Non-thermal Ablation Research Articles

A network meta-analysis on the efficacy and safety of thermal and nonthermal endovenous ablation treatments

A network meta-analysis on the efficacy and safety of thermal and nonthermal endovenous ablation treatments

EUropean real-world outcomes with Pulsed field ablatiOn in patients with symptomatic atRIAl fibrillation: lessons from the multi-centre EU-PORIA registry.

Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40-87) and 14 (9-21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323-386) days, the Kaplan-Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

Irreversible electroporation: Beyond the limits of tumor ablation

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated.Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer.The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Synergistic Enzyme-Mimetic Catalysis-Based Non-Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation.

Non-invasive cancer treatment strategies that enable local non-thermal ablation, hypoxia relief, and reactive oxygen species (ROS) production to achieve transiently destroying tumor tissue and long-term killing tumor cells would greatly facilitate their clinical applications. However, continuously generating oxygen cavitation nuclei, reducing the transient cavitation sound intensity threshold, relieving hypoxia, and improving its controllability in the ablation area still remains a significant challenge. Here, in this work, an Mn-coordinated polyphthalocyanine sonocavitation agent (Mn-SCA) with large d-π-conjugated network and atomic Mn-N sites is identified for the non-thermal sonocavitation and sonodynamic therapy in the liver cancer ablation. In the tumor microenvironment, the catalytical generation of oxygen assists cavitation formation and generates microjets to ablate liver cancer tissue and relieve hypoxia, this work reports for the first time to utilize the enzymatic properties of Mn-SCA to lower the cavitation threshold in situ. Moreover, under pHIFU irradiation, high reactive oxygen species (ROS) production can be achieved. The two merits in liver cancer ablation are demonstrated by cell destruction and high tumor inhibition efficiency. This work will help deepen the understanding of cavitation ablation and the sonodynamic mechanisms related to the nanostructures and guide the design of sonocavitation agents with high ROS production for solid tumor ablation.

The story of N-butyl cyanoacrylate saphenous vein ablation

In 2009, our group was approached by an experienced radiologist who proposed to close refluxing saphenous veins with glue; an idea based on his experience with N-butyl cyanoacrylate (TRUFILL) embolization of cerebral arterial venous malformations. We henceforth began with a swine model, 1 Almeida J.I. Min R.J. Rabe R. McLean D.J. Madsen M. Cyanoacrylate adhesive for the closure of truncal veins: 60-day swine model results. Vasc Endovascular Surg. 2011; 45: 631-635 Crossref PubMed Scopus (74) Google Scholar and then moved to first-in-human studies 2 Almeida J.I. Javier J.J. Mackay E. Bautista C. Proebstle T. One-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. J Vasc Surg Venous Lymphatic Disord. 2013; 1: 174-180 Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar for nonthermal ablation of the saphenous vein with their proprietary N-butyl cyanoacrylate glue. Of interest, during the regulatory development pathway, this product was approved as a device, not a drug. It's efficacy has proved excellent, and during the past decade cyanoacrylate closure (CAC) has been adopted widely worldwide. However, reports of hypersensitivity-related adverse events, and granulomas, have begun to surface. It is timely that Dr Athavale and his team have recently published an excellent systematic review on CAC. Based on the available literature, the adverse events related to cyanoacrylate glue can be divided into the following: phlebitis, hypersensitivity (type I and type IV), foreign body granuloma, endovenous glue induced thrombosis and infection. These adverse events may require prolonged steroid use or vein excision. Cyanoacrylate glue reactions: A systematic review, cases, and proposed mechanismsJournal of Vascular Surgery: Venous and Lymphatic DisordersVol. 11Issue 4PreviewCyanoacrylate glue closure was first used in humans 10 years ago to treat venous reflux of the axial veins. Studies have since shown its clinical efficacy in vein closure. However, great need exists to elucidate further the types of specific adverse reactions that cyanoacrylate glue can cause for better patient selection and to minimize these events. In the present study, we systematically reviewed the literature to identify the types of reported reactions. In addition, we explored the pathophysiology contributing to these reactions and proposed the mechanistic pathway with inclusion of actual cases. Full-Text PDF

