Novel Radiofrequency Ablation Strategies for Terminating Atrial Fibrillation in the Left Atrium: A Simulation Study

Abstract

Pulmonary vein isolation (PVI) with radiofrequency ablation (RFA) is the cornerstone of atrial fibrillation (AF) therapy, but few strategies exist for when it fails. To guide RFA, phase singularity (PS) mapping locates reentrant electrical waves (rotors) that perpetuate AF. The goal of this study was to test existing and develop new RFA strategies for terminating rotors identified with PS mapping. It is unsafe to test experimental RFA strategies in patients, so they were evaluated in silico using a bilayer computer model of the human atria with persistent AF (pAF) electrical (ionic) and structural (fibrosis) remodeling. pAF was initiated by rapidly pacing the right (RSPV) and left (LSPV) superior pulmonary veins during sinus rhythm, and rotor dynamics quantified by PS analysis. Three RFA strategies were studied: (i) PVI, roof, and mitral lines; (ii) circles, perforated circles, lines, and crosses 0.5-1.5 cm in diameter/length administered near rotor locations/pathways identified by PS mapping; and (iii) 4-8 lines streamlining the sequence of electrical activation during sinus rhythm. As in pAF patients, 2 ± 1 rotors with cycle length 185 ± 4 ms and short PS duration 452 ± 401 ms perpetuated simulated pAF. Spatially, PS density had weak to moderate positive correlations with fibrosis density (RSPV: r = 0.38, p = 0.35, LSPV: r = 0.77, p = 0.02). RFA PVI, mitral, and roof lines failed to terminate pAF, but RFA perforated circles and lines 1.5 cm in diameter/length terminated meandering rotors from RSPV pacing when placed at locations with high PS density. Similarly, RFA circles, perforated circles, and crosses 1.5 cm in diameter/length terminated stationary rotors from LSPV pacing. The most effective strategy for terminating pAF was to streamline the sequence of activation during sinus rhythm with >4 RFA lines. These results demonstrate that co-localizing 1.5 cm RFA lesions with locations of high PS density is a promising strategy for terminating pAF rotors. For patients immune to PVI, roof, mitral, and PS guided RFA strategies, streamlining patient-specific activation sequences during sinus rhythm is a robust but challenging alternative.

Keywords: ablation; computer modeling; fibrosis; persistent atrial fibrillation; phase singularity mapping.

Figure 1

Structural remodeling was incorporated probabilistically based on late-gadolinium enhancement data. (A) Late-gadolinium enhancement likelihood data averaged across 26 patients with pAF from Cochet et al. (2015). (B) Longitudinal fiber directions in the pAF bilayer model. (C) Mesh element edges selected with probability weighted by the enhancement likelihood (A) and edge direction compared to the longitudinal fiber direction (B). (D) Inset of the mesh showing element edges with no flux boundary conditions imposed to create structural discontinuities. Split mesh element edges and removed elements in (C) and (B) are marked in black.

Figure 2

pAF initiation via PV pacing. (A) Transmembrane voltage (Vm) map post pAF initiation via RSPV pacing. (B) Vm plot from a point in the RSPV showing the transition of sinus rhythm to pAF via RSPV pacing. (C) Vm map post pAF initiation via LSPV pacing. (D) Vm plot from a point in the LSPV showing the transition of sinus rhythm to pAF via LSPV pacing. The * symbols in (A,C) indicate the pacing sites and Vm plot locations, and the arrows indicate the direction of rotor rotations.

Figure 3

PS locations during pAF from RSPV pacing. (A) PS trajectories on the posterior (shown on the left) and anterior (shown on the right) walls, colored by time (ms) during the simulation post RSPV pacing. (B) Spatially smoothed PS density map, indicating that one rotor is found on the posterior wall in an area of high fibrosis density, and another moves across the anterior wall. (C) Eight LA subdivisions were used for analysis and correspond to the LA location numbers in Figure 6. (D) Regional assessment of the mean and standard deviation of PSs and the mean number of rotors (shown in a darker shade) over the duration of the simulation show that subdivisions 3, 5, and 7 have the highest PS density. (E) Regional assessment of average CL for each vertex in the pAF bilayer model indicates that mean average CL is constant across subdivisions, while the minimum average CL varies (shown in a darker shade).

Figure 4

PS locations during pAF from LSPV pacing. (A) PS trajectories on the posterior (shown on the left) and anterior (shown on the right) walls, colored by time (ms) during the simulation post LSPV pacing. (B) Spatially smoothed PS density map, indicating rotors localized only in the area of high fibrosis density on the posterior wall. (C) Eight LA subdivisions were used for analysis and correspond to the LA location numbers in Figure 6. (D) Regional assessment of the mean and standard deviation of PSs and the mean number of rotors (shown in a darker shade) over the duration of the simulation show that subdivision 3 has the highest PS density. (E) Regional assessment of average CL for each vertex in the pAF bilayer model indicates that mean average CL is constant across subdivisions, while the minimum average CL varies (shown in a darker shade).

Figure 5

RFA with PVI, mitral, and roof lines failed to terminate AF from RSPV pacing. (A) RFA starting with PVI, followed by a roof line, and then a mitral line. (B) Transmembrane voltage (Vm) maps showing pAF rotor behavior after the respective RFA in (A). The arrows indicate the direction of rotor rotations.

Figure 6

PS guided RFA terminates pAF from RSPV and LSPV pacing. The effects of PS guided RFA administered to the eight LA subdivision locations in Figures 3C, 4C with circles (A), perforated circles (B), lines (C), or crosses (D) 1.5 cm in diameter/length on pAF initiated via RSPV or LSPV pacing: being either by terminating pAF back to sinus rhythm (green +); converting pAF to AT (yellow +); or no change with pAF persisting (red X).

Figure 7

Outcomes for PS guided RFA for pAF from RSPV pacing. (A) RFA lesion shapes used for PS guided RFA with a diameter or length of 1.5 cm. (B) Transmembrane Voltage (Vm) maps 5 s post RFA in (A) showing pAF to either persist, terminate into sinus rhythm, or convert to AT. The arrows indicate the direction of rotor rotations.

Figure 8

Streamlining the sequence of LA activation during sinus rhythm with >4 lines effectively terminates pAF from RSPV pacing. (A) LA activation times during sinus rhythm at 86 beats per min. (B) four or five RFA lines that streamline the activation time sequence in (A). (C) Transmembrane voltage (Vm) maps 5 s post streamlining showing unsuccessful pAF termination with four RFA lines, but successful pAF termination with five RFA lines. (D) Vm plotted at the point indicated by the * in (A) before and after streamlining with four and five RFA lines.