Catheter Development for Epicardial Atrial Gene Painting

ABSTRACT Atrial fibrillationAFis the most common rhythm disturbance in the US and other developed countriesAF significantly affects the lives of the afflictedcausing symptoms that range from palpitations to fatigueweakness and activity intoleranceand substantially increasing the risks of strokecongestive heart failure and deathThe impact on public health is substantialwith more thanhospital admissions per year and $billion in healthcare costsAdding to the problems caused by AF is the lack of safe and effective therapies for this rhythm disorderPharmacotherapy for AF has a long history of poor efficacy and potentially lethal side effectsAblation strategies are making inroads in paroxysmal AFbut they are longdifficult procedures with less than optimal success rates and too frequent adverse eventsWe propose gene therapy as a new strategy to treat AFWe have published efficacy and safety data in a pig model of AF showing that interventions to prevent or reverse electrical and structural remodeling can eliminate the ability of the atria to fibrillateTo dateour atrial gene painting delivery method has required chest opening surgery which will ultimately limit clinical utilityHerewe propose development of a delivery catheter that will allow atrial gene painting from a percutaneous approach to the pericardial spaceTo develop this catheterwe propose the following specific aimsto verify performance of the gene painting catheter in bench top testingto confirm complete and specific atrial painting with the percutaneous catheter in acute animal studiesSuccessful completion of these aims will provide critical design and feasibility data that will move us toward our ultimate goal of curing AF with gene therapy Project Narrative Atrial fibrillationAFis the most common rhythm disturbance in the US and other developed countriesAF significantly affects the lives of the afflictedcausing symptoms that range from palpitations to fatigueweakness and activity intoleranceand substantially increasing the risks of strokecongestive heart failure and deathThe impact on public health is substantialwith more thanhospital admissions per year and $billion in added healthcare costsAdding to the problems caused by AF is the lack of safe and effective therapies for this rhythm disorderPharmacotherapy for AF has a long history of poor efficacy and potentially lethal side effectsNewer ablation strategies are making inroads in paroxysmal AFbut they are longdifficult procedures with less than optimal success rates and too frequent adverse eventsThis proposal focuses on developing gene therapy to treat and potentially cure AFWe have published efficacy and safety data showing that gene therapies can eliminate AFTo dateall of our data have been acquired using an atrial gene painting method that requires open chest surgeryIn this proposalwe will develop a catheter that will allow percutaneous access to the pericardium for atrial gene paintingThis advance will substantially increase clinical utility of the atrial gene painting method