In vivo porcine characterization of atrial lesion safety and efficacy utilizing a circular pulsed-field ablation catheter including assessment of collateral damage to adjacent tissue in supratherapeutic ablation applications

Abstract

Introduction: Pulsed-field ablation (PFA), an ablative method that causes cell death by irreversible electroporation, has potential safety advantages over radiofrequency ablation and cryoablation. Pulmonary vein (PV) isolation was performed in a porcine model to characterize safety and performance of a novel, fully-integrated biphasic PFA system comprising a multi-channel generator, variable loop circular catheter, and integrated PFA mapping software module.

Methods: Eight healthy porcine subjects were included. To evaluate safety, multiple ablations were performed, including sites not generally targeted for therapeutic ablation, such as the right inferior PV lumen, right superior PV ostium, and adjacent to the esophagus and phrenic nerve. To evaluate the efficacy, animals were recovered, followed for 30(±3) days, then re-mapped. Gross pathological and histopathological examinations assessed procedural injuries, chronic thrombosis, tissue ablation, penetration depth, healing, and inflammatory response.

Results: All eight animals survived follow-up. PV narrowing was not observed acutely nor at follow-up, even when ablation was performed deep to the PV ostium. No injury was seen grossly or histologically in adjacent structures. All PVs were durably isolated, confirmed by bidirectional block at re-map procedure. Histological examination showed complete, transmural necrosis around the circumference of the ablated section of right PVs.

Conclusion: This preclinical evaluation of a fully-integrated PFA system demonstrated effective and durable ablation of cardiac tissue and PV isolation without collateral damage to adjacent structures, even when ablation was performed in more extreme settings than those used therapeutically. Histological staining confirmed complete transmural cell necrosis around the circumference of the PV ostium at 30 days.

Keywords: catheter ablation; irreversible electroporation; preclinical model; pulmonary vein isolation; pulsed-field ablation.

Figure 1

Biosense Webster PFA system. (A) Components of the Biosense Webster PFA system. (B) Circular PFA catheter deployed in the RSPV and RIPV visualized on fluoroscopy and CARTO images. PFA, pulsed field ablation; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.

Figure 2

Mean RSPV and RIPV diameters^a after treatment with PFA. ^aPV measurements were performed for all animals as per the protocol, but some values were missing from the analyses due to loss of ultrasound or fluoroscopy images at the laboratory; five animals had deep vein assessment. Statistical tests performed include one‐way ANOVA and Tukey's pairwise tests for comparisons between groups. ANOVA, analysis of variance; PFA, pulsed‐field ablation; PV, pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein; SD, standard deviation

Figure 3

Effect of PFA procedure on adjacent cardiac tissues. (A) CARTO map showing position of phrenic nerve, gross pathology at 30 days postablation showing no tissue damage, and Masson's trichrome and H&E stain at 30 days postablation showing structural integrity of phrenic nerve; (B) Gross pathology and histology of mitral valve at 30 days postablation showing no tissue damage; (C) Gross pathology and histology of left atrial appendage at 30 days postablation showing no tissue damage. H&E, hematoxylin‐eosin; LAA, left atrial appendage; PFA, pulsed‐field ablation

Figure 4

Effect of PFA procedure on adjacent esophagus. (A) CARTO map showing that the anatomic position of esophagus and aorta are in close proximity, also apparent during gross pathology; (B) Gross pathology at 30 days after ablation delivered to the aorta wall showing no damage to the adjacent esophagus, even when indentations on the aorta are present indicating some mechanical pressure applied during original energy applications, with Masson's trichrome and H&E stain of esophagus section 30 days postablation showing structural integrity. H&E, hematoxylin‐eosin; PFA, pulsed‐field ablation

Figure 5

Contiguous circumferential lesions made at the RSPV. From left to right: RSPV orifice is covered with yellowish‐white scar tissue; H&E and Masson's trichrome stained section of the RSPV, with blue color indicating fully circumferential ablation and fibrosis/fibroplasia. H&E, hematoxylin‐eosin; PFA, pulsed‐field ablation; PV, pulmonary vein; RSPV, right superior pulmonary vein

Figure 6

Durability of electrical isolation with the PFA procedure. (A) Pre‐PFA voltage map and post‐PFA voltage maps acquired directly after the first procedure and after 30 days of follow up for re‐mapping; (B) EGMs taken before PFA, directly after PFA, and 30 days after the procedure during a re‐mapping procedure, showing acute electrical isolation with persistence of isolation in follow‐up. EGM, electrogram; PFA, pulsed‐field ablation.