Analytic Study On Explanted Liotta Bioprostheses From Patients: The Adaptation In Human Environment

For many years, artificial heart valves have been largely and successfully accepted for the replacement of pathological heart valves in humans. Bioprosthetic heart valves have good hemodynamics, and usually have good thrombo-resistance in comparison with mechanical heart valves. Moreover, they can be inserted in small diameter delivery conduits and implanted using percutaneous valve replacement techniques.The development of percutaneous valves requires a particular understanding of the in vivo fate of bioprostheses as these valves are inserted through small diameter delivery conduits. In order to improve the bioprosthetic heart valves and develop suitable heart valves for the percutaneous valve replacement, it is very important to study systematically the bioprosthetic heart valves explanted from patients.This study analysed sixty-two explanted Liotta Low Profile (LLP) porcine bioprostheses from patients by morphology, histology and mineralogy methods to highlight the issues related to their biocompatibility, biofunctionality and biodurability, through these aspects to know the adaptation of porcine valve in human environment. Among these 62 valves, some valves were implanted in patients by percutaneous valve replacement. A special attention was paid to ventricularis and to the fibrosa, as well as to the spongiosa. We tried to know their changes as time went on. The analysis of this series explanted devices that were obtained after a spectrum of duration provides abstract knowledge and experiment data for progress durability of bioprosthesis, also offers good suggestion of optimizations of the process and storage.The etiology of the reoperations was as follows: hemodynamic, thrombosis and endocarditis . The primary failure modes leading to reoperation were as follows: in the short-term: blood infiltration, fibrin build-up, thrombosis; in the mid-term: endocarditis and hemodynamic insufficiency; and in the long-term: mineralization and tears, causing hemodynamic incompetence.Objective: Sixty-two explanted Liotta porcine bioprostheses were revisited to highlight the issues related to their biocompatibility, biofunctionality and biodurability by morphology, histology and mineralogy, through these aspects to know their adaptation in human environment and to know the failure mechanisms as first percutaneous valve replacement and the adaptation for this technology.Methods: Sixty-two LLP porcine valves from patients were harvested after a few hours to more than nine years of implantation: 10 short- term (i.e., t < 1 year) 19 mid-term (i.e., 1< t < 5 years) and 33 long-term (i.e., t > 5 years). Valves were examined macroscopically for gross morphology, and photographed with photomacroscopy equipment. The histological investigations involved light microscopy, scanning electron microscopy and transmission electrons microscopy. Mineralogy( involved X-ray and NMR) tests the mineral deposits of valves.Results:①Short term( t≤1 year):1) Morphology: The 10 valves mostly preserved their hemodynamic biofunctionality. Tears and perforations were present on 20% valves. The valves, which were implanted by percutaneous valve replacement, were damaged, had some tears or were not in natural position. The valves were kept on the shelf for a long time, there were tissue degradation and calcification after short implantation.2) Histology: Both surfaces of ventricularis and fibrosa were almost totally devoid of endothelium exposing fibrillous structures. A few scattered modified endothelial cells were still visible on the fibrosa. Platelets were frequently anchored in the invaginations of the surfaces entrapped in fibrin networks. After two months of implantation, a pannus developed slowly from the textile suturing ring on both sides with a fragile layer of endothelial like-cells on the fibrosa side that extended slowly. However, most of the surface was free from mural thrombi. In the very few valves, thrombi were anchored within the cusps or at the commissures. Progressively, the flow surface became covered with a proteins biofilm , about 10 um thick, both surfaces remained smooth. In the absence or weak of biofilm, small numbers of cells mainly macrophage as well as droplets were adhering to the flow surface of the ventricularis. The biofilm was becoming progressively more fibrillar as time went on.3) Mineralogy: Few valves showed early endophitic or exophitic mineralization in one leaflet.②Mid-term (1 < t≤5 years):1) Morphology: The biofunctionality of the explanted devices at mid-term was seriously impaired in 70% bioprostheses due to tears and mineralizations. The exophitic mineralization was because of thrombi and damage, the endophitic mineralization was on stress area. Few valves were splited at the commissures.2) Histology: The pannus developed on both surfaces, at the same time developing from outside to inside the leaflets. The pannus expanded more and more and developed irregularly until appositional area of leaflets. The endothelium covered fibrosa over the commissures. In the absence of biofilm, small numbers of cells mainly monocytes and lymphocytes as well as droplets were adhering to the flow surface of the ventricularis. Where the biofilm was on the flow surface and well developed, it incorporated number of monocytes and lymphocytes. The structure of fibrosa was generally well preserved. As time went, the macrophages, monocytes and lymphocytes were progressively penetrated from outside to inside the leaflets leading to the formation of void spaces and initiating some nidus of mineralization. The structure of the flow surfaces were changed to lead exophitic mineralization, specially on the fibrosa.3) Mineralogy: The hydroxyapatite was present in all valves.