Comparison of pulsed‐field ablation versus very high power short duration‐ablation for pulmonary vein isolation

The newly introduced nonthermal pulsed field ablation (PFA) is a promising technology to achieve fast pulmonary vein isolation (PVI) with high acute success rates and good safety features. However, previous studies have shown that very high power short duration ablation (VHPSD) is also highly effective and fast to achieve PVI with potentially less arrhythmia recurrence compared to conventional radiofrequency ablation. Data comparing PFA to VHPSD‐PVI is lacking.


| INTRODUCTION
Pulmonary vein isolation (PVI) for the treatment of symptomatic paroxysmal and persistent atrial fibrillation (PAF and persAF) is a firstline therapy option. 1 Point-by-point radiofrequency (RF) catheter ablation or single-shot devices like the cryoballoon (CB) are mostly used to achieve PVI. 1,2Single-shot devices deliver comparable results with shorter procedure duration in comparison to low power long duration RF ablation (LPDL). 3,4Therefore, for example, CB-PVI has become the gold standard for de novo PVI. 5,6Since implementation of very high RF power short duration ablation (VHPSD) technique for PVI this alleged advantage for CB-PVI is debatable.A power setting of 70 W with an application duration of 7 s (5 s at the posterior wall) using a flexible tip noncontact force ablation catheter with enhanced irrigation increases resistive heating with a decrease in conductive heating.This results in wider and shallower tissue lesions as compared to conventional, considered as low power long duration (LPLD) energy settings (e.g., 30 W, 30-60 s per lesion).An in vitro animal model from Bourier et al. showed that lesions set with LPLD (30 W, 30 s) had a mean width of 7.5 mm with a depth of 5.7 mm, while VHPSD lesions had a mean width of 10.3 mm with a depth of 3.9 mm.Therefore, the power setting of VHPSD potentially spares adjacent tissues (e.g., esophagus and phrenic nerve). 7,8[11] As a new "single shot" device the new nonthermal pulsed field ablation (PFA) modality has been implemented into clinical routine.
Efficacy and safety of PFA have been described in previous studies showing low complication rates, short procedure times, and superior efficiency. 123][14] Furthermore, the MANIFEST registry revealed no permanent technology-specific complications. 15ta comparing the novel nonthermal PFA to the novel thermal VHPSD point-by-point ablation modality is sparse.
This study sought to investigate efficacy and procedural differences for PFA-PVI versus VHPSD-PVI in patients undergoing de novo ablation in the setting of PAF and persAF.

| Study population
Between September 2021 and October 2022 all consecutive patients undergoing de novo PFA-PVI for symptomatic PAF or persAF were included in this retrospective analysis and matched to patients receiving VHPSD-PVI during the same period at our center.Exclusion criteria were an age of <18 years, previous left atrial ablation, and lack or withdrawal of written informed consent.Data acquisition was performed using an electronic case report form (CRF) (RedCap Database).
The trial complied with the Declaration of Helsinki, the local ethics committee approved the protocol and all patients provided written informed consent for the procedure, general data acquisition, processing, and analysis.

| Procedure
In both groups oral anticoagulation was discontinued the day before ablation in patients receiving DOACs (if on twice daily DOACs the morning dose was given).In patients on vitamin K antagonists an international normalized ratio (INR) of 2-3 was targeted.All procedures were performed under deep analgo-sedation using propofol, midazolam, and fentanyl. 16ansesophageal echocardiography (TEE) was performed if patients presented in AF or atrial tachycardia (AT) to exclude intracardiac thrombi.In SR, TEE was conducted only in patients with interrupted OAC and CHA 2 DS 2 -VASc-Score ≥2.In both groups after successful TSP an activated clotting time (ACT) > 300 s was targeted using a weight-adjusted bolus of unfractionated heparin with repetitive boli adjusted to every 30 min ACT measurement.
Esophageal temperature was monitored using a temperature probe (S-Cath, Esophageal Temperature Probe; Circa Scientific Inc.) in VHPSD procedures.
Ablation was stopped when esophageal-probe temperatures exceeded temperatures of >41°C to prevent atrio esophageal fistula formation or esophageal erosion.
Procedure duration was defined as the time from groin puncture to sheath removal (skin-to-skin-time).
After PVI in both groups for access closure a figure-of-eightsuture in conjunction with compression bandage was used. 17,18al anticoagulation was continued the same day.All patients were ECG-monitored for 48 h after the procedure.Antiarrhythmic drugs (AAD) were discontinued at operators' discretion.Routinely AAD are discontinued immediately after PVI in patients suffering from PAF and after 3 months in patients in the setting of persAF.

| PFA-PVI
All PFA procedures were performed with the FARAPULSE™ system (Boston Scientific).After TSP, the 8,5-F TSX sheath was replaced by the 13-F sheath (FARADRIVE™; Boston Scientific).In the first 30 procedures, a straight guidewire (Amplatz extra stiff straight wire™; Cook Group Incorporated) was used to intubate the PVs.Over wire the PFA catheter (FARAWAVE™; Boston Scientific) was then positioned at the respective PV antrum.After 30 procedures, a J-tip guidewire (InQWire™; Merit Medical) was used instead of the straight guidewire as recommended by the manufacturer.At every PV antrum, 8 PFA impulses were delivered in the "flower" and "basket" configuration of the catheter.The delivery of more PFA applications was at operator's discretion.The FARAWAVE TM catheter was used to display the local electrograms at the PV antrum (before and between the PFA impulses) and inside the PV (after the impulses) to reveal entrance block.In the first 14 (25%) procedures, an electroanatomic map (EAM) of the left atrium (LA) was acquired with a multipolar mapping catheter (Pentaray™; Biosense Webster or HD-Grid; Abbott Abbott Park) after treatment of all PVs to verify entrance block.In the following procedures, proof of PV isolation was obtained by abolishment of local PV electrograms obtained by the FARAWAVE™ catheter.

| VHPSD-PVI
All VHPSD procedures were performed using an EAM system (Ensite Precision™ or Ensite X™; Abbott).All LA-EAM were acquired using a circumferential decapolar catheter (Advisor FL™ Sensor Enabled; Abbott).A noncontact-force ablation catheter with enhanced tip irrigation (20 mL/min) and distally positioned thermocouples (Flexibility D-or F-Curve; Abbott) was used due to its favorable design for VHPSD ablation and thermal tissue conduction and measurement. 9,19tral PVI was achieved using point-by-point ablation with isolation of both PV pairs avoiding overlap of the ablation lesion projections.
For circumferential PVI a power setting of 70 W for 7 s was used at all sites except for the posterior wall where RF duration was reduced to 5 s.Ablation with VHPSD was performed in a power-controlled mode which has been shown to be safe and effective by Winkle et al. and Kottmaier et al.Time limits were set at 7/5 s and a temperature cut-off of 42°C was used. 9,20Lesion projections were set to 5 mm, since lesion width is reported to range from 5 to 11 mm in in vitro studies for VHPSD. 21Interlesion-distance, as well as lesion-overlap, was avoided.An interlesion-distance of max. 2 mm was accepted followed by reassessment using pacing along the ablation line with the endpoint of non-excitability.This setting using an enhanced irrigated tip catheter showed the most favorable outcomes in terms of arrhythmia-free survival and procedure duration and was therefore as the comparator in this study. 7,9All patients irrespective of their AF history (PAF or persAF) received PVI only without additional ablation of atrial substrate or anatomical lines.Aside from recent studies only few data support ablation beyond PVI in a de novo ablation. 22Therefore, in accordance to the current guidelines only PVI was performed in all cases. 1,23rcumferential PVI (entrance block) was monitored with the circumferential mapping catheter.The endpoint was defined as complete PVI (entrance and if applicable exit block) with the additional endpoint of unexcitability of the ablation line evaluated by pacing along the ablation line. 24After a waiting time of 10 min PVI was reassessed.No adenosine challenge of PVI was performed since previous studies showed that the approach of the unexcitability of the ablation line alone is non-inferior to adenosine challenge for dormant conduction. 25
Patients receiving PPG-based tele-consultation were encouraged to record a PPG twice daily for 60 s, if abnormal PPGs were encountered patients underwent 24 h holter ECG or 12-lead ECG to ensure relapse of AF.Any detected atrial arrhythmia (atrial fibrillation, atrial tachycardia, atrial flutter) longer than 30 s was defined as recurrence of arrhythmia after a 90 days blanking period.

