Specific effects of Pulsed Field Ablation on the cardiac tissue, the nervous system and the conduction system in experimental and clinical studies

Figures

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  Figure 1. Summary of preferential effects of PFA on cardiac tissue. (A) Schematic representation of the transmembrane voltage induced under an electric field in different directions at the cell and tissue levels. (B) Summary of main biological mechanisms involved in cardiomyocyte cell death after PFA. (C) Example of differential response of cardiac tissue and oesophageal tissue in the event of acute damage by PFA; as extracellular matrix is preserved, oesophageal cells have the ability to regenerate and tissue heals, cardiac tissue does not have the ability to regenerate.

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  Figure 2. Schematic comparison of electric field distribution in homogenous vs. scar cardiac tissue. Computational models predict electric field penetration even with a dense scar tissue. Presence of fibrosis and fat can produce localized distortions of electric field distribution. Partially adapted from ref.58.

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  Figure 3. PFA lesions; histology, intracardiac echocardiography, and MRI. (A) Gross findings of PFA lesions on the right ventricular surface 24 h after PFA, stained with triphenyltetrazolium chloride. Uniform lesion formation is observed even in tissue with relatively developed trabeculae, with clearly demarcated borders. In addition, intralesional haemorrhage is minimal. Modified from ref.59. (B) ICE images obtained before PFA lesion formation and 70 min after PFA show a hyperechoic lesion becoming visible at 70 min. PFA lesions are difficult to visualize immediately after ablation on ICE. Modified from ref.59. (C) MRI images acquired 24–48 h after PFA demonstrate no obvious findings of microvascular obstruction in PFA lesions, with homogeneous late gadolinium enhancement and minimal enhancement on T1-weighted images. Black arrows indicate right ventricular lesions, and white arrows indicate left ventricular PFA lesions.

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  Figure 4. Different stages of lesion formation after PFA and RFA. (A) Acute phase: Histologic (left and middle) and macroscopic images (right) of PFA (monopolar, biphasic, top row) and RFA (bottom row) delivered via a 3.5 mm focal ablation catheter. Note the subtle macroscopic features of the acute PFA lesion as compared with the clearly demarcated coagulative RFA lesion. Histopathology shows well-demarcated non-coagulative acute myocardial damage in the ablated area (right of dashed line) with intact vessels (arrow). In contrast, histopathology of RFA lesions shows coagulation necrosis (blue) surrounded by haemorrhagic contraction band necrosis (dark purple). Modified from ref.75. (B) PFA lesion 2 days after epicardial delivery using a 9 mm lattice-tip catheter showing a homogeneous, sharply demarcated lesion with preservation of intralesional fat and blood vessels. Modified from ref.59. (C) Gross pathology (left) and histopathology (Masson’s trichrome staining) of a PFA lesion created with an investigational 2.3 mm tip focal ablation catheter using an output of 2.0 kV. The lesion is composed of two areas. The central, shallower area (yellow dotted line) shows evidence of coagulative…

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  Figure 5. Schematic representation of the interaction of an electric field with a myelinated axon. Electric field concentrates in the unmyelinated areas leading to depolarization and stimulus propagation or local cell membrane electroporation leading to a possible transient conduction block.

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  Figure 6. Possible nerve regeneration mechanisms after electroporation. Axons and myelin sheath can be transiently disrupted after exposure to very strong electric fields. However, nerve structures such as the endoneurium and perineurium are not thermally damage in PFA enabling subsequent nerve regeneration mechanisms and nerve function restoration.