Donkey pericardium compares favorably with commercial xenopericardia used in the manufacture of transcatheter heart valves

Transcatheter aortic valve implantation (TAVI) has gained considerable acceptance in the past decade due to its lower risks than conventional open‐heart surgery. However, the deformation and delamination of the leaflets during the crimping procedure have raised questions about the durability and long‐term serviceability of the pericardium tissue from which the leaflets are made. The collagen architecture, wall thickness and mechanical properties of donkey pericardium were investigated to assess its suitability as an alternative material for the manufacture of heart valves. Coupons sampled from different locations of donkey pericardium were investigated. Bovine, equine, and porcine pericardium specimens served as controls. The donkey pericardium had a similar surface morphology to that of the control pericardia except for the wavy topology on both the fibrous and serous sides. The average thickness of donkey pericardium (ca. 120 µm) was significantly lower than that from bovine (375 µm) and equine (410 µm), but slightly higher than that from porcine (99 µm) specimens. The interlaced wavy collagen bundles in the pericardium were composed of collagen fibers about 100 nm in diameter. This unique structure ensures that the donkey pericardium has a comparable ultimate tensile strength (UTS) and a much higher failure strain than the commercial pericardia used for the manufacture of heart valves. The donkey pericardium has an organized wavy collagen bundle architecture similar to that of bovine pericardium and has a satisfactory UTS and high failure strain. The thin and strong donkey pericardium might be a good candidate valve leaflet material for TAVI.     

Native Bovine and Porcine Pericardia Respond to Load With Additive Recruitment of Collagen Fibers

Bovine and porcine pericardia are currently used for manufacturing prosthetic heart valves: their design has become an increasingly important area of investigation in parallel with progressively expanding indications for the transcutaneous approach to heart valves replacement. Before being cut and shaped, pericardial tissues are expected to be properly characterized. Actually, the mechanical assessment of these biomaterials lacks standardized protocols. In particular, the role of preconditioning for achieving a constant mechanical response of tissue samples is still controversial. In the present work, the mechanical response to uniaxial load of native bovine and porcine pericardia, with and without preconditioning was assessed; moreover, the mechanical behavior of pericardia was investigated and explained. It was demonstrated that: (i) pericardial tissue samples hold memory of the loading history but just within the extent of the deformation applied; (ii) the behavior of native bovine and porcine pericardia in response to load is explained by a mechanism based on the additive recruitment of collagen fibers; (iii) the current concept that plasticity is absent in pericardium has to be at least in part reconsidered.     

Structural Model for Viscoelastic Properties of Pericardial Bioprosthetic Valves

The benefit of bioprosthetic aortic valve over mechanical valve replacements is the release of thromboembolism and digression of long‐term anticoagulation treatment. The function of bioprostheses and their efficiency is known to depend on the mechanical properties of the leaflet tissue. So it is necessary to select a suitable tissue for the bioprosthesis. The purpose of the present study is to clarify the viscoelastic behavior of bovine, equine, and porcine pericardium. In this study, pericardiums were compared mechanically from the viscoelastic aspect. After fixation of the tissues in glutaraldehyde, first uniaxial tests with different extension rates in the fiber direction were performed. Then, the stress relaxation tests in the fiber direction were done on these pericardial tissues by exerting 20, 30,40, and 50% strains. After evaluation of viscoelastic linearity, the Prony series, quasilinear viscoelastic (QLV) and modified superposition theory were applied to the stress relaxation data. Finally, the parameters of these constitutive models were extracted for each pericardium tissue. All three tissues exhibited a decrease in relaxation rate with elevating strain, indicating the nonlinear viscoelastic behavior of these tissues. The three‐term Prony model was selected for describing the linear viscoelasticity. Among different models, the QLV model was best able to capture the relaxation behavior of the pericardium tissues. More stiffness of porcine pericardium was observed in comparison to the two other pericardium tissues. The relaxation percentage of porcine pericardium was less than the two others. It can be concluded that porcine pericardium behaves more as an elastic and less like a viscous tissue in comparison to the bovine and equine pericardium.     

