Injectable Hydrogel Electrodes to Prevent Ventricular Arrhythmias In the United States, sudden cardiac death accounts for 350,000 deaths per year with the leading cause being lethal ventricular arrhythmias. The underlying electrophysiologic derangement mechanistically responsible for ventricular arrhythmias is delayed conduction velocity in scarred or otherwise diseased myocardium. Access to the smaller vessels and tributaries that cross over scarred region of the heart could provide improved pacing; however, there are no pacing leads small enough to navigate these smaller tributaries. In this research, we propose a novel method to treat and manage ventriculararrhythmias – developmentof a newconductive material that can fill both large and small coronary vessels and convert these tributaries into flexible electrodes to restore capture across regions of scarring. Our collaborative team that combines clinical expertise (Razavi) and biomaterial science (Cosgriff-Hernandez) has demonstrated early feasibility of pacing myocardium with an in situ curing hydrogel in a pig model. We plan to build on this initial proof of concept to develop a combined material and delivery system that can interface with existing pacemaker technology to greatly expand their capability to treat ventricular arrhythmias. Upon successful completion of these aims, we will have utilized a battery of in vitro and in vivo tests to establish the safety and efficacy of this new injectable hydrogel electrode. Confirmation of increased activation area as compared to standard-of-care single point pacing will validate the efficacy of this innovative approach to eliminate the conduction delay in scarred myocardium that results in lethal ventricular arrhythmias. We will use a post-myocardial infarct model to demonstrate that hydrogel electrode pacing reduces the frequency of ventricular arrhythmias and defibrillation shocks. Painless stimulation of wide areas of the heart using planar wavefront propagation from these hydrogel electrodes provides a new cardiac resynchronization therapy that will alter the landscape of cardiac rhythm management.