Atrial fibrillation is the most common sustained arrhythmia; however, its mechanism is not well understood. Several conditions such as valvular disease, heart failure, and hypertension predispose to atrial fibrillation. Identifying the electrophysiological substrate in these clinical conditions would yield insight into the mechanism of atrial fibrillation and aid in developing strategies to prevent or cure it. Rheumatic mitral stenosis is associated with high prevalence of atrial fibrillation. While atrial stretch itself may be adequate to explain the occurrence of atrial fibrillation in this population, it is not known if the disease process would remodel the atria so as to increase its propensity. Chapters 2 and 3 present the results of the studies evaluating the substrate for atrial fibrillation in both the left and right atria in rheumatic mitral stenosis. These studies have demonstrated extensive conduction abnormalities both regional and site specific associated with low voltage area and scar. Despite the prolonged atrial refractoriness, the propensity for atrial fibrillation was increased; lending support to the theory that structural remodelling associated with conduction abnormalities plays a greater role in the substrate predisposing to atrial fibrillation. Chapters 4 and 5 present the results of the studies evaluating the immediate effects of chronic atrial stretch reversal on the atrial electrical remodelling. These studies demonstrated that immediately after percutaneous mitral commissurotomy there was decrease in P wave duration, improvement in site specific conduction delay and conduction velocity associated with increase in the voltage. However, there was no change in atrial refractoriness. Chapter 6 studies the substrate long-term after reduction of stretch. There was further increase in conduction velocity and voltage associated with decrease in atrial refractoriness and conduction delay across the crista terminalis. These observations suggest that strategies aimed at reducing atrial stretch in different disease conditions would potentially decrease the burden or prevent atrial fibrillation. There is mounting evidence of the effect of stretch on the atria; however, the effect of stretch on the triggers of atrial fibrillation has not been evaluated before. Chapter 7 and 8 present the results of the study examining the effect of acute and chronic stretch on human pulmonary veins. Simultaneous pacing of the right ventricle and pulmonary vein induced acute stretch. The effect of chronic stretch was evaluated in patients with mitral stenosis. The atrial refractoriness was abbreviated in acute stretch while it was prolonged in the chronic form. Nevertheless, both resulted in marked pulmonary vein conduction abnormalities that were pronounced with chronic stretch and extra-stimuli. Additionally, structural remodelling was seen with chronic stretch. These abnormalities implicate stretch in the milieu for re-entry and pulmonary vein arrhythmogenesis in conditions predisposed to atrial fibrillation. In summary, this thesis has evaluated the effects of stretch on the substrate and triggers of atrial fibrillation. It provides evidence for the importance of structural changes and the associated abnormalities in conduction in predisposing to atrial fibrillation. These observations may be important in the development of tools to treat, cure and prevent atrial fibrillation. / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2008
| Identifer | oai:union.ndltd.org:ADTP/285350 |
| Date | January 2008 |
| Creators | John, Bobby |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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