Pulsed Field Ablation Research Articles

Preliminary real-world experience on mitral isthmus ablation with a novel catheter that toggles between radiofrequency and pulsed field ablation

Abstract Background The mitral isthmus (MI) is frequently targeted during the ablation of persistent atrial fibrillation (AF). Nevertheless, achieving a complete bidirectional MI block using radiofrequency (RF) is often technically challenging and time-consuming1,2. Previously, we described a fluoroscopy-guided technique to achieve MI block using a penta-spline pulsed field ablation (PFA) catheter3. Recently, a new catheter was introduced, which toggles between RF and PFA and is integrated into a 3D mapping system, thus supposedly facilitating its use for the ablation of extra-pulmonary vein structures4. Purpose To describe the acute efficacy and procedural features of the first cases of posterior MI ablation performed with the toggling catheter at two centers. Methods We collected and reviewed demographic, clinical and procedural features of all patients who underwent ablation of the posterior MI at our centers between September and October 2023. Ablation of the MI was performed with either RF or PFA according to operator’s discretion. Bidirectional MI block was validated through activation mapping and differential pacing. Results During the study period, 44 patients were treated with the toggling catheter. Out of them, 16 patients (aged 68.3±10.1 years; 29% females) underwent posterior MI ablation for persistent AF, in addition to PVI and posterior wall isolation. Mean history of AF was 29.8±34.5 months and mean LA volume 135.6±54.9 ml. Skin-to-skin procedural time (93 minutes, IQR 64-112), LA mapping time (9.0 min, IQR 7.3-12.1) and time required for MI ablation (4.0 min, IQR 3.3-6.5) were remarkably short. In PFA-treated patients (10 cases), first-pass MI block was achieved in 8 (80%), with 16 (IQR 12-22) applications; none of these patients required RF touch-up. In the remaining 6 RF-treated patients, first-pass MI block was achieved in 3 (50%) patients with 8 (IQR 6-13) applications. Additional PFA applications (median 3, IQR 2-5) on the most venous portion of the MI were required in all RF-treated patients. In the 5 patients in whom bidirectional block could not be achieved at first-pass, remapping and touch-up application time were 2.6 (IQR 2.6- 6.3) and 2.0 (IQR 0.8-5.2) minutes, respectively. Eventually, bidirectional MI block was achieved in 16/16 (100%) patients by the end of the procedure. Importantly, no patients in the entire cohort experienced complications such as coronary artery spasm or clinically significant pericardial effusion. Conclusions Several observations can be made on this first real-world experience on posterior MI ablation with the toggling catheter: first, acute safety and efficacy in achieving a bidirectional MI block are high with both PFA and RF; secondly, patients undergoing RF ablation often require additional PFA applications on the venous segment of the MI; lastly, the time required to achieve MI block is remarkably short even when remapping and touch-up applications are needed.Figure 1Figure 2

The new "olive strategy" for pulsed field ablation of atrial fibrillation: procedural data and early follow-up

Abstract Background Pulsed field ablation (PFA) is a new myocardial-specific ablation technology for atrial fibrillation (AF). Direct current electric energy is applied to cells and disrupts cell membranes by creating pores. Purpose The aim of this single-center study was to report procedural data and early recurrence of atrial tachyarrhythmia (ERAT) following a new PFA-based ablation strategy for pulmonary vein isolation (PVI). Methods Consecutive patients with symptomatic AF were enrolled to undergo PFA-PVI using the pentaspline catheter. A new ablation strategy was performed: In total 10 applications per pulmonary vein (PV) were delivered. In addition to the conventional four applications in flower- and four applications in basket-configuration, two applications were delivered in a smaller "olive"-configuration. ERAT was defined as any documented AF/atrial tachycardia (AT) lasting more than 30 seconds during a 90-days blanking period. Procedural and demographic data were analysed. Results 60 patients (37% female, age 67±12, 43% paroxysmal atrial fibrillation [PAF]) were included in this preliminary analysis. 239 PVs were identified, and all PVs could be isolated using solely the PFA device. All PVs were isolated with the first application. 40 applications per patient were delivered. No complications occurred. Procedure time was 30±11 min, fluoroscopy time was 6±3 min. Median follow-up time was 100 days. 20% of patients experienced an early recurrence after a median of 2 days (IQR 1-7.25; 92% AF, 8% AT). Kaplan Meier estimated freedom of AF/AT was 83.3 % at 3 months, 92.3% for PAF and 76.5% for persistent atrial fibrillation (p=0.11). Conclusions Our data show feasibility of a new ablation strategy with the pentaspline PFA-catheter. This study indicates high acute efficacy and safety. 83.3% of patients are free of AF/AT at 3 months. Longer follow-up times are needed to assess the clinical outcome and will be available at the time of presentation.

Pulsed-field ablation using a lattice-tip catheter without general anesthesia is feasible for atrial fibrillation ablation

Abstract Background General anesthesia (GA) was employed to titrate lesion formations for a pulsed-field ablation (PFA) using a lattice-tip catheter. The evidence using a lattice-tip catheter without the use of GA is limited. Purpose We conducted a series of exploratory evaluation of a lattice-tip PFA catheter ablation without GA. Methods Patients undergoing their first atrial fibrillation (AF) ablation procedures using a lattice-tip catheter were enrolled in the study. To assess acute outcomes and safety, the patients were divided into two groups: one undergoing the procedure with GA and the other without GA. Procedural characteristics were collected. Results In total, 20 patients (6 with GA, 14 without GA) were enrolled in the current study. One patient in non-GA group needed a larynx mask due to apnea from anesthesia. The pre-ablation 3D mapping time was equivalent between the two group (with GA versus without GA: 17±7 versus 16±5; P=0.762). All first-pass isolations of the pulmonary veins (PV) were successfully achieved, and there was no difference in the number of applications between the right and left PV (with GA versus without GA: 45±8 versus 53±12; P=0.206 and 47±14 versus 49±9; P=0.792). Linear lesions including anterior linear ablation (33% with GA and 36% without GA: P=1.000), roof linear ablation (67% with GA and 71% without GA: P=1.000) and cavo-tricuspid isthmus ablation (0% with GA and 7% without GA: P=1.000) were performed. The ablation, laboratory stay and fluoroscopy times were equivalent between the two group (with GA versus without GA:88±22 versus 97±20; P=0.483, 128±25 versus 111±18; P=0.216 and 9±4 versus 10±2; P=0.902), while the pre-ablation preparation times were shorter in the group without GA (with GA versus without GA:40±17 versus 14±4; P<0.01). There was no major and minor procedural complication in both groups. Conclusions The use of a lattice-tip catheter for ablation without GA has a potential to shorten the whole procedural work-flow including preparing time while maintaining comparable safety and lesion formation to cases where GA is utilized.

Acute procedural characteristics and safety of pulsed field cryoablation for persistent AF: multicenter results from the first in human PARALELL trial

Abstract Introduction Pulsed Field Cryoablation (PFCA) is dual-energy cardiac ablation modality consisting of short-duration ultra-low temperature cryoablation (ULTC) followed immediately by pulsed electric field ablation (PFA) delivered from the same catheter. It has been hypothesized that it may be beneficial to combine the efficiency of PFA with the contact and stability offered by ULTC. In patients with persistent atrial fibrillation, PFCA could be of particular benefit when creating extended lesion sets beyond pulmonary vein isolation such as posterior wall ablation. By focusing the electric field in high-impedance frozen tissue, PFCA may increase lesion depth and durability despite lower delivered current, while minimizing PFA-related microbubbles and skeletal muscle contraction. Purpose To report the acute outcomes of PFCA observed in the first-in-human PARALELL trial. Methods PFCA was performed using a novel stylet-driven catheter connected to the dedicated ULTC and PFA energy sources. The protocol-defined lesion set included pulmonary vein isolation and posterior wall (PW) ablation, with additional left and right atrial targets per operator discretion. Circular and linear lesions of varying dimensions were created by in-vivo shaping of the flexible, 11 cm-long ablation element of the catheter using exchangeable stylets. The ULTC freeze of 30 second duration was followed immediately by bipolar, biphasic PFA pulse trains delivered sequentially between the pairs of sixteen 3-mm electrodes evenly spaced along the ablation element. Results At 5 European and Canadian sites, 26 patients (age 68±9 years, 88.5% male, median left atrial size 45 mm, IQR [43 mm-48 mm]) underwent PFCA with 22.6 ± 9.6 ablation lesions per patient. The lesion set included 11.9 ± 4.1 lesions to PVs, 7.4 ± 2.7 to the PW, and in 14 patients, 6.6 ± 9.0 lesions to other atrial targets (left atrial roof and floor, PV carinas, mitral and cavotricuspid isthmuses). Isolation was achieved in 94.2% (98 of 104) of PVs and 92.3% (24 of 26) of PWs. The average procedure time was 130.3 ± 40.9 minutes, with catheter dwell time of 78.8 ± 26.0 minutes. Procedure-related groin hematoma at discharge was the only serious adverse event by site adjudication. Intracardiac echocardiography (ICE) performed in 18 patients identified Grade I (FEW) microbubbles in 1.3% (5 of 398) of ablations. Similarly, only faint muscular contractions were observed in 2 of 26 patients, occurring during 1.2% (4 of 339) of lesions placed in 15 patients not receiving any paralytic agents. Conclusions This initial multi-center experience suggests that PFCA can be efficiently performed on multiple atrial targets using a single versatile catheter system, with high acute success and good early safety profile, including minimal occurrence of PFA-related microbubbles and skeletal muscle contractions. The evaluation of the chronic 12-month effectiveness vs ULTC benchmarks and PFA comparators is ongoing.

Pulsed electric field ablation for perimitral flutter - retrospective comparison of anterior vs lateral mitral block strategy

Abstract Introduction Catheter ablation of atrial fibrillation has become a standard of care for symptomatic patients. Patients with persistent atrial fibrillation might require additional substrate modification on top of pulmonary vein isolation. In case of spontaneous or inducible perimitral flutter, RF ablation to achieve anterior or lateral mitral block is challenging. A pulsed electric field (PEF) is a novel energy source that enables the rapid and safe creation of larger lesions. Purpose A retrospective study aimed to compare the safety and early outcome data of either anterior or lateral mitral block strategy performed by PEF using a pentaspline multipolar ablation catheter. Methods The population consists of 67 patients (23 women, age: 68 ± 8 years) with either spontaneous or inducible perimitral flutter. Fifty-five percent of patients had previous ablation of atrial fibrillation using radiofrequency energy (2.0 ± 1.2 procedures/patient). Using a pentaspline multipolar catheter, all patients underwent isolation (or reisolation) of pulmonary veins and posterior wall. The same catheter was used for the treatment of perimitral flutter. Creating either anterior (ANTERIOR group) or lateral (LATERAL group) mitral block was selected at the discretion of the operator. Results A total of 37 and 30 patients were treated in the ANTERIOR and LATERAL groups, respectively. The perimitral flutter was terminated in all cases. However, complete and persistent block across the ablated region was more likely achieved in the ANTERIOR vs LATERAL group (92 vs 73%, p=0.04). There was one tamponade in the ANTERIOR group. A clinically relevant spasm of the coronary artery was not observed in any patient. At 3-month follow-up, non-significantly more patients were in sinus rhythm in the ANTERIOR vs LATERAL group (81% vs 63%, p=0.1). Conclusion Creating both anterior and lateral mitral block for the treatment of perimitral flutter is feasible and safe using a pentaspline multipolar catheter and PEF. Achievement of the anterior mitral block is more likely. Whether this will impact the long-term outcome remains to be determined.

High efficacy and safety of endocardial pulsed electrical field ablation via contact force-controlled catheters for mitral isthmus ablation

Abstract Background A new technology of a pulsed field generator enables established contact force-controlled radiofrequency (RF) catheters to apply point by point monopolar pulsed electrical field (PEF) energy for linear lesions in atrial fibrillation (AF) ablation. Purpose We evaluated this novel monopolar PEF ablation technique for creating lateral mitral isthmus ablation lines in case of perimitral flutter or complex AF patients non responder to pulmonary vein isolation (PVI). Methods Patients (n=44, age 65±11 years) referred for ablation/re-ablation of AF with spontaneous or inducible perimitral atrial flutter (n=34, 77%) or persistent AF and severe enlarged atrium (n=7) or de novo longstanding persistent AF (n=3) without signs of atrial fibrosis were included in our patient cohort for lateral mitral isthmus ablation with PEF applications. After 3D high density voltage mapping of the left atrium with multipolar microelectrode catheters, and confirmation/completion of PVI, an endocardial lateral mitral isthmus line was performed. Using contact force sensing catheter, 25A PEF energy pulses were applied targeting a minimum of 10g contact force and an interlesion distance ≤5mm. Before PEF application 0.2 mg nitroglycerin was intravenously injected. If the inferolateral mitral isthmus line to the left inferior pulmonary vein could not be blocked, a more superior lateral line to the left superior pulmonary vein was performed. If the mitral isthmus could not be blocked by endocardial PEF application or conduction recurred after adenosine injection an additional epicardial ablation via RF application in the coronary sinus was performed. Results Exclusively endocardial PEF application blocked the lateral mitral line in 37 out of 42 cases (88%) with 23±14 PEF applications. After an unsuccessful inferior lateral mitral line, in 34% of cases a second superior lateral mitral line have to be performed. Only in five cases additional epicardial RF applications via coronary sinus were necessary to complete the mitral isthmus block. Block time between superior lateral mitral anulus and infero lateral coronary sinus was 196±48 ms. One pericardial tamponade which could be successfully drained, and no other serious complication occurred throughout all procedures (no ST segment elevation, no tamponade requiring surgery, no cerebrovascular event). Limited follow-up will be available at the time of presentation. Conclusion Blockade of left atrial mitral isthmus line with PEF application via contact force-sensing catheters for ablation of complex atrial fibrillation patients is very efficient and safe. Especially the high efficacy of exclusively endocardial PEF application for creation of a lateral mitral isthmus block in most patients is very promising. However, the long term permanence of the linear lines have to be awaited.

Real life experience with point by point pulsed field ablation for recurrent ventricular arrhythmias

Abstract Introduction The safety and effectiveness of electroporation/point by point pulsed field ablation (PP PFA) as emerging technoloy for catheter ablation (CA) of ventricular arrhythmias (VAs) has been described till now only in case reports. Purpose The aim of this observational retrospective study is to present real life data concerning the overall performance of PP PFA for CA of recurrent VA. Methods A total number of 13 consecutive patients (11 VTs and 2 PVCs), in whom recurrent VTs after RF ablation documented, were included. In all patients the substrate location was documented beforehand based on cardiac MRI or CT with myocardial thinning. For substrate mapping a high resolution multipoint mapping catheter was used. A complete success was defined as non inducibility of any arrhythmia at the end of procedure respectively lack of VA recurrence at follow – up. Results Excepting 2 patients, all other had a non ischemic cardiomyopathy as underlying heart disease (mean age 63 ± 8 y/o, mean LVEF 42 % ± 9 %). In every patient at least one conventional RF CA has been performed previously (mean 2 ± 1) and 38 % of patients had a previous epicardial RF VT ablation. The PP PFA VT ablation was performed endocardialy in 11 patients (84 %), respectively epicardialy in 2 patients. The ablation sites had a septal location in 53 % of patients and other localisation in 47 % of patients. The applied energy was 25 A. The overall acute complete success was achieved in 77 % patients. At medium 6 ± 3 months follow up a complete success was present in 46 % cases. Most frequently a VT recurrence after PP PFA ablation was encountered in patients with combined septal and nonseptal substrate distrubution. After PP PFA, the RF CA strategy due to recurrent VAs was endocardial in 2 patients, respectively epicardial 2 in cases and bipolar in 1 case. No PP PFA redos were undergone. Three major complications have been documented (1 tamponade, 1 AV block III° and 1 complete LBBB). Conclusion As bailout strategy in patients with failed conventional CA, PP PFA represents a safe strategy. Specific complications like temporary atrioventricular or intraventricular conduction disturbancies are extremely rare, reversible but not life threathening. The midterm success is satisfactory but still limited in patients with intramural substrate.

The CellFX Percutaneous Electrode System for Nanosecond Pulsed Field Ablation.

The purpose of this study was to demonstrate the safety and performance of the CellFX Percutaneous Electrode for delivering nanosecond pulsed field ablation (nsPFA) energy to soft tissues. Three different porcine tissue types were treated, namely, liver, kidney, and skeletal muscle, at treatment levels of three times greater than clinical treatment levels. The histological characteristics of the ablation zone for each of these tissues compared with that of radiofrequency (RF) ablation on day 0 and 2 days post-treatment. Ablation zone dimensions were measured during gross necropsy after tetrazolium chloride staining and compared between the nsPFA and RF groups at 2 days post-ablation. The CellFX system successfully achieved ablation and necrosis of all treatment sites in all target tissues. No evidence of thermal effects or collagen degeneration was found at any of the nsPFA treatment sites. Overall systemic tolerability was evidenced by the absence of clinically significant changes in urinalysis and serum chemistry before and after treatments.

