Sophocleous, Froso

English

Background: Bicuspid aortic valve (BAV) is the most common congenital heart disease (1-2% prevalence) and can present with coarctation (CoA) in up to 85% of cases, resulting in aortic vasculopathy with high morbidity and mortality. This research aims to explore the multi-scale nature of BAV-aortopathy through imaging and molecular biomarkers of potential clinical impact in risk stratifying patients.Methods: A database of n=521 BAV patients including CMR scans was created. Analysis of CMR data focused on changes in aortic growth and hemodynamic assessment. Statistical shape modelling (SSM) was employed to characterise aortic and left ventricular (LV) morphological changes in BAV patients with/without CoA. A prospective study collecting blood/biopsies in BAV patients undergoing surgery was carried out, performing NGS, miRCURY LNA PCR assay, proteomic, histological and pathway analysis and studying the role of desmosine as circulating aortopathy biomarker. Results: CMR analysis revealed that presence of CoA and cusp fusion morphotype were associated with aortic root growth rate in BAV patients. A longitudinal SSM framework was successfully developed to extract information regarding differences in disease progression and shape variability in 3D. Three-dimensional morphological analysis in BAV patients with/without CoA revealed significant changes in LV sphericity associated to reduced LV strain irrespective of sex, age and valve stenosis or regurgitation. Validation of miRNA targets revealed five significantly dysregulated miRNAs between dilated versus non-dilated segments along the aortic circumference, in association with gene target pathways and CMR-derived hemodynamic changes. Also, histomorphometric analysis showed elastic fiber dysregulation. Conversely, desmosine quantification in the circulation was not associated with ascending aortic dilation. Conclusion: BAV and CoA have distinct disease phenotypes. Knowledge of aortic growth patterns and shape biomarkers like aortic gothicity and LV sphericity could inform risk stratification. Local aortic wall changes in BAV-aortopathy should be further studied considering the observed correspondence with elevated WSS. <br/

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Exploration of the multi-scale nature of bicuspid aortic valve aortopathy:New hemodynamic, molecular, and functional insights

https://research-information.bris.ac.uk/files/317047245/Final_Copy_2022_03_22_Sophocleous_F_PhD_Redacted.pdf

Exploration of the multi-scale nature of bicuspid aortic valve aortopathy:New hemodynamic, molecular, and functional insights

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