++
APs are important because they provide a substrate for antidromic and orthodromic AV reciprocating tachycardia, are associated with sudden cardiac death, and may be detected in asymptomatic patients on a routine screening ECG. The sections that follow cover the pathophysiology, diagnosis, and management of this fascinating clinical entity.
++
APs are anomalous, typically extranodal connections that connect the epicardial surfaces of the atrium and ventricle along the AV groove. Accessory bypass tracts, which conduct antegrade from the atrium to the ventricle and, therefore, are detectable on an ECG, are reportedly present in 0.15% to 0.25% of the general population. A higher prevalence of 0.55% has been reported in first-degree relatives of patients with WPW syndrome.
++
APs can be classified based on their site of origin and insertion, location along the mitral or tricuspid annulus, type of conduction, and properties of conduction (decremental or nondecremental). APs usually exhibit rapid, nondecremental conduction, similar to that which is present in normal His-Purkinje tissue and atrial or ventricular myocardium. Approximately 8% of APs display decremental antegrade or retrograde conduction. Whereas APs that are capable only of retrograde conduction are referred to as concealed, those capable of antegrade conduction are referred to as manifest, demonstrating preexcitation on a standard ECG (Fig. 84–9). APs usually conduct both antegrade and retrograde. Antegrade-only APs are particularly uncommon. When present, they are usually right sided and frequently demonstrate decremental conduction (Mahaim fiber). Concealed APs are less common, accounting for approximately 15% of all APs. Patients with Ebstein anomaly who also have WPW syndrome frequently have more than one AP.
++
++
Variant APs include those that connect the atrium to the distal or compact AV node (James fibers), the atrium to the His bundle (the Brechenmacher fiber), and the AV node or His bundle to the distal Purkinje fibers or ventricular myocardium (the Mahaim fibers) (see Fig. 84–1B).
+++
Concept of Preexcitation
++
The hallmark of an AP function during sinus rhythm is depolarization of all or part of the ventricles earlier than expected if conduction has occurred only over the normal AV conduction system, resulting in preexcitation (Fig. 84–10).
++
++
The degree of shortening of the PR interval and the extent of ventricular preexcitation depend on several factors, including location of the AP, the relationship between antegrade conduction times and refractory periods of the AV bypass tract, and the normal AV conduction system. A bypass tract that crosses the AV groove in the left lateral region may also result in inapparent preexcitation and minimal PR interval shortening during sinus rhythm because of greater interatrial distance for impulse propagation from the sinus node to this site of atrial input into the AP. Conversely, an AP on the right side is more likely to demonstrate marked preexcitation. Preexcitation may be less apparent during sinus tachycardia, when sympathetic tone is high and vagal tone low, resulting in faster AV node conduction time than that in the AP. On the other extreme, during conditions of slowed conduction through the AV node by intrinsic nodal factors, withdrawal of sympathetic tone, or increased vagal tone, the amount of preexcitation apparent on the 12-lead ECG is maximized because of relatively greater conduction through the AP. Rapid intravenous administration of adenosine causing blocking or slowing of AV node conduction and exposing the anterograde AP conduction has been used as a diagnostic maneuver. The degree of preexcitation can also be enhanced with atrial pacing directly over the AP, eliminating the intra-atrial conduction delay from the sinus node to the atrial insertion site of AP (Fig. 84–11).
++
++
Intermittent preexcitation is characterized by abrupt loss of delta wave, normalization of the QRS duration, and an increase in the PR interval during a continuous ECG recording, often despite only minor variations in resting sinus rhythm heart rate. This should be distinguished from day-to-day variability in preexcitation or inapparent preexcitation caused by factors described above. The presence of intermittent preexcitation has been considered to suggest that the refractory period in the AP is long, making them very unlikely to mediate a rapid, preexcited ventricular response during atrial fibrillation.
+++
Tachycardias Associated with Accessory Pathways
++
Tachycardias associated with APs can be subdivided into those in which the AP is necessary for initiation and maintenance of tachycardia and those in whom the AP acts as a bystander.
