Non-thermal Ablation Research Articles

Advances in Tumor Management: Harnessing the Potential of Histotripsy.

Tissue ablation techniques have long been used in clinical settings to treat various oncologic diseases. However, many of these techniques are invasive and can cause substantial adverse effects. Histotripsy is a noninvasive, nonionizing, nonthermal tissue ablation technique that has the potential to replace surgical interventions in various clinical settings. Histotripsy works by delivering high-intensity focused ultrasound waves to target tissue. These waves create cavitation bubbles within tissues that rapidly expand and collapse, thereby mechanically fractionating the tissue into acellular debris that is subsequently absorbed by the body's immune system. Preclinical and clinical studies have demonstrated the efficacy of histotripsy in treating a range of diseases, including liver, pancreatic, renal, and prostate tumors. Safety outcomes of histotripsy have been generally favorable, with minimal adverse effects reported. However, further studies are needed to optimize the technique and understand its long-term effects. This review aims to discuss the importance of histotripsy as a noninvasive tissue ablation technique, the preclinical and clinical literature on histotripsy and its safety, and the potential applications of histotripsy in clinical practice. Keywords: Tumor Microenvironment, Ultrasound-High-Intensity Focused (HIFU), Ablation Techniques, Abdomen/GI, Genital/Reproductive, Nonthermal Tissue Ablation, Histotripsy, Clinical Trials, Preclinical Applications, Focused Ultrasound © RSNA, 2024.

Effects of bipolar irreversible electroporation with different pulse durations in a prostate cancer mouse model.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300μs) were significantly increased compared to the short pulse duration-treated groups (100μs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

Irreversible electroporation promotes a pro-inflammatory tumor microenvironment and anti-tumor immunity in a mouse pancreatic cancer model.

Pancreatic cancer is a significant cause of cancer-related mortality and often presents with limited treatment options. Pancreatic tumors are also notorious for their immunosuppressive microenvironment. Irreversible electroporation (IRE) is a non-thermal tumor ablation modality that employs high-voltage microsecond pulses to transiently permeabilize cell membranes, ultimately inducing cell death. However, the understanding of IRE's impact beyond the initiation of focal cell death in tumor tissue remains limited. In this study, we demonstrate that IRE triggers a unique mix of cell death pathways and orchestrates a shift in the local tumor microenvironment driven, in part, by reducing the myeloid-derived suppressor cell (MDSC) and regulatory T cell populations and increasing cytotoxic T lymphocytes and neutrophils. We further show that IRE drives induce cell cycle arrest at the G0/G1 phase in vitro and promote inflammatory cell death pathways consistent with pyroptosis and programmed necrosis in vivo. IRE-treated mice exhibited a substantial extension in progression-free survival. However, within a span of 14 days, the tumor immune cell populations reverted to their pre-treatment composition, which resulted in an attenuation of the systemic immune response targeting contralateral tumors and ultimately resulting in tumor regrowth. Mechanistically, we show that IRE augments IFN-γ signaling, resulting in the up-regulation of the PD-L1 checkpoint in pancreatic cancer cells. Together, these findings shed light on potential mechanisms of tumor regrowth following IRE treatment and offer insights into co-therapeutic targets to improve treatment strategies.

The Induction of Combined Hyperthermal Ablation Effect of Irreversible Electroporation with Polydopamine Nanoparticle-Coated Electrodes.

Irreversible electroporation (IRE) is a prominent non-thermal ablation method widely employed in clinical settings for the focal ablation therapy of solid tumors. Utilizing high-voltage, short-duration electric pulses, IRE induces perforation defects in the cell membrane, leading to apoptotic cell death. Despite the promise of irreversible electroporation (IRE) in clinical applications, it faces challenges concerning the coverage of target tissues for ablation, particularly when compared to other thermal ablation therapies such as radiofrequency ablation, microwave ablation, and cryoablation. This study aims to investigate the induced hyperthermal effect of IRE by applying a polydopamine nanoparticle (Dopa NP) coating on the electrode. We hypothesize that the induced hyperthermal effect enhances the therapeutic efficacy of IRE for cancer ablation. First, we observed the hyperthermal effect of IRE using Dopa NP-coated electrodes in hydrogel phantom models and then moved to in vivo models. In particular, in in vivo animal studies, the IRE treatment of rabbit hepatic lobes with Dopa NP-coated electrodes exhibited a two-fold higher increase in temperature (ΔT) compared to non-coated electrodes. Through a comprehensive analysis, we found that IRE treatment with Dopa NP-coated electrodes displayed the typical histological signatures of hyperthermal ablation, including the disruption of the hepatic cord and lobular structure, as well as the infiltration of erythrocytes. These findings unequivocally highlight the combined efficacy of IRE with Dopa NPs for electroporation and the hyperthermal ablation of target cancer tissues.

Abstract 6640: Zap! Irreversible electroporation in pancreatic cancer cells induces proinflammatory cell death and improves progression free survival

Abstract Pancreatic cancer is the third leading cause of cancer-related death due to its late diagnosis, few treatment options, and extremely low survival rates due to its immunosuppressive microenvironment. Irreversible electroporation (IRE),is a tumor non-thermal ablation technique that applies high-voltage electrical pulses to permeabilize the cell membrane that is irreversible and leads to necrotic cell death. IRE has had strong success in clinical trials nevertheless, little is known about the effect of IRE beyond the initiation of cell death in the tumor tissue. We hypothesize that IRE can not only induce cell death by membrane disruption to facilitate a proinflammatory microenvironment but also causes death via cell cycle arrest. We utilized in-vitro, and immunocompetent in-vivo murine models to investigate changes to pancreatic cancer and the tumor microenvironment. Our findings show that treating the cells with an increasing voltage of IRE induces more cell death. We observed cell cycle arrest in the G1 phase which may have been caused by DNA damage. There was upregulation of DNA damage repair machinery in the treated samples. Our histopathology data suggests increased necrosis on the tumor treated with IRE, as also PCR array analysis showed more proinflammatory cell death caused by pyroptosis. Finally, we demonstrated a reduction in the tumor size and a better survival rate aftertreatment. Our data suggest that Irreversible electroporation has a promising future in inducing proinflammatory type of cell death in the tumor and benefits increased patient survival. More investigation is needed to define ideal parameters for the electrical pulses and device development for tumor ablation in larger animals like porcine models. Citation Format: Manali Powar, Khan Mohammad Imran, Irving C. Allen, Rafael V. Davalos, Zaid Salamah, Kenneth Aycock, Rebecca M. Brock, Sheryl Coutermarsh-Ott, Katie Orr. Zap! Irreversible electroporation in pancreatic cancer cells induces proinflammatory cell death and improves progression free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6640.

Venous ablation procedures by provider type, including advanced practice providers

ObjectiveThe necessary training and certification of providers performing venous ablation has become a topic of debate in recent years. As venous interventions have shifted away from the hospital, the diversity of provider backgrounds has increased. We aimed to characterize superficial venous ablation practice patterns associated with different provider types. MethodsWe analyzed Medicare Fee-For-Service data from 2010 through 2018. Procedures were identified by their Current Procedural Terminology code and included radiofrequency ablation, endovenous laser ablation, chemical adhesive ablation (ie, VenaSeal; Medtronic, Inc), and mechanochemical ablation. These procedures were correlated with the practitioner type to identify provider-specific trends. ResultsBetween 2010 and 2018, the number of ablation procedures increased by 107% from 114,197 to 236,558 per year (P < .001). Most procedures were performed by surgeons without vascular board certification (28.7%; 95% confidence interval [CI], 28.7%-28.8%), followed by vascular surgeons (27.1%; 95% CI, 27.0%-27.2%). Traditionally noninterventional specialties, which exclude surgeons, cardiologists, and interventional radiologists, accounted for 14.1% (95% CI, 14.1%-14.2%), and APPs accounted for 3.5% (95% CI, 3.4%-3.5%) of all ablation procedures during the study period. The total number of ablations increased by 9.7% annually (95% CI, 9.7%-9.8%), whereas procedures performed by APPs increased by 62.0% annually (95% CI, 61.6%-62.4%). There were significant differences between specialties in the use of nonthermal ablation modalities: APPs had the highest affinity for nonthermal ablation (odds ratio [OR], 2.60; 95% CI, 2.51-2.69). Cardiologists were also more likely to use nonthermal ablation (OR, 1.62; 95% CI, 1.59-1.66). Similarly, the uptake of new nonthermal technology (ie, chemical adhesives) was greatest among APPs (OR, 3.57; 95% CI, 3.43-3.70) and cardiologists (OR, 1.86; 95% CI, 1.81-1.91). Vascular surgeons were less likely to use nonthermal modalities (OR, 0.95; 95% CI, 0.92-0.97), including new nonthermal technology in the first year of availability (OR, 0.93; 95% CI, 0.90-0.95). ConclusionsThe use of venous procedures has increased rapidly during the past decade, particularly as endovenous ablations have been performed by a wider practitioner base, including APPs and noninterventionalists. Practice patterns differ by provider type, with APPs and cardiologists skewing more toward nonthermal modalities, including more rapid uptake of new nonthermal technology. Provider-specific biases for specific ablation modalities might reflect differences in training, skill set, the need for capital equipment, clinical privileges, or reimbursement. These data could help to inform training paradigms, the allocation of resources, and evaluation of appropriateness in a real-world setting.

Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation.

Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA. hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterizations were performed to study PFA mechanisms and electrophysiological outcomes. PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minutes post-PFA. Irreversibly electroporated regions persisted at 24-hours post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca2+ levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of conduction block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets. Cardiac electroporation may be studied using hiPSC-derived cardiac tissue, providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties.

Pulsed field versus cryoballoon ablation for atrial fibrillation: areal-world observational study on procedural outcomes and efficacy.

Atrial fibrillation often necessitates catheter ablation when antiarrhythmic drug therapy fails. Single-shot technologies using thermal energy, such as cryoballoon ablation, are commonly used, but pulsed field ablation (PFA), an innovative non-thermal ablation technique, is apotential alternative. This retrospective observational study aimed to compare the safety and efficacy of cryoballoon ablation and PFA in patients undergoing their first pulmonary vein isolation (PVI) procedure for atrial fibrillation treatment. We utilised real-world data from patients who underwent PVI using cryoballoon ablation or PFA. The primary outcome encompassed procedural complications, including phrenic nerve palsy, cardiac tamponade, thromboembolic complications, bleeding complications and mortality. Secondary outcomes were procedural characteristics including procedure duration, length of hospital admission, and re-do ablation rates within 6months. Atotal of 1714 procedures were analysed: 1241 in the cryoballoon group and 473 in the PFA group. Gender distribution (p = 0.03) and estimated glomerular filtration rate (p = 0.01) differed significantly. With regard to the primary outcome, the cryoballoon group demonstrated ahigher incidence of phrenic nerve palsy compared with the PFA group (15 vs0; p = 0.02). The procedure duration was shorter in the PFA group, even after adjusting for baseline characteristics (95.0 vs 74.0 min; p < 0.001). After adjustment for baseline characteristics, admission duration differed between the groups as well (p = 0.04). The study results supported the safety and efficacy of PFA over cryoballoon ablation for PVI, highlighting advantages such as shorter procedure duration and absence of phrenic nerve palsy.

Pulsed field ablation and cryoballoon ablation for pulmonary vein isolation: insights on efficacy, safety and cardiac function.

Pulmonary vein isolation (PVI) has become the cornerstone treatment of atrial fibrillation (AF). While in cryoablation cell damage is caused by thermal effects, lately, pulsed field ablation (PFA) has been established as a novel non-thermal tissue-specific ablation modality for PVI. However, data comparing outcomes of patients undergoing either PFA or cryoballoon ablation (CBA) for primary PVI are sparse. Consecutive patients with AF undergoing PVI by either CBA or PFA were included in the analysis. The primary outcome was the time to AF/AT recurrence. For secondary outcomes, clinical and periprocedural parameters were compared. In total, outcomes of 141 AF patients treated by PFA (94 patients) or CBA (47 patients) were compared. After 365 days, 70% of patients in the PFA group and 61% of patients in the CBA group were free from AF/AT (HR 1.35, 95% CI 0.60-3.00; p = 0.470). No deaths occurred. While symptoms alleviated in both groups, only after PFA, we observed significant improvement of left atrial volume index (PFA group baseline: 40 [31;62] ml/m2, PFA group follow-up: 35 [29;49] ml/m2; p = 0.015), NT-pro BNP levels (PFA group baseline: 1106 ± 2479 pg/ml, PFA group follow-up: 1033 ± 1742 pg/ml; p = 0.048), and left ventricular ejection fraction (LVEF) (PFA group baseline: 55 [48;60] %, PFA group follow-up: 58 [54;63] %; p = 0.006). PVI by PFA was the only independent predictor of LVEF improvement. In our study, we show that CBA and PFA for PVI are of similar efficacy when it comes to AF recurrence. However, our findings suggest that PFA rather than CBA might induce left atrial reverse remodeling thereby contributing to left ventricular systolic function.

Factors associated with ablation-related thrombus extension following microfoam versus radiofrequency saphenous vein closure

ObjectivePolidocanol endovenous microfoam ablation (MFA) is approved by the US Food and Drug Administration for great saphenous vein (GSV) closure, yet there are few published data on the subsequent risk of ablation-related thrombus extension (ARTE). Recent societal practice guidelines recommend against routine postprocedure duplex ultrasound (DU) examination after thermal ablation of the GSV in asymptomatic patients. At present, limited data do not allow this recommendation to extend to MFA. Our aim is to identify characteristics and outcomes associated with ARTE following MFA vs radiofrequency ablation (RFA). MethodsA retrospective review of a prospectively maintained database was conducted of patients who underwent MFA and RFA closure of incompetent above-knee GSVs. Patients treated for isolated tributary vein treatment or did not have a postprocedure DU examination within 48 to 72 hours were not included. Patients were classified into two groups: ARTE and no ARTE. Demographic data, Clinical, Etiologic, Anatomic and Pathophysiologic class, Venous Clinical Severity Score, operative details, postprocedure (48-72 hours) DU findings, and adverse events were analyzed. Variables that were significant on univariate analysis were evaluated using multivariate logistic regression with the primary outcome being development of ARTE. ResultsBetween June 2018 and February 2023, 800 limbs were treated with either MFA (n = 224) or RFA (n = 576). Ninety-six GSVs treated with MFA met the study criteria. One hundred fifty successive GSVs treated with RFA during the same period were included as a comparison group. There was no statistically significant difference in baseline demographics between the two groups. Six patients (2.4%) demonstrated ARTE on postoperative DU examination at 48 to 72 hours (MFA, n = 5 [5.2%]; RFA, n = 1 [0.7%]; P = .02). Saphenous vein ablation with MFA (P = .045) and a vein diameter of >10 mm (P = .017) were associated with ARTE on both univariable and multivariable analysis. All patients who developed ARTE were treated with oral anticoagulants (mean, 15.6 days). Body mass index, Clinical, Etiologic, Anatomic and Pathophysiologic class, Venous Clinical Severity Score, microfoam volume, operative time, and prior deep venous thrombosis were not predictive of ARTE. ConclusionsARTE after above-knee GSV closure occurred more frequently after MFA. Our results suggest that a saphenous vein diameter of >10 mm may be associated with ARTE. Despite this finding, all patients with ARTE were treated with short-term anticoagulation with no related complications. Until larger studies with high-risk subgroups have been studied after MFA, DU examination should be performed routinely after this procedure and patients with ARTE anticoagulated until the thrombus retracts caudal to the saphenofemoral junction or is no longer present on DU examination. Current societal guidelines recommending against routine post-thermal ablation DU examination should not be applied to similar patients after saphenous nonthermal MFA ablation.

A Systematic Review and Meta-Analysis of Randomised Controlled Trials Comparing Thermal Versus Non-Thermal Endovenous Ablation in Superficial Venous Incompetence

A Systematic Review and Meta-Analysis of Randomised Controlled Trials Comparing Thermal Versus Non-Thermal Endovenous Ablation in Superficial Venous Incompetence

The Effects of Interphase and Interpulse Delays and Pulse Widths on Induced Muscle Contractions, Pain and Therapeutic Efficacy in Electroporation-Based Therapies.

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation's efficacy. We investigated the effect of varying pulse parameters such as interphase and interpulse delay while keeping the duration and number of pulses constant on nerve stimulation, muscle contraction and assessing pain and electroporation efficacy, conducting experiments on human volunteers, tissue samples and cell lines in vitro. Our results show that using specific pulse parameters, particularly short high-frequency biphasic pulses with short interphase and long interpulse delays, reduces muscle contractions and pain sensations in healthy individuals. Higher stimulation thresholds were also observed in experiments on isolated swine phrenic nerves and human esophagus tissues. However, changes in the interphase and interpulse delays did not affect the cell permeability and survival, suggesting that modifying the pulse parameters could minimize adverse effects while preserving therapeutic goals in electroporation.

Non-Thermal Liver Ablation: Existing and New Technology.

Cancer has and continues to be a complex health crisis plaguing millions around the world. Alcohol ablation was one of the initial methods used for the treatment of liver lesions. It was surpassed by thermal ablation which has played a big role in the therapeutic arsenal for primary and metastatic liver tumors. However, thermal ablation has several shortcomings and limitations that prompted the development of alternative technologies including electroporation and histotripsy. Percutaneous alcohol injection in the liver lesion leads to dehydration and coagulative necrosis. This technology is limited to the lesion with relative sparing of the surrounding tissue, making it safe to use adjacent to sensitive structures. Electroporation utilizes short high-voltage pulses to permeabilize the cell membrane and can result in cell death dependent on the threshold reached. It can effectively target the tumor margins and has lower damage rates to surrounding structures due to the short pulse duration. Histotripsy is a novel technology, and although the first human trial was just completed, its results are encouraging, given the sharp demarcation of the targeted tissue, lack of thermal damage, and potential for immunomodulation of the tumor microenvironment. Herein, we discuss these techniques, their uses, and overall clinical benefit.

Esophageal injury, perforation, and fistula formation following atrial fibrillation ablation.

Esophageal perforation and fistula formation are rare but serious complications following atrial fibrillation ablation. In this review article, we outline the incidence, pathophysiology, predictors, and preventative strategies of this dreaded complication. We conducted an electronic search in 10 databases/electronic search engines to access relevant publications. All articles reporting complications following atrial fibrillation ablation, including esophageal injury and fistula formation, were included for systematic review. A total of 130 manuscripts were identified for the final review process. The overall incidence of esophageal injury following atrial fibrillation ablation was significantly higher with thermal ablation modalities (radiofrequency 5-40%, cryoballoon 3-25%, high-intensity focused ultrasound < 10%) as opposed to non-thermal ablation modalities (no cases reported to date). The incidence of esophageal perforation and fistula formation with the use of thermal ablation modalities is estimated to occur in less than 0.25% of all atrial fibrillation ablation procedures. The use of luminal esophageal temperature monitoring probe and mechanical esophageal deviation showed protective effect toward reducing the incidence of this complication. The prognosis is very poor for patients who develop atrioesophageal fistula, and the condition is rapidly fatal without surgical intervention. Esophageal perforation and fistula formation following atrial fibrillation ablation are rare complications with poor prognosis. Various strategies have been proposed to protect the esophagus and reduce the incidence of this fearful complication. Pulsed field ablation is a promising new ablation technology that may be the future answer toward reducing the incidence of esophageal complications.

Boiling Histotripsy Using Dual-Frequency Protocol on Murine Breast Tumor Model and Promotes Immune Activation.

