The goal of this observational study is to understand the processes of what causes and accelerates the disease progress in aortic stenosis and following aortic valve replacement.

Participants will undergo transthoracic echocardiography every 6 months, with annual visits for state-of-the-art scanning techniques including positron-emission tomography combined with computed tomography or magnetic resonance imaging with radiotracers designed to look at disease processes including fibrosis, calcification, inflammation and thrombosis activity.

This will be an observational cohort study using existing and prospectively recruited cohorts for both cross-sectional and longitudinal comparison across the spectrum of aortic stenosis severity. For existing cohorts of patients who have previously undergone research assessments, we will invite them for repeated assessments.

Participants will be reviewed every 6 months in the Clinical Research Facility (CRF) over a 4-year period. They will undergo clinical assessment, blood sampling, transthoracic echocardiography and advanced imaging annually including CT angiography, magnetic resonance and positron emission tomography (PET).

Inclusion Criteria:

• Male or female aged >50 years
• Provision of informed consent prior to any study specific procedures
• Patients with bioprosthetic aortic valve replacements, including both surgically and transcatheter implanted valves
• Patients with severe aortic stenosis (peak velocity >4.0 m/s; previously recruited patients)
• Patients with moderate aortic stenosis (peak velocity 3.0-4.0 m/s; new prospectively recruited patients)
• Patients with mild aortic stenosis (peak velocity 2.5-2.9 m/s; new prospectively recruited patients)
• Patients with aortic sclerosis (tri-leaflet thickened aortic valve with no obstruction of ventricular outflow)
• Age and sex-matched healthy volunteers

Exclusion Criteria:

• Inability or unwilling to give informed consent.
• Those with an allergy to iodinated contrast
• Patients with impaired renal function (eGFR of <30 mL/min/1.73m2)
• Women who are pregnant or breastfeeding.
• Patients with known Rheumatic Heart Disease
• Patients with known Ochronosis
• Patients with known Familial Homozygous Hypercholesterolaemia

We will recruit up to 300 patients with aortic valve disease across the spectrum of disease severities from aortic sclerosis through to mild, moderate and severe aortic stenosis as defined by the European Society of Cardiology. We will also include those who have undergone bioprosthetic aortic valve replacement, and age and sex-matched control subjects with normal aortic valves.

End of Study to 15 years