2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society (HRS), the Asia Pacific HRS, and the Latin American HRS.

Predictors of Success for Pulmonary Vein Isolation With Pulsed-Field Ablation Using a Variable-Loop Catheter With 3D Mapping Integration: Complete 12-Month Outcomes From inspIRE.

BACKGROUND: We previously presented the safety and early efficacy of inspIRE study (Pulsed-Field Ablation (PFA) System for the Treatment of Paroxysmal Atrial Fibrillation by Irreversible Electroporation). With the study's conclusion, we report the outcomes of the full pivotal study cohort, with an additional analysis of predictors of success. METHODS: InspIRE was a prospective, multicenter, single-arm clinical trial of drug-refractory paroxysmal atrial fibrillation. Pulmonary vein isolation was performed with a variable-loop circular catheter integrated with a 3-dimensional mapping system. Follow-up with 24-hour Holter was at 3, 6, and 12 months, as well as remote rhythm monitoring: weekly from 3 to 5 months, monthly from 6 to 12 months, and for symptoms. The primary effectiveness end point (PEE) was acute pulmonary vein isolation plus freedom from any atrial arrhythmia at 12 months. Additional subanalyses report predictors of PEE success. RESULTS: The patient cohort included 186 patients: aged 59±10 years, female 30%, and CHA2DS2-VASc 1.3±1.2. The previously reported primary adverse event rate was 0%. One serious procedure-related adverse event, urinary retention, was reported. The PEE was achieved in 75.6% (95% CI, 69.5%-81.8%). The clinical success of freedom from symptomatic recurrence was 81.7% (95% CI, 76.1%-87.2%). Simulating a monitoring method used in standard real-world practice (without protocol-driven remote rhythm monitoring), this translates to a freedom from all and symptomatic recurrence of 85.8% (95% CI, 80.8%-90.9%) or 94.0% (95% CI, 90.6%-97.5%), respectively. Multivariate analyses revealed that left ventricular ejection fraction ≥60% (adjusted odds ratio, 0.30) and patients receiving ≥48 PFA applications (adjusted odds ratio, 0.28) were independent predictors of PEE success. Moreover, PEE success was 79.2% in patients who received ≥12 PFA applications/vein compared with 57.1% in patients receiving fewer PFA applications. CONCLUSIONS: The inspIRE study confirms the safety and effectiveness of pulmonary vein isolation using the novel 3-dimensional mapping integrated circular loop catheter. An optimal number of PFA applications (≥48 total or ≥12 per vein) resulted in an improved 1-year success rate of ≈80%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04524364.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

Durable pulmonary vein isolation with optimized high-power and very high-power short-duration temperature-controlled ablation: A step-by-step guide.

INTRODUCTION: Through systematic scientific rigor, the CLOSE guided workflow was developed and has been shown to improve pulmonary vein isolation durability. However, this technique was developed at a time when using power-controlled ablation catheters with conventional power ranges was the norm. There has been increased adoption of a high-power and very high-power short-duration ablation practice propelled by the availability of the temperature-controlled radiofrequency QDOT MICRO catheter. METHODS: There are fundamental differences in biophysics between very high-powered temperature guided ablation and conventional ablation strategy that may impact patient outcomes. The catheter's design and ablation modes offer flexibility in technique while accommodating the individual operator's clinical discretion and preference to deliver a durable, transmural, and contiguous lesion set. RESULTS: Here, we provide recommendations for 3 different workflows using the QDOT MICRO catheter in a step-by-step manner for pulmonary vein isolation based on our cumulative experience as early adopters of the technology and the data available in the scientific literature. CONCLUSIONS: With standardization, temperature-controlled ablation with the QDOT MICRO catheter provides operators the flexibility of implementing different ablation strategies to ensure durable contiguous pulmonary vein isolation depending on patient characteristics.

Procedural performance and outcome after pulsed field ablation for pulmonary vein isolation: comparison with a reference radiofrequency database.

Aims: Pulsed field ablation (PFA) is a promising ablation technique for pulmonary vein isolation (PVI) with appealing advantages over radiofrequency (RF) including speed, tissue selectivity, and the promise of enhanced durability. In this study, we determine the procedural performance, efficacy, safety, and durability of PFA and compare its performance with a dataset of optimized RF ablation. Methods and results: After propensity score matching, we compared 161 patients who received optimized RF-guided PVI in the PowerPlus study (CLOSE protocol) with 161 patients undergoing PFA-guided PVI for paroxysmal or persistent atrial fibrillation (AF; pentaspline basket catheter). The median age was 65 years with 78% paroxysmal AF in the PFA group (comparable characteristics in the RF group). Pulsed field ablation-guided PVI was obtained in all patients with a procedure time of 47 min (vs. 71 min in RF, P < 0.0001) and a fluoroscopy time of 15 min (vs. 11 min in RF, P < 0.0001). One serious adverse event [transient ischaemic attack] occurred in a patient with thrombocytosis (0.6 vs. 0% in RF). During the 6-month follow-up, 24 and 27 patients experienced a recurrence with 20 and 11 repeat procedures in the PFA and the RF groups, respectively (P = 0.6 and 0.09). High-density mapping revealed a status of 4 isolated veins in 7/20 patients in the PFA group and in 2/11 patients in the RF group (35 vs. 18%, P = 0.3). Conclusion: Pulsed field ablation fulfils the promise of offering a short and safe PVI procedure, even when compared with optimized RF in experienced hands. Pulmonary vein reconnection is the dominant cause of recurrence and tempers the expectation of a high durability rate with PFA.

Prediction of certainty in artificial intelligence-enabled electrocardiography.

BACKGROUND: The 12­lead ECG provides an excellent substrate for artificial intelligence (AI) enabled prediction of various cardiovascular diseases. However, a measure of prediction certainty is lacking. OBJECTIVES: To assess a novel approach for estimating certainty of AI-ECG predictions. METHODS: Two convolutional neural networks (CNN) were developed to predict patient age and sex. Model 1 applied a 5 s sliding time-window, allowing multiple CNN predictions. The consistency of the output values, expressed as interquartile range (IQR), was used to estimate prediction certainty. Model 2 was trained on the full 10s ECG signal, resulting in a single CNN point prediction value. Performance was evaluated on an internal test set and externally validated on the PTB-XL dataset. RESULTS: Both CNNs were trained on 269,979 standard 12­lead ECGs (82,477 patients). Model 1 showed higher accuracy for both age and sex prediction (mean absolute error, MAE 6.9 ± 6.3 years vs. 7.7 ± 6.3 years and AUC 0.946 vs. 0.916, respectively, P < 0.001 for both). The IQR of multiple CNN output values allowed to differentiate between high and low accuracy of ECG based predictions (P < 0.001 for both). Among 10% of patients with narrowest IQR, sex prediction accuracy increased from 65.4% to 99.2%, and MAE of age prediction decreased from 9.7 to 4.1 years compared to the 10% with widest IQR. Accuracy and estimation of prediction certainty of model 1 remained true in the external validation dataset. CONCLUSIONS: Sliding window-based approach improves ECG based prediction of age and sex and may aid in addressing the challenge of prediction certainty estimation.

Long-term outcomes of the pentaspline pulsed-field ablation catheter for the treatment of paroxysmal atrial fibrillation: results of the prospective, multicentre FARA-Freedom Study.

AIMS: Pulmonary vein isolation (PVI) is a well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long-term efficacy and safety data demonstrating single-procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate the long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS AND RESULTS: FARA-Freedom, a prospective, non-randomized, multicentre study, enrolled patients with PAF undergoing de novo PVI with PFA, who were followed for 12 months with weekly transtelephonic monitoring and a 72-h Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success, which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. The study enrolled 179 PAF patients (62 ± 10 years, 39% female) at 13 centres. At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high, with 88.4 and 90.3% with weekly events and 72-h Holter monitors, respectively. Freedom from the composite primary effectiveness endpoint was 66.6%, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in two patients (1.1%), one tamponade and one transient ischaemic attack. There was no coronary spasm, PV stenosis, or AE fistula. There were four cases of transient phrenic nerve palsy, but all resolved during the index procedure. CONCLUSION: In this prospective, non-randomized, multicentre study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigourous endpoint definitions and high monitoring compliance and demonstrated favourable safety. REGISTRATION: Clinical Trials.gov Identifier: NCT05072964 (sponsor: Boston Scientific Corporation).

