Cryocure-VT: the safety and effectiveness of ultra-low-temperature cryoablation of monomorphic ventricular tachycardia in patients with ischaemic and non-ischaemic cardiomyopathies.

AIMS: The ultra-low-temperature cryoablation (ULTC) ablation system using -196°C N2 cryogen has been reported to create lesions with freeze duration-dependent depth titratable to over 10 mm with minimum attenuation by scar. Cryocure-VT (NCT04893317) was a first-in-human clinical trial evaluating the safety and efficacy of a novel, purpose-built ULTC catheter in endocardial ablation of scar-dependent ventricular tachycardias (VTs). METHODS AND RESULTS: This prospective, multi-centre study enrolled patients referred for de novo or second ablations of recurrent monomorphic VT of both ischaemic and non-ischaemic aetiologies. Primary safety and efficacy endpoints of the study were freedom from device- or procedure-related major adverse events (MAEs) up to 30 days post-ablation, acute non-inducibility of clinical VTs at the end of the procedure, and freedom from sustained VT or implantable defibrillator intervention at 6 months. Ultra-low-temperature cryoablation was performed in 64 patients (age 67 ± 11 years, 78% ischaemic, ejection fraction = 35 ± 10%) at 9 centres. The primary acute effectiveness endpoint was achieved in 94% (51/54) of patients in whom post-ablation induction was attempted. There were no protocol-defined MAEs; four procedure-related serious adverse events resolved without clinical sequelae. At 6-month follow-up, 38 patients (60.3%) remained VT-free, and freedom from defibrillator shock was 81.0%, with no significant difference between ischaemic and non-ischaemic cohorts. In 47 patients with defibrillator for at least 6 months prior to the ablation, the VT burden was reduced from median of 4, inter-quartile range (IQR, 1-9) to 0, IQR (0-2). CONCLUSION: In this first-in-human multi-centre experience, endocardial ULTC ablation of monomorphic VT appears safe and effective in patients with both ischaemic-cardiomyopathy and non-ischaemic-cardiomyopathy. CLINICAL TRIAL REGISTRATION: NCT04893317.

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.

First-in-Human Clinical Series of a Novel Conformable Large-Lattice Pulsed Field Ablation Catheter for Pulmonary Vein Isolation.

BACKGROUND/AIMS: Pulsed field ablation (PFA) has significant advantages over conventional thermal ablation of atrial fibrillation (AF). This first-in-human, single-arm trial to treat paroxysmal AF (PAF) assessed the efficiency, safety, pulmonary vein isolation (PVI) durability and one-year clinical effectiveness of an 8-Fr, large-lattice, conformable single-shot PFA catheter together with a dedicated electroanatomical mapping system. METHODS: After rendering the PV anatomy, the PFA catheter delivered monopolar, biphasic pulse trains (5-6 secs per application; ∼4 applications per PV). Three waveforms were tested: PULSE1, PULSE2 and PULSE3. Follow-up included ECGs, Holters at 6 and 12 months, and symptomatic and scheduled transtelephonic monitoring. The primary and secondary efficacy endpoints were acute PVI and post-blanking atrial arrhythmia recurrence, respectively. Invasive remapping was conducted ∼75 days post-ablation. RESULTS: At three centers, PVI was performed by five operators in 85 patients using PULSE1 (n=30), PULSE2 (n=20), and PULSE3 (n=35). Acute PVI was achieved in 100% of PVs using 3.9±1.4 PFA applications per PV. Overall procedure, transpired ablation, PFA catheter dwell and fluoroscopy times were 56.5±21.6, 10.0 ± 6.0, 19.1±9.3 and 5.7±3.9 min, respectively. No pre-defined primary safety events occurred. Upon remapping, PVI durability was 90% and 99% on a per vein basis for the total and PULSE3 cohort, respectively. The Kaplan-Meier estimate of one-year freedom from atrial arrhythmias was 81.8% (95% CI 70.2-89.2%) for the total, and 100% (95% CI 80.6-100%) for the PULSE3 cohort. CONCLUSION: PVI utilizing a conformable single-shot PFA catheter to treat PAF was efficient, safe, and effective, with durable lesions demonstrated upon remapping.

Early real-world implant experience with a helix-fixation ventricular leadless pacemaker.