CT-guided local ablative interventions

Applicator-based local ablations under computed tomography (CT) guidance for the treatment of malignant tumors have found their way into clinical routine. The basic principles of the different ablation technologies and their specific clinical field of application are described. Acomprehensive literature review regarding applicator-based ablation techniques was carried out. Radiofrequency (RFA) and microwave ablation (MWA) represent two image-guided hyperthermal treatment modalities that have been established for the treatment of primary and secondary liver malignancies. In addition, both techniques are also applied for local ablative therapy of lung- and kidney tumors. Cryoablation is mainly used for the local ablation of T1 kidney cancer and due to its intrinsic analgetic characteristics for application in the musculoskeletal system. Nonresectable pancreatic tumors and centrally located liver malignancies can be treated with irreversible electroporation. This nonthermal ablation modality preserves the structure of the extracellular matrix including blood vessels and ducts. Technical advancements in the field of CT-guided interventions include the use of robotics, different tracking and navigation technologies and the use of augmented reality with the goal to achieve higher precision, shorter intervention time and thereby reduce radiation exposure. Percutaneous ablation techniques under CT guidance are an essential part of interventional radiology and they are suited for local treatment of malignancies in most organ systems.

Electroporación irreversible: ampliando las fronteras de la ablación

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated.Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer.The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Sedation strategies for pulsed-field ablation of atrial fibrillation with monitored anesthesia care versus general anesthesia: a single-center experience

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial Fibrillation (AF) ablation has been performed successfully under different methods of anesthesia and varies between centers, from general anaesthesia (GA) to conscious sedation. Recently, a novel pulsed-field ablation (PFA, Farapulse) technology based on non-thermal ablation has become available for clinical use. To date, no structured sedation strategy has been implemented for this specific energy source. Purpose We sought to compare a GA protocol and a monitored anesthesia care (MAC) protocol used at a high-volume center, with special consideration on efficiency and optimization of mapping and ablation conditions. Methods All consecutive patients (pts) undergoing AF ablation with PFA at our center were included. Briefly, PFA was delivered by a protocol-directed PVI using 2kV with eight applications per vein, that is, four applications each in the basket and flower poses. The choice of anesthesia’s protocol depends on the preference and experience of operator and general conditions of the patient. The MAC protocol includes propofol as only anesthetic agent and analgesia with fentanyl. The GA protocol include propofol and sevofluorane as anesthetic agents and fentanyl and remifentanyl for analgesia. Anesthesia related complications (hypotension and hemodinamic instability, respiratory complications, postoperative nausea and vomit) operative pain, chest movements, operator and patient satisfaction have been reported. Data are reported as mean±DS. Results Thirty-six pts were included in this analysis, 28 (78%) indicated for ablation of paroxysmal AF and 8 (22%) of persistent AF. MAC protocol was applied in 16 (44%) procedures and GA protocol in 30 (56%) procedures. No differences were found in terms of procedural and management parameters according with these two strategies, that is MAC vs GA: 114±28min vs 121±19min for lab occupancy time, p=0.3521; 66±14min vs 81±25min for total support time, p=0.0683; 63±9min vs 63±18min for skin-to-skin time, p=0.3887; and 19±6min vs 20±5min for fluoroscopy time, p=0.3313, respectively). No major procedure-related adverse events were reported. Operative pain and chest movements were less in GA protocol, operator satisfaction was greater in GA protocol. No significant differences in post-operative nausea and vomit and patient satisfaction were found. Conclusion The adoption of a structured workflow with proper perioperative assessment during pulsed-field ablation of AF, both general anesthesia and monitored anesthesia care showed similar efficacy and safety profile.

Comparision of pulsed field ablation vs. high power short duration-ablation for pulmonary vein isolation

Abstract Funding Acknowledgements Type of funding sources: None. Background The newly introduced non-thermal pulsed field ablation (PFA) is a promising technology to achieve fast pulmonary vein isolation (PVI) with high acute success rates and comparable safety features. However, previous studies have shown that high power short duration ablation (HPSD) is also highly effective and fast to achieve PVI with potentially less AF recurrence. Data comparing PFA to HPSD-PVI is lacking. Objective This study compared procedural parameter and outcome using the novel PFA-PVI to HPSD-PVI in patients with paroxysmal or persistent atrial fibrillation (PAF/persAF). Methods Between 09/2021 and 10/2022 all consecutive patients undergoing de-novo PVI (PFA or HPSD) were included in this analysis. For PFA-PVI a shapeable (flower/basket shape) 5 spline 20 electrode catheter was used. For HPSD-PVI a power setting of 70W/7s (70W/5s at posterior wall) was considered as HPSD. Furthermore, a 3D mapping system was used. Follow-up consisted of out-clinic pts visit, teleconsultation, 48h Holter ECG and CIED interrogation if applicable. Results A total of 114 patients (57 PFA [17(30%) PAF; 40(70%) persAF 40(70%)] were included in this analysis. PVI was successful in all patients. The PFA group revealed a significantly shorter procedure duration (65±17 min vs. 95±23 min, p<0.01) but longer fluoroscopy time (PFA 15±5min and HPSD 12±3min; p<0.001). However, the overall fluoroscopy dosage was comparable between groups (PFA: 3484±2072mGy*cm2; HPSD: 3168±2346mGy*cm2; p=0.448). Two tamponades occurred in the PFA while in HPSD two pts suffered groin bleedings. At follow-up after three months (33±12 days) 46 PFA (80.7%) and 44 HPSD pts (77.2%) were free from atrial arrhythmia after a single procedure (p=0.819). One clinically non.significant PV stenosis occurred in the HPSD group. Conclusion PFA and HPSD-PVI seem to be highly effective and safe to achieve PVI in the setting of PAF and persAF with comparable arrhythmia free survival. However, procedure duration for PFA PVI is significantly shorter and therefore may be of potential benefit.

Cardiac Troponin I kinetic after pulmonary vein isolation for atrial fibrillation ablation with pulsed-field ablation and cryo-energy

Abstract Funding Acknowledgements Type of funding sources: None. Background Previous studies have demonstrated that cardiac biomarkers elevate after both cryoballoon (CB) and radiofrequency atrial fibrillation (AF) ablation, depending on the amount of energy delivered and the site of ablation. To date no comparison has been made between these thermal energy source and a novel non-thermal pulsed-field ablation (PFA) technology based on cells electroporation. Purpose Our analysis aims to compare acute myocardial injury through cardiac troponin I variation after pulmonary vein isolation (PVI) performed with different technologies (PFA vs CB). Methods All consecutive patients undergoing paroxysmal AF ablation with CB and PFA at our center from July to November 2022 were included. Protocol-directed cryoablation (CBA) was delivered for 180 sec or 240 sec according to operator’s preference for isolation achieved in ≤60 sec, or 240 sec if isolation occurred >60 sec or when time to isolation was not available. A standard PFA protocol-directed PVI was applied using 2kV with eight applications per vein (four applications each in the basket and flower poses). The ablation endpoint was PVI as assessed by entrance and exit block. Pre- and post-procedure samples of cardiac troponin I (CTpI) were collected before CBA/PFA and at 24h after ablation. Only patients with normal baseline values for myocardial injury were included. Results A total of 71 patients met inclusion criteria and were included in this analysis. The CBA group consists of 50 (70%) patients and the PFA group comprises 21 (30%) patients. The number of CBA applications to reach PVI was 5.0±1.4 and the number of PFA applications to achieve PVI was 32±4. All (100%) patients were in sinus rhythm at the time of the procedure. Evaluating the kinetic of CTpI, baseline values were homogeneous between CBA and PFA groups (p=0.979) whereas CTpI values significantly rose from baseline (7±2 ng/L) to 24h (8979±3691 ng/L, p<0.0001) and were significantly different between groups after CBA/PFA (8148±3311 ng/L for CBA vs 11900±7143 ng/L for PFA, p=0.0056). PVI was achieved in all patients (100%) using only CB or PFA. No major procedure-related adverse events were reported. Conclusion Our preliminary results showed that cardiac troponin I enzyme level increased after PVI by means of both cryoballoon and pulsed-field ablation and were higher after cellular electroporation by PFA than cryoablation.

