JMIR Publications

ABSTRACT

Background Type 2 Diabetes has been established as an important independent risk factor for aortic stenosis with patients presenting with a high degree of valve calcification and left ventricular dysfunction compared to patients without diabetes due to myocardial fibrosis. Currently there is no reliable method of determining the optimal timing of intervention for a patient with asymptomatic aortic stenosis or predicting when a patient will become symptomatic. Research into serum biomarkers to predict subclinical onset and track progression of aortic stenosis is hampered by the multimodal nature of the pathological processes ultimately responsible for of aortic stenosis. Presentation of the hypothesis Validated serum biomarkers for the separate processes of calcification, inflammation, oxidative stress and fibrosis can be used to quantify onset and rate of progression of aortic stenosis. This, in combination with the echocardiographic parameter global longitudinal strain, can be compared with other objective investigations of calcification and fibrosis with the aim of developing a quick, non-invasive ‘one-stop’ assessment of aortic stenosis in patient with type 2 diabetes. Testing the hypothesis The serum biomarkers BNP, Gal-3, GDF-15, sST2, OPG and microRNA 19b and 21 will be samples from patients undergoing aortic valve replacement (with and without type 2 diabetes), patients with type 2 diabetes without aortic valve disease and healthy volunteers. These patients will also undergo Computed Tomography (CT) scans for calcium scoring, Magnetic Resonance Imaging (MRI) to quantify myocardial fibrosis, and myocardial strain imaging with speckle-tracking echocardiography. Samples of calcified native aortic valve and a biopsy of ventricular myocardium will be examined histologically to determine the quantity and distribution of calcification and fibrosis, and the secretome of these tissue samples will also be analysed for levels of the same biomarkers as in the serum samples. All patients will be followed up in three months and twelve months for repeat blood sampling, echocardiography, and CT and MRI imaging to assess disease progression or regression. The results of tissue analysis, CT and MRI scanning will be used to validate the findings of the serum biomarkers and echocardiographic assessment. Implications of the hypothesis A reliable, validated set of serum biomarkers combined with an inexpensive bedside echocardiographic examination can now form the basis of a ‘one-stop’ outpatient-based assessment service in providing an accurate risk assessment in patients with aortic stenosis at first contact.