Histotripsy is an ultrasound-guided, noninvasive, nonthermal ablation therapy that can mechanically lyse target tissues. There have been no reports of enhanced histotripsy for large-volume triple-negative breast cancer (TNBC). This study aims to verify the ability of a novel approach of dual-frequency mode combined with two-stage millisecond-length ultrasound pulses (DF-TS) to accelerate the treatment of murine subcutaneous 4T1 tumors and determine immune changes after treatment. A custom-designed 1.1-/2.2-MHz two-element confocal-annular array was used to treat approximately 6-mm tumors under ultrasound guidance and real-time monitoring. Two-stage millisecond-length ultrasound pulses were used to generate approximate cuboid ablation volumes (diagonal 5-6 mm) within each tumor, with a dose of 100 pulses/point. Immune effects were characterized by changes of pro-inflammatory cytokine levels and infiltration levels of immune cells. In all targeted treatment areas, bubble cloud activity was visualized by ultrasound monitoring. The novel protocol resulted in elliptical and controllable sized lesions, reducing the number of scanning points, and was generally well tolerated. After treatment, tumor growth experienced a seven-day stagnation period, the survival period of mice was prolonged, and the levels of pro-inflammatory cytokines and immune cell infiltration increased. This study demonstrates that DF-TS boiling histotripsy (BH) has a noninvasive, efficient, and precise ablation ability for TNBC and potentially enhances immune responses.

Liver-tumor mimics as a potential translational framework for planning and testing irreversible electroporation with multiple electrodes.

Irreversible electroporation (IRE) has emerged as an appealing non-ionizing, non-thermal ablation therapy, independent of antineoplastic drugs. Limited but successful outcomes in IRE conducted in vivo, in small focal hepatocellular carcinomas (HCC), have been reported. Nonetheless, the electric parameters of IRE are usually delivered in an unplanned manner. This work investigates the integration of computational modeling to hydrogels mimicking the HCC microenvironment, as a powerful framework to: circumvent ethical concerns of in vivo experimentation; safely tune the electric parameters reaching the IRE electric field threshold; and propel the translation of IRE as a routine clinical alternative to the treatment of HCC. Therefore, a parametric study served to evaluate the effects of the pulse amplitude, the number of pulses and electrodes, the treatment time, the hydrogel-tumor size, and the cell type. The ablation extent was surveyed by confocal microscopy and magnetic resonance imaging (MRI) in cylindrical and realistic tumor-shaped hydrogels, respectively. A large ablation (70%-100%) was verified in all constructs.

Abstract 17813: Markers of Cellular Damage, Inflammatory Response, Coagulation and Platelet Activity, and Apoptosis During Catheter Ablation for Atrial Fibrillation Using Radiofrequency and Pulsed-Field Energy

Introduction: Pulsed-field ablation (PFA) presents a new technology for the ablation of AF using non-thermal ablation energy. Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation cascade activation. The study aimed to compare markers of cell damage and platelet and coagulation activation in patients undergoing PVI using PF and radiofrequency (RF) energy. Hypothesis: PFA will be associated will more pronounced myocardial damage, but less pronounced activation of platelets and inflammation. Methods: Patients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster, USA) or PF (Farapulse, Boston-Scientific, USA) energy. Markers of myocardial damage (high-sensitivity troponin I), apoptosis (Fas ligand, caspase-3), inflammation (interleukin-6), coagulation (D-dimers, Fibrin monomers, von Willebrand antigen and factor activity), platelet activation (P-selectin, activated Gp IIb/IIIa antigen and CD42b), and neuron axon damage (NGF-β) were measured before the procedure (T1), after transseptal puncture, (T2), after completing the ablation in the left atrium (T3), and one day after the procedure (T4). Results: Sixty-five patients were enrolled in the PFA (n=33) and RFA (n=32) groups. Both groups were similar in baseline characteristics (age 60.5±12.7 vs. 64.0±10.7 and 20 (60.6%) non-paroxysmal vs. 20 (62.5%) paroxysmal AF). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09±11:57 vs. 151:19±41:25 min, p&lt; 0.001; 36:00±8:05 vs. 115:58±36:49 min, p&lt;0.001). Troponin release (1 d after the procedure) was substantially higher in the PFA group (10,102, IQR 8,272-14,207 vs. 1,006, IQR 603-1,433) and was ten times higher in PFA patients. However, during the procedure, markers of platelet activation, coagulation activation, and inflammation were similar between groups. Conclusions: PF ablation was associated with substantially more myocardial damage compared to radiofrequency ablation. However, coagulation activation, platelet activation, and inflammatory responses were similar.