++
AVRT is a macro-reentrant tachycardia involving the atrium, the AP, the AV node, and the ventricle. AVRT is further subclassified into orthodromic and antidromic AVRT (Fig. 84–12). During orthodromic AVRT, the reentrant impulse uses the AV node and specialized conduction system for conduction from the atrium to the, ventricle and uses the AP for conduction from the ventricle to the atrium. Orthodromic AVRT can be initiated by atrial or ventricular premature depolarizations (atrial premature beats [APDs] or ventricular premature beats [VPDs]). APDs initiating the tachycardia block antegradely in the AP and conduct relatively slowly over the AV nodal tissue to the ventricles. The impulse then retrogradely conducts over the AP reentering the atria at the atrial insertion site of the pathway, thus completing the reentrant loop (Fig. 84–13). A VPD, conversely, blocks in the His-Purkinje system and retrogradely reaches the atria through retrogradely conducting AP. The impulse then antegradely conducts through the AV nodal tissue, completing the circuit. The QRS complex during orthodromic AVRT hence is not preexcited.
++
++
++
During antidromic AVRT, however, the reentrant impulse travels in the reverse direction, with conduction from the atrium to the ventricle occurring via the AP. Antidromic AV reciprocating tachycardia is rare, occurring in only 5% to 10% of patients with WPW syndrome. APDs that occur at a coupling interval that is longer than the refractory period of the AP and shorter than the AV nodal refractory period can initiate the antidromic AVRT; the converse is true with a VPD. Susceptibility of antidromic AVRT appears to depend on the existence of adequate separation between the AP and the AV nodal tissue. Hence, most of the antidromic AVRTs seem to occur only with left-sided bypass tracts.
++
Other forms of SVTs, including atrial tachycardia, junctional tachycardia, AVNRT, and even ventricular tachycardia, may occur in patients with bypass tracts. Dual AV nodal physiology has been noted in nearly 12% of patients with WPW syndrome. Coexisting ventricular tachycardia is less likely because patients with WPW syndrome tend to present at a younger age and have less structural heart disease.
++
Atrial fibrillation is a less common, but potentially more serious, arrhythmia in patients with the WPW syndrome. If an AP has a short antegrade refractory period, atrial fibrillation may result in a rapid ventricular response with subsequent degeneration to ventricular fibrillation.11,12,13 The risk of sudden death has been shown to be higher if the shortest R-R interval is less than 250 ms during spontaneous or induced atrial fibrillation.11 It has been estimated that one-third of patients with WPW syndrome also have atrial fibrillation. APs appear to play a pathophysiologic role in the development of atrial fibrillation in these patients, because most are young and do not have structural heart disease. Furthermore, surgical or catheter ablation of APs usually results in elimination of atrial fibrillation as well.
++
Preexcitation occurs in the general population at a frequency of around 1.5 per 1000. Of these, 50% to 60% of patients become symptomatic. Approximately one-third of all patients with PSVT are diagnosed as having an AP-mediated tachycardia. Patients with AP-mediated tachycardias most commonly present with the syndrome of PSVT. Population-based studies have demonstrated a bimodal distribution of symptoms for patients with preexcitation, with a peak in early childhood followed by a second peak in young adulthood. Nearly 25% of patients will become asymptomatic over time. More than half the patients with an episode will experience a recurrence.
++
Symptoms range from palpitations to syncope. As in AVNRT, episodes of tachycardia may be associated with dyspnea, chest pain, decreased exercise tolerance, anxiety, dizziness, or syncope. Although syncope is often considered a bad prognostic sign, the evidence is not clear. Physical examination demonstrates a fast, regular pulse with a constant-intensity first heart sound. The jugular venous pressure waveform is usually constant, but it can sometimes be elevated. The incidence of sudden cardiac death in patients with WPW syndrome has been estimated to range from 0.15% to 0.39%.11,12,13 It is distinctly unusual for cardiac arrest to be the first symptomatic manifestation of WPW syndrome. A recent report by Bunch et al compared the outcomes of 872 WPW patients who underwent ablation, 1461 WPW patients who did not have ablation, and 11,175 control patients.14 Among all WPW patients, the mortality and incidence of sudden death was no different than in the control population. However, the risk of atrial fibrillation was greater in WPW patients. It is also notable that patients with WPW who underwent ablation had a lower mortality than those who did not. Surprisingly, however, there was no difference in the incidence of sudden death in these two groups. Given the high prevalence of atrial fibrillation among patients with WPW syndrome and the concern for sudden cardiac death resulting from rapid preexcited atrial fibrillation, the low annual incidence of sudden death among patients with WPW syndrome is reassuring.
++
Patients with functioning AV bypass tracts tend to have certain congenital abnormalities, particularly Ebstein anomaly of the tricuspid valve. Nearly 10% of patients with Ebstein anomaly have preexcitation. APs also commonly occur in patients with corrected transposition of great vessels. In this case, the Ebstein anomaly of the left (tricuspid) valve is associated with APs to the functioning systemic ventricle (anatomic right ventricle). In addition, multiple bypass tracts are frequently seen in patients with Ebstein anomaly. Conversely, of patients with WPW syndrome presenting with SVT early in childhood, only 5% have Ebstein anomaly, even though it is the most common from of congenital heart disease associated with WPW syndrome.
