First-in-human clinical series of a novel conformable large-lattice pulsed field ablation catheter for pulmonary vein isolation.

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 AND RESULTS: After rendering the PV anatomy, the PFA catheter delivered monopolar, biphasic pulse trains (5-6 s 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. At three centres, 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: Pulmonary vein isolation (PVI) utilizing a conformable single-shot PFA catheter to treat PAF was efficient, safe, and effective, with durable lesions demonstrated upon remapping.

Impact of Left Atrial Posterior Wall Ablation During Pulsed-Field Ablation for Persistent Atrial Fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) alone is insufficient to treat many patients with persistent atrial fibrillation (PersAF). Adjunctive left atrial posterior wall (LAPW) ablation with thermal technologies has revealed lack of efficacy, perhaps limited by the difficulty in achieving lesion durability amid concerns of esophageal injury. OBJECTIVES: This study aims to compare the safety and effectiveness of PVI + LAPW ablation vs PVI in patients with PersAF using pulsed-field ablation (PFA). METHODS: In a retrospective analysis of the MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-approval Clinical Use of Pulsed Field Ablation) registry, we studied consecutive PersAF patients undergoing post-approval treatment with a pentaspline PFA catheter. The primary effectiveness outcome was freedom from any atrial arrhythmia of ≥30 seconds. Safety outcomes included the composite of acute and chronic major adverse events. RESULTS: Of the 547 patients with PersAF who underwent PFA, 131 (24%) received adjunctive LAPW ablation. Compared to PVI-alone, patients receiving adjunctive LAPW ablation were younger (65 vs 67 years of age, P = 0.08), had a lower CHA2DS2-VASc score (2.3 ± 1.6 vs 2.6 ± 1.6, P = 0.08), and were more likely to receive electroanatomical mapping (48.1% vs 39.0%, P = 0.07) and intracardiac echocardiography imaging (46.1% vs 17.1%, P < 0.001). The 1-year Kaplan-Meier estimate for freedom from atrial arrhythmias was not statistically different between groups in the full (PVI + LAPW: 66.4%; 95% CI: 57.6%-74.4% vs PVI: 73.1%; 95% CI: 68.5%-77.2%; P = 0.68) and propensity-matched cohorts (PVI + LAPW: 71.7% vs PVI: 68.5%; P = 0.34). There was also no significant difference in major adverse events between the groups (2.2% vs 1.4%, respectively, P = 0.51). CONCLUSIONS: In patients with PersAF undergoing PFA, as compared to PVI-alone, adjunctive LAPW ablation did not improve freedom from atrial arrhythmia at 12 months.

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.

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.

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.

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.

Reversible Pulsed Electrical Fields as an In Vivo Tool to Study Cardiac Electrophysiology: The Advent of Pulsed Field Mapping.

BACKGROUND: During electrophysiological mapping of tachycardias, putative target sites are often only truly confirmed to be vital after observing the effect of ablation. This lack of mapping specificity potentiates inadvertent ablation of innocent cardiac tissue not relevant to the arrhythmia. But if myocardial excitability could be transiently suppressed at critical regions, their suitability as targets could be conclusively determined before delivering tissue-destructive ablation lesions. We studied whether reversible pulsed electric fields (PFREV) could transiently suppress electrical conduction, thereby providing a means to dissect tachycardia circuits in vivo. METHODS: PFREV energy was delivered from a 9-mm lattice-tip catheter to the atria of 12 swine and 9 patients, followed by serial electrogram assessments. The effects on electrical conduction were explored in 5 additional animals by applying PFREV to the atrioventricular node: 17 low-dose (PFREV-LOW) and 10 high-dose (PFREV-HIGH) applications. Finally, in 3 patients manifesting spontaneous tachycardias, PFREV was applied at putative critical sites. RESULTS: In animals, the immediate post-PFREV electrogram amplitudes diminished by 74%, followed by 78% recovery by 5 minutes. Similarly, in patients, a 69.9% amplitude reduction was followed by 84% recovery by 3 minutes. Histology revealed only minimal to no focal, superficial fibrosis. PFREV-LOW at the atrioventricular node resulted in transient PR prolongation and transient AV block in 59% and 6%, while PFREV-HIGH caused transient PR prolongation and transient AV block in 30% and 50%, respectively. The 3 tachycardia patients had atypical atrial flutters (n=2) and atrioventricular nodal reentrant tachycardia. PFREV at putative critical sites reproducibly terminated the tachycardias; ablation rendered the tachycardias noninducible and without recurrence during 1-year follow-up. CONCLUSIONS: Reversible electroporation pulses can be applied to myocardial tissue to transiently block electrical conduction. This technique of pulsed field mapping may represent a novel electrophysiological tool to help identify the critical isthmus of tachycardia circuits.

Electrographic flow-guided ablation in redo patients with persistent atrial fibrillation (FLOW-AF): design and rationale.

Background: Electrographic flow (EGF) mapping enables the dynamic detection of functional or active atrial fibrillation (AF) sources outside the pulmonary veins (PVs), and the presence or absence of these sources offers a novel framework for classifying and treating persistent AF patients based on the underlying pathophysiology of their AF disease. Objective: The primary objective of the FLOW-AF trial is to evaluate the reliability of the EGF algorithm technology (Ablamap software) to identify AF sources and guide ablation therapy in patients with persistent AF. Methods: The FLOW-AF trial (NCT04473963) is a prospective, multicenter, randomized clinical study in which patients with persistent or long-standing persistent AF who have failed prior PV isolation (PVI) undergo EGF mapping after confirmation of intact PVI. In total, 85 patients will be enrolled and stratified based on the presence or absence of EGF-identified sources. Patients with an EGF-identified source above the predetermined activity threshold of ≥26.5% will be randomized in a 1:1 fashion to PVI only vs PVI + ablation of EGF-identified extra-PV sources of AF. Results: The primary safety endpoint is freedom from serious adverse events related to the procedure through 7 days following the randomization procedure; and the primary effectiveness endpoint is the successful elimination of significant sources of excitation with the target parameter the activity of the leading source. Conclusions: The FLOW-AF trial is a randomized study designed to evaluate the ability of the EGF mapping algorithm to identify patients with active extra-PV AF sources.

Safety and Effectiveness of Pulsed Field Ablation to Treat Atrial Fibrillation: One-Year Outcomes From the MANIFEST-PF Registry.

BACKGROUND: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. RESULTS: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA2DS2-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P=0.001). Acute major adverse events occurred in 1.9% of patients. CONCLUSIONS: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

A Focal Ablation Catheter Toggling Between Radiofrequency and Pulsed Field Energy to Treat Atrial Fibrillation.

BACKGROUND: Because of its safety, "single-shot" pulsed field ablation (PFA) catheters have been developed for pulmonary vein isolation (PVI). However, most atrial fibrillation (AF) ablation procedures are performed with focal catheters to permit flexibility of lesion sets beyond PVI. OBJECTIVES: This study sought to determine the safety and efficacy of a focal ablation catheter able to toggle between radiofrequency ablation (RFA) or PFA to treat paroxysmal or persistent AF. METHODS: In a first-in-human study, a focal 9-mm lattice tip catheter was used for PFA posteriorly and either irrigated RFA (RF/PF) or PFA (PF/PF) anteriorly. Protocol-driven remapping was at ∼3 months postablation. The remapping data prompted PFA waveform evolution: PULSE1 (n = 76), PULSE2 (n = 47), and the optimized PULSE3 (n = 55). RESULTS: The study included 178 patients (paroxysmal/persistent AF = 70/108). Linear lesions, either PFA or RFA, included 78 mitral, 121 cavotricuspid isthmus, and 130 left atrial roof lines. All lesion sets (100%) were acutely successful. Invasive remapping of 122 patients revealed improvement of PVI durability with waveform evolution: PULSE1: 51%; PULSE2: 87%; and PULSE3: 97%. After 348 ± 652 days of follow-up, the 1-year Kaplan-Meier estimates for freedom from atrial arrhythmias were 78.3% ± 5.0% and 77.9% ± 4.1% for paroxysmal and persistent AF, respectively, and 84.8% ± 4.9% for the subset of persistent AF patients receiving the PULSE3 waveform. There was 1 primary adverse event-inflammatory pericardial effusion not requiring intervention. CONCLUSIONS: AF ablation with a focal RF/PF catheter allows efficient procedures, chronic lesion durability, and good freedom from atrial arrhythmias-for both paroxysmal and persistent AF. (Safety and Performance Assessment of the Sphere-9 Catheter and the Affera Mapping and RF/PF Ablation System to Treat Atrial Fibrillation; NCT04141007 and NCT04194307).

Provocation and Localization of Arrhythmogenic Triggers from Persistent Left Superior Vena Cava in Patients with Atrial Fibrillation.

BACKGROUND: Although pulmonary vein isolation (PVI) is an established procedure for atrial fibrillation (AF), non-PV foci play a crucial role in AF recurrence. Persistent left superior vena cava (PLSVC) has been reported as critical non-PV foci. However, the effectiveness of provocation of AF triggers from PLSVC remains unclear. This study was designed to validate the usefulness of provoking AF triggers from PLSVC. METHODS: This multicenter retrospective study included 37 patients with AF and PLSVC. To provoke triggers, AF was cardioverted, and re-initiation of AF was monitored under high-dose isoproterenol infusion. The patients were divided into two groups: those whose PLSVC had arrhythmogenic triggers initiating AF (Group A) and those whose PLSVC did not have triggers (Group B). Group A underwent isolation of PLSVC after PVI. Group B received PVI only. RESULTS: Group A had 14 patients, whereas Group B had 23 patients. After a 3-year follow-up, no difference in the success rate for maintaining sinus rhythm was observed between the two groups. Group A was significantly younger and had lower CHADS2-VASc scores than Group B. CONCLUSIONS: The provocation of arrhythmogenic triggers from PLSVC was effective for the ablation strategy. PLSVC electrical isolation would not be necessary if arrhythmogenic triggers are not provoked.

Pulsed Field Ablation to Treat Atrial Fibrillation: Autonomic Nervous System Effects.

BACKGROUND: During atrial fibrillation ablations using thermal energy, the treatment effect is attributed to not just pulmonary vein isolation (PVI), but also to modulation of the autonomic nervous system by ablation of cardiac ganglionated plexi (GP). OBJECTIVES: This study sought to assess the impact of pulsed field ablation (PFA) on the GP in patients undergoing PVI. METHODS: In the retrospective phase, heart rate was assessed pre- versus post-PVI using PFA, cryoballoon ablation, or radiofrequency ablation. In the prospective phase, a pentaspline PFA catheter was used in a protocol: 1) pre-PFA, high-frequency stimulation (HFS) identified GP sites by vagal effects; 2) PVI was performed assessing for repetitive vagal effects over each set of PF applications; 3) mapping defined PVI extent to identify those GP in the ablation zone; and 4) repeat HFS at GP sites to assess for persistence of vagal effects. RESULTS: Between baseline and 3 months, heart rates in the retrospective radiofrequency ablation (n = 40), cryoballoon (n = 40), and PFA (n = 40) cohorts increased by 8.9 ± 11.4, 11.1 ± 9.4, and -0.1 ± 9.2 beats/min, respectively (P= 0.01 PFA vs radiofrequency ablation; P= 0.01 PFA vs cryoballoon ablation). In the prospective phase, pre-PFA HFS in 20 additional patients identified 65 GP sites. During PFA, vagal effects were noted in 45% of first PF applications, persisting through all applications in 83%. HFS post-PFA reproduced vagal effects in 29 of 38 sites (76%) in low-voltage tissue. CONCLUSIONS: PFA has minimal effect on GP. Unlike with thermal ablation, the mechanism by which PFA treats atrial fibrillation is mediated solely by durable PVI.

PV Isolation Using a Spherical Array PFA Catheter: Application Repetition and Lesion Durability (PULSE-EU Study).

BACKGROUND: Preclinical studies have revealed that pulsed field ablation (PFA) lesion dimensions increase with repetitive applications at a similar electric field. OBJECTIVES: This study investigated whether pulmonary vein isolation (PVI) durability varies with single vs repetitive pulsed field (PF) applications. METHODS: Atrial fibrillation patients underwent PVI using a spherical multielectrode array PFA catheter delivered with a 19-F deflectable sheath under intracardiac echocardiographic guidance. Esophagogastroduodenoscopy and brain magnetic resonance imaging were performed within 1 to 3 days, and invasive remapping at ∼2 to 3 months. RESULTS: The patient cohort (n = 21; age 63 ± 11 years; 67% women) underwent PVI in either of 2 groups: group 1 (n = 11)-single PF application/PV; and group 2 (n = 10)-3 PF applications/PV. In both groups, PVI was acutely successful in all (100%) patients. Despite significantly longer pulse delivery times (75.2 ± 7.4 s/patient vs 24.5 ± 5.5 s/patient) the procedure times (73.2 ± 13.7 minutes vs 93.7 ± 18.5 minutes) were shorter with group 2 vs group 1. There was no stroke/transient ischemic attack, pericardial effusion, phrenic nerve injury, or esophageal complications. Esophagogastroduodenoscopy was normal in both groups of patients (n = 9). Screening brain magnetic resonance imaging revealed asymptomatic cerebral lesions (diffusion weighted imaging+/fluid attenuated inversion recovery-) in 3 of 16 (18.7%) patients. PV remapping revealed durable PVI in 62.5% PVs in group 1 (n = 10), compared with all 100% PVs in group 2 (n = 9); this translates to all PVs being durably isolated in 30% vs 100% (P < 0.05) of patients in groups 1 and 2, respectively. CONCLUSIONS: In his first-in-human trial, the "single-shot" spherical array PFA catheter was shown to safely isolate PVs. Repetitive PF application is key for lesion consolidation to maximize PVI durability.

Translational Rabbit Model of Chronic Cardiac Pacing.

Animal models of cardiac pacing are beneficial for testing novel devices, studying the pathophysiology of artificially paced heart rhythms, and studying arrhythmia-induced cardiomyopathies and subsequent heart failure. Currently, only a few such models are available, and they mostly require extensive resources. We report a new experimental cardiac pacing model in small mammals with the potential to study arrhythmia-induced heart failure. In six New Zealand white rabbits (mean weight: 3.5 kg) under general inhalational anesthesia the jugular region was dissected and a single pacing lead was inserted via the right external jugular vein. Using fluoroscopic guidance, the lead was further advanced to the right ventricular apex, where it was stabilized using passive fixation. A cardiac pacemaker was then connected and buried in a subcutaneous pocket. The pacemaker implantation was successful with good healing; the rabbit anatomy is favorable for the lead placement. During 6 months of follow-up with intermittent pacing, the mean sensed myocardial potential was 6.3 mV (min: 2.8 mV, max: 12 mV), and the mean lead impedance measured was 744 Ω (min: 370 Ω, max: 1014 Ω). The pacing threshold was initially 0.8 V ± 0.2 V and stayed stable during the follow-up. This present study is the first to present successful transvenous cardiac pacing in a small-mammal model. Despite the size and tissue fragility, human-size instrumentation with adjustments can safely be used for chronic cardiac pacing, and thus, this innovative model is suitable for studying the development of arrhythmia-induced cardiomyopathy and consequent heart failure pathophysiology.

Radiofrequency ablation using the second-generation temperature-controlled diamond tip system in paroxysmal and persistent atrial fibrillation: results from FASTR-AF.

BACKGROUND: Catheter ablation (CA) technology development reflects the need to improve the effectiveness of atrial fibrillation (AF) treatment. Recently, the DiamondTemp Ablation (DTA) RF generator software was updated with a more responsive power ramp. METHODS: DIAMOND FASTR-AF was a prospective, single-arm, multicenter trial. This study sought to characterize the performance of the updated DTA system for the treatment of patients with drug-refractory paroxysmal and persistent AF (PAF and PsAF). The primary effectiveness endpoint was freedom from atrial arrhythmia recurrence following a 90-day blanking period through 12 months, and the primary safety endpoint was a composite of serious adverse events. RESULTS: In total, 60 subjects (34 PAF and 26 PsAF) underwent CA at three centers. Patients were 71.7% male, (age 63.9 ± 10.2 years, with an AF diagnosis duration 3.1 ± 3.9 years and left atrial size 4.4 ± 0.8 cm). Pulmonary vein isolation-only ablation strategy was performed in 34 (56.7%) subjects. The procedural characteristics show a procedure time 90.8 ± 31.6 min, total RF time 14.7 ± 7.7 min, ablation duration 10.7 ± 3.6 s, and fluid infusion 284.7 ± 111.5 ml. The serious adverse event rate was 8.3% (5/60), 3 pulmonary edema and 2 extended hospitalizations. Freedom from atrial arrhythmia recurrence was achieved in 67.6% of subjects by 12 months. CONCLUSIONS: The updated DTA system demonstrated long-term safety and effectiveness through 12 months of post-ablation follow-up for patients with atrial fibrillation. Additionally, procedures were demonstrated to be highly efficient with short procedure times and low levels of fluid infusion. TRIAL REGISTRATION: Sponsored by Medtronic, Inc.; FASTR-AF ClinicalTrials.gov; NCT03626649.