7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Treatment of arrhythmias associated with the Wolff- Parkinson-White syndrome : Luigi Di Biase, MD, PhD, FHRS, FACC, Edward P Walsh, MD : Samuel L vy, MD, Bradley P Knight, MD, FACC : Susan B Yeon, MD, JD, FACC All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: May 30, 2023. INTRODUCTION Conduction from the atria to the ventricles normally occurs via the atrioventricular node (AV)- His-Purkinje system. Patients with a preexcitation syndrome have an additional pathway, known as an accessory pathway, which directly connects the atria and ventricles, bypassing the AV node. Normal conduction through the AV node is slower than conduction over the accessory pathway. Thus, when there is conduction over an accessory pathway, the ventricles are activated earlier than if the impulse had traveled through the AV node. This early activation, referred to as preexcitation, is responsible for the classic electrocardiographic (ECG) findings of a shortened PR interval and, in most patients, a delta wave ( waveform 1). Symptoms, ranging from mild palpitations to syncope and, rarely, even sudden cardiac death, are the result of tachycardia, usually due to a macroreentrant circuit involving the AV node, the ventricles, the accessory pathway, and the atria. This classic supraventricular tachycardia associated with WPW syndrome is called AV reentrant or reciprocating tachycardia (AVRT). However, preexcited atrial fibrillation (AF) or atrial flutter with a rapid ventricular response may also result in symptoms. Fortunately, the incidence of sudden death in patients with the WPW syndrome is quite low, ranging from 0 to 0.39 percent annually in several large case series, with the lowest risk seen in asymptomatic patients. Patients with the WPW syndrome are usually treated because of symptomatic arrhythmias. Treatment may sometimes be extended to asymptomatic patients with a WPW pattern if certain https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 1/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate "high-risk" features are present. However, most asymptomatic patients with the WPW electrocardiographic pattern are not treated. Treatment options for persons with arrhythmias and the WPW syndrome include nonpharmacologic therapies (ie, catheter ablation of the accessory pathway) as well as pharmacologic therapy (to slow ventricular heart rates or to prevent arrhythmias). The choice of the optimal therapy depends on the acuity of the arrhythmia(s) and the risk of sudden cardiac death, with pharmacologic agents being the treatment of choice for most acute arrhythmias, while catheter ablation is nearly always preferred for the long-term prevention of recurrent arrhythmias involving the accessory pathway. This topic will review the available therapeutic options for the treatment of arrhythmias in the WPW syndrome. The clinical manifestations, approach to diagnosis, and the types of arrhythmias which can occur in persons with an accessory pathway and the WPW pattern are discussed separately. (See "Wolff-Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) ACUTE TREATMENT OF SYMPTOMATIC ARRHYTHMIAS While the preferred long-term treatment approach for patients with an accessory pathway, preexcitation, and symptomatic arrhythmias is catheter-based radiofrequency ablation, patients who present with an acute arrhythmia often require initial pharmacologic therapy for ventricular rate control or restoration of sinus rhythm. However, because of the electrophysiologic differences between AV nodal tissue and tissue comprising an accessory pathway, standard therapy for heart rate control may actually worsen symptoms and lead to clinical deterioration in patients with a tachycardia involving an accessory pathway. Knowledge of the presence of an accessory pathway is critical in choosing the correct initial pharmacologic therapy. (See 'Treatment to prevent recurrent arrhythmias' below and "Overview of the acute management of tachyarrhythmias".) Initial assessment of hemodynamic stability As with any patient presenting with a symptomatic tachyarrhythmia, patients with a tachycardia suspected to involve an accessory pathway should undergo an initial assessment of hemodynamic status. Patients who are hemodynamically stable can be evaluated and treated according to the type of suspected arrhythmia. However, patients with hemodynamic instability or compromise related to an ongoing tachycardia should undergo urgent electrical cardioversion [1,2]. The technique for urgent https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 