are inverted in leads II, III, aVF, and V₃ to V₆.

FIGURE 18-11 Surface ECG of permanent junctional reciprocating tachycardia (PJRT). Note the incessant nature of the arrhythmia, stopping and starting spontaneously every few beats without initiating atrial or ventricular ectopic beats. Slow retrograde conduction over the bypass tract causes the RP interval during PJRT to be long (long RP tachycardia). The P waves resulting from retrograde conduction are easily seen on the ECG and are inverted in the inferior leads.

Atrioventricular Nodal Reentrant Tachycardia and Atrial Tachycardia

Both AVNRT and AT can be associated with partially or fully preexcited QRS complex secondary to anterograde conduction to the ventricles over the bystander BT. When AVNRT occurs in the WPW syndrome, the arrhythmia can be difficult to distinguish from orthodromic AVRT without EP testing.

Atrial Fibrillation

There are several characteristic findings on the ECG in patients with AF conducting over a BT, so-called preexcited AF (see Fig. 18-10). The rhythm is irregularly irregular, and can be associated with very rapid ventricular response caused by the nondecremental anterograde AV conduction over the BT. However, a sustained rapid ventricular rate of more than 180 to 200 beats/min will often create pseudo-regularized R-R intervals when the ECG is recorded at 25 mm/sec. Although the QRS complexes are conducted aberrantly, resembling those during preexcited NSR, their duration can be variable and they can become normalized. This is not related to the R-R interval (i.e., it is not a rate-related phenomenon), but rather is related to the variable relationship between conduction over the BT and AVN-HPS. Preexcited and normal QRS complexes often appear “clumped” (see Fig. 18-10). This can result from concealed retrograde conduction into the BT or the AVN.

The QRS complex during preexcitation is a fusion between the impulse that preexcites the ventricles caused by rapid conduction through a BT and the impulse that takes the usual route through the AVN. The number of impulses that can be transmitted through the BT and the amount of preexcitation depend on the refractoriness of both the BT and AVN. The shorter the anterograde ERP of the BT, the more rapid is anterograde impulse conduction and, because of more preexcitation, the wider the QRS complexes. Patients who have a BT with a very short ERP and rapid ventricular rates represent the group at greatest risk for development of VF.

Anterograde block in the BT abolishes retrograde conduction into the AVN, which in turn allows the AVN to recover its excitability and conduct anterogradely. These conducted impulses through the AVN can result in retrograde concealment into the BT, causing anterograde block of the BT, thereby slowing the ventricular rate.

Atrial Flutter

AFL, like AF, can conduct anterogradely via a BT resulting in a preexcited tachycardia (see Fig. 18-10). Depending on the various refractory periods of the normal and pathological AV conduction pathways, AFL potentially can conduct 1:1 to the ventricles during a preexcited tachycardia, making the arrhythmia difficult to distinguish from VT (see

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