Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation

Abstract

Background Human atrial fibrillation (AF) can terminate after ablating localized regions, that supports the existence of localized rotors (spiral waves) or focal drivers. However, it is unclear why ablation near a spiral wave tip would terminate AF and not anchor reentry. We addressed this question by analyzing competing mechanisms for AF termination in numerical simulations, referenced to clinical observations. Methods and Results Spiral wave reentry was simulated in monodomain 2D myocyte sheets using clinically realistic rate-dependent values for repolarization and conduction. Heterogeneous models were created by introduction of parameterized variations in tissue excitability. Ablation lesions were applied as non-conducting circular regions. Computational models confirmed localized ablation may anchor spiral wave reentry, producing organized tachycardias. Several mechanisms also explained termination of AF to sinus rhythm. First, lesions may create an excitable gap vulnerable to invasion by fibrillatory waves. Second, ablation of rotors in regions of low-excitability (from remodeling) produced reentry in more excitable tissue allowing collision of wave-front and back. Conversely, ablation of rotors in high-excitability regions migrated spiral waves to less excitable tissue, where they detached to collide with non-conducting boundaries. Third, ablation may connect rotors to non-conducting anatomic orifices. Fourth, reentry through slow conducting channels may terminate if ablation closes these channels. Conclusions Limited ablation can terminate AF by several mechanisms. These data shed light on how clinical AF may be sustained in patients’ atria, emphasizing heterogeneities in tissue excitability, slow-conducting channels and obstacles that are increasingly detectable in patients and should be the focus of future translational studies.

Fast propagation regions cause self-sustained reentry in excitable media

“…In the modern literature, the Fenton-Karma (FK) model (34,35) is widely used to simulate electrical activity in atrial tissue in more detail (35,36). To validate the applicability of our findings, the simulations with the FK model have been performed and are shown in SI Text.…”

“…S1-S3). It is shown that for the chosen parameter set of the FK model, the propagation block is achievable at the relatively strong inhomogeneity, which is, however, not unusual for cardiac tissue (36)(37)(38).…”

Ablation of Atrial Fibrillation

“…While AF sources have been questioned, those studies had issues such as atrial cycle lengths of 250–500ms (dominant frequencies 2–4 Hz) in many patients ostensibly with AF and analysis of unipolar signals using indices designed for bipolar signals (Shannon's entropy) 19 , or mapped very small areas 8 . Recent data showing how localized ablation can terminate AF rotors, by interacting with non-uniformities in remodeled atria, explain and thus strengthen the results of AF source ablation 20 . At the other end of the spectrum, it has been proposed that debulking should be further extended – such as by posterior LA wall ablation.…”

The continuous challenge of AF ablation: From foci to rotational activity

“…This model is now supported by wide evidence in many patients ranging from optical mapping of human AF, 7 multicenter (non-randomized) clinical trials of AF rotor ablation, [8][9][10][11][12][13] optical mapping of animal AF, 14 and mathematical analyses. 15 Moreover, this model can reconcile the paradox that limited ablation can terminate persistent AF in some patients, 8,16,17 while extensive (untargeted) ablation of left atrial regions can be ineffective in others. 1,2,18 The source model may contradict the multiwavelet hypothesis, in which AF is caused by disordered waves alone, 19,20 although ongoing studies on the interaction between organized sources and disordered waves may reconcile this.…”