Degenerative pathologic findings after long-term implantation of bovine pericardial bioprosthetic heart valves

Degeneration of bioprosthetic heart valves constitutes the most important limitation to their long-term durability and the factor that avoids a wider clinical use of these devices. We studied 26 degenerated bovine pericardial valves that belong to a series of 55 prostheses explanted for various reasons. Age of the patients at implantation of the valve and other factors predisposing to primary tissue failure did not seem to significantly influence the results obtained. Mean implantation time was longer for aortic than for mitral valves (p less than 0.05). Also, the mode of failure was different for mitral and aortic prostheses. Tearing of one or more leaflets without mineralization was more frequent (p less than 0.0025) among mitral than among aortic specimens. Coverage of the valve cusps by a macroscopically visible host sheath was more extensive on the outflow than on the inflow aspect (p less than 0.0015 aortic valves; p less than 0.015 mitral valves). On radiological examination the majority of valves had diffuse and severe mineralized lesions. Collagen degeneration was the most frequent histologic lesion to be found in both mineralized and calcium-free valves. Calcification was also frequent and appeared as mineral deposits that extended between different collagen planes. Scanning electron microscopy revealed the almost complete lack of "endothelium-like" cover on any of the valves and exposure of the underlying fibrous components of the pericardial tissue in areas subjected to abrasion. Transmission electron microscopy confirmed the collagen degeneration and disclosed electron-dense microparticles (probably mineralized) both in the extracellular space and within degenerated host connective tissue cells.     

The role of pannus in the longevity of an Ionescu-Shiley pericardial bioprosthesis

As the population ages, bioprosthetic heart valves are increasingly being used to replace diseased native valves. Bioprosthetic valve durability depends on patient age and other factors, but rarely exceeds 15 years. Explanted bioprosthetic valves commonly show tissue degeneration, tears, and calcification. Host tissue overgrowth (pannus), to the extent of interfering with their function, is another finding in bioprostheses that have been in place for long periods. We present a case in which a bovine pericardial valve was explanted after more than 20 years of implantation. The longevity of this pericardial valve may have been related to excessive pannus growth, which most likely protected the valve from earlier failure.     

On Stress Reduction in Bioprosthetic Heart Valve Leaflets by the Use of a Flexible Stent

It has been postulated that flexible stent posts can reduce tensile stress at the commissures of tissue heart valves by about 90% when compared with the same valve mounted on a rigid stent. We have used a detailed computer model to investigate the role of flexible stent posts in reducing stress in the leaflets of three types of bioprosthetic heart valves: the bovine pericardial and the high- and zero-pressure fixed porcine valves. The models use stress/strain data from biaxial experiments to characterize the tissue properties and are subjected to a back pressure of 120 mmHg. We found that strain was reduced linearly with stent post deflection and that this was a purely static process--it did not require the load to be applied impulsively. This finding was in close agreement with earlier experimental studies, which measured the same strain reduction whether the valve was loaded quasi-statically or at physiological rates. In addition, we found that for this mechanism to be effective the valve must have good coaptation at the center and the tissue should be stiff; in other cases, the advantages of strain reduction through the use of a flexible stent are considerably diminished.     

In vitro hemodynamic characteristics of tissue bioprostheses in the aortic position

