Bioprosthetic heart valves--replacing order with chaos: electron microscopic study

Rheumatic heart disease is a significant clinical entity in young children, especially in the developing world. One of the major long-term effects of ill managed rheumatic fever is irreversible damage to the cardiac valve leaflets, primarily on the left side. With the limited success of currently available mechanical and bioprosthetic valves, there is an urgent need for new directions in bioprosthetic valves, both in material, including source, degree of fixation, surface, bulk modifications, etc., and design. In the present paper, new proposals in the material selection and fabrication of bioprosthetic valves are proposed based on electron microscopic studies of natural valve leaflets and the pericardial surface. Current approaches for bioprosthetic valve fabrications include the wide use of the pericardium as a leaflet material. The present study indicates a need for nondestructive surface examination of pericardial sheets for the elimination of areas of surface voids resulting from gross fiber disorientation. Also, there seems to be a need for incorporation of an in situ fiber renewal mechanism in bioprosthetic leaflets to emulate the natural valve more closely. Apparently natural leaflets have built-in fiber renewal mechanism(s).     

Rapid and untypical calcification of the Sorin pericarbon stentless pericardial xenograft in a child

Stentless valves are designed to reduce mechanical stress and it is hypothesized that degeneration is reduced. We report early calcification of a Sorin pericarbon stentless pericardial xenograft in aortic position leading to valve failure 2 years after valve replacement in an 11-year-old boy. Morphological evaluation of the explant revealed severe calcification of the leaflets in a uniformly distributed pattern. Positive staining for non-collagen bone matrix proteins was found in the organic matrix of calcific deposits and in infiltrated macrophages. The stentless design of the Sorin valve does not mitigate calcification and therefore cannot be recommended for children.     

Comparison of tensile properties of xenopericardium from three animal species and finite element analysis for bioprosthetic heart valve tissue

Bioprosthetic heart valves still have poor long-term durability due to calcification and mechanical failure. The function and performance of bioprostheses is known to depend on the collagen architecture and mechanical behavior of the target tissue. So it is necessary to select an appropriate tissue for such prostheses. In this study, porcine, equine, and bovine pericardia were compared histologically and mechanically. The specimens were analyzed under light microscopy. The planar biaxial tests were performed on the tissue samples by applying synchronic loads along the axial (fiber direction) and perpendicular directions. The measured biaxial data were then fitted into both the modified Mooney-Rivlin model and the anisotropic four parameter Fung-type model. The modified Mooney-Rivlin model was applied to the modeling of the bovine, equine, and porcine pericardia using finite element analysis. The equine pericardium illustrated a wavy collagen bundle architecture similar to bovine pericardium, whereas the collagen bundles in the porcine pericardium were thinner and structured. Wavy pericardia may be preferable candidates for transcutaneous aortic valves because they are less likely to be delaminated during crimping. Based on the biaxial tensile test, the specimens indicated some degree of anisotropy; the anisotropy rates of the equine specimens were almost identical, and higher than the other two specimens. In general, porcine pericardium appeared stiffer, based on the greater strain energy magnitude and the average slope of the stress–stretch curves. Moreover, it was less distensible (due to lower areal strain) than the other two pericardial tissues. Furthermore, the porcine model induced localized high stress regions during the systolic and diastolic phases of the cardiac cycle. However, increased mechanical stress on the bioprosthetic leaflets may cause tissue degeneration and reduce the long-term durability of the valve. Based on our observations, the pericardial specimens behaved as anisotropic and nonlinear tissues—well-characterized by both the modified Mooney-Rivlin and the Fung-type models. The results indicate that, compared to bovine pericardium, equine tissue is mechanically and histologically more appropriate for manufacturing heart valve prostheses. The results of this study can be used in the design and manufacture of bioprosthetic heart valves.     

A morphologic study of Carpentier-Edwards pericardial xenografts in the mitral position exhibiting primary tissue failure in adults in comparison with Ionescu-Shiley pericardial xenografts

