41. High Efficiency, Catheter-Based, Gene Transfer to the Large Animal Heart

Abstract

Congestive heart failure (HF) is a leading cause of hospitalization, disability and death. Despite significant advances in pharmacotherapy, HF remains a progressive disorder with an unacceptably high mortality rate. While the molecular and cellular basis of the impairment of myocardial contractility has been determined in detail, current beneficial therapies for heart failure only act indirectly, by interfering with neurohormonal control of the heart. Accordingly, considerable attention has recently been directed at the identification of appropriate targets for gene therapy. In particular, studies directed at the excitation-contraction pathway of the heart have identified genes (particularly phospholamban and SERCA) that can be manipulated to improve contractility. As such, translation into clinical practice now requires the development of safe, minimally invasive methods that provide homogeneous delivery to the heart.