Xenograft Valves Research Articles

Differences between heart valve allografts and xenografts in the incidence and initiation of dystrophic calcification

Following surgical removal because of primary tissue failure, 30 antibiotic-sterilized human aortic valve allografts and 27 glutaraldehyde-treated porcine aortic valve xenografts were examined for macroscopic and microscopic evidence of dystrophic calcification. These grafts had been mounted on stents and used for from 34 to 166 months to replace diseased mitral valves. After explantation the grafts were carefully examined then prepared for light microscopy, for transmission electron microscopy and for energy dispersive X-ray microanalysis. Gross calcification occurred significantly (p = 0.002) more frequently in xenografts (89%), and was more extensive than in allografts (53%). Calcification usually appeared as nodular excrescences on the cusps, although occasionally it formed plates within them. This reduced tissue pliability and was usually associated with either valvular stenosis or regurgitation. The calcified deposits contained calcium and phosphate in ratios approaching those of hydroxyapatite. In xenograft valves the smallest discrete deposits of calcification were spherical and usually associated with membranous debris of porcine donor fibroblasts, but allografts did not contain donor cell remnants and early calcification was linearly arranged along collagen fibres.

Calcification and cusp rupture in heart valve allografts and xenografts

Calcification and cusp rupture in heart valve allografts and xenografts

Ten-year experience with pericardial xenograft valves

Five hundred fifty-three pericardial xenografts were inserted in 520 patients during a 9-year period at the Fu Wai Hospital in Beijing. The bovine pericardial xenograft was modeled after a similar type of prosthesis manufactured by Shiley Inc. (Irvine, Calif.). The late mortality rate in this series was only 1.8% per annum and the actuarial survival rate was 73.0% +/- 12% at 10 years. There was a very acceptable low incidence of thromboembolism of 0.41% per annum without the need for permanent anticoagulation. This is similar to the clinical reports with other tissue valves. The main question is the durability of the tissue prosthesis or, in other words, the freedom from valve-related clinical complications. In this series, the expected actuarial valve durability rate was 75.0% +/- 8.8% at 10 years. Whether this will continue to hold up over the next follow-up period is unclear. Certainly other tissue prostheses have shown significant degeneration rates beginning after the sixth year that have risen progressively thereafter. In any case, given the relatively low probability of thromboembolic phenomenon without anticoagulation, the trade-off of a prosthesis that may not be as durable as the mechanical ones is certainly acceptable.

A Bayes model for automatic detection and quantification of bioprosthetic valve degeneration

The performance of a pattern recognition algorithm using a Bayes model for detecting bioprosthetic valve degeneration was evaluated using diagnostic features extracted from the sound spectra of 57 normal and 47 degenerated porcine xenograft valves. The data base was subdivided into training sets and test sets composed of various combinations of diagnostic features. The training sets were used to select the feature subset that minimized the classification error. The performance of the Bayes' classifier was evaluated with the test set by computing the percentage of correct classifications, false positives and false negatives. The test set was then exchanged with the training set and the classifier re-trained and tested. Mean values of correct classifications, false negatives and false positives were then computed. Results show that a mean correct classification rate of 74% was obtained for the automatic classification of normal and degenerated bioprostheses. The percentage of false positives was 13% while that of false negatives was 40%.

Intermediate-term Fate of Cryopreserved Allograft and Xenograft Valved Conduits

Actuarial freedom from reoperation for obstruction in 147 patients receiving cryopreserved or fresh allograft valved conduits between a ventricle and the pulmonary arteries was 94% at 3.5 years. The 2 patients undergoing reoperation were 6 and 36 months of age at the time of insertion of the allograft. Among 24 patients in whom cardiac catheterization was performed on indication late postoperatively, 5 had gradients of more than 40 mm Hg across the conduit. For comparison, among 78 patients receiving xenograft or irradiated allograft valved conduits, the percentages of freedom from conduit reoperation at 3.5, 5, 10, and 15 years were 99%, 95%, 59%, and 11%, respectively. The diameters of the allograft and xenograft valves inserted varied directly with the age and size of the patients, but in patients 3 to 5 years of age, allografts with a diameter of at least 21 mm could usually be used.