BACKGROUND: Roughly one in six patients receiving conventional transvenous pacemaker systems experience significant complications within 1 year of implant, mainly due to the transvenous lead and subcutaneous pocket. A new helix-fixation single-chamber ventricular leadless pacemaker (LP) system capable of pre-deployment exploratory electrical mapping is commercially available. Such an LP may mitigate complications while streamlining the implantation. In this study, the initial real-world implant experience of the helix-fixation LP was evaluated following its commercial release. METHODS: In patients indicated for single-chamber right ventricular pacing, helix-fixation Aveir VR LPs (Abbott, Abbott Park, IL) were implanted using the dedicated loading tool, introducer, and delivery catheter. Implant procedural characteristics, electrical parameters, and any 30-day procedure-related adverse events of consecutive implant attempts were retrospectively evaluated. RESULTS: A total of 167 patients with Class I indication for permanent pacing received implants in four North American centers (57% male, 70 years old). Pre-fixation electrical mapping of potential sites allowed repositioning to be avoided in 95.7% of patients. Median [interquartile range] LP procedure and fluoroscopy durations were 25.5 min [20.0, 35.0] and 5.7 min [4.0, 9.2], respectively. Pacing capture threshold, sensed R-wave amplitude, and impedance were 0.8 V [0.5, 1.3], 9.0 mV [6.0, 12.0], and 705 Ω [550, 910], respectively. Implantation was successful in 98.8% of patients, with 98.2% free from acute adverse events. CONCLUSIONS: The initial, real-world experience of the helix-fixation ventricular leadless pacemaker demonstrated safe and efficient implantation with minimal repositioning, viable electrical metrics, and limited acute complications.

Comparative Costs to Medicare and Medicare Beneficiaries of Alternative AF Stroke Risk Reduction Strategies.

Background: As healthcare costs are increasingly being shifted from payers to patients, it is important to understand the economic consequences of therapeutic strategies to both payers and patients. Objective: To determine the relative costs to Medicare and Medicare beneficiaries (patients) of warfarin, non-vitamin K oral anticoagulants (NOACs), and left atrial appendage closure (LAAC) for stroke risk reduction in nonvalvular atrial fibrillation. Methods: An economic model was developed to assess costs at 5 and 10 years. For warfarin and NOACs, inputs were derived from published meta-analyses; for LAAC with the Watchman device, inputs were derived from pooled 5-year PROTECT AF and PREVAIL trial results. The model captured therapy costs vs clinical event costs, including procedural complications and follow-up clinical outcomes. Costs were based on 2023 Medicare reimbursement and copayment rates. Results: At 10 years, overall LAAC costs ($48,337) were lower than those of NOACs ($81,198) and warfarin ($52,359). Overall LAAC costs were lower than those of NOACs by year 5 and warfarin by year 9. At 5 years, patient LAAC costs were lowest at $4,764, compared to $7,146 and $6,453 for NOACs and warfarin, respectively. LAAC patient costs were lower than those of NOACs by year 3 and warfarin by year 4. Clinical events comprised 96% of overall warfarin costs vs 48% for LAAC and 40% for NOACs. Conclusion: LAAC yielded the lowest overall and patient costs. Warfarin costs were largely driven by clinical events, which may represent an unplanned financial burden for patients. These considerations should be incorporated into shared decision-making discussions about stroke prophylaxis strategies.

Nitroglycerin to Ameliorate Coronary Artery Spasm During Focal Pulsed-Field Ablation for Atrial Fibrillation.

BACKGROUND: In treating atrial fibrillation, pulsed-field ablation (PFA) has comparable efficacy to conventional thermal ablation, but with important safety advantages: no esophageal injury or pulmonary vein stenosis, and rare phrenic nerve injury. However, when PFA is delivered in proximity to coronary arteries using a pentaspline catheter, which generates a broad electrical field, severe vasospasm can be provoked. OBJECTIVES: The authors sought to study the vasospastic potential of a focal PFA catheter with a narrower electrical field and develop a preventive strategy with nitroglycerin. METHODS: During atrial fibrillation ablation, a focal PFA catheter was used for cavo-tricuspid isthmus ablation. Angiography of the right coronary artery (some with fractional flow reserve measurement) was performed before, during, and after PFA. Beyond no nitroglycerin (n = 5), and a few testing strategies (n = 8), 2 primary nitroglycerin administration strategies were studied: 1) multiple boluses (3-2 mg every 2 min) into the right atrium (n = 10), and 2) a bolus (3 mg) into the right atrium with continuous peripheral intravenous infusion (1 mg/min; n = 10). RESULTS: Without nitroglycerin, cavo-tricuspid isthmus ablation provoked moderate-severe vasospasm in 4 of 5 (80%) patients (fractional flow reserve 0.71 ± 0.08). With repetitive nitroglycerin boluses, severe spasm did not occur, and mild-moderate vasospasm occurred in only 2 of 10 (20%). Using the bolus + infusion strategy, severe and mild-moderate spasm occurred in 1 and 3 of 10 patients (aggregate 40%). No patient had ST-segment changes. CONCLUSIONS: Ablation of the cavotricuspid isthmus using a focal PFA catheter routinely provokes right coronary vasospasm. Pretreatment with high doses of parenteral nitroglycerin prevents severe spasm.

Pulmonary vein narrowing after pulsed field versus thermal ablation.

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

Endovascular Ablation of the Right Greater Splanchnic Nerve in Heart Failure With Preserved Ejection Fraction: Rationale, Design and Lead-in Phase Results of the REBALANCE-HF Trial.

OBJECTIVE: Splanchnic vasoconstriction augments transfer of blood volume from the abdomen into the thorax, which may increase filling pressures and hemodynamic congestion in patients with noncompliant hearts. Therapeutic interruption of splanchnic nerve activity holds promise to reduce hemodynamic congestion in patients with heart failure with preserved ejection fraction (HFpEF). Here we describe (1) the rationale and design of the first sham-controlled, randomized clinical trial of splanchnic nerve ablation for HFpEF and (2) the 12-month results of the lead-in (open-label) trial's participants. METHODS: REBALANCE-HF is a prospective, multicenter, randomized, double-blinded, sham-controlled clinical trial of endovascular, transcatheter, right-sided greater splanchnic nerve ablation for volume management (SAVM) in patients with HFpEF. The primary objectives are to evaluate the safety and efficacy of SAVM and identify responder characteristics to inform future studies. The trial consists of an open-label lead-in phase followed by the randomized, sham-controlled phase. The primary efficacy endpoint is the reduction in pulmonary capillary wedge pressure (PCWP) at 1-month follow-up compared to baseline during passive leg raise and 20W exercise. Secondary and exploratory endpoints include health status (Kansas City Cardiomyopathy Questionnaire), 6-minute walk test distance, New York Heart Association class, and NTproBNP levels at 3, 6 and 12 months. The primary safety endpoint is device- or procedure-related serious adverse events at the 1-month follow-up. RESULTS: The lead-in phase of the study, which enrolled 26 patients with HFpEF who underwent SAVM, demonstrated favorable safety outcomes and reduction in exercise PCWP at 1 month post-procedure and improvements in all secondary endpoints at 6 and 12 months of follow-up. The randomized phase of the trial (n = 44 SAVM; n = 46 sham) has completed enrollment, and follow-up is ongoing. CONCLUSION: REBALANCE-HF is the first sham-controlled randomized clinical trial of greater splanchnic nerve ablation in HFpEF. Initial 12-month open-label results are promising, and the results of the randomized portion of the trial will inform the design of a future pivotal clinical trial. SAVM may offer a promising therapeutic option for patients with HFpEF. TRIAL REGISTRATION: NCT04592445.

Acute and long-term results with the 3rd generation visually guided laser balloon ablation system for pv isolation.

BACKGROUND: Visually guided laser balloon ablation is known as an effective pulmonary vein (PV) isolation device. The third-generation laser balloon ablation system (X3) equipped with compliant balloon and an automated motor-driven laser output mechanism, namely RAPID mode, has been clinically proven for PV isolation. METHODS: PV isolation with X3 was performed in all the patients with paroxysmal and early-stage persistent atrial fibrillation (AF). Acute data for PV isolation and clinical outcomes including supraventricular tachyarrhythmia (SVT: AF, atrial flutter, or atrial tachycardia)-free survival rate beyond 1 year were analyzed. RESULTS: A total of 110 patients (62 ± 13 years old, 80% of paroxysmal AF) were treated with X3. RAPID mode with was utilized to achieve PV isolation in all cases. In combination with RAPID mode and spot mode laser ablation, 91.1% (380/417) of veins were isolated on the first circumferential lesion set and did not require touch-up ablation and during the index procedure 100% of attempted veins were isolated. The mean procedure time was 77.0 ± 22.7 min and LA dwell time was 61.9 ± 22.0 min. Total duration of laser application was 5.1 ± 2.3 min per vein. At 1 year, SVT-free survival rate was 93.7% in paroxysmal AF patients, and 81.1% in persistent AF patients. CONCLUSIONS: A novel continuous automatic laser balloon ablation system was proved to be safe and effective for both paroxysmal and persistent AF patients. The clinical result demonstrated that PV isolation with X3 could achieve a high SVT-free survival rate.

Coronary Artery Spasm During Pulsed Field vs Radiofrequency Catheter Ablation of the Mitral Isthmus.

Importance: In treating atrial fibrillation, pulsed field ablation (PFA) is a novel energy modality with comparable efficacy to conventional thermal ablation, such as radiofrequency ablation (RFA), but with the benefit of some preferentiality to myocardial tissue ablation. Studies have demonstrated important safety advantages, including the absence of esophageal injury or pulmonary vein stenosis and only rare phrenic nerve injury. However, there is emerging evidence of coronary artery vasospasm provoked by PFA. Objective: To compare the incidence and severity of left circumflex arterial vasospasm between PFA and RFA during adjacent ablation along the mitral isthmus. Design, Setting, and Participants: This prospective cohort study enrolled consecutive adult patients receiving first-ever PFA or RFA of the mitral isthmus during catheter ablation of atrial fibrillation in 2022 with acute follow-up at a single referral European center. Exposure: A posterolateral mitral isthmus line was created using either a multielectrode pentaspline PFA catheter (endocardial ablation) or a saline-irrigated RFA catheter. Simultaneous diagnostic coronary angiography was performed before, during, and after catheter ablation. Nitroglycerin was planned for spasm persisting beyond 20 minutes or for significant electrocardiographic changes. Main Outcomes and Measures: The frequency and severity of left circumflex arterial vasospasm was assessed and monitored, as were time to remission and any need for nitroglycerin administration. Results: Of 26 included patients, 19 (73%) were male, and the mean (SD) age was 65.5 (9.3) years. Patients underwent either PFA (n = 17) or RFA (n = 9) along the mitral isthmus. Coronary spasm was observed in 7 of 17 patients (41.2%) undergoing PFA: in 7 of 9 (77.8%) when the mitral isthmus ablation line was situated superiorly and in 0 of 8 when situated inferiorly. Conversely, coronary spasm did not occur in any of the 9 patients undergoing RFA. Of 5 patients in whom crossover PFA was performed after RFA failed to achieve conduction block, coronary spasm occurred in 3 (60%). Most instances of spasm (9 of 10 [90%]) were subclinical, with 2 (20%) requiring nitroglycerin administration. The median (range) time to resolution of spasm was 5 (5-25) minutes. Conclusion and Relevance: When creating a mitral isthmus ablation line during catheter ablation of atrial fibrillation, adjacent left circumflex arterial vasospasm frequently occurred with PFA and not RFA but was typically subclinical.

Severity of Ischemic Stroke After Left Atrial Appendage Closure vs Nonwarfarin Oral Anticoagulants.

BACKGROUND: Strokes after left atrial appendage closure (LAAC) prophylaxis are generally less severe than those after warfarin prophylaxis-thought to be secondary to more hemorrhagic strokes with warfarin. Hemorrhagic strokes are similarly infrequent with direct oral anticoagulant (DOAC) prophylaxis, so the primary subtype after either LAAC or DOAC prophylaxis is ischemic stroke (IS). OBJECTIVES: The purpose of this study was to compare the severity of IS using the modified Rankin Scale in atrial fibrillation patients receiving prophylaxis with DOACs vs LAAC. METHODS: A retrospective analysis was performed of consecutive patients undergoing LAAC at 8 centers who developed an IS (ISLAAC) compared with contemporaneous consecutive patients who developed IS during treatment with DOACs (ISDOAC). The primary outcome was disabling/fatal stroke (modified Rankin Scale 3-5) at discharge and 3 months later. RESULTS: Compared with ISDOAC patients (n = 322), ISLAAC patients (n = 125) were older (age 77.2 ± 13.4 years vs 73.1 ± 11.9 years; P = 0.002), with higher HAS-BLED scores (3.0 vs 2.0; P = 0.004) and more frequent prior bleeding events (54.4% vs 23.6%; P < 0.001), but similar CHA2DS2-VASc scores (5.0 vs 5.0; P = 0.28). Strokes were less frequently disabling/fatal with ISLAAC than ISDOAC at both hospital discharge (38.3% vs 70.3%; P < 0.001) and 3 months later (33.3% vs 56.2%; P < 0.001). Differences in stroke severity persisted after propensity score matching. By multivariate regression analysis, ISLAAC was independently associated with fewer disabling/fatal strokes at discharge (OR: 0.22; 95% CI: 0.13-0.39; P < 0.001) and 3 months (OR: 0.25; 95% CI: 0.12-0.50; P < 0.001), and fewer deaths at 3 months (OR: 0.28; 95% CI: 0.12-0.64; P < 0.001). CONCLUSIONS: Ischemic strokes in patients with atrial fibrillation are less often disabling or fatal with LAAC than DOAC prophylaxis.

Stroke Prevention in Atrial Fibrillation: Our Current Failures and Required Research.

Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients. Left atrial appendage closure is a nonpharmacological method to prevent ischemic strokes in atrial fibrillation without the need for lifelong anticoagulant use, but this procedure has the potential for complications and residual embolic events. This workshop of the Roundtable of Academia and Industry for Stroke Prevention discussed future research needed to further decrease the ischemic and hemorrhagic risks among patients with atrial fibrillation. A direct thrombin inhibitor, factor Xa inhibitors, and left atrial appendage closure are FDA-approved approaches whereas factor XIa inhibitors are currently being studied in phase 3 randomized controlled trials for stroke prevention. The benefits, risks, and shortcomings of these treatments and future research required in different high-risk patient populations are reviewed in this consensus statement.

Ultrastructural insights from myocardial ablation lesions from microsecond pulsed field vs radiofrequency energy.

BACKGROUND: Ultrastructural findings immediately after pulsed field ablation (PFA) of the myocardium have not been described. OBJECTIVES: The purpose of this study was to elucidate ultrastructural characteristics and differences between microsecond PFA at the 1- and 4-hour timepoints after pulse delivery and to compare them to irrigated radiofrequency ablation (RFA) lesions. METHODS: Healthy swine underwent endocardial PFA or RFA followed by necropsy. Discrete microsecond PFA and irrigated RFA lesions were created in the ventricles with a lattice tip ablation catheter. Lesions were delivered in a manner so as to allow sampling to occur 1 and 4 hours after ablation. All lesions were located at necropsy, and samples were carefully obtained from within the lesion core, lesion periphery, and adjacent healthy myocardium. Transmission electron microscopic assessment was performed after fixation using paraformaldehyde and glutaraldehyde. RESULTS: One hour after microsecond PFA delivery, myocytes were noted to be significantly and uniformly disrupted. Clustered, misaligned, swollen mitochondria coupled with degenerating nuclei and condensed chromatin were visualized. These findings progressed over the subsequent few hours with worsening edema. Similar changes were seen with RFA but reduced in severity. However, there was prominent extravasation of red blood cells with occlusion of capillaries that was not seen in PFA. At the lesion periphery, an abrupt change in the degree of myocyte damage was observed with PFA but not RFA. CONCLUSION: Transmission electron microscopy demonstrates evidence of widespread destruction of myocytes as early as an hour after PFA and corroborates known histologic features such as sparing of vessels and sharp lesion margins.

Clinical Outcomes by Sex After Pulsed Field Ablation of Atrial Fibrillation.

Importance: Previous studies evaluating the association of patient sex with clinical outcomes using conventional thermal ablative modalities for atrial fibrillation (AF) such as radiofrequency or cryoablation are controversial due to mixed results. Pulsed field ablation (PFA) is a novel AF ablation energy modality that has demonstrated preferential myocardial tissue ablation with a unique safety profile. Objective: To compare sex differences in patients undergoing PFA for AF in the Multinational Survey on the Methods, Efficacy, and Safety on the Postapproval Clinical Use of Pulsed Field Ablation (MANIFEST-PF) registry. Design, Setting, and Participants: This was a retrospective cohort study of MANIFEST-PF registry data, which included consecutive patients undergoing postregulatory approval treatment with PFA to treat AF between March 2021 and May 2022 with a median follow-up of 1 year. MANIFEST-PF is a multinational, retrospectively analyzed, prospectively enrolled patient-level registry including 24 European centers. The study included all consecutive registry patients (age ≥18 years) who underwent first-ever PFA for paroxysmal or persistent AF. Exposure: PFA was performed on patients with AF. All patients underwent pulmonary vein isolation and additional ablation, which was performed at the discretion of the operator. Main Outcomes and Measures: The primary effectiveness outcome was freedom from clinically documented atrial arrhythmia for 30 seconds or longer after a 3-month blanking period. The primary safety outcome was the composite of acute (<7 days postprocedure) and chronic (>7 days) major adverse events (MAEs). Results: Of 1568 patients (mean [SD] age, 64.5 [11.5] years; 1015 male [64.7%]) with AF who underwent PFA, female patients, as compared with male patients, were older (mean [SD] age, 68 [10] years vs 62 [12] years; P < .001), had more paroxysmal AF (70.2% [388 of 553] vs 62.4% [633 of 1015]; P = .002) but had fewer comorbidities such as coronary disease (9% [38 of 553] vs 15.9% [129 of 1015]; P < .001), heart failure (10.5% [58 of 553] vs 16.6% [168 of 1015]; P = .001), and sleep apnea (4.7% [18 of 553] vs 11.7% [84 of 1015]; P < .001). Pulmonary vein isolation was performed in 99.8% of female (552 of 553) and 98.9% of male (1004 of 1015; P = .90) patients. Additional ablation was performed in 22.4% of female (124 of 553) and 23.1% of male (235 of 1015; P = .79) patients. The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was similar in male and female patients (79.0%; 95% CI, 76.3%-81.5% vs 76.3%; 95% CI, 72.5%-79.8%; P = .28). There was also no significant difference in acute major AEs between groups (male, 1.5% [16 of 1015] vs female, 2.5% [14 of 553]; P = .19). Conclusion and Relevance: Results of this cohort study suggest that after PFA for AF, there were no significant sex differences in clinical effectiveness or safety events.

Electrographic flow mapping of persistent atrial fibrillation: intra- and inter-procedure reproducibility in the absence of 'ground truth'.

AIMS: Validating mapping systems that identify atrial fibrillation (AF) sources (focal/rotational activity) is confounded by the absence of ground truth. A key concern of prior mapping technologies is spatiotemporal instability, manifesting as poor map reproducibility. Electrographic flow (EGF) employs a novel algorithm that visualizes atrial electrical wavefront propagation to identify putative AF sources. We analysed both intra- (3 min) and inter- (>3 months) procedure EGF map reproducibility. METHODS AND RESULTS: In 23 persistent AF patients, after pulmonary vein isolation (PVI), EGF maps were generated from 3 serial 1 min recordings using a 64-electrode basket mapping catheter (triplets) at right and left atrial locations. Source prevalence from map triplets was compared between recordings. Per protocol, 12 patients returned for 3-month remapping (1 non-inducible): index procedure post-PVI EGF maps were compared with initial EGF remapping at 3-month redo. Intra-procedure reproducibility: analysing 224 map triplets (111 right atrium, 113 left atrium) revealed a high degree of map consistency with minimal min-to-min shifts: 97 triplets (43%), exact match of leading sources on all 3 maps; 95 triplets (42%), leading source within 1 electrode space on 2 of 3 maps; and 32 triplets (14%), chaotic leading source pattern. Average deviation in source prevalence over 60 s was low (6.4%). Inter-procedure reproducibility: spatiotemporal stability of EGF mapping >3 months was seen in 16 of 18 (89%) sources mapped in 12 patients with (re)inducible AF. CONCLUSION: Electrographic flow mapping generates reproducible intra- and inter-procedural maps, providing rationale for randomized clinical trials targeting these putative AF sources.