A novel approach for quantitative electrogram analysis for driver identification: Implications for ablation in persistent atrial fibrillation

Abstract

Objective: This study sought to study the feasibility, efficacy, and safety of using multiscale entropy (MSE) analysis to guide catheter ablation for persistent atrial fibrillation (PsAF) and predict ablation outcomes.

Methods: We prospectively enrolled 108 patients undergoing initial ablation for PsAF. MSE was calculated based on bipolar intracardiac electrograms (iEGMs) to measure the dynamical complexity of biological signals. The iEGMs data were exported after pulmonary vein isolation (PVI), then calculated in a customed platform, and finally re-annotated into the CARTO system. After PVI, regions of the highest mean MSE (mMSE) values were ablated in descending order until AF termination, or three areas had been ablated.

Results: Baseline characteristics were evenly distributed between the AF termination (n = 38, 35.19%) and the non-termination group. The RA-to-LA mean MSE (mMSE) gradient demonstrated a positive gradient in the non-termination group and a negative gradient in the termination group (0.105 ± 0.180 vs. -0.235 ± 0.256, P < 0.001). During a 12-month follow-up, 29 patients (26.9%) had arrhythmia recurrence after single ablation, and 18 of them had AF (62.1%). The termination group had lower rates of arrhythmia recurrence (15.79 vs. 32.86%, Log-Rank P = 0.053) and AF recurrence (10.53 vs. 20%, Log-Rank P = 0.173) after single ablation and a lower rate of arrhythmia recurrence (7.89 vs. 27.14%, Log-Rank P = 0.018) after repeated ablation. Correspondingly, subjects with negative RA-to-LA mMSE gradient had lower incidences of arrhythmia (16.67 vs. 35%, Log-Rank P = 0.028) and AF (16.67 vs. 35%, Log-Rank P = 0.032) recurrence after single ablation and arrhythmia recurrence after repeated ablation (12.5 vs. 26.67%, Log-Rank P = 0.062). Marginal peri-procedural safety outcomes were observed.

Conclusion: MSE analysis-guided driver ablation in addition to PVI for PsAF could be feasible, efficient, and safe. An RA < LA mMSE gradient before ablation could predict freedom from arrhythmia. The RA-LA MSE gradient could be useful for guiding ablation strategy selection.

Keywords: AF driver mapping; catheter ablation; long-term outcomes; multiscale entropy; persistent atrial fibrillation.

FIGURE 1

Flow chart of the enrollment process.

FIGURE 2

Multiscale entropy (MSE) calculation process and cases display. Panel (A) demonstrated the workflow for the calculation of MSE. Panel (B) displayed 1 case with successful AF termination by mMSE-guided ablation. The termination sites were located in the dotted circles, and the MSE values were listed below. Panels (C,D) displayed another case; yellow points indicated the area with the highest mMSE value, green points indicated the area with the second highest mMSE value, blue points indicated the area with the third highest mMSE value. We ablated the area with yellow points, and the AF terminated into sinus rhythm during the ablation. Therefore, we stopped the mMSE-guided ablation.

FIGURE 3

Comparison of mMSE values between groups. (A) The left atrial mMSE value was significantly higher in the termination group than in the non-termination group, with a P-value for comparison < 0.001. (B) Non-termination had a higher right atrial mMSE value than the termination group, with a P-value for comparison < 0.001. (C) RA-to-LA mMSE gradient was significantly higher in the non-termination group than in the termination group (P < 0.001).

FIGURE 4

Kaplan–Meier curve for the survival rates after mMSE guided catheter ablation. The median follow-up time was 12.0 months. (A) The termination group had a substantially higher rate of arrhythmia survival after a single mMSE-guided catheter ablation, with a trend toward statistical significance (Log-Rank P = 0.053). (B) AF survival rate was higher in the termination group than in the non-termination group (Log-Rank P = 0.173). (C) Arrhythmia survival was significantly higher in the termination group than in the non-termination group (Log-Rank P = 0.018). (D,E) Subjects with a negative RA-to-LA mMSE gradient had a lower arrhythmia recurrence rate (Log-Rank P = 0.028) and AF recurrence rate (Log-Rank P = 0.032) than their counterparts after a single ablation process. (F) The negative RA-to-LA mMSE gradient group had higher rates of arrhythmia-free survival than the positive RA-to-LA mMSE gradient group after repeated ablation.

FIGURE 5

Cox proportional hazards regression model assessing the association between RA < LA mMSE gradient, intraprocedural termination, and follow-up outcomes. All models were adjusted for age, gender, AF duration, and LA volume. (A) RA < LA mMSE gradient reduced the risk of arrhythmia recurrence after single ablation by 54.4% (P = 0.101). Similarly, the risk of AF recurrence after single ablation was decreased to 51.5% in RA < LA mMSE gradient group than that in RA > LA mMSE gradient group (P = 0.264). Finally, RA < LA mMSE gradient group had a significant 73.6% risk reduction for arrhythmia recurrence after repeated ablation than RA > LA mMSE gradient group (P = 0.037). (B) Intraprocedural termination also showed associations with reduced risk of arrhythmia recurrence after single ablation, AF recurrence after single ablation, and arrhythmia recurrence after repeated ablation. However, the associations between intraprocedural termination and follow-up outcomes did not achieve statistical significance.