Subclinical markers of disease burden of severe aortic stenosis in patients with type 2 Diabetes Mellitus and the Metabolic Syndrome

Background: Aortic valve stenosis (AS) is the most common valvular disease in the developed world with a global prevalence of around 2-9% in people over the age of 65. Patients with both Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) have been reported to have worse outcomes following aortic valve replacement surgery (AVR). Mechanisms leading to aortic valve calcification and left ventricular changes in AS patients are distinct from coronary calcification. This study aimed to identify preoperative and postoperative differences in the ventricular function of patients with severe AS undergoing AVR, and to assess the preoperative levels of selected biomarkers of lipid metabolism in three different subsets of people from a separate cohort. Methods: This thesis is comprised of two separate study cohorts. The first study involved a retrospective cohort of 367 people who underwent isolated aortic valve replacement at a secondary care cardiothoracic surgery unit in Wessex. They were subdivided into three groups; people without T2DM or MetS, people with MetS, and people with diabetes. Alongside baseline demographic and biochemical data, preoperative transthoracic parameters were collated. This was compared with 1-year postoperative transthoracic echocardiography. Changes in ventricular dimensions and mass were interrogated. The second study involved a separate, prospective cohort of forty-two participants, who were also subdivided into the same three groupings as the first study. The same demographic, biochemical and echocardiographic data was once again collated. In addition to this, serum samples were collected to test for six biomarkers of lipid metabolism. Results: The first study noted that patients with MetS and T2DM had more severe left ventricular remodelling preoperatively. Postoperatively however, these same participants experienced less reverse remodelling (a beneficial sequelae of aortic valve replacement) than patients without T2DM or MetS. The second study, which focused on adipokine and lipoprotein profiles, demonstrated that people with T2DM and MetS had increased levels of resistin, lipoprotein-A and apolipoprotein-B1 compared to the control group. The control group, on the other hand, had increased levels of adiponectin and leptin compared to the other two groups. Although variations in these markers were distinct, no direct correlation with preoperative echocardiographic findings was demonstrated. Conclusion: This thesis concludes that in essence, MetS and T2DM patients with similar presentations of severe AS have significantly worse subclinical myocardial changes. The observed differences in the levels of adiponectin, leptin, resistin, lipoprotein-A and apolipoprotein-B1 adds to the current knowledge base and ongoing understanding of these biomarkers in specific cohorts of people with MetS, T2DM and symptomatic AS

Feasibility of a novel, synthetic, self-assembling peptide for suture-line haemostasis in cardiac surgery

Abstract Backgroud To assess the feasibility and efficacy of PuraStat®, a novel haemostatic agent, in achieving suture line haemostasis in a wide range of cardiac surgical procedures and surgery of the thoracic aorta. Methods A prospective, non-randomised study was conducted at our institution. Operative data on fifty consecutive patients undergoing cardiac surgery where PuraStat® was utilised in cases of intraoperative suture line bleeding was prospectively collected. Questionnaires encompassing multiple aspects of the ease of use and efficacy of PuraStat® were completed by ten surgeons (five consultants and five senior registrars) and analysed to gauge the performance of the product. Results No major adverse cardiac events were reported in this cohort. Complications such as atrial fibrillation, pacemaker requirement and pleural effusions were comparable to the national average. Mean blood product use of packed red cells, platelets, fresh-frozen plasma (FFP) and cryoprecipitate was below the national average. There was one incidence of re-exploration, however this was due to pericardial constriction rather than bleeding. Analysis of questionnaire responses revealed that surgeons consistently rated PuraStat® highly (between a score of 7 and 10 in the various subcategories). The transparent nature or PuraStat® allowed unobscured visualisation of suture sites and possessed excellent qualities in terms of adherence to site of application. The application of PuraStat® did not interfere with the use of other haemostatic agents or manipulation of the suture site by the surgeon. Conclusion PuraStat® is an easy-to-use and effective haemostatic agent in a wide range of cardiac and aortic surgical procedures

Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System

Background: Type 2 diabetes mellitus (T2DM) has been established as an important independent risk factor for aortic stenosis. T2DM patients present with a higher degree of valve calcification and left ventricular dysfunction compared to patients without diabetes. This may be due to an increase in incidence and severity of 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 aortic stenosis.Objective: The aim of this study is to prove that an approach using a combination of serum biomarkers and the echocardiographic parameter global longitudinal strain (GLS) can be used to establish baseline status of fibrocalcific aortic valve disease, predict rate of progression, and quantitatively assess any regression of these processes following aortic valve replacement in patients with T2DM.Methods: 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 GLS, can be compared with other objective investigations of calcification and fibrosis with the aim of developing a quick, noninvasive one-stop assessment of aortic stenosis in patients with T2DM. The serum biomarkers BNP (B-type natriuretic peptide), Gal-3 (Galectin-3), GDF-15 (growth differentiation factor-15), sST2 (soluble suppression of tumorigenicity 2), OPG (osteoprotegerin), and microRNA 19b and 21 will be sampled from patients undergoing aortic valve replacement (with and without T2DM), patients with T2DM but 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 analyzed for levels of the same biomarkers as in the serum samples. All patients will be followed up with in 3 months and 12 months for repeat blood sampling, echocardiography, and CT and MRI imaging to assess disease progression or regression. The results of tissue analysis and CT and MRI scanning will be used to validate the findings of the serum biomarkers and echocardiographic assessment.Results: Using all of the information gathered throughout the study will yield a ranking scale for use in the clinic, which will provide each patient with a fibrocalcific profile. This can then be used to recommend an optimal time for intervention.Conclusion: 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, which will provide an accurate risk assessment in patients with aortic stenosis at first contact