The case of an explanted 16-year-old mitral Carpentier-Edwards pericardial bioprosthesis

We report the case of a mitral Carpentier-Edwards pericardial bioprosthesis that was explanted from a 43-year-old female patient because of structural valve deterioration 16 years following implantation. Upon removal, the prosthesis was found to be discolored and all leaflets were stiff and hard, showing extensive calcification, pannus overgrowth, leaflet hematoma, and multiple disruptions. One leaflet presented a wavy free margin due to commissural disruptions, leading to incomplete cusp coaptation. The accumulated physical symptoms of the patient were consistent with these findings.     

Morphological findings in explanted Toronto stentless porcine valves.

BACKGROUND: Stentless porcine valves have many documented advantages over stented valves. Since its introduction in 1991, the Toronto stentless porcine valve (T-SPV) has shown excellent hemodynamic performance. METHODS: A total of 332 T-SPVs have been implanted at our institution up to December 2003, 25 of which have been explanted at surgery. Herein, we report a study of 30 explanted T-SPVs seen at our institution over a 5-year period. RESULTS: The mean patient age at explant was 61.2+/-11.8 years with a mean implant duration of 100.7+/-27.8 months (after excluding one valve removed early postoperatively for infective endocarditis). Twenty-seven of 30 valves (90%) showed structural deterioration characterized by tissue degeneration, cusp tears, calcification, and lipid insudation. Eight valves (26.7%) showed evidence of calcification on gross inspection and a total of 23 valves (76.7%) showed at least one microscopic focus of calcification, located primarily in the basal and commissural regions of the cusp. Twenty valves (66.6%) showed cusp tears. Pannus was visible grossly on the surface of 27 of 30 valves (90%), while histologically, at least some degree of pannus was observed on both the inflow and outflow surfaces of all but two valves. Twelve T-SPV (40.0%) showed calcification in the porcine aortic tissue, four of which involved calcification of the porcine muscle shelf in the right coronary cusp. Two T-SPV showed no significant structural deterioration. Their clinical reason for explantation was incompetence or infective endocarditis. CONCLUSION: With a freedom from reoperation of about 87.0% at up to 10 years, the T-SPV shows excellent durability. The majority of explanted valves show structural valve deterioration similar to that seen in other porcine heart valves.     

Characterizing the inflammatory reaction in explanted Medtronic Freestyle stentless porcine aortic bioprosthesis over a 6-year period

BackgroundThe Medtronic Freestyle valve is a stentless porcine valve with reportedly excellent clinical and hemodynamic results, but little has been reported about its long-term pathology.MethodsSeventeen Freestyle valves were explanted (from 2003 to 2009) and reviewed to assess reasons for bioprosthesis failure. All valves were examined in detail, using histochemistry and immunohistochemistry to identify morphological changes, as well as cellular and humoral responses.ResultsOne Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. The average implant duration was 71.1±35.2 months. Six valves were explanted for infective endocarditis, six for aortic insufficiency, and four for aortic stenosis. Calcification was seen in 11 explants, pannus in 15, thrombus in 12, cusp tears in 9, and 10 explants showed needle tract-like injuries. A chronic inflammatory reaction involving the xenograft arterial wall was seen in 15 of 16 valves. The cells were composed of macrophages and lymphocytes, including T cells (CD8 positive) and B cells. Significant damage to the porcine aortic wall was seen in 15 cases, and cusp myocardial shelf damage in 7 cases. All cases stained positively for IgG and C4dpar.ConclusionsThe porcine aortic tissue showed T cell-mediated rejection and significant aortic medial damage, consistent with dilatation of the porcine aortic root. The demonstration of IgG suggests the likelihood of humoral rejection, in addition to cellular rejection. One of the underlying possibilities is that the porcine aortic tissues are inadequately fixed, hence the retained antigenicity.     

Pulmonary valve-in-valve implants: how long do they prolong reintervention and what causes them to fail?

