Mechanical
In the past heart valve dysfunction was assumed as a degenerative and passive deposition of calcium crystals. However, it has been established that biological prosthetic valve dysfunction is a very dynamic and progressive process, including noncalcific deterioration with important mechanical and environmental contributions.
As part of the fabrication model of bioprosthesis, the structure is fixed in a static geometry. The collagenous network is locked into a single configuration of one phase of the cardiac cycle, inhibiting the normal extracellular matrix readjustments of the valve during the cardiac cycle (39, 40). The collagen crimps and corrugations are preloaded in a defined configuration similar to that of a closed valve (55). Thereby, functional and normal cardiac cycle stresses have to be absorbed by the noncompliant and fixed collagen fibers (55). Having a fixed configuration will produce damage in pericardial valves during closure (in porcine valves mostly during opening but also during closing), inducing repetitive accumulation of mechanical stress with increased tissue fatigue (39, 40). Leaflets should display anisotropic proprieties, especially regarding strain in the circumferential and radial directions. It has been established that non-physiological strain leads to pathologic processes by deregulation of inflammation and remodeling, leading to calcification (18).
The pressure used during fixation is also important for the mechanical changes induced in the tissues, as it determines the stress-strain relation of the tissue strips (58). Low pressures have better mechanical proprieties and most of the bioprosthesis used nowadays, such as Edwards Lifesciences® Magna Perimount and LivaNova® Perceval Plus, are manufactured with low pressure fixation (59). However, studies have shown that as low as 2-4 mmHg are sufficient to induce significant changes in collagen compliance (55), so zero-pressure methods have been studied. Although in theory zero-pressure would offer a new approach to reduce biological prosthetic dysfunction, the technique has not achieved clinically significant results (60).
Although Glut-related dysfunction is more associated with calcification, it also induces mechanical alterations to the valve tissue. It has been shown that glut alters the stress-strain curves of strips of bovine and porcine valve tissues (58). During the fixation process there is also a considerable loss and incomplete stabilization of the GAGs (61), which are responsible for the viscoelasticity and accommodation of the cuspal layers. GAGs have an essential role in absorbing compressive loads, modulating shear stress and avoiding tissue buckling, and they may be important in mechanical abnormalities that lead to valve dysfunction.
The chemical and mechanical changes are possible synergetic, since changes in tissue configuration can induce stress and fatigue (especially in flexion lines of the cusps) that can expose and disrupt collagen, initiating the calcification process. On the other hand, calcifications can also induce structural changes and stiffness that will eventually lead to more mechanical changes and damage.