Novel pulsed-field ablation technology for pulmonary vein isolation in patients with atrial fibrillation: preliminary experience from a large multicenter clinical practice

Abstract Funding Acknowledgements Type of funding sources: None. Background Complete electrical pulmonary vein isolation (PVI) by thermal energy sources is a well-established ablation strategy of atrial fibrillation (AF). Recently, a non-thermal ablation approach by means of irreversible cellular electroporation has been made available for clinical use. Purpose We report the preliminary experience of a new pulsed-field ablation (PFA) system in the context of AF ablation in a multicenter Italian setting. Methods All consecutive patients (pts) undergoing AF ablation with PFA at 7 Italian centres were included. Protocol-directed PVI was delivered using 2000 V with eight applications per vein, that is, four applications each in the basket and flower poses. Applications were delivered in pairs at any given catheter position, rotating by ≈30–40° after the first two applications in each configuration. Additional lesions were performed at the operator’s discretion. The ablation endpoint was PVI as assessed by entrance and exit block. Data are reported as median [IQ range]. Results With a median of 32[25-38] pts treated per center, a total of 205 cases were included (n=150 73.2%, paroxysmal AF, n=55, 26.9% persistent AF). Of them 187 (91.2%) were de novo cases, whereas 18 (8.8%) were redo cases. A mapping system was used in 55 (21.5%) procedures and an intracardiac echocardiography in 65 (31.7%) cases. The number of PFA applications to reach PVI was 32[32-36]. Procedural parameters were: fluoroscopy time = 16[12-22] min, skin-to-skin time = 60[55-85] min, support time (preparation plus skin-to-skin) =75[64-95] min, lab occupancy time was 97[75-120] min and PFA LA dwell time was 23[20-28] min. The first pass isolation (FPI) rate per vein was 99.6% resulting from 202 patients (98.5%) with FPI. At the end of the procedure, PVI was achieved in all pts (100%) using only PFA. Additional PFA delivery outside PVs was performed in 19% (n=39) of the cases, mostly at the posterior wall area only (n=34, 87%), requiring 16[12-24] PFA deliveries. All the additional lesion sets were validated through differential pacing and/or 3D mapping. The learning curve was extremely fast. After only 5 cases time to PVI and total support time have significantly improved, whereas we did not notice any additional improvement after 10 or 20 cases (LA dwell time: 27[22-32] min during the first 5 cases vs 23[19-27] min after the first 5 cases, p=0.0172; support time: 100[65-120] min vs 75[65-90] min, p=0.0181, respectively). In 13 (6.3%) cases a transient bradycardia or asystole occurred after the first PFA application requiring temporary high-output pacing. No major procedure-related adverse events were reported. Conclusion In this first multicentric experience, the novel PFA system proved to be safe and effective in both paroxysmal and persistent AF patients. The learning curve seems to be very fast according with procedural parameters.

Electrophysiological findings during re-do procedures after single-shot pulmonary vein isolation for atrial fibrillation with pulsed field ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulsed field ablation (PFA) is a novel non-thermal ablation modality which applies electroporation to destabilize the cell membranes, leading to selective ablation of the atrial myocardium whilst sparing surrounding tissues and structures. It’s discriminating nature and potential for minimal adnexal injury opens new, promising horizons into catheter ablation of AF. However, one of the major issues to address is long-term results of the technique. Purpose To investigate the electrophysiological findings and type of arrhythmias during redo-ablation in 15 patients who underwent pulmonary vein isolation (PVI) for atrial fibrillation (AF) using single-shot PFA. Methods We investigated patients who underwent redo-ablation due to occurrence of AF/ atrial flutter (AFL) or tachycardia (AT) following initial PVI with PFA. We report the electrophysiological findings and ablation strategy during redo-ablation. Results Out of 447 patients undergoing index PVI with PFA, 15 patients (age: 61.8±10.4 years; 8 (53%) males; left atrial volume index (n=10): 39.4±14.6 mL/m2) were referred for redo-ablation after index PFA. Indication for the index ablation was paroxysmal-AF in 8 patients, persistent-AF in 6 and long-standing-persistent-AF in one patient. Mean time-to-recurrence was 5.0±1.8months. Three patients received additional posterior-wall-isolation during index PFA. Thirteen (85%) patients suffered AF recurrence and 5/13 had concomitant AFL. In the remaining 2 patients, one had a recurrence of (box-dependent) AFL, and one had AT. No patients had all PVs reconnected. Reconnection in zero, one, two or three PVs was found in 33%, 20%, 20%, and 27% of patients, respectively. All 7 patients with zero or one reconnection with AF recurrence received additional/repeat posterior-wall-isolation during re-ablation, while in the others PVs were re-isolated. In 1/3 patients who had posterior-wall ablation during index PFA, durable isolation of the posterior wall was confirmed during re-do procedure. Patients with only AFL/AT had no reconnection of PVs, and the substrate was successfully ablated. Conclusion We observed durable PVI in 62% of the PVs in patients with AF/AFL recurrence after PFA PVI. In one-third of patients all PVs were isolated. The predominant recurrent arrhythmia following PVI-only was AF. Concomitant (33%) or isolated (14%) AFL/AT recurrence was observed in 47% of patients.

