The objective of the PULSED AF trial was to evaluate the safety and efficacy of treating patients with PAF and PsAF via a PFA system (PulseSelect™ Pulsed Field Ablation System, Medtronic, Minneapolis, MN). The global, prospective, multicenter, non-randomized, and single-arm design of the PULSED AF trial design has been previously described in detail [7]. An international steering committee supervised study design and execution, data analysis, and evidence dissemination. Following principles outlined in the Declaration of Helsinki, this sub-analysis was conducted to assess outcomes of PFA treatment in patients with PAF and PsAF in Japan. Each of the four centers in Japan received approval from their local ethics review boards.

Patients, ranging from 18 to 80 years old, who had failed at least one class I or class III antiarrhythmic drug (AAD) and who had recurrent symptomatic PAF or PsAF were included. A prior publication encompasses the comprehensive list of study inclusion and exclusion criteria [7]. This sub-analysis includes patients with PAF and PsAF that were enrolled and underwent pulmonary vein isolation (PVI) via PFA in Japan at the four participating centers. All patients provided written informed consent before enrolling in the study.

A detailed description of the PFA procedure has been described in two previous PULSED AF publications [7, 17]. Briefly, clinicians introduced the PulseSelect catheter (9F) into the left atrium over a guidewire via transseptal puncture. A controlled biphasic, bipolar waveform was dispensed through a circular arrangement of 9 gold (3-mm-long electrodes) in the PulseSelect catheter. Fluoroscopy, intracardiac echocardiography (ICE) imaging, or mapping systems were employed to determine the positioning of the PFA catheter’s 25-mm circular array at every pulmonary vein (PV) (Figure 1). The PFA procedure did not require contrast media. One application was comprised of a series of four biphasic, bipolar pulse trains, each lasting 100–200 ms. After each application, the catheter was repositioned to achieve full circumferential isolation of the PV; a minimum of four ostial and four antral applications were delivered for each PV, as described previously. Following a mandatory 20-min wait period, confirmation of complete PVI via entrance block was required.

Pulmonary vein isolation using the PulseSelectTM pulsed field ablation system. A biphasic pulse waveform is delivered via the generator, creating a bipolar electric field that is sustained around the electrode array of the catheter to ablate the cardiac tissue. PulseSelect’s waveform is optimized to induce irreversible electroporation in cardiomyocytes, leading to tissue specific cell death without disrupting the cellular matrix

Study participants were monitored for 12 months via a combination of scheduled weekly and symptomatic transtelephonic monitoring (TTM), 12-lead ECGs (at 3, 6, and 12 months), and 24-h Holter monitoring (at 6 and 12 months). An independent core laboratory adjudicated arrhythmia monitoring events. Virtual or in-person visits at 1 week, 1, 3, and 12 months post-ablation were also conducted.

After the 90-day blanking period, efficacy was determined via freedom from a composite primary endpoint of acute procedural failure, arrhythmia recurrence of ≥ 30 s, repeat ablation, direct current cardioversion for atrial tachyarrhythmia recurrence, any subsequent left atrial surgery or ablation, or AAD escalation through 12 months. Within the blanking period, recurrent arrhythmias could be managed with AADs, cardioversion, or one repeat pulsed field ablation without being deemed a primary efficacy failure. Acute procedural failure was defined as the occurrence of any of the following: (1) inability to isolate all accessible, targeted PVs, which were minimally assessed for entrance block (and where assessable, exit block) and (2) ablation in the left atrium using a non-study device during the index procedure. AAD escalation included (1) prescribing of new class I or III AAD after the blanking period; (2) a class I or III AAD dose increase from the historic maximum ineffective dose after the blanking period; or (3) starting or using amiodarone at a dose greater than the maximum previous ineffective dose during the blanking period. Freedom from a composite of serious procedure- and device-related adverse events comprised the primary safety endpoint. The clinical events committee adjudicated whether each adverse event was associated with either the PulseSelect system or the PFA procedure.

The self-administered AF Effect on Quality of Life (AFEQT) Questionnaire, which is specific to AF health, and the European Quality of Life-5 Dimensions (EQ-5D) were utilized to assess QoL at baseline and 12 months. AFEQT scores range from 0 (complete AF-related disability) to 100 (no AF-related disability). The EQ-5D questionnaire has a composite score based on a five-question survey that ranges from 0 (least healthy) to 1 (most healthy). A clinically meaningful improvement in QoL is > 19 points for AFEQT and > 0.03 for EQ-5D [18, 19]. The study also collected episodes of healthcare utilization including hospitalizations, cardiovascular-related hospitalizations, emergency department visits, repeat ablations, and direct current cardioversions (12 months prior and post-ablation).

In the text, continuous variables are presented as a mean and standard deviation and categorical variables are presented as a percentage. The primary effectiveness endpoint was evaluated using Kaplan–Meier analysis. QoL is reported as the change from baseline to 12 months and was evaluated using the paired students t-test. Statistical analyses were performed using SAS software Version 9.4 (SAS Institute, Cary, NC). p-values of < 0.05 were considered statistically significant.