2/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate electrical cardioversion is discussed elsewhere. (See "Cardioversion for specific arrhythmias".) Orthodromic AVRT In patients with orthodromic atrioventricular reciprocating tachycardia (AVRT), antegrade conduction occurs via the AV node with retrograde conduction via an accessory pathway. In such patients, antegrade conduction across the AV node is typically the "weak link" of the reentrant circuit. Thus, the approach to patients with orthodromic AVRT is similar to patients with other types of paroxysmal supraventricular tachycardia, where relatively specific therapies that lengthen AV nodal refractoriness and depress its conduction can block the impulse within the AV node and terminate and prevent the tachycardia. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Narrow complex AVRT' and "Overview of the acute management of tachyarrhythmias", section on 'Regular narrow QRS complex tachyarrhythmias'.) We employ a step-wise approach to termination of orthodromic AVRT ( table 1). We recommend initial treatment of acute symptomatic orthodromic AVRT with one or more vagal maneuvers (such as the Valsalva maneuver and carotid sinus massage) [1,2]. These may be sufficient to cause AV node block and tachycardia termination in many patients [3]. (See "Vagal maneuvers".) If vagal maneuvers are ineffective, pharmacologic therapy with an AV nodal blocking agent (ie, adenosine, verapamil, beta blockers) should be instituted: We suggest intravenous adenosine rather than intravenous verapamil as the initial choice based on its efficacy and short half-life. Intravenous adenosine is effective for acute termination of orthodromic AVRT in 80 to 90 percent of patients [4-6]. Its ultrashort duration of action makes it a preferred agent before resorting to emergent DC cardioversion in the patient whose hemodynamic state is more tenuous. The protocol for intravenous adenosine administration is described in the algorithm ( algorithm 1). Prior to adenosine administration, the patient should be advised of the possibility of feeling lightheaded, dizzy, or near syncopal during the injection. On rare occasions, adenosine has been reported to transiently increase atrial vulnerability to AF, a potentially serious proarrhythmic effect, and cause atrial ectopy that can reinitiate orthodromic AVRT after acute tachycardia termination [4,7-9]. If adenosine is ineffective, we proceed with intravenous verapamil as the second line agent. Intravenous verapamil, given as 5 mg boluses in a full-grown patient (0.1 mg/kg in children to a maximum dose of 5 mg; contraindicated in children less than 12 months of age) every https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 3/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate two to three minutes (up to a cumulative initial dose of up to 15 mg), is as effective as adenosine for acutely terminating orthodromic AVRT, provided that the patient is not profoundly hypotensive or suffering from heart failure associated with severely depressed ventricular systolic function rather than the rapid heart rate ( table 1) [10,11]. (See "Calcium channel blockers in the treatment of cardiac arrhythmias".) If vagal maneuvers, adenosine, and verapamil are all ineffective in terminating orthodromic AVRT, second line therapy choices include intravenous procainamide and beta blockers approved for intravenous administration (propranolol, metoprolol, and esmolol) ( table 1) [12-14]. Procainamide (20 to 50 mg/minute given intravenously while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 17 mg/kg [1.2 g for a 70 kg patient] has been given) slows conduction and prolongs refractoriness in atrial and ventricular myocardium, accessory pathways, and the His-Purkinje system, while having no effect or causing slight shortening of AV nodal refractory period [15,16]. For young children, the dose for procainamide is a bolus given over 15 to 30 minutes (7 to 10 mg/kg bolus for infants <12 months of age compared with 10 to 15 mg/kg bolus for children older than 12 months), followed by an infusion of 20 to 50 micrograms/kg/minute. Procainamide is the preferred drug if the orthodromic AVRT presents as a wide QRS complex tachycardia due to functional or preexisting chronic bundle branch block or if the diagnosis of orthodromic AVRT is in doubt. (See "Wide QRS complex tachycardias: Approach to management".) Metoprolol 2.5 to 5 mg IV bolus over two to five minutes; if no response, an additional 2.5 to 5 mg IV bolus may be administered every 10 minutes to a total dose of 15 mg. Permanent junctional reciprocating tachycardia Permanent junctional reciprocating tachycardia (PJRT) is a persistent tachycardia (with a long RP interval on the surface electrocardiogram) that most often occurs in early childhood and is usually caused by a rare type of orthodromic AVRT involving a slowly conducting concealed accessory pathway, which is usually posteroseptal in location. As implied by the name, PJRT is incessant. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Permanent junctional reciprocating tachycardia'.) Ablation of the accessory pathway is the preferred treatment for PJRT caused by a slowly conducting accessory pathway since this arrhythmia is often refractory to medical therapy. In a cohort of 194 patients (median age at diagnosis 3.2 months, 57 percent less than one year of age) from 11 institutions treated for PJRT between 2000 and 2010, initial medical management https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 4/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate (attempted in 76 percent of patients) led to complete control of the arrhythmia in only 23 percent of patients [17]. An additional 47 percent of patients had clinical improvement with slower and/or less sustained tachycardia, but perfect pharmacologic control is less common. However, in patients presenting with acute symptomatic PJRT, the choice of initial medical therapy is similar to conventional orthodromic AVRT [18]. Adenosine and verapamil can be tried but usually only interrupt PJRT for a few beats. Intravenous procainamide will occasionally result in a longer-lasting interruption of PJRT, but it rarely results in perfect control. As a temporizing measure prior to ablation, effective medical control of PJRT can often be achieved with oral flecainide. (See 'Orthodromic AVRT' above and 'Catheter ablation' below.) Antidromic AVRT In patients with antidromic atrioventricular reciprocating tachycardia (AVRT), antegrade conduction occurs via the accessory pathway with retrograde conduction usually via the AV node (or sometimes via a second accessory pathway if multiple pathways are present). Even though retrograde AV node conduction may be a "weak link" during antidromic AVRT, in the acute setting it is difficult to exclude the possibility of a second accessory pathway as the retrograde limb without formal electrophysiologic testing, and treatment must be done cautiously. Assuming the tachycardia is strictly regular and monomorphic, a trial of a short- acting AV node-specific blocking drug such as adenosine ( algorithm 1) can still be attempted, but failure to convert the tachycardia should make one suspicious of a second accessory pathway participating in the circuit, at which point an alternate agent such as procainamide should be considered. Practically speaking, verification of an antidromic AVRT is difficult outside the electrophysiology laboratory, so the intravenous drug of choice for acute treatment to terminate known or suspected antidromic AVRT is procainamide [2]. Procainamide is typically infused intravenously at 20 to 50 mg/minute given while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 17 mg/kg (1.2 g for a 70 kg patient) has been given. Even if it does not result in tachycardia termination, intravenous procainamide will usually slow the tachycardia rate and improve the hemodynamic state ( table 1). If the diagnosis is not certain, the patient should be considered to have an undiagnosed wide QRS tachycardia; of particular concern is ventricular tachycardia, which can become hemodynamically unstable or even degenerate into ventricular fibrillation following administration of one of these drugs. If uncertainty ever exists about the exact tachycardia mechanism, a presumptive diagnosis of ventricular tachycardia should be made, and the patient https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 5/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate treated accordingly. (See "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway", section on 'Wide complex AVRT' and "Wide QRS complex tachycardias: Approach to the diagnosis" and "Wide QRS complex tachycardias: Approach to management".) Atrial fibrillation with preexcitation In patients with an accessory pathway capable of antegrade conduction who develop AF, conduction to the ventricle often occurs through a combination of the normal conduction pathway (via the AV node) and the accessory pathway. However, because most accessory pathways have a shorter refractory period than the AV node, the ventricular rate can be more rapid if AV conduction occurs preferentially via the accessory pathway. As such, AV nodal blocking drugs (adenosine, verapamil, beta