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Type: Theses
Title: Thrombogenesis in substrates of atrial fibrillation
Author: Schultz, Carlee Deanne
Issue Date: 2014
School/Discipline: School of Medicine
Abstract: Background: Atrial Fibrillation (AF) is the most common atrial arrhythmia affecting Australia and the world, with patients with AF known to be at a 5times higher risk of stroke than that of the normal population. The substrates of AF are also known to significantly impact of this risk of stroke. Mitral stenosis (MS) is one of the leading causes of valvular AF in the developing world. Enlargement of the LA is one of the most common structural changes that occurs in MS and is known to lead to fibrosis and oxidative stress. These alterations can also cause atrial electrical remodelling leading to the development of AF. Patients with MS have been shown to have an increase in thrombogenic properties which include platelet reactivity, inflammation and endothelial dysfunction. The precise mechanisms which underlie this phenomenon of atrial thrombus formation in AF are still unknown, furthermore it is also unknown if the substrate (cause) of AF influences the thromboembolic profile in AF patients. This thesis aims to evaluate the peripheral and atrial thrombogenic profile of both AF and the major substrate MS and their differing disease states alter the thrombus potential. Methods: A total of 166 patients were collected for this study, 55 patients undergoing a radiofrequency ablation as a curative procedure for paroxysmal AF, at the Royal Adelaide Hospital, Adelaide, 59 patients with mitral stenosis (MS)undergoing a balloon valvuloplasty at the Christian Medical Centre in Vellore, India, and 52 with aged matched control subjects, diagnosed with left sided accessory pathway supraventricular tachycardia (SVT) undergoing a routine elective electrophysiological study. Blood samples were collected from the peripheral, RA and LA circulation, during each of these procedures, for further analysis through flow cytometry, platelet aggregation and ELISA tests. Echocardiographic studies were used for atrial structure measurements. Results: We found that within the AF population there is increase in thrombogenic markers within the heart compared to the peripheral circulation. More interestingly when comparing the MS and AF populations each of the different factors involved in thrombogenesis is altered differently, with AF having an increase in platelet reactivity and endothelial function (ADMA and ET-1) and inflammation through VCAM-1 and ICAM-1. However of inflammation through MPO, CD40L and IL-6 and structural remodelling (MMP-9 and TIMP-1) were more pronounced within the MS population. Conclusion: This study has shown that AF and the valvular AF substrate mitral stenosis (MS) have two distinctly different mechanisms leading to atrial thrombus formation. This shows that MS as a substrate for valvular AF impacts on atrial thrombus formation through remodelling and inflammation whereas non valvular AF affects endothelial function and tissue inflammation. This illustrates that the pathophysiology of each of the diseases states is different when comparing it to the normal haemostatic properties of the heart within a control (SVT) population to determine if these factors are in fact altered from the norm.
Advisor: Willoughby, Scott Richard
Brooks, Anthony Graham
John, Bobby
Gasean, Anand
Sanders, Prash
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2014
Keywords: thrombogenesis
atrial fibrillation
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at:
Appears in Collections:Research Theses

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