Project Summary Valvular heart disease is an important health problem afflicting over 2.5% of the US population and, while surgical repair of native tissue remains the gold standard, the reduced risk of catheter-based interventions has provided the capability to intervene earlier in the disease process as well as in the sickest patients while avoiding the risks of cardiopulmonary bypass. The outcomes of transcatheter procedures are not, however, consistently superior to alternative treatments. For example, those patients receiving transcatheter edge-to- edge repair of mitral regurgitation benefit from a significantly shorter hospital stay but require follow-up surgery for recurrent mitral regurgitation substantially more often than those undergoing initial surgical repair. As a second example, when transcatheter tricuspid valve repair devices are successfully deployed, they substantially reduce the risk of death compared to medical therapy, but device implantation is successful less than 3/4 of the time. Optimal patient care should combine the benefits of beating-heart interventions with the effectiveness and patient-specific tailoring of surgical repair. We hypothesize that the fundamental limitation is that catheter-based delivery greatly reduces the interventionalist's capability to visualize and to intuitively control device delivery. To address these issues, in the prior funding period, we created the first cardioscopic imaging systems for performing valve repair inside the blood-filled beating heart. We demonstrated that cardioscopy can improve local visualization to such a degree that certain procedures can be accomplished in minutes rather than hours. We also created a joystick-controlled robotic catheter that provided an intuitive control interface and a standardized platform for performing valve repairs. These results were achieved using transapical access to the left ventricle of the heart. For broad adoption, we need to further develop this technology to enable its percutaneous delivery via the femoral vein. Percutaneous delivery presents significant new challenges since the cardioscopes must be compact during vascular navigation and then enlarge for valvular imaging. Furthermore, to enable broad adoption of transcatheter valve repairs and to make those repairs as effective as surgical repairs, the robotic catheter should not just make a single repair technique easy to perform, but instead should allow a clinician to easily perform a sequence of complementary repairs as is now done in surgery. In Aim 1, we will overcome the challenges of percutaneous cardioscope delivery by creating balloon-based cardioscope designs and demonstrating this technology for the specific repair of mitral chordae implantation through ex vivo and in vivo testing. In Aim 2, we will design a modular robotic catheter platform to create the capability for a single delivery system to be used to perform two important complementary mitral valve repairs, chordae imp...