Lesion morphology and cell death mechanisms in high frequency pulsed field ablation in cardiac tissue
A novel technique for the ablation of cardiac arrhythmias based on irreversible electroporation, Pulsed Field Ablation (PFA), has been developed over the last years. Despite PFA is already in clinical use, there are many aspects that are poorly understood or characterized. We have decided to carry o...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/694212 |
| Acceso en línea: | http://hdl.handle.net/10803/694212 |
| Access Level: | acceso embargado |
| Palabra clave: | Irreversible electroporation Pulsed field ablation Radiofrequency ablation Cardiac ablation Cell death Necroptosis Pyroptosis Computational model High frequency pulses PFA IRE H-FIRE H9C2 62 |
| Sumario: | A novel technique for the ablation of cardiac arrhythmias based on irreversible electroporation, Pulsed Field Ablation (PFA), has been developed over the last years. Despite PFA is already in clinical use, there are many aspects that are poorly understood or characterized. We have decided to carry out a first study to learn more details about the PFA, such as the morphology of the lesion, as well as to determine the influence that the blood velocity may have on the lesion or the effect of the orientation of the catheters on the lesion size. These two parameters have been observed to considerably affect lesion morphology in thermal cardiac ablation technique, Radiofrequency ablation, RFA. For that, we did a computational comparison in terms of lesion morphology, using computational models, considering different multiphysics, including electrical, thermal, and fluid dynamics, in a simplified cardiac chamber slab (with blood in motion). Two catheter configurations: monopolar and bipolar were studied. RFA was simulated using a conventional temperature-controlled approach while the PFA protocol consisted of a sequence of 20 biphasic bursts (100 µs duration). To make a fair lesion comparison, PFA voltage was adjusted to obtain the same lesion depth as for the RFA model. Computational simulations indicate that, for equivalent lesion depths, PFA lesions are wider, more symmetrical and have a higher volume than RFA lesions for both catheter configurations. Regarding the effects of blood velocity, RFA lesions display a great dependence while PFA lesions remain immune to it. For the monopolar configuration, catheter angle with respect to cardiac surface impacted both ablation techniques but in opposite directions. The orientation of the catheter with respect to blood flow direction only affected RFA lesions. Comparing the morphology of the lesions predicted for PFA in our first study (where symmetrical lesions are observed) with real lesions published by other authors, we see that there are significant differences, the lesions are not perfectly symmetrical, and above all, we observe differences between the lesion obtained right after the application of the pulses, and the final injury after a period of hours. Since the cell death mechanisms underlying PFA are not clearly known, we decided to perform a second study to study the dynamics of different cell death mechanisms previously observed in other PFA studies. An in vitro study was carried out using a circular 2D model with H9C2 cells (myoblast from cardiac rat tissue) was implemented. Conventional IRE and H-FIRE pulses were used for different internal frequencies. Voltages were adapted to have similar lesions width after 24 hours of pulses application. In vitro results indicate that after 4 hours of the pulses application, there was a peak of pyroptosis while the peak of necroptosis was detected after 18 hours of the pulses application. Both cell death mechanisms were frequency-dependent phenomena and lesions suggested that there must be another death mechanisms involved and not detected since lesions widths were smaller than lesions after 24 hours of the pulses application. |
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