Alterations in ascending aortic hemodynamics and aortic length correlate with sex-specific thoracic aortic aneurysm dilation and lifespan in a mouse model of severe Marfan syndrome

Thoracic aortic aneurysm (TAA) is a dilation of the aorta that may eventually dissect and/or rupture. It is associated with genetic disorders such as Marfan syndrome (MFS) and is a life-threatening cardiovascular condition if left untreated. Current clinical guidelines for TAA management are primarily based on maximum diameter thresholds that are often inadequate, particularly in MFS patients. Moreover, the diameter thresholds are not sex-specific, despite growing evidence that TAA outcomes in MFS are influenced by sex. The aim of this study was to identify non-invasive biomarkers for better management of TAA using male and female mice that are a genetic model of severe MFS and their littermate controls. Fluid-structure interaction (FSI) simulations were performed to assess aortic geometry, hemodynamics, and wall mechanical stresses during TAA progression (as measured by aortic dilation) and outcomes (as measured by mouse lifespan). Oscillatory shear index (OSI) correlated significantly with TAA progression in males, but not females, while time averaged wall shear stress (TAWSS) correlated significantly with TAA progression in females, but not males. Endothelial cell activation potential (ECAP), a metric that combines OSI and TAWSS, was significantly correlated with TAA progression in both sexes and had the strongest correlation with lifespan of all hemodynamic metrics. The geometric metric of aortic elongation ratio (AER) (i.e. length) also had strong correlations with TAA progression and lifespan in male and female mice. This study demonstrates that hemodynamic and geometric metrics hold promise as non-invasive biomarkers for personalized management of TAA in MFS.