Feasibility of Linear Irreversible Electroporation Ablation in the Coronary Sinus.

INTRODUCTION: Previous studies demonstrated that the coronary sinus (CS) is an important target for ablation in persistent atrial fibrillation. However, radiofrequency ablation in the CS is associated with coronary vessel damage and tamponade. Animal data suggest irreversible electroporation (IRE) ablation can be a safe ablation modality in vicinity of coronary arteries. We investigated the feasibility of IRE in the CS in a porcine model. METHODS: Ablation and pacing was performed in the CS in six pigs (weight 60-75 kg) using a modified 9-French steerable linear hexapolar Tip-Versatile Ablation Catheter. Pacing maneuvers were performed from distal to proximal segments of the CS to assess atrial capture thresholds before and after IRE application. IRE ablations were performed with 100 J IRE pulses. After 3-week survival animals were euthanized and histological sections from the CS were analyzed. RESULTS: A total of 27 IRE applications in six animals were performed. Mean peak voltage was 1509 ± 36 V, with a mean peak current of 22.9 ± 1.0 A. No complications occurred during procedure and 3-week survival. At 30 min post ablation 100% isolation was achieved in all animals. At 3 weeks follow-up pacing thresholds were significant higher as compared to baseline. Histological analysis showed transmural ablation lesions in muscular sleeves surrounding the CS. CONCLUSION: IRE ablation of the musculature along the CS using a multi-electrode catheter is feasible in a porcine model.

Multielectrode Contact Measurement Can Improve Long-Term Outcome of Pulmonary Vein Isolation Using Circular Single-Pulse Electroporation Ablation.

BACKGROUND: Irreversible electroporation (IRE) ablation is generally performed with multielectrode catheters. Electrode-tissue contact is an important predictor for the success of pulmonary vein (PV) isolation; however, contact force is difficult to measure with multielectrode ablation catheters. In a preclinical study, we assessed the feasibility of a multielectrode impedance system (MEIS) as a predictor of long-term success of PV isolation. In addition, we present the first-in-human clinical experience with MEIS. METHODS: In 10 pigs, one PV was ablated based on impedance (MEIS group), and the other PV was solely based on local electrogram information (EP group). IRE ablations were performed at 200 J. After 3 months, recurrence of conduction was assessed. Subsequently, in 30 patients undergoing PV isolation with IRE, MEIS was evaluated and MEIS contact values were compared to local electrograms. RESULTS: In the porcine study, 43 IRE applications were delivered in 19 PVs. Acutely, no reconnections were observed in either group. After 3 months, 0 versus 3 (P=0.21) PVs showed conduction recurrence in the MEIS and EP groups, respectively. Results from the clinical study showed a significant linear relation was found between mean MEIS value and bipolar dV/dt (r2=0.49, P<0.001), with a slope of 20.6 mV/s per Ohm. CONCLUSIONS: Data from the animal study suggest that MEIS values predict effective IRE applications. For the long-term success of electrical PV isolation with circular IRE applications, no significant difference in efficacy was found between ablation based on the measurement of electrode interface impedance and ablation using the classical EP approach for determining electrode-tissue contact. Experiences of the first clinical use of MEIS were promising and serve as an important basis for future research.

Safety and feasibility study of non-invasive robot-assisted high-intensity focused ultrasound therapy for the treatment of atherosclerotic plaques in the femoral artery: protocol for a pilot study.

INTRODUCTION: Peripheral arterial disease (PAD) is an atherosclerotic disease leading to stenosis and/or occlusion of the arterial circulation of the lower extremities. The currently available revascularisation methods have an acceptable initial success rate, but the long-term patency is limited, while surgical revascularisation is associated with a relatively high perioperative risk. This urges the need for development of less invasive and more effective treatment modalities. This protocol article describes a study investigating a new non-invasive technique that uses robot assisted high-intensity focused ultrasound (HIFU) to treat atherosclerosis in the femoral artery. METHODS AND ANALYSIS: A pilot study is currently performed in 15 symptomatic patients with PAD with a significant stenosis in the common femoral and/or proximal superficial femoral artery. All patients will be treated with the dual-mode ultrasound array system to deliver imaging-guided HIFU to the atherosclerotic plaque. Safety and feasibility are the primary objectives assessed by the technical feasibility of this therapy and the 30-day major complication rate as primary endpoints. Secondary endpoints are angiographic and clinical success and quality of life. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained in 2019 from the Medical Ethics Committee of the University Medical Center Utrecht, the Netherlands. Data will be presented at national and international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NL7564.

Efficacy of multi-electrode linear irreversible electroporation.

AIMS: We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model. METHODS AND RESULTS: The study was performed in six pigs (weight 60-75 kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1-3.6] and 5.5 mm (IQR 4.6-6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7-4.8) and 5.4 mm (IQR 5.0-6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications. CONCLUSION: Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions.

In vivo analysis of the origin and characteristics of gaseous microemboli during catheter-mediated irreversible electroporation.

