An ascending thoracic aortic aneurysm (ATAA) is a life-threatening cardiovascular consequence of vessel dilatation that portends adverse events and death. From a clinical perspective, ATAA should not be treated as an isolated disease, and surgery is often carried out in the presence of AS, aortic insufficiency or a calcified valve leaflet. Aortic stenosis (AS) is common in ATAAs and leads to both vessel rigidity and left ventricular (LV) impairment. In this study, lumped-parameter modeling and computational analysis were used to assess the change in the wall shear stress (WSS) and intramural wall stress of patient-specific ATAA models with different degrees of AS (i.e., mild to severe). The ATAAs of four patients were reconstructed from imaging data and AS was simulated virtually using the lumped-based CircAdapt tool using clinical and echocardiographic data. Results show that LV work derived from pressure-volume loops increased with the severity of AS. Post-stenotic hemodynamic and structural variables markedly increased with AS severity, with WSS showing a 10-fold increase for the most severe AS model as compared to the baseline model with a well-functioning aortic valve. Most importantly, the increase in WSS and aortic wall stress was associated with pronounced values of valvulo-arterial impedance as an indicator of LV dysfunction. This study provides novel insights into progression of AS in patients with ATAAs at high risk of adverse events, and the potential value of valvulo-arterial impedance to predict changes in hemodynamic and structural parameters with the severity of AS. �� 2020