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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.

> “I’ll follow him around the Horn, and around the Norway maelstrom, and around perdition’s flames before I give him up.” > > -Captain Ahab, Moby Dick > “The mysterious thing you look for your whole life will eventually eat you alive.” > > -Laurie Anderson on Moby Dick Optimal strategy and end points for ablation of persistent atrial fibrillation (AF) have not been well established. Although antral pulmonary vein isolation (PVI) is often effective for ablation of paroxysmal AF, it is an insufficient stand-alone strategy for many patients with persistent AF. Selection of adjunctive targets and determination of procedural end points are variable and at the discretion of the operator. Several studies suggested that termination of AF should be the procedural end point during ablation in patients with persistent AF, as a higher probability of maintaining sinus rhythm after the ablation was reported, despite a long procedure duration and a high rate of repeat ablation procedures. However, these studies were not consistently reproducible, and conversion usually occurred to an atrial tachycardia rather than sinus rhythm after extensive ablation. In patients with persistent AF, there is insufficient experimental, mechanistic, or clinical evidence to support termination of AF during ablation as a procedural end point. Response by Lim et al on p 980 Rapid and repetitive depolarizations originating within or at the antra of the pulmonary veins (PVs) and the other thoracic veins are the predominant mechanism in the initiation and perpetuation of paroxysmal atrial fibrillation (PAF).1–3 Antral isolation of PVs and elimination of focal triggers and drivers from other thoracic veins often result in termination and noninducibility of PAF in response to various pharmacological and pacing protocols. Patients with PAF whose AF terminated during ablation and were rendered noninducible, also were more likely to remain in sinus rhythm during long-term clinical follow-up.4 …

Background— Pulmonary vein reconnection after electrical isolation is commonly observed in the context of atrial fibrillation ablation and is associated with recurrent atrial tachyarrhythmias. Adenosine test was been performed to identify acute dormant conduction immediately after pulmonary vein isolation at index procedure. However, the utility of adenosine test at repeat procedure has not been reported. Methods and Results— We report 5 paroxysmal atrial fibrillation cases without any structural heart disease in which dormant thoracic vein conduction was associated with recurrent atrial tachyarrhythmias. All patients had undergone circumferential ipsilateral pulmonary vein isolation at the index procedure. Superior vena cava isolation was performed if superior vena cava–triggered atrial fibrillation was identified. At the index procedure, adenosine test did not provoke venous reconduction. At the repeat procedure, adenosine provoked clinical arrhythmia in 4 out of 5 cases after transient reconnection between culprit thoracic vein and atrium despite absence of reconnection at the start of the procedure. After the elimination of the dormant conduction gaps, all patients were free from recurrent arrhythmia. Conclusions— Adenosine provokes dormant thoracic vein conduction associated with the late recurrence of atrial tachyarrhythmias after previous thoracic vein isolation. Thus, adenosine provocation test can specifically help identify and target the cause of recurrent atrial arrhythmia.