Long-term results of porcine bioprosthetic valves

Between November 1977 and October 1980, 54 patients underwent valve replacements with porcine bioprostheses at Hyogo Kenritsu Amagasaki Hospital. The late complications and the long term durability of 53 porcine bioprostheses were documented in 48 patients after discharge (34 mitral, 7 aortic, 2 tricuspid, and 5 multiple, consisting of 38 Hancock, 15 Carpentier-Edwards prostheses). Cumulative duration of follow-up is 420 patient-years. The valve related late mortality was 0.52%/patient-years. There were 6 thromboembolic events (1.6% patient-years), only 1 episode of endocarditis (0.26%/patient-years). Valve dysfunction is defined as stenosis or regurgitation by echocardiogram or cardiac catheterization. There were 21 instances of porcine bioprosthetic dysfunction (6.6% patient-years). Freedom from valve dysfunction at 12 years was 24.4%. There were 17 valves of mitral bioprosthetic dysfunction (6.4% patient-years). The incidences of mitral stenosis (MS), mitral regurgitation (MR), and paravalvular leakage were 4.5, 3.6, and 0.7%/patient-years respectively. Freedom from MR was higher than MS at 8 years. The 14 patients were needed reoperation due to valve dysfunction (3.6%/patient-years). We concluded that the porcine bioprostheses showed a high incidence of valve dysfunction at 7 to 8 years after operation, we presently choose mechanical valve in most cases.     

Binding of preformed xenoantibodies to porcine bioprosthetic valves

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.     

Fifteen-year experience with 1678 Hancock porcine bioprosthetic heart valve replacements

The Hancock porcine valve was the first commercially available biologic heart valve and has been in continuous use at the Brigham and Women's Hospital since January 1972. Through December 1987 we implanted 1678 valves in 1533 patients (885 male; 648 female; 17 to 95 years of age, with a mean of 60 years). There were 825 aortic valve replacements (AVR), 562 isolated mitral valve replacements (MVR), and 146 aortic mitral replacements (DVR). Ninety-four per cent of the patients were functional class III or IV. Associated coronary bypass was done in 25% of patients. Four per cent of patients were lost to follow up during a 1- to 16-year period with a mean of 6 years. Morbidity and mortality rates on a actuarial basis were calculated 10 and 15 years after operation for AVR, MVR, and DVR. The data indicates that the probability of reoperation for structural valve failure is quite reasonable as of 10 years, but from 10 to 15 years the numbers sharply fall off so that the probable effective life of the valve is 10 years. However in the elderly age group (equal to or greater than 70 years of age) the incidence of structural valve degeneration is markedly diminished, making this an ideal valve substitute for the elderly. It is also an ideal valve substitute in any patient who has a contraindication to long-term anticoagulation because of current medical or surgical problems.     

Seven year experience with mounted porcine valves.

From March, 1969, through June 1976, 108 porcine aortic xenograft valves were used for mitral or aortic valve replacement in 95 patients. This experience provides one of the longest follow-ups available for evaluation of the porcine bioprosthesis. The first fifteen valves were locally mounted on Cutter stents and preserved in buffered formalin. Subsequent valves were prepared by the Edwards and Hancock Companies with glutaraldehyde preservation. Oral anticoagulation was routinely used for the first 6 weeks following surgery. Hospital mortality was unrelated to the valve type. All but four of the surviving patients with formalin preserved valves have required reoperation because of valve failure. There have been two valve failures in the patients who received gluteraldehyde valves, but there have been no embolic or thrombotic complications. Late cardiac catheterization has shown hemodynamic results equal to or better than prosthetic valves. The continuing long-term results indicate that the porcine xenograft is the valve of choice for cardiac valve replacement.     

Effect of warfarin on calcification of spontaneously degenerated porcine bioprosthetic valves

Synthesis of a calcium-binding amino acid, gamma-carboxyglutamic acid, is a vitamin K-dependent enzymatic process. Warfarin inhibits gamma-carboxyglutamic acid synthesis and, therefore, might diminish the calcification of porcine bioprosthetic valves. To evaluate this, we studied 40 porcine bioprosthetic valves removed because of spontaneous degeneration; 17 patients were treated with warfarin (prothrombin time greater than or equal to 1.5 control) and 23 were untreated. Gross visualization of calcification corresponded closely to x-ray visualization of calcification in explanted valves. No grossly visible calcification or only a single localized nodule was shown in 11 of 17 valves (65%) in treated patients and in only five of 23 valves (22%) in untreated patients (p less than 0.02). Histologic examination showed no calcium or only fine specks of calcium in nine of 13 valves (69%) among warfarin-treated patients and three of 19 valves (16%) from untreated patients. Warfarin, therefore, administered in usual clinical doses, appeared to diminish calcification in spontaneously degenerated porcine bioprosthetic valves.     

Incidence of primary tissue valve failure in porcine bioprosthetic heart valves

This report provides retrospective follow-up data on 324 consecutive patients who received a Hancock-I porcine valve in the aortic or the mitral position, or in both positions, between June, 1974, and December, 1976. This analysis included 319 valves (193 mitral, 126 aortic) available for study of the incidence of primary tissue valve failure after 10 to 12.5 years of follow-up. Of the 319 prostheses at risk, 114 instances of primary tissue valve failure occurred. Seventy-three of the failed valves were in the mitral position, and 41 were in the aortic position. The calculated actuarial probability of freedom from primary tissue valve failure was 52 +/- 5% for the mitral and 58 +/- 6% for the aortic prostheses at 12.5 years of follow-up. For patients older than 40 years at the time of operation, the rate of freedom from primary failure was 68 +/- 8% and 55 +/- 6% for aortic and mitral prostheses, respectively, at 12.5 years. Comparison of both actuarial curves disclosed no meaningful difference. However, a tendency toward greater failure rate was observed in the mitral prosthesis group.     

Relation of calcification to torn leaflets of spontaneously degenerated porcine bioprosthetic valves

The gross appearance of 54 spontaneously degenerated porcine bioprosthetic valves was evaluated to determine the relation of calcium deposition to cusp disruption. Tears or perforations were shown in 89% (48) of the degenerated valves. The most common site of tears or perforations was near the commissural attachment (60% of all tears). Grossly visible deposits of calcium salts that ruptured to the surface of the cusps or caused changes in the topography were observed in 70% (38) of the 54 valves. Calcification was adjacent to tears or perforations in 56% (27) of the 48 valves with torn cusps. Among the valves that showed calcification, the deposits of calcium salts were adjacent to tears or perforations in 71% (27 of 38). The location of deposits of calcium did not relate to the age or sex of the patient or to the position of the valve, but valves with calcium were inserted longer than valves with no calcium (87 +/- 4 versus 58 +/- 7 months; p less than 0.001). The outflow surfaces showed more calcification than the inflow surfaces, irrespective of whether the valves were in the aortic or mitral position. Among the 38 valves with calcification, 92% (35) showed calcification at the commissural attachments, 53% (20) showed calcification in the body of 1 or more cusps, 11% (4) near the base, and 8% (3) near the free edge. In conclusion, most patients with spontaneous porcine valve degeneration showed calcification. The calcification was associated with tears or perforations of the cusps in 50% of all degenerated valves, in 56% of valves with torn cusps, and in 71% of valves that showed gross calcification.     

LVAD support in patients with bioprosthetic valves

The presence of mechanical or bioprosthetic valves has traditionally excluded patients from mechanical circulatory support. However, several centers have now developed algorithms for the surgical management of native or prosthetic valve disease in patients requiring left ventricular assist device insertion. We report adverse events associated with bioprosthetic valves in the mitral and tricuspid positions in 2 patients who received long-term mechanical support. We recommend anticoagulation for all patients with prosthetic valves in the mitral or tricuspid position to avoid thromboembolism, inflow conduit occlusion, or valvular incompetence.     

Cardiac transplantation: An eight-year experience

From June 1985 to June 1993, a total of 199 orthotopic (2 retransplanted) and one heterotopic cardiac transplants were performed in patients whose ages ranged from 17to 66(average 53)years. There were 175 (87.5%) males and 25 (12.5%) females. The aetiology of end-stage heart disease included: ischaemic heart disease 138 (69%); idiopathic cardiomyopathy 53 (26.5%); valvular disease 7 (3.5%); and adriamycininduced cardiomyopathy in 2 (1%). At the time of surgery, 56 (26.5%) patients were in United Network for Organ sharing (UNOS) Status I (ICU, intra-aortic balloon other assists, inotropic support) and 144 (72%) were UNOS Status II. The majority of donors were local or within the state. Two immunosuppressive protocols have been utilised, viz., conventional triple drug therapy and OKT3 induction. The mean rejection has been 2.5 episodes/patient. The majority of these episodes, (72 %) occurred within the first three months. Of the 1.8 infectious episodes per patient, opportunistic organisms predominated with a 98 per cent recovery. We have experienced 53 postoperative deaths. Currently, 147 (73.5%) recipients are alive and well. Our one-year actuarial survival is approximately 82per cent, the five year figure being 64 per cent. Tampa General Hospital is, at present, one of the most active cardiac transplant centres in the USA. Our eightyear experience has allowed us to mature through our learning curve to become an established, successful cardiac transplant program.     

Mechanical stresses on closed cusps of porcine bioprosthetic valves: correlation with sites of calcification

The purpose of this study was to (1) evaluate the magnitude and distribution of mechanical stresses on closed leaflets of porcine bioprosthetic valves (PBVs) by using a nonlinear, finite-element model, and (2) determine if a relationship exists between the magnitude of stresses at various sites on the leaflet and the incidence of calcification at those sites. Mechanical stresses were found to be highest near the commissures and lowest at the base of the leaflet. At a pressure of 100 mm Hg applied to the closed valve, the maximal principal normal stress was 160 kPa near the commissures, 140 kPa in the body of the leaflet, 70 kPa at the free margin, and 60 kPa near the base. Similarly, the maximal shear stress, at an applied pressure of 100 mm Hg, was 80 kPa near the commissures, 70 kPa in the body of the leaflet, 50 kPa at the free margin, and 40 kPa near the base. This distribution of mechanical stresses on the PBV leaflet coincided with the incidence of calcification of the various regions of the leaflet. Calcification was found most frequently near the commissures, less frequently in the body of the leaflet and free margin, and least frequently at the base. These observations suggest a possible causative relation between the magnitude of mechanical stresses and the site of calcification of PBV leaflets.     

The porcine bioprosthetic heart valve: experience at 15 years

The porcine bioprosthetic valve has been in use at Henry Ford Hospital since 1971. In this review, 980 patients with 1,081 porcine bioprosthetic valves were examined from 1 month to 16.4 years after implantation with a 99% complete follow-up. Patient survival was 59% +/- 2.2% (+/- standard error of the mean) at 10 years and 38% +/- 4.0% at 15 years. Factors associated with decreased survival after hospital discharge were age greater than 35 years and New York Heart Association functional class IV. Freedom from thromboembolism was 92% +/- 1.2% at 10 years and 89% +/- 3.2% at 15 years. Freedom from endocarditis was 93% +/- 1.2% at 10 years and 92% +/- 1.3% at 15 years. Freedom from structural valve degeneration for all valves was 71% +/- 2.6% at 10 years and 31% +/- 5.6% at 15 years. Factors associated with increased risk of structural valve degeneration were age younger than 35 years, female sex, and preoperative cardiac index greater than 2 L/min/m2. Among a total of 172 patients undergoing removal of a degenerated valve, mortality was 12.5%, and significant risk factors for death at reoperation were emergency operation and functional class IV. Experience with the porcine bioprosthetic valve after 15 years suggests that its use be confined to older patients or patients with a contraindication of anticoagulation.     

