Novel approaches to mechanism-based atrial fibrillation ablation

Abstract

Modern cardiac electrophysiology has reported significant advances in the understanding of mechanisms underlying complex wave propagation patterns during atrial fibrillation (AF), although disagreements remain. One school of thought adheres to the long-held postulate that AF is the result of randomly propagating wavelets that wonder throughout the atria. Another school supports the notion that AF is deterministic in that it depends on a small number of high-frequency rotors generating three-dimensional scroll waves that propagate throughout the atria. The spiralling waves are thought to interact with anatomic and functional obstacles, leading to fragmentation and new wavelet formation associated with the irregular activation patterns documented on AF tracings. The deterministic hypothesis is consistent with demonstrable hierarchical gradients of activation frequency and AF termination on ablation at specific (non-random) atrial regions. During the last decade, data from realistic animal models and pilot clinical series have triggered a new era of novel methodologies to identify and ablate AF drivers outside the pulmonary veins. New generation electroanatomical mapping systems and multielectrode mapping catheters, complimented by powerful mathematical analyses, have generated the necessary platforms and tools for moving these approaches into clinical procedures. Recent clinical data using such platforms have provided encouraging evidence supporting the feasibility of targeting and effectively ablating driver regions in addition to pulmonary vein isolation in persistent AF. Here, we review state-of-the-art technologies and provide a comprehensive historical perspective, characterization, classification, and expected outcomes of current mechanism-based methods for AF ablation. We discuss also the challenges and expected future directions that scientists and clinicians will face in their efforts to understand AF dynamics and successfully implement any novel method into regular clinical practice.

Keywords: Arrhythmia mechanisms; Cardiac mapping; Rotors; Atrial fibrillation.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1

(A) Schematics of postulated mechanisms for atrial fibrillation (AF) maintenance that do not involve localized drivers. (B) Schematics of postulated AF maintenance mechanisms that involve localized drivers. (C) The Maze-Cox procedure may be effective for treating AF allegedly maintained either by non-localized or localized mechanisms. (D) Successful treatment for AF by ablation at specific target sites supports the idea of relatively localized drivers maintaining AF. (E) Schematic of some potential 3D patterns giving rise to 2D rotors and/or breakthroughs as observed by current 2D mapping methodologies. (F) Schematic of structurally and electrically remodelled atria, where several reported patterns might coexist. However, AF may still be driven in a hierarchical fashion by specific regions with higher than surrounding activation rate (leading drivers). Such regions would host re-entrant drivers in many cases, albeit not all re-entrant activity would act as a driver, since rotors are also commonly found in passive bystander regions.

Figure 2

(A). During AF, the morphology, amplitude and frequency modulations often displayed by electrical signals considerably affects the shape of their corresponding spectra. Therefore, the frequency of the highest peak in a given spectrum (dominant frequency, DF) need not be the best estimator of the underlying average activation rate (8 Hz for all signals shown in (A)). (B). Spectral analyses of 2 actual atrial electrograms during persistent AF. (C). Time domain analysis of signals during AF may offer many advantages, although this requires reliable and robust algorithms. iAM, instantaneous amplitude modulation; iFM, instantaneous frequency modulation.

Figure 3

Study population and AF alleged drivers in mechanistic approaches for AF mapping. (A) AF type distribution in the mechanistic mapping groups of the selected studies. (B) Proportion of patients with persistent AF presenting in sinus rhythm. (C) Proportion of first AF ablations (de novo) and repeated procedures (redo) in the mechanistic mapping groups. (D) Description of the alleged AF drivers as defined by each approach. (E) Number of alleged drivers per patient displayed as median and interquartile range (percentile 25th, percentile 75th). In the studies where these data were not reported, they were estimated from means and standard deviations assuming normal distributions. (F) Proportion of alleged drivers in the pulmonary vein region Vs. extra-pulmonary drivers. (G) Proportion of alleged drivers in the right and left atria. (H) Classification of AF alleged drivers according to their activation patterns. CS, coronary sinus; LA, left atrium; LAA, left atrial appendage; m, month; N/A, not available; Ps, persistent; PsSR, persistent presenting in sinus rhythm; Px, paroxysmal; RA, right atrium; SR, sinus rhythm; y, year. Rest of abbreviations as in Table 4.

Figure 4

Acute and long-term outcomes of mechanistic approaches for AF mapping and ablation. (A) Ablation procedures in the mechanistic mapping groups from the selected studies. (B) Radiofrequency time for driver ablation only, unless otherwise specified. Data are displayed as median and interquartile range (percentile 25th, percentile 75th). In the studies where these data were not reported, they were estimated from means and standard deviations assuming normal distributions. (C) AF acute termination rates with driver ablation only, unless otherwise specified. (D) Long-term outcomes after a single procedure. (E) Proportion of patients who were submitted to an additional ablation procedure for AF or AT recurrence after the index procedure. (F) Long-term outcomes after multiple procedures. f.u., follow-up. Rest of abbreviations as in Figure 3.