Development of an injectable hydrogel electrode for the treatment of ventricular arrhythmias

Ventricular arrhythmias (VA) are the leading cause of sudden death in the United States. The only effective treatment for VA is cardiac defibrillation, where a high-energy shock extinguishes the reentrant circuits that initiate and sustain VA. However, these high-energy shocks exceed the pain threshold. The primary goal of this research is to develop new painless strategies to extinguish reentrant VA. The current treatment requires large energy because the current leads capture the tissue from a single point far from the heterogeneous scarred tissue responsible for the electrical disruptions. We hypothesized that flexible electrodes that can access midmyocardium near the scarred area via the cardiac veins, we could terminate arrhythmias with low-energy shocks. However, there were no pacing electrodes small enough to navigate these tributaries to test this hypothesis. The focus of my dissertation was to develop a conductive hydrogel electrode that could be injected across the affected areas of the myocardium, filling the epicardial coronary veins and their mid-myocardial tributaries. When connected to a standard pacing lead, these hydrogels can then act as flexible electrodes that directly capture the previously inaccessible mid-myocardial tissue. Using in vitro and ex vivo models, we developed a hydrogel formulation with adequate viscosity and kinetics to form and retain the hydrogel in the cardiac veins to enable this approach. We tuned the hydrogel composition and combined new macromers chemistries with small molecules to obtain a biostable and biocompatible gel that matches the myocardium modulus. The conductivity is conferred by the ions on the hydrogel matrix and is above the target myocardium values. We demonstrated that the conductivity and network properties were retained after in vivo implantation and successful in vivo deployment demonstrated that the hydrogel electrode reaches cardiac veins and tributaries more deeply than current technologies allow. Feasibility of this approach was then confirmed with successful capture and pacing in a large animal model. This is the first report of an injectable electrode used to successfully pace the midmyocardium and mimic physiologic conduction. In vivo cardiac mapping studies showed fast and uniform capture along the hydrogel before and after myocardium ablation, as well as increased capture compared to traditional point pacing. As such, this injectable hydrogel electrode provides a novel way to improve current defibrillation strategies and opens opportunities for new therapeutic approaches. By capturing a larger area and deeper into the midmyocardium, this technology enhances new ways to study tissue activation that were not possible with current pacing leads.