Pulsed field ablation (PFA) of atrial fibrillation is a new method in clinical practice. Despite a favorable safety profile of PFA in atrial fibrillation ablation, rare cases of renal failure, ...probably due to hemolysis, have recently been reported.
The aim of this study was to determine the rate of hemolysis and cardiac cell death during in vitro PFA with different electric field intensities.
Blood samples from healthy volunteers and mouse HL-1 cardiomyocyte cell lines were subjected to in vitro irreversible electroporation using 216 bipolar pulses, each lasting 2 μs with intervals of 5 μs, repeated 20 times at a frequency of 1 Hz. These pulses varied from 500 V to 1500 V. Cell-free hemoglobin levels were assessed spectrophotometrically, and red blood cell microparticles were evaluated by flow cytometry. Cardiomyocyte death was quantified with propidium iodide.
Pulsed field energy (1000 V/cm, 1250 V/cm, and 1500 V/cm) was associated with a significant increase in cell-free hemoglobin (0.32 ± 0.16 g/L, 2.2 ± 0.96 g/L, and 5.7 ± 0.39 g/L; P < .05) and similar increase in the concentration of red blood cell microparticles. Significant rates of cardiomyocyte death were observed at electric field strengths of 750 V/cm, 1000 V/cm, 1250 V/cm, and 1500 V/cm (26.5% ± 5.9%, 44.3% ± 6.2%, 55.5% ± 6.9%, and 74.5% ± 17.8% of cardiomyocytes; P < .05).
The most effective induction of cell death in vitro was observed at 1500 V/cm. This intensity was also associated with a significant degree of hemolysis.
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Introduction: Prostate, pancreatic and liver cancers are a major cause of death in Europe and including Bulgaria. Some methods for treatment include the use of electric current to create pores in the ...cells' membranes, and can be used in combination with other techniques, while an electric field with enough strength causes irreversible electroporation (IRE) and is a separate technique. Material and methods:Search was conducted for scientific articles about electroporation and IRE. Results: Most important parameters reported in scientific articles are electric field distribution, tissue characteristics and interaction, electric pulse settings. Articles that report patient outcomes suggest several possible advantages of – retaining urinary and sexual functions, possible increase of overall survival rate, low rate of serious adverse events and promising results when applied with chemotherapy. However, there are some studies that do not corroborate these results. The technique is also used for the treatment of renal cancer, and there are researches indicating a potential for use in ovarian, cervical and breast cancer. Conclusion: Studies suggest the IRE method is safe and feasible for the treatment of prostate cancer, pancreatic cancer and liver cancer, but improvements in the protocols is needed to prevent a decrease of quality of life.
Percutaneous treatment of hepatocellular carcinoma (HCC) encompasses a vast range of techniques, including monopolar radiofrequency ablation (RFA), multibipolar RFA, microwave ablation, cryoablation ...and irreversible electroporation. RFA is considered one of the main curative treatments for HCC of less than 5 cm developing on cirrhotic liver, together with surgical resection and liver transplantation. However, controversies exist concerning the respective roles of ablation and liver resection for HCC of less than 3 to 5 cm on cirrhotic liver. In line with the therapeutic algorithm of early HCC, percutaneous ablation could also be used as a bridge to liver transplantation or in a sequence of upfront percutaneous treatment, followed by transplantation if the patient relapses. Moreover, several innovations in ablation methods may help to efficiently treat early HCC, initially considered as “non-ablatable”, and might, in some cases, extend ablation criteria beyond early HCC, enabling treatment of more patients with a curative approach.
High-frequency irreversible electroporation (H-FIRE) has emerged as an alternative to conventional irreversible electroporation (IRE) to overcome the issues associated with neuromuscular electrical ...stimulation that appear in IRE treatments. In H-FIRE, the monopolar pulses typically used in IRE are replaced with bursts of short bipolar pulses. Currently, very little is known regarding how the use of a different waveform affects the cell death dynamics and mechanisms. In this study, human pancreatic adenocarcinoma cells were treated with a typical IRE protocol and various H-FIRE schemes with the same energized time. Cell viability, membrane integrity and Caspase 3/7 activity were assessed at different times after the treatment. In both treatments, we identified two different death dynamics (immediate and delayed) and we quantified the electric field ranges that lead to each of them. While in the typical IRE protocol, the electric field range leading to a delayed cell death is very narrow, this range is wider in H-FIRE and can be increased by reducing the pulse length. Membrane integrity in cells suffering a delayed cell death shows a similar time evolution in all treatments, however, Caspase 3/7 expression was only observed in cells treated with H-FIRE.
Background: Tumors at the hepatocaval confluence are difficult to treat, either surgically or ablatively. Methods: A retrospective longitudinal study on patients ineligible for thermal ablation who ...underwent computed tomography-guided IRE for hepatic tumors at the hepatocaval confluence was conducted. Factors analyzed included patient and tumor characteristics, IRE procedure details, treatment-related complications, and prognosis. Results: Between 2017 and 2021, 21 patients at our institute received percutaneous IRE. Of the 38 lesions, 21 were at the hepatocaval confluence. Complete ablation was achieved in all cases. Local and distant recurrence was observed in 4.8% (1/21) and 42.6% (9/21) of the ablated tumors, respectively. All postcava remained perfused at follow-up, except for 1 (4.8%) hepatic vein near the lesion found to be temporarily occluded and restored within 1 month. The ratio of the maximum diameter of ablation area at 1, 3, and 6 months post procedure compared to that immediately after IRE was 0.68 (0.50–0.84), 0.49 (0.27–0.61), and 0.38 (0.25–0.59), respectively. Progression-free survival of the patients with recurrence was 121 (range, 25–566) days. Four (19.0%) patients died at the end of follow-up with median overall survival of 451.5 (range, 25–716) days. Conclusions: IRE could be a safe and effective treatment for hepatic tumors at the hepatocaval confluence. This article provides valuable prognostic data; further clinical research is needed for better prognosis.
