Project Summary / Abstract: Significance: Each year 300,000 to 400,000 patients experience sudden cardiac death in the United States. For patients at risk, implantable cardiac defibrillators (ICDs) improve survival, largely through the delivery of high energy shocks to restore sinus rhythm. While high energy shocks are clearly life-saving, they are not necessarily benign. Patients receiving high energy shocks have increased mortality and programming the device to reduce the number of shocks delivered can improve mortality. High energy shocks are associated with myocardial stunning, injury, and cell death. In addition, they are painful to the patient, are associated with significant healthcare costs, and result in more rapid battery depletion. Innovation: Arrhythmia Dynamics, LLC is developing the IntelliSync ICD control algorithm which enable ICDs to save lives while minimizing the use of harmful and damaging high energy shocks. IntelliSync will do this in two ways: 1) recognizing ventricular arrhythmia episodes which have high probability of terminating on their own without therapy; and 2) making the delivery of low energy defibrillation more likely to terminate the arrhythmia by optimally timing it to a period of high baseline synchronization in the ventricular chambers. Approach: In this grant we propose testing the feasibility of these algorithms in computational and rat models of ventricular fibrillation. In order to be clinically relevant, the algorithms must function and guide the defibrillator’s decision quickly. The goal of our IntelliSync algorithm are 2-fold: 1) Analyze the first 6-8 seconds of an arrythmia within 2 seconds, recognize patterns of regional coupling within the heart that herald imminent arrhythmia termination. If identified, the algorithm would trigger the ICD to wait for VF to terminate on its own, and only deliver therapy after a time-out period has occurred. 2) Measure patterns of coupling within the heart and time low energy therapy (if appropriate) to a period of high synchronization when it is more likely to succeed. IntelliSync may also work for atrial fibrillation (AF) and could make an atrial defibrillator palatable if shocks above the pain threshold could be avoided. Aim 1 (months 1-6): Optimize algorithm performance in computational models of ventricular fibrillation Sub-aim 1A: Determine minimum spatiotemporal resolution needed to represent high density intracellular voltage maps. Sub aim 1B: Identify threshold of change in the RQA variable Entropy which predicts imminent termination. Sub-aim 1C: Demonstrate that low energy therapies can be effectively timed to periods of greater tissue synchronization. Aim 2 (months 3-9): Demonstrate feasibility of delivering low energy therapy timed to period of high synchronization based on real-time calculations in a small animal model of VF Sub aim 2A: Demonstrate that synchrony measured from limited epicardial sensors are representative of full optical maps Sub-aim 2B: ...