Early atrial fibrillation recurrence post catheter ablation: Analysis from insertable cardiac monitor in the era of optimized radiofrequency ablation.

BACKGROUND: Early recurrence of atrial tachyarrhythmia (ERAT) is associated with ablation-induced proarrhythmogenic inflammation; however, existing studies used intermittent monitoring or nonoptimized radiofrequency (RF) applications (noncontiguous or without ablation index target value). OBJECTIVE: The purpose of this study was to investigate the relationship between ERAT and late recurrence based on insertable cardiac monitor (ICM) data. METHODS: We compiled data from Close-To-Cure and Close Maze studies, which enrolled patients who underwent RF ablation for paroxysmal or persistent atrial fibrillation (AF). All patients were implanted with an ICM 2-3 months before ablation. RESULTS: We studied 165 patients (104 with paroxysmal AF, 61 with persistent AF). Over the 1-year follow-up period, 41 of the patients experienced late recurrence. The risk of late recurrence was higher in patients experiencing ERAT (hazard ratio [HR] 6.2; 95% confidence interval [CI] 3.0-13.0), with negative and positive predictive values of 90.5% and 45.7%, respectively. Median burden of AF during the blanking period was significantly higher in patients with late recurrence (7.9% [0.0%-99.6%]) compared to those without recurrence (0.0% [0.0%-6.0]; P <.001). For each 1% increase in AF burden during the blanking period, late recurrence increased by 4.6% (HR 1.046; 95% CI 1.035-1.059). The best tradeoff for predicting AF from ERAT occurrence was AF burden of 0.6% and last ERAT at 64 days. CONCLUSION: In patients ablated for paroxysmal and persistent AF with a durable RF lesion set and implanted with a continuous monitoring device, postablation early AF recurrence and burden significantly predict late recurrence. The post-AF ablation blanking period should be reduced to 2 months.

Successful caudal vena cava and pulmonary vein isolation in healthy horses using 3D electro-anatomical mapping and a contact force-guided ablation system.

BACKGROUND: Recently, treatment of equine atrial tachycardia by three-dimensional electro-anatomical mapping (3D EAM) and radiofrequency catheter ablation (RFCA) has been described. Myocardial sleeves in the caudal vena cava and pulmonary veins are a potential trigger for initiation and perpetuation of atrial tachycardia and atrial fibrillation in the horse. Isolation of these myocardial sleeves by RFCA may be an effective treatment for these arrhythmias. OBJECTIVES: To describe the feasibility of 3D EAM and RFCA to isolate caudal vena cava and pulmonary veins in adult horses using 3D mapping and a contact force (CF)-guided ablation system. STUDY DESIGN: In vivo experiments. METHODS: 3D EAM and RFCA was performed in five horses without cardiovascular disease under general anaesthesia, using the CF-guided system CARTO®3. Point-by-point RFCA aimed for isolation of caudal vena cava and pulmonary veins. Radiofrequency energy was delivered in power-controlled mode with a target power of 45 W, CF between 10 and 15 g and 30 mL/min irrigation rate, until an ablation-index of 450-500 was reached. RESULTS: In the right atrium, myocardial sleeves of the caudal vena cava were isolated (n = 5). In the left atrium, isolation of ostium II (n = 3), ostium III (n = 1) and ostium I, II and III en bloc (n = 1) was performed. Successful isolation was confirmed by entrance and exit block. MAIN LIMITATIONS: Horses were euthanised at the end of the procedure, so long term effects such as potential reconnection of isolated veins could not be studied. CONCLUSIONS: This is the first description of 3D EAM and RFCA with CARTO®3 in horses, thereby showing the technical feasibility and successful caudal vena cava and pulmonary vein isolation. CF measurement allowed monitoring of catheter-tissue contact, resulting in efficient acute lesion creation as confirmed by entrance and exit block. This is a promising treatment for cardiac arrhythmias in horses.