General anesthesia in spontaneous respiration with intravenous ketamine in patients undergoing pulsed-field ablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Thermal ablation of atrial fibrillation (AF) by means of radiofrequency or cryo-balloon is usually performed under general anesthesia, deep sedation, or conscious sedation at operator’s discretion and based on the general condition of the patient. However, a standardized sedation protocol when performing a non-thermal ablation, such as pulsed-field ablation (PFA) through irreversible cellular electroporation, has not been well established. Purpose We report our preliminary experience of a general anesthesia in spontaneous respiration protocol with ketamine used at a high-volume center during ablation of AF with a new PFA system. Methods All consecutive patients (pts) undergoing AF ablation with PFA at our center were included. Our sedation protocol consists of intravenous administration of midazolam (1+1 mg), fentanyl (25+25+25+25 mcg/kg) at low doses before local anesthesia with lidocaine (200mg) administration. Patients underwent sedation under spontaneous respiration by administering oxygen (4-6 l/min) through a face mask with nasal cannula. Local anesthesia was performed before the percutaneous femoral venous access. Soon after the trans-septal puncture, heparin (1 mg/kg) and atropine (1 mg, to mitigate anticipated bradycardia) were injected, followed by a second bolus of midazolam (1 mg). Ketamine adjunct (1 mg/kg) was then injected about 5 minutes before the first PFA delivery which was titrated to effect based on patient’s condition, response and changes in vital signs (total ketamine adjunction of 2 mg/kg). For quantitative assessment the Numeric Rating Scale for Pain (NRS) was applied. For qualitative assessment a 3-levels satisfaction evaluation was retrieved. The ablation endpoint was PVI as assessed by entrance and exit block. Results Forty-two pts were included in this analysis (mean age of 66±9 years,72% were male, CHA2DS2VASc score=2 [IQR 1–3], median body mass index 24[20-48]kg/m2, 35% had respiratory diseases – e.g. asthma, OSAS, COPD –). At baseline, before sedation, mean systolic blood pressure was 140.5+20.1mmHg and mean oxygen saturation was 97.9+2.1%. PVI was achieved in all the patients. The number of PFA applications to reach PVI was 33.4+3 (time to PVI = 25+4min). In two cases additional PFA lesion sets were deployed outside the PVs. Lab occupancy time was 122±32min, skin-to-skin time was 78±35min and fluoroscopy time was 23±14min. All the patients achieved a NRS ≤ 3. Satisfaction level was found to be acceptable in all procedures by both the patient and the primary operator (Score equal to 0). No major procedure-related adverse events were reported. Conclusion The PFA procedure has a short execution time. The standardized anesthetic protocol with the administration of drugs with rapid onset and pharmacological offset at low doses was effective and safe with an optimal degree of patient and operator satisfaction.