Novel Ablation Catheters for Atrial Fibrillation.

Various ablation technologies with different energy sources are currently being either used or being investigated for atrial fibrillation (AF) ablation. Potential complications continue to occur due to the indiscriminate thermal effects on non-targeted tissues adjacent to the myocardium that are common to all thermal ablation modalities. Pulsed field ablation (PFA) has recently gained significant attention and interest as an approach to AF ablation. PFA uniquely has the ability to circumvent certain complications related to thermal energy. PFA is a non-thermal ablation modality with the potential for unique-tissue selectivity that can minimize damage to collateral cardiac structures. Several PFA systems for AF ablation are currently being investigated. Some PFA systems have been designed to serve as single-shot approaches to achieve pulmonary vein isolation (PVI), and others have focal designs enabling flexible PVI lesion sets as well as linear/focal ablations. Favorable acute success rates and low incidence of complications with short procedure times have been reported with several PFA systems regardless of catheter design (single-shot or focal catheter). Clinical PFA studies in which chronic remapping was conducted, demonstrated pulmonary vein (PV) durability improved with evolutional modifications of pulsed field waveforms/dosing, achieving over 90% PV durability with optimized waveforms. Rare adverse events related to PFA may surface with its increasing use worldwide and as sicker patients get exposed to PFA. We believe that both excitement and vigilance are in order as we embark on yet another new chapter of AF ablation.

Pulsed field ablation in patients with cardiac implantable electronic devices: an ex vivo assessment of safety.

Pulse field ablation (PFA) is a novel catheter ablation technology with potential safety benefits due to its tissue selectivity. It has the potential to directly damage or interact with the functionality of cardiac implantable electronic devices (CIEDs) in the form of electromagnetic interference (EMI). The aim of our study was to assess the impact of PFA on CIEDs. PFA lesions (45 per CIED) were applied from the Farapulse system to CIEDs (< 5 cm from the lead tip and < 15 cm from the generator). All devices were checked before and after PFA application for proper sensing and pacing functionality as well as for integrity of shock circuits in ICDs using a heart simulator. Moreover, devices were then interrogated for any spontaneous reprogramming, mode switching or other EMI effects. In total, 44 CIEDs were tested (16 pacemaker, 21 ICDs, 7 CRT-P/D) with 1980 PFA applications. There was no change in device settings, functionality and electrical parameters, and there was no macroscopic damage to the devices. The risk of damage to the electric components or leads on a patient-based analysis is 0/44 (95% CI 0-8%) and on a PFA pulse-based analysis is 0/1980 (95% CI 0-0.2%). Clinically relevant EMI appeared with oversensing and pacing inhibition but not tachycardia detection. Bipolar PFA appears safe and does not result in damage to CIEDs or leads. Clinically relevant EMI does occur, but appropriate peri-procedural programming may mitigate this. In vivo studies are needed to confirm our findings.

Technical principles of ablation therapy

Catheter ablation is astandard procedure in modern cardiology. It can significantly improve the quality of life and life expectancy of cardiac arrhythmia patients. Besides cardiac mapping, ablation itself is afundamental step tosuccessfully treat cardiac arrhythmias. There are various ablation technologies at hand: In traditional radiofrequency (RF) ablation, electrical current flow generates coagulation necrosis. When understanding the biophysical principles of RF ablation, the investigator is capable to adapt lesion geometry and size to the requirements of the procedure and vary them individually. In addition, lesion metric indices evaluate and integrate important parameters such as power, duration, impedance and contact force to standardize and control RF lesions. Cryoablation induces ice crystals within myocardial tissue, which lead to destruction and electrical scarring of the treated tissue. Histologically, cryolesions are well-delineated with preserved tissue architecture and intact endocardium. Pulsed field ablation (PFA) is anovel rising technology, particularly used for pulmonary vein isolation. In contrast to classic thermal technologies (RF and cryoablation), PFA uses pulsed electrical fields to electroporate cardiac tissue and thereby creates damage on acellular level only.

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

BackgroundThe ADVENT randomized trial revealed no significant difference in 1-year freedom from atrial arrhythmias (AA) between thermal (radiofrequency/cryoballoon) and pulsed field ablation (PFA). However, recent studies indicate that the postablation AA burden is a better predictor of clinical outcomes than the dichotomous endpoint of 30-second AA recurrence. ObjectivesThe goal of this study was to determine: 1) the impact of postablation AA burden on outcomes; and 2) the effect of ablation modality on AA burden. MethodsIn ADVENT, symptomatic drug-refractory patients with paroxysmal atrial fibrillation underwent PFA or thermal ablation. Postablation transtelephonic electrocardiogram monitor 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 transtelephonic electrocardiogram monitors. Quality-of-life assessments were at baseline and 12 months. ResultsFrom 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 antiarrhythmic drugs 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 antiarrhythmic drugs pre-ablation had no difference in AA burden between ablation groups. ConclusionsCompared with thermal ablation, PFA more often resulted in an AA burden less than the clinically significant threshold of 0.1% burden. (The FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation [ADVENT]; NCT04612244)

Pulsed Field Energy in Atrial Fibrillation Ablation: From Physical Principles to Clinical Applications.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

AF ablation using a novel “single-shot” map-and-ablate spherical array pulsed field ablation catheter: 1-Year outcomes of the first-in-human PULSE-EU trial

BackgroundDuring pulsed field ablation (PFA), electrode-tissue proximity optimizes lesion quality. A novel “single-shot” map-and-ablate spherical multielectrode PFA array catheter that is able to verify electrode-tissue contact was recently studied in a first-in-human trial of atrial fibrillation (AF). ObjectiveThe aim of this study was to report lesion durability data, safety, and 12-month effectiveness outcomes. MethodsThe spherical PFA catheter, an all-in-one mapping and ablation system, was used to render anatomy and to deliver biphasic pulses (ungated 1.7 kV pulses; ∼40 seconds/application). Ablation sites included pulmonary veins (PVs) and, in selected patients, posterior wall and mitral isthmus. Follow-up was invasive remapping at ∼3 months, electrocardiograms, Holter monitoring at 6 and 12 months, and symptomatic and scheduled transtelephonic monitoring. The primary and secondary efficacy end points were acute PV isolation (PVI), PVI durability, and atrial arrhythmia recurrence. ResultsIn the 48-patient AF cohort (paroxysmal, 48%; persistent, 52%), lesion sets included PVI (n = 48; 1.2 applications/PV), posterior wall (n = 20; 3.6 applications/posterior wall), and mitral isthmus (n = 11; 2.9 applications/mitral isthmus). Lesions were acutely successful for all 187 of 187 PVs (100%), 20 of 20 posterior walls (100%), and 10 of 11 mitral isthmuses (91%). Pulse delivery time, left atrial catheter dwell time, and procedure time were 61.5 ± 32.8 seconds, 53.9 ± 26.5 minutes, and 87.8 ± 29.8 minutes, respectively. Remapping (43/48 patients [89.5%]) revealed that 158 of 169 PVs (93.5%) were durably isolated. The only complication was a drug-responsive pericarditis. The 1-year Kaplan-Meier estimates of freedom from atrial arrhythmia were 84.2% (paroxysmal AF) and 80.0% (persistent AF). ConclusionThe single-shot spherical array PFA catheter can safely achieve durable lesions, translating into good clinical efficacy.

Safety and Effectiveness of Pulsed Field Ablation for Atrial Fibrillation in Patients With Heart Failure