OBJECTIVE: We sought to investigate the durability and mechanism of the Carpentier-Edwards pericardial xenograft in the mitral position in comparison with that of the Ionescu-Shiley pericardial xenograft. METHODS: A total of 284 patients who received the Ionescu-Shiley pericardial xenograft in the mitral position between 1980 and 1984 and 84 patients who received the Carpentier-Edwards pericardial xenograft in the mitral position between 1984 and 1999 were included in the study. The freedom from reoperation rates for both graft types were determined. For morphologic study, the pathologic findings of 23 valves of 123 explanted Ionescu-Shiley pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both were determined and compared with those of 20 explanted Carpentier-Edwards pericardial xenografts with structural valve deterioration, nonstructural valve deterioration, or both. Each pathologic finding was graded and assigned a score. Both types were matched for age at reoperation (50-75 years) and duration of valve function (8-11 years). RESULTS: Freedom from reoperation caused by structural valve deterioration, nonstructural valve deterioration, or both was significantly better for Carpentier-Edwards pericardial xenografts than for Ionescu-Shiley pericardial xenografts at 8 years after the operation (Carpentier-Edwards pericardial xenografts: 91.3% vs Ionescu-Shiley pericardial xenografts: 71.9%, P =.0061), but it was similar for both types at 12 years (Carpentier-Edwards pericardial xenografts: 43.6% vs Ionescu-Shiley pericardial xenografts: 43.6%, P =.2865). No severe leaflet tears were seen among Carpentier-Edwards pericardial xenografts. The mean area percentage of tissue overgrowth was 15.3% in Carpentier-Edwards pericardial xenografts and 3.4% in Ionescu-Shiley pericardial xenografts (P =.0001). The mean calcification area percentage was 13.6% in Carpentier-Edwards pericardial xenografts and 31.5% in Ionescu-Shiley pericardial xenografts (P =.0001). CONCLUSIONS: Tissue overgrowth on the atrial surface, ventricular surface, or both was the cause of structural valve deterioration, nonstructural valve deterioration, or both of Carpentier-Edwards pericardial xenografts in adults. This was different from Ionescu-Shiley pericardial xenograft failure, which resulted from severe calcification and leaflet tears. Organized thrombi on cusps, in addition to valve design, may have contributed to such tissue overgrowth on Carpentier-Edwards pericardial xenografts.     

The Autogenous Tissue Heart Valve: Current Status

Residual antigenicity of xenograft tissue after glutaraldehyde tanning may be a factor that determines calcification and durability of bioprostheses. We have pursued the concept of a nonantigenic, noncalcifying, more durable bioprosthesis. We previously described a technique for rapid intraoperative fabrication of an autogenous tissue heart valve (ATHV). That technique has been modified to improve reliability and ease of learning. With the modified technique, a geometrically perfect trileaflet valve can be made in 5 minutes. Although any suitable tissue can be used, the pericardial ATHV is the subject of this report. Autogenous pericardium immersed for 5 minutes in glutaraldehyde has proven satisfactory for valve construction. In vitro testing in the pulse duplicator and accelerated life tester has shown that the stent assembly is capable of function beyond 800,000,000 cycles without failure. In vivo testing has been performed in the juvenile sheep model as described by the National Institutes of Health group. Five sheep were maintained for 5 months postimplant before sacrifice. Explanted valves showed no tissue thickening or shrinkage, problems seen with earlier valves made with untreated autogenous tissue, and the leaflets remained pliable, free of the degenerative changes usually seen in the sheep model.     

Stent and leaflet stresses in a 26-mm first-generation balloon-expandable transcatheter aortic valve

Objective

Transcatheter aortic valve replacement is established therapy for high-risk and inoperable patients with severe aortic stenosis, but questions remain regarding long-term durability. Valve design influences durability. Increased leaflet stresses in surgical bioprostheses have been correlated with degeneration; however, transcatheter valve leaflet stresses are unknown. From 2007 to 2014, a majority of US patients received first-generation balloon-expandable transcatheter valves. Our goal was to determine stent and leaflet stresses in this valve design using finite element analyses.

Primary tissue failure in pericardial heart valves

A number of centers have recorded a significant incidence of primary tissue failure with the standard Ionescu-Shiley pericardial valve. In most cases severe regurgitation was caused by leaflet tears adjacent to the edge of the cloth-covered stent. Our early clinical experience (up to 4 years' follow-up) with two new pericardial valves (Ionescu-Shiley low-profile and Hancock pericardial valves) has shown that primary tissue failure also occurs in these new valves. In vitro accelerated fatigue studies on seven of these valves (size 29 mm) showed that in vitro premature leaflet failure was caused by abrasion of the leaflet on the cloth-covering at the edge of the stent. Clinically, endothelialization and host tissue ingrowth on the cloth and the leaflets at the edge of the frame greatly reduced the amount of abrasion and the incidence of tissue failure. In seven of the eight explanted valves studied, leaflet tears occurred at the top of the stent posts where there was less endothelialization and tissue ingrowth, close to the points where sutures pass through the leaflets. It is likely that both abrasion and stress concentration around these sutures contributed to the tissue failures in the clinical valves.     