The in vitro hemodynamic characteristics of a variety of old and new generation porcine and bovine pericardial bioprostheses were investigated in the aortic position under pulsatile flow conditions. The following valves were studied: Carpentier-Edwards porcine (Models 2625 and 2650), Carpentier-Edwards pericardial, Hancock porcine (Models 242, 250, and 410), Hancock pericardial, and Ionescu-Shiley (standard and low-profile) bioprostheses. The pressure drop results indicated that the old design valves had performance indices in the range of 0.30 to 0.42, whereas the new low-pressure fixed designs have performance indices of 0.50 to 0.70. Flow visualization and velocity and turbulent shear stress measurements, conducted with a two-dimensional laser Doppler anemometer system, indicated that all tissue valve designs created jet-type flow fields. The intensity of the jets and turbulence levels were less severe with the new designs. The old designs created higher peak jet velocities and higher levels of turbulent shear stresses. On the whole, pericardial bioprostheses have better in vitro hemodynamic characteristics than porcine bioprostheses. These observations should have applications regarding the clinical choice of bioprosthetic valves and have implications regarding further improvements in the preparation and design of bioprosthetic valves.     

Bioprosthetic heart valve rupture associated with trauma

Disruption of a bovine pericardial bioprosthetic aortic heart valve occurred in a motor vehicle accident, and was treated by valve replacement for progressive aortic insufficiency. Leaflet rupture was through areas of noninflammatory tissue degeneration, corresponding to regions of repeated mechanical stress and trauma that occur during the normal function of tissue valves. Patients with bioprosthetic heart valves may be predisposed to traumatic valve injury. Early diagnosis and replacement of these disrupted valves should be accomplished to avoid sudden, unpredictable heart failure.     

The behavior of pericardial versus porcine valve xenografts in the growing sheep model

The comparative long-term behavior of the pericardial versus the porcine bioprostheses is not yet known. The need for long follow-up times to answer this question makes the growing sheep model an attractive alternative, given its ability to induce early valve degeneration. Sixty-three sheep, 12 to 16 weeks old, were operated on and received 39 porcine (11 Xenomedica, 10 Carpentier-Edwards S, nine Hancock I standard, and nine Hancock I T6-treated) and 24 pericardial (14 Mitroflow and 10 Ionescu-Shiley low profile) prostheses of clinical quality in the tricuspid position. Of the 52 operative survivors (32 received porcine valves and 20 received pericardial bioprostheses), six animals (five pericardial and one porcine) were eliminated because of bioprosthetic infection. Late sudden death before the scheduled killing occurred significantly more often (p less than 0.0001) in the pericardial (8/15 or 53%) than in the porcine group (1/31 or 3%). Calcium content of the explanted valves was significantly correlated with time in the pericardial group and the Xenomedica porcine prostheses (p less than 0.05) but not in the Hancock I and Carpentier-Edwards S valves, where it was only marginally significant (0.1 greater than p greater than 0.05). Linear regression analysis of tissue calcium content showed a similar slope for the pericardial group and Xenomedica porcine valves, in comparison with the remaining porcine valves. Comparison between the two lines using covariance analysis demonstrated a statistically significant difference between them, which shows that the pericardial and Xenomedica porcine valves appear to reach higher levels of calcification in a shorter follow-up time than the Hancock I, standard and T6-treated, and the Carpentier-Edwards S valve in this animal model.     

A multi-step approach in anti-calcification of glutaraldehyde-preserved bovine pericardium

AIM: Bioprosthetic cardiovascular substitutes, manufactured from glutaraldehyde-preserved bovine or porcine tissues, are prone to calcification after implantation. The aim of the study was to evaluate the ultrastructure, material stability and calcification behaviour of glutaraldehyde-preserved bovine pericardium, treated with a multi-step anti-calcification process which addresses each of the major causes of calcification and tissue degeneration. METHODS: Bovine pericardium samples were divided into 2 groups. Group I (control) consisted of tissue fixed with 0.625% glutaraldehyde and Group II (study group) consisted of tissue fixed with 0.625% glutaraldehyde and exposed to a multi-step anti-calcification process. Ultrastructure was examined by scanning electron microscopy and material stability was assessed by mechanical testing, shrinkage temperature and enzymatic degradation. Calcification was assessed by histology (Von Kossa stain) and by atomic absorption spectrophotometry in the subcutaneous rat model. RESULTS: Bovine pericardium in the study group revealed less visible changes in the ultrastructure of the collagen matrix, improved material stability (P<0.05) and significantly (P<0.001) reduced calcification compared to control tissues (4.5+/-1.2 versus 136.03+/-11.39 ug/mg tissue). CONCLUSIONS: In conclusion, results demonstrate that the multi-step anticalcification process improved the material stability and reduced the calcification potential of bovine pericardial tissue. These improvements in the quality of the bovine pericardium should enhance the long-term durability of the tissue as a bioprosthetic substitute for cardiovascular application.     

