Funding outcome

The tricuspid valve (TV) is an important valve for the right heart pumping chamber. Leakage and failure of the TV directly impacts on survival and quality of life of children born with various heart defects. The most vulnerable group of children for TV failure are those born with Hypoplastic left heart syndrome (HLHS). In HLHS, the left heart pumping chamber did not form properly and to survive, these children undergo a series of surgeries to allow the right heart to pump to the body instead. As a result, the TV in HLHS must work in a high-pressure and high-volume stress environment for which it was not designed to do. One in four children with HLHS, the TV fails causing them to die young. Unfortunately, current surgical repairs for TV failure are limited and the repair does not last. Although we recognize that newer therapy is required, it hasn't occurred in part because we do not fully understand why some TV is able to adapt whereas others fail. Previously we have used a piglet model that mimics the high stress environment, similar to those in HLHS TV, we found that the TV was able to compensate to stretching of the valve by rapidly growing it valve leaflets keep the TV from leaking. However, this has also led to changes in the stretchiness of the TV leaflets. All these finding is very exciting as this is the first time anyone has shown this in an experiment. We are proposing a follow-up project to study in detail the TV changes, and whether it is a response just high-pressure or high-volume stress or both. We want to identify chemical signals controls the TV response to these stressors, from which we might eventually be able to use to make new therapies.