Pericardial heterograft valves: An assessment of leaflet stresses and their implications for heart valve design

Bovine pericardium, stabilized with glutaraldehyde, is used widely in the construction of heart valve substitutes, but the design and construction of valve substitutes from this material are empirically based. Collagenous tissue can support tension, but experimental evidence indicates that flexure-induced compressive stresses can lead to fatigue failure. This study uses experimental results obtained from cyclic uniaxial load tests to predict the type and magnitude of operational stresses which occur in pericardial heterograft leaflets. Both Young's modulus and Poisson's ratio varied with uniaxial loading in pericardium, chemically modified free of tension. Leaflet stresses were analysed by using effective incremental representations of these parameters. In leaflets with unrestricted rotation at the point of attachment to the stent, the mid-plane tensions always exceeded the bending stresses, and no zones of leaflet compression were predicted. In contrast, with totally restricted leaflet rotation induced by clamping (possibly between a male and female frame) the bending stresses were greater than the mid-plane tensions at the hinge line and significant compressive stresses were predicted at this site. If elastic boundary conditions were introduced at the stent (possibly by wrapping the stent in pericardium) then the compressive stresses were reduced as the degree of elasticity was increased. Glutaraldehyde fixation of the pericardium under load produced a stiffer material; higher compressive stresses at the stent and significant increases in total stress were predicted for this tissue. The application of elevated pressure loading also increased the compressive and total stresses in the leaflet. Finally, it was shown that bicuspid leaflets were likely to experience higher stresses than tricuspid leaflets. This simple stress analysis should help valve designers of pericardial heterografts to identify those conditions which lead to tissue compression, high total stress, and ultimately material fatigue.

Evaluation of long-term results of homograft and heterograft valves in extracardiac conduits

Between 1971 and 1982, 249 patients received right heart extracardiac conduits. The 173 patients who survived 30 days were reviewed retrospectively; 72 had antibiotic-sterilized aortic homografts, 97 had xenografts of various types, and four had valveless tubes. Reoperation for conduit obstruction was required as early as 13 months after the original operation, but actuarial analysis showed no differences in overall performance of homograft and heterograft conduit groups with respect to late death or survival free of conduit obstruction. More important risk factors for late death or the need for reoperation were the severity of the underlying cardiac lesions and the influence of early postoperative complications. When analyzed statistically, the performance of conduits bearing homografts was disappointing, influenced sometimes by complications in the Dacron extension tubes. Repairs dispensing with conduits entirely should be evaluated.

Valve Replacement in Children

The performance of the St. Jude prosthetic valve is reviewed in 81 patients aged 3 to 15 years. All 66 mitral (2 re-replacements), 8 aortic and 9 double valve replacements between February 1979 and August 1984 are included. The early mortality was 3.7% and actuarial analysis shows a 90% event free survival up to 5 years. Anticoagulant therapy was used in most patients, but comparison between groups receiving warfarin or aspirin or no therapy reveals no differences in the complication rate. The valve is well suited for use in children since the early degeneration seen with heterograft valves does not occur, and anticoagulation is not essential.

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.

Frequency analysis of Ionescu-Shiley prosthetic closing sounds in patients with normally functioning prostheses.

To document the frequency distribution of lonescu-Shiley (IS) bovine pericardial xenograft valve sounds, a study was conducted on three groups of clinically stable subjects with valves implanted for less than 5 years. These groups consisted of 61 subjects with aortic IS valves, 28 subjects with mitral IS valves and 18 subjects with mitral Hancock porcine xenograft valves. Multiple comparisons with a Scheffe with mitral Hancock porcine xenograft valves. Multiple comparisons with a Scheffe test at level a=0.01 showed that the spectral characteristics of closing sounds produced by normal IS and Hancock xenografts implanted in the mitral position were both significantly different from those of IS xenografts implanted in the aortic position but not significantly different from each other. In addition, the spectral distribution of IS closing sounds was highly reproducible and very slightly affected by the duration of the implant up to 5 years.

生体弁による僧帽弁置換術後の再手術

生体弁による僧帽弁置換術後の再手術

Studies on the in vitro calcification of porcine xenograft valves and its prevention

Studies on the in vitro calcification of porcine xenograft valves and its prevention

Ionescu-Shiley Bovine Pericardial Bioprostheses

Early and late follow-up data are presented for a series of 2701 patients who had lonescu-Shiley pericardial xenograft valves implanted over a 6-year period at the Texas Heart Institute. The study confirms the advantages of the valve with regard to thromboembolism and hemodynamic function and indicates that durability is acceptable at 5 years. The lonescu-Shiley pericardial xenograft valve is suitable for patients who require a bioprosthesis, but further follow-up is necessary to determine long-term durability

Prognosis in valvular heart disease: I. Description of Purpose, Organization, Data Collection Techniques, Estimates of Statistical Power, and Criteria for Termination of Patient Entry

This report describes the design of a multicenter study with two major goals: (1) the identification of valvular heart disease patients at risk for death or a serious complication, and (2) the comparison of hemodynamic function and late outcome of a mechanical prosthetic valve (Björk-Shiley) with a bioprosthesis (Hancock porcine heterograft valve). Strengths of the study design are quantitative assessment of valvular and left ventricular function before and 6 months after valve replacement, measurement in a central laboratory of critical data items such as valve orifice area and left ventricular volumes, and assignment of cause of death and valve-related complications by a committee blinded to valve type. Statistical power calculated by a simulation technique shows only modest loss of power with frequent examination of outcome compared to infrequent examination. Guidelines for premature termination of the study because of superiority of one valve type are described; this includes a critical region with a sloping boundary, which allows for greater chance variation early in the study when the number of patients and events is small, gives the greatest statistical power, and yet appears to provide adequate protection for the subjects in the study.

Aortic root enlargement with glycerol-preserved homologous dura mater patch during aortic valve replacement.

Aortic root enlargement with a patch is sometimes indicated either to prevent aortic homograft valve distortion during implantation or to facilitate easy, tension-free closure of the aortotomy. Patches made of prosthetic material have been widely used for this purpose. The use of autogenous pericardium has recently been reported. Although dura mater has been shown to have great strength, low antigenicity, athrombogenicity, easy availability in large sizes and rapid bonding to most tissues, its use for patch enlargement of the aortic root has not been previously documented. From 1979 to 1983, 38 patients had dura mater aortic root gussets placed during aortic valve replacement at the Southampton General Hospital. In all cases, the patches were placed to facilitate aortic closure, or to prevent homograft valve distortion by enlarging the non-coronary sinus. Aortic homografts were implanted in 11 patients, Carpentier Edwards' Xenograft valves in 16, Björk-Shiley valves in 8 and Wessex Xenografts in 3 patients. All the patients survived and in a mean follow-up of 30 +/- 12.8 months (range 3 to 48 months) there has been no clinical evidence of patch failure due to leakage, rupture or aneurysm formation. These results suggest that glycerol-preserved dura mater is a satisfactory patch material for aortic root enlargement during aortic valve replacement.

Immunogenicity of glutaraldehyde‐treated bovine pericardial tissue xenografts in rabbits

Xenograft valves of glutaraldehyde-treated bovine pericardial tissue have been claimed to be an excellent choice for the replacement of malfunctioning human heart valves. These valves exhibit low thrombogenicity, hemodynamic function, and transvalvular gradients superior to their mechanical and tissue counterparts. However, there are differences of opinion concerning the immunogenic properties of these valvular devices. This study was conducted to evaluate the immune reactivity of such implants. Data obtained indicated that whole xenograft sections of both untreated and treated valvular tissue remain immunogenic following initial and secondary subcutaneous implantations in rabbits. Homologous and cross-reacting antibodies were detected by means of indirect hemagglutination test 30 days after initial implantation of the grafts. Presence of cellular immune response as judged by skin reaction and leukocyte migration inhibition tests indicated that glutaraldehyde treatment of tissues does not destroy cellular immunity. Data obtained also suggest that chemical modification of such implants by glutaraldehyde probably alters, but does not abolish some antigenic determinant sites on the tissue surface. Glutaraldehyde treatment of bovine pericardial tissue does not render the tissue immunologically inert.

The platelet release reaction in cardiovascular disease: evaluation of plasma betathromboglobulin as a marker of a prothrombotic state.

Plasma betathromboglobulin as a marker of in vivo platelet release was found to be significantly higher in 131 patients with prosthetic cardiac valves and 104 patients with coronary artery disease, compared with 133 normal individuals. Patients with double mechanical valves had a higher mean betathromboglobulin than those with single mechanical valves, who in turn had higher values than those with single heterograft valves. Thirteen patients adequately anticoagulated at the time of a thromboembolic event had significantly higher betathromboglobulin levels than 5 with thromboemboli when not anticoagulated, suggesting platelets were responsible for the emboli in the former group. The presence of coronary risk factors in normal individuals did not affect betathromboglobulin; however, when two or more risk factors were present in patients with ischaemic heart disease, mean betathromboglobulin was higher than when only one or no risk factors were present. This suggests greater platelet activation in the presence of more widespread atherosclerotic disease. Thus mean plasma betathromboglobulin is higher in groups of patients with disorders known to have thrombotic complications, but the wide range of values, which overlap with normals, prevent the clinical interpretation of the plasma betathromboglobulin level found in any individual patient.

Durability of the pericardial valve.

The fate of 1001 pericardial xenograft valves was analysed during a maximum follow-up period of 13 years. Two basic types of pericardial valves have been implanted. Between 1971 and 1975, 213 patients received 'hospital made' valves (single replacement). Between 1976 and 1983, 601 patients received 788 pericardial valves manufactured by Shiley Inc. (474 Standard and 314 Low profile valves) for both single and multiple replacement. There were 27 instances of valve dysfunction between 13 and 92 months after operation, 20 with 'hospital made' and 7 with Shiley valves. The actuarial freedom from valve failure at 8 years is 94.0 +/- 4.6% for aortic and 98.8 +/- 1.2% for mitral replacement in patients with Shiley valves. In patients with 'hospital made' valves the actuarial freedom from valve failure at 12 years of follow-up is 86.7 +/- 7.6% for aortic and 84.7 +/- 14.1% for mitral replacement. The linearised rate of valve dysfunction was 0.31% per annum for Shiley valves and 1.27% per annum for 'hospital made' valves. This analysis demonstrates that the pericardial xenograft has a low risk of valve failure and a predictable behaviour over a period of 13 years. The Shiley made valves have shown improved durability when compared with the 'hospital made' valves.

Reoperation for obstructed pulmonary ventricle-pulmonary artery conduits: Early and late results

Obstruction of pulmonary ventricle-pulmonary artery conduits can result from neointimal peel formation or valvular degeneration and calcification. To determine the risks and outcome of reoperation, we reviewed the records of 100 consecutive patients who had replacement of severely stenotic pulmonary ventricle-pulmonary artery conduits. At reoperation, the 70 male and 30 female patients had a mean age of 13.3 +/- 4.8 years. During operation, 37 homografts, 62 Dacron grafts with integral xenograft valves, and one nonvalved conduit were replaced with valved (80) or nonvalved (17) prostheses. The mean transconduit pressure gradient decreased from 81 +/- 26 mm Hg preoperatively to 7 +/- 8 mm Hg postoperatively (p less than 0.01). Concomitant cardiac valve replacement was performed in seven patients, and residual ventricular septal defect closure was accomplished in 28. Operative mortality (less than 30 days) was 7%, but there were no deaths among the 47 patients who had no associated defects. At 3 and 5 years postoperatively, probability of survival among patients dismissed from the hospital was 94% +/- 3% and 86% +/- 6%, respectively. In our experience, risk of reoperation for conduit obstruction alone is low, so that the effect of graft failure on overall survival is minimized.

Late Results of Valve Xenograft Conduits between the Right Ventricle and the Pulmonary Arteries in Patients with Pulmonary Atresia and Extreme Tetralogy of Fallot

Between 1975 and 1982, valve xenograft conduits were used to establish continuity between the right ventricle and the pulmonary arteries in 28 patients between the ages of 3 to 39 years (mean 14.7 years) with 4 hospital deaths (14%). The indications for operation were pulmonary atresia types I and II in 7, extreme tetralogy of Fallot with hypoplastic pulmonary artery and valvular ring in 10, secondary obliteration of the infundibulum following Waterston shunt in 4, pulmonary valve insufficiency after transannular right ventricular outflow tract patch in 5 and tetralogy of Fallot with anomalous coronary artery in 2. Twenty-one patients (87%) between 9 and 41 years of age (mean 17.4 years) were available for follow-up 1/2 to 8 years after operation. The late death incidence during the follow-up period was 8% (2/24). Postoperative cardiac catheterization, which included right and left ventriculogram and measurements of gradients, was performed in 14 patients 4 months to 6 years after operation. Four patients were in New York Heart Association (NYHA) class 1, 6 in class II and 4 in class III. The other 7 non-catheterized patients were in class II. There were resting peak systolic gradients of 15 to 35 mmHg in 4, 36 to 55 mmHg and more than 55 mmHg across the xenograft valve and the proximal anastomosis in 4 other patients. The right and left ventricular end-diastolic pressures (RVEDP, LVEDP) averaged 18 and 17.5 mmHg, respectively, in 3 patients. The mean ratio of PRV/PLV quotient in NYHA class I group was 0.3, in class II 0.45 to 0.7 and in class III greater than 0.7 (including 2 with residual VSD and pulmonary hypertension). Late densitometric studies for assessing pulmonary valve competence revealed regurgitant fraction of up to 40% of the total stroke volume in the absence of a residual shunt 2 to 4 years after conduit implantation. Three children underwent uneventful surgical replacement of calcified xenograft conduit 1 1/2 to 4 1/2 years after surgery with antibiotic-sterilized valve allograft. Four other patients have residual ventricular septal defects (VSD), 2 of them underwent surgical reclosure while the other 2 patients with pulmonary hypertension still have their residual VSD open.(ABSTRACT TRUNCATED AT 400 WORDS)