What Preexcitation Wrought: Wolff-Parkinson-White

History

In their 1930 case series and three-lead EKG analysis of 11 healthy patients with a propensity for paroxysmal tachycardia, Drs. Wolff, Parkinson, and White described most of the phenomena associated with the condition that now bears their name.¹ Specifically, they observed short PR intervals with bundle branch block aberrancy that normalized with exercise or parasympathetic inhibition, all in patients that had little other organic heart disease. In an unfortunate subset of the patients exhibiting these phenomena, symptoms had lasted for decades. The electrophysiological substrate leading to this condition (and the road toward definitive treatment), namely an accessory atrioventricular (AV) conduction pathway, remained a matter of speculation until 1943. ² Definitive treatment of the accessory pathway (AP) would not be undertaken until decades later, with surgical approaches, later followed by catheter-based approaches. ^3-5 In the present day, symptomatic patients undergo catheter ablation with over 90% success rates,6 faring significantly better than the initial cohort of Wolff, Parkinson, and White.

Pathophysiology and EKG Findings

The Wolff-Parkinson-White (WPW) pattern on EKG consists of: 1) a short PR interval of less than 120 msec, and 2) a widened QRS complex. The PR is shortened due to conduction down the accessory pathway, which bypasses the delaying effects of the AV node and depolarizes the ventricle sooner than expected. Widening of the QRS results from the fusion of bypass-tract conduction with normal AV nodal conduction, leading to varying degrees of bundle branch block aberrancy. The ventricle is thus said to be pre-excited by the AP conduction preceding normal excitation via the AV node (Figure 1). The morphologic pattern of the beginning of the QRS complex is called the delta wave. The WPW syndrome is the combination of clinical arrhythmia and delta waves on EKG; clinical tachycardia occurs in 20-30 percent of patients with the EKG pattern in natural-history studies. ⁷ Definitive treatment of the WPW syndrome, namely catheter ablation, is guided partly by localization of the AP on the surface EKG. Several algorithms have been developed for precise determination of the AP site. Often, the polarity of the delta wave in the lateral and inferior leads can provide initial clues to the AP location. In the example in Figure 1, the delta wave is positive in the lateral leads, negative in V1, and isoelectric to mildly positive in the inferior leads, pointing to a posteroseptal location.

Tachycardias Arising from WPW

Tachyarrhythmias arising from WPW syndrome can include AV reciprocating (or reentrant) tachycardia (AVRT), atrial flutter (AFL), or atrial fibrillation (AF). AVRT is a reentrant circuit involving the atrium, AV node, ventricle, and accessory pathway. A tachycardia consisting of conduction in that direction, namely anterograde down the AV node and back up the AP, is called orthodromic AVRT. As the atrial signal reaches the ventricle completely through the AV node in this case (i.e., a normal conduction pattern), the QRS will be narrow during the tachycardia (Figure 2). If conduction proceeds in the opposite direction (i.e., down the AP and retrograde through the AV node), it is antidromic AVRT. The QRS in such a rhythm will be wide, owing to slower ventricular depolarization over the muscular AP rather than via the rapid, specialized His-Purkinje system. Besides tachyarrhythmias involving the AP itself, patients with WPW syndrome have increased susceptibility to atrial fibrillation and atrial flutter. Paroxysmal AF (PAF) is seen in up to one-third of patients with WPW syndrome. ⁸ An early investigation into this relationship by Rosen and colleagues looked at 88 WPW patients at the University of Illinois at Chicago between 1972 and 1980, and assessed the differences between the 34% of patients with PAF and those without it. ⁸ They found that 77% of the PAF patients were inducible for AVRT on EP study, while only 48% of the non-PAF group were inducible, leading to the theory that the increase in AF/AFL indeed depends on AVRT and, therefore, the AP itself. Furthermore, the EPS-induced AVRT degenerated to AF in 26% of the spontaneous PAF group but in none of the non-AF patients, reinforcing the AVRT-AF connection in WPW. In the era of catheter-based ablation of the AP, an early investigation found a 91% success rate of AP ablation in the prevention of AF recurrences. ⁹ More recently, a study of WPW patients with PAF pre- and post-ablation of the AP found a subset of patients with persistent-inducible PAF post-ablation. ¹⁰ This group demonstrated atrial conduction properties different from those that were no longer inducible post-ablation, suggesting the role of other mechanisms in the WPW-AF relationship.

