Improved Myocardial Mechanics as Assessed by MRI Generated Pressure-Volume Loops Following AAV6-Mediated βARKct Gene Delivery.

James J. Pilla¹, Jabaris D. Swain, Michael G. Katz, Anthony Fargnoli, Marina Sumaroka, Catherine Tomasulo, Mihail Petrov, Rose Nolen-Walston, JanLee Jensen, Hansell Stedman, Walter J. Koch², Joseph Rabinowitz², Charles R. Bridges

Genetic modulation of ventricular function and remodeling may offer a novel therapeutic strategy for patients with acute ischemic left ventricular (LV) dysfunction. We hypothesize that ARKct gene therapy will amplify the cardiac response to a beta-adrenergic agonist resulting in improved function and efficiency as measured by MRI. MRI generated PV loops demonstrated that ARKct expression improves global LV systolic performance and efficiency relative to controls. These results in a normal ovine subject, using a novel, cardiac-specific gene delivery platform (MCARDTM) are predictive of long term efficacy in a clinically relevant large animal HF model.