Virtual cardiac electrophysiologic testing for sudden death risk stratification

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DESCRIPTION (provided by applicant): Sudden cardiac death is a leading cause of death in the United States. Although implanted cardioverter defibrillators (ICD) have been shown to be effective in preventing sudden cardiac death in patients who experience ventricular arrhythmias, current risk stratification methods in determining who will or will not benefit from an ICD have been suboptimal. In this application, the development and evaluation of a novel risk stratification tool to predict sudden cardiac death in patients who have had a myocardial infarction (i.e. heart attack) is proposed. This method is based on electrophysiologic testing; a risk stratification approach in which programmed stimulation via catheters placed in the ventricle is used to test for inducibility of potentially life threatening ventricular tachyarrhythmias. We hypothesize that computer simulations could be used to non- invasively test for inducibility of these ventricular tachyarrhythmias. It has been shown that the scars and partially viable tissue resulting from an infarction provide the substrate for these ventricular arrhythmias to occur. Contrast-enhanced magnetic resonance imaging (MRI) can effectively differentiate between viable myocardium, partially viable myocardium, and infarction scar. By assigning realistic electrophysiologic characteristics and conduction properties to the three-dimensional MRI image that is imported to the workstation, it is hypothesized that simulated programmed stimulation using this model will identify the patients who have inducible ventricular tachyarrhythmias and thus would benefit from an ICD. The integration of electrophysiologic computer modeling and cardiac MRI may have other potential clinical applications beyond sudden death risk stratification, including the evaluation of electrical dyssynchrony in candidates for bi- ventricular pacing therapy, pre-procedure planning for catheter ablation of patients with documented ventricular tachycardias, and as an educational software tool for training doctors and medical professionals. In the first stage of this study we plan to develop and implement of the tool using MRI data from healthy volunteers and patients undergoing electrophysiology testing to adjust model parameters. In the second stage, we will focus on comparing the results of "virtual" electrophysiologic testing to actual electrophysiologic testing in a larger cohort of patients and evaluating its ability to predict risk for ventricular arrhythmias. PUBLIC HEALTH RELEVANCE Effective risk stratification for sudden cardiac death is necessary for timely and appropriate therapy. A non- invasive approach to detect whether a patient has the necessary substrate for arrhythmias could significantly improve the prevention of sudden cardiac death, a leading cause of mortality in the United States.