Long-term results of bioprosthetic valves mounted on flexible stent]

From April, 1984 to April, 1989, 104 heart valve replacements were performed in 103 patients. The atrio-ventricular valves (97 mitral and 7 tricuspid valves) were replace by bioprosthetic valves mounted on the flexible stent made of Elgiloy. They included 91 porcine aortic valves and 13 bovine pericardial valves. Only 74 patients recovered and discharged from the hospital because of high operative mortality of re-replacement and double valve replacement (19 and 30 patients, respectively). These patients were followed-up for 8 to 68 months with a total follow-up period of 297 patient-years. Two patients developed cerebral embolism and two developed bacterial endocarditis. The incidence of the two complications was 0.67%/patient-year. No valve failure occurred. Long-term results of bioprosthetic heart valves mounted on flexible stent were better than those mounted on rigid stent.     

Hemodynamic and pathologic evaluation of a unileaflet pericardial bioprosthetic valve

This study investigated the in vivo hemodynamics and pathologic changes of a unileaflet pericardial bioprosthetic valve 3 to 5 months after implantation in juvenile sheep. Group 1 had 10 sheep with tricuspid valve replacement. Group 2 had nine sheep with mitral valve replacement. Group 3 served as a control with 10 sheep that had tricuspid valve replacement with a trileaflet porcine bioprosthesis. Hemodynamic performance was satisfactory in all three groups despite prominent pathologic changes, particularly in unileaflet valves. Intrinsic cuspal calcification was present in 66% of the unileaflet tricuspid, 88% unileaflet mitral, and 25% porcine tricuspid valves. Neither cuspal tearing nor perforations were found. However, cuspal stretching and redundancy of the mobile cusp was present in six tricuspid, seven mitral unileaflet valves, and no porcine valves. Gross pericardial redundancy correlated with the microscopic appearance of distorted and separated collagen bundles. These findings suggest that multiple modes of primary tissue failure may limit the durability of this unileaflet pericardial valve.     

Bovine pericardium versus porcine aortic valve: comparison of tissue biological properties as prosthetic valves

The choice of a bioprosthetic valve substitute remains controversial with the major concern being primary tissue failure after implantation. We compared biological properties of the two most frequently used bioprosthetic valve materials, bovine pericardium and porcine aortic valve, before and 90 days after subcutaneous implantation in rats. Before implantation, tissue collagen and water content were measured in nine pieces of bovine pericardium and porcine valves, each fixed in 0.625% glutaraldehyde; calcium, tissue collagen, and water content were measured in another nine pieces of the same tissues after 90 days' implantation. Bovine pericardium had higher collagen content than that of porcine valve (hydroxyproline, 7.98 +/- 0.05* vs. 4.56 +/- 0.02 micrograms/mg, dry weight) but lesser water content (72.16 +/- 3.22%* vs. 87.36 +/- 1.62%) before implantation (*p < 0.001, mean +/- SD, t test); after implantation, bovine pericardium still maintained higher collagen content (hydroxyproline, 4.89 +/- 0.04* vs. 2.61 +/- 0.06 micrograms/mg, dry weight) but contained the same amount of water (60.24 +/- 5.08% vs. 61.43 +/- 9.00%) and calcium (214.43 +/- 34.34 vs. 199.33 +/- 53.44 micrograms/mg, dry weight) (*p < 0.001, mean +/- SD, t test). We conclude that bovine pericardium has superior intrinsic biological properties for prosthetic valve manufacture. With proper integration of properties and design it will in some applications be superior to the porcine aortic valve.     