BackgroundAtrial fibrillation (AF) and heart failure (HF) coexist, increasing morbidity and mortality. Studies have demonstrated improved outcomes following AF ablation in HF patients with reduced ejection fraction (EF). ObjectivesThis study sought to assess the outcomes of pulsed field ablation (PFA) in HF. MethodsMANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a multicenter, patient-level registry of consecutive patients undergoing PFA for paroxysmal AF or persistent AF (PerAF). In this substudy, patients were stratified as no history of HF (no-HF), HF with preserved EF (HFpEF) (left ventricular EF of ≥50%) or HF with reduced/mildly reduced EF (HFmr/rEF) (left ventricular EF of <50%). The primary effectiveness and safety endpoints were freedom from documented atrial arrhythmias lasting ≥30 seconds and major adverse events, respectively. ResultsOf the 1,381 patients, 85% (n = 1,174) were no-HF, 6.2% (n = 87) were HFpEF, and 8.6% (n = 120) were HFmr/rEF. No-HF patients had less PerAF than patients with HF (P < 0.001), with no difference between HF subtypes (P > 0.99). The 1-year freedom from atrial arrhythmia was significantly higher in no-HF patients than in those with HFpEF or HFmr/rEF (79.9%, 71.3%, and 67.5%, respectively; P < 0.001) but similar between patients with HFmr/rEF and HFpEF (P = 0.26). However, there was no significant difference in freedom from atrial arrhythmia among patients with no-HF vs HFpEF vs HFmr/rEF for those with paroxysmal AF (82.8%, 82.4%, and 71.7%, respectively; P = 0.09) and PerAF (73.3%, 64.2%, and 64.9%, respectively; P = 0.14). Major adverse event rates were similar between the no-HF, HFpEF, and HFmr/rEF groups (1.9%, 0%, and 2.5%, respectively). ConclusionsPFA appears to be potentially safe and effective in AF patients with HF. Freedom from atrial arrhythmia post-PFA was higher in patients without a history of HF, with no significant difference between HF subtypes.

Cost, efficiency, and outcomes of pulsed field ablation vs thermal ablation for atrial fibrillation: A real-world study

BackgroundWith the exponential growth of catheter ablation for atrial fibrillation (AF), there is increasing interest in associated health care costs. Pulsed field ablation (PFA) using a single-shot pentaspline multielectrode catheter has been shown to be safe and effective for AF ablation, but its cost efficiency compared to conventional thermal ablation modalities (cryoballoon [CB] or radiofrequency [RF]) has not been evaluated. ObjectiveThe purpose of this study was to compare cost, efficiency, effectiveness, and safety between PFA, CB, and RF for AF ablation. MethodsWe studied 707 consecutive patients (PFA: 208 [46.0%]; CB: 325 [29.4%]; RF: 174 [24.6%]) undergoing first-time AF ablation. Individual procedural costs were calculated, including equipment, laboratory use, and hospital stay, and compared between ablation modalities, as were effectiveness and safety. ResultsSkin-to-skin times and catheter laboratory times were significantly shorter with PFA (68 and 102 minutes, respectively) than with CB (91 and 122 minutes) and RF (89 and 123 minutes) (P < .001). General anesthesia use differed across modalities (PFA 100%; CB 10.2%; RF 61.5%) (P < .001). Major complications occurred in 1% of cases, with no significant differences between modalities. Shorter procedural times resulted in lower staffing and laboratory costs with PFA, but these savings were offset by substantially higher equipment costs, resulting in higher overall median costs with PFA (£10,010) than with CB (£8106) and RF (£8949) (P < .001). ConclusionIn this contemporary real-world study of the 3 major AF ablation modalities used concurrently, PFA had shorter skin-to-skin and catheter laboratory times than did CB and RF, with similarly low rates of complications. However, PFA procedures were considerably more expensive, largely because of higher equipment cost.

Ablating Myocardium Using Nanosecond Pulsed Electric Fields: Preclinical Assessment of Feasibility, Safety, and Durability.

Unlike conventional microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation in swine. A novel endocardial nanosecond pulsed field ablation system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Predetermined survival periods were <1 (n=1), ≈2 (n=7), ≈7 (n=6), 14 (n=2), or ≈28 (n=9) days, and venous isolation was assessed before euthanasia. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathologic examination. All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed, and all 13 (100%) were transmural (depth, 6.4±0.4 mm). Ventricular lesions were 14.7±4.5 mm wide and 7.1±1.3 mm deep, with high-dose lesions deeper than low-dose (7.9±1.2 versus 6.2±0.8 mm; P=0.007). The esophagus revealed nontransmural adventitial surface lesions in 5 of 5 (100%) animals euthanized early (2 days) post-ablation. In the 10 animals euthanized later (14-28 days), all animals demonstrated significant esophageal healing-8 with complete resolution, and 2 with only trace fibrosis. A novel, endocardial nanosecond pulsed field ablation system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and nontransmural esophageal lesions can occur with worst-case assessments suggesting limits to pulsed field ablation tissue selectivity and the need for dedicated assessments during clinical studies.

