Comparison of cerebral safety after 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). Although "silent," these may have long-term clinical implications and are challenging to study as postprocedural magnetic resonance imaging (MRI) is not standard of care. OBJECTIVE: The neurological assessment subgroup (NAS) of ADVENT compared cerebral effects of pulsed field ablation (PFA) with standard-of-care thermal ablation. METHODS: The NAS included consecutive randomized PFA and thermal ablation patients who received postprocedural brain MRI 12-48 hours after ablation. Patients with apparent SCE or SCL findings underwent a modified Rankin scale 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 1 patient with 2- to 4-mm SCEs, 1 patient with a 3-mm SCE, and 1 patient with 2 SCLs (5.5 mm and 11 mm). All modified Rankin scale and National Institutes of Health Stroke Scale scores were 0 before discharge and at 90-day follow-up. There were only 2 neurological safety events (1 transient ischemic attack [PFA] and 1 stroke [thermal ablation]) in the ADVENT study, neither of which was part of the NAS. CONCLUSION: The ADVENT trial provides the first prospective, randomized data on the cerebral impact of PFA and thermal ablation of AF. Incidence of SCE/SCL after ablation in the NAS was low.

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.

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.).

A randomized controlled trial of pulsed field ablation versus standard-of-care ablation for paroxysmal atrial fibrillation: The ADVENT trial rationale and design.

Background: Pulmonary vein isolation (PVI) is an effective treatment for paroxysmal atrial fibrillation (PAF). However, potential complications can occur due to the propagation of thermal energy into nontarget tissues adjacent to the targeted myocardium. Pulsed field ablation (PFA) is a novel ablation modality with the potential for preferential myocardial tissue ablation to minimize damage to collateral cardiac structures. A multielectrode pentaspline catheter has demonstrated safety and efficacy in treating PAF in single-arm, first-in-human studies. Objective: The study sought to perform a randomized clinical trial to directly compare this PFA catheter with conventional ablation-either radiofrequency or cryoballoon ablation. Methods: The ADVENT (Randomized Controlled Trial for Pulsed Field Ablation versus Standard of Care Ablation for Paroxysmal Atrial Fibrillation) trial is a multicenter, prospective, single-blind, randomized controlled trial to compare PVI using PFA vs conventional thermal ablation for drug-resistant PAF-with each site employing either (but not both) cryoballoon or radiofrequency ablation as a control condition. The sample size is adaptively determined based on Bayesian statistical methods. All patients will undergo PVI, and be followed for 12 months. Results: The primary effectiveness endpoint is a composite of acute procedural success and freedom from any documented atrial arrhythmia recurrence, repeat ablation, or use of antiarrhythmic drugs after a 3-month postablation blanking period. The primary safety endpoint is a composite of defined acute and chronic device- and procedure-related serious adverse events. Both primary endpoints will be evaluated for noninferiority of the novel PFA system compared with standard-of-care thermal ablation. Conclusions: By providing objective, comparative data, this study aims to scientifically determine whether the pentaspline PFA catheter is safe and effective for PVI ablation to treat drug-resistant PAF.

Incidence and significance of early recurrences of atrial fibrillation after cryoballoon ablation: insights from the multicenter Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) Trial.

BACKGROUND: Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. METHODS AND RESULTS: The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03-4.61; P=0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P<0.001). Among patients with ERAF, only current tobacco use (HR, 3.84; 95% CI, 1.82-8.11; P<0.001) was associated with LR. Conversely, early reablation was associated with greater freedom from LR (3.3% LR with early reablation versus 55.6% without; HR, 0.04; 95% CI, 0.01-0.32; P=0.002). CONCLUSIONS: ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.

Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial.

OBJECTIVES: This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. BACKGROUND: Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. METHODS: Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. RESULTS: Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p < 0.001]). Sixty-five (79%) drug-treated patients crossed over to cryoablation during 12 months of study follow-up due to recurrent, symptomatic AF, constituting drug treatment failure. There were 7 of the resulting 228 cryoablated patients (3.1%) with a >75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. CONCLUSIONS: The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978).