Aortic stenosis (AS) occurs when one of the heart's valves narrows and blood cannot flow to the rest of the body normally. The disease can range from mild to severe and AS progression is unpredictable often occurring over many years. If severe aortic valve disease is left untreated this can lead to life-threatening problems, such as heart failure. Current treatments are limited to replacement of the faulty valve, ideally before the level of heart damage becomes too severe. However, predicting which patients will benefit from valve replacement and when to intervene is currently challenging due to lack of reliable clinical tools. In this project, we will follow patients before and after valve replacement, collecting information on how well their heart is functioning and their quality of life. Alongside this, we will comprehensively screen extracellular vesicles present in their blood to identify predictors of poor prognosis. Together this information will enable us to identify new markers associated with patient outcome, an important step towards the development of a much needed tool for AS disease management that can be used to identify the highest risk individuals for closer monitoring and timely intervention, improving patient outcomes.

The optimal iPSC progeny for cardiac repair is currently unknown and to date the majority of iPSC studies for cardiac repair have focused on generating fully differentiated iPSC-cardiomyocytes. While this approach has shown some promise, a major drawback is that only a single replacement cell type is delivered to the heart. Furthermore, iPSC-cardiomyocytes display an immature phenotype and their integration with the host myocardium often leads to arrhythmias.