Cyanoacrylate adhesive closure in the European and American 2022 clinical practice guidelines

Over the last decade non-thermal non-tumescent (NTNT) methods of truncal reflux elimination in chronic venous disease (CVD) are becoming increasingly popular. The main NTNT modalities are mechanochemical ablation and cyanoacrylate adhesive closure (CAC). The advantages of non-thermal ablation are avoidance of tumescent anesthesia, low periprocedural pain and bruising, high patient comfort and satisfaction rates. CAC method has an additional benefit of avoiding the postprocedural compression. CAC is one of promising non-thermal ablation procedures, that leads to truncal vein occlusion and reflux elimination via endovenous delivery of n-butyl-2-cyanoacrylate. This review is aimed at assessment of the updated European and American clinical practice guidelines on CVD management, particularly the role of CAC. Current evidence shows high efficacy and safety of the CAC, its advantages regarding the periprocedural pain and ecchymoses, risk of adverse events, closure rates in the long-term, procedure and recovery time and patients’ quality of life. Therefore, along the current gold standard of varicose vein treatment – thermal ablation, the updated 2022 European and American clinical practice guidelines have significantly emphasized the role of NTNT modalities in general and CAC in particular. Specifically, the European Society for Vascular Surgeons guidelines recommend CAC for patients with great saphenous vein (GSV) incompetence when the NTNT technique is preferred. American guidelines recommend both thermal and non-thermal ablation for the patients with symptomatic axial reflux of the GSV, depending on the available expertise of the treating physician and the preference of the patient.

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

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. 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. 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. 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.

LB-456091-3 EUROPEAN REAL WORLD OUTCOMES WITH PULSED FIELD ABLATION IN PATIENTS WITH SYMPTOMATIC ATRIAL FIBRILLATION - LESSONS FROM THE MULTICENTER EU-PORIA REGISTRY

Pulsed field ablation (PFA) is a new non-thermal ablation energy modality for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). The multi-center EU-PORIA (EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation) registry sought to determine the safety, efficacy, and learning curve characteristics for a novel pentaspline multielectrode catheter.

Role of genomics in intrahepatic cholangiocarcinoma for liver-directed therapy

Only a minority of patients with intrahepatic cholangiocarcinoma are candidates for curative resection. Even those with disease limited to the liver may not be surgical candidates due to patient, liver, and tumor factors, including comorbidities, intrinsic liver disease, inability to establish a future liver remnant, and tumor multifocality. In addition, even after surgery, recurrence rates are high, with the liver being a predominant site of relapse. Lastly, tumor progression in the liver can sometimes result in demise for those with advanced disease. Therefore, it is not surprising that non-surgical, liver-directed therapies have emerged as both primary and complementary treatments for intrahepatic cholangiocarcinoma for multiple stages. Liver-directed therapies can be performed directly into the tumor via thermal or non-thermal ablation, catheter-based infusion into the hepatic artery containing either cytotoxic chemotherapy or radioisotope bearing spheres/beads, or delivered via external beam radiation. Presently, these therapies' selection criteria have been based on tumor size, location, liver function, and referral to particular specialists. In recent years, molecular profiling of intrahepatic cholangiocarcinoma has revealed a high rate of actionable mutations, and several targeted therapies have been approved for treatment in the second-line metastatic setting. However, little is known about these alterations' role in localized disease treatments. Therefore, we will review the current molecular landscape of intrahepatic cholangiocarcinoma and how it has been applied to liver-directed therapy.

Pilot ex vivo study on non-thermal ablation of human prostate adenocarcinoma tissue using boiling histotripsy

Focused ultrasound technologies are of growing interest for noninvasive ablation of localized prostate cancer (PCa). Here we present the results of the first case study evaluating the feasibility of non-thermal mechanical ablation of human prostate adenocarcinoma tissue using the boiling histotripsy (BH) method on ex vivo tissue. High intensity focused ultrasound field was generated using a 1.5-MHz custom-made transducer with nominal F#=0.75. A sonication protocol of 734 W acoustic power, 10-ms long BH-pulses, 30 pulses per focal spot, 1 % duty cycle, and 1 mm distance between single foci was tested in an ex vivo human prostate tissue sample containing PCa. The protocol used here has been successfully applied in the previous BH studies for mechanical disintegration of ex vivo prostatic human tissue with benign hyperplasia. BH treatment was monitored using B-mode ultrasound. Post-treatment histologic analysis demonstrated BH produced liquefaction of the targeted tissue volume. BH treated benign prostate parenchyma and PCa had similar tissue fractionation into subcellular fragments. The results of the study demonstrated that PCa tumor tissue can be mechanically ablated using the BH method. Further studies will aim on optimizing protocol parameters to accelerate treatment while maintaining complete destruction of the targeted tissue volume into subcellular debris.