+++
Electrocardiographic Characteristics
++
The ECG hallmark of an antegradely conducting AP is the delta wave along with a shorter than usual PR interval. Conversely, the presence of retrograde conduction only in an AP will not be apparent on a surface ECG during sinus rhythm. Whereas ECG during orthodromic AVRT has a normal QRS complex with retrogradely conducting P wave after the completion of the QRS complex in the ST segment or early in the T wave (see Fig. 84–4), the QRS during antidromic AVRT is fully preexcited.
++
Numerous algorithms have been described to localize the site of the AP using the axis of the delta wave and QRS morphology. The location of the AP along the AV ring is classified variously into five or ten regions, which can be broadly divided into those on the left and the right of the AV groove. Distribution along these lines is not homogenous. Some 46% to 60% of the pathways are found on the left free wall space. Nearly 25% are within the posteroseptal and midseptal spaces, 15% to 20% in the right free wall space, and 2% in the anteroseptal space. A simple algorithm that includes both the delta wave axis and the QRS axis is shown in Fig. 84–14.
++
++
ST-segment depression may also occur during orthodromic AVRT. It may occur even in young individuals, who are unlikely to have coronary artery disease. The location of the ST-segment depression may vary with the location of the AP. ST-segment depression in V3 to V6 is almost invariably seen with a left lateral pathway; a negative T wave in the inferior leads is associated with a posteroseptal or posterior pathway; and a negative or notched T wave in V2 or V3 with a positive retrograde P wave in at least two inferior leads suggests an anteroseptal pathway. However, ST-segment depression occurring during orthodromic AVRT episodes in older patients or associated with symptoms of ischemia mandate the consideration of coexisting coronary artery disease.
+++
Electrophysiologic Testing
++
EPS in patients with AVRT is done to not only confirm the presence of an AP and differentiate this condition from other forms of SVT, but also to find the pathway participating in the tachycardia and aid in ablative therapy.
++
By definition, if an AP is present and conducting antegradely, some part of the ventricle begins activation earlier than expected, so that the HV interval is less than normal at rest (see Fig. 84–10). Because the QRS complex is a fusion complex of conduction down both the AV node and the AP, slowing of conduction down the normal pathway results in an increasing degree of preexcitation.
++
Eccentric atrial activation with ventricular pacing makes it easy to identify the presence of an AP (Fig. 84–15). Retrograde conduction over most APs is nondecremental. Hence, in the absence of intraventricular conduction delay or the presence of multiple bypass tracts, the VA conduction time is the same over a range of pace cycle lengths (see Fig. 84–15). The exception to this is the slowly conducting decremental posteroseptal pathway found in the permanent form of junctional reciprocating tachycardia, in which the VA conduction time increases with increasing ventricular pacing rate.
++
++
It is important and often challenging to differentiate retrograde conduction over septal pathway from conduction over the normal AV system. One maneuver that can make this differentiation is differential pacing (ie, pacing both from the right ventricular apex and the right ventricular base) and measuring the VA conduction time. Retrograde conduction over the normal AV conduction system is fastest when pacing from the apex because conduction can occur rapidly over the His-Purkinje system. VA intervals are longer when the pacing site is moved from the apex to the base. The converse is true in the presence of an AP, with VA intervals shortest when pacing from the base, closer to the site of pathway insertion, than from the apex. The technique of para-Hisian pacing is useful in differentiating the anteroseptal pathway from AVNRT.
++
Development of BBB aberration during tachycardia can be useful in determining both presence of, and participation of, an AP in tachycardia (Fig. 84–16). An increase in tachycardia cycle length caused by an increase in VA conduction time with functional BBB is consistent with the presence of an AP ipsilateral to the BBB.
++
+++
Catheter Ablation of Accessory Pathways
++
Catheter ablation of APs is performed in conjunction with a diagnostic EPS. After the AP has been localized to a region of the heart, precise mapping and ablation are performed using a steerable electrode catheter. No prospective, randomized clinical trials have evaluated the safety and efficacy of catheter ablation of APs. However, the results of catheter ablation of APs have been reported in a large number of other trials.5,8,9,15,16,17,18,19,20,21 The largest prospective, multicenter clinical trial to evaluate the safety and efficacy of RF ablation was reported by Calkins and colleagues.5 This study involved analysis of 1050 patients, of whom 500 had APs. Overall success of catheter ablation in curing APs was 93%. The success rate for catheter ablation of left free wall APs was slightly higher than for catheter ablation of right-sided APs (95% vs 90%, P = .03). After an initially successful procedure, recurrence of AP conduction was found in approximately 5% of patients. The recurrence-free interval postablation was also best with left-sided pathways (Fig. 84–17). APs that recur can usually be successfully ablated again. Complications associated with catheter ablation of APs may result from obtaining vascular access (hematomas, deep venous thrombosis, perforation of the aorta, arteriovenous fistula, pneumothorax), catheter manipulation (valvular damage, microemboli, perforation of the CS or myocardial wall, coronary dissection or thrombosis), or delivery of RF energy (AV block, myocardial perforation, coronary artery spasm or occlusion, transient ischemic attacks, or cerebrovascular accidents).
++
++
Calkins and coworkers,5 reported the incidence of major complications in their trial to be 3% and of minor complications around 8%. The procedure-related mortality associated with catheter ablation of APs has ranged from 0% to 0.2%. The two most common types of major complications reported during catheter ablation of APs are inadvertent complete AV block and cardiac tamponade. The incidence of inadvertent complete AV block ranges from 0.17% to 1.0%. Most instances of complete AV block occur in the setting of the ablation of septal and posteroseptal APs. The frequency of cardiac tamponade as a result of the ablation of APs varies between 0.13% and 1.1%.
++
In the past several years, cryoablation has become available as an alternative energy source for creation of myocardial lesions, which can be used for catheter ablation of APs. The main advantage of cryoenergy compared with RF energy is that the risk of heart block appears to be lower.16 This potential benefit must be balanced against longer procedure times and lower acute and long-term efficacy.16 Because of the lower acute and long-term success rates of catheter ablation of APs using cryoenergy, this energy source is generally used only for ablation of APs located in the anteroseptal and para-Hisian locations.
++
Antiarrhythmic drugs represent one therapeutic option for management of patients with AP-mediated arrhythmias (see Table 84–4). Antiarrhythmic drugs that primarily modify conduction through the AV node include verapamil, β-blockers, and adenosine. In contrast, the antiarrhythmic drugs, which primarily modify conduction across the AP, consist of class 1 drugs such as procainamide, propafenone, and flecainide as well as class 3 antiarrhythmic drugs such as sotalol and amiodarone. The approach to acute termination of these arrhythmias generally differs from that used for long-term suppression and prevention of further episodes of SVT. In general, the approach used does not vary based on the specific tachycardia mechanism, which generally is unknown when the patient first presents to an emergency department. Pharmacologic agents are in general more effective in terminating an acute episode of tachycardia than in preventing future recurrences. Verapamil or diltiazem should not be administered intravenously to patients with atrial fibrillation and preexcitation because they may accelerate conduction through the AP and precipitate a cardiac arrest.
++
There have been no controlled trials of drug prophylaxis involving patients with AV reentry. However, a number of small, nonrandomized trials have been performed which have demonstrated reasonable effectiveness of propafenone, flecainide, and amiodarone.
+++
Management Considerations
+++
Management of Asymptomatic Preexcitation
++
Most patients with asymptomatic preexcitation have a good prognosis. Because of the small, but real, risks associated with invasive procedures, EPS is not mandated for risk stratification or ablative therapy. The ACC/AHA/HRS Guidelines for Management of Patients with Supraventricular Arrhythmias gives electrophysiologic testing and catheter ablation when indicated a 2A classification for treatment of patients with asymptomatic preexcitation.1 A 2A designation means that it is reasonable to offer EPS with or without ablation in selected patients after a thorough discussion of the risks and benefits of the procedure. Similar recommendations have been made in the PACES/HRS Expert Consensus Statement on the Management of Asymptomatic Young Patients with a WPW ECG Pattern.14
++
Several noninvasive and invasive tests have been proposed as useful in stratifying patients for the risk of sudden death.1,17 The detection of intermittent preexcitation—which is characterized by an abrupt loss of the delta wave, normalization of the QRS complex, and an increase in the PR interval during a continuous ECG recording—is evidence that an AP has a relatively long refractory period and is unlikely to precipitate ventricular fibrillation. The loss of preexcitation after administration of antiarrhythmic drugs such as procainamide or ajmaline has also been used to indicate a low-risk subgroup. These noninvasive tests are generally considered inferior to EPS in the assessment of risk of sudden cardiac death. Because of this, they play little role in patient management at present.
