**4. Aortic valve biomechanics during LVAD support**

Human heart valves change their shapes and size during the cardiac cycle in response to their surrounding hemodynamics [43]. This mechanism helps facilitate the leaflet function and reduces the effect of flexural stress on the valve surface [43]. An average heart valve opens and closes more than three billion times in a lifetime and experiences various stress and strain types (e.g., tensile, compressive, stretching, and bending) [43]. The AV is a thin tissue structure with three leaflets attached to the aortic root wall in a u-shaped pattern in a roughly symmetric arrangement. Each leaflet forms a pocket with the corresponding sinus, which plays a vital role in the fluid mechanics of opening and closing [44]. During diastolic filling, the valve is closed, and the leaflets stretch in opposition to the high transvalvular pressure [17]. When the AV opens during systole, the leaflets relax as blood flows over the ventricular surface and into the aorta. Some of the flow is captured as vortices that form behind the valve leaflets, ensuring smooth closure. The unidirectional laminar blood flow produces shear stress of up to 80 dynes/cm2 on the ventricular endothelial surface [45]. In contrast, the aortic surface has a small magnitude oscillatory flow in the range of ±10 dyn/cm2 shear stress [46].

During LVAD support, the pressure difference across the AV remains high for a longer fraction of the cardiac cycle, producing a decrease in flow that corresponds to a reduction in valve opening. The valve opening area decreases with LVAD support, with more of the valve commissures coapted over the entire cardiac cycle. LVAD support also reduces the duration of AV opening, which increases the time that the leaflet tissue experiences maximum pressure loading. Simultaneously, the shear across the ventricular surface of the valve leaflet is reduced and eventually eliminated when the AV remains closed.

**Figure 6.**

*Flow field images during early and mid-diastole illustrate the vortex ring generated by the regurgitant jet that collides with the mitral valve inflow.*

At the level of the valve tissue and cells, the impact of LVAD hemodynamics produces a sudden change in the mechanical signals that can initiate a sequence of remodeling that results in AI. Measurements of valve tissue stretch during LVAD support show that the aortic leaflets are stiffer in the circumferential direction and

#### **Figure 7.**

*A. Aortic valve opening area and duration with different cardiac function and LVAD support, B. Aortic valve opening area, C. Surface marker movement was used to measure stretch in the circumferential (hoop) and radial directions D. Stretch is highest for series flow when the aortic valve remains closed.*

more compliant in the radial direction. This behavior corresponds to the alignment of collagen fibers with the circumferential direction, termed the anisotropy of the tissue. The peak stretch increases and extends for a longer duration as the normal flow pattern is compared to LVAD parallel and series conditions (**Figure 7**). Thus, the valve tissue experiences large and continuous tensile loading and significantly reduced ventricular shear during LVAD support.
