Wolff-Parkinson-White Syndrome: Diagnosis and Risk Stratification

Definition and Pathophysiology

Wolff-Parkinson-White (WPW) syndrome is defined as the presence of ventricular pre-excitation on ECG combined with symptomatic paroxysmal arrhythmias, caused by an accessory electrical pathway that bypasses the normal AV node conduction system, affecting 0.15-0.25% of the general population, with higher prevalence in first-degree relatives, suggesting genetic predisposition 1, 2
The syndrome has a pre-excitation degree that varies based on relative conduction through the AV node versus the accessory pathway 2

The European Society of Cardiology recommends that the diagnostic ECG criteria for WPW syndrome include a delta wave, which is the defining feature and must be present for diagnosis, and is often associated with a shortened PR interval and widened QRS complex 3
Left lateral accessory pathways may show minimal delta waves due to fusion with normal AV nodal conduction, potentially appearing as intermittent pre-excitation when actually continuously present 3

The American Heart Association notes that orthodromic AVRT is the most common arrhythmia in WPW syndrome, accounting for 90-95% of episodes, and is characterized by a narrow QRS complex tachycardia using the AV node anterogradely and accessory pathway retrogradely 1, 4, 5
Antidromic AVRT is a less common but more dangerous arrhythmia, characterized by a wide QRS complex tachycardia with anterograde conduction via the accessory pathway 5
Atrial fibrillation occurs in up to 50% of WPW patients and is particularly dangerous due to the risk of rapid ventricular response 4, 1
Ventricular fibrillation is a rare but life-threatening complication, particularly when triggered by pre-excited AF 1, 4

The European Heart Journal recommends that patients with WPW syndrome be risk-stratified for sudden cardiac death, with high-risk features including a shortest pre-excited R-R interval <250 ms during atrial fibrillation, accessory pathway refractory period <240 ms, history of symptomatic tachycardia, multiple accessory pathways, associated Ebstein's anomaly, and familial WPW 1, 3, 4, 5
The American College of Cardiology notes that population-based sudden cardiac death risk is 0.15-0.24% over 10 years, while symptomatic WPW patients have a 2.2% risk, and lifetime risk in symptomatic WPW approaches 4% 1, 4, 5

The European Society of Cardiology recommends that echocardiography be used to exclude associated conditions, such as Ebstein's anomaly, hypertrophic cardiomyopathy, and PRKAG2-related familial WPW 1, 3
Ebstein's anomaly is a congenital tricuspid valve abnormality that is associated with an increased risk of sudden cardiac death in WPW patients 1, 3

The American Heart Association recommends a step-wise approach to evaluating patients with suspected or confirmed WPW syndrome, including history and physical examination, 12-lead ECG, echocardiography, 24-hour Holter monitoring, exercise testing, and electrophysiological study 1, 3

Sinus WPW is defined by the American Heart Association (AHA) as a baseline electrocardiographic pattern during normal sinus rhythm that shows ventricular pre‑excitation manifested by a delta wave, a PR interval < 120 ms, and a QRS duration > 120 ms【6】【7】.
Antidromic AVRT (antidromic WPW) is defined by the AHA as a re‑entrant tachycardia in which the accessory pathway conducts anterogradely (atrium → ventricle) while the AV node conducts retrogradely (ventricle → atrium), producing a wide‑QRS tachycardia【6】【7】.
During sinus rhythm, the accessory pathway conducts in parallel with the AV node, creating fusion of pre‑excited ventricular activation with normal AV‑nodal conduction【8】【9】.
In rare cases a second accessory pathway can serve as the retrograde limb, a mechanism termed “pre‑excited AVRT”【8】【10】.

Manifest sinus WPW is present in approximately 0.1 %–0.3 % of the general population【8】【9】.
Patients may be asymptomatic (isolated pre‑excitation) or symptomatic when documented arrhythmias occur, constituting WPW syndrome【6】【7】.

Sinus WPW ECG: PR interval < 120 ms, slurred upstroke of the QRS (delta wave), and QRS width > 120 ms【7】.
Antidromic AVRT ECG: Wide‑QRS complex tachycardia with maximal pre‑excitation because ventricular activation occurs entirely via the accessory pathway, without fusion with normal AV‑nodal conduction【6】【7】.

Antidromic AVRT accounts for 5 %–10 % of tachycardia episodes in patients with manifest accessory pathways, whereas orthodromic AVRT accounts for the remaining 90 %–95 %【8】【9】.
Risk stratification for sudden cardiac death in sinus WPW focuses on accessory‑pathway properties (e.g., refractory period, conduction speed) as recommended by the AHA【8】【10】.
Antidromic AVRT is an active tachyarrhythmia that requires acute termination and consideration for definitive catheter ablation【10】.

Hemodynamically unstable antidromic AVRT: Immediate synchronized cardioversion is a Class I recommendation (strong evidence)【10】.
Hemodynamically stable antidromic AVRT: Intravenous procainamide or ibutilide is recommended as first‑line pharmacologic therapy【10】.
AV‑nodal blocking agents (adenosine, β‑blockers, calcium‑channel blockers, digoxin) are absolutely contraindicated in antidromic AVRT and pre‑excited atrial fibrillation because they may precipitate ventricular fibrillation by allowing unopposed rapid conduction through the accessory pathway【10】.
Definitive therapy for both sinus WPW (high‑risk pathways) and antidromic AVRT is catheter ablation of the accessory pathway, as endorsed by the AHA guidelines【10】.

The term “antidromic WPW” specifically refers to the re‑entrant mechanism using the accessory pathway anterogradely; it should not be used generically for any wide‑QRS tachycardia in a WPW patient【6】【7】.