++
When screening studies are performed in patients with asymptomatic preexcitation, approximately 20% of those who are asymptomatic will demonstrate a rapid ventricular rate during atrial fibrillation induced at EPS. Studies have identified markers that identify patients at increased risk. These include (1) a short preexcited R-R interval below 250 ms during spontaneous or induced atrial fibrillation, (2) a history of symptomatic tachycardia, (3) multiple APs, and (4) Ebstein anomaly.1,17,18 A short preexcited R-R interval during atrial fibrillation above 250 ms has been reported to have a negative predictive value greater than 95%.
++
More recent evidence makes a stronger case for use of EPS in risk stratifying all asymptomatic patients with preexcitation.23 Pappone and coworkers24 studied 212 consecutive asymptomatic WPW patients after a baseline EPS over 5 years. After a mean follow-up of 37.7 months, 33 patients became symptomatic. Of these, 29 had inducible SVT on EPS, and only 4 were not inducible. More importantly, there were three sudden deaths in the entire population, and all of them occurred in patients in whom AVRT and atrial fibrillation were inducible during EPS. In a more recent study, Pappone and colleagues (24) examined the role of prophylactic catheter ablation in children with asymptomatic preexcitation. Of the 165 eligible children, 60 were determined to be at high risk of an arrhythmia based on their results of EPS. Of these 60 patients, 20 underwent prophylactic catheter ablation, 27 had no treatment, and 13 withdrew from the study. During a mean follow-up of 34 months, 1 child in the ablation group (5%) and 12 in the control group (44%) had arrhythmic events. Among these 12 patients in the control group, 2 experienced ventricular fibrillation, and one died suddenly.
++
Santinelli and coworkers25,26 published two papers describing the natural history of asymptomatic preexcitation. Among 293 adults with asymptomatic preexcitation followed for a median of 67 months, 31 patients (10.6%) developed a first arrhythmic event. Among these patients, the event was classified as potentially life threatening in 17 patients. One of these patients experienced a cardiac arrest. Multivariate analysis identified inducibility, an anterograde effective refractory period shorter than 250 ms as predictive of potentially life-threatening arrhythmias.24 And among 184 children with asymptomatic preexcitation followed for a median of 57 months, 51 patients (28%) developed a first arrhythmic event. Among these patients, the event was classified as potentially life threatening in 19 patients. Three of these patients experienced a cardiac arrest. Multivariate analysis identified an anterograde effective refractory period shorter than 240 ms and the presence of multiple APs as predictive of potentially life-threatening arrhythmias.25,26 Pappone et al went on to publish an outcome registry involving 2169 WPW patients followed for 8 years27; among this group, 1001 (550 asymptomatic) did not undergo ablation and 1168 (206 asymptomatic) did have ablation. VF occurred during follow-up in 1.5% of patients who did not have catheter ablation. In contrast, no patients with WPW who underwent ablation experienced VF during follow-up. Based on the results of these studies, as well as the well-established safety and efficacy of catheter ablation of APs, an increasing proportion of electrophysiologists, particularly pediatric electrophysiologists, now advocate screening EPS and prophylactic catheter ablation when a high-risk AP is uncovered. The recommendations made for management of asymptomatic preexcitation in the AHA/ACC/HRS 2015 SVT Guidelines are summarized in Table 84–5.
++
+++
Management of Symptomatic Wolff-Parkinson-White Syndrome
++
The ACC/AHA/HRS Guidelines for Management of Patients with SVT states that catheter ablation is considered first-line therapy (class 1) and the treatment of choice for patients with WPW syndrome (ie, patients with manifest preexcitation along with symptoms).1,19,20 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. Catheter ablation is also considered first-line therapy (class 1) for patients with PSVT involving a concealed AP. However, because concealed APs are not associated with an increased risk of sudden cardiac death in these patients, catheter ablation can be presented as one of a number of potential therapeutic approaches, including pharmacologic therapy and clinical follow-up alone (see discussion of management of AVNRT). When pharmacologic therapy is selected for patients with concealed APs, it is reasonable to consider a trial of β-blocker therapy, CCB therapy, or a class 1C antiarrhythmic agent. It is important to note that β-blockers and CCBs generally are not recommended for the management of patients who have evidence of preexcitation.
++
The recommendations for the acute and long-term management of patients with AP-mediated arrhythmias developed by the ACC/AHA/HRS are shown in Tables 84–6 and 84–7.1 Catheter ablation is considered class 1 therapy for treatment of patients with WPW syndrome and for those with AVRT in the absence of preexcitation.
++
++