Wolff-Parkinson-White Syndrome Workup

The extent of the workup is determined by the acuity of the patient’s illness. In the patient who has cardiogenic shock or is unconscious, direct-current (DC) cardioversion is indicated as soon as a dysrhythmia is identified to be causative. Once the patient is hemodynamically stable or in the context of assessment following an arrest, selected laboratory studies may be considered.

No specific diagnostic laboratory studies are indicated. If laboratory values are obtained, it is reasonable to check electrolytes, including potassium, magnesium, and calcium, which may all potentially contribute to dysrhythmias. Assessment of arterial blood gases, electrolyte levels, and lactate levels may be appropriate, as well as drug screening.

The diagnosis of Wolff-Parkinson-White (WPW) syndrome is typically made with formal electrocardiographic (ECG) monitoring in conjunction with clues from the history and physical examination. Evaluate patients presenting with symptomatic tachycardia (supraventricular tachycardia [SVT] or wide-complex tachycardia) for the presence of preexcitation on the 12-lead ECG results, and consider consultation with a cardiac electrophysiologist. Noninvasive mapping of cardiac arrhythmias is also possible with a 252-lead ECG and computed tomography (CT)-based three-dimensional (3D) electroimaging. ^[25]

Evaluate patients with WPW syndrome for the presence of very short refractory periods, because these patients carry higher probabilities of developing symptoms or complications. The patients also respond poorly to drug therapy. Identify these patients, even if asymptomatic, and treat them aggressively using electrophysiologic study (EPS) and ablative therapy.

Routine blood studies may be needed to help rule out noncardiac conditions triggering tachycardia. These may include the following:

• Complete blood count (CBC)
• Chemistry panel (blood urea nitrogen [BUN] and creatinine to assess renal status)
• Liver function tests
• Thyroid panel

Blood levels of antiarrhythmic medications during therapy and monitoring are typically not helpful for oral medications. Intravenous (IV) lidocaine and procainamide do require serum measurements during treatment. Digoxin is a medication that should typically be avoided in WPW patients because of a preferential decrease in atrioventricular (AV) nodal, rather than pathway, conduction. However, digoxin levels may be helpful if digoxin toxicity is suspected.

Echocardiography, focusing on cardiac function and dimensions, is needed to evaluate left ventricular (LV) function, septal thickness, and wall motion abnormalities and to help rule out cardiomyopathy and an associated congenital heart defect (CHD), such as hypertrophic cardiomyopathy [HOCM], Ebstein anomaly, or L-transposition of the great vessels. Significantly depressed function may be observed in the setting of an acute dysrhythmia but should typically normalize in the absence of an incessant tachycardia.

The diagnosis and management of any cardiac dysrhythmia may first be accomplished by analysis of 12-lead ECG and rhythm strips and their relationship to the clinical setting. Recognizing dysrhythmias on 12-lead ECG findings requires a detailed knowledge of atrial and ventricular activation patterns and deductions related to the mechanisms of atrioventricular (AV) conduction.

Diagnosis of accessory pathways (APs) is indicated. During ventricular pacing, premature ventricular stimulation activates the atria before retrograde depolarization of the His bundle. This indicates that the impulse reached the atria before it depolarized the His bundle and must have traveled via a different pathway (bypass tract).

If the ventricles can be stimulated prematurely during tachycardia at a time when the His bundle is refractory and the impulse still conducts to the atrium (His-refractory or His-synchronous premature ventricular complex [PVC]), this indicates that retrograde propagation traveled to the atrium over a pathway other than the bundle of His, representing the usual inferior input to the AV node.

In addition, if a PVC, delivered at a time when the His bundle is refractory, terminates the tachycardia without retrograde activation of the atria, it most likely invaded, and blocked in, an AP. If repeatable, this is diagnostic of orthodromic reentrant tachycardia (ORT).

The ventriculoatrial (VA) interval (a measurement of conduction over the accessory pathway) is generally constant over a wide range of ventricular-paced rates and coupling intervals of PVCs and during the tachycardia in the absence of aberration. Similar short VA intervals can be observed in some patients during AV nodal reentry, but if the VA conduction time or RP interval is the same during tachycardia and ventricular pacing at comparable rates, an AP is almost certainly present (VA linking).

Tachycardia can be easily initiated after premature ventricular stimulation that conducts in retrograde fashion in the AP but blocks in the AV node or His bundle.