MP-453081-11 PULSED FIELD ABLATION OF ATRIAL FIBRILLATION: SAFE TECHNOLOGY WITHOUT COLLATERAL DAMAGE TO THE ESOPHAGUS? FINDINGS OF POST-PROCEDURAL ENDOSCOPY

Severe injuries of the esophagus causing major complications after catheter ablation (CA) of atrial fibrillation are rare. However, endoscopically detected esophageal lesions (EDEL) have been described in up to 30% after radiofrequency current energy ablation. The novel non-thermal ablation technology pulsed field ablation (PFA) allows for unique ablation of the myocardium, sparing adjacent tissues, including the esophagus. Due to the proximity of the esophagus to the left atrial posterior wall (LAPW), this study sought to investigate the safety profile of PFA after left atrial posterior wall isolation (LAWPI) in patients undergoing catheter ablation of AF. Consecutive patients underwent PFA-guided catheter ablation for AF/atrial tachycardia including LAPWI. No esophagus probe was used due to the non-thermal energy form of PFA. To rule out esophageal lesions, all patients underwent post-procedural esophageal endoscopy, possibly, the next day. In total, 44 patients were included in the study. Patients’ mean age was 68 ± 13 years, 32 of 44 patients were male (72.7%) with a median CHA2DS2-VASc Score of 2 (q1-q3:1.5-4). Of all 44 PFA procedures, 13 (29.5%) were first ablation procedures for persistent AF and 31 (70.5%) were re-ablation procedures, including AF and AT. All patients underwent PFA-guided CA with a procedure duration of 113 ± 35.2 mins and a fluoroscopy time of 14.0 ± 5.7 mins. Pulmonary vein isolation (PVI) and/or Re-PVI was performed in 32 (72.3%) of patients. Successful LAPWI with PFA was performed in all patients (100%) including one (1/44, 2.3%)% early reconnection during remapping that required additional PFA. Additional PFA (including roof line, anterior line and mitral isthmus ablation) was performed in 22/44 patients (50%). Post-procedural endoscopy was performed at a median of one day after the procedure (q1-3: 1-2 days). No ablation-associated esophageal lesion was found (0%). There was no tamponade, and only one minor groin complication (2.3%, AV fistula not requiring intervention). After pulsed field ablation, no EDEL were detected on post-procedural esophageal endoscopy. Therefore, AF ablation including left posterior wall isolation performed by pulsed field ablation seems to be safe regarding any collateral damage to the esophagus.

Characterization of Experimentally Observed Complex Interplay between Pulse Duration, Electrical Field Strength, and Cell Orientation on Electroporation Outcome Using a Time-Dependent Nonlinear Numerical Model.

Electroporation is a biophysical phenomenon involving an increase in cell membrane permeability to molecules after a high-pulsed electric field is applied to the tissue. Currently, electroporation is being developed for non-thermal ablation of cardiac tissue to treat arrhythmias. Cardiomyocytes have been shown to be more affected by electroporation when oriented with their long axis parallel to the applied electric field. However, recent studies demonstrate that the preferentially affected orientation depends on the pulse parameters. To gain better insight into the influence of cell orientation on electroporation with different pulse parameters, we developed a time-dependent nonlinear numerical model where we calculated the induced transmembrane voltage and pores creation in the membrane due to electroporation. The numerical results show that the onset of electroporation is observed at lower electric field strengths for cells oriented parallel to the electric field for pulse durations ≥10 µs, and cells oriented perpendicular for pulse durations ~100 ns. For pulses of ~1 µs duration, electroporation is not very sensitive to cell orientation. Interestingly, as the electric field strength increases beyond the onset of electroporation, perpendicular cells become more affected irrespective of pulse duration. The results obtained using the developed time-dependent nonlinear model are corroborated by in vitro experimental measurements. Our study will contribute to the process of further development and optimization of pulsed-field ablation and gene therapy in cardiac treatments.