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Calcific aortic stenosis (CAS) is the most common valvular heart disease and is associated with aortopathy and ventricular dysfunction. Hemodynamic alterations due CAS could affect the aorta lining (endothelium), that is in direct contact with the blood, triggering adverse biological responses that may possibly cause aortic dilation and dissection. Also, CAS could impose excessive ventricular load leading to ventricular wall thickening, thus putting an individual at a higher risk of heart attack or stroke. These pathophysiological effects of CAS are highly dependent on the degree of calcification. However, the impact of CAS development on aorta flow and left ventricular workload remains largely unknown. Hence the objective of this study is to measure experimentally the effect of CAS on aorta hemodynamics using particle image velocimetry; and left ventricular function in terms of left ventricular work, at different stages of calcification. This study will provide insights on aorta flow abnormalities and left ventricular overload, due CAS, which can be linked to aortopathy and heart failure.

Blood vessels experience complex hemodynamics marked by three-dimensionality and pulsatility. Arterial endothelial cells interact with the characteristics of the fluid wall shear stress (WSS) to maintain homeostasis or promote disease states. In particular, the bicuspid aortic valve (BAV), a congenital heart valve anatomy consisting of two leaflets instead of three, is associated with aortic complications presumably promoted by hemodynamic abnormalities. While devices have been used to test this hypothesis, their capabilities are limited to the generation of time-varying WSS magnitude in one direction. However, the increased flow helicity generated by BAVs in the aorta is expected to result in increased WSS multidirectionality. Therefore, the objectives of this thesis were to characterize the magnitude and directionality of the regional WSS in a BAV aorta, and to design a bioreactor capable of replicating these characteristics in vitro. This device will provide new insights into the mechanobiology of BAV aortopathy and other flow-mediated cardiovascular diseases.