The Role of Valvular Fibrosis in Patients with Aortic Stenosis

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In patients with narrowing of the aortic valve (aortic stenosis), the valve becomes thickened with scarring (fibrosis) and hardening (calcification) of the valve leaflets. Progression of the disease is also due to scarring (fibrosis) of the heart muscle. This condition is very common, affecting more than 10% of patients aged over 75 years. No medical therapy has been shown to slow progression of the disease or improve survival. The progressive decline in valve function means that many patients require aortic valve replacement, now the most common form of valve surgery in high income countries. We estimate this costs up to £1 billion per year for the NHS alone. In order to be able to develop effective treatments to slow down or stop progression of aortic stenosis, understanding the balance between fibrosis and calcification at varying stages of the disease will be crucial. In order to better understand this process, we will use currently available scanning techniques including echocardiography (ultrasound) and CT scans, as well as state-of-the-art scanning technology called Positron Emission Tomography (PET) using radiotracers (a colourless liquid injected into a vein in order to take the pictures). These radiotracers havebeen used in recent research studies investigating heart muscle and heart valve diseases. These tests will help us measure the severity of aortic stenosis and the amount of activity of fibrosis and calcification at different time points during the study.In this study we will collect up to 2000 CT scans, echocardiograms and linked anonymised clinical data from around the world, and analyse the images using new image analysis software which we believe will improve on the current analysis of CT scans done routinely in the NHS. We will also recruit 85 patients and 10 healthy volunteers and invite them for an echocardiogram, CT scan with contrast and state-of-the-art PET scan with a new radiotracer looking at scarring activity within the aortic valve, to see when the scarring activity is at its highest and how it relates to the severity of the disease. We will ask these participants to return 12 months later for repeat assessments, to see if the radiotracer can predict disease progression.Overall we hope this research can support widespread clinical adoption of an improved diagnostic tool to aid clinical decision making, and through looking at scarring activity identify a target biomarker which would be helpful for potential clinical trials.