Preliminary Validation of Electroporation-Electrolysis (E2) for Cardiac Ablation Using a Parameterisable In-Vivo Model

Abstract

Atrial fibrillation is the most common arrhythmia, increasing the risk of stroke, heart failure and mortality, and a growing epidemic affecting tens of millions of people and costing economies billions worldwide. The gold standard in atrial fibrillation ablation relies on thermal cell-kill, which may limit efficacy, speed and risk. Electroporation is emerging in cardiac ablation as a fast, non-thermal and tissue-specific alternative. Successful irreversible electroporation ablation in tumour has spurred similar use of kilovolt pulses in cardiac ablation. However, high voltages in the heart would compound clinical, technical and regulatory challenges. A novel ablation technique, “E2”, augments low-voltage electroporation with electrolytic cell-kill. Specialised electrodes and a custom E2 pulse generator were developed based on numerical modelling. Following in vitro validation of electric field morphology and the spread of electrolytic pH fronts, the system was and tested on the in-vivo thigh muscle tissue model of cardiac ablation using three sheep – anaesthetised and sedated but not paralysed. Histopathology with haematoxylin and eosin showed continuous lesions of clinical relevance below the electrodes, extending radially. There was no inflammation or pathology away from the ablation site. With tolerable muscle contraction comparable to implantable cardioverter-defibrillator testing and the absence of acute complications, these findings may be useful for pulmonary vein isolation. Lesions were mapped onto a numerical model, which can inform prototype development and treatment planning. This study validates E2 ablation in muscle tissue and preliminary prototyping, while scaffolding the workflow for parametrising electroporation ablation towards endocardial application.