NSF/FDA SIR: Numerical heart model for irreversible electroporation ablation

Virginia Polytechnic Institute And State University, Blacksburg VA

Investigators

Abstract

Traditional cardiac ablation is a medical procedure that uses thermal energy to destroy a small area of heart tissue that is causing rapid and irregular heartbeats in atrial fibrillation (AF) patients. Non-thermal irreversible electroporation (IRE) ablation devices use short but strong electrical fields to create permanent pores in heart cells and are currently under safety and effectiveness review by the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). In this project, a first-of-its-kind numerical IRE ablation heart model will be developed using quantifiable measurements of cell death and electrical properties of heart tissue to predict the size of ablation zone for a particular set of ablation pulse parameters. This model has the potential to decrease clinical and animal testing in the IRE device development, inform the FDA regulatory review process and ultimately accelerate AF patients access to innovative, safe and effective devices. The work will partner faculty and students at Virginia Tech (VT) and regulatory scientists at the CDRH/FDA. The goal of this project is to develop a numerical three-dimensional heart model on COMSOL Multiphysics with a representative geometry of heart tissue suitable for simulation of reversible, irreversible electroporation and thermal damage effects in pulsed electric field cardiac ablation. The model will use electric field thresholds of electroporation obtained from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and dynamic conductivity of cardiac tissues measured in ex vivo porcine heart to inform a modified Laplace equation to determine electric potential distribution of a two-needle electrode setup. The model will be validated with limited ex vivo studies to confirm the capability of the numerical model to predict lesion volume in tissues using a large animal tissue model. Therefore, using the novel in silico-in vitro approach, Virginia Tech and the FDA will develop a numerical heart model for irreversible electroporation ablation, producing a scalable tool that can be extended to predicting IRE ablation treatments of other organs with varied electrode arrays. Successful accomplishment of this project will address current gaps in fundamental and regulatory knowledge, provide robust tool for optimization of IRE pulse parameters for cardiac ablation device development, advance understanding of IRE technology for AF treatment, and help address an urgent public health need for 2.7-6.1 million Americans affected by this common cardiac arrhythmia that can lead to heart failure and stroke. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.