Rescue retrograde coronary venous ethanol ablation of ventricular tachycardia storm in a patient with Lamin A/C cardiomyopathy: a case report.

Background: Left ventricular (LV) summit arrhythmias account for up to 14% of LV arrhythmias. The ablation of LV summit arrhythmias is challenging, as testified by the fact that radiofrequency (RF) catheter ablation failure is frequent. Retrograde coronary venous ethanol infusion has been proposed as an alternative approach for the ablation of LV summit arrhythmias. Case summary: A 47-year-old man with Lamin A/C cardiomyopathy was referred for the ablation of a pleiomorphic ventricular tachycardia (VT) storm, with dominant morphology compatible with LV summit origin. He first received a combined endo- and epicardial RF ablation with the elimination of three clinically relevant VTs. However, the dominant VT could not be ablated due to the proximity of the coronary vasculature and phrenic nerve and remained inducible. Accordingly, an urgent rescue redo procedure consisting of retrograde coronary venous ethanol ablation was performed. Based on the best pace-match and precocity, the first septal, retro-pulmonary branch and the first diagonal branch were infused with ethanol with immediate cessation of the tachycardia and non-inducibility. Anti-arrhythmic drugs were withdrawn, while guideline-directed medical therapy for heart failure was continued. No complications occurred. After 3 months, the patient remained free from any arrythmias. Discussion: Ablation of LV summit arrythmias is challenging, especially in the context of an electrical storm or in patients with structural heart disease. In such a situation, rescue ablation with retrograde coronary venous ethanol infusion represents an attractive alternative ablation modality.

Risk assessment of esophageal ulceration following left atrial radiofrequency linear ablation.

INTRODUCTION: Esophageal safety following radiofrequency (RF) left atrial (LA) linear ablation has not been established. To determine the esophageal safety profile of LA linear RF lesions, we performed systematic esophagogastroduodenoscopy in all patients with intraesophageal temperature rise (ITR) ≥ 38.5°C. METHODS AND RESULTS: Between December 2021 and July 2023, a total of 200 consecutive patients with atrial tachyarrhythmia (ATA) underwent linear ablation with posterior dome (roof or floor) or posterior mitral isthmus line transection. Patients with ITR ≥ 38.5°C were scheduled for esophageal endoscopy ~3 weeks after ablation. Patient and ATA characteristics, procedural parameters, endoscopy findings and ablation lesion data were collected and analyzed. One hundred thirty-three out of 200 (67%) patients showed ITR ≥ 38.5°C during LA linear ablation. ITR (with maximal temperature of 45.7°C) was more frequently observed during floor line ablation (82% of cases). ITR was less observed during roof line ablation (34%) and posterior mitral isthmus ablation (4%). Endoscopy, performed in 115 patients after 24 ± 10 days, showed esophageal ulceration in four patients (two patients Kansas City classification [KCC] 2a and two patients KCC 2b). No patient showed esophageal perforation or fistula. CONCLUSION: Temperature rise during LA linear ablation is frequent and ulceration risk exists, particularly when floor line is performed. Safety measures are needed to avoid potential severe complications like esophageal perforation and fistula.

Dual energy for pulmonary vein isolation using dual-energy focal ablation technology integrated with a three-dimensional mapping system: SmartfIRE 3-month results.