Dynamic in vitro calcification of bioprosthetic porcine valves: evidence of apatite crystallization

OBJECTIVE: Calcification is the most important cause of structural deterioration of glutaraldehyde-fixed bioprosthetic valves. Devitalization of tissue favors calcium deposits in the shape of apatite crystals. Host factors influence the extent and progression of calcification, but the phenomenon can also occur in vitro in the absence of a viable milieu. Whether calcific deposits obtained in vitro are similar to those found in vivo is unknown. METHODS: Four porcine frame-mounted bioprostheses (St Jude Medical Bioimplant; St Jude Medical, Inc, St Paul, Minn) were tested in vitro by using a pulsatile accelerated calcification testing device at a frequency of 300 cycles per minute at 37 degrees C for 19 x 10(6) cycles with a rapid synthetic calcification solution (final product [calcium x phosphate], 130 mg/dL(2)). Three of the same type of xenografts explanted from human subjects because of calcific failure (time in place, 108 +/- 25.63 mo) served as control grafts. Each sample underwent gross and x-ray examination, histology, transmission and scanning electron microscopy, atomic absorption spectroscopy, electron microprobe analysis, and x-ray powder diffraction methods. RESULTS: All in vitro bioprostheses were heavily calcific, with intrinsic Von Kossa stain-positive deposits and a mean calcium content of 205.285 +/- 64.87 mg/g dry weight. At transmission electron microscopy, nuclei of calcification involved mostly collagen fibers and interfibrillar spaces and, more rarely, cell debris and nuclei. Electron microprobe analysis showed a Ca/P atoms ratio of 4.5:3, a value intermediate between hydroxyapatite and its precursor, octacalciumphosphate. X-ray powder diffraction showed a well-separated and sharp peak, which is typical of hydroxyapatite. Aggregates of plate-like crystals up to 8 microm in size were observed at scanning electron microscopy, with a typical tabular hexagonal shape consistent with apatite. The morphologic and chemical findings in human explants were similar. CONCLUSIONS: Intrinsic calcification of glutaraldehyde-fixed porcine valves was induced in vitro. Electron microprobe analysis and x-ray powder diffraction findings were in keeping with apatite crystallization, such as that occurring in valve xenografts implanted in vivo. The model may be of value to accelerate the screening of anticalcific agents and may reduce the need for animal experiments.     

Late results with bioprosthetic valves in the elderly

AIM: We report the long-term outcome of aortic and mitral bioprostheses in patients over 65 years of age at the time of implantation. The aim was to determine actuarial patient survival, causes of death, and the rate of documented primary structural deterioration. METHODS: One hundred ten patients > or = 65 years of age (mean, 73.4; range, 65-82) underwent successful bioprosthetic valve replacement (aortic, n = 71; mitral, n = 32; both, n = 7) from 1979 to 1985. The valve was pericardial in 39 cases and porcine in 78. The mean follow-up was 8.5 years (101.9 months-total; 934 patient-years; range, 2 months to 15 years). RESULTS: Actuarial patient survival was 79.6% (71-86) at 5 years and 62.4% (52-71) at 10 years. Forty-four patients died, 21 from valve-related causes and 23 from other causes. Thirteen patients (11.8%) had reoperation for valve-related complications: 10 structural deteriorations, 2 paravalvular leaks, and 1 case of endocarditis. One surgical death occurred (7.7%). Twenty-six percent of the patients were receiving anticoagulants because of atrial fibrillation, and 6.4% developed severe bleeding (2.9% patient-years). CONCLUSIONS: Long-term follow-up of these patients > 65 years of age, undergoing bioprosthetic value replacement surgery revealed a low rate of documented primary structural deterioration (0.95% per patient-year), a low mortality rate on reoperation (7.7%), and a high mortality rate due to non-value-related causes (52.3%).     

