Preclinical Evaluation of Pulsed Field Ablation: Electrophysiological and Histological Assessment of Thoracic Vein Isolation

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.

Keywords: atrial fibrillation; catheter ablation; endocardium; phrenic nerve; pulmonary vein.

Figure 1.

Multielectrode pulsed field ablation catheter deployed in flower pose.

Figure 2.

Catheter based pulsed field ablation (PFA).A–C, PFA catheter deployed over-the-wire in right superior pulmonary vein (RSPV), inferior common pulmonary vein (ICPV), and superior vena cava (SVC) of swine through a deflectable sheath. Pacing catheters are placed in the coronary sinus and the right ventricular outflow tracts. D, Baseline and post-ablation (after survival) pulmonary vein electrograms from a multipolar circular catheter. E and F, Voltage maps performed at follow-up showing level of isolation in the RSPV, ICPV, and SVC.

Figure 3.

Twelve lead EKGs demonstrating transient repolarization changes. A, Right superior pulmonary vein (RSPV) ablation with artifact of pulsed field ablation (PFA) pulse, followed by ST elevation in the precordial leads. B, Inferior common pulmonary vein (ICPV) ablation followed by ST elevation in inferior leads.

Figure 4.

Gross appearance of pulsed field ablation (PFA) lesions seen after formalin fixation. A, Monophasic PFA lesion in the superior vena cava (SVC) with presence of a visual gap (arrow). B, Biphasic PFA lesion in the SVC with contiguous and broad lesion (between dotted lines). C, Biphasic PFA lesion in the right superior pulmonary vein (RSPV) with contiguous broad lesion (arrows point in direction of distal pulmonary vein).

Figure 5.

Masson’s trichrome stain of sections from Biphasic cohort. A, Transmural pulsed field ablation (PFA) lesion in the superior vena cava (SVC; 10× magnification). B, Transmural PFA lesion in the right superior pulmonary vein (RSPV). C, Transmural PFA lesion in the inferior common pulmonary vein (ICPV). D, 200× view of fibrotic core of PFA—SVC lesion demonstrating a spared arteriole and nerve surrounded by fibrosis. E/F, 200× view of fibrotic core of radiofrequency (RF)-SVC lesion demonstrating a normal arteriole and a nerve infiltrated by fibrosis. E, Hematoxylin and Eosin; and F, Masson’s trichrome. A indicates arteriole; F, fibrosis; IF, infiltrating fibrosis in nerve (dotted lines); and N, nerve.