BackgroundThe valve-in-valve (VinV) procedure is a minimally invasive, transcatheter, off-pump, alternative to conventional valve replacement, which uses a failing bioprosthesis to anchor a second transcatheter-delivered prosthesis. This technique appears effective for prolonging freedom from reintervention and treating early device failure. However, it is unknown as to how long reintervention can be avoided.MethodsWe present the pathological findings of a VinV explanted after 47 months, as well as the failure modes of these devices.ResultsThe VinV approach in our case ultimately failed, likely due to the proximity of the host's tissues to the prosthetic device, resulting in a combination of pannus, calcification, and a cusp tear.ConclusionsAdditional long-term follow-up of pulmonary VinV implantations is needed in order to determine the life span of VinVs and what causes them to fail.     

A case of Carpentier–Edwards pericardial bioprosthesis in mitral position explanted 22 years after implantation

A case of Carpentier–Edwards PERIMOUNT (CEP) mitral pericardial bioprosthesis explanted 22 years after the valve replacement is reported. This patient underwent the previous replacement at the age of 50. The extracted bioprosthesis showed three rigid leaflets, one of which had a tear causing severe mitral regurgitation. The X-ray demonstrated calcification of varied extent among these leaflets, ranging from none to severe. When leaflet calcification is suppressed, perhaps the lifespan of a CEP valve can be prolonged more than previously expected. When a literature search was conducted, this case was found to represent the longest reported interval from the implantation of a CEP valve in the mitral position to the explantation as a result of severe mitral regurgitation caused by structural valve deterioration (SVD).     

Morphologic findings and causes of failure in 24 explanted Ionescu-Shiley low-profile pericardial heart valves.

From 1981 to 1987 just over 608 Ionescu-Shiley low-profile bovine pericardial bioprostheses were implanted at the Toronto Hospital. Twenty-four prostheses (11 aortic and 13 mitral) were surgically explanted from 1988 to 1990 from 20 adults (10 men and 10 women). Prosthesis failure was caused by primary tissue failure in 17 valves or by other mechanisms in seven valves. Variable degrees of tissue failure were also seen in four of the seven valves from the latter group. Primary tissue failure was characterized by fluid insudation between collagen bundles, para stent post tears (alignment stitch related, 20 valves), cusp perforation with prolapse, and calcification. The earliest cusp tears occurred at 28 months. Calcification (10 of 24 cases) was minimal in seven of 10 valves (occurring primarily at the margins of the torn cusp), moderate in two, and severe in one. Tissue overgrowth (pannus) was seen in all but three prostheses. Like its predecessor, the Ionescu-Shiley standard pericardial valve, this prosthesis failed at 2 to 5 years largely due to design-related (alignment stitch) causes and tissue degeneration. Calcification was less prominent, while tissue overgrowth (pannus) was more marked.     

Pathological findings in explanted prosthetic heart valves from ventricular assist devices

AIMS: Ventricular assist devices (VADs) are now a mainstay in the management of patients with end-stage heart failure. An important consideration in the long-term durability of these devices is the structural integrity of the prosthetic valves. Herein, we report the morphological findings in inflow and outflow explanted bioprostheses from seven such devices. METHODS: The porcine bioprostheses (n = 7; HeartMate, Novacor) were examined from inflow and outflow valve conduits. Cusp tears were assessed on gross examination. Tissues were then processed for histology and graded for pannus, thrombus, and calcification. Immunohistochemistry was performed using anti-CD68 (macrophages), CD45 (leukocytes) and CD31 (endothelial cells) antibodies to assess inflammation. RESULTS: There was no evidence of infection, host tissue growth, or calcification in either the inflow or the outflow valves in any case. A mild-to-moderate mononuclear cell 'deposit' was present on all porcine bioprostheses, largely on the non-flow surface of the valve cusps. In the case of the longest implant (HeartMate, duration 567 days), a significant mononuclear cell infiltrate was seen on the flow surface, the non-flow surface, as well as the base of the cusp tissue. Variably sized cusp tears were found in all inflow porcine bioprostheses at and beyond 3 months post-implantation, with the longest duration implant showing multiple tears. No tears were identified in the outflow valves. Histology revealed thrombus deposition in all inflow and outflow porcine valves. In addition, inflow valve cusps were characterised by the presence of longitudinally running 'cystic' spaces, which seem to increase in size with increasing implant duration. CONCLUSION: Bioprosthetic heart valves in VADs show significant changes which appear to correlate with duration post-implantation. These changes suggest that haemodynamic forces and the inflammatory reaction may play a significant role in the long-term durability of the porcine bioprostheses in these devices.     