Atria and ventricles are required components of the macroreentrant circuit in ORT or AV reentrant tachycardia (AVRT); therefore, continuation of the tachycardia in the presence of AV or VA block excludes an accessory AV pathway as part of the reentrant circuit.

Characteristic features of WPW syndrome

The classic ECG morphology of WPW syndrome is described as a shortened PR interval (often <120 ms) and a slurring and slow rise of the initial upstroke of the QRS complex (delta wave; see the image below), a widened QRS complex with a total duration greater than 0.12 seconds, and secondary repolarization changes reflected as ST segment–T wave changes that are generally directed opposite the major delta wave and QRS complex. In reality, the ECG morphology varies widely.

Depending on the location of the AP in relation to the sinus node (see below) and the relative transmission characteristics of the AP and the AV node, the morphology of the ECG may vary from a classic presentation, termed manifest preexcitation, to near normal.

In some cases, the electrical impulse’s arrival at the ventricles occurs slightly earlier through the AP (by not undergoing the typical slowing through the AV node), creating preexcitation.

The QRS interval is widened because the ventricles are initially activated via the AP, which lies outside the normal conducting system, producing an early, albeit relatively slow, initial propagation of depolarization forces through the ventricular tissue. This produces the delta wave. The delta wave makes the QRS appear wider than expected and the PR interval somewhat shortened. This is known as a manifest AP because it is easily identifiable on ECG.

WPW syndrome has been described by some as either type A or type B, depending on the appearance of the delta wave/QRS complex in the precordial leads. Type A is described as having an upright positive delta wave in all precordial leads with a resultant R greater than S amplitude in lead V1. Type B has a predominantly negative delta wave and QRS complex in V1 and V2 and becomes positive in transition to the lateral leads, much as in left bundle-branch block (LBBB).

Lown-Ganong-Levine (LGL) syndrome has a shortened PR interval because of the presence of the AP bypassing the AV node, but it has a normal QRS because the AP (James fibers) connects directly with the His bundle and does not depolarize the ventricles directly but depolarizes them via the typical conduction pathway through the His-Purkinje system. The true pathophysiology of this classic description has recently been brought into question.

In other WPW syndrome cases, arrival of the electrical impulse to the ventricle occurs nearly simultaneously through both the accessory pathway and the AV node. When this occurs, preexcitation is absent, and ECG appears normal. Thus, ECG morphology depends directly on the degree of preexcitation (ie, relative conduction speeds).

An AP that does not manifest on ECG is revealed when the rate exceeds the refractory period of the AV node. This has been described as a latent AP. A latent AP can conduct both antegrade and retrograde transmissions.

An AP in which only retrograde transmission of impulses can occur is called a concealed AP and is used only during circus movement tachycardia (CMT or ORT). A concealed AP is not detectable on the regular surface ECG findings, because the ventricle is not preexcited. Tachycardia due to a concealed AP should be considered when the QRS complex is normal and the retrograde P wave occurs well after completion of the QRS complex, out in the ST segment or even in the T wave (long R-P tachycardia).

Although many types of dysrhythmias can occur in a patient with WPW syndrome, ORT and atrial fibrillation (AF) are the most common. ORT is the more common of the two.

A critically timed premature atrial beat that occurs during the refractory period of the AP typically initiates ORT. The impulse, therefore, travels solely down the AV node but returns in a retrograde manner through the AP, resulting in reciprocating tachycardia.

This is a narrow-complex heart rhythm limited by the refractory period of the AV node. The QRS complex is narrow, because the impulses travel in an antegrade manner (orthodromically) through the AV node, and regular, because circus (circular) movement occurs at a regular rate.

Differential diagnosis of this type of WPW dysrhythmia includes paroxysmal supraventricular tachycardia (PSVT). Differentiating between the 2 in an acutely symptomatic patient with a regular-rhythm, narrow-complex tachycardia is difficult. Cardiac dysrhythmias with rates higher than 220 bpm in adults suggest that the dysrhythmia is bypassing the AV node and may reflect an AP or ventricular tachycardia (VT).

Antidromic CMTs are wide and potentially faster because of the relatively short refractory period of most APs. They are termed antidromic because antegrade transmission occurs down the AP from the atria to the ventricles, creating preexcitation of the ventricle adjacent to the AP. These dysrhythmias are regular due to the nature of the circus movement. They are likely to have the classic delta wave appearance of the QRS on the resting ECG.