Long-term results of porcine bioprosthetic heterograft; a 13-years' experience

One hundred and ninety-four patients underwent valve replacements with the glutaraldehyde-preserved porcine bioprostheses (133 Hancock valves, 39 Angell-Shiley valves, 22 Carpentier-Edwards valves and 3 other valves) from 1974 through 1979. There were 105 women and 89 men, whose age ranged 18 to 62 (mean 38.8) years. One hundred and eighty-two patients had mitral bioprosthetic valve replacement (BVR)s, of which 52 had combined aortic mechanical valve replacements, 8 had aortic BVR's, 3 had tricuspid BVR's and 3 had multi-BVR's. Operative mortality was 10.8%. Only one patient was lost to follow-up. Cumulative duration of follow-up is 1421 patient-years. Linearized rate of anticoagulant related hemorrhage, thromboembolism (TE), prosthetic valve endocarditis (PVE), primary tissue failure (PTF) and valve dysfunction (VD) were 0.07, 1.62, 0.49, 2.74 and 3.66% per patient-year. Actuarial freedom from TE, PVE, PTF and VD were 87.0 +/- 2.7%, 95.6 +/- 1.5%, 65.2 +/- 4.9% and 56.9 +/- 5.6% at 13 years. Actuarial survival rate was 67.4 +/- 4.0% at 13 years. Long term follow-up after valve replacement with porcine bioprosthetic valve confirms low thrombogenicity. But primary tissue failure was the chief cause of valve dysfunction and represent a major problem. At this time, we are going to use porcine bioprosthetic valve in the selected patients, that is in the situations in which anticoagulation is contraindicated.     

Structural valve deterioration of bioprosthetic aortic valves: An underestimated complication

Objectives

Structural valve deterioration (SVD) remains a major bioprosthesis-related complication, as recently described for the Mitroflow valve (models LX and 12A) (LivaNova, London, United Kingdom). The real incidence of the SVD risk remains unclear, often due to methodologic pitfalls by systematically using the Kaplan-Meier estimator and/or the Cox model. In this report, we propose for the first time a precise statistical modeling of this issue.

Fresh porcine cardiac valves are not rejected in primates

OBJECTIVE: Transplanted porcine hearts are hyperacutely rejected by human immunoglobulin M antibodies against a porcine vascular endothelial molecule, galactose alpha-1,3-galactose, with ensuing human complement activation and membrane attack complex deposition. It is unclear, however, whether porcine valve endothelium triggers a similar immune response. We sought to investigate whether fresh porcine valves implanted into primates are rejected. METHODS: Wild-type porcine hearts before (n = 6) and after (n = 3) heterotopic transplantation into baboons underwent sectioning and were examined by hematoxylin and eosin staining and immunohistochemistry for galactose alpha-1,3-galactose, primate immunoglobulin M, and membrane attack complex. RESULTS: Examination of untransplanted porcine hearts showed that although cardiac microvascular endothelium strongly expressed the galactose alpha-1, 3-galactose antigen, galactose alpha-1,3-galactose was not detected on the endothelium of porcine aortic and pulmonary valves. Porcine hearts transplanted into baboon recipients were hyperacutely rejected 60 to 80 minutes after implantation. Despite dramatic tissue damage associated with extensive immunoglobulin M and membrane attack complex binding on the microvascular endothelium, the aortic and pulmonary valves were entirely spared. Valves remained morphologically intact at explant and showed no signs of immunoglobulin M- and membrane attack complex-mediated damage. CONCLUSIONS: The absence of galactose alpha-1,3-galactose expression may protect unfixed porcine valves from xenograft rejection in primates. Further investigation of viable porcine valves appears warranted.     

Bioprosthetic valves — An initial experience

Aim. The aim of the study was to assess the functional status, performance and complications of bioprosthetic valves implanted in forty five consecutive patients at All India Institute of Medical Sciences, New Delhi between January 2000 and September 2001. Method. The preoperative, operative and postoperative data were collected from case records and at follow up. Results. Hospital Mortality was 6.6% (3 out of 45) and incidence of all complications was 4.9%. There was one valve related death (2.4%). There was no structural failure or anticoagulant related haemorrhage. The incidence of thromboembolism and infective endocarditis were 2.4%. Postoperative gradients were low. Conclusion. The early clinical performance and in vivo hemodynamics of Carpentier Edwards (Porcine) bioprosthesis in our experience is satisfactory.