Degeneration of Biological Heart Valve Prosthesis: Review of Pathophysiological Mechanisms, Current Interventions and Future Perspectives

The aim of this review is to review the main pathophysiological mechanisms of bioprosthesis’ degeneration, the current interventions, either conventional or transcatheter therapies, and the future perspectives of bioengineering tissues in the degeneration of the bioprosthesis. Bioprosthesis are primarily used in valve replacements, both because they eliminate the need for oral anticoagulation and because of the specific profile of patients with valvular heart disease (elderly with higher risks of bleeding due to oral anticoagulation with warfarin, mandatory on mechanical heart valve prosthesis). However, bioprosthesis have limited durability and degeneration occurs due to the following factors: the bioprosthetic's heterologous tissue shows throughout time deposition of crystals of calcium phosphate, favored by the remnants of dead cells and fibrous structures of the tissue, resulting in dystrophic calcification; mechanical factors, since the assembly and design of the biorpothesis favors greater shear stress on the heterologous pericardial leaflets, compared to the native valve; and also to factors related to the patient, such as hypertension, left ventricular hypertrophy and patient-prosthesis mismatch (which enhances shear stress), and age (under 60 years of age), rheumatic diseases, excessive calcium excretion and up-regulation of angiotensin-coverting enzyme activity (which enhances formation of crystals of calcium phosphate). In this context, conventional reoperation for degenerated bioprosthesis is indicated; still, reoperation, especially in older patients with comorbidities, can add significant surgical risk. Transcatheter therapy (valve-in-valve and sequential valve-in-valve) emerges as recent, expanding and a viable alternative, in which a transcatheter valve is implanted within a degenerated bioprosthesis. Additionally, biological tissue engineering may enable longer-lasting bioprosthesis in the future. Tissue derived from autologous cells or pluripotent cells with decellularized xenogenic tissues may represent greater durability for bioprostheses, but require further researches and does not solve the main problem: the inexorable process of bioprothesis’ degeneration.