Treatment for Acute Tachycardias Orthodromic AVRT.

In narrow-complex tachycardias consistent with AVRT, a treatment that blocks the anterograde limb of the reentrant circuit (i.e., the AV node) can terminate the rhythm. Vagal maneuvers and IV nodal acting agents such as verapamil, adenosine, or beta blockers can often be successful in patients that are hemodynamically stable. ¹¹ Second-line treatments include IV procainamide to directly address the AP conduction properties by slowing AP conduction and increasing AP refractoriness. In unstable cases, emergent DC cardioversion may be necessary. In known AVRT patients, oral antiarrhythmics can be taken on an as-needed basis for symptomatic tachycardia.

Antidromic AVRT.

In patients presenting with wide-complex tachycardia, ventricular tachycardia (VT) must always be considered in the differential diagnosis. Patients with hemodynamic instability require emergent DC cardioversion. In WPW patients with wide-complex tachycardia, IV procainamide can be used, as it may terminate the AVRT while also providing some efficacy for VT if the diagnosis is in question. ¹¹

Preexcited AF

The treatment of AF in the setting of WPW is very different from that of AF without preexcitation. Specifically, IV procainamide is the first-line agent, with ibutilide another choice due to direct AP effects.^12,13 Beta blockers, calcium channel blockers, and digoxin are contraindicated in this situation due to their lack of effect on the AP while slowing conduction through the AVN.¹² In rare cases, preexcited AF can lead to sudden cardiac death due to rapid conduction causing ventricular fibrillation (VF).

Treatment: Definitive Therapy

The accessory pathway as the etiology for WPW was first demonstrated in 1943 in pathology sections of a 13-year-old with a history of Wolff-Parkinson-White syndrome who experienced sudden cardiac arrest. ² Surgical division of an AP was first performed by Duke surgeons in 1968, ³ providing the first treatment of the underlying condition. Catheter-based approaches were developed in the 1980s, first with trans-catheter direct-current shocks⁴ and later by radiofrequency ablation. ⁵ More recently, cryoablation techniques have been introduced to allow for predictable placement of ablative lesions, particularly in areas near the AV node and His bundle, which pose a higher risk for the development of heart block. ¹⁴ Catheter ablation of the accessory pathway is successful in over 90 percent of cases, ⁶ and is the treatment of choice by the AHA/ACC guidelines (Figure 3). ¹⁵ Ablation may also be considered for appropriate asymptomatic or minimally symptomatic cases. With the known procedural risks of infection, bleeding, cardiac perforation, tamponade, and complete heart block, proper patient selection is crucial for asymptomatic cases. ¹⁶ High-risk features, including short anterograde refractory period (RP) of the AP and development of rapid AF, can lead to degeneration to VF. Noninvasive testing may help determine the anterograde RP of the accessory pathway and further risk-stratify the asymptomatic patient. ¹⁶

Conclusion

True to the initial 1930 description, the WPW EKG pattern and syndrome remain phenomena “of considerable interest.”¹ Knowledge of the appropriate management of preexcited tachycardias is essential to proper patient care in the emergency room and other acute settings. For the electrophysiology professional, the mechanisms of the WPW-AF connection, patient selection for catheter ablation, and the use of new ablation methods are all areas of active investigation and debate. The ongoing development of technologies such as cryoablation and new mapping techniques continues to enhance the safety and efficacy of WPW treatment, adding to the tremendous advances since the three-lead EKGs of Wolff, Parkinson, and White.