Dual-energy lattice-tip ablation system for persistent atrial fibrillation: a randomized trial

Clinical outcomes of catheter ablation for atrial fibrillation (AF) are suboptimal due, in part, to challenges in achieving durable lesions. Although focal point-by-point ablation allows for the creation of any required lesion set, this strategy necessitates the generation of contiguous lesions without gaps. A large-tip catheter, capable of creating wide-footprint ablation lesions, may increase ablation effectiveness and efficiency. In a randomized, single-blind, non-inferiority trial, 420 patients with persistent AF underwent ablation using a large-tip catheter with dual pulsed field and radiofrequency energies versus ablation using a conventional radiofrequency ablation system. The primary composite effectiveness endpoint was evaluated through 1 year and included freedom from acute procedural failure and repeat ablation at any time, plus arrhythmia recurrence, drug initiation or escalation or cardioversion after a 3-month blanking period. The primary safety endpoint was freedom from a composite of serious procedure-related or device-related adverse events. The primary effectiveness endpoint was observed for 73.8% and 65.8% of patients in the investigational and control arms, respectively (P < 0.0001 for non-inferiority). Major procedural or device-related complications occurred in three patients in the investigational arm and in two patients in the control arm (P < 0.0001 for non-inferiority). In a secondary analysis, procedural times were shorter in the investigational arm as compared to the control arm (P < 0.0001). These results demonstrate non-inferior safety and effectiveness of the dual-energy catheter for the treatment of persistent AF. Future large-scale studies are needed to gather real-world evidence on the impact of the focal dual-energy lattice catheter on the broader population of patients with AF. ClinicalTrials.gov identifier: NCT05120193.

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

BackgroundAutonomic 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. ObjectivesThis 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. MethodsADVENT (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. ResultsThis 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). ConclusionsPFA’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.

Periprocedural Intravascular Hemolysis During Atrial Fibrillation Ablation: A Comparison of Pulsed Field With Radiofrequency Ablation

BackgroundHemolysis-related renal failure has been described after pulmonary vein isolation (PVI) with pulsed-field ablation (PFA). ObjectivesThis study sought to compare the potential for hemolysis during PVI with PFA vs radiofrequency ablation (RFA). MethodsIn consecutive patients, PVI was performed with PFA or RFA. Blood samples were drawn at baseline, immediately postablation, and 24 hours postablation. Using flow cytometry, the concentration of red blood cell microparticles (RBCμ) (fragments of damaged erythrocytes) in blood was assessed. Lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin were measured at baseline and 24 hours. ResultsSeventy patients (age: 64.7 ± 10.2 years; 47% women; 36 [51.4%] paroxysmal atrial fibrillation) were enrolled: 47 patients were in the PFA group (22 PVI-only and 36.4 ± 5.5 PFA applications; 25 PVI-plus, 67.3 ± 12.4 pulsed field energy applications), and 23 patients underwent RFA. Compared to baseline, the RBCμ concentration increased ∼12-fold postablation and returned to baseline by 24 hours in the PFA group (median: 70.8 [Q1-Q3: 51.8-102.5] vs 846.6 [Q1-Q3: 639.2-1,215.5] vs 59.3 [Q1-Q3: 42.9-86.5] RBCμ/μL, respectively; P < 0.001); this increase was greater with PVI-plus compared to PVI-only (P = 0.007). There was also a significant, albeit substantially smaller, periprocedural increase in RBCμ with RFA (77.7 [Q1-Q3: 39.2-92.0] vs 149.6 [Q1-Q3: 106.6-180.8] vs 89.0 [Q1-Q3: 61.2-123.4] RBCμ/μL, respectively; P < 0.001). At 24 hours with PFA, the concentration of LDH and indirect bilirubin increased, whereas haptoglobin decreased significantly (all P < 0.001). In contrast, with RFA, there were only smaller changes in LDH and haptoglobin concentrations (P = 0.03) and no change in bilirubin. ConclusionsPFA was associated with significant periprocedural hemolysis. With a number of 70 PFA lesions, the likelihood of significant renal injury is uncommon.