Hancock II porcine bioprosthesis: excellent durability at intermediate-term follow-up.

OBJECTIVES: This study aimed to assess the clinical performance and durability of a new generation of porcine valve, the Hancock II bioprosthesis, at intermediate-term follow-up. BACKGROUND: Standard porcine bioprostheses undergo progressive structural deterioration, mainly due to cusp and commissural calcification, affecting durability and requiring reoperation. The Hancock II bioprosthesis, which is currently undergoing clinical investigation, is made from a porcine aortic valve treated with a calcium-retarding agent (sodium dodecyl sulfate [T6]), which should delay onset of calcification and increase durability. METHODS: From May 1983 to December 1992, we used the Hancock II bioprothesis in aortic (59 patients), mitral (101 patients) and mitral-aortic (25 patients), valve replacement procedures. Postoperative follow-up ranged from 0.1 to 8.7 years (mean [+/- SD] 4.5 +/- 2.6 years) and was 100% complete. Freedom from major postoperative events was calculated at 7 years for patients with aortic valve replacement and at 8 years for those with mitral and mitral-aortic valve replacement. RESULTS: The actuarial survival rate was 48 +/- 10%, 76 +/- 3% and 63 +/- 6%; freedom from valve-related mortality was 91 +/- 4%, 94 +/- 2% and 89 +/- 6%; freedom from thromboembolism was 80 +/- 11%, 90 +/- 2% and 79 +/- 7%; and freedom from reoperation was 100%, 97 +/- 1% and 89 +/- 6% after aortic, mitral and mitral-aortic valve replacement, respectively. No structural valve deterioration occurred. CONCLUSIONS: At intermediate-term follow-up the Hancock II bioprosthesis showed excellent durability in all positions. However, the effectiveness of anticalcification treatment must be assessed with longer follow-up studies.

Calcific degeneration as the main cause of porcine bioprosthetic valve failure.

Sixty-seven glutaraldehyde-processed porcine bioprostheses (PBs), recovered at autopsy or reoperation from 65 patients, were evaluated by roentgenologic and pathologic examination. Seven patients with 8 PBs were younger than 20 years of age. The time interval of function was 2 to 138 months (average 62). Pathologically, 53 explants had signs of intrinsic dysfunction, which was ascribed to calcification in 36 (68%). By x-ray examination, calcific deposits were found in 55 of 67 PBs (82%). The mean duration of function was 70 +/- 32 months in calcified PBs vs 27 +/- 18 months in noncalcified PBs (p less than 0.001). All 26 PBs that had been in place for longer than 6 years were calcified. In 45 PBs the Ca++ deposits were considered severe (mean time of function 76 +/- 32 months) and mild in 10 (mean time of function 44 +/- 22 months) (p less than 0.005). The Ca++ deposits were located at the commissures in 54 PBs (98%), at the body of cusps in 41 (75%), at the free margin in 37 (67%) and at the aortic wall in 37 (67%). When mild, Ca++ deposits involved the commissures in 90% of cases, the body of cusps in 30% and the free margin only in 10%. Forty-seven calcified PBs were mounted on a flexible stent, and 8 had a rigid stent, with an average time of function of 63 +/- 28 and 113 +/- 18 months, respectively (p less than 0.00001). Ca++ dysfunction occurred earlier in the aortic than in the mitral position (59 +/- 19 vs 86 +/- 35 months, p less than 0.05). All the PBs explanted from young patients and 47 of 59 PBs removed from adult patients were calcified, with an average time of function of 50 +/- 21 vs 73 +/- 33 months, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Glutaraldehyde-preserved porcine bioprosthesis. Factors affecting performance as determined by pathologic studies.

The causes of porcine valve failure were evaluated pathologically in 129 bioprostheses (BP) removed at surgery or necropsy. Fifty-one BP had been in place for less than two months (early explants); most of the complications of this group were observed in the mitral position: left ventricular outflow obstruction (43 percent), thrombosis (23.5 percent), myocardial dysruption (20 percent), cardiac rupture (10 percent), and perivalvular leak (3.5 percent). Among the 78 explants in place for more than two months (late explants), 66 had evidence of dysfunction. Calcification was the leading cause of failure (46 percent), followed by thrombosis (17 percent), endocarditis (12 percent), fibrous tissue overgrowth (10 percent), perivalvular leak (9 percent), and primary cusp tears (6 percent). Calcific degeneration is a hallmark of the phenomenon of biodegradation, and experimental animal models are encouraged since they may represent the clue to preventing calcification and therefore enhancing performance and durability of the porcine BP.

