BICUSPID AORTIC ANEURYSM PROGRESSION: INSIGHTS FROM HISTOLOGY

Abstract

Patients with bicuspid valves (BAV) are known to have higher instances of ascending aortic aneurysms and these complications occur at younger ages than the general trileaflet population (TAV). There is lack of consensus on the mechanical differences of ascending aortic aneurysms associated with BAV vs. TAV. The current theory surrounding heightened aneurysm risk for BAV patients suggests a genetic as well as a mechanical component related to long term elevated aortic wall shear stress (WSS) resulting in BAV specific tissue remodeling. This study aims to examine the correlations between histopathology and mechanical properties of aortic tissue with respect to the BAV and TAV populations, in order to establish a relationship between biomechanical alterations and disease progression. Tissue samples were collected from 58 patients undergoing elective ascending aortic replacement surgery. All samples were subjected to planar biaxial testing to assess mechanical properties such as tangent modulus (stiffness), and energy loss. A subset of samples (26) underwent to histopathologic analysis for elastin fragmentation and collagen alteration. The histopathology evaluation was completed by a pathology resident, in accordance with the consensus statement from Society for Cardiovascular Pathology. For statistical analysis, ANOVA or non-parametric equivalent test was implemented (depending on normality) with a significance threshold of 0.05. Tissues with higher energy loss, calculated as the percent differences between the loading and unloading curves from the mechanical tests, were seen to have more severe elastin fragmentation (p=0.047) and collagen alteration (p=0.046), reduced elastin (p=0.003) and proteoglycan content (0.0004). When comparing the TAV and BAV populations, it was seen that energy loss in BAV patients had a significant positive correlation with age (p=0.002, R2=0.32) while no significant correlation with an increase in age was found for TAV patients. No other mechanical property showed significant differences between the populations when age was considered. In ascending aortic aneurysm tissue, it was determined that energy loss was significantly correlated with histological properties and associated disease progression. Elastin fibres degradation related directly with energy loss as measured on biaxial testing. There was also a correlation between energy loss and age within the BAV population. These results could suggest that exposure to elevated WSS over time in BAV patients leads to elastin degeneration and accelerated energy loss in the tissue resulting in disease progression.View Large Image Figure ViewerDownload Hi-res image Download (PPT)