Differential diagnoses include VT, which also is regular (unless it is torsade de pointes) or PSVT with aberrancy. One should initially consider any regular wide-complex tachycardia to be VT until proven otherwise.

Most cases of regular wide-complex AVRT (AV reentry tachycardia) associated with WPW syndrome that are treated with adenosine consequently are converted to sinus rhythm, though adenosine may induce atrial fibrillation, and DC cardioversion equipment should be available.

AF in patients with WPW syndrome is very common and has an incidence of 11-38%. It is also the deadliest dysrhythmia for these patients because of the possibility of deterioration into ventricular fibrillation (VF).

Another concerning feature of AVRT in patients with WPW is that it can disorganize into AF, which can have disastrous consequences in patients with accessory AV pathways capable of antegrade conduction. Atrial impulses can reach an AP at a rate of 300-400 times per minute and may result in hemodynamic instability due to rapid rates of ventricular response, far in excess of that allowed by the AV node-His-Purkinje axis. ^[26]

In normal hearts, an individual is protected from exceptionally high ventricular rates by the relatively long refractory period of the AV node. In patients with WPW syndrome, however, the AP often has a much shorter antegrade refractory period, allowing much faster transmission of impulses and correspondingly higher rates (may exceed 300 bpm).

In addition, sympathetic discharge secondary to hypotension may lead to further shortening of the refractory period and subsequent increases in the ventricular rate. If the rate becomes too high, VF may result.

AF through an AP appears as a bizarre, wide-complex, irregular tachycardia on ECG, with rates often in the 250 bpm range or higher. The combination of a rapid rate, a widened QRS complex, and unusual or changing QRS complex morphologies in a young patient strongly suggests the diagnosis. ^[27]

Localization of accessory pathways

The location of the AP can often be determined through analysis of the spatial direction of the delta wave in the 12-lead ECG by reviewing the maximally preexcited QRS complexes. ^[28] A general rule is that Q waves (negative delta waves) point away from the earliest site of ventricular activation, which is typically the insertion point of the bypass tract. The most common locations for APs, in decreasing order of frequency, are the left free wall, the posteroseptal and right free wall, and finally the midseptal and anteroseptal regions of the heart.

Several algorithms are available to predict the location of the AP. These algorithms may not be totally accurate because maximal preexcitation is needed, and usually the QRS in WPW pattern is a fusion between AV node and AP depolarization (ie, absent AP depolarization may be present at certain points due to enhanced AV node conduction, although the AP is present), precordial lead placement may vary, as well as chest shape and size and heart shape, size, and location.

A practical concept is that a negative delta wave usually signals the location of the AP, as follows:

• A negative delta wave in a left-side lead such as I and aVL indicates a left-side AP
• A negative delta in a right-side lead such as V1 predicts a right-side AP
• An isoelectric delta in V1 predicts an anteroseptal AP
• A negative delta in the inferior leads (II, III, and aVF) indicates a posteroseptal AP
• A positive delta in the inferior leads predicts an anteroseptal AP

A more specific algorithm for location of the AP, based on the polarity of the delta wave or first 40 ms of the QRS, predicts the following AP locations:

• Left lateral wall - Negative delta waves in lead I and aVL; positive or isoelectric delta waves in II, III, aVF (inferior leads), and V1-4; and negative or isoelectric delta waves in V5-6
• Left posterior free wall - Positive delta waves in lead I and aVL; negative delta waves in II, III, and aVF; positive delta waves in V1-5; and negative or isoelectric delta wave in V6
• Posteroseptal - Positive delta waves in lead I and aVL with negative delta waves in II, III, and aVF; isoelectric or positive delta waves in V1; and positive delta waves in the rest of the precordial leads (see the images below)
• Right free wall - Positive delta waves in I and II, negative delta waves in aVR, isoelectric or negative delta wave in aVF, isoelectric delta wave in V1, isoelectric or positive delta waves in V2-3, and positive delta waves in V4-6
• Left anteroseptal - Positive delta waves in I, II, and aVF; negative delta wave in aVR; isoelectric or positive delta wave in V1; and positive delta waves in V2-6
• Right anteroseptal - Positive delta waves in I, II, and aVF; negative delta wave in aVR; negative or isoelectric delta waves in V1-3; and positive delta waves in V4-6

During orthodromic tachycardia, a narrow complex QRS is evident, with the P wave often detectable as a subtle deflection within the T wave. During antidromic tachycardia, a wide complex QRS is seen and may not be distinguishable from VT (in which case it must be treated as such).