blockers, and digoxin) should be avoided in patients with preexcited AF since blocking the AV node will promote conduction down the accessory pathway and may sometimes directly enhance the rate of conduction over the accessory pathway. (See 'When to avoid AV nodal blockers' below.) The goals of acute drug therapy for preexcited AF are prompt control of the ventricular response and, ideally, termination of AF. If the patient is unstable because of a rapid ventricular response, electrical cardioversion should be performed. For more stable patients, trials of intravenous medications can be performed cautiously. Treatment of preexcited AF requires a parenteral drug with rapid onset of action that lengthens antegrade refractoriness and slows conduction in both the AV node/His-Purkinje system and the accessory pathway. The following is our approach to the acute treatment of patients with preexcited AF, which is consistent with published professional society guidelines [1,2,19]: For patients who are hemodynamically unstable, we recommend urgent electrical cardioversion [1,2,19]. (See "Cardioversion for specific arrhythmias", section on 'External cardioversion/defibrillation'.) For patients who are hemodynamically stable, we suggest initial medical therapy for rhythm control versus rate control. This is based on the greater ease of controlling the ventricular rate in sinus rhythm. While there is no clear first-line medication for rhythm control, options include procainamide and ibutilide [1,2]. Intravenous procainamide is effective for acute therapy of preexcited AF because of its effects on atrial and ventricular myocardium without any AV nodal blocking effect. Because of its effect on atrial myocardium, procainamide may terminate AF; however, if AF persists, the ventricular rate usually slows due to effects on refractoriness and conduction in the accessory pathway. The pediatric experience with ibutilide is very limited, so procainamide is usually the preferred intravenous drug option for preexcited AF in the younger population. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 6/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Procainamide is typically infused intravenously at 20 to 50 mg/minute given while monitoring the blood pressure closely every 5 to 10 minutes until the arrhythmia terminates, hypotension ensues, the QRS is prolonged by more than 50 percent, or a total of 17 mg/kg (1.2 g for a 70 kg patient) has been given. Even if it does not result in tachycardia termination, intravenous procainamide will usually slow the tachycardia rate and improve the hemodynamic state ( table 1). This is often followed by an infusion of 1 to 4 mg/minute. For young children, the dose for procainamide is a bolus given over 15 to 30 minutes (7 to 10 mg/kg bolus for infants <12 months of age compared with 10 to 15 mg/kg bolus for children older than 12 months), followed by an infusion of 20 to 50 micrograms/kg/minute. Ibutilide, a class III antiarrhythmic drug that prolongs the refractoriness of the AV node, His-Purkinje system, and accessory pathway, is useful for acute termination of AF and atrial flutter. In one series of 22 patients with WPW and AF during an electrophysiologic study, ibutilide prolonged the shortest preexcited RR interval and terminated the arrhythmia in 95 percent [20]. (See "Therapeutic use of ibutilide".) For all patients with preexcited AF, we recommend not using standard AV nodal blocking medications (ie, beta blockers, non-dihydropyridine calcium channel blockers [verapamil and diltiazem], digoxin, adenosine, and amiodarone). Blocking the AV node may result in increased conduction of atrial impulses to the ventricle by way of the accessory pathway, increasing the ventricular rate and potentially resulting in hemodynamic instability. (See 'When to avoid AV nodal blockers' below.) The class IC antiarrhythmic drugs flecainide and propafenone and the class III agent dofetilide are effective when used in this setting, but the parenteral formulations of these drugs are not approved for use in some countries, including the United States [21-24]. When to avoid AV nodal blockers AV node-specific antiarrhythmic drugs that are normally used to control the ventricular rate during AF are contraindicated ( table 1) for patients with preexcited AF: Verapamil is perhaps the most dangerous AV nodal blocker to administer to patients with preexcited AF [25-27]. Intravenous verapamil lengthens AV node refractoriness, decreases concealed conduction into the accessory pathway, and has no direct effect on the accessory pathway. Myocardial contractility and systemic vascular resistance are also reduced; these effects may cause a reflex increase in already elevated sympathetic tone that further shortens accessory pathway refractoriness. Precipitation of cardiac arrest by https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 7/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate degeneration of preexcited AF to ventricular fibrillation has been reported after intravenous verapamil administration [27]. Adenosine causes an effect similar to verapamil and also can precipitate ventricular fibrillation. Adenosine will not convert AF and has only a transient effect on the AV node. Its use is contraindicated in AF. Beta blockers, when used alone, do not increase accessory pathway refractoriness. Additionally, inhibition of AV node conduction may enhance the preexcited ventricular rate response by decreasing the degree of concealed retrograde conduction into the accessory pathway. An accessory pathway with a short intrinsic antegrade refractory period that was initially competing with the AV node could then become the dominant route for rapid, antegrade conduction. Amiodarone, which may slow conduction in an accessory pathway during chronic oral administration, is not known to slow accessory pathway conduction with acute IV administration [28,29]. Because amiodarone also has beta blocking properties, it may increase conduction via the accessory pathway, leading to a faster ventricular rate and the potential for ventricular fibrillation [19]. Amiodarone should generally not be used in patients with AF and accessory pathway. Digoxin is also contraindicated because of blockade of AV nodal conduction and its unpredictable effect on accessory pathway refractoriness [30]. The vagomimetic action of digoxin lengthens AV node refractoriness and reduces concealed retrograde conduction into the accessory pathway. TREATMENT TO PREVENT RECURRENT ARRHYTHMIAS Once patients with the Wolff-Parkinson-White syndrome have been stabilized following an acute episode of symptomatic tachyarrhythmia, patients should be evaluated for additional therapy aimed at preventing recurrent symptomatic arrhythmias. The preferred long-term treatment approach for nearly all patients with an accessory pathway, preexcitation, and a symptomatic arrhythmia is catheter ablation of the accessory pathway. However, for patients who are not candidates for ablation procedures, or for very select patients with rare, well-tolerated arrhythmias, antiarrhythmic therapy is an alternative. When antiarrhythmic drugs are used, the choice of agent is determined by the etiology of the arrhythmia and its electrophysiologic properties ( table 1). https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 8/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Catheter ablation For patients with an accessory pathway and symptomatic arrhythmias including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter, we recommend catheter ablation rather than pharmacologic therapy [1]. Initial case-series demonstrated both the safety and efficacy of this approach, data which have been replicated in numerous studies [31-37]. The standard energy source used to ablate accessory pathways is radiofrequency current, although cryoenergy can be used as an alternative to radiofrequency energy to ablate accessory pathways that are in close proximity to the AV node or bundle of His [38]. (See "Overview of catheter ablation of cardiac arrhythmias".) Indications for ablation Patients with an accessory pathway are candidates for ablation in the following settings: Symptomatic tachyarrhythmias. Occupations in which the development of symptoms would put themselves or others at risk (eg, truck drivers or airline pilots, some athletes). Selected asymptomatic patients. (See 'Asymptomatic patients' below.) Symptomatic patients Symptom control is the most common indication for ablation. The 2015 ACC/AHA/HRS guidelines on the management of supraventricular arrhythmias recommended catheter ablation as a first-line therapy for patients who have had symptomatic AVRT or preexcited AF [1]. Asymptomatic patients The optimal approach is controversial in asymptomatic patients who are coincidentally found to have evidence of an accessory pathway on an ECG (ie, WPW pattern) [39-41]. The risk of sudden cardiac death (SCD) is low, and the risk of developing symptoms also appears to be low, although a wide range of incidences have been reported [42,43]. Among those with a WPW ECG pattern, the likelihood of developing symptoms varies with age. Children are at the highest risk, while those who remain asymptomatic over age 35 years are unlikely to