PROJECT SUMMARY/ABSTRACT Hypoplastic left heart syndrome (HLHS) is characterized by incomplete development of the left heart and affects over 1,000 live born infants in the United States per year. Staged surgical treatment allows children with HLHS to survive and flourish, but the right ventricle (RV) remains the sole functioning ventricle and the tricuspid valve (TV) is their only functional atrioventricular valve. Tricuspid regurgitation is thus highly associated with heart failure and death. Thirty percent of HLHS patients require surgical intervention to treat tricuspid regurgitation. Despite incremental progress, understanding of the relationship between TV structure and tricuspid regurgitation in HLHS is limited, and results of surgical repair are suboptimal. 3D echocardiography and quantitative 3D echocardiography based analysis have dramatically improved adult mitral valve surgical planning and repair. However, despite preliminary work with basic tools suggesting relationships between the 3D structure of the TV and patient survival, and the unmet need for precise structural information to guide TV repair, there is no commercial or readily available method sufficiently adaptable to model and quantify the unique and highly variable TV anatomy in HLHS. As a result, the information in 3D echocardiography images remains latent, limiting understanding of the relationship between TV structure and tricuspid regurgitation, as well as the design of patient-specific repairs informed by 3D structural analysis. This proposal builds upon Dr. Jolley’s experience with modeling of atrioventricular valves in congenital heart disease and the development of flexible open-source modeling tools. The specific goals are to 1) investigate methods for quantifying TV structure from 3D echocardiography images using metric based tools as well as novel shape parameterization and statistical shape analysis; and 2) use these tools to identify TV structural correlates of TV dysfunction in 100 HLHS patients who have completed staged surgical repair. The methods developed will be incorporated into the open-source 3D Slicer imaging processing platform to catalyze future studies of congenital and adult structural heart disease, particularly those not possibly using current modalities. These studies are the first step toward individualized surgical repair of the TV informed by 3D structural analysis, and a detailed understanding of structural features of TV dysfunction in HLHS. The proposal leverages the existing infrastructure and extensive expertise at the Children’s Hospital of Philadelphia, Queen’s University, and Kitware Inc. Overall, this study represents a significant advance in the understanding of tricuspid valve disease in HLHS, as well as a flexible, and extensible armamentarium of tools for the future image-based investigation of congenital and adult structural heart disease.

Project Narrative Tricuspid regurgitation is associated with heart failure and death in children with Hypoplastic Left Heart Syndrome (HLHS). 3D echocardiography based quantification and modeling has significantly informed the understanding of the adult mitral valve dysfunction and repair, but similar progress in tricuspid valve repair in HLHS is prohibited by the lack of customizable modeling methods suitable for the tricuspid valve. The proposed study will create tricuspid valve computer modeling methods, including statistical shape analysis, and apply them to a large cohort of HLHS patients, allowing delineation of the relationship between 3D tricuspid valve structure and valve dysfunction(regurgitation) in HLHS, as well as the design of patient-specific repairs informed by 3D structural analysis.