| Endpoints
The primary endpoint was defined as arrhythmia-free survival during follow-up.Secondary endpoints were procedural differences (procedure duration, fluoroscopy-time and -dose, use of contrast medium) and complications.

| Outcome
After a median follow-up of 125 (IQR: 109-162) days the Kaplan-Meier analysis (displayed in Figure 2) showed no significant differences in arrythmia-free survival between both groups.The logrank analysis showed a Chi-square of 0.911 (p = 0.340) indicating no significance in the multivariate analysis.
Ablation with PFA showed a HR of 0.680 for the primary endpoint failing significance with a 95% confidence interval (CI: 0.304-1.520).
A total of n = 3 (5%, all amiodarone) patients in the PFA group and n = 5 (9%, three amiodarone and two flecainide) patients in the VHPSD group were on AAD at the time of follow-up.All these patients suffered from persAF.
Re-ablation was performed in two PFA patients (3.5%).One of whom showed reconnection of all veins and reconnection of the right superior PV for the second patient.In the VHPSD group n = 4 (7.0%)patients underwent re-ablation showing two patients with reconnection (one patient all 4 PV's and one of the right superior and left inferior PV) and two patients with atrial tachycardia who received anterior and roof line ablation.
T A B L E 1 Baseline data of PFA and VHPSD-patients.F I G U R E 2 Kaplan-Meier-analysis showing arrhythmia-free survival during follow-up in PFA and VHPSD; Chi-square: 0.911 (p = 0.340).PFA, pulsed-field ablation; VHPSD, very high power short duration ablation.
first procedure.The incidence of complications did not differ between both groups (p = 0.500).

| Main findings
This trial compared, for the first time, the novel non-thermal PFA ablation modality to VHPSD for PVI in PAF and persAF patients and revealed that PFA is as safe and efficient as VHPSP-PVI but with significantly shorter procedure duration.However, the outcome regarding arrhythmia-free survival remains comparable to the established VHPSD.
In a recently published meta-analysis significantly higher rates of atrial arrhythmia-free survival after various HPSD ablation strategies were observed as compared to LPLD-PVI. 27 our analysis, the arrhythmia-free survival for PFA after 125 days was noninferior with a trend towards superiority compared to VHPSD-PVI in both PAF and persAF patients.The midterm overall arrhythmia-free survival in PFA patients was 81% among both PAF and persAF patients, which aligns with a multicenter study using the Farapulse™ (MANIFEST-PF) that demonstrated a similar arrhythmiafree survival of 78% in a large mixed cohort of PAF and persAF patients. 14 a retrospective analysis comparing PFA to HPSD with a setting of 50 W using a contact-force catheter in a mixed cohort arrhythmia free survival after 6 months was comparable in PFA (85% vs. 81% in our cohort) and HPSD patients (79% vs. 77% in our cohort). 28wever the "moderate" power settings used in the trial by Badertscher et al. 2023 do not correspond to our definition of VHPSD (70 W/7 s).
The complication rate was low and comparable to previous data for both groups.
Two tamponades occurred in the PFA group while using the extra stiff guidewire, also reported in the MANIFEST-PF registry. 15e possible complications using the extra stiff guidewire have been discussed previously, resulting in abandoning the use of this certain guidewire in PFA procedures. 29ter switching to a J-tip guidewire, no further wire-nor devicerelated pericardial tamponades occurred.
In the VHPSD group, one subclinical PV stenosis occurred.The latter was detected in a redo-procedure and confirmed in CT-scan.A trial by Ptaszek et al. 8 comparing LPLD to VHPSD (70 W/7 s) did not show significant differences in the occurrence of PV-stenosis using both technologies. 8PV stenosis remains a rare complication of singletip RF ablation but is rather associated with a distal isolation of PV then the power setting used in our trial.
In the context of HPSD the recently presented POWERFAST-III trial by Castrejón et al. has to be discussed.This trial showed a nearly 60% rate of silent brain ischemia in the VHPSD arm (70 W 10 s). 30 Although these finding are worrisome one should point out that the used catheter might not have been ideal for the use of VHPSD.
Irrigation mode and ablation duration potentially led to more charring  and thrombogenesis as compared to other catheters. 19Although not specifically evaluating occurrence of TIA or stroke no clinical appearance of the latter was observed.In the setting of PFA a recent trial showed a low incidence of 3% for silent brain ischemia. 31mparing data of both modalities is not yet available.
A potential benefit of PFA is an alleged more durable PVI compared to RF modalities.
First data of redo-procedures after PFA demonstrated a PV reconnection rate of <10%. 32In our analysis there was no difference in PV reconnection between PFA and VHPSD, however the total rate of redo procedures was low in our cohort.
An additional advantage of PFA is the shorter procedure duration compared to RF ablation modalities, which was confirmed by this study also in comparison to the "faster" VHPSD modality.
The short procedure duration shown in our data aligns with previous registries such as the MANIFEST trial. 15 line to our data, prior trials showed shorter fluoroscopy times for VHPSD compared to PFA. 9 The lack of difference in total fluoroscopy dosage in our study might be explicable due to the use of an enhanced irrigated tip catheter without contact force (not commercially available at that time).This potentially led to more fluoroscopic reassurance compared to the "standard" LPLD for safety reasons.Furthermore, significantly more angiographies were performed in the VHPSD group which is a potential driver for a higher fluoroscopy dose.The use of contrast medium was marginal but still significantly lower in the PFA group which might arise from more LA angiographies performed in the VHPSD group.However, one might also argue if a difference of 5 mL contrast medium has any clinical impact.The longer procedure time for VHPSD procedures was assumingly driven by the EAM time.However, a prospective structural analysis is required to validate this assumption.The use of VHPSD in conjunction with EAM enables to target concomitant or consecutive atrial arrhythmias (e.g., atrial flutter) after PVI within the first procedure, foremost in patients with persAF undergoing catheter ablation which might be of potential benefit compared to PFA.

