Biological Prosthetic Heart Valves Research Articles

Ultra-High-Resolution and K-Edge Imaging of Prosthetic Heart Valves With Spectral Photon-Counting CT: A Phantom Study.

The contribution of cardiac computed tomography (CT) for the detection and characterization of prosthetic heart valve (PHV) complications is still limited due mainly to artifacts. Computed tomography systems equipped with photon-counting detectors (PCDs) have the potential to overcome these limitations. Therefore, the aim of the study was to compare image quality of PHV with PCD-CT and dual-energy dual-layer CT (DEDL-CT). Two metallic and 3 biological PHVs were placed in a tube containing diluted iodinated contrast inside a thoracic phantom and scanned repeatedly at different angles on a DEDL-CT and PCD-CT. Two small lesions (~2 mm thickness; containing muscle and fat, respectively) were attached to the structure of 4 valves, placed inside the thoracic phantom, with and without an extension ring, and scanned again. Acquisition parameters were matched for the 2 CT systems and used for all scans. Metallic valves were scanned again with parameters adapted for tungsten K-edge imaging. For all valves, different metallic parts were measured on conventional images to assess their thickness and blooming artifacts. In addition, 6 parallelepipeds per metallic valve were drawn, and all voxels with density <3 times the standard deviation of the contrast media were recorded as an estimate of streak artifacts. For subjective analysis, 3 expert readers assessed conventional images of the valves, with and without lesions, and tungsten K-edge images. Conspicuity and sharpness of the different parts of the valve, the lesions, metallic, and blooming artifacts were scored on a 4-point scale. Measurements and scores were compared with the paired t test or Wilcoxon test. The objective analysis showed that, with PCD-CT, valvular metallic structures were thinner and presented less blooming artifacts. Metallic artifacts were also reduced with PCD-CT (11 [interquartile (IQ) = 6] vs 40 [IQ = 13] % of voxels). Subjective analysis allowed noticing that some structures were visible or clearly visible only with PCD-CT. In addition, PCD-CT yielded better scores for the conspicuity and for the sharpness of all structures (all Ps < 0.006), except for the conspicuity of the leaflets of the mechanical valves, which were well visible with either technique (4 [IQ = 3] for both). Both blooming and streak artifacts were reduced with PCD-CT (P ≤ 0.01). Overall, the use of PCD-CT resulted in better conspicuity and sharpness of the lesions compared with DEDL-CT (both Ps < 0.02). In addition, only with PCD-CT some differences between the 2 lesions were detectable. Adding the extension ring resulted in reduced conspicuity and sharpness with DEDL-CT (P = 0.04 and P = 0.02, respectively) and only in reduced sharpness with PCD-CT (P = 0.04). Tungsten K-edge imaging allowed for the visualization of the only dense structure containing it, the leaflets, and it resulted in images judged having less blooming and metallic artifacts as compared with conventional PCD-CT images (P < 0.01). With PCD-CT, objective and subjective image quality of metallic and biological PHVs is improved compared with DEDL-CT. Notwithstanding the improvements in image quality, millimetric lesions attached to the structure of the valves remain a challenge for PCD-CT. Tungsten K-edge imaging allows for even further reduction of artifacts.

Chitosan/hyaluronic acid polyanion bilayer applied from carbon acid as an advanced coating with intelligent antimicrobial properties for improved biological prosthetic heart valves

The tightly bonded shielding coating on biomatrix significantly enhances the functionality of medical devices, bioprostheses in particular. In our work we have obtained a polyelectrolyte coating on a biomatrix by sequentially depositing chitosan and hyaluronic acid (HA) from solutions in carbonic acid under pressure. This approach makes it possible to obtain hybrid biomatrix with a firmly bonded polymer screen due to the electrostatic bonding of polyions. High-precision analysis using a tritium label shows a 3-fold increase in quantity of HA in carbonic acid under pressure compared to the conventional method. The presence of the chitosan layer increases the HA adsorption by 15–20 % due to electrostatic interaction of differently charged polymers. Antimicrobial results show the possibility of implementing an induced antimicrobial response, due to the lysis of the upper layer of the coating (HA) and the release of antimicrobial agents in the case of growth of pathogens on the bioprosthesis.

Method for non-invasive assessment of the structure of a heart valve bioprosthesis

Background. The study of explanted heart valve bioprostheses is a valuable source of information about the destructive processes in their components that develop as a result of prolonged contact with the recipient’s body. An analysis of the morphology, staging and degree of involvement of various valve prosthesis materials in the prevalence of pathological processes – calcification, mechanical damage, growth of the connective tissue capsule, is the basis for developing potential methods for increasing the service life of these products and reducing the risk of re-interventions. The aim of the study was to evaluate the potential of computed microtomography to analyze the internal structure of a biological prosthetic heart valve explanted due to dysfunction. Material and methods. In this work, we investigated the prevalence of pathological mineralization of the PeriCor bioprosthesis, explanted as a result of the developed dysfunction of the leaflet apparatus with a clinical picture of grade 2B prosthetic insufficiency. The material was described macroscopically, after which it was subjected to high-resolution computed microtomography. In the structure of the sample, X-ray dense areas of pathological mineralization were identified and described, and the volume of the material involved in calcification was assessed. Results. It was shown that the main pathological changes that led to prosthetic dysfunction were degenerative changes in the biomaterial with signs of calcification, thickening and rupture of the leaflets. It was quantitatively determined that the areas of radiologically dense inclusions (calcifications) occupy 11.1 % of the volume of the material. It has been established that the described areas are associated with the sheathing of the frame and with the elements of the suture material used in the production of this bioprosthesis. Conclusion. The method of non-destructive analysis of the internal structure of altered materials of a biological prosthesis studied in this work has demonstrated the possibility of а qualitative and quantitative assessment of areas of pathological mineralization, their distribution and connection with other processes leading to the development of prosthetic dysfunction. The method makes it possible to visualize macro- and microsites of calcification and can become a valuable tool to complement existing approaches to the study of explanted bioprostheses.

