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) 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%, CHA ₂ DS ₂ -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.

Pulsed field ablation (PFA) is a novel atrial fibrillation (AF) ablation modality that has demonstrated preferential tissue ablation, including no oesophageal damage, in first-in-human clinical trials. In the MANIFEST-PF survey, we investigated the ‘real world’ performance of the only approved PFA catheter, including acute effectiveness and safety—in particular, rare oesophageal effects and other unforeseen PFA-related complications. This retrospective survey included all 24 clinical centres using the pentaspline PFA catheter after regulatory approval. Institution-level data were obtained on patient characteristics, procedure parameters, acute efficacy, and adverse events. With an average of 73 patients treated per centre (range 7–291), full cohort included 1758 patients: mean age 61.6 years (range 19–92), female 34%, first-time ablation 94%, paroxysmal/persistent AF 58/35%. Most procedures employed deep sedation without intubation (82.1%), and 15.1% were discharged same day. Pulmonary vein isolation (PVI) was successful in 99.9% (range 98.9–100%). Procedure time was 65 min (38–215). There were no oesophageal complications or phrenic nerve injuries persisting past hospital discharge. Major complications (1.6%) were pericardial tamponade (0.97%) and stroke (0.4%); one stroke resulted in death (0.06%). Minor complications (3.9%) were primarily vascular (3.3%), but also included transient phrenic nerve paresis (0.46%), and TIA (0.11%). Rare complications included coronary artery spasm, haemoptysis, and dry cough persistent for 6 weeks (0.06% each). In a large cohort of unselected patients, PFA was efficacious for PVI, and expressed a safety profile consistent with preferential tissue ablation. However, the frequency of ‘generic’ catheter complications (tamponade, stroke) underscores the need for improvement.

Aims: Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centres and involved a limited number of operators. We aimed to describe the electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF. Methods and results: In the MANIFEST-REDO study, we investigated patients who underwent repeat ablation due to clinical recurrence—AF or atrial tachycardia (AT)—following first-ever PVI with a pentaspline PFA catheter (Farawave, Boston Scientific Inc.). At 22 centres, 427 patients (age 64 ± 11 years; 37% female) were included. Of note, the recurrent arrhythmia leading to the repeat ablation was paroxysmal AF (51%), persistent AF (30%), or AT (19%). At the repeat procedure, the PV reconnection rates were 30% (left superior pulmonary vein), 28% (left inferior pulmonary vein), 33% (right superior pulmonary vein), and 32% (right inferior pulmonary vein). In 45% of patients, all PVs were durably isolated at the beginning of the repeat procedure, with the previous use of any imaging or mapping modality being univariately associated with durable PVI. After a post-redo follow-up period of 284 (90–366) days, the primary effectiveness endpoint (freedom from documented AF/AT lasting ≥30 s after 3-month blanking without class I/III antiarrhythmic drugs or symptoms) was achieved in 65% of patients, with significant differences between groups (PAF 65% vs. PersAF 56% vs. AT 76%; P = 0.04). Persistent AF as recurrent arrhythmia after the initial PFA ablation predicted AT/AF recurrence after repeat ablation [hazard ratio 1.241 (95% confidence interval 1.534–1.005); P = 0.045]. The procedural complication rate was 2.8%. Conclusion: In repeat procedures for AF/AT performed after an index procedure with PFA for AF, PV reconnections are not uncommon. Repeat procedures can be performed safely and with an acceptable subsequent success rate.

Aims: Pulsed field ablation (PFA) has emerged as a promising alternative to thermal ablation for treatment of atrial fibrillation (AF). We report performance and safety using the CENTAURI™ System (Galvanize Therapeutics) with three commercial, focal ablation catheters. Methods and results: ECLIPSE AF (NCT04523545) was a prospective, single-arm, multi-centre study evaluating safety and acute and chronic pulmonary vein isolation (PVI) durability using the CENTAURI System in conjunction with the TactiCath SE, StablePoint, and ThermoCool ST ablation catheters. Patients with paroxysmal or persistent AF were treated at two centres. Patients were analysed in five cohorts based upon ablation settings, catheter, and mapping system. Pulsed field ablation was performed in 82 patients (74% male, 42 paroxysmal AF). Pulmonary vein isolation was achieved in 100% of pulmonary veins (322/322) with first-pass isolation in 92.2% (297/322). There were four serious adverse events of interest (three vascular access complications and one lacunar stroke). Eighty patients (98%) underwent invasive remapping. Pulsed field ablation development Cohorts 1 and 2 showed a per-patient isolation rate of 38% and 26% and a per-PV isolation rate of 47% and 53%, respectively. Optimized PFA Cohorts 3–5 showed a per-patient isolation rate of 60%, 73%, and 81% and a per-PV isolation rate of 84%, 90%, and 92%, respectively. Conclusion: ECLIPSE AF demonstrated that optimized PFA using the CENTAURI System with three commercial, contact force-sensing, solid-tip focal ablation catheters resulted in transmural lesion formation and high proportion of durable PVI with a favourable safety profile, thus providing a viable treatment option for AF that integrates with contemporary focal ablation workflows.