No Effect of Continued Antiarrhythmic Drug Treatment on Top of Optimized Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: Results From the POWDER-AF2 Trial.

BACKGROUND: In patients with persistent atrial fibrillation (PersAF), catheter ablation aiming for pulmonary vein isolation (PVI) is associated with moderate clinical effectiveness. We investigated the benefit of continuing previously ineffective class 1C or 3 antiarrhythmic drug therapy (ADT) in the setting of a standardized PVI-only ablation strategy. METHODS: In this multicenter, randomized controlled study, patients with PersAF (≥7 days and <12 months) despite ADT were prospectively randomized 1:1 to PVI with ADT continued versus discontinued beyond the blanking period (ADT ON versus ADT OFF). Standardized catheter ablation was performed aiming for durable isolation with stable, contiguous, and optimized radio frequency applications encircling the pulmonary veins (CLOSE protocol). Clinical visits and 1-to-7-day Holter were performed at 3, 6, and 12 months. The primary end point was any documented atrial tachyarrhythmia lasting >30 seconds beyond 3 months. Prospectively defined secondary end points included repeat ablations, unscheduled arrhythmia-related visits, and quality of life among groups. RESULTS: Of 200 PersAF patients, 98 were assigned to ADT OFF and 102 to ADT ON. The longest atrial fibrillation episode qualifying for PersAF was 28 (10-90) versus 30 (11-90) days. Clinical characteristics and procedural characteristics were similar. Recurrence of atrial tachyarrhythmia was comparable in both groups (20% OFF versus 21.2% ON). No differences were observed in repeat ablations and unscheduled arrhythmia-related visits. Marked improvement in quality of life was observed in both groups. CONCLUSIONS: In patients with PersAF, there is no benefit in continuing previously ineffective ADT beyond the blanking period after catheter ablation. The high success rate of PVI-only might be explained by the high rate of durable isolation after optimized PVI and the early stage of PersAF (POWDER-AF2). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03437356.

Progress in atrial fibrillation ablation during 25 years of Europace journal.

The first edition of Europace journal in 1999 came right around the time of the landmark publication of the electrophysiologists from Bordeaux, establishing how elimination of ectopic activity from the pulmonary veins (PVs) resulted in a marked reduction of atrial fibrillation (AF). The past 25 years have seen an incredible surge in scientific interest to develop new catheters and energy sources to optimize durability and safety of ablation, as well as study the mechanisms for AF and devise ablation strategies. While ablation in the beginning was performed with classic 4 mm tip catheters that emitted radiofrequency (RF) energy to create tissue lesions, this evolved to using irrigation and contact force (CF) measurement while increasing power. Also, so-called single-shot devices were developed with balloons and arrays to create larger contiguous lesions, and energy sources changed from RF current to cryogenic ablation and more recently pulsed field ablation with electrical current. Although PV ablation has remained the basis for every AF ablation, it was soon recognized that this was not enough to cure all patients, especially those with non-paroxysmal AF. Standardized approaches for additional ablation targets have been used but have not been satisfactory in all patients so far. This led to highly technical mapping systems that are meant to unravel the drivers for the maintenance of AF. In the following sections, the development of energies, strategies, and tools is described with a focus on the contribution of Europace to publish the outcomes of studies that were done during the past 25 years.

Impact of Catheter Ablation on Arrhythmia Burden in Patients With Shock-Resistant Persistent Atrial Fibrillation.