Comparative analysis of long-term results with porcine-aortic, bovine pericardial and tilting disc valves

The three series with the first-generation valve prostheses were reviewed for long-term clinical evaluation in isolated aortic and mitral valve replacement. Hancock porcine xenograft was implanted in 71 patients from 1977 to 1979, ionescu-Shiley pericardial xenograft (standard model) in 271 patients from 1979 to 1983, and Bjork-Shiley tilting disc valve in 194 from 1978 to 1986. In aortic position, no any significant difference among three valve types could be demonstrated in the actuarial survival and freedom from thromboembolism and valve infection, while the actuarial freedom from valve dysfunction in lonescu-Shiley valve was significantly lower than that in other two valves. Bj?rk-Shiley valve in mitral position showed satisfactory clinical performance in terms of valve-related complications and survival in comparison with two types of bioprosthetic valves. In our conclusion at present time, Bj?rk-Shiley valve is suitable for the first choice of both aortic and mitral valve prostheses. In case of valve replacement with a bioprosthesis, however, porcine aortic valve is a better choice for aortic, and bovine pericardial valve likely for mitral replacement.     

Synergistic effect of released aspirin/heparin for preventing bovine pericardial calcification

Calcification is a frequent cause of the clinical failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated bovine pericardium (GATBP). Aspirin, a potent antiplatelet drug, and heparin, an anticoagulant, are commonly used for postimplant complications such as thrombosis and thromboembolism. Aspirin and heparin were embedded in chitosan/polyethylene vinylacetate co-matrix to develop a prolonged release form. The effect of these drugs towards the bioprosthetic calcification was investigated by in vitro and in vivo models. In vitro and in vivo evaluation suggest that the released aspirin/heparin from the co-matrix had a synergistic effect in inhibiting GATBP calcification. In vivo subcutaneous co-implantation was performed with PEG-20,000 grafted bovine pericardium (PEG-GABP), aspirin, and heparin. Biochemical, histological, and scanning electron microscopic evaluation of retrieved samples demonstrated a significant reduction in calcium deposition and alkaline phosphatase activity on PEG-GABP compared to GATBP. It seems that the aspirin/heparin combination synergistically inhibits the pericardial calcification in addition to their antithrombotic function.     

Quantification and Analysis of Leaflet Flutter on Biological Prosthetic Cardiac Valves

The use of porcine or bovine pericardium biological cardiac valves has as its main disadvantage a relatively short lifespan, with failures due to calcification and fatigue. Increasing these valves’ durability constitutes a great challenge. An understudied phenomenon is the effect of flutter, an oscillation of the leaflets that can cause regurgitation and accelerate calcification and fatigue. As a starting point to study how to reduce or prevent these oscillations, a method was developed to quantify the flutter frequencies occurring at the point of the valve's full opening. On a test bench that simulates the heart flow, the cusp behaviors of eight biological valves were filmed with a high speed camera at 2000 frames per second at different flow rates and motion capture software obtained the frequencies and amplitudes of the vibrations of each leaflet. Oscillations in the range of 200 Hz with average amplitudes of 0.4 mm were found; larger nominal diameter valves obtained lower values, and bovine pericardial valves had superior performance compared to porcine valves. A dimensionless analysis was performed to find a relationship between the geometric and mechanical properties of the valves with the critical speed of the onset of fluttering. This relationship inspired a method to predict whether flutter will occur in the bioprosthesis. This method is a new tool for the consideration of maximizing the life of prosthetic valves.     

Age-related complications and optimal choice of artificial heart valves in elderly patients

The use of bioprosthetic heart valves in elderly patients is presently advocated by many since implanting mechanical valves are considered to result in unacceptable rates of thromboembolism and bleeding. However the somewhat limited durability of bioprostheses has to be acknowledged since a group of elderly patients will eventually require a reoperation due to tissue failure. We have evaluated our policy to implant mechanical heart valve prostheses even in elderly patients based on the conception that we believe that anticoagulation in this group of patients can be handled with a low rate of complications.     

内皮化环氧交联牛心包材料动物体内抗钙化的研究

目的研究生物材料内皮化延缓钙化的效果，从材料学上改进生物瓣性能，以提高其耐久性。方法将环氧交联的牛心包材料体外内皮化后同时进行犬股动脉间位移植和腹部皮下包埋，与单纯戊二醛处理者和单纯环氧处理者进行钙化程度对比。结果钙含量测试结果以内皮化环氧交联材料皮下包埋最低，未内皮化材料中以环氧处理者钙含量较低。结论环氧交联牛心包材料可实现体外快速内皮化，生物材料的内皮化“活化”有赖于表面全部被自体存活内皮细胞覆盖才能实现，完全的内皮化确有抗钙化作用，用两种动物模型研究生物材料抗钙化和内皮化时各有优缺点     

Durability of Prosthetic Heart Valves

Accelerated fatigue testing of clinical heart valves has been performed at cyclic rates of 33 to 35 cycles per second at 37° using water for non-biological valves and glutaraldehyde solutions for tissue valves. Flows were in the physiological range, and the pressure difference across each valve during closure was 100 ± 25 mm Hg. The results showed that major fatigue occurred for the Starr-Edwards 2320 at 150 million cycles, the Hufnagel trileaflet at 124 million cycles, the Björk-Shiley Delrin disc at 140, the Björk-Shiley Pyrolite disc at 973, the Beall 103 at 60, the Hancock porcine at 62, the Carpentier-Edwards porcine at 34, and the Ionescu-Shiley porcine pericardial prosthesis at 65 million cycles. The Lillehei-Kaster was removed after 762 million cycles without discernible wear.Three facts emerged from the testing data: (1) the component worn in vitro wears in vivo; (2) the sites of in vitro fatigue on the component are identical to clinical specimens; and (3) those valves that have high durability in vitro have given similar performance in patients. The in vitro and clinical data for tissue valves do not correlate. The possible reasons for the discrepancy are discussed, and a note of caution is made regarding realistic expectations of clinical durability of tissue valves.     

Evaluation of kangaroo aortic valved conduits in a juvenile sheep model: preliminary findings

BACKGROUND: Biological heart valve substitutes, manufactured from either porcine or bovine tissue, have been in use for more than 30 years. Despite low thrombogenicity and excellent performance, bioprosthetic heart valves tend to degenerate and calcify early in young patients because of patient and valve related factors. The aim of this study was to examine the calcification behavior of glutaraldehyde-preserved kangaroo heart valves in a juvenile sheep model. METHODS: Porcine (n = 10) and kangaroo (n = 10) valved conduits were implanted in the descending aortic position of juvenile sheep and retrieved after 6, 8, and 12 months. Retrieved valved conduits were examined for morphological changes and calcification of the valve tissue, using Von Kossa's stain technique and atomic absorption spectrophotometry. RESULTS: Structural valve deterioration, characterized by increased stiffness and severe calcification, occurred in 100% of the porcine conduits within 4 months. Kangaroo valve leaflets were significantly (p < 0.001) less calcified at 6 months (3.39+/-1.80 microg/mg), 8 months (5.86+/-4.57 microg/mg), and at 12 months (14.38+/-6.72 microg/mg), compared to porcine valves at 3 months (176.45+/-42.88 microg/mg ) and at 4 months (154.67+/-52.67 microg/mg ). Porcine aortic wall tissue was more calcified (118.24+/-42.86 microg/mg) than kangaroo aortic wall tissue (79.55+/-26.40 microg/mg). CONCLUSIONS: Kangaroo heart valves calcify less than porcine heart valves. These findings suggest that a different donor valve tissue has a lower calcification potential probably due to a difference in the morphological ultrastructure. This could result in improved long-term durability of kangaroo heart valves.