Cardioneuroablation Using Epicardial Pulsed Field Ablation for the Treatment of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people worldwide. The cardiac autonomic nervous system (ANS) is widely recognized as playing a key role in both the initiation and propagation of AF. This paper reviews the background and development of a unique cardioneuroablation technique for the modulation of the cardiac ANS as a potential treatment for AF. The treatment uses pulsed electric field energy to selectively electroporate ANS structures on the epicardial surface of the heart. Insights from in vitro studies and electric field models are presented as well as data from both pre-clinical and early clinical studies.

Keywords: atrial fibrillation; cardiac autonomics; cardioneuroablation; ganglionated plexi; pulsed electric field.

Figure 1

Location of key atrial ganglionated plexi (GP). Oblique sinus (OS), right superior (RS), transverse sinus (TS), left superior (LS) and ligament of Marshall (LM).

Figure 2

Tyrosine kinase staining of an unablated GP (left) and a pulsed field ablated GP (right). The unablated control shows uptake of the stain, confirming neuron functionality, while the ablated sample shows no uptake, indicating cell death.

Figure 3

Temporal dynamics of cell death in neurons and cardiomyocytes. The permeability of cells to PI was measured at 1000 V/cm 30 pulses, 1000 V/cm 60 pulses, 1250 V/cm 30 pulses, and 1250 V/cm 60 pulses in neurons (A) and cardiomyocytes (C). The evolution of PI permeable cells was detected at 0.5 (in red), 3 (in blue) and 24 (in green) hours for neurons (B) and cardiomyocytes (D). All data shown as mean ± SEM. Statistical significance was performed using two-way ANOVA (* p < 0.05, ** p < 0.005, *** p < 0.001, **** p < 0.0001). Reprinted with permission from [60] through the Creative Commons attribution license.

Figure 4

Electric field distribution around the target epicardial site, without (A) and with (B) a saline layer. The electrode is embedded 0.25 mm in the fat layer. The white contour corresponds to the 1000 V/cm electric field isoline. Reprinted with permission from [66] through the Creative Commons Attribution License.

Figure 5

Paired baseline and post-ablation AERP values for patients in safety and feasibility study.

Figure 6

Schematic of endocardial PVI lesions (blue) and epicardial GP locations (yellow).

Figure 7

Patient heart rates collected at baseline, day 1 postablation, and 3 months postablation. The asterisk (*) indicates statistical significance (p ≤ 0.05, paired t-test) compared to baseline heart rates. Total of 40 patients in each group. Bars indicate median heart rate. BPM = beats/min; Cryo = cryoballoon ablation; PFA = pulsed field ablation; RFA = radiofrequency ablation. Reprinted with permission from [78]; Copyright © 2022 Elsevier.