BACKGROUND: Persistent shock-resistant atrial fibrillation (AF) is a challenging entity, with modest results from catheter ablation according to conventional survival analysis. OBJECTIVES: The aim of this study was to determine the effect of catheter ablation on atrial tachyarrhythmia (ATA) burden in persistent AF patients undergoing first-time ablation with the use of an implantable cardiac monitor (ICM). METHODS: Patients with drug-resistant ongoing persistent AF and at least 1 previous failed cardioversion were implanted with an ICM 2 months before the procedure. All patients underwent pulmonary vein isolation with or without additional substrate ablation depending on the presence of self-terminating AF on ICM and left atrium size. Median AF burden before and after ablation, off antiarrhythmic medication, was determined from ICM recordings after review by 2 independent investigators. RESULTS: Sixty patients were recruited (mean age 66 ± 9 years, 70% male). Mean left atrial diameter was 48 ± 6 mm and median CHA2DS2VASc score was 2. Ten patients (17%) unexpectedly demonstrated self-terminating AF before ablation. The median burden of ATA before ablation was 100% (95% CI: 19.6%-100%), decreasing to 0% (95% CI: 0%-95.8%) after ablation during the post-blanking follow-up period (median reduction 100%; 95% CI: 4%-100%; P < 0.001). Twenty-seven patients (45%) experienced recurrent ATA during 12-month follow-up. In these patients, median burden before ablation was 100% (95% CI: 26.9%-100%), decreasing to 11.4% (95% CI: 0.35%-99.7%) after ablation (P < 0.001). Quality of life improved significantly from baseline, driven by lack of recurrence. CONCLUSIONS: Patient-tailored catheter ablation results in a significant reduction in ATA burden (off antiarrhythmic medication) in shock-resistant persistent AF patients using ICMs implanted 2-months pre-procedure. These data suggest that conventional arrhythmia-free survival analysis does not capture the true impact of catheter ablation in this challenging cohort.

Safety and efficacy of catheter ablation on patients with persistent atrial fibrillation by targeting repetitive activation patterns and focal impulses.

BACKGROUND: The study is intended to evaluate the acute and long-term effectiveness and peri-procedural safety in ablation of persistent atrial fibrillation (PsAF) using the CartoFinder algorithm guided ablation (CFGA) targeting on repetitive activation patterns (RAPs) and focal impulses (FIs) identified in dynamic maps. METHODS: This is a prospective, single-arm, multicenter study. A 64-pole multielectrode basket catheter was used for intracardiac global electrogram (EGM) mapping. The RAPs or FIs were repeatedly mapped and ablated for up to five iterations by the CartoFinder algorithm to achieve sinus rhythm (SR) or organized atrial tachycardia (AT), which were followed by PVI. All patients were followed up for 12 months after procedure. RESULTS: Sixty-four PsAF patients (age, 60.7 ± 9.1 years; male, 76.6%; median PsAF duration, 6.0 months) underwent CFGA on RAPs/FIs. Six patients (9.4%) reported primary adverse event (PAE) including groin hematoma (2), complete heart block (1), tamponade (1), pericarditis (1), and pseudoaneurysm (1). Repeated mapping and ablation on RAPs/FIs resulted in the cycle length (CL) increase from 191.0 ± 167.6 ms at baseline to 365.7 ± 296.7 ms in the LA and from 167.8 ± 41.6 ms to 379.4 ± 293.5 ms in the RA and 30.2% (19/63) AF termination to SR or organized AT. The 12-month arrhythmia-free and symptomatic AF-free rates were 60.9% and 75.0%, respectively. Patients with acute AF termination showed a higher 12-month arrhythmia-free rate (76.9%) than those without (50.0%, p = .04). CONCLUSIONS: The study demonstrated that the CartoFinder algorithm can be used for global activation mapping during PsAF ablation. Patients with acute AF termination had a lower 12-month AF recurrence rate compared to patients without.

Very High-Power Ablation for Contiguous Pulmonary Vein Isolation: Results From the Randomized POWER PLUS Trial.