AIMS: Irreversible electroporation (IRE) ablation is a non-thermal ablation method based on the application of direct current between a multi-electrode catheter and skin electrode. The delivery of current through blood leads to electrolysis. Some studies suggest that gaseous (micro)emboli might be associated with myocardial damage and/or (a)symptomatic cerebral ischaemic events. The aim of this study was to compare the amount of gas generated during IRE ablation and during radiofrequency (RF) ablation. METHODS AND RESULTS: In six 60-75 kg pigs, an extracorporeal femoral shunt was outfitted with a bubble-counter to detect the size and total volume of gas bubbles. Anodal and cathodal 200 J IRE applications were delivered in the left atrium (LA) using a 14-electrode circular catheter. The 30 and 60 s 40 W RF point-by-point ablations were performed. Using transoesophageal echocardiography (TOE), gas formation was visualized. Average gas volumes were 0.6 ± 0.6 and 56.9 ± 19.1 µL (P < 0.01) for each anodal and cathodal IRE application, respectively. Also, qualitative TOE imaging showed significantly less LA bubble contrast with anodal than with cathodal applications. Radiofrequency ablations produced 1.7 ± 2.9 and 6.7 ± 7.4 µL of gas, for 30 and 60 s ablation time, respectively. CONCLUSION: Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations.

Pulmonary Vein Isolation With Single Pulse Irreversible Electroporation: A First in Human Study in 10 Patients With Atrial Fibrillation.

BACKGROUND: Irreversible electroporation (IRE) is a promising new nonthermal ablation technology for pulmonary vein (PV) isolation in patients with atrial fibrillation. Experimental data suggest that IRE ablation produces large enough lesions without the risk of PV stenosis, artery, nerve, or esophageal damage. This study aimed to investigate the feasibility and safety of single pulse IRE PV isolation in patients with atrial fibrillation. METHODS: Ten patients with symptomatic paroxysmal or persistent atrial fibrillation underwent single pulse IRE PV isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping (EnSite Precision, Abbott) of left atrium and PVs were performed using a conventional circular mapping catheter. PV isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 J direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16-27 mm). A deflectable sheath (Agilis, Abbott) was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if PV potentials were abolished after the first application. Bidirectional PV isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing (30 mg) was used to reveal dormant PV conduction. RESULTS: All 40 PVs could be successfully isolated with a mean of 2.4±0.4 IRE applications per PV. Mean delivered peak voltage and peak current were 2154±59 V and 33.9±1.6 A, respectively. No PV reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. CONCLUSIONS: In the 10 patients of this first-in-human study, acute bidirectional electrical PV isolation could be achieved safely by single pulse IRE ablation.

Development of an algorithm for automatic classification of right ventricle deformation patterns in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Different disease stages of arrhythmogenic right ventricular cardiomyopathy (ARVC) can be identified by right ventricle (RV) longitudinal deformation (strain) patterns. This requires assessment of the onset of shortening, (systolic) peak strain, and postsystolic index, which is time-consuming and prone to inter- and intra-observer variability. The aim of this study was to design and validate an algorithm to automatically classify RV deformation patterns. METHODS: We developed an algorithm based on specific local characteristics from the strain curves to detect the parameters required for classification. Determination of the onset of shortening by the algorithm was compared to manual determination by an experienced operator in a dataset containing 186 RV strain curves from 26 subjects carrying a pathogenic plakophilin-2 (PKP2) mutation and 36 healthy subjects. Classification agreement between operator and algorithm was solely based on differences in onset shortening, as the remaining parameters required for classification of RV deformation patterns could be directly obtained from the strain curves. RESULTS: The median difference between the onset of shortening determined by the experienced operator and by the automatic detector was 5.3 ms [inter-quartile range (IQR) 2.7-8.6 ms]. 96% of the differences were within 1 time frame. Both methods correlated significantly with ρ = 0.97 (P < .001). For 26 PKP2 mutation carriers, there was 100% agreement in classification between the algorithm and experienced operator. CONCLUSION: The determination of the onset of shortening by the experienced operator was comparable to the algorithm. Our computer algorithm seems a promising method for the automatic classification of RV deformation patterns. The algorithm is publicly available at the MathWorks File Exchange.

In vitro analysis of the origin and characteristics of gaseous microemboli during catheter electroporation ablation.

INTRODUCTION: Recent studies demonstrated that irreversible electroporation (IRE) ablation may be an alternative method for thermal ablation for pulmonary vein isolation. Development of gaseous microemboli during catheter ablation might lead to asymptomatic ischemic events and is therefore an important research topic. Gas formation during arcing with direct current catheter ablation has been studied in the past, however not for nonarcing IRE-ablation. OBJECTIVE: The aim of the present study was to visualize, quantify, and characterize gas formation during nonarcing millisecond IRE-pulses using a multielectrode circular catheter. METHODS: In vitro, gas formation during IRE-pulses was studied using a high-speed imaging, direct volume measurements, and a bubble counter. Gas formation was compared between cathodal and anodal IRE-pulses and between a small and large catheter hoop diameter. RESULTS: High-speed images showed the location and dynamics of gas formation during cathodal and anodal millisecond IRE-pulses. The direct volume measurements demonstrated a significantly larger volume for cathodal than for anodal IRE-pulses (P < .001), and no significant difference between small and large hoop diameters. A strong linear relationship was found between delivered charge and total gas volume (r = 0.99). Bubble counter measurements showed that cathodal IRE-pulses produced more and larger gas bubbles than anodal IRE-pulses. The ratio of total gas volume between cathodal and anodal IRE-pulses is different as predicted from electrolysis theory. CONCLUSION: In vitro, millisecond anodal IRE-pulses produce significantly less and smaller gas bubbles than millisecond cathodal IRE-pulses. In vivo experiments are required to investigate the clinical implication of these observations.