Expression of tissue inhibitors of metalloproteinases type 1 and type 2 in the leaflets of explanted bioprosthetic heart valves: a new pathogenetic parallel between structural valve degeneration and calcific aortic stenosis

Objective: to study cellular and lipid infiltration, as well as the expression of tissue inhibitors of metalloproteinases (TIMP) types 1 and 2 in biological prosthetic heart valves (BPHVs) explanted due to dysfunction.Material and Methods. We examined 17 leaflets from 6 BPHVs, dissected from the aortic and mitral positions during valve replacement. For microscopic analysis, fragments of the BPHV leaflets were frozen and serial sections were made using a cryotome. In order to study cellular infiltration and the degree of degenerative changes in the prosthetic biomaterial, the sections were stained with Gill’s hematoxylin and eosin; Oil Red O stain was used to assess lipid deposition. Immunohistochemistry was used for cell typing and detection of TIMP-1/-2. The stained samples were analyzed by light microscopy.Results. Cellular and lipid infiltration of xenogeneic tissues was detected in all BPHV flaps studied. Recipient cells coexpressed pan-leukocyte and macrophage markers PTPRC/CD45 and CD68. Positive staining for TIMP-1/-2 co-localized with cell clusters but was absent in acellular sections.Conclusion. Cells infiltrating xenogeneic BPHV tissues express TIMP-1/-2. This suggests that BPHV immune rejection pathophysiology is partially similar to that of calcific aortic stenosis.

Analysis of leaflet flutter in biological prosthetic heart valves using PIV measurements

The use of biological prosthetic valves has increased considerably in recent decades since they have several advantages over mechanical ones, but they still possess the great disadvantage of having a relatively short lifetime. An understudied phenomenon is the flutter effect that causes oscillations in the cusps, which is associated with regurgitation, calcification and fatigue, which can reduce even more the lifetime of bioproteses. In an experimental bench that simulates the cardiac flow, the behavior of a porcine and a bovine pericardium valves was recorded by a high-speed camera to quantify the oscillations of the cusps and an experiment using particle image velocimetry was conducted to study the velocity profiles and shear stresses and their relations with flutter. Results showed that the pericardial valve has lower values of frequencies and amplitudes compared to the porcine valve. Lower velocity values were found in the cusps that did not have flutter, but no relationship was observed between shear stress values and leaflet vibrations. These results may assist in future projects of biological prosthetic valves that have less flutter and longer lifespan.

Biological versus mechanical heart valve prosthesis during pregnancy in women with congenital heart disease

BackgroundWe evaluate pregnancy outcome and anticoagulation regimes in women with mechanical and biological prosthetic heart valves (PHV) for congenital heart disease. MethodsRetrospective multicenter cohort studying pregnancy outcomes in an existing cohort of patients with PHV. Results52 women had 102 pregnancies of which 78 pregnancies (46 women) ≥20 weeks duration (59 biological, 19 mechanical PHV). Miscarriages (n = 19, ≤20 weeks) occurred more frequently in women using anticoagulation (P < .05). During 42% of pregnancies of women with mechanical PHV a combined low molecular weight heparin (LMWH) vitamin-K-antagonist anticoagulation regime was used (n = 8). Overall, cardiovascular, obstetric and fetal/neonatal complications occurred in 17% (n = 13), 68% (n = 42) and 42% (n = 27) of the pregnancies. Women with mechanical PHV had significantly higher cardiovascular (12% vs 32%, P < .05), obstetric (59% vs 85%, P = .02) and fetal/neonatal (34% vs 61%, P < .05) complication rates than women with biological PHV. This was related to PHV thrombosis (n = 3, P < .02), post-partum hemorrhage (P < .02), cesarean section (P < .02), low birth weight and small for gestational age (both P < .05). PHV thrombosis occurred in 3 pregnancies, including 2/5 pregnancies with pulmonary mechanical PHV. PHV thrombosis was related to necessary cessation of anticoagulation therapy or insufficient monitoring of LMWH. Other cardiovascular complications occurred equally frequent in both groups. ConclusionComplications occur more often in pregnancies of women with a mechanical PHV than in women with a biological PHV, mainly caused by PHV thrombosis and bleeding complications. Meticulous monitoring of anticoagulation in pregnant women is necessary. Women with a pulmonary mechanical PHV are at high risk of complications.

Analytical approach on leaflet flutter on biological prosthetic heart valves

Biological prosthetic valves are known for having good hemodynamics and resistance to clot formation, but they also have the disadvantage of possessing a short lifespan. An understudied effect is the fluttering of cusps, which is associated with calcification, hemolysis, and fatigue. The present study used a mathematical model of eigenvalues calculation to predict the critical speed of flutter onset in porcine and bovine pericardium valves, comparing the results with experiments on a test bench. Most results were below the speeds found experimentally, an outcome usually found in other flutter analytical theories. The analytical method demonstrated that pericardial valves have greater resistance to the onset of flutter than porcine valves, which agrees with experimental results. The sensitivity analysis showed that the internal diameter has a high impact on the critical speed, while thickness has greater importance when considering critical flow. The same analysis demonstrated that the higher thickness and elastic modulus values of pericardