Funding outcome

Most research on heart valves tend to focus on the mitral valve, the valve that guards the left pumping chamber of the heart, which tends to be more affected in heart disease acquired as adults. Whereas diseases of the tricuspid valve (TV), the valve that guards the right pumping chamber of the heart, tend to occur more commonly in newborns and children born with heart disease. It is estimated that currently there are 257 000 Canadians that were born with heart disease. Leakage and failure of the TV directly impacts on survival and quality of life of children and adults born with various heart defects that either have an abnormally formed TV or TV working in a different environment than originally intended. Perhaps the most vulnerable group of children to develop TV failure is children with Hypoplastic left heart syndrome (HLHS). In HLHS, the left pumping chamber of the heart did not form correctly. To survive, children undergo three major open-heart surgeries in the first five years of their lives to redirect blood flow to utilize the right pumping chamber to pump to the body instead of the left heart pump. As a result, the TV in HLHS faces prolonged periods of high pressure and high volume stress. These surgeries are not curative and three children out of 10 with HLHS will die by 10 years of age. One contributing factor is that 1 out of 4 children develop significant leakage of the TV. Unfortunately, treatment options for TV failure are limited. The lack of new therapies is largely due to our limited understanding of why the TV fails. Recently, researchers found that the mitral valve have an intrinsic ability to change and adapt to new heart environments. Failure of adequate adaptation results in valve leakage. Currently, no such data exist for the TV. Our research team would like to study the TV's adaptive ability at the structural level and its changes on the cellular level. We aim to also identify signals in the body that tells the TV to grow while adapting to changes in the heart environment. In children it is also important to study if the signals that control the rapid TV growth are present as a baby and as the child matures. Experiments to study the TV in such detail are not ethical or possible in children, hence we have developed a piglet model that simulates HLHS physiology to allow for an indepth study of TV adaptive changes. We anticipate that our research findings will lay the knowledge foundation for the research community and will spur further research. Each piece of new knowledge has the potential to then spark new innovation in medical or surgical treatment for TV failure. Although our project is focused on the most vulnerable of our children with congenital heart disease (HLHS), the knowledge gained is widely transferrable to numerous other childhood and adult heart diseases affected by TV failure