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

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug–drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

Background: Pulsed-field ablation (PFA) is a tissue-selective, nonthermal cardiac ablation modality. A novel PFA ablation system consisted of a multichannel irreversible electroporation generator system and a multielectrode circular irreversible electroporation catheter has been developed for catheter ablation. To understand the progression and immediate impacts of PFA, this study evaluated the subchronic (7±3 day) and chronic (30±3 day) safety and performance of the novel PFA system when simulating pulmonary vein and superior vena cava isolation in a porcine beating heart model. Methods: Ten swine models were divided into subchronic (n=6) and chronic cohorts (n=4). Lesions were performed within the right and left atrium to conduct right pulmonary veins and superior vena cava isolations, in addition to creating stacked lesions in the left atrium roof and right atrium posterior wall. Results: Acute pulmonary vein and superior vena cava isolation were achieved in 10 out of 10 swine and demonstrated 100% lesion durability in both cohorts, including sustained elimination of electrical activity at the left atrium roof and right atrium posterior wall. Histology demonstrated that all the cardiac sites ablated showed discrete zones of loss of myocardial fibers or smooth muscle cells with preservation of the tissue architecture with resultant fibrocellular replacement, neovascularization, and neocollagen deposition. Mineralization findings were present in association with residual necrotic muscle fibers. Only in 7 days group, areas of mineralization were frequently associated with inflammation. There were no treatment-related changes in other tissues, including complete sparing of the phrenic nerve. Conclusions: Pulsed-field ablation for pulmonary vein and superior vena cava isolation with the novel PFA system was feasible, safe with myocardial-specific ablative effect. Durable lesions were observed at the target areas. with inflammation phenomena mainly documented at 7 days.

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 CHA ₂ DS ₂ -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

Background: Pulsed field ablation (PFA) is a novel, largely nonthermal ablative modality that, by virtue of its putative preferential action on myocardial tissue through the process of irreversible electroporation (IRE), may replace conventional thermal ablation for atrial fibrillation (AF). The recent inspIRE study confirmed safety and effectiveness of a fully integrated biphasic PFA system with a variable loop circular catheter for the treatment of paroxysmal AF. The majority of PFA procedures were performed using general anesthesia. However, due to the risks of general anesthesia we report the data regarding our sedation protocol used during inspIRE study. Methods: A total of 29 patients (mean age 55±9 years; 72% male) were enrolled as part of this analysis within the inspIRE trial. The sedation protocol is reported in the manuscript. The Richmond Agitation-Sedation Scale (RASS), the Visual Analogue Scale (VAS) and the Patient State Index were collected during sedation. Each patient was monitored using the Masimo Sedline. At the end of ablation, the Likert Scale Questionnaire (LSQ) was used to assess the patients' satisfaction with intraoperative analgesia-sedation. Results: No procedural complications were documented. Sufficient oxygen saturation was maintained in all patients during procedure. Non-invasive ventilation or tracheal intubation were not required for any patient. The RAAS score between -1 to -5 was obtained in 27 patients (93%) while the value 0 was obtained in 2 patients (7%). The VAS score between 0 to 2 was obtained in 24 patients (83%); the VAS score 3 in 3 patients (10%) and the VAS score 4 in 2 patients (7%). The PSI score <50 was achieved in 16 patients (55%) while the PSI between 50 and 70 was achieved in 9 patients (31%). Positive answers to LSQ were obtained in most patients. Conclusion: During PFA ablation procedures with the variable-loop circular catheter and its accompanying biphasic pulse, our deep sedation protocol is a valid alternative to general anesthesia.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and catheter ablation, which can be used in symptomatic patients refractory to antiarrhythmic therapy. Pulmonary vein isolation (PVI) remains the cornerstone of any ablation procedure. A major limitation of current catheter ablation procedures is important to recognize because even when the PVI is performed in highly experienced centers, PVI reconnection was documented in about 20% of patients. Therefore, better technology is needed to improve ablation lesions. One of the novelties in recent years is pulsed filed ablation (PFA), a non-thermal energy that uses trains of high-voltage, very-short-duration pulses to kill the cells. The mechanism of action of this energy consists of creating pores in the myocardiocyte cell membrane in a highly selective and tissue-specific way; this leads to death of the target cells reducing the risk of damage to surrounding non-cardiac tissues. In particular during the animal studies, PVI and atrial lines were performed effectively without PV stenosis. Using PFA directly on coronary arteries, there was no luminal narrowing, there has been no evidence of incidental phrenic nerve injury, and finally, PFA has been shown not to injure esophageal tissue when directly applied to the esophagus or indirectly through ablation in the left atrium. The aim of this review is to report all published animal and clinical studies regarding this new technology to treat paroxysmal and persistent AF.