BACKGROUND: Very high-power, short-duration (90-W/4-second) ablation for pulmonary vein isolation (PVI) may reduce procedural times. However, shorter applications with higher power may impact lesion quality. OBJECTIVES: In this multicenter, randomized controlled trial, the authors compared procedural efficiency, efficacy, and safety of PVI using 90-W/4-second ablation to 35/50-W ablation. METHODS: Patients with paroxysmal or persistent atrial fibrillation undergoing first-time PVI were randomized to pulmonary vein encirclement with contiguous applications using very high-power, short-duration applications (90 W over 4 seconds) or 35/50-W applications (titrated up to ablation index >550 anteriorly and >400 posteriorly). Prospective endpoints were procedural efficiency (procedure time and first-pass isolation), safety (including esophageal endoscopic evaluation), and 6-month effectiveness using repetitive Holter monitoring. RESULTS: A total of 180 patients were randomized, 90 to the 90-W group (mean age: 64.2 ± 8.9 years) and 90 to the 35/50-W group (mean age: 62.3 ± 10.8 years). Procedural time was shorter in the 90-W group vs the 35/50-W group (70 [IQR: 60-80] minutes vs 75 [IQR: 65-88.3] minutes; P = 0.009). A nonsignificant trend towards lower rates of first-pass isolation was seen in the 90-W group (83.9% vs 90%; P = 0.0852). No major complications were observed in both groups with esophageal injury occurring in 1 patient per group. At 6 months, 17% of patients in the 90-W group vs 15% in the 35/50-W group experienced recurrent arrhythmia (P = 0.681). CONCLUSIONS: Contiguous ablation using very high-power, short-duration applications results in a significant but modest reduction in procedure time with similar safety and 6-month efficacy vs a conventional approach. A hybrid approach combining both ablation modalities might be the most optimal strategy. (POWER PLUS [Very High Power Ablation in Patients With Atrial Fibrillation Schedule for a First Pulmonary Vein Isolation]; NCT04784013).

Paroxysmal Atrial Fibrillation Ablation Using a Novel Variable-Loop Biphasic Pulsed Field Ablation Catheter Integrated With a 3-Dimensional Mapping System: 1-Year Outcomes of the Multicenter inspIRE Study.

BACKGROUND: The inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed Field Ablation [PFA] System With Irreversible Electroporation [IRE]) evaluated safety and effectiveness of a fully integrated biphasic pulsed field ablation (PFA) system with a variable-loop circular catheter for the treatment of drug-refractory paroxysmal atrial fibrillation. METHODS: Subjects underwent pulmonary vein (PV) isolation with the PFA system, using at least 12 applications per vein; adenosine/isoproterenol was administered to confirm entrance block. Wave I assessed initial safety, including for esophageal lesions, silent cerebral lesions, and PV stenosis. Wave II (pivotal phase) tested (1) primary safety, incidence of early-onset primary adverse events, and (2) primary effectiveness, confirmed PV isolation with freedom from documented atrial arrhythmia at 12 months. The study design specified an interim analysis to determine early success once 30 subjects reached the 12-month follow-up and all subjects reached 3-month follow-up. RESULTS: Across 13 centers in Europe/Canada, 226 subjects were enrolled, met criteria for safety and effectiveness evaluations, and received PFA (Wave I, 40; Wave II, 186). Wave I demonstrated no esophageal thermal lesions or PV stenosis. Among 39 subjects with cerebral magnetic resonance imaging, silent cerebral lesions were detected in 4 of the first 6 subjects, after which workflow enhancements, including a 10-second pause between PFA applications, were implemented; subsequently, only 4 of 33 subjects had silent cerebral lesions. In the Wave II phase, no primary adverse events were reported. Upon declaring early success, 83 subjects reached 12-month follow-up. With 100% entrance block, PV isolation without acute reconnection was achieved in 97.1% of targeted veins. For Wave II, the primary effectiveness end point per Kaplan-Meier at the time of interim analysis was 70.9%; 12-month freedom from symptomatic atrial fibrillation/atrial flutter/atrial tachycardia recurrence and repeat ablation was 78.9% and 92.3%, respectively. Total procedure and transpired PFA times were 70.1±27.7 and 26.7±14.0 minutes, respectively. CONCLUSIONS: The inspIRE trial confirmed the safety and effectiveness of the novel mapping-integrated PFA system. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT04524364.