Do heart valve bioprostheses degenerate for metabolic or mechanical reasons?

Although heart valve bioprostheses provide a normal quality of life, their durability is still of great concern. Their durability failure is defined as "degeneration," which is considered to be a consequence of metabolic factors. In this study, we demonstrate that mechanical and design factors can also be responsible for bioprosthesis failure. Large numbers of porcine and pericardial bioprostheses were tested in a fatigue-testing system in which the test conditions were proved to be reproducible and accurate by a laser Doppler anemometer. The results have allowed us to define causes of failure, previously insufficiently stressed, in each type of valve tested. There is a clear difference in factors influencing tissue disruption between porcine and pericardial valves. We have compared these in vitro results with in vivo clinical findings. The main inferences are as follows: (1) Bioprostheses rupture and fail in the same fashion in both in vitro and in vivo studies. (2) Mechanical and design factors are involved in tissue failure. (3) The in vitro/in vivo durability ratio is not 1:1. This ratio depends on the test conditions. (4) Pericardial valves fail because of damage during closure, whereas porcine valves are damaged during both opening and closing (mostly opening) because of design features. (5) Once one cusp fails and prolapses, the other cusps will fail in an accelerated fashion. (6) In vitro durability of 100 X 10(6) cycles can be considered excellent and is an achievable goal. (7) Variability is the key impediment to predicting the durability of bioprostheses. Valves can fail within 2 to 3 million cycles or can last more than 100 million cycles. Similarly, bioprostheses may require explantation within a few months or can last 10 to 13 years in patients. (8) Fatigue testing is an excellent and valuable tool to elucidate the mechanical factors responsible for this variability.     

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.     

Abdominal cavity unidirectional shunt for refractory pericardial effusion 7 months after cardiac valve replacement: A case report

Refractory pericardial effusion after repeated pericardial drainage and drug therapy for nearly half a year after cardiac valve replacement is rare. We present the case of a 36‐year‐old female patient who underwent an abdominal cavity unidirectional shunt for refractory massive pericardial effusion through a subxiphoid mini‐incision, 7 months after cardiac valve replacement. The head end of a prefabricated bovine pericardial short tube with double leaflets on the tail was sutured to the small incised hole of the diaphragm, whereas the body and the tail of the short tube were dissociated in the left anterior hepatic space. Three months later, the pericardial effusion completely disappeared, no peritoneal effusion occurred, and all symptoms vanished.     

The myth of the aortic annulus: the anatomy of the subaortic outflow tract

Surgical repair of the small aortic root is limited in part by the very structure of the outflow tract from the left ventricle. The root is not constructed on the basis of a ringlike annulus supporting the leaflets of the aortic valve. The only truly circular structure within the outflow tract is the junction of the aortic wall with the underlying ventricular structures, themselves partly muscular and partly fibrous. This circular ventriculoarterial junction is crossed by the semilunar attachments of the leaflets of the aortic valve, producing an interlinking arrangement between the expanded aortic sinuses and three triangles of fibrous tissue placed beneath the apexes of the commissures between the valve leaflets. The triangles form extensions of the left ventricle that are related, in part, to the pericardial cavity surrounding the heart. The arrangements of the attachment of the leaflets in malformed valves with two (or only one) effective leaflets are highly abnormal, although these valves are usually produced on the template of three aortic sinuses. The valve with two leaflets rarely gives problems during childhood. In valves producing "critical stenosis", there is usually only one effective leaflet, a condition due to incomplete liberation of two of the anticipated three commissures. Detailed study shows that, in these malformed hearts, the attachment of the leaflets is much more annular than in normal valves, with inadequate formation of the fibrous triangles.     

Left Main Coronary Artery and Supravalvular Aortic Stenosis in Adult: Treatment with Ostial Patchplasty and Modified Brom Procedure

Abstract   Left main coronary artery (LMCA) stenosis accompanying to supravalvular aortic stenosis is a very uncommon, serious congenital abnormality. Aortic valve leaflet fusions and intimal thickening of the aortic valve leaflets and coronary artery are the underlying pathologies for the LMCA stenosis. We operated on a 21-year-old male patient for supravalvar aortic stenosis with LMCA ostial stenosis. We enlarged the LMCA with a pericardial patch (ostial plasty) and reconstructed the aortic root with a modified Brom procedure. Postoperative course was uneventful; echocardiographic evaluation revealed a normal functioning aortic valve with a normal left ventricular function. Gradient at left ventricular outflow tract was decreased a great deal. Although supravalvular aortic stenosis with LMCA stenosis is a very rare congenital abnormality, this clinical entity can be successfully corrected with detailed and selected surgical procedures.     

