Comparison of cerebral safety following atrial fibrillation using pulsed field and thermal ablation: Results of the Neurological Assessment Subgroup in the ADVENT Trial.

BACKGROUND: Atrial fibrillation (AF) ablation carries the risk of silent cerebral event (SCE) and silent cerebral lesion (SCL). Though "silent," these may have long-term clinical implications and are challenging to study as post-procedural MRI is not standard-of-care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) to standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received post-procedural brain MRI 12-48 hours post-ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin Scale (mRS) assessment. MRI images were subsequently reviewed by a blinded Brain Imaging Core Laboratory. RESULTS: In total, 77 patients with paroxysmal AF were enrolled at 6 centers; 71 had analyzable scans (34 PFA; 37 thermal ablation). Through individual center review, 6 PFA and 4 thermal scans were identified as SCE/SCL positive, of which, 3 PFA and 0 thermal SCE/SCL findings were confirmed by a blinded core laboratory. MRI findings revealed one patient with 2-4mm SCEs, one patient with a 3mm SCE, and one patient with 2 SCLs (5.5mm and 11mm). All mRS and NIHSS scores were 0 prior to discharge and at 90-day follow-up. There were only two neurological safety events (1 TIA (PFA) and 1 stroke (thermal) in the ADVENT study, neither of which was part of the NAS. CONCLUSIONS: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCLs following ablation in the NAS was low.

Pulsed Field vs Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: Recurrent Atrial Arrhythmia Burden.

BACKGROUND: The ADVENT randomized trial revealed no significant difference in 1-year freedom from atrial arrhythmias (AA) between thermal (RF/Cryo) and pulsed field ablation (PFA). However, recent studies indicate that the post-ablation AA burden is a better predictor of clinical outcomes than the dichotomous endpoint of 30-second AA recurrence. OBJECTIVES: To determine i) the impact of post-ablation AA burden on outcomes, and ii) the effect of ablation modality on AA burden. METHODS: In ADVENT, symptomatic drug-refractory paroxysmal AF (PAF) patients underwent PFA or thermal ablation. Post-ablation transtelephonic ECG monitor (TTM) recordings were collected weekly or for symptoms, and 72-hour Holters were at 6- and 12-months. AA burden was calculated from percentage AA on Holters and TTMs. Quality-of-life assessments were at baseline and 12-months. RESULTS: From 593 randomized patients (299 PFA, 294 thermal), using aggregate PFA/thermal data, an AA burden exceeding 0.1% was associated with a significantly reduced quality-of-life and an increase in clinical interventions: redo ablation, cardioversion and hospitalization. There were more patients with residual AA burden <0.1% with PFA than thermal ablation (OR 1.5, 95%CI: 1.0, 2.3; p=0.04). Evaluation of outcomes by baseline demographics revealed that patients with prior failed Class I/III AADs had less residual AA burden after PFA compared to thermal ablation (OR 2.5, 95%CI: 1.4, 4.3; p=0.002); patients receiving only Class II/IV AADs pre-ablation had no difference in AA burden between ablation groups. CONCLUSION: Compared to thermal ablation, PFA more often resulted in an AA burden less than the clinically-significant threshold of 0.1% burden.

Autonomic Effects of Pulsed Field vs Thermal Ablation for Treating Atrial Fibrillation: Subanalysis of ADVENT.

BACKGROUND: Autonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA's relative myocardial selectivity may minimize autonomic effects. OBJECTIVES: This study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation. METHODS: ADVENT (The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation) was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months. RESULTS: This study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01). CONCLUSIONS: PFA's effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study.

Pulmonary vein narrowing after pulsed field versus thermal ablation.

AIMS: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. METHODS AND RESULTS: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. CONCLUSION: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue.

Durability of Pulmonary Vein Isolation Using Pulsed-Field Ablation: Results From the Multicenter EU-PORIA Registry.

BACKGROUND: Pulsed-field ablation (PFA) is a novel nonthermal ablation technology with high procedural safety and efficiency for pulmonary vein isolation (PVI). Premarket data showed high PVI durability during mandatory remapping studies. Data on lesion durability in real-world patients with clinically indicated redo procedures are scarce. OBJECTIVES: This study sought to report PVI durability rates in patients undergoing a clinically indicated redo procedure after an index PVI using PFA. METHODS: Patients from 7 European centers undergoing an index PVI using PFA were included the EU-PORIA (European Real-world Outcomes With Pulsed Field Ablation in Patients With Symptomatic Atrial Fibrillation) registry. In patients with subsequent left atrial redo procedures due to arrhythmia recurrence, 3-dimensional electroanatomical maps were acquired. PVI durability was assessed on a per-vein and per-patient level, and sites of reconnections and predictors of lesion durability were identified. RESULTS: Of 1,184 patients (62% paroxysmal atrial fibrillation) undergoing an index PVI using PFA, 272 (23%) had an arrhythmia recurrence. Of these, 144 (53%) underwent a left atrial redo procedure a median of 7 (Q1-Q3: 5-10) months after the first ablation. Three-dimensional electroanatomical maps identified 404 of 567 pulmonary veins (71%) with durable isolation. In 54 patients (38%), all pulmonary veins were durably isolated. Prior operator experience with cryoballoon ablation was associated with a higher PVI durability compared to operators with only point-by-point radiofrequency experience (76% vs 60%; P < 0.001). Neither the operators' cumulative experience in atrial fibrillation ablation (≤5 vs >5 years) nor the size of the PFA device used (31 mm vs 35 mm) had an impact on subsequent lesion durability (both P > 0.50). CONCLUSIONS: In 144 patients with arrhythmia recurrence after PFA PVI, durable isolation was observed in 71% of the pulmonary veins during the redo procedure, and 38% of all patients showed durable isolation of all veins.

Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

AIMS: Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. METHODS AND RESULTS: All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. CONCLUSION: The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

Acute procedural efficacy and safety of a novel cryoballoon for the treatment of paroxysmal atrial fibrillation: Results from the POLAR ICE study.

INTRODUCTION: Pulmonary vein isolation (PVI) is well established as a primary treatment for atrial fibrillation (AF). The POLAR ICE study was designed to collect prospective real world data on the safety and effectiveness of the POLARxTM cryoballoon for PVI to treat paroxysmal AF. METHODS: POLAR ICE, a prospective, non-randomized, multicenter (international) registry (NCT04250714), enrolled 399 patients across 19 European centers. Procedural characteristics, such as time to isolation, cryoablations per pulmonary vein (PV), balloon nadir temperature, and occlusion grade were recorded. PVI was confirmed with entrance block testing. RESULTS: Data on 372 de novo PVI procedures (n = 2190 ablations) were collected. Complete PVI was achieved in 96.8% of PVs. Procedure and fluoroscopy times were 68.2 ± 24.6 and 15.6 ± 9.6 min, respectively. Left atrial dwell time was 46.6 ± 18.3 min. Grade 3 or 4 occlusion was achieved in 98.2% of PVs reported and 71.2% of PVs isolation required only a single cryoablation. Of 2190 cryoapplications, 83% had a duration of at least 120 s; nadir temperature of these ablations averaged -56.3 ± 6.5°C. There were 6 phrenic nerve palsy events, 2 of which resolved within 3 months of the procedure. CONCLUSION: This real-world usage data on a novel cryoballoon suggests this device is effective, safe, and relatively fast in centers with cryoballoon experience. These data are comparable to prior POLARx reports and in keeping with reported data on other cryoballoons. Future studies should examine the long-term outcomes and the relationship between biophysical parameters and outcomes for this novel cryoballoon.

Rhythmia zero-fluoroscopy workflow with high-power, short-duration ablation: retrospective analysis of procedural data.

BACKGROUND: Fluoroscopy is commonly used during atrial fibrillation (AF) ablation to guide catheter navigation and placement. Technology improvements have significantly reduced fluoroscopy time, and subsequent radiation dose, necessary to perform successful ablations. However, there is still no amount of radiation exposure known to be completely safe. The aim of this manuscript is to describe a detailed zero-fluoroscopy RHYTHMIA HDx workflow for AF ablation. METHODS: This was an observational, single-center experience to describe the technique, acute procedural success, and safety using a novel zero-fluoroscopy workflow with the RHYTHMIA HDx mapping system and intracardiac echocardiography (ICE). Seventy-two consecutive patients undergoing de novo or redo AF ablation were retrospectively analyzed. Venous access was guided with ultrasound. ICE combined with the mapping system's magnetic tracking and sheath detection was used for precise catheter placement in the coronary sinus, at the transseptal puncture, and in the left atrium. A high-power, short-duration ablation strategy guided by local impedance was used. Pulmonary vein isolation was performed or touched up for all patients with additional lines added at the operator's discretion. RESULTS: Using this zero-fluoroscopy workflow, all patients achieved acute isolation with no significant procedure-related complications. Average procedure time was 73.7 ± 16.2 min, which included persistent (58%) and paroxysmal (42%) AF cases, and no procedures required conversion to fluoroscopy. CONCLUSIONS: In this experience, a zero-fluoroscopy workflow using the RHYTHMIA HDx mapping system combined with ICE was feasible and safe for ablation in a heterogenous AF population. This approach, in the appropriate patient population, can eliminate radiation exposure to patients and staff.

Novel cryoballoon to isolate pulmonary veins in patients with paroxysmal atrial fibrillation: long-term outcomes in a multicentre clinical study.

BACKGROUND: Recently, a novel cryoballoon ablation catheter has demonstrated acute safety and efficacy in de novo pulmonary vein isolation (PVI) procedures in patients with paroxysmal atrial fibrillation (PAF). However, there are limited studies demonstrating the long-term efficacy. The aim of this study was to evaluate the long-term safety and efficacy of this novel cryoballoon in treating PAF. METHODS: This was a non-randomized, prospective, multicentre study enrolling 58 consecutive patients. Cryoablation was delivered for 180 s if time to isolation was ≤ 60 s. Otherwise a 240-s cryoablation was performed. One centre performed pre- and post-ablation high-density mapping (n = 9) to characterize lesion formation. After a 3-month blanking period, recurrence was defined as having any documented, symptomatic episode(s) of AF or atrial tachycardia. All patients were followed for 1 year. RESULTS: Acute PVI was achieved in 230 of 231 pulmonary veins (99.6%) with 5.3 ± 1.6 cryoablations per patient (1.3 ± 0.7 cryoablations per vein). Forty-three (77%) patients remained arrhythmia-free at 1-year follow-up. Four patients (6.9%) experienced phrenic nerve injury (3 resolved during the index procedure; 1 resolved at 6 months). One serious adverse device event was reported: femoral arterial embolism event occurring 2 weeks post-index procedure. For patients who underwent high-density mapping, cryoablation was antral with 50% of the posterior wall ablated. CONCLUSIONS: Initial multicentre clinical experience with a novel cryoballoon has demonstrated safety and efficacy of PVI in patients with PAF. Ablation with this cryoballoon provides a wide, antral lesion set with significant debulking of the posterior wall of the left atrium.