Reentry in an accessory atrioventricular pathway as a trigger for atrial fibrillation initiation in manifest Wolff-Parkinson-White syndrome: a matter of reflection?

Abstract

Background: Patients with an accessory pathway (AP) have an increased propensity to develop atrial fibrillation (AF), but the mechanism is unknown.

Objective: The purpose of this study was to identify crucial risk factors and to test the hypothesis that reflection and/or microreentry of atrial impulses propagating into the AP triggers AF.

Methods: Five hundred thirty-four patients successfully treated with radiofrequency ablation of AP at two university hospitals were evaluated. Patients were separated into those with concealed vs those with manifest AP in terms of their propensity to develop AF. To investigate AF triggering mechanisms, linear and branched two-dimensional models of atrium-to-ventricle propagation across a heterogeneous 1 x 6 AP using human ionic kinetics were simulated.

Results: A history of AF was twice as common in patients with manifest AP vs concealed AP irrespective of AP location. AF was more likely to occur in older males and in patients with larger atria. There was no correlation between AF history and AP refractory measures. However, the electrophysiologic properties of APs seemed to fulfill the prerequisites for reflection and/or microreentry of atrially initiated impulses. In the linear AP model, repetitive atrial stimulation resulted in progressively larger delay of atrium-to-ventricle propagation across the passive segment. Eventually, sufficient time for repolarization of the atrial segment allowed for reflection of an impulse that activated the entire atrium and by wavefront-wavetail interaction with a new atrial stimulus AF reentry was initiated. Simulations using the branched model showed that microreentry at the ventricular insertion of the AP could also initiate AF via retrograde atrial activation as a result of unidirectional block at the AP-ventricle junction.

Conclusion: Propensity for AF in patients with an AP is strongly related to preexcitation, larger atria, male gender, and older age. Reflection and microreentry at the AP may be important for AF initiation in patients with manifest (preexcited) Wolff-Parkinson-White syndrome. Similar mechanisms also may trigger AF in patients without an AP.

Figure 1

Overview of the studied patients divided after accessory pathway location and the presence (mWPW) or absence (cWPW) of preexcitation on the surface electrocardiogram.

Figure 2

A. Schematic representation of a left-sided accessory pathway with single atrial and ventricular epicardial insertion and its surroundings, and the mechanistic model of “reflection” or “reflected reentry” within the pathway. B. Schematic representation of a left-sided accessory pathway with single atrial and branched ventricular epicardial insertion and its surroundings. Arrows indicate direction of propagation. C. Two-dimensional computer model of unbranched AP in which the reflected reentry hypothesis was tested. The model consisted of a 2×1 cm² “atrium”, a 2×1 cm² “ventricle” and a short 6×2 mm² accessory pathway (AP). The AP consisted of a 3 mm active atrial segment, an active 2.8 mm ventricular segment, and a 200 µm-long passive element (gap) in between. D. Branched AP with dual pathways used to test for microreentry hypothesis. The dimensions were similar to those in the unbranched AP model with the exception of the presence of the fast and slow pathways. Bottom action potentials recorded from atrial and ventricular segments of the AP. The white vertical bar in the atrium indicates the site of application of atrial stimuli. E. Transmembrane potentials recorded from single model cells in the atrial and ventricular segments.

Figure 3

Computer model of reflection and AF initiation induced by and S1S2S3S4 protocol in an unbranched AP. A. Left, diagrammatic representation of the AP with an excitable atrial segment (top), an unexcitable “gap” segment (middle) and a ventricular segment (bottom). Right, transmembrane potentials demonstrate conduction delay, block and electrotonically mediated reflection with retrograde propagation to the atria and initiation of atrial reentry. Two atrial tracings are given at proximal and distal locations to the AP. The proximal tracing (2^nd from top) shows an elevated phase 2 resulting from electrotonic influence of the ventricular action potential mediated by the unexcitable gap. B. Time-space plot constructed along the horizontal dashed line in the inset. Green bars show direction and velocity of wavefront propagation. Read areas indicate refractoriness. White vertical bar in inset, stimulus site. A1 and A2 propagated at a constant velocity through the atrial side but became discontinuous upon reaching the gap. The slightly longer delay of A2 allowed for reflection (red arrow), retrograde propagation and initiation of sustained atrial reentry (see online Movie 1).

Figure 4

Bipolar electrograms show the events leading to AF by reflection at the AP. Left, location of the bipolar electrodes (white balls). Right, electrograms from atrium, AP and ventricle. Atrium-to-ventricle propagation appears continuous for A1 despite the presence of the unexcitable gap. A slightly more delayed A2 impulse reflects and set the stage for AF initiation.

Figure 5

Simulation using the micro-reentry model. A. Conditions are similar to reflection model but the AP bifurcates in slow and fast pathways. A1 impulse in the atrium propagated through both AP pathways but was blocked unidirectionally at the fast pathway-to-ventricle insertion. Slow propagation in the other pathway activated the ventricle and allowed for AP reentry and retrograde conduction to the atrium with subsequent AF initiation. B. Time space plot along the white dashed line in the inset shows slow to fast pathway reentry and subsequent front-tail interaction in the atrium between the reentrant beat and the subsequent atrial impulse resulted in a wavebreak and initiation of sustained reentry (see online Movie 2).

Figure 6

Simulated bipolar electrograms for the atrium, slow pathway in AP and ventricle demonstrate similarity between reentry patterns in micro-reentry and reflection models (compare with Figure 4).