Effect of Contact Force on Pulsed Field Ablation Lesions in Porcine Cardiac Tissue.

BACKGROUND 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 g 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). CONCLUSIONS 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. This article is protected by copyright. All rights reserved

Elucidating the mechanisms of microbubble formation in intracardiac pulsed field ablation

Delivery of electrical energy for sensing or therapeutic purposes often involves electrochemical phenomena at the electrode-electrolyte solution interface. Release of gaseous bubbles that accompanies delivery of pulsed electric fields to tissues in applications such as electrochemotherapy of tumours and irreversible electroporation or pulsed field ablation in cardiac electrophysiology needs to be understood and characterized. We present an in vitro study using pulsed field delivery into saline, employing multiple different treatment protocols, two electrode geometries (pair of needles and a modified RF catheter), and two imaging systems to elucidate the complex relationship between the electrical treatment protocol, temperature changes at and around the electrodes, and gas release due to pulse delivery. Our primary objective was to identify the key parameters responsible for bubble formation and to highlight the importance of the treatment parameters and their interplay – ranging from the temperature to appropriate choice of electrode geometry, and, most importantly, to the choice of the treatment protocol. We found that bubbles originating from electrochemical reactions are more prevalent in monophasic pulsing protocols, whereas in high frequency biphasic pulsing protocols the bubbles are mainly caused by boiling of the medium. Degassing of liquid due to lower solubility of gasses at elevated temperatures does seems to play a role, though a minor one. We also observed that bubbles caused by boiling collapse very rapidly, whereas electrochemically produced bubbles or those produced through degassing appear to have longer lifetimes. Therefore, the treatment protocols most suited to minimizing gas release are biphasic trains of short ($mu$s) pulses with a significant inter-pulse delay (i.e. low duty cycle) to prevent excessive heating. Moreover, electrodes must be designed to avoid high local current densities. Our findings have broad implications extending from lab-on-a-chip cell electroporation devices to intracorporeal pulsed field applications in the cardiovascular system, particularly pulsed field ablation procedures

DNA methylation networks underlying mammalian traits

Using DNA methylation profiles ( = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species