What is the issue for NSW?
Aortic stenosis, the abnormal narrowing of the aortic valve of the heart, is currently the most prevalent heart disease relating to the valves of the heart. Current estimates are that around 100,000 Australians live with severe aortic stenosis, with NSW having the highest number of cases in Australia. The incidence of severe aortic stenosis is expected to dramatically increase with the ageing population. In the long term, the constricted valve causes chronic pressure overload of the cardiac chambers causing them to increase in size. This ultimately leads to cardiac dysfunction and high mortality rates.
Transcatheter aortic valve implantation has revolutionised the treatment of this disease as it is a minimally invasive procedure to replace a diseased or malfunctioning valve. However, given limited understanding of the reverse remodelling process after valve replacement and short lifespans of current valvular devices, it is difficult to predict who will benefit from valve replacement, and the optimal timing of this intervention.
Consequently, there is a need for new routes to limit the cardiac chambers increasing in size, innovative ways to predict when to surgically intervene and who will benefit most from intervention.
What does the research aim to do and how?
Using pre-clinical models that mimic aortic stenosis and advanced cardiac imaging techniques, the research plans to uncover new mechanisms of cardiac remodelling caused by increased biomechanical forces, unveiling new therapeutic targets. The project aims to identify baseline factors that can predict positive outcomes after aortic valve replacement and ultimately enhance or aid clinical decision making. This includes coupling pre-clinical models with serum proteomics to identify biomarkers that can help understand the molecular mechanisms of pressure overload induced remodelling caused by aortic stenosis.
The top three key measures/indicators being used to assess the research outcomes are:
1) identify novel mechanisms of pressure-overload induced remodelling revealing therapeutic routes to prevent adverse remodelling,
2) identify baseline factors that predict reverse remodelling in a pre-clinical model of pressure-overload and
3) identify novel biomarkers of left ventricular strain that can be verified in ongoing clinical studies, ultimately as a mechanism to predict positive responses to valve replacement