ECG imaging is a recently described noninvasive technique that reconstructs epicardial electrograms from body surface potentials. ^[29] This modality has been used to identify the exact location of pathways responsible for ventricular preexcitation. ^[30]

Recording devices

Continuous ECG recordings (eg, via telemetry, 24-hour Holter monitors, event monitors, or implantable loop recorders) are indicated. Continuous monitoring of cardiac rhythm with telemetry can be performed on hospitalized patients in the coronary or progressive care units.

In the outpatient setting, a number of portable recording devices (eg, Holter monitors, event monitors) can be used and should be aimed at symptom-rhythm correlation.

Portable recording systems provide simultaneous two-lead recording that improves the diagnostic yield tremendously. The 2 leads most commonly used for monitoring are II and MCL-I, the latter being similar to V1. These devices have long-term storage capabilities that permit off-line analysis of complex dysrhythmias, even if the physician is not available at the time the rhythm disturbance occurs.

For infrequently occurring dysrhythmias, a number of event recorders are available. They allow the patient to activate the device by pressing a button when an event occurs, providing internal storage and transmission by telephone or wireless communication to a central station for later review.

A small loop recorder can be implanted and can be remotely interrogated for rhythm analysis. This can be used in patients with dysrhythmias that are infrequent or difficult to capture. External loop recorders can be valuable in assessing palpitations after ablation, which are very common and often represent isolated extrasystoles rather than signaling the return of more serious arrhythmias.

In the presence of WPW syndrome without documented SVT and in the presence of symptoms, a transtelephonic transient cardiac event monitor or a longer-term monitoring system may be appropriate.

Stress testing is an ancillary test and may be used (1) to reproduce a transient paroxysmal SVT (PSVT), which is triggered by exercise, (2) to document the relationship of exercise to the onset of tachycardia, or (3) to evaluate the efficacy of antiarrhythmic drug therapy (class Ic antiarrythmic medications and effects on antegrade preexcitation).

If preexcitation is abruptly lost, stress testing may reveal the refractory periods of APs in patients with WPW syndrome. Such testing may be unreliable, however, because exercise also alters the competing conduction properties of the atrioventricular (AV) node and will favor conduction over the AV node if a septal or left-side AP is present.

Esophageal EPS can be used to assess the behavior of the AP, the inducibility of SVT, and the response to drug therapy. This procedure can be performed safely as an outpatient procedure requiring only sedation. Invasive EPS can also be performed for these risk-stratification indications, but this is usually reserved for patients undergoing radiofrequency (RF) ablation.

Intracardiac EPS is performed in a cardiac electrophysiology laboratory. With the use of multipolar catheter electrode systems, recordings from many intracardiac sites can be performed simultaneously, facilitating delineation of the sequence of depolarization and impulse conduction in the atria, AV junction, and ventricle. ^[4]

Indications

EPS can be used in patients with WPW syndrome to determine the following:

• The mechanism of the clinical tachycardia
• The electrophysiologic properties (eg, conduction capability, refractory periods) of the AP and the normal AV nodal and His Purkinje conduction system
• The number and locations of APs (which are necessary for catheter ablation)
• The response to pharmacologic or ablation therapy

Features of preexcitation

If a Kent bundle (AV)-type accessory bypass tract conducts in an antegrade fashion, two parallel paths can potentially carry the impulse. The first is the natural one, which comes with inherent physiologic delay over the AV node (decremental conduction). The second is the bypass tract (Kent bundle), which allows the impulse to pass directly without delay from the atrium to the ventricle (nondecremental conduction).

This dual-path mechanism produces a unique QRS complex that is a form of fusion beat. The delta wave results from ventricular activation by the impulse traveling over the AP. The degree of delta (preexcitation) is directly related to the distance of the bypass tract to the sinus node and the speed of conduction over the AV node and His Purkinje system.