The Hancock pericardial xenograft: incidence of early mechanical failures at a medium-term follow-up

The Hancock pericardial xenograft has been used in our Institution since August 1981 as an alternative to porcine bioprostheses. Up to July 1984, 97 Hancock pericardial xenografts have been implanted in 84 patients; of 76 operative survivors with a mean age of 55.2±13 years (range 13–75 years), 50 had undergone aortic valve replacement, 16 mitral valve replacement and 10 mitral-aortic valve replacement. Follow-up ranged from 0.5 to 5.2 years with a cumulative duration of 239 patient/years and is 99% complete. Actuarial survival is 92%±4% for patients with aortic valve replacement and 84%±10% for patients with mitral valve replacement at 5 years, and 77%±14% for those with mitral-aortic valve replacement at 4 years. Thromboembolic episodes occurred in 2 patients (1 after aortic and 1 after mitral valve replacement). The actuarial freedom from emboli is 100% for patients with mitral-aortic valve replacement at 4 years, and 96%±3% for patients with aortic and 93%±6% for patients with mitral valve replacement at 5 years. Reoperation was performed in 13 patients (9 aortic, 2 mitral and 2 mitral-aortic valve replacements), because of endocarditis in 3 (2 aortic and 1 mitral valve replacement), paravalvular leak in 1 (aortic valve replacement), and primary tissue failure in 9 (6 aortic, 1 mitral and 2 mitral-aortic valve replacements). Actuarial freedom from primary tissue failure is 72%±9% for aortic and 83%±8% for mitral Hancock pericardial xenografts at 5 years. Eleven xenografts explanted because of primary tissue failure were studied pathologically. All showed commissural tears with gross regurgitation; calcium deposits were severe in 2, mild but unrelated to the tears in 2 and absent in 7. Collagen disarray was observed at the site of cusp rupture while the collagen was well preserved in the intact areas of the leaflets. Our results show that: 1) Hancock pericardial xenografts have a high rate of early primary tissue failure, 2) primary tissue failure is caused by cusp rupture at the commissures and can be considered fatigue-induced, 3) tissue calcification does not influence the durability of pericardial xenografts which do not represent a valid alternative to porcine bioprostheses.     

In Vitro Evaluation of a Novel Autologous Aortic Valve (Biovalve) With a Pulsatile Circulation Circuit

We have used in‐body tissue architecture technology to develop an autologous valved conduit with intact sinuses of Valsalva (biovalve). In this study, we fabricated three different forms of biovalves and evaluated their function in vitro using a mock circulation model to determine the optimal biovalve form for aortic valve replacement. A cylindrical mold for biovalve organization was placed in a dorsal subcutaneous pouch of a goat, and the implant that was encapsulated with connective tissue was extracted 2 months later. The cylindrical mold was removed to obtain the biovalve (16 mm inside diameter) that consisted of pure connective tissue. The biovalve was connected to a pulsatile mock circulation system in the aortic valve position. The function of the three biovalves (biovalve A: normal leaflets with the sinuses of Valsalva; biovalve B: extended leaflets with the sinuses of Valsalva; biovalve C: extended leaflets without the sinuses of Valsalva) was examined under pulsatile flow conditions using saline. In addition, the mock circuit was operated continuously for 40 days to evaluate the durability of biovalve C. The regurgitation rate (expressed as a percent of the mean aortic flow rate during diastole) was 46% for biovalve A but only 3% for biovalves B and C. The durability test demonstrated that even after biovalve C pulsated more than four million times (heart rate, 70 bpm; mean flow rate, 5.0 L/min; mean aortic pressure, 92 mm Hg), stable continuous operation was possible without excessive reduction of the flow rate or bursting. The developed biovalve demonstrated good function and durability in this initial in vitro study.     

The pericardial valve in the aortic position ten years later

To assess the behavior of the pericardial valve at 10 years after implantation, the cases of 240 patients who had undergone aortic valve replacement with the standard Ionescu-Shiley (Shiley, Inc., Irvine, Calif.) bovine pericardial valve between February 1977 and December 1983 were reassessed. Follow-up of the 224 hospital survivors was 99.6% complete. Fifty-seven valve-related events occurred. Fourteen were thrombotic events (1.2%/patient-year), 28 were intrinsic tissue failures (2.4%/patient-year), 13 were cases of prosthetic valve endocarditis (1.1%/patient-year), and 2 were paravalvular leaks (0.17%/patient-year). The linearized rate for death, reoperation, or both resulting from valve-related events was 3.6%/patient-year. Time-related hazard function for the instantaneous risk of death and/or reoperation resulting from valve-related events demonstrated an exponential increase after 80 months. These data, in conjunction with our previous reports on the histologic changes in pericardial collagen and the incidence of calcification (26/28), should be considered regarding new and future generations of pericardial bioprostheses. Although this device provides good hemodynamics and carries a low incidence of thromboembolism, it has a limited durability. New generations of pericardial valves may have improved structural features, but the behavior of glutaraldehyde-fixed, formaldehyde-stored bovine pericardium as currently selected and prepared is unlikely to change.     

