**5. Aortic valve commissural fusion during LVAD support**

The AV leaflet tissue varies in thickness, being thicker at the free margin and annulus and thinner in the belly and coaptation areas. The leaflet tissue is composed of a layered structure of collagen, elastin, and proteoglycans. The textured fibrosa is a dense layer of circumferentially oriented collagen along the aortic face and bears most of the mechanical load [47]. The smooth ventricularis is an elastin layer adjacent to the ventricle, and the spongiosa is a central layer of loose connective tissue [47]. Naturally arising AV disease is preceded by tissue changes that occur over decades. Previous studies have shown that these are side-specific [48], manifesting as focal lesions that form preferentially from the aortic face, whereas the ventricular face is relatively disease-protected [49].

Post-transplant evaluation of LVAD-supported hearts has revealed the presence of extensive tissue remodeling of the AV, particularly commissural fusion, in 71–88% of LVAD patients [50, 51]. Aortic leaflet fusion creates adhesions between adjacent leaflets, preventing the complete opening of the valve [52, 53]. Increased fusion has been correlated with a longer duration of LVAD support [1, 6, 20] and with the development of AI [4, 51–53]. The aortic leaflets become more fibrotic and lose their elastic layer in the fusion areas, resulting in pathological remodeling, which progresses from the annulus towards the center of the valve (**Figure 8**). In contrast to naturally occurring AV disease, focal lesions arise from the ventricularis layer on the opposite side, as shown in **Figure 9** [17]. The hypothesis for this manifestation of valve dysregulation is that the high and continuous transvalvular pressure produces stretch and bending that is highest in the ventricular layer, activating a cellular process that results in extracellular matrix alterations. Fibrotic tissue often undergoes a consolidation and contraction stage, which preferentially affects the ventricular surface and may contribute to the improper coaptation that produces AI.