develop symptoms [40]. In a prospective study of 550 asymptomatic patients with WPW ECG pattern who were followed for a median of 22 months, 13 patients (2.4 percent) developed ventricular fibrillation (VF) [44], most of whom (11 of 13) were children. Fortunately, all of the patients developed warning symptoms (usually presyncope or dizziness) and sought medical attention, and none died from the VF episode. The 2015 ACC/AHA/HRS guidelines state that observation of patients with WPW pattern alone is reasonable; however, the guidelines also state that catheter ablation is reasonable in asymptomatic patients [1]. Additionally, in a 2012 consensus statement on the management of asymptomatic young patients with the WPW pattern, ablation is recommended for patients felt https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 9/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate to be at higher risk of SCD based on the results of electrophysiologic testing [45]. (See "Wolff- Parkinson-White syndrome: Anatomy, epidemiology, clinical manifestations, and diagnosis", section on 'Electrophysiology studies (EPS)'.) For most asymptomatic patients with preexcitation, particularly those over age 35 to 40 years, we suggest observation. However, in some asymptomatic patients, particularly children, who are felt to be at higher risk of an arrhythmia or SCD, we suggest risk stratification to identify individuals who may benefit from treatment ( algorithm 2). Localizing the accessory pathway The location of most accessory pathways can be estimated using the preexcitation pattern on the surface electrocardiogram. However, more precise localization of the accessory pathway during catheter-based mapping prior to catheter ablation utilizes several parameters [34]. To determine the atrial insertion site, the earliest site of retrograde atrial activation during orthodromic atrioventricular (AV) reciprocating tachycardia (AVRT) or ventricular pacing must be identified [46,47]. The assumption is that the local retrograde ventriculoatrial (VA) interval on the recording electrode will be shortest at the atrial insertion site. Compared with pacing at sites more remote from the accessory pathway, atrial pacing near the atrial insertion of the accessory pathway will create a greater degree of preexcitation with a shorter delay between the stimulus and the onset of the delta wave [48]. More precise localization of the ventricular insertion site is obtained by mapping along the AV groove in sinus rhythm to determine the site of earliest ventricular activation during preexcited beats. Local ventricular activation at the ventricular insertion site frequently precedes the onset of the delta wave on the surface ECG by 10 to 40 milliseconds ( waveform 2) [49,50]. If preexcitation is minimal in sinus rhythm, then atrial pacing can be performed to facilitate ventricular preexcitation by delaying AV nodal conduction. Efficacy The acute success rate with catheter-based ablation is approximately 85 to 95 percent but can approach 100 percent depending upon the location of the accessory pathway and the precision of pathway localization [34-37,44]. Success rates are lower (84 to 89 percent) for septal accessory pathways ( waveform 3 and waveform 4) [31,32,35,36,51-55]. Additionally, long-term success rates may be closer to 80 percent at five years post-ablation [56]. As examples of the efficacy of ablation: In a meta-analysis that included data from 64 studies, including 3495 patients undergoing radiofrequency catheter ablation (RFA) and 749 patients undergoing cryoablation of septal accessory pathways, acute procedural success was similar with either approach (89 versus https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 10/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate 86 percent with RFA versus cryoablation, respectively) [55]. Long-term success rates were higher with RFA (88 versus 76 percent with cryoablation), although cryoablation resulted in lower risk of persistent AV block (0 versus 3 percent with RFA). In a study of 519 patients from a single, large volume center who underwent EP study and radiofrequency ablation of accessory pathways in the late 1990s and were followed for an average of 22 months, accessory pathway conduction was abolished in 92 percent of patients, although one or two additional ablation procedures were required in 6 percent [54]. In a single-center, prospective observational study of 1168 patients who underwent RFA between May 2005 and May 2010 and were followed for a median of eight years, there were no episodes of ventricular fibrillation or sudden cardiac death [44]. In addition to location (ie, septal, lateral, etc) of the accessory pathway, the efficacy of catheter ablation can be affected by the presence of multiple accessory pathways and the depth of the accessory pathway within the myocardial (ie, epicardial versus endocardial). Multiple accessory pathways Multiple accessory pathways are found in as many as 13 percent of patients with WPW syndrome. Ablation of multiple accessory pathways is possible, but it requires a longer procedure time and is associated with a higher rate of recurrence [35,57,58]. As an example, in one study of 858 patients undergoing EP study and ablation for WPW syndrome in which multiple accessory pathways were identified in 8.5 percent of patients, procedural success was similar for single and multiple pathways, but the rate of recurrent arrhythmias over a mean follow-up of 43 months was significantly higher in persons with multiple accessory pathways (9.5 versus 2.5 percent) [58]. Epicardial accessory pathway location One reason that catheter ablation may fail is with an accessory pathway that is located closer to the epicardial surface. In such patients, the usual ablation procedure via transvenous catheters at the endocardial surface may not affect the critical tissue. Although not widely done, percutaneous epicardial ablation is possible via subxiphoid access of the pericardial space. The feasibility of this approach was demonstrated in a report of 48 patients with a variety of arrhythmias (10 with WPW syndrome) who had failed endocardial ablation [59]. Via subxiphoid instrumentation, 5 of the 10 patients had accessory pathways localized to the epicardial surface, and three were successfully ablated. Catheter ablation is also effective in the treatment of PJRT. From a cohort of 194 patients (median age at diagnosis 3.2 months, 57 percent less than one year of age) from 11 institutions treated for PJRT between 2000 and 2010, 140 patients underwent a total of 175 catheter ablation https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 11/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate procedures [17]. PJRT was successfully eliminated in 90 percent of patients, with minor complications reported in only 9 percent of patients, and no major complications. Arrhythmia recurrence Recurrent arrhythmias involving an accessory pathway, manifested by return of delta waves on the electrocardiogram or spontaneous paroxysmal supraventricular tachycardia, have been reported in 5 to 12 percent of patients [36,51,52,58,60]. The recurrence rate is higher with ablation of multiple pathways or right free wall or septal accessory pathways [53,58,60]. Approximately one-half of recurrences occur in the first 12 hours after the procedure [60]. Repeat ablation usually leads to permanent cure in patients who experience a recurrence [60]. To unmask any residual conduction via an accessory pathway prior to ending the ablation procedure, intravenous adenosine can be administered to transiently block the AV node. We primarily use adenosine when there is difficulty determining if the pathway has been successfully ablated. AF can recur following accessory pathway ablation; however, the ability for AF to be preexcited with conduction via an accessory pathway should be reduced or eliminated following ablation. In a series of 91 patients with documented paroxysmal AF prior to successful ablation of an accessory pathways, 18 (20 percent) had recurrent episodes of AF at two-year follow-up, although advancing age was the only independent predictor of recurrent AF on multivariate analysis [61]. Complications Data on complication rates come from both case series and a voluntary national registry. The reported incidence of nonfatal complications is on the order of 2 to 4 percent, which is similar to rates seen with ablation procedures for other arrhythmias [35,36,45]. (See "Overview of catheter ablation of cardiac arrhythmias", section on 'Complications'.) The incidence and nature of complications in general clinical practice was illustrated in a report from a voluntary national registry in the United States of 3357 patients undergoing EP study and ablation for a variety of indications [36]. Among the 654 patients treated for WPW syndrome, major procedural complications occurred in 2 percent, most commonly cardiac tamponade. Specific complications may occur that are related to the anatomic site of ablation, including complete AV block resulting from ablation of a septal accessory pathway near the AV node, acute interatrial shunting related to transseptal catheterization for ablation of left-sided accessory pathways (although there are usually no adverse long-term sequelae), and inappropriate sinus tachycardia may be present following ablation of a posteroseptal accessory pathway, suggesting disruption of the parasympathetic and/or sympathetic innervation of the sinus and AV nodes [62-68]. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 12/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate Surgical ablation Prior to the advent of catheter-mediated radiofrequency ablation, surgical ablation of accessory pathways was the standard technique in patients with drug-refractory WPW syndrome. The long-term success rate for WPW surgery is now almost 100 percent with an operative mortality rate of less than 1 percent [69-71]. Despite these excellent outcomes, catheter-mediated radiofrequency ablation has emerged as the preferred therapy for treatment of accessory pathways. However, surgical ablation remains an effective treatment strategy in patients suffering from highly symptomatic and hemodynamically unstable, drug-refractory arrhythmias in whom radiofrequency energy catheter ablation has failed, when performed at centers with a proven track record of success in performing the procedure [72]. Medical therapy for arrhythmia prevention For patients with an accessory pathway and symptomatic arrhythmias (including orthodromic AVRT, antidromic AVRT, and preexcited AF or atrial flutter) who are not candidates for or who refuse ablation of the accessory pathway, we suggest pharmacologic therapy aimed at preventing further arrhythmias and/or slowing the ventricular response rate [1]. Chronic therapy with verapamil or digoxin should be avoided in all patients with WPW syndrome. For recurrent orthodromic AVRT The efficacy of an antiarrhythmic drug in preventing orthodromic atrioventricular reciprocating tachycardia (AVRT) is related to its ability to alter the electrophysiologic properties of the circuit, rendering it incapable of sustaining reentry. Antiectopic activity to decrease the number of arrhythmia triggers (eg, premature atrial complex [PACs; also referred to a premature atrial beat, premature supraventricular complex, or premature supraventricular beat] and ventricular premature beats) is another desirable effect. The class IC antiarrhythmic drugs flecainide and propafenone ( table 2) possess the most favorable benefit/risk ratio and are the drugs of choice for prevention of recurrent orthodromic AVRT [73-76]. An important exception is the presence of known coronary disease, a setting in which class IC drugs can increase mortality due to proarrhythmia [77]. Both flecainide and propafenone have been approved for prevention of paroxysmal supraventricular tachyarrhythmias, including orthodromic AVRT. Propafenone has a potential advantage since it also has mild beta blocking activity [75,76]. Beta blockers are still occasionally used as second-line therapy for chronic suppression of orthodromic AVRT in patients with "low-risk" WPW accessory pathways (eg, only intermittently manifest or know to have a long effective refractory period), but they are not advised for patients who have developed or may develop preexcited AF. Chronic therapy with verapamil or digoxin should be avoided in all patients with WPW syndrome. https://www.uptodate.com/contents/treatment-of-arrhythmias-associated-with-the-wolff-parkinson-white-syndrome/print 13/40 7/6/23, 11:14 AM Treatment of arrhythmias associated with the Wolff-Parkinson-White syndrome - UpToDate The class IA antiarrhythmic drugs ( table 2) lengthen antegrade and retrograde refractoriness and slow conduction in the accessory pathway. However, these drugs are less potent than the class IC drugs, they only minimally lengthen AV node refractoriness, and they have a substantial risk of intolerable noncardiac adverse effects. Amiodarone has multiple electrophysiologic effects that make it effective in suppressing orthodromic AVRT, including beta blocking activity, class III effects to prolong action potential repolarization, blockade of the fast sodium and slow calcium inward currents, and suppression of ectopic beats [78-80] (see "Amiodarone: Clinical uses"). These effects result in slowing of impulse conduction and lengthening of refractoriness in both the bypass tract and the AV node/His-Purkinje system. However, it has a number of common adverse effects, including pulmonary, thyroid, and hepatic toxicity, which is a concern for patients with WPW who are often young and may require many years of therapy. (See "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) For recurrent antidromic AVRT Ablation of the accessory pathway is the preferred therapy