Electrolytic Electroporation (E2): first in vivo demonstration for cardiac ablation

Introduction Pulsed field ablation (PFA) is an emerging ablation technique for the treatment of cardiac arrhythmias. Despite its advantages, PFA requires high voltages to induce irreversible electroporation (IRE), frequently necessitating deep sedation or general anaesthesia. These protocols inherently generate a surrounding border zone of reversible electroporation. Electrolytic electroporation (E2) is a novel PFA approach in which tailored pulse waveforms generate electrolysis products simultaneously with electroporation, thereby converting transient membrane permeabilization into durable tissue injury. By targeting this border zone, E2 represents a fundamentally different ablation strategy with the potential to achieve effective lesion formation at lower applied voltages. Purpose To evaluate the feasibility and acute histopathological effects of E2 for cardiac tissue ablation in a porcine model. Methods Intracardiac ablations were performed using a modified circular pulmonary vein isolation catheter in anesthetized, ventilated pigs (n=3). E2 ablations were delivered to the left atrial appendage, right superior pulmonary vein, superior vena cava, and right atrium. Catheter-tissue contact was confirmed via intracardiac echocardiography. Four tailored pulse waveform protocols were tested across the anatomical locations: 3x750V, 3x1000V, 6x750V, and 6x1000V (Lesions 1–4). Animals were euthanized after 24 hours post-procedure. Macroscopic lesion evaluation was performed using triphenyltetrazolium chloride (TTC) staining, followed by histopathological analysis to determine penetration depth and transmurality. Results E2 applications were successful at all targeted ablation sites. On one occasion, self-terminating atrial fibrillation was observed after pulse delivery; otherwise, no procedural complications were observed. Macroscopic evaluation confirmed distinct lesion formation in all dosage groups. Histopathological analysis showed dose-dependent increases in lesion depth (770 µm, 1795 µm, 1501 µm, and 2495 µm for Lesions 1-4, respectively) and transmurality (42%, 54%, 69%, 94% for Lesions 1-4, respectively). Conclusion E2 is a feasible method for achieving targeted myocardial ablation at lower voltages than conventional PFA. By addressing the reversibly electroporated border zone, this novel approach may enhance lesion durability and reduce the likelihood of conduction recovery. The findings of the study support further investigation to define optimal dosing parameters and to assess chronic lesion durability and electrophysiological outcomes.