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

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

Pericardial heterografts: why do these valves fail?

Eighteen explanted pericardial heterografts were studied (16 standard Ionescu-Shiley, one Hancock, and one Mitroflow). Regurgitation was the reason given for explantation of all the Ionescu-Shiley valves. The other two valves were removed for technical reasons. All the Ionescu-Shiley valves had commissural tears and there was concomitant gross calcification in 10 of the 16 valves. In addition, an apparent increase in cusp area had caused "leaflet sagging". The explanted leaflets were thicker and stiffer than leaflets from an unimplanted valve. These features were confirmed directly with an animal model of subcutaneous implantation. Examination with an electron microscope revealed that these changes in mechanical properties seemed to be linked to fiber separation and infiltration by an amorphous proteinlike matrix. The durability of the glutaraldehyde-fixed pericardium depended on a number of factors. Early and midterm failure appeared to be stress induced. Predisposition to high mechanical stresses near the stent was exacerbated by the changes induced by the host environment. This problem was aggravated further in the Ionescu-Shiley valves by stress concentrations around the hole associated with the holding suture. In the long term, collagen disruption associated with leaflet flexure was followed by secondary calcification at the boundary between the intact and disrupted material.     

Stent and leaflet stresses in 26-mm,third-generation,balloon-expandable transcatheter aortic valve

Objectives

Transcatheter aortic valve replacement has proven successful in treating intermediate-risk, high-risk, and inoperable patients with severe aortic stenosis. Third-generation, balloon-expandable transcatheter aortic valves were developed with an outer sealing skirt to reduce paravalvular leakage. As transcatheter aortic valve replacement use expands, long-term durability questions remain. Valve design influences durability, where regions of increased leaflet stress are vulnerable to early degeneration. However, third-generation transcatheter aortic valve stresses are unknown. Our goals were to determine the stent and leaflet stresses of third-generation, balloon-expandable transcatheter aortic valves.

Flow patterns in the aortic root and the aorta studied with time-resolved, 3-dimensional, phase-contrast magnetic resonance imaging: implications for aortic valve-sparing surgery

OBJECTIVE: Sparing the aortic valve has become a surgical option for patients who require repair of aortic root ectasia and have normal valve leaflets. Surgical approaches to valve sparing differ with regard to preservation of the native sinuses of Valsalva. The role of the sinuses and the importance of maintaining them remain controversial. METHODS: By using a time-resolved, 3-dimensional, phase-contrast magnetic resonance imaging technique, aortic root and aortic blood velocity data were acquired from 2 patients with Marfan syndrome 6 months after aortic valve-sparing surgery with straight Dacron grafts and contrasted with data from 6 normal volunteers. RESULTS: In normal aortas vortical blood flow became apparent in the individual sinuses after peak systole. The vortices filled the available space behind the valve leaflets and persisted until diastole, expanding and moving inward during aortic valve closure. In contrast, no vortices were observed in the postoperative patients with Marfan syndrome with negligible sinuses. CONCLUSIONS: Changes in supravalvular flow accompany loss of sinus architecture. Whether the presence, size, and velocity of supravalvular vortices affects the function or durability of the preserved aortic valve remains to be studied.     

Aortic valve reconstruction in the young infants and children

Considering the structure and function of the aortic root, changes in the aortic valve leaflets and changes in the geometry of the aortic root are the two primary causes of aortic valve dysfunction. In adults, aortic valve sparing reconstruction has a long history beginning in the 1970s, where tensor fascia was used for leaflet repair in patients with isolated aortic regurgitation and ascending aortic replacement was used in patients with ascending aortic aneurysms or aortic ectasia. Subsequent progress in the 1980s and 1990s led to pericardial leaflet replacement and aortic root re-implantation and remodeling. However, it has not been until the last decade that these concepts and techniques have been applied in younger patients focusing on the conotruncus, valvar apparatus, sino-tubular junction, and ascending aorta.