Otsuka, Naoto

Abstract Background Many patients with atrial fibrillation (AF) suffer life-limiting symptoms and heart failure. Although enormous advances in rhythm control have been made, device-based therapies for treating recurrent episodes are limited. Using pulsed electric fields (PEF) to induce reversible electroporation of cardiac tissue may effectively terminate AF. Purpose To assess the feasibility of PEF delivery for converting atrial arrhythmias via reversible electroporation. Methods Four swine models were used in this acute study. Custom-made decapolar catheters for PEF delivery were deployed with the following configurations: 1. Endocardial right atrium (RA) and coronary sinus (CS), n=2; 2. Endocardial RA and epicardial left atrium (epiLA), n=2. AF and atrial flutter (AFL) were induced with programmed stimulation. PEF delivery was performed using the BTX 830 generator. For each attempt, a single monophasic pulse at 10 or 20µs pulse width was administered, with voltage varied across attempts (range 750-3000V). Successful (type 1 and 2 breaks) and unsuccessful conversion attempts were recorded. Post-PEF signal changes and arrhythmias were identified. Results A total of 58 AF/AFL (28 and 30 respectively) episodes were induced. Of the 37 successful conversion attempts, 33 (89.1%) were type 1 breaks. Conversion success probabilities generally increased with higher voltages for both configurations. >70% conversion success was seen with ≥1500V for the RA/CS configuration and ≥2000V for the RA/epiLA configuration. Arrhythmias including intra-atrial delay and high-grade atrioventricular block were seen, usually following successive PEF deliveries. Significant muscle stimulation was provoked with the current experimental setup. Conclusion Termination of atrial arrhythmias with PEF delivery is feasible, although further work is required to optimize its efficacy and safety.

Abstract Background Ventricular fibrillation (VF) is a leading cause of sudden cardiac death worldwide. Defibrillation via direct current shocks is effective but associated with significant pain and morbidity, prompting the need for alternative approaches. Reversible electroporation of cardiac tissue with pulsed electric fields (PEF) may be an effective means of terminating VF. Purpose To assess the feasibility of PEF delivery for terminating VF. Methods 5 acute swine models were used. Mechanical circulatory support with peripheral veno-arterial extracorporeal membrane oxygenation +/- percutaneous left ventricular assist device (Impella 5.5 L) was implemented and titrated to a mean arterial pressure ≥65 mmHg. Decapolar catheters were introduced into the endocardial right and/or left ventricle as well as epicardium. VF was induced with R on T shocks or rapid ventricular pacing. PEF was delivered with the endocardial catheter as the cathode and epicardial catheter as the anode; monophasic pulses (5-10) at 3000V, 100µs, and 200ms inter-pulse intervals were used. If VF persisted post-PEF, catheters were repositioned into regions of intact voltages for repeat delivery. Results 10 VF episodes were induced, 7 of which were successfully terminated with PEF delivery (70.0%). The median number of attempts to achieve VF termination was 2 (range 1-5). The post-VF rhythm was complete heart block with ventricular asystole in all successful defibrillation attempts, with no recovery after 30 minutes of observation. Significant muscle stimulation was seen with the utilized PEF parameters and catheter configurations. Conclusion Termination of VF using PEF – pulsed field defibrillation – is possible. However, further study is required to optimize delivery parameters/configurations to improve effectiveness and avoid muscle stimulation as well as conduction abnormalities.

