Background: Pulsed field ablation (PFA) is a novel energy modality for treatment of cardiac arrhythmias. The impact of electrode-tissue proximity on lesion formation by PFA has not been conclusively assessed. The objective of this investigation was to evaluate the effects of electrode-tissue proximity on cardiac lesion formation with a biphasic, bipolar PFA system. Methods: PFA was delivered on the ventricular epicardial surface in an isolated porcine heart model (n=8) via a 4-electrode prototype catheter. An offset tool was designed to control the distance between electrodes and target tissue; deliveries were placed 0 mm (0 mm offset), 2 mm (2 mm offset), and 4 mm away from the tissue (4 mm offset). Lesions were assessed using tetrazolium chloride staining. Numerical models for the experimental setup with and without the offset tool validated and supported results. Results: Cardiac lesion dimensions decreased proportional to the distance between epicardial surface and electrodes. Lesion depth averaged 4.3±0.4 mm, 2.7±0.4 mm, and 1.3±0.4 mm for the 0, 2, and 4 mm and lesion width averaged 9.4±1.1 mm, 7.5±0.8 mm and 5.8±1.4 mm for the 0, 2, and 4 mm offset distances, respectively. Numerical modeling matched ex vivo results well and predicted lesion creation with and without the offset tool. Conclusions: Using a biphasic, bipolar PFA system resulted in cardiac lesions even in the 0 mm offset distance case. The relationship between lesion depth and offset distance was linear, and the deepest lesions were created with 0 mm offset distance, that is, with electrodes in contact with tissue. Therefore, close electrode-tissue proximity increases the likelihood of achieving transmural lesions by maximizing the electric field penetration into the target tissue.

Background: Phrenic nerve palsy is a well-known complication of cardiac ablation, resulting from the application of direct thermal energy. Emerging pulsed field ablation (PFA) may reduce the risk of phrenic nerve injury but has not been well characterized. Methods: Accelerometers and continuous pacing were used during PFA deliveries in a porcine model. Acute dose response was established in a first experimental phase with ascending PFA intensity delivered to the phrenic nerve (n=12). In a second phase, nerves were targeted with a single ablation level to observe the effect of repetitive ablations on nerve function (n=4). A third chronic phase characterized assessed histopathology of nerves adjacent to ablated cardiac tissue (n=6). Results: Acutely, we observed a dose-dependent response in phrenic nerve function including reversible stunning (R ² =0.965, P <0.001). Furthermore, acute results demonstrated that phrenic nerve function responded to varying levels of PFA and catheter proximity placements, resulting in either: no effect, effect, or stunning. In the chronic study phase, successful isolation of superior vena cava at a dose not predicted to cause phrenic nerve dysfunction was associated with normal phrenic nerve function and normal phrenic nerve histopathology at 4 weeks. Conclusions: Proximity of the catheter to the phrenic nerve and the PFA dose level were critical for phrenic nerve response. Gross and histopathologic evaluation of phrenic nerves and diaphragms at a chronic time point yielded no injury. These results provide a basis for understanding the susceptibility and recovery of phrenic nerves in response to PFA and a need for appropriate caution in moving beyond animal models.

Introduction: Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed field ablation (PFA) is a field‐based ablation technology for which limited evidence on the impact of contact force on lesion size is available.Methods: Porcine hearts (n = 6) were perfused using a modified Langendorff set‐up. A prototype focal PFA catheter attached to a force gauge was held perpendicular to the epicardium and lowered until contact was made. Contact force was recorded during each PFA delivery. Matured lesions were cross‐sectioned, stained, and the lesion dimensions measured.Results: A total of 82 lesions were evaluated with contact forces between 1.3 and 48.6 g. Mean lesion depth was 4.8 ± 0.9 mm (standard deviation), mean lesion width was 9.1 ± 1.3 mm, and mean lesion volume was 217.0 ± 96.6 mm³. Linear regression curves showed an increase of only 0.01 mm in depth (depth = 0.01 × contact force + 4.41, R² = 0.05), 0.03 mm in width (width = 0.03 × contact force + 8.26, R² = 0.13) for each additional gram of contact force, and 2.20 mm³ in volume (volume = 2.20 × contact force + 162, R² = 0.10).Conclusion: Increasing contact force using a bipolar, biphasic focal PFA system has minimal effects on acute lesion dimensions in an isolated porcine heart model and achieving tissue contact is more important than the force with which that contact is made.

Background: Irreversible electroporation is an energy form utilizing high-voltage pulsed electric field, leading to cellular homeostasis disruption and cell death. Recently, irreversible electroporation has shown promising results for the treatment of cardiac arrhythmias. However, reversible and irreversible effects of pulsed electric field on cardiac myocytes remain poorly understood. Here, we evaluated the influence of a monophasic single electric pulse (EP) on the contractility, Ca ²⁺ homeostasis and recovery of cardiac myocytes. Methods: Isolated rat left ventricular myocytes were electroporated using single monophasic EP of different durations and voltages. Sarcomere length and intracellular Ca ²⁺ were simultaneously monitored for up to 20 minutes after EP application in Fura-2 loaded left ventricular myocytes. Lethal voltage thresholds were determined using 100 µs and 10 ms pulses and by discriminating cell orientation with respect to the electric field. Results: Electroporation led to an immediate increase in intracellular Ca ²⁺ which was dependent upon the voltage delivered to the cell. Intermediate-voltage EP (140 V, 100 µs) increased sarcomere shortening, Ca ²⁺ transient amplitude, and diastolic Ca ²⁺ level measured 1 minute post-EP. Although sarcomere shortening returned to pre-EP level within 5 minutes, Ca ²⁺ transient amplitude decreased further below pre-EP level and diastolic Ca ²⁺ level remained elevated within 20 minutes post-EP. Spontaneous contractions were observed after sublethal EP application but their frequency decreased progressively within 20 minutes. Lethal EP voltage threshold was lower in myocytes oriented perpendicular than parallel to the electric field using 100 µs pulses while an opposite effect was found using 10 ms pulses. Conclusions: Sublethal EP affected rat left ventricular myocytes contractility and disrupted Ca ²⁺ homeostasis as a function of the EP voltage. Moreover, EP-induced lethality was preceded by a large increase in intracellular Ca ²⁺ and was dependent upon the EP duration, amplitude and left ventricular myocytes orientation with respect to the electric field. These findings provide new insights into the effect of pulsed electric field on cardiac myocytes.