Inflammation and infection in nine surgically explanted Medtronic Freestyle stentless aortic valves.

BACKGROUND: The Medtronic Freestyle valve is fixed in glutaraldehyde at zero pressure on the cusps and treated with alpha-amino oleic acid. This valve reportedly has excellent clinical and hemodynamic results, but little has been reported about its long-term pathology. METHODS AND RESULTS: Nine Freestyle valves explanted between 2003 and 2005 were reviewed to assess the reasons for bioprosthesis failure (six implanted at our institution). All valves were examined in detail, using histochemistry and immunohistochemistry to identify the cellular response. One Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. Average implant duration was 52.8+/-35.5 months. Four valves were explanted for infective endocarditis, three for aortic insufficiency, two for aortic stenosis with cusp calcification seen in five valves, pannus and thrombus in all valves and a chronic inflammatory reaction involving the xenograft arterial wall seen in eight of nine valves. This was associated with significant damage to the porcine aortic wall in seven cases, and cusp myocardial shelf damage in six cases. CONCLUSIONS: In this series of valves, we found (1) infective endocarditis; (2) pannus, thrombus, and calcification; and (3) unusual and significant inflammatory reaction and aortic tissue damage, which could by itself lead to aortic incompetence.     

Comparison of long-term results between Hancock porcine bioprosthesis and Carpentier-Edwards pericardial bioprosthesis in the aortic and the mitral positions

The aim of this study was to compare the long-term results with the Carpentier-Edwards pericardial bioprosthesis, a second-generation bioprosthesis, and the Hancock porcine valve in the aortic and mitral position. Long-term results of isolated valve replacement with the Carpentier-Edwards pericardial bioprosthesis (73 valves in the aortic position and 73 valves in the mitral position) were compared with those with the Hancock porcine bioprosthesis (41 valves in the aortic and 124 valves in the mitral position). In the aortic position, the mean follow-up period was 8.2±4.0 years with the Carpentier-Edwards pericardial bioprosthesis and 9.9±4.4 years with the Hancock porcine bioprosthesis. In the mitral position, the mean follow-up period was 7.5±4.3 years with the Carpentier-Edwards pericardial bioprosthesis and 10.0±5.3 years with the Hancock porcine bioprosthesis. The results showed that the mean age at implantation was significantly higher in patients with a Carpentier-Edwards pericardial bioprosthesis (58±13 years in the aortic and 51±15 years in the mitral) than in those with a Hancock bioprosthesis (42±13 years in the aortic and 45±10 years in the mitral). In the aortic position, actuarial freedom from structural deterioration of the Carpentier-Edwards pericardial bioprosthesis was significantly better (85±6% at 13 years) than that with the Hancock bioprosthesis (40±10%,P<0.02). In the mitral position, actuarial freedom from structural deterioration of the Carpentier-Edwards pericardial bioprosthesis was similar to that with the Hancock bioprosthesis (32±9% and 44±6% at 13 years, respectively). It is concluded that the durability of the Carpentier-Edwards pericardial bioprosthesis in the aortic position was satisfactory in the elderly patients. In the mitral position, the superior durability of the Carpentier-Edwards pericardial bioprosthesis against the Hancock bioprosthesis failed to be proved.     

Structural valvular deterioration of Hancock standard valve in the mitral position 33 years after initial implantation

A 77-year-old woman who had undergone mitral valve replacement (MVR) with a 29 mm Hancock standard (H–S) bioprosthesis (Model 242) and tricuspid annuloplasty (Kay’s method) at the age of 44 years was admitted urgently with acute heart failure. Echocardiography showed severe transvalvular leakage of the prosthesis and moderate tricuspid regurgitation. The patient underwent reMVR with a 29 mm Carpentier-Edwards Perimount Magna Mitral bioprosthesis and tricuspid annuloplasty with a 30 mm MC3 ring. The explanted bioprosthesis showed mild calcification and a tear in the leaflet, dehisced commissures and pannus overgrowth. To our knowledge there are no reports describing H–S valves that were still functioning over 30 years after implantation. Herein, we report a case of reMVR in a patient with an H–S valve that had been implanted 33 years previously.     

Severe aortic insufficiency secondary to an aortic bioprosthesis tear.

A patient with a 10-year-old Medtronic Hancock II porcine aortic bioprosthesis developed severe aortic insufficiency. A transesophageal echocardiogram showed a long and mobile mass attached to the bioprosthesis which was consistent with a torn cusp. The patient underwent replacement of the prosthesis with a mechanical valve. Pathological examination showed two subacute tears arising from the same suture buttressing site. These two tears allowed a portion of the valve apparatus to prolapse.     

Dissecting cuspal hematomas. A rare form of porcine bioprosthetic valve dysfunction

Large dissecting cuspal hematomas (DCHs) were present in six (3%) of 193 porcine bioprostheses (PBs) explanted at reoperation. In four mitral PBs, the DCHs contributed to valve dysfunction; in one aortic PB, DCH was the only determinant of failure, causing stenosis by cusp thickening and rigidity. In another mitral PB, DCHs were occasionally found in the setting of valve incompetence due to commissural tears. While confirming that DCHs are a potential but infrequent cause of PB failure, these observations demonstrate that they may involve PBs implanted both in mitral and aortic position and might be a complication of anticoagulation.     

Pannus overgrowth after mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis

A Carpentier-Edwards pericardial (CEP) bioprosthesis was explanted from an 81-year-old woman due to nonstructural dysfunction 9 years after mitral valve replacement. The nonstructural dysfunction produced severe regurgitation in the mitral position. During the surgery, excessive pannus overgrowth was seen on the left ventricular side of the CEP bioprosthesis. Pannus overgrowth was prominent on one leaflet. That leaflet was stiff and shortened due to the excessive overgrowth of pannus. In this patient, the distortion of one leaflet was the main reason for transvalvular leakage of the CEP bioprosthesis in the mitral position. A new CEP bioprosthesis was implanted in the mitral position. Pathological analysis revealed fibrotic pannus with a small amount of cellular material over the leaflets of the resected CEP valve. This change was marked on the distorted leaflet.     

Ionescu-Shiley bovine pericardial bioprostheses. Histologic and ultrastructural studies.

Studies were done on the structural changes that develop in Ionescu-Shiley valves that are used as replacement heart valves for 4 to 8 years. These changes were compared with those found in similarly used porcine aortic valve (PAV) bioprostheses. A variety of morphologic differences were observed between bovine pericardial valve (BPV) and PAV bioprostheses after orthotopic implantation including: primary tissue failure associated with the use of an alignment suture, thickening of valve leaflet, leaflet tissue delamination, leaflet calcification, and dystrophic alterations of collagen. These findings indicate that valve design criteria directly influence the durability of pericardial valves. However, other factors unique to pericardial tissue also affect the durability and performance of BPVs. These factors include the inability of pericardial tissue to accommodate dynamic stresses; the extensive insudation of plasma proteins and lipids; and the inability to reduce leaflet calcification using agents that effectively mitigate calcification in PAV bioprostheses.     

Collagen fiber disruption occurs independent of calcification in clinically explanted bioprosthetic heart valves

The durability of bioprosthetic heart valves (BHV) is severely limited by tissue deterioration, manifested as calcification and mechanical damage to the extracellular matrix. Extensive research on mineralization mechanisms has led to prevention strategies, but little work has been done on understanding the mechanisms of noncalcific matrix damage. The present study tested the hypothesis that calcification-independent damage to the valvular structural matrix mediated by mechanical factors occurs in clinical implants and could contribute to porcine aortic BHV structural failure. We correlated quantitative assessment of collagen fiber orientation and structural integrity by small angle light scattering (SALS) with morphologic analysis in 14 porcine aortic valve bioprostheses removed from patients for structural deterioration following 5-20 years of function. Calcification of the explants varied from 0 (none) to 1+ (minimal) to 4+ (extensive), as assessed radiographically. SALS tests were performed over entire excised cusps using a 0.254-mm spaced grid, and the resultant structural information used to generate maps of the local collagen fiber damage that were compared with sites of calcific deposits. All 42 cusps showed clear evidence of substantial noncalcific structural damage. In 29 cusps that were calcified, structural damage was consistently spatially distinct from the calcification deposits, generally in a distribution similar to that noted in porcine BHV subjected to in vitro durability testing. Our results suggest a mechanism of noncalcific degradation dependent on cuspal mechanics that could contribute to porcine aortic BHV failure.     

Pathological and clinical study of calcification of the mitral valve ring

The pathology and clinical features of 258 cases of mitral ring calcification were reviewed. The overall incidence in patients over 50 years of age was 8.5%; it was more than twice as high in women (11.5%) as in men (4.5%) and rose sharply with age.Cardiac failure and systolic murmurs were each noted in over half the patients. Hypertension was slightly commoner than in age- and sex-matched groups without ring calcification, although the difference was not statistically significant.Small nodules of calcification were more frequent in men and heavy deposits in women. Distortion and atrial displacement of the posterior mitral cusp was present in 26% of the hearts with early ring calcification, in 56% of the hearts with moderate, and in almost all hearts with marked changes. Systolic murmurs had been heard in 73% of these cases. ;Caseation' of the calcified ring was seen in seven hearts and haemorrhagic valvulitis in three. Calcium had ulcerated through the cusp in 12 cases, with thrombotic and/or bacterial endocarditis in five. Aortic valve calcification was present in 36% of men and was quantitatively related to the severity of mitral ring calcification. In women the incidence was 30% and there was no corresponding quantitative relationship.Microscopy showed nonspecific chronic inflammatory changes adjacent to calcium in about half the cases in both sexes, with foreign body type giant cells in 6%. Similar inflammatory changes in the valve cusp were almost twice as common in women as in men.There was no evidence that previous endocarditis was responsible for mitral ring calcification, neither did parity influence its incidence. Severe coronary atherosclerosis was unrelated but severe aortic atherosclerosis was commoner in patients with calcified mitral rings. The difference, in women, was statistically significant.The higher incidence of severe degrees of ring calcification, complications, and valvular inflammation in women suggests a sex-determined difference in tissue response in the mitral area. Possible provoking factors apply to both sexes and both left side valves, and such a difference would account for the relative frequency and sex incidence of mitral ring calcification.     

Freestyle stentless bioprosthesis for active aortic infectious endocarditis with undetermined causative organism

A 52-year-old woman developed congestive heart failure and was diagnosed with aortic regurgitation with approximately 20 mm of vegetation located on the noncoronary cusp of the aortic valve. The patient had undergone tooth extraction 3 months earlier, and various antibiotics had been given in the treatment of refractory high fever for 1 month. The damage to the aortic valve extended to the fibrous trigone near the mitral valve, and aggressive debridement of necrotic and infected tissue was done. The excised defect was repaired and reinforced with a pericardial patch, and the Freestyle stentless bioprosthesis was implanted using the full-root technique. Although the causative organism was never isolated, recurrent endocarditis has not occurred during 3 years of follow-up. The Freestyle stentless bioprosthesis was useful in the management of active aortic infectious endocarditis with undetermined causative organism for the prevention of recurrent endocarditis in the early postoperative period.     

Selective bundle reconstruction in partial ACL tears leads to excellent long-term functional outcomes and a low percentage of failures

BackgroundThe optimal treatment of partial anterior cruciate ligament (ACL) tears continues to be debatable. Short-term results of selective bundle reconstruction have already been widely shown. The purpose of this study was to assess functional outcomes, subjective satisfaction and the failure rate of selective bundle reconstructions for partial ACL tears over a five to nine year follow-up period.MethodsPatients who underwent ACL selective bundle reconstruction between October 2008 and October 2012 were studied. Functional assessment was performed with the objective International Knee Documentation Committee (IKDC) ligament evaluation form, the Lysholm knee scale and the Tegner activity level scale. Cumulative failure and level of satisfaction have also been investigated.ResultsSeventy-six patients were included. The average follow-up period was 85 months (range 65–110). Thirty-four had AMB tear and 42 had PLB tears. An overall statistically significant improvement (p < 0.001) was obtained in terms of the subjective IKDC and the Lysholm questionnaire between preoperative and last follow-up. The same or no more than one level lower Tegner score was restored in 97.3% of the cases. Cumulative failure was observed in two patients (2.6%). Dissatisfied patient percentage was 15% (4/76).ConclusionsSelective bundle reconstruction in partial ACL tears leads to excellent long-term functional outcomes, a low percentage of failures and a high degree of subjective satisfaction in patients.Level of evidenceTherapeutic case series; level 4.     

HIF-1α and VEGF: Immunohistochemical Profile and Possible Function in Human Aortic Valve Stenosis

Calcific aortic stenosis (CAS) is the most common valvular disease in Western countries. Histological findings in patients with CAS extremely resemble those of atherosclerosis and include accumulation and modification of lipoproteins, inflammation, extracellular matrix remodeling, and calcification. Angiogenesis is another prominent feature of CAS; however, there is only a limited amount of data available regarding the mechanisms behind the pathological neovascularization of a structure that is originally avascular. The present study aims to identify the molecular basis that regulates blood vessel growth in stenotic aortic valves, focusing on the role of HIF-1α and VEGF pathway. A total of 19 native degenerating aortic valves obtained at valve replacement surgery have been processed for Western blot, immunohistochemical, morphometric, and ultrastructural analyses. First, we have demonstrated the adverse ECM remodeling and the significant thickening of the leaflet also showing that HIF-1α and VEGF are significantly upregulated in the stenotic valves, are locally produced and colocalize with angiogenesis and areas of calcification. Next, we have characterized, for the first time to the best of our knowledge, the morphological features of the neovasculature evidencing the presence of intact blood vessels in close proximity to the mineralized zones. These results suggest that the complex structural remodeling of the matrix might reduce oxygen availability in the valve cusp contributing to the stabilization of HIF-1α that in turn induces a metabolic adaptation through the upregulation of VEGF and the formation of new blood vessels not only to overcome the hypoxic state but also to sustain the calcification process.     

Surface-immobilized biomolecules on albumin modified porcine pericardium for preventing thrombosis and calcification.

The search for a noncalcifying tissue material to be used for valve replacement application continues to be a field of extensive investigation. A series of porcine pericardial membranes was prepared by modifying the glutaraldehyde--treated tissues with albumin and subsequently immobilizing bioactive molecules like PGE1, PGI2 or heparin via the carbodiimide functionalities. The in vitro calcification and collagenase degradation of these modified tissues were studied as a function of exposure time. Furthermore, the biocompatibility aspects of such novel interfaces were established by platelet adhesion and fibrinogen adsorption. The results reported in this article propose that the treatment with antiplatelet agents such as albumin, heparin and prostaglandins (PGE1 or PGI2) change the surface conditioning of pericardial tissues, suggesting a possible role of deposited serum components in affecting mineralization process on bioprosthesis. Therefore, it is worthy to hypothesize that besides inhibiting the accumulation of calcium in the devitalized cells, the early formation of a conditioning layer on the bioprosthesis surface may affect salt precipitations, determining the propensity of the implant to calcify. More detailed studies are needed to understand the involvement of plasma proteins and cellular components of the recipient blood in tissue-associated calcification.