Title: Bicuspid aorRtic vAlVe gEnetic research – tHoracic aortic 18F-fluoridE microcAlcification to monitoR aorTopathy (BRAVE-HEART substudy)
Funder: The Academy of Medical Sciences

Abstract: Introduction Around 50% of patients with BAV develop thoracic aortic aneurysm (TAA) resulting in a nine-fold increase in risk of aortic dissection. Development of TAA is caused by the abnormality of blood flow through BAV as well as pathophysiological processes within the aortic wall. Imaging of arterial wall using positron-emitting radiotracer sodium fluoride (NaF) can identify areas of micro-calcification caused by necrotic inflammation. NaF PET-CT has been shown to correlate with abdominal aortic aneurysm growth and risk of clinical events. A newly developed standardised approach to quantifying arterial micro-calcification allows for reproducible assessment of the aortic wall. Hypothesis: We hypothesise that BAV aortopathy is characterised by necrotic aortic media degeneration that can be visualised using NaF PET-CT. Study Group: The study group will consist of ten patients with thoracic aortic aneurysm (>45mm) and haemodynamically competent BAV (no more than moderate stenosis and/or regurgitation). The control group will comprisef age and sex matched patients with normal aortic dimensions and haemodynamically competent BAV. Study protocol: Participants of the study will undergo NaF PET-CT scan of thoracic aorta. The intensity of the signal will be assessed using aortic micro-calcification activity, as well as maximum and mean tissue to background ratios. The parameters will be compared between the study and control samples using Student t-test. Further work: Proving difference in the activity of necrotic inflammation within aortic media of patients with BAV aortopathy will allow for further use of NaF PET-CT to predict the risk of developing this complication at the preclinical level.

Lay abstract: The aortic valve is a structure that lets the blood out from the main pumping chamber of the heart to the aorta (the main blood vessel in the body). One in one hundred people is born with an abnormal aortic valve called bicuspid aortic valve, where the valve has two rather than three parts. Patients with bicuspid valves have increased risk of developing thoracic aortic aneurysm; a dilatation of the main artery in the chest. Rupture of a dilated aorta can lead to death. Doctors are not able to predict which of the patients with abnormal valves will develop dilatation of aorta and be at risk of rupture. Instead they organise repeated scans for all patients to check the change in size of the aorta. A special, newly developed dye can show very small abnormalities of the wall of aorta called micro-calcifications. We believe that detecting these abnormalities may be a way of predicting, which of the patients will develop problems in their aorta. We will ask 10 patients with dilated aortas and 5 patients with normal aortas to undergo a special scan with the new dye. If the results from our study are positive we could use these scans to predict which patients have increased risk of aneurysm and rupture.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR