Effect of pulmonary vein isolation on rotor/multiple wavelet dynamics in persistent atrial fibrillation, association with vagal response and implications for adjunctive ablation

Abstract

Persistent atrial fibrillation (PeAF) may develop arrhythmogenic substrates of rotors/multiple wavelets. However, the ways in which pulmonary vein isolation (PVI) affects the dynamics of rotor/multiple wavelets in PeAF patients remain elusive. Real-time phase-mapping (ExTRa mapping, EXT) in the whole left atrium (LA) was performed during PeAF before and after PVI (n = 111). The percentage of time in which rotor/multiple wavelets (phase singularities) was observed during each 5-s phase-mapping recording (non-passive activation ratio, %NP) was measured as an index of its burden. The mapping areas showing %NP ≥ 50% were defined as rotor/multiple-wavelet substrates (RSs). Before PVI, RSs were globally distributed in the LA. After PVI, %NP decreased (< 50%) in many RSs (PVI-modifiable RSs) but remained high (≥ 50%) in some RSs, especially localized in the anterior/septum/inferior regions (PVI-unmodifiable RSs, 2.3 ± 1.0 areas/patient). Before PVI, vagal response (VR) to high-frequency stimulation was observed in 23% of RSs, especially localized in the inferior region. VR disappearance after PVI was more frequently observed in PVI-modifiable RSs (79%) than in PVI-unmodifiable RSs (55%, p < 0.05), suggesting that PVI affects autonomic nerve activities and rotor/multiple wavelet dynamics. PVI-unmodifiable RSs were adjunctively ablated in 104 patients. The 1-year AT/AF-free survival rate was 70% in those with PVI alone (n = 115), and 86% in patients with the adjunctive ablation (log-rank test = 7.65, p < 0.01). PVI suppresses not only ectopic firing but also rotor/multiple wavelets partly via modification of autonomic nerve activities. The adjunctive ablation of PVI-unmodifiable RSs improved the outcome in PeAF patients and might be a novel ablation strategy beyond PVI.

Keywords: Atrial fibrillation; Catheter ablation; Phase mapping; Pulmonary vein isolation; Rotor.

Fig. 1

Study protocol

Fig. 2

Excitation patterns of reentrant activities. a, Whole LA mapping with a 20 polar spiral-shaped mapping catheter. b, Excitation patterns of reentrant activities in real-time phase mapping. Representative phase maps (PMs) were shown. Open white circle indicates phase singularity (PS). Single rotation (R, left): PS = 1. Multiple wavelets (M, middle): PS ≥ 2. Passive activation (P, right): PS = 0. c, Non-passive activation ratio (%NP). %NP: time ratio of non-passive activation (R + M) to 5-s recording

Fig. 3

Real-time phase mapping in EXT. a, Representative PMs (left) and intracardiac electrocardiogram (IEGM, right) in high %NP (≥ 50%) area. b, PMs (left) and IEGM (right) in low %NP (< 50%) area. IEGM was recorded using a 20 polar spiral-shaped mapping catheter. Open white circle indicates phase singularity

Fig.4

Distribution of rotor/multiple wavelet substrates (RSs). a, Distribution of RSs (%NP ≥ 50%) in real-time phase mapping before and after PVI. b, Representative PMs of a PVI-modifiable RS. c, Representative PMs of a PVI-unmodifiable RS

Fig. 5

Vagal response (VR) to high frequency stimulation (HFS) in RSs. a, Representative PMs of VR[ +]/VR[ +] and VR[ +]/VR[ – ]. b–e, %NP, %R, %M, and M/R before and after PVI. Black box: RSs which showed positive VRs before and after PVI (VR[ +]/VR[ +], n = 30). White box: RSs which showed a positive VR before PVI but did a negative VR after PVI (VR[ +]/VR[ – ], n = 80)

Fig. 6

Adjunctive ablation targeting PVI-unmodifiable RSs. a, RS distribution in real-time phase mapping before PVI. b, RS distribution after PVI. c, PVI-unmodifiable RSs. d, Adjunctive ablation targeting PVI-unmodifiable RSs

Fig. 7

1-year AF/AT Free survival rate. a, 1-year atrial tachycardia (AT)/AF free survival rate in Group EXT (n = 111) and Group CON (n = 108). b, 1-year AT/AF free survival rate in PVI + adjunctive ablation (n = 104) and PVI alone (n = 115)