Introduction
Aortic stenosis is the most common primary valve disease with indication to surgery in Europe, with an increased prevalence in the last few decades due to ageing population (1). In fact, more than 400.000 surgical aortic valve replacements (SAVR) are performed yearly worldwide (2), contributing to a significant economic and social health issue (3). It is expected that in 2050 there will be over 850.000 aortic valve replacements, worldwide (4).
There are two major types of prosthetic heart valves: mechanical or biological. Randomized clinical trials (5–7) comparing both types of prosthesis found similar generic outcomes. However, from the published studies we can draw two important conclusions: mechanical prostheses are associated with higher rates of bleeding due to anticoagulation, while bioprosthesis are associated with higher rates of reintervention due to bioprosthesis dysfunction.
Across the world, in the past decades, there has been a considerable increase in the use of bioprosthesis over mechanical valves (8–10), with a major shift from mechanical to bioprosthetic valves in the last 20 years.. In proportion, bioprosthesis increased from 40% in the 90s to more than 80% of all implanted prosthetic heart valves nowadays (11). This exponential increase in bioprosthetic valve implantation is likely related to an elderly patient population undergoing SAVR, a perceived improvement in valve durability, and a desire to avoid short and long-term anticoagulation (8).
Despite the continuous efforts in the past few years, still there is no ”ideal” bioprosthesis. The implementation of a prosthetic heart valve always initiates several pathophysiological processes, which can lead to structural valve degeneration (SVD) and progressive clinical deterioration. Signs and symptoms of SVD depend on the type of valve, its location and the nature of the complication. There are several types of prosthetic dysfunction, ranging from structural/non-structural deterioration of the valve, thrombosis, and endocarditis (12).
For the past 50 years, glutaraldehyde (Glut) has been the most used chemical product and is currently widely used to preserve and stabilize biological prosthetic tissues. Glut is responsible for chemical cross-linking, improving the material’s stability and reducing antigenicity. Bioprosthetic heart valves show several histological differences from native heart valves, being unable to remodel and repair. The manufacture process of prostheses is also crucial, especially regarding fixed configuration of the pericardial valves and the pressure used in tissue fixation.
Recently, research has brought new ideas about the inflammatory and immunological role in the dysfunction of the bioprosthesis, describing the immunological rejection and the inflammatory state also as a cause of the failure of the bioprosthesis.
In terms of durability, new generations bioprosthesis may have promising results (11). The reported durability is excellent, with rates of reintervention due to failure of the bioprosthesis of 2% to 10% in 10 years, 10% to 20% in 15 years and 40% in 20 years (13, 14). However, these findings do not show the true rates of deterioration of the bioprosthesis. Some studies have identified higher rates of structural deterioration, including hemodynamic changes, in up to 10% and 30% patients 5 and 10 years after surgery (11).
The significant increase in the use of aortic bioprosthesis will inevitably lead to a proportionally rising number of patients diagnosed with prosthesis dysfunction in the next decade. This should stimulate cardiac surgery centers and medical prosthesis manufacturers to understand all underlying mechanisms. This review aims to review the most debated topics on the pathophysiology of aortic bioprosthesis dysfunction, exploring the biological grounds on the chemical, mechanical and inflammatory contribution to better understand the most recent innovations in this field.