Bicuspid Aortic Valve and Associated Aortic Disease - Patterns, Pathogenesis and Outcomes.

Abstract

Bicuspid aortic valve (BAV) is associated with serious complications involving the aortic valve and ascending aorta. There is substantial clinical heterogeneity, however, and predictive clinical markers and therapies are lacking. The work of this thesis therefore aimed to identify distinguishing clinical and pathological features of the various BAV phenotypes. Using the National Echo Database of Australia (NEDA), the echocardiographic characteristics of BAV patients were described, providing a comprehensive estimate of the clinical diversity of the condition. BAV patients with moderate or more aortic stenosis (AS) were then compared to those with AS and tricuspid aortic valves (TAV) within NEDA, revealing patients with BAV-AS are younger, have larger aortic dimensions and more mixed aortic valve disease, but with better overall survival compared to their TAV counterparts. Next, a retrospective series of adults who had undergone surgery for BAV was described, and sub-analysis comparing BAV morphotypes revealed associations between the number of valve raphes and the types of and ages at surgery. In view of the frequent co-occurrence of BAV with coarctation of the aorta (CoA), the incidence of BAV related surgery and late cardiovascular interventions were documented in patients with both conditions, compared to those with either BAV or CoA alone, respectively. These studies highlighted the complexities of the association between BAV and CoA, and identified yet another unique clinical profile in the subset of patients with both conditions. Finally, candidate long non-coding RNA expression was compared in aneurysmal BAV aortas and healthy aortic tissue, to elucidate potential epigenetic mechanisms of BAV aortopathy. Together, these studies identify important distinguishing clinical and pathological features relating to the heterogeneous sequalae of BAV, providing a foundation for individualized risk assessment and management of this clinically diverse group of patients.