To validate the performance of a multipolar pulsed-field ablation (PFA) catheter compared to a standard pentaspline 3D-mapping catheter for endpoint assessment of pulmonary vein isolation (PVI). PFA ...for PVI using single-shot devices combines the benefits of high procedural efficacy and safety. A newly available multipolar PFA catheter allows real-time recording of pulmonary vein (PV) signals during PVI.
Patients undergoing first PVI using PFA with the standard ablation protocol (eight applications per PV) were studied. Entrance and exit block (10 V/2 ms) were assessed using the PFA catheter. Subsequently, a high-density 3D electroanatomical bipolar voltage map (3D-EAM) was constructed using a standard pentaspline 3D-mapping catheter. Additional PFA applications were delivered only after confirmation of residual PV connection by 3D-EAM. In 56 patients, 213 PVs were targeted for ablation. Acute PVI was achieved in 100% of PVs: in 199/213 (93%) PVs with the standard ablation protocol alone and in the remaining 14 PVs after additional PFA applications. The accuracy of PV assessment with the PFA catheter after the standard ablation protocol was 91% (194/213 veins). In 5/213 (2.3%) PVs, the PFA catheter incorrectly indicated PV-isolation. In 14/213 (6.6%), the PFA catheter incorrectly indicated residual PV-conduction due to high-output pace-capture. Lowering the output to 5 V/1 ms reduced this observation to 0.9% (2/213) and increased the overall accuracy to 97% (206/213).
A novel multipolar PFA catheter allows reliable endpoint assessment for PVI. Due to its design, far-field sensing and high-output pace-capture can occur. Lowering the pacing output increases the accuracy from 91 to 97%.
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%, CHA
DS
-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%;
=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.
Radiofrequency (RF) has become an accepted energy source for myocardial ablation but may result in discontinuous lesions and nontargeted tissue injury. We examined the feasibility and safety of ...lesion formation using high-amplitude, bipolar pulsed electric fields delivered from a multielectrode array catheter.
The purpose of this study was to compare duty-cycled radiofrequency ablation (RFA) to pulsed field ablation (PFA) in terms of acute electrical effects, 2-week lesion formation, and injury to nontargeted tissues.
Intracardiac ablations were performed in 6 pigs using a circular pulmonary vein ablation catheter. The energy source for ablation delivery was randomized to deliver either PFA or RFA to 3 atrial endocardial sites. Bipolar pace capture and electrogram amplitude measurements were recorded at each site. Histopathology and necropsies were performed after 2 weeks.
The circular pulmonary vein ablation catheter was used to deliver pulsed electric fields to produce cardiac lesions without skeletal muscle stimulation. Evaluating all ablations in each site, electrogram amplitudes were reduced to <0.5 mV in 67.5% of PFA vs 27.0% of RFA deliveries (P <.001). Bipolar cardiac capture was lost after 100% vs 92.0% of PFA vs RFA (P = .005). At 2 weeks, PFA resulted in consistent transmural and homogeneous replacement fibrosis devoid of lingering myocyte “sequesters.” RFA lesions showed a stronger inflammatory response extending to the epicardial fat, arterial injury, and thrombosis. Neither PFA nor RFA lesions showed endocardial thrombus.
Intracardiac PFA can be feasibly delivered from a circular catheter to create fibrotic lesions that have acute electrical effects, without injury to nontargeted tissue.
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Objective: The use of high-voltage, high-frequency bipolar pulses (HFBPs) is an emerging electroporation-based therapy for the treatment of solid tumors. In this study, we quantify the extent of ...nonlinearity and dispersion during the HFBP treatment. Methods: We utilize flat-plate electrodes to capture the impedance of the porcine liver tissue during the delivery of a burst of HFBPs of widths 1 and 2 μs at different pulse amplitudes. Next, we fit the impedance data to a frequency-dependent parallel RC network to determine the conductivity and permittivity of the tissue as a function of frequency, for different applied electric fields. Finally, we present a simple model to approximate the field distribution in the tissue using the conductivity function at a frequency that could minimize the errors due to approximation with a nondispersive model. Results: The conductivity/permittivity of the tissue was plotted as a function of frequency for different electric fields. It was found that the extent of dispersion reduces with higher applied electric field magnitudes. Conclusion: This is the first study to quantify dispersion and nonlinearity in the tissue during the HFBP treatment. The data have been used to predict the field distribution in a numerical model of the liver tissue utilizing two needle electrodes. Significance : The data and technique developed in this study to monitor the electrical properties of tissue during treatment can be used to generate treatment-planning models for future high-frequency electroporation therapies as well as provide insights regarding treatment effect.
Abstract Pulsed electric field (PEF) is a novel energy source by which high-voltage electric pulses are used to create irreversible electroporation. PEF is non-thermal and highly tissue-dependent in ...which specific targeting of the atrial myocardium is achieved and sparing of adjacent tissues is feasible, theoretically increasing the safety of the procedure, which could potentially break the trade-off between effective lesions and collateral damage and substantially improve risk-benefit ratios in atrial fibrillation (AF) ablation. Although recently published trials have shown a clear effect of AF ablation, large-scale clinical trials are lacking. Current clinical evidence has demonstrated significant efficacy in achieving durable pulmonary vein isolation without ablation-related adverse events. However, their putative benefits regarding efficacy, efficiency, and safety remain to be proven in randomized controlled trials.
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