AIMS: Contact force (CF)-sensing radiofrequency (RF) catheters with an ablation index have shown reproducible outcomes for the treatment of atrial fibrillation (AF) in large multicentre studies. A dual-energy (DE) focal CF catheter to deliver RF and unipolar/biphasic pulsed field ablation (PFA), integrated with a three-dimensional (3D) mapping system, can provide operators with additional flexibility. The SmartfIRE study assessed the safety and efficacy of this novel technology for the treatment of drug-refractory, symptomatic paroxysmal AF. Results at 3 months post-ablation are presented here. METHODS AND RESULTS: Pulmonary vein isolation (PVI) was performed using a DE focal, irrigated CF-sensing catheter with the recommendation of PFA at posterior/inferior and RF ablation at the anterior/ridge/carina segments. Irrespective of energy, a tag size of 3 mm; an inter-tag distance ≤6 mm; a target index of 550 for anterior, roof, ridge, and carina; and a target index of 400 for posterior and inferior were recommended. Cavotricuspid isthmus ablation was permitted in patients with documented typical atrial flutter. The primary effectiveness endpoint was acute procedural success. The primary safety endpoint was the rate of primary adverse events (PAEs) within 7 days of the procedure. A prespecified patient subset underwent oesophageal endoscopy (EE; 72 h post-procedure), neurological assessment (NA; pre-procedure and discharge), and cardiac computed tomography (CT)/magnetic resonance angiogram (MRA) imaging (pre-procedure and 3 months post-procedure) for additional safety evaluation, and a mandatory remapping procedure (Day 75 ± 15) for PVI durability assessment. Of 149 patients enrolled between February and June 2023, 140 had the study catheter inserted (safety analysis set) and 137 had ablation energy delivered (per-protocol analysis set). The median (Q1/Q3) total procedure and fluoroscopy times were 108.0 (91.0/126.0) and 4.2 (2.3/7.7) min (n = 137). The acute procedural success rate was 100%. First-pass isolation was achieved in 89.1% of patients and 96.8% of veins. Cavotricuspid isthmus ablations were successfully performed in 12 patients [pulsed field (PF) only: 6, RF only: 5, and RF/PF: 1]. The PAE rate was 4.4% [6/137 patients; 2 pulmonary vein (PV) stenoses, 2 cardiac tamponades/perforations, 1 stroke, and 1 pericarditis]. No coronary artery spasm was reported. No oesophageal lesion was seen in the EE subset (0/31, 0%). In the NA subset (n = 30), microemboli lesions were identified in 2 patients (2/30, 6.7%), both of which were resolved at follow-up; only 1 was symptomatic (silent cerebral lesion, 3.3%). In the CT/MRA subset (n = 30), severe PV narrowing (of >70%) was detected in 2 patients (2/30, 6.7%; vein level 2/128, 1.6%), of whom 1 underwent dilatation and stenting and 1 was asymptomatic; both were associated with high index values and a small inter-tag distance. In the PV durability subset (n = 30), 100/115 treated PVs (87%) were durably isolated and 18/30 patients (60.0%) had all PVs durably isolated. CONCLUSION: A DE focal CF catheter with 3D mapping integration showed a 100% acute success rate with an acceptable safety profile in the treatment of paroxysmal AF. Prespecified 3-month remapping showed notable PVI durability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05752487.

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 .

Vein of Marshall Ethanol Infusion for AF Ablation; A Review.

The outcomes of persistent atrial fibrillation (AF) ablation are modest with various adjunctive strategies beyond pulmonary vein isolation (PVI) yielding largely disappointing results in randomised controlled trials. Linear ablation is a commonly employed adjunct strategy but is limited by difficulty in achieving durable bidirectional block, particularly at the mitral isthmus. Epicardial connections play a role in AF initiation and perpetuation. The ligament of Marshall has been implicated as a source of AF triggers and is known to harbour sympathetic and parasympathetic nerve fibres that contribute to AF perpetuation. Ethanol infusion into the Vein of Marshall, a remnant of the superior vena cava and key component of the ligament of Marshall, may eliminate these AF triggers and can facilitate the ease of obtaining durable mitral isthmus block. While early trials have demonstrated the potential of Vein of Marshall 'ethanolisation' to reduce arrhythmia recurrence after persistent AF ablation, further randomised trials are needed to fully determine the potential long-term outcome benefits afforded by this technique.

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 the inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed-field Ablation [PFA] System With Irreversible Electroporation [IRE]). 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 per 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.

Validation of a machine learning algorithm to identify pulmonary vein isolation during ablation procedures for the treatment of atrial fibrillation: results of the PVISION study.

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation. Confirmation of PVI can be challenging due to the presence of far-field electrograms (EGMs) and sometimes requires additional pacing manoeuvres or mapping. This prospective multicentre study assessed the agreement between a previously trained automated algorithm designed to determine vein isolation status with expert opinion in a real-world clinical setting. METHODS AND RESULTS: Consecutive patients scheduled for PVI were recruited at four centres. The ECGenius electrophysiology (EP) recording system (CathVision ApS, Copenhagen, Denmark) was connected in parallel with the existing system in the laboratory. Electrograms from a circular mapping catheter were annotated during sinus rhythm at baseline pre-ablation, time of isolation, and post-ablation. The ground truth for isolation status was based on operator opinion. The algorithm was applied to the collected PV signals off-line and compared with expert opinion. The primary endpoint was a sensitivity and specificity exceeding 80%. Overall, 498 EGMs (248 at baseline and 250 at PVI) with 5473 individual PV beats from 89 patients (32 females, 62 ± 12 years) were analysed. The algorithm performance reached an area under the curve (AUC) of 92% and met the primary study endpoint with a sensitivity and specificity of 86 and 87%, respectively (P = 0.005; P = 0.004). The algorithm had an accuracy rate of 87% in classifying the time of isolation. CONCLUSION: This study validated an automated algorithm using machine learning to assess the isolation status of pulmonary veins in patients undergoing PVI with different ablation modalities. The algorithm reached an AUC of 92%, with both sensitivity and specificity exceeding the primary study endpoints.

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.

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.

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).

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.

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.