Myocardial Damage, Inflammation, Coagulation, and Platelet Activity During Catheter Ablation Using Radiofrequency and Pulsed-Field Energy

BackgroundPulsed-field ablation (PFA) represents a new, nonthermal ablation energy for the ablation of atrial fibrillation (AF). Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation activation. ObjectivesThis study aimed to compare the systemic response in patients undergoing pulmonary vein isolation (PVI) using pulsed-field and radiofrequency (RF) energy. MethodsPatients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster) or pulsed-field (Farapulse, Boston-Scientific) energy. Markers of myocardial damage (troponin I), inflammation (interleukin-6), coagulation (D-dimers, fibrin monomers, von Willebrand antigen and factor activity), and platelet activation (P-selectin, activated GpIIb/IIIa antigen) were measured before the procedure (T1), after trans-septal puncture (T2), after completing the ablation in the left atrium (T3), and 1 day after the procedure (T4). ResultsA total of 65 patients were enrolled in the pulsed-field ablation (n = 33) and RF ablation (n = 32) groups. Both groups were similar in baseline characteristics (age 60.5 ± 12.7 years vs 64.0 ± 10.7 years; paroxysmal AF: 60.6% vs 62.5% patients). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09 ± 11:57 min vs 151:19 ± 41:25 min; P < 0.001; 36:00 ± 8:05 min vs 115:58 ± 36:49 min; P < 0.001). Peak troponin release was substantially higher in the PFA group (10,102 ng/L [IQR: 8,272-14,207 ng/L] vs 1,006 ng/L [IQR: 603-1,433ng/L]). Both procedures were associated with similar extents (>50%) of platelet and coagulation activation. The proinflammatory response 24 h after the procedure was slightly but nonsignificantly higher in the RF group. ConclusionsDespite 10 times more myocardial damage, pulsed-field ablation was associated with a similar degree of platelet/coagulation activation, and slightly lower inflammatory response. (The Effect of Pulsed-Field and Radiofrequency Ablation on Platelet, Coagulation and Inflammation; NCT05603637)

Zero-fluoroscopy ablation with multielectrode pulse field ablation system: Case series.

Pulse field ablation (PFA) is a novel nonthermal ablation modality for treatment of atrial fibrillation. While mostly lacking 3D electroanatomical mapping integration, reported radiation doses in procedures using multielectrode PFA catheters are relatively high. We report a first case series of three patients where a zero-fluoroscopy approach by intracardiac echocardiography was utilized and present a possible workflow for zero-fluoroscopy ablation with the Farapulse PFA system.

Comparison of pulsed-field ablation versus very high power short duration-ablation for pulmonary vein isolation.

The newly introduced nonthermal pulsed field ablation (PFA) is a promising technology to achieve fast pulmonary vein isolation (PVI) with high acute success rates and good safety features. However, previous studies have shown that very high power short duration ablation (VHPSD) is also highly effective and fast to achieve PVI with potentially less arrhythmia recurrence compared to conventional radiofrequency ablation. Data comparing PFA to VHPSD-PVI is lacking. This study compared procedural and outcome data for PFA-PVI to VHPSD-PVI in patients with paroxysmal or persistent atrial fibrillation (PAF/persAF). Consecutive patients undergoing de novo PVI (PFA or VHPSD) were included in this analysis. For PFA-PVI a pentaspline 20 electrode catheter was used. For VHPSD-PVI an enhanced irrigated catheter with a power setting of 70 W/7 s (70 W/5 s at posterior wall) was employed in conjunction with electro-anatomical mapping. All procedures were performed in deep analgo-sedation. A total of n = 114 patients (n = 57[50%] PFA, n = 17[30%] PAF; n = 40[70%] persAF) 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 ± 5 min and VHPSD 12 ± 3 min; p < 0.001). At follow-up after median 125 days (interquartile range: 109-162) n = 46 PFA (80.7%) and n = 44 VHPSD pts (77.2%) were free from atrial arrhythmia after a single procedure (p = 0.819). Two tamponades occurred in the PFA while in VHPSD two pts suffered groin bleedings. One clinically nonsignificant PV stenosis occurred in the VHPSD group. Pulsed-field ablation and VHPSD-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. Compared to PFA VHPSD-PVI might ensure information on left atrial substrate allowing to target concomitant secondary tachycardias.