ABSTRACT Background Pulsed‐field ablation (PFA) offers myocardial selectivity with minimal thermal injury, but depth for ventricular lesions may be insufficient or heterogeneous at clinically tolerable field strengths. Calcium electroporation—local calcium chloride (CaCl₂) infusion after PFA—may amplify electroporation‐mediated cell death while maintaining low energy settings. Objective To determine whether immediate post‐PFA CaCl₂ infusion enhances acute and chronic ventricular lesion formation in vivo. Methods Nine swine underwent focal ventricular PFA (750–1000 V, biphasic, 20 μs × 50 pulses, 200 ms interpulse) via an irrigated focal catheter and benchtop electroporator. Immediately post‐PFA, lesions were randomized to saline, 0.2 g Ca, or 0.4 g Ca infused locally through the catheter tip. Acute hearts were explanted for TTC analysis; surviving animals were studied at 7 days for chronic lesion geometry. Results Among 41 acute lesions (17 control, 12 Ca 0.2 g, 12 Ca 0.4 g), Ca 0.4 g increased dark‐zone depth (3.5 ± 1.4 vs. 2.3 ± 0.8 mm; p = 0.038) and pale‐zone depth (2.6 ± 1.3 vs. 1.3 ± 0.8 mm; p = 0.011) versus control. At 7 days ( n = 33 lesions), Ca 0.4 g produced larger scars than control (width 11.6 ± 2.1 vs. 10.0 ± 1.9 mm; p = 0.027; depth 4.2 ± 1 vs. 3.0 ± 0.8 mm; p < 0.001; volume 193.6.4 ± 82.3 vs. 109.4 ± 48.2 mm³; p = 0.001). Conclusions Local CaCl₂ infusion after ventricular PFA significantly augments acute electroporation effect and chronic lesion size at low output, supporting facilitated PFA as a strategy for deeper, more durable ventricular ablation.

BACKGROUND: Power-controlled radiofrequency ablation with irrigated-tip catheters has been the norm for ventricular ablation for almost 2 decades. New catheter technology has recently integrated more accurate tissue temperature sensing enabling temperature-controlled irrigated ablation. We aimed to investigate the in vivo ablation parameters and lesion formation characteristics in ventricular myocardium using a novel temperature-controlled radiofrequency catheter. METHODS: Twenty canines were divided into 3 groups: 4 noninfarcted, acute (phase I); 8 noninfarcted, chronic (phase II); and 8 infarcted, chronic (phase III). Lesions were delivered with a temperature-controlled radiofrequency system utilizing a chemical vapor deposit diamond for efficient thermal diffusivity. In phase I, 17 ablation settings were tested (temperature set points, 50/60/70 °C; ablation duration, 15/30/60/90/120 s; and power limit, 30/50 W). Four and one of these sets of parameters were further tested in phases II and III, respectively. Lesions were assessed by ex vivo contrast-enhanced magnetic resonance imaging and gross pathology 5 weeks after ablation in phases II/III. RESULTS: Across all phases, 111 ablation lesions were delivered. Ablation with the power limit of 50 W, the temperature set point of 60 °C, and the duration of 60 s produced significantly larger and deeper lesions (mean, 569.2 mm 3 ; mean maximal depth, 9.8 mm) compared with 50 W/60 °C/30 s (mean, 340.4 mm 3 ; mean maximal depth, 8.3 mm) and 50 W/50 °C/60 s (mean, 227 mm 3 ; mean maximal depth, 6.9 mm), with P <0.05 for all pairwise comparisons. Ablation of infarcted myocardium in phase III (50 W/60 °C/30 s) resulted in smaller impedance and bipolar electrogram amplitude changes and lesion size compared with ablation in normal myocardium with the same settings. No steam pop, myocardial perforation, or char formation was observed in any of the 111 ablations across all phases. CONCLUSIONS: In vivo radiofrequency ablation in a canine model with a diamond-tip temperature-controlled catheter using a temperature set point of 60 °C and a power limit of 50 W created large lesions without steam pop risk in both normal and infarcted ventricular myocardia.

ABSTRACT Background Pulsed‐field ablation (PFA) is an innovative non‐thermal method for arrhythmia treatment. The efficacy of various PFA configurations in relation to contact force (CF) has not been well‐studied in vivo. Objectives This study evaluated the effect of CF on acute bipolar PFA lesions in both a vegetal and an in vivo porcine heart model. Methods Bipolar PFA (500 V, 20 μs for 50 pulses) was applied to eight porcine ventricles, with CF categorized as standard (5–15 g), high (16–30 g), or very high (> 30 g) using the CARTO 3 system. PFA lesions were assessed by gross pathology, histology, and post‐ablation voltage amplitude. Additionally, a vegetal model using oscillating russet potatoes replicated the motion of a beating heart to compare lesion parameters under dynamic conditions and various PFA configurations (monopolar vs. bipolar). Results A total of 61 in vivo bipolar PFA lesions across all groups were analyzed. No significant differences in lesion surface diameter, depth, or volume were found among CF groups. In the vegetal model, monopolar setting had a better correlation between CF and lesion depth compared to bipolar setting. In addition, oscillations and catheter position (perpendicular or parallel) significantly affected lesion dimensions. Conclusion Increasing CF has a minimal effect on the size of acute bipolar PFA lesions in the porcine ventricle, suggesting that, for bipolar PFA, adequate CF is more critical than its intensity in a beating heart. For monopolar PFA, greater CF can impact lesion depth.