③Long-term implantation (t > 5 years)1) Morphology: Endocarditis and thrombosis were much less frequent. Tears and perforations were present frequent on the long-term as almost all the devices were involved (97%). The biofunctionality of the explanted devices was seriously impaired. The leaflets became stiff due to the presence of calcification. On the fibrosa, endophitic mineralization became exophitic mineralization. Fibrinous vegetations covered the leaflets, the motility of the leaflets became progressively reduced.2) Histology: The fragile layers of endothelial cells were observed on the fibrosa of few valves, so the structure of these valves were preserved better than others. The biofilm was frequently fragmented. The cells and blood debris penetrated within the spongiosa, the disorganization of the spongiosa was rapidly evidenced. The cells, the fibers and the amorphous extracellular matrix formed a homogeneous mass with tissue necrosis were progressing. The mineralization proved to be less and less endophitic: as they progressed, ruptures and crevices permitted the mineralization to become exophitic.3)Mineralogy: The calcifications were present in all the valves more or less.Conclusion:①Biocompatibility: After the implantation of LLP, the capacity to become adapted to the blood and tissue environment without any thrombotic event related to flowing blood/valve leaflets interactions nor exacerbated tissue reaction at the site of anchorage of the bioprostheses. But we have to improve LLP from following aspects: 1) As the time goes after implantation, the flow surfaces become not smooth. If endothelial cells can develop on the flow surfaces, the surfaces of leaflets will become smooth and ideal. 2) To have more fibrous tissue for bioprostheses. The polyester of the sewing ring shall become encapsulated with fibrous tissue to prevent any endoleak. 3) Try to find a solution to prevent the pannus from extending over the leaflet.②Biofunctionality: The valves shall be able to open and close under normal physiological conditions i.e. 130 mm Hg, 75 cycles/min ratio systole/diastole 45% without any leak detectable on the atrium side. The bioprosthesis must maintain its capacity over the years. Any pathological degeneration impairs the biofunctionality of the device. Stiffening of the leaflets can eventually be tolerated but holes and tears causing tears greatly handicap the biofunctionality. Anyway, preventing the pathological degeneration for bioprostheses is a big problem to solve.③Biodurability: An ideal valve substitute shall have a biodurability overpassing the life expectancy of the patient. As the pathological damages to the bioprostheses develop, the biodurability is considerably reduced. During harvesting of LLP bioprosthesis in the process, the endothelium is destroyed as well as the basement membrane. The fibrillous structures are exposed, blood debris and blood cells can penetrate rapidly, so that leads to the formation of void spaces and initiating some nidus of mineralization, the biodurability is considerably reduced. The endothelial cells from host cover the flow surfaces of bioprostheses is a solution, but this way is limited by a lot of factors. From our study, we discovered that the biofilm can increase the biocompatibility of bioprosthesis, at the same time, it can be a protective barrier to prevent the penetrating of blood debris and blood cells. Therefore, we suggest that before implantation we cover the bioprostheses with an artificial biofilm, the artificial biofilm can be a protective barrier to prevent the penetrating of blood debris and blood cells and calcification to improve the biodurability.④The valves, which kept on the shelf for a long time, were degraded in a short period after implantation. Therefore, we suggest that the shelf-life of bioprostheses should not exceed 2 years.⑤Liotta bioprostheses have unique design and flexible stents, they are low profile valve, so shear strains reduce internal fibre strains and protect the leaflets against fatigue, Liotta valve is more like a natural heart valve. However, the Liotta bioprosthesis did not provide any clear cut advantage over standard porcine bioprosthesis and its long-term biostability appeared affected by its low profile design. ⑥We examined the morphology of the valves, which were implanted in the patients through percutaneous valve replacement, and discovered that these valves had tears and damage, some leaflets were not in the natural position. The biofunctionality was seriously impaired. Therefore, at the present the percutaneous valve replacement affects the biofunctionality of bioprostheses, it is very necessary to improve this technology and to decrease the damage at implantation. Otherwise, the bioprostheses do not adapt to percutaneous valve replacement.