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.