Significance: Each year 300,000 to 400,000 patients experience sudden cardiac death in the United States. For patientsat risk, implantable cardiac defibrillators (ICDs) improve survival, largely through the delivery of high energy shocks torestore sinus rhythm. While high energy shocks are clearly life-saving, they are not necessarily benign. Patients receivinghigh energy shocks have increased mortality and programming the device to reduce the number of shocks delivered canimprove mortality. High energy shocks are associated with myocardial stunning, injury, and cell death. In addition, theyare 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 liveswhile 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 aperiod 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 ofventricular fibrillation. In order to be clinically relevant, the algorithms must function and guide the defibrillator'sdecision quickly. The goal of our IntelliSync algorithm are 2-fold: 1) Analyze the first 6-8 seconds of an arrythmia within 2seconds, recognize patterns of regional coupling within the heart that herald imminent arrhythmia termination. Ifidentified, the algorithm would trigger the ICD to wait for VF to terminate on its own, and only deliver therapy after atime-out period has occurred. 2) Measure patterns of coupling within the heart and time low energy therapy (ifappropriate) to a period of high synchronization when it is more likely to succeed. IntelliSync may also work for atrialfibrillation (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 fibrillationSub-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 synchronizationbased on real-time calculations in a small animal model of VFSub aim 2A: Demonstrate that synchrony measured from limited epicardial sensors are representative of full optical mapsSub-aim 2B: Establish threshold values for the RQA variable Entropy which identify episodes likely to self-terminateSub-aim 2C: Prospectively test threshold value of Entropy from Aim 2B.Sub-Aim 2D: Demonstrate feasibility of performing real-time RQA calculations to guide delivery of low energy therapy.
Public Health Relevance Statement: Project narrative: Arrhythmia Dynamics, LLC is developing the IntelliSync ICD control algorithm which enable ICDs to save lives will minimizing the use of harmful and damaging high energy shocks. 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 benign. High energy shocks are associated with myocardial stunning, injury, and cell death and patients receiving them have increased mortality. The IntelliSync ICD control algorithm which enable ICDs to save lives will minimizing the use of harmful and damaging high energy shocks by 1) recognizing ventricular arrhythmia episodes which have high probability of terminating on their own without therapy; and 2) timing low energy defibrillation to periods of synchronization where it is more likely to be effective.
Project Terms: Algorithms ; Arrhythmia ; Cardiac Arrhythmia ; Heart Arrhythmias ; Atrial Fibrillation ; Auricular Fibrillation ; Cell Death ; necrocytosis ; Electric Countershock ; Cardiac Electroversion ; Cardioversion ; Electric Defibrillation ; defibrillation ; Goals ; Grant ; Heart ; Heart Atrium ; Atrial ; Cardiac Atrium ; atrium ; Learning ; Maps ; mortality ; Optics ; optical ; Pain ; Painful ; Sinus ; Accessory Sinuses ; Nasal Sinuses ; Nasal cavity/Paranasal ; Nasal cavity/Paranasal sinuses ; Paranasal Sinuses ; Patients ; Probability ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Risk ; Savings ; Shock ; Circulatory Collapse ; circulatory shock ; Time ; Tissues ; Body Tissues ; United States ; Ventricular Fibrillation ; Work ; Measures ; sudden cardiac death ; Health Care Costs ; Health Costs ; Healthcare Costs ; Ventricular Arrhythmia ; Pain Threshold ; Pain Tolerance Level ; pain tolerance ; Injury ; injuries ; base ; density ; Defibrillators ; Electric Shock Cardiac Stimulators ; Stimulators, Electrical, Cardiac, Shock ; sensor ; improved ; Benign ; Phase ; Myocardial Stunning ; Stunned Myocardium ; Electroporation ; electroporative delivery ; gene electrotransfer ; Stimulus ; Randomized Controlled Trials ; Entropy ; Life ; Pattern ; experience ; Performance ; voltage ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Devices ; Palate ; Modeling ; Data ; pre-clinical testing ; Preclinical Testing ; Predictive Value ; Resolution ; Energy Therapy ; Ventricular ; Cardiac ; Development ; developmental ; Coupling ; innovation ; innovate ; innovative ; clinically relevant ; clinical relevance ; spatiotemporal ; prospective test ; Computer Models ; Computerized Models ; computational modeling ; computational models ; computer based models ; computerized modeling ; myocardial injury ; injury to the myocardium ; feasibility testing ;
