Results
During this study, 94 structures were ablated in 25 healthy animals including 23 swine, 1 canine, and 1 ovine. The targeted structures included: RA (5), LA posterior wall (2), RAA (6), LAA (14), right superior PV (22), right inferior PV (20), left PV (16), SVC (4) and IVC (5). Each structure was ablated using 1.1±0.2 PFA applications resulting in successful ablation/isolation (Figure 3). Real-time locations of the spiral PFA catheter during ablation were recorded within the 3D map (Figure 4). Given the advent of QRS gating, no ventricular arrhythmias were inadvertently triggered during PFA. Meanwhile, PFA resulted in marked reduction in the post- versus pre-PFA electrogram amplitudes (0.17±0.21 mV vs. 1.18±1.08 mV; P<0.0001) as well as a significant increase in the post- versus pre-PFA pacing threshold at the ablated sites (>15 mA versus 0.6±0.7 mA, P<0.001) (Table 1). Minimal microbubbling and no discernable skeletal muscle twitching was observed during PFA. Though administration of an intravenous paralytic agent (succinylcholine 1 mg/kg) temporarily abolished all forms of skeletal muscle twitch/activation; in the absence of a paralytic agent, PFA at sites adjacent to the right/left PN (e.g., lateral RA or LAA) commonly resulted in visible PN capture and hemi-diaphragmatic stimulation. Yet, there was no incidence of diminished PN function during or post-PFA as confirmed by low-output PN pacing capture using the PFA catheter. When PN pacing capture was present (e.g., when targeting the right superior PV), acceleration levels were measured in the range of 5–9 m/s2. When ablating structures remote from the right/left PNs (e.g., the left PV), the absolute mean acceleration was only 0.05 m/s2 which was indiscernible from the background noise level (Supplemental Figure).
Complete and durable conduction block was demonstrated acutely and up to 3 months post-PFA (Figure 5). All lesions were large and durable at follow-up (range: 3 weeks to 3 months). Histologically, the PFA lesions were contiguous and transmural (Figure 6),measuring 25±9 mm x 21±7 mm and 7.6±1.6 mm deep. No evidence of collateral injury or abnormalities involving the PN (Figure 6)could be detected in any of the animals, including the 8 swine in which the PNs were intentionally targeted – neither acutely, nor during follow-up at 3–4 weeks post-PFA. Additionally, there were no observed cases of vascular injury. Likewise, gross and microscopic examinations of the brain, the rete mirabile, the kidneys, the liver, the lungs, and the bronchi revealed no evidence of embolization or adjacent structure/tissue injury in any of the animals (Figure 7).Moreover, post- versus pre-PFA T2-weighted MRI scanning (n=3 swine) did not show any evidence of embolic events.
In 5 swine (62 ± 12 kg), 14 PFA applications were delivered within the IVC toward an opposing esophagus, intentionally deviated toward/adjacent to this structure. All 14 animals completed the follow-up period without clinical sequelae. Their body weights increased by 15±4% during follow-up. All IVC treatments were transmural, measuring 15.6±5.5 mm x 5.9±1.4 mm. Histopathologic examinations revealed acute PFA-related changes in the esophageal muscular layer which appeared within 2 h of PFA (Figure 8). However, these changes completely resolved by 21±5 days of follow-up. No other acute or chronic lesions/abnormalities were detected in the esophageal mucosa or submucosa in any of the 5 animals at 3 weeks of follow-up.