| Limitations
Limitations of this study include its retrospective nature and the absence of a randomized controlled comparison between both techniques.Obtaining multicenter data for analysis will likely remain challenging due to the limited number of centers performing VHPSD with 70 W/7 s. 27 Furthermore, the follow-up of our analysis is relatively short compared to other publications investigating outcomes of PVI technologies.However, our data provide first outcome data comparing two novel technologies.
Since cerebral imaging for silent cerebral ischemia is not part of the clinical practice in our center, we cannot provide data for silent brain ischemia for both technologies.The possible clinical implications have been discussed above.

| CONCLUSION
PFA and VHPSD-PVI appear to be highly effective and safe for achieving PVI in the setting of PAF and persAF with comparable arrhythmia-free survival and a trend in favor of PFA.Additionally, the procedure duration for PFA-PVI is significantly shorter and therefore may be of potential benefit.However, the ability of tailored substrate modification might be a potential benefit of VHPSD.The choice between these ablation modalities should be based on individual patient characteristics, the presence of concomitant atrial arrhythmias, and the expertise of the operator.Further research, including randomized controlled trials, is needed to validate and compare these techniques more comprehensively, considering long-term outcomes and potential complications.
Statistical analysis was performed usingPrism for Mac version 9.0 and Excel for Mac version 16.69.Continuous variables are WÖRMANN ET AL. | 2419 presented as mean ± standard deviation, categorical variables as percentages.Unpaired t-tests were used for continuous variables if they were normally distributed.Otherwise, Mann-Whitney Utests were performed.Fisher's exact test was performed in case of dichotomous variables.Multivariate analysis was performed using Kaplan-Meier survival and cox-regression.Gehan-Breslow-Wilcoxon test for p-value and Mantel-Haenszel test were conducted for hazard ratio.A p < 0.05 was considered statistically significant.
TSP.The other was detected on the following day and was managed by pericardiocentesis.For the VHPSD group two groin bleedings (3.5%) were reported.Furthermore, one patient (1.8%) suffered from a subclinical pulmonary vein stenosis of the left superior pulmonary vein (LSPV) (severity of 99% in the CT angiography) observed during redo-ablation.The LSPV was described small during the F I G U R E 1 Arrhythmia-free survival after median follow-up of 125 days (interquartile range: 109-162).

F I G U R E 3
Procedural data of PFA and VHPSD patients.Procedure duration was significantly shorter in PFA while fluoroscopy duration was significantly shorter in VHPSD.PFA, pulsed field ablation; VHPSD, very high power short duration ablation.T A B L E 2 Procedural complications of PFA and VHPSD-patients.