Preclinical Evaluation of Pulsed Field Ablation

Abstract

Background: Pulsed field ablation (PFA) is a uniquely tissue-selective, nonthermal cardiac ablation modality. Delivery parameters such as the electrical waveform composition and device design are critical to PFA’s efficacy and safety, particularly tissue specificity. In a series of preclinical studies, we sought to examine the electrophysiological and histological effects of PFA and compare the safety and feasibility of durable pulmonary vein and superior vena cava (SVC) isolation between radiofrequency ablation and PFA waveforms. Methods: A femoral venous approach was used to gain right and left atrial access under general anesthesia in healthy swine. Baseline potentials in right superior pulmonary and inferior common vein and in SVC were assessed. Bipolar PFA was performed with monophasic (PFA Mono ) and biphasic (PFA Bi ) waveforms in 7 and 7 swine sequentially and irrigated radiofrequency ablation in 3 swine. Vein potentials were then assessed acutely, and at ≈10 weeks; histology was obtained. Results: All targeted veins (n=46) were successfully isolated on the first attempt in all cohorts. The PFA Bi waveform induced significantly less skeletal muscle engagement. Pulmonary vein isolation durability was assessed in 28 veins: including the SVC, durability was significantly higher in the PFA Bi group (18/18 PFA Bi , 10/18 PFA Mono , 3/6 radiofrequency, P =0.002). Transmurality rates were similar across groups with evidence of nerve damage only with radiofrequency. Pulmonary vein narrowing was noted only in the radiofrequency cohort. The phrenic nerve was spared in all cohorts but at the expense of incomplete SVC encirclement with radiofrequency. Conclusions: In this chronic porcine study, PFA-based pulmonary vein and SVC isolation were safe and efficacious with demonstrable sparing of nerves and venous tissue. This preclinical study provided the scientific basis for the first-in-human endocardial PFA studies.