The extent to which the wavefront over each route contributes to ventricular depolarization varies, as follows:

• If delay in AV nodal conduction occurs from either rapid atrial pacing or a premature atrial complex, a greater proportion of the ventricle activates via the bypass tract, and the QRS becomes more preexcited
• On the other hand, if the bypass tract is far from the sinus node (as in the presence of a left lateral pathway) or if AV nodal conduction is rapid, a larger proportion of the ventricle activates via the normal pathway, and preexcitation will be subtle
• The normal fusion beat during sinus rhythm has a short or negative His-ventricle (HV) interval; pacing the atrium rapidly at premature intervals accentuates the abnormal ventricular depolarization and further shortens the HV interval
• Localization of the potential site of pathway for RF ablation may be facilitated by analysis of the delta wave axis as initially described in the classic article by Arruda et al ^[28]

A negative HV interval during sinus rhythm in the presence of WPW syndrome means that the His deflection occurs after the beginning of the QRS deflection. The more preexcitation, the later the His deflection (ie, more toward the end of the QRS).

This occurs whenever the AP conducts more rapidly than the AV node and the depolarizing wavefront from the AP thus reaches the ventricle before that from the AV node. The earlier that the depolarization from the AP reaches the ventricle with respect to the depolarization from the AV node, the more preexcitation occurs (ie, the wider the QRS and the shorter the RP interval).

During antidromic SVT, a premature atrial extrastimulation that shortens the SVT cycle length with no change in QRS morphology or that terminates SVT with an atrial depolarization (ie, not followed by a QRS) rules out VT. In the first case, the premature atrial depolarization conducts to the ventricles through the AP. In the second case, the premature atrial depolarization reaches the AP’s effective refractory period terminating the SVT in the antegrade limb, also proving that the AP participated in the SVT (ie, it is an AP-mediated SVT and not a VT).

Recognition and localization of accessory pathways

When retrograde atrial activation during tachycardia occurs over an AP that connects the left atrium to the left ventricle, the earliest retrograde activity is recorded from a left atrial electrode (usually positioned in the coronary sinus). This is a left lateral pathway.

When retrograde atrial activation during tachycardia occurs over an AP that connects the right ventricle to the right atrium, the earliest retrograde atrial activity is generally recorded from a lateral right atrial electrode. This is a right ventricular free wall pathway.

Participation of a septal accessory pathway creates earliest retrograde atrial activation in the low-right atrium situated near the septum, anteriorly or posteriorly (depending on the insertion site).

Retrograde atrial activation over the AP can be confirmed by inducing premature ventricular complexes (PVCs) during tachycardia to determine whether retrograde atrial excitation can occur from the ventricle at a time when the His bundle is refractory (His refractory PVCs). Failure to advance the atrium when the His is refractory does not exclude an AP, particularly if far from the pacing site (left lateral pathway).

With entrainment pacing from the right ventricular (RV) apex, orthodromic reentrant tachycardia (ORT) will return with a V-A-V response, typically with a short (<115 ms) postpacing interval (PPI)–tachycardia cycle length (TCL) difference (PPI-TCL) if septal in origin. VA intervals remain fixed during SVT, and AV block cannot occur if the AV AP is critical to the circuit.

Activation mapping using three-dimensional (3D) electroanatomical mapping systems (CARTO, En-Site) may improve pathway localization, particularly when the AP is anteroseptal or midseptal and concern for AV block during RF ablation is present.

Typically, one should ablate on the side being mapped. If mapping the earliest A, ablate in the atrium via transseptal access if necessary). If mapping the earliest V antegrade, perform ablation via a retrograde aortic approach, if on the left side.

Risk assessment and need for ablation

If AF is induced during either an intraesophageal or an EPS, the shortest RR interval between two consecutive preexcited QRSs is measured. If the interval is less than 220 ms, then the risk of sudden death due to VF is believed to be high. Specifically, according to one study, the most discriminating predictor of VF in patients with WPW syndrome was the shortest RR interval during AF of 172 ± 23 ms (vs 230 ± 50 ms). ^[23] Those patients were considered to be at high risk for developing VF and sudden death should AF occur.

A study of asymptomatic children with WPW pattern who underwent EPS for risk stratification reported that a high proportion of subjects experienced sustained AVRT, AF, or both, with the shortest RR between two consecutive preexcited QRSs being 230-250 ms (mean, 237.5 ± 9.6 ms). ^[5] The authors concluded that those results may be indicative of the necessity of RF ablation in all asymptomatic individuals with WPW pattern.

An extremely detailed postmortem assessment of histology from multiple sections around the AV ring may identify APs. However, this approach is impractical for assessment of every patient with unexplained sudden death.