GOALI: Model and Experimental Studies of the Evolution of the Excitable Gap for Improved Anti-Tachycardia Pacing

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9903466PollardThe introduction of implantable cardioverter defibrillators (ICDs) into patients surviving myocardial infarction (MI) makes up a $2 billion per year industry. As a result, there is considerable interest in improving ICDs' ability to manage life-threatening arrhythmias. ICDs sense heart rate, and when appropriate they either deliver a high-energy defibrillation shock to resynchronize the heart's electrical activity or they deliver trains of low-energy anti-tachycardia pacing (ATP) stimuli. Since ATP obviates the need for shocks, battery depletion and pain from the shock are both minimized. While ATP can be highly effective, the individual stimuli must be applied during the arrhythmia's excitable gap, when tissue adjacent to the pacing electrode has had sufficient time to recover excitability from the preceding cycle but has not yet been excited in the present cycle. A basic understanding of how the excitable gap evolves during arrhythmias with variable complexity would therefore be advantageous for improved ATP because that understanding could be used to insure pacing in the excitable gap. We hypothesize improved ATP efficacy with stimuli that: (i) occur early, near the onset of the arrhythmia, when the excitable gap is relatively large; and (ii) come from multiple sites, increasing the likelihood that excitable tissue can be captured. While improved rate sensing capabilities of ICDs can facilitate early ATP and the introduction of left-sided leads can facilitate multiple site ATP, there is a clear need to demonstrate improved efficacy before such approaches become generally accepted. We will: (1) develop a numerical approach to estimate the evolution of the excitable gap for arrhythmia substrates of increasing complexity. Excitable gap will be assessed in comprehensive simulations that will allow careful determination of the relationship between the MIs' geometric properties and arrhythmia formation in a setting where the arrhythmias will be undeniably repeatable; (2) develop an experimental approach to measure the evolution of the excitable gap for arrhythmia substrates of increasing complexity. Arrhythmia induction by programmed pacing will be performed in a rabbit freeze lesion model in which the endocardium and mid-myocardium are rapidly cryoablated and an anatomic obstacle is introduced epicardially (simple substrate), a 48h MI model with cryoablated endocardium (intermediate complexity), and a 48h MI model (realistic substrate). We will map the excitable gap in these arrhythmia substrates to document its evolution during ventricular tachycardia (VT); and (3) quantify early, late, single site and multiple site ATP efficacy in substrates of increasing complexity. Using the computer simulations and the animal experiments, such quantification will allow tests of our main hypotheses. This Industry-University Collaborative project will be performed by a research team made up of academic scientists from the University of Alabama at Birmingham and industry scientists from Guidant Corp., Cardiac Pacemakers, Inc.