Background: Pulsed field ablation (PFA) is an innovative modality for treating arrhythmias that is mostly non-thermal and renders myocardial tissue non-viable by creating pores in cardiac cell membranes. The impact of contact force (CF) on PFA efficacy is not well characterized. Hypothesis: We hypothesize that, while contact is necessary for PFA, increasing CF will not have a significant effect on in vivo ablation lesion size. Aim: We seek to investigate the effects of CF on acute PFA lesions in a beating porcine heart model. Methods: The ventricles of 7 porcine animals were ablated in vivo with PFA (500V, at 20μs for 50 pulses separated by 200ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). CF was measured before and after each PFA application using CARTO 3. Lesions were divided into standard CF (5-15g), high CF (16-30g), and very high CF (>31g). Results: A total of 46 lesions were analyzed. Gross pathology showed no significant difference in maximum width, lesion depth, and lesion volume between the three groups ( Figure 1A-B ). Linear regression showed a decrease of 0.003 mm in depth (depth = -0.003 × CF + 1.8, R = 0.05), an increase of 0.01 mm in width (width = 0.01 × CF + 5.7, R = 0.09), and a decrease of 0.05 mm 3 in volume (volume = -0.05 × CF + 26.8, R = 0.03) for each additional gram of CF ( Figure 1C ). Conclusion: While contact is necessary, increasing CF did not have a significant effect on in-vivo PFA lesion dimensions in a beating porcine heart model.

Background: Pulsed field ablation (PFA) has emerged as an innovative technology for treating cardiac arrhythmias. PFA increases cell permeability, which can lead to apoptosis. Greater PFA energy may be necessary to ablate ventricular myocardium for ventricular tachycardia circuits, but this carries risks of side effects such as gaseous formation (microbubbles) and hemolysis. Ethanol (EtOH) infusion has been used to ablate pathologic myocardial tissues in hypertrophic cardiomyopathy and for refractory arrhythmias. Hypothesis: We hypothesize that PFA in the ventricle can increase EtOH uptake through PFA-generated pores, thereby enhancing ablation efficacy, even at low powers, by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effect of local EtOH infusion after PFA on lesion size in porcine ventricles. Methods: The ventricles of five porcine subjects were ablated in vivo with a PFA low power setting (750 V, at 20 μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA was performed, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared the electrograms voltage amplitude reduction before and after PFA, and the ablation lesion characteristics. Results: A total of 10 lesions in the control group and 9 lesions in the EtOH group were analyzed. For the controls, the voltage after PFA was not reduced. In contrast, for the EtOH group, the voltage after PFA was significantly reduced ( Figure 1A ). On gross pathology, there were significant differences in ablation lesion depths and volumes between the 2 lesion sets ( Figure 1A-B ). Conclusion: Local EtOH infusion after ventricular PFA enhanced acute efficacy of electroporation. Concurrent PFA with local EtOH infusion has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Future studies on chronic efficacy are warranted.

Background: Pulsed field ablation (PFA) is a promising modality for treatment of cardiac arrhythmias. PFA increases cell permeability, thereby promoting cell apoptosis. Although greater PFA energy may produce larger lesions, it also carries risks of side effects such as arcing, hemolysis, and microbubbles. Chemical ablation using ethanol (EtOH), such as with injection of the Vein of Marshall, has been used to treat atrial myocardium for refractory atrial arrhythmias. Hypothesis: We hypothesize that PFA in the atria can increase EtOH uptake through PFA-generated pores, thereby augmenting ablation efficacy by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effects of local EtOH infusion after PFA on lesion size in porcine atria. Methods: The atria of five porcine subjects were ablated in vivo with low PFA power settings (250V, at 20μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared electrogram voltage amplitude reduction and ablation lesion parameters before and after PFA. Results: A total of 14 control lesions and 14 EtOH lesions were analyzed. There was significant difference in voltage reduction between two groups ( Figure 1A-B ). On gross pathology, there were significant differences in ablation lesion maximum surface diameter, lesion depth, and volume between the 2 lesion sets ( Figure 1C ). Conclusion: Concurrent EtOH infusion after PFA enhanced acute efficacy of electroporation in porcine atria. Adjuvant therapy has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Further studies to assess chronic efficacy are warranted.

