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Atrial and ventricular Pulsed field ablation in a porcine animal model, correlated with clinical biomolecule data: Tissue specificity and lesion formation over 8 weeks

Applicant Dr. Moritz Nies
Subject Area Cardiology, Angiology
Term from 2023 to 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 523496205
 
Final Report Year 2025

Final Report Abstract

Catheter ablation of cardiac arrhythmias is one of the cornerstones in arrhythmia therapy. Conventional, thermal ablation modalities are associated with the risk for severe complications like atrio-esophageal fistula. Pulsed field ablation (PFA) is a novel, mostly nonthermal energy source that offers a certain degree of tissue specificity. The resulting safety advantages have led to PFA’s rapid implementation into clinical practice for atrial ablation. However, current catheter designs and waveforms face several limitations, calling for further developments: • The most frequently used pentaspline PFA system does not have mapping capabilities which can only be overcome by the insertion of additional mapping catheters. Also, multiple PF-applications are needed to achieve pulmonary vein isolation (PVI). The large catheter tip also faces limitations in maneuverability, especially when ablation sets are extended beyond PVI. • PFA-specific complications like coronary artery spasm and hemolysis have recently been reported using the pentaspline PFA system. It is essential for patient safety to explore whether these can be mitigated by changing waveforms or catheter designs. • Current PFA systems have been optimized for atrial ablation. Ablating ventricular myocardium is significantly more challenging as the cardiac ventricles have a complex anatomy, including mobile intracavitary structures. Also, ventricular walls are much thicker than the atria which makes creating effective ablation lesions more difficult. In this preclinical research project, we evaluated novel catheter designs and PFA waveforms for endocardial PFA both in atrial and ventricular myocardium. Specifically, we evaluated a novel ablation system using nanosecond pulsed fields. The shorter pulse width compared with conventional systems (using microsecond pulses) showed promising lesion depth and facilitated PVI with fewer, often singular applications. Several other systems are under investigation, including a focal ablation catheter employing high field strengths and a novel „field-bending“ technology to optimize lesion creation, and a balloon system designed for „single-shot“ PVI. However, further results are unpublished and proprietary. We also explored new strategies to overcome the main limitations for ventricular PFA. Using a large focal catheter, ablation of mobile intracavitary structures was successfully performed and showed promising results. Using dual catheter bipolar PFA, we were also able to create transmural ablation lesions with a depth exceeding 20mm. To our knowledge, this is the highest lesion depth ever reported with endocardial PFA thus far. One of the main advantages of PFA over thermal ablation modalities is its safety regarding the esophagus. Thermal damage to the esophagus after ablation can lead to the formation of atrio-esophageal fistulas, which is a lethal and dreaded complication. Even after more than 50.000 patients have been treated with the pentaspline PFA system, there have been no clinical reports of esophageal damage or atrio-esophageal fistula. However, the exact mechanism behind this apparent esophageal sparing had not been evaluated yet. In a separate preclinical study, we were able to show that esophageal effects do occur after PFA, but sparing of the extracellular matrix allows for complete restitution over time.

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