Objectives. To explore the relationship between IL-6 levels and echocardiographic abnormalities, and N-terminal probrain natriuretic peptide (NT-proBNP) levels in SSc patients and to correlate tested parameters with European Scleroderma Activity (EUSTAR) score. Methods. This case–control study included 31 SSc patients with preserved left ventricular ejection fraction (LVEF) and 32 matched healthy controls. Serum IL-6 and NT-proBNP levels were measured and subjects were evaluated by conventional and pulsed-wave tissue Doppler echocardiography. Results. The level of IL-6 was significantly increased in patients with SSc (3.2 vs 2.2 pg/ml, P < 0.001). SSc patients had significantly lower values of LV systolic (7.7 vs 9.25 cm/s, P < 0.001) and early diastolic (8.7 vs 10.3 cm/s, P = 0.014) myocardial velocities and higher E/e′ (9.04 vs 7.37, P = 0.001) ratio, although there was no between-group difference according to LVEF (68% vs 65%, P = 0.248). On evaluating the right ventricle there was no significant between-group difference in systolic tricuspid annular velocity (13 vs 13.9 cm/s, P = 0.105), but the peak early diastolic velocity was significantly lower (11.7 vs 13.6, P = 0.044) and E/e′ was significantly higher (4.3 vs 3.38, P = 0.008) in SSc patients. IL-6 level showed correlation with LV mean e′ (r = −0.57, P = 0.001), E/e′ (r = 0.55, P = 0.001) and NT-proBNP (r = 0.52, P = 0.003). EUSTAR score correlated with LV E/e′ (r = 0.48, P = 0.006), mean e′ (r = −0.67, P < 0.001), mean s′ (r = −0.51, P = 0.004), NT-proBNP (r = 0.60, P < 0.001) and IL-6 (r = 0.79, P < 0.001). Conclusion. IL-6 level is increased in patients with SSc and significantly correlates with LV diastolic dysfunction, NT-proBNP and EUSTAR score. These results support the role of IL-6 in the development of cardiac disease in SSc patients.

BACKGROUND: Pulsed field ablation (PFA) is a promising treatment for atrial fibrillation. We report 1-year freedom from atrial arrhythmia outcomes using monopolar PFA delivered through 3 commercial, contact force–sensing focal catheters. METHODS: ECLIPSE AF (Safety & Clinical Performance Study of Catheter Ablation With the Centauri System for Patients With Atrial Fibrillation; NCT04523545) was a prospective, single-arm, multicenter study evaluating acute and chronic safety and performance using the CENTAURI system to deliver focal PFA with TactiCath SE, StablePoint, and ThermoCool ST. Patients with paroxysmal or persistent atrial fibrillation underwent pulmonary vein (PV) isolation under deep sedation or general anesthesia and returned for remapping at 90 days to evaluate chronic durability. Freedom from atrial arrhythmia was evaluated continuously through 12 months using standard rhythm monitoring for symptomatic episodes and 24-hour Holter at 6 and 12 months. RESULTS: Eighty-two patients (74% male, 51.2% paroxysmal, and 58.5% deep sedation) were treated. PV isolation was achieved in 100% of targeted veins (322/322) with first-pass isolation in 92.2% (297/322). There were 4 primary safety events in 4 patients (4.9%, 4/82); 1 nonembolic stroke due to exacerbated cardiac tamponade secondary to catheter perforation and 3 hemorrhagic vascular access complications. There were no incidences of adverse event fistula, diaphragmatic paralysis, myocardial infarction, pericarditis, thromboembolism, PV stenosis, transient ischemic attack, or death. Eighty patients (98%) underwent remapping. Optimized PFA cohorts 3, 4, and 5 showed per-patient isolation rates of 60%, 73%, and 81% and per-PV isolation rates of 84%, 90%, and 92%, respectively. One-year freedom from atrial arrhythmia was 80.2% (95% CI, 69.7%–87.4%) for the entire patient sample, including 41 patients who underwent repeat focal PFA with the CENTAURI system at remapping. CONCLUSIONS: This study demonstrated that optimization of focal PFA with 3 contact force–sensing, solid-tip ablation catheters resulted in the progressive improvement of PV isolation durability at 3-month remapping and high freedom from atrial arrhythmia survival rates, providing a promising focal PFA treatment option integrated with current ablation workflows.