AbstractIntroductionPulsed field ablation (PFA) has emerged as an innovative therapy for cardiac arrhythmias. Drawing parallels with PFA's application in solid tumors, calcium chloride (CaCl2) as an adjuvant therapy, known as calcium electroporation, may amplify PFA's apoptotic effects. We propose that PFA in the atrium could enhance calcium uptake through PFA‐created pores, thereby increasing ablation efficacy even at reduced power levels by exploiting PFA's permeabilization effects.MethodsWe conducted in vivo ablations on the atria of seven pigs using low PFA power (250 V, 20 μs for 50 pulses at 200 ms intervals). Post‐PFA, we randomly administered an infusion of either 200 mg/2 ml CaCl2 (calcium group) or saline (control) directly to the ablation site via the catheter tip. We evaluated reduction in electrogram voltage amplitude, electrocardiography (ECG) parameters, ablation lesion parameters, and histology after PFA.ResultsNineteen lesions from control and calcium groups were examined. Control lesions showed no voltage decrease post‐PFA, whereas calcium‐treated lesions exhibited a significant voltage reduction. Gross pathology indicated marked differences in maximum lesion surface diameter, depth, and volume between the lesion groups. Histologically, calcium group lesions were characterized by a more severe acute PFA response with contraction band necrosis, myocytolysis and nuclear pyknosis in adjacent myocardium, in addition to microhemorrhages.ConclusionInfusing calcium chloride locally after PFA markedly improves the immediate efficacy of electroporation in porcine atria. This study suggests that calcium electroporation could bolster PFA outcomes without higher energy levels, potentially diminishing associated risks. These preliminary findings warrant further research into the long‐term efficacy and potential clinical application of calcium electroporation in PFA.

Introduction: Recently, there have been numerous strategies for treating atrial fibrillation, including the choice of catheters However, the thermal characteristics of each catheter, particularly in terms of safety, have not been fully understood. Hypothesis: Our aim was to characterize the thermal damage to collateral tissues during 50W-HPSD ablation and 90W/4sec-vHPSD ablation using three different ablation catheters. Methods: In 28 pigs, we implanted thermocouples on the superior vena cava, close to the phrenic nerve, and on the esophageal, close to the inferior vena cava. We performed endocardial ablation near the fiducial markers of the thermocouples using three different RF catheters: ablation index (AI)-guided HPSD (Qmode) and vHPSD ablation (Qmode+) with QDOTMICRO, lesion size index-guided HPSD ablation (targeting 5.0) with TactiCath Sensor Enabled (Tacti), and AI-guided HPSD ablation (targeting 400) with Thermocool Smart Touch (STSF). We measured tissue temperatures during ablation, including maximum tissue temperature (Tmax), time to maximum tissue temperature (t-Tmax), time to achieve a lethal temperature of 50°C (t-50°C), and time to return to baseline from Tmax (t-Tbase). Results: In terms of the frequency of esophageal injury, there were no significant differences among the different catheters. However, the depth of esophageal injury from the adventitia showed a significant difference. In terms of phrenic nerve injury, Tacti had the highest frequency compared to the other catheters (100%, p=0.0012). Tmax, t-Tmax, t-50°C, and t-Tbase showed significant differences, as shown in figure. Conclusions: The thermal effects on collateral tissues differ among the three different catheters and settings. STSF and Qmode result in a gradual increase in tissue temperature, while Tacti and Qmode+ lead to a rapid temperature increase. These distinct thermal distributions may contribute to the risk of phrenic nerve and esophageal injuries.