Results of reoperation for primary tissue failure of porcine bioprostheses.

Results of reoperation for primary tissue failure of porcine bioprostheses were evaluated in 574 patients discharged from the hospital from 1970 to 1981. A total of 413 had undergone isolated mitral valve replacement and 161 isolated aortic valve replacement. Through March, 1984, 88 patients (15%) had required reoperation: 59 had undergone mitral and 29, aortic valve replacement. Primary tissue failure was the main cause of bioprosthetic dysfunction; it occurred in 64 patients (46 mitral and 18 aortic) at a mean postoperative interval of 93 +/- 4 months (range 34 to 158). During the same period, 11 patients required reoperation for bioprosthetic endocarditis, 11 for paravalvular leak, and two for thrombosis. These patients are not included in this review. Reoperation for primary tissue failure was performed after a mean interval of 72 +/- 6 months (range 38 to 158) for patients with aortic bioprostheses and after 101 +/- 5 months (range 34 to 153) for those with mitral bioprostheses (p less than 0.05). Overall mortality at reoperation was 12.5%: 11% for the mitral group and 16% for the aortic group. In 62 patients (45 mitral and 17 aortic) primary tissue failure was caused by calcification of the cusps, associated with severe fibrous tissue overgrowth in seven. Bioprosthetic failure was caused by an intracuspal hematoma in one patient with mitral valve replacement and by lipid infiltration of the cusps in one patient with aortic valve replacement. Actuarial freedom from bioprosthetic primary tissue failure at 12 years is 61% +/- 5% for the mitral group and 69% +/- 7% for the aortic group. On the basis of our long-term follow-up of patients after mitral or aortic replacement with a porcine bioprosthesis, we conclude: primary tissue failure is the most frequent indication for reoperation in patients with a porcine bioprosthesis; calcification of the cusp tissue is the leading cause of primary tissue failure; reoperation for primary tissue failure may be a major concern, although mortality for elective cases is low; and the limited durability of porcine bioprostheses suggests their use be restricted to selected patients.

Experimental evaluation of porcine-valved conduits processed with a calcium-retarding agent (T6).

The effectiveness of a water-soluble C-12 alkyl sulfate (T6) (U.S. Patent No. 4,323,358) in retarding bioprosthetic calcification was evaluated in 23 porcine-valved conduits (13 T6-treated conduits and 10 controls) implanted in young sheep between the right ventricle and the pulmonary trunk. The grafts were divided into three groups according to the period of function: Group I, less than 2 months; Group II, 2 to 4 months; and Group III, 5 to 7 months. In Group I (four T6 and four controls), endocarditis occurred in five cases. In Group II (three T6 and three controls), four conduits showed severe fibrous peel ingrowth. In Group III (six T6 and three controls), fibrous peel was the main feature in four conduits and calcium deposits occurred in the porcine aortic wall in all cases, with cusp involvement in two; in both T6-treated and control conduits, chemical analysis showed a much lower calcium content of the cusps (8.45 +/- 80 versus 2.95 +/- 1.52 mg/gm dry weight, respectively) than that reported in other animal or human explants. The grade of calcification in control and T6-treated conduits was equal on x-ray analysis, and no differences in calcification patterns were noted on electron microscopy. This experimental model shows a low degree of cusp calcification and no significant differences between T6-treated and control conduits. Peel formation markedly interferes with performance of the porcine-valved conduit. The results of this analysis indicate that valved conduits are not the optimum model for evaluating calcium-retardant agents in biological valves.

Early mechanical failures of the Hancock pericardial xenograft.

From August 1981 to July 1984, a total of 97 Hancock pericardial xenografts were implanted in 84 patients, whose ages ranged from 13 to 75 years (mean 55.7 +/- 13). Mitral value replacement was performed in 17, aortic valve replacement in 54, and mitral-aortic valve replacement in 13. Operative survivors were reevaluated from July to September 1985. Cumulative duration of follow-up is 167 patient-years (range 0.5 to 4.1 years), and follow-up is 99% complete. The overall late mortality (at 4 years) is 3.6% +/- 1.4% per patient year, and the actuarial survival rate is 95.4% +/- 3% for aortic valve replacement, 74.7% +/- 16.5% for mitral valve replacement, and 67.1% +/- 20.7% for mitral-aortic valve replacement. One patient sustained a thromboembolic event after mitral valve replacement, but no such complications occurred after aortic or mitral-aortic valve replacement. Actuarial freedom from embolism at 4 years is 100% for aortic and mitral-aortic valve replacement and 93.3% +/- 6.4% for mitral valve replacement. Reoperation for Hancock pericardial xenograft dysfunction was performed in seven patients (five aortic and two mitral-aortic). In the aortic valve replacement group the causes were endocarditis in one, paravalvular leak in one, and primary tissue failure in three; all survived reoperation. The two patients with mitral-aortic valve replacement required reoperation because of primary tissue failure of both Hancock pericardial xenografts, and one died. All values explanted because of primary tissue failure showed commissural tears causing severe prosthetic regurgitation. Calcium deposits were severe in one and mild but unrelated to the cusp rupture in another. Collagen disarray was seen only at the site of the tears, whereas the collagen structure was well preserved in the intact parts of the cusps. Four patients with aortic valve replacement and one with mitral valve replacement show evidence of Hancock pericardial xenograft failure and are awaiting reoperation. The actuarial freedom from primary tissue failure at 4 years is 74.3% +/- 9.8% for aortic and 78.9% +/- 13.2% for mitral Hancock pericardial xenografts. At medium-term follow-up, the Hancock pericardial xenograft has shown poor durability and an extremely high rate of early mechanical failure, especially in the aortic position. These observations suggest the need for a close follow-up of Hancock pericardial xenograft recipients and possibly elective reoperation in asymptomatic patients with clinical evidence of prosthetic failure. These results have led us to discontinue the clinical use of this pericardial xenograft.

Long-term performance of the Hancock porcine bioprosthesis in the tricuspid position. A review of forty-five patients with fourteen-year follow-up.

Because little information is available regarding the clinical performance of the Hancock porcine bioprosthesis (Johnson & Johnson Cardiovascular, King of Prussia, Pa.) implanted in the tricuspid position, we reviewed the long-term follow-up of patients who had tricuspid valve replacement with this device. From March 1970 to December 1983, 45 patients had tricuspid valve replacement, either isolated (seven patients) or combined with replacement of other valves (38 patients) by means of a standard, glutaraldehyde-preserved Hancock porcine bioprosthesis. Follow-up ranged from 0.2 to 14.7 years (mean, 7.6 +/- 3.6 years) and was complete. The late mortality rate was 6.6% +/- 1.6%/pt-yr and the actuarial survival rate at 14 years was 23% +/- 9%. Reoperation because of structural deterioration of the tricuspid, the mitral, or both bioprostheses was performed in nine patients (3.7% +/- 1.2%/pt-yr) from 40 to 177 months (mean, 112 +/- 43 months) and resulted in no deaths. Actuarial freedom from structural deterioration of a Hancock tricuspid porcine bioprosthesis at 14 years is 68% +/- 13%. Morphologic examination of explanted porcine bioprostheses showed that those implanted in the tricuspid position had lower degrees of calcification and less severe structural changes than those simultaneously explanted from the mitral position. We conclude that the Hancock porcine bioprosthesis has an acceptable long-term durability and satisfactory performance after tricuspid valve replacement, and we continue to favor its use in the tricuspid position even in association with mechanical prostheses in the left side of the heart.

Long-term durability of the Hancock porcine bioprosthesis following combined mitral and aortic valve replacement: an 11-year experience.

Long-term evaluation of patients undergoing combined mitral and aortic valve replacement (MVR + AVR) with a porcine bioprosthesis provides the opportunity for a direct comparison of the durability of the mitral versus the aortic porcine bioprosthesis in the same patient. From 1970 to 1983, 71 patients underwent MVR + AVR with Hancock porcine bioprostheses. There were 46 men an 25 women ranging in age from 21 to 64 years (mean, 47.5 +/- 5 years). Sixteen patients (22.5%) died at operation. The survivors were followed from 0.2 to 11.5 years (mean, 5.7 +/- 3 years). Duration of follow-up was 313 patient-years and was 100% complete. Overall late mortality was 6.7 +/- 1.4% per patient-year (linearized incidence), and actuarial survival was 54.2 +/- 8% at 11 years. Endocarditis occurred in 4 patients (linearized incidence of 1.3 +/- 0.6% per patient-year); thromboembolic events were sustained by 4 patients (linearized incidence of 1.3 +/- 0.6% per patient-year); the event was fatal in 1 patient. Actuarial freedom from thromboembolism was 90 +/- 4.8% at 11 years. Reoperation for primary tissue failure was performed in 11 patients (linearized incidence of 3.5 +/- 1% per patient-year) with no deaths; in 7 patients both bioprostheses were explanted, and in 4, only the mitral bioprosthesis was replaced. The durability of explanted aortic and mitral porcine bioprostheses was not significantly different, and the evaluation of seven pairs of explanted aortic and mitral bioprostheses showed similar amounts of calcification. Actuarial freedom from reoperation because of primary tissue failure was 44.6 +/- 13.7% at 11 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of prosthetic design on durability of the Liotta porcine valve in the mitral position.

From March 1979 to December 1984, the Liotta low-profile porcine bioprosthesis was employed for mitral valve replacement in 71 patients to avoid potential left ventricle-prosthesis mismatch occasionally observed with the standard, high-profile, Hancock porcine xenograft. Follow-up of 61 operative survivors showed at 10 years an actuarial survival of 67% +/- 7%, freedom from thromboemboli of 96% +/- 2%, freedom from structural deterioration of 63% +/- 11% and freedom from all Liotta bioprosthesis-related complications of 53% +/- 10%. Complications related to excessive protrusion of the stent into the left ventricular cavity were eliminated with the Liotta bioprosthesis; the peculiar stent configuration, however, was responsible for an increased rate of structural deterioration requiring reoperation in 10 patients (2.8% +/- 0.9%/patient-year) at a mean interval of 76 +/- 18 months after mitral valve replacement (range, 45 to 106 months). Common findings in all explants were cusp prolapse, cusp tears, and commissural rupture related to various degrees of tissue calcification, constantly leading to severe prosthetic incompetence. As also shown experimentally, such structural changes have been attributed to increased systolic stresses on the closed cusps, favored by excessive reduction of the stent height. Our experience shows that the Liotta bioprosthesis used for mitral valve replacement does not provide any clear-cut advantage over standard porcine bioprostheses and that its long-term durability appears affected by the unique prosthetic design.

The aortic valve after heart transplantation.

We studied the aortic root (wall, semilunar cusp, septal myocardium) in 37 patients (29 male and 8 female; mean age; 41 years) who died 2 to 4,380 days (mean, 398 days) after heart (n = 34) and heart-lung (n = 3) transplantation. The aim of the study was to assess tissue viability, graft-host biological interaction, and cusp mineralization with time. Study methods included gross inspection and photos of each specimen, microradiography, histology and immunohistochemistry, scanning and transmission electron microscopy, and atomic absorption spectroscopy. There were no cases of valve dysfunction; in particular, cusp tears or perforations never occurred. Only 1 valve, in place for 12 years, had a pin-point calcification visible to the naked eye. Optimal preservation of the tissue components (endothelium, fibroblasts, collagen and elastic fibers, proteoglycans, intrinsic nervous ganglia) was observed at both short and long term. Concomitant acute rejection of valve leaflets and myocardium was seen in 7, mild valve thickening in 14, myxoid degeneration in 4, and graft aortic atherosclerosis in 26. Mineralization was negligible and was not progressive with time. No linear correlation was found between mineralization and number of acute rejections. In conclusion, we observed optimal cusp viability and integrity even at long term, concomitant valve and myocardium rejection with no valvular sequelae, and negligible, non-progressive cusp calcification. Donor-recipient blood group matching, heart-beating donor, and chronic immunosuppression are the reasonable explanations of the optimal durability of the aortic valve after heart transplantation.

Performance of the Hancock porcine bioprosthesis following aortic valve replacement: considerations based on a 15-year experience.

All patients undergoing isolated aortic valve replacement with a standard Hancock porcine bioprosthesis (PB), from 1970 to 1983, were reviewed. There were 196 patients, 162 male and 34 female patients, with a mean age of 48 +/- 12 years. Operative survivors were followed up from 3 to 15.6 years (mean follow-up, 6.6 +/- 1.5 years), with a cumulative follow-up of 1,140 patient-years, being 100% complete. Actuarial survival was 51 +/- 15% at 14 years. Eight patients sustained systemic embolic episodes (0.7 +/- 0.2%/patient-year); actuarial freedom from emboli is 89.4 +/- 4.3% at 14 years. Reoperation was performed in 53 patients: in 6 because of endocarditis (0.5 +/- 0.2%/patient-year), in 7 because of perivalvular leak (0.6 +/- 0.2%/patient-year), and in 40 because of PB primary tissue failure (3.5 +/- 0.5%/patient-year). Actuarial freedom from PB-related deaths, PB failure, and overall PB-related complications at 14 years was 66.3 +/- 19, 34.3 +/- 11, and 30 +/- 10%, respectively. This long-term experience shows that the performance of the Hancock PB appears satisfactory up to 8 years, while it progressively deteriorates beyond 10 years because of the impact of primary tissue failure on valve durability, justifying the restriction of its use in the aortic position in selected patients.

The Meadox-Gabbay pericardial xenograft: failure of the unicusp principle.

Durability of a new bioprosthesis, the Meadox-Gabbay unileaflet pericardial xenograft, was evaluated by reviewing a series of 12 patients who received this device in the mitral position from 1983 to 1985. Bioprosthetic failure necessitated reoperation in 5 patients 21, 22, 53, 66, and 81 months after placement. Three patients died of cardiac failure after 31, 52, and 70 months; no postmortem examinations were done. In 2 of the 3 patients, an echocardiographic study had shown signs of valvular dysfunction. Pathological examination of five available explants revealed the presence of redundancy and stretching of the single pericardial leaflet in all of them; in one, this lesion alone caused severe prosthetic incompetence. Other pathological findings included cusp and commissural calcification and commissural tears with or without calcification. Histologic examination and electron microscopy showed intrinsic calcification involving both collagen bundles and cellular debris and various degrees of collagen disruption. In this limited series of patients, the Meadox-Gabbay pericardial xenograft demonstrated various modes of failure that markedly impair its durability and render it unsuitable as a cardiac valve substitute.

Diabetic fibrous breast disease: a clinical entity that mimics cancer.

Three typical cases of fibrous mastopathy associated with diabetes mellitus are described. The histological change is a connective-tissue overgrowth with vasculitis and some proliferation of duct epithelium. The clinical changes are indistinguishable by physical or radiographic findings from malignancy. In young patients with long-standing diabetes the presence of one or more suspicious clinical and imaging findings can suggest the presence of this lesion but a surgical biopsy or, at least, a close follow-up is required.

Pulmonary vascular disease in infants with complete atrioventricular septal defect.

In order to assess incidence and time of occurrence of pulmonary vascular disease, the lungs of 49 patients were studied histologically. Thirty-four lung specimens were obtained at autopsy, and 15 were open lung biopsies. Patients consisted of 24 males and 25 females ranging in age from 10 days to 14 years (median 9 months); 37 had Down's syndrome. Overall incidence of irreversible pulmonary vascular disease (grade 3 or more) under 1 year of age was 34.6%; grade 4 of pulmonary vascular disease was observed only in Down patients. In correlating pulmonary vascular resistance, measured during heart catheterization, with pulmonary vascular disease severity at histology, 6 out of 7 patients with pulmonary vascular resistance over 7 units per metre squared showed grade 4 of pulmonary vascular disease, and of these 4 were under 1 year of age. These findings suggest that a significant rate of pulmonary vascular disease occurs under 1 year of age, with most severe degrees in the time interval 7-12 months. They show that good correlation exists between pulmonary vascular resistance over 7 units per metre squared and grade 4 of pulmonary vascular disease. They demonstrate that the most severe pulmonary vascular disease is seen in Down's syndrome. Finally, they indicate that early surgical correction is mandatory and should be accomplished within 6 months of age.

Abnormal pulmonary artery branching in tetralogy of Fallot with "absent" pulmonary valve.

Microangiographic postmortem study in a case of tetralogy of Fallot with so-called absent pulmonary valve disclosed an abnormal branching pattern of the intrapulmonary arteries, but failed to detect any compression of intrapulmonary bronchi as a consequence of the distorted segmental arteries. The case also featured the absence of the ductus arteriosus, which should be considered a basic associated anomaly in the development of this malformative complex.

Low-profile porcine bioprosthesis (Liotta): pathologic findings and mode of failure in the long-term.

BACKGROUND AND AIMS OF THE STUDY: The Liotta low profile porcine bioprosthesis (LBP) was designed in order to minimize complications due to excessive protrusion of the stent prongs in the left ventricle. MATERIALS AND METHODS: From April 1984 to November 1993, 25 LBP surgical explants were available for pathology study, which included gross and X-ray evaluations. Reoperation was performed after a mean period of 95 +/- 25 months (range 46 to 143 months), in five males and 20 females (mean age at implantation 51.1 +/- 11.4 years). RESULTS: The cause of failure was stenosis due to cusp stiffness caused by dystrophic calcification in one and incompetence in 24 LBPs. In only one case was incompetence ascribable to endocarditis; in the remaining 23 the mechanism of regurgitation was due to commissural tearing (21 LBPs), commissural dehiscence (one LBP) and both tears and dehiscence (one LBP). Overall, 28 commissural tears were observed: 20 involved the right coronary cusp, eight the left coronary cusp, and none the non-coronary cusp. The anterior commissure was most frequently involved by tears (n = 17) followed by the right posterior (n = 9) and the left posterior (n = 2). Tears were calcium-related in all but two cases. Calcific deposits were observed in each explant, involving a total of 62 commissural attachments, 17 cusp bodies and five right muscular shelves. CONCLUSION: In conclusion, valve regurgitation is the usual mode of LBP failure in the mitral position; commissural tearing of the right coronary cusp was the most common cause of valve regurgitation, and occurred even in the presence of pin-point calcification. These pathologic findings seem to confirm that low profile design, which implies bulging of the right coronary cusp, entails the risk of increased stress at the commissures, accelerated calcification and tearing.

Durability of glutaraldehyde-fixed pericardial valve prostheses: clinical and animal experimental studies.

Bovine pericardium has been widely employed as a xenograft tissue for the manufacture of bioprosthetic valve substitutes. Early three-leaflet valve models showed poor tissue preservation and shortcomings in valve design, which accounted for tissue wear and prosthesis failure due to cuspal tear. Reducing the number of cusps in the unicusp pericardial valve has proved unsuccessful due to stretching of the single pericardial leaflet with consequent valvular incompetence. The new generation of pericardial xenografts present basic changes in valve design and optimal tissue preservation after industrial processing, with no evidence of leaflet tear at medium term follow up. However, clinical experience is limited and, similarly to porcine xenografts, dystrophic calcification still appears to be a major problem.

Pathology of the Pericarbon bovine pericardial xenograft implanted in humans.

BACKGROUND AND AIMS OF THE STUDY: Pericarbon is a new-generation bovine pericardial bioprosthesis designed to withstand mechanical wear. Following optimal in vitro testing and animal experiments, clinical trials were initiated in many European centers and explants sent to our department for pathological evaluation. This included gross, radiographic, histologic and ultrastructural investigations. METHODS: Between 1986 and 1996, 24 bioprostheses (eight aortic, 11 mitral, two mitro-aortic, one tricuspid) were collected from 22 patients (10 males and 12 females; mean age 57.0 +/- 18.9 years) either at autopsy (nine) or reoperation (15). RESULTS: Ten bioprostheses explanted < 2 months after surgery were either normal or failed because of surgical problems or non-structural causes. Among the other 14 bioprostheses (mean placement 41.9 +/- 23.6 months; range: 7 to 90 months), structural deterioration occurred in seven and was due to dystrophic calcification with stenosis in five (three aortic, two mitral), mixed lesion in one (mitral), and incompetence in one by calcium-related commissural tear (mitral). At the ultrastructural level, calcification was detected either on cell debris or upon collagen fibers. No bioprosthesis failed because of fibrous tissue overgrowth. Of the remaining seven bioprostheses, vegetative endocarditis occurred in two, thrombosis in one, and aseptic paravalvular leak in one; whereas three showed no signs of dysfunction. CONCLUSIONS: This pathologic experience with the Pericarbon valve showed calcification to be the main cause of late structural failure, causing mainly cusp stiffness and bioprosthesis stenosis. Tissue rupture or abrupt dysfunction never occurred. Thus, prevention of mineralization remains the main challenge.

Is the tricuspid position suitable for testing replacement bioprosthetic valves in the sheep model?

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde may promote calcification in xenograft tissue by the action of toxic aldehyde group residues involved in the cross-link process. Post-fixation treatment with homocysteic acid (HA) neutralizes this toxicity by bonding aldehyde groups, and enhances biocompatibility on the basis of strongly electronegative sulfonic groups. Previous studies in a rat subcutaneous model showed significant long-term mitigation of mineralization of glutaraldehyde-fixed pericardium treated with HA. This study aimed to assess the anticalcific efficacy of HA in a valvular implant in growing sheep, and establish if the tricuspid position is suitable for testing replacement bioprosthetic valves. METHODS: Eleven stented 25 mm Pericarbon bioprostheses (seven HA-treated, four standard) were implanted in the tricuspid position of growing sheep. Infective endocarditis occurred in four prostheses. Among the remaining seven, three (two HA-treated, one standard) were explanted at 91 days (mid-term), and four (two HA-treated, two standard) at 140-141 days (long-term). All explants were studied by gross, X-ray, light, transmission and scanning electron microscopy, as well as by atomic absorption spectroscopy. RESULTS: No histological and ultrastructural difference in tissue preservation were observed between HA-treated and standard Pericarbon bioprostheses, either in the mid or long term. The mean calcium content of mid-term HA-treated explants was 9.55 mg/g compared with 16.26 mg/g in mid-term standard explants. Only one late standard explant failed as a result of severe stenosis caused by massive dystrophic calcification. Among four late explants, two showed significant increase in mineralization (HA-treated, 87.45 mg/g; standard, 181.20 mg/g), while two showed calcium contents similar to those in mid-term explants (HA-treated, 11.96 mg/g; standard, 17.32 mg/g). CONCLUSION: Post-fixation treatment with HA preserves structural properties after tricuspid implantation in growing sheep. The tricuspid implant in the sheep model failed to reproduce remarkable accelerated progressive calcification in all xenografts so as to demonstrate a significant difference between HA and standard explants. The tricuspid position for testing replacement bioprosthetic valves should be abandoned, and investigations repeated with the prosthesis in the mitral position.

Detoxified glutaraldehyde cross-linked pericardium: tissue preservation and mineralization mitigation in a subcutaneous rat model.

BACKGROUND AND AIM OF THE STUDY: Glutaraldehyde is considered a promoter of calcification by the action of toxic aldehyde group residuals from cross-linking. Post-fixation treatment with homocysteic acid (HA), besides bonding aldehyde groups and neutralizing toxicity, should enhance biocompatibility due to the strongly electronegative sulfonic group. The aim of this investigation was to evaluate HA efficacy on tissue preservation and dystrophic calcification mitigation in glutaraldehyde cross-linked bovine pericardium (BP) using a subcutaneous rat model. METHODS: Four samples of BP, two with glutaraldehyde-HA and two with glutaraldehyde treatment, were implanted in each of 24 male Sprague-Dawley rats. Three rats were killed at 14 days, eight at 28 days, eight at 56 days and five at 84 days. Unimplanted glutaraldehyde-HA- and glutaraldehyde-treated samples served as controls. All samples were studied by gross examination, mammography, light transmission and scanning electron microscopy, and atomic absorption spectroscopy. The nature of mineralization was investigated by coupling techniques of scanning electron microscopy, electron microprobe analysis and X-ray powder diffraction. RESULTS: No histological and ultrastructural differences were found between glutaraldehyde-HA- and glutaraldehyde-treated BP, whether implanted or unimplanted. In both groups, calcification progressed with time, but significantly less after glutaraldehyde-HA treatment than after glutaraldehyde alone and at all time intervals (14.63 +/- 21.34 versus 43.17 +/- 15.99 at 28 days, p = 0.003; 56.42 +/- 40.20 versus 90.59 +/- 32.90 at 56 days, p = 0.008; 91.68 +/- 67.68 versus 156.23 +/- 17.85 at 84 days, p = 0.01). Differences were evident by mammography and histology (von Kossa stain). Electron microprobe analysis in both groups showed the composition of calcified nuclei to be calcium phosphate, stoichiometrically close to apatite (Ca5(PO4)3(OH)). The occurrence of crystallized apatite was supported by X-ray powder diffraction findings, the amount of crystallized apatite being higher in glutaraldehyde-treated samples. CONCLUSIONS: Post-fixation treatment with HA preserves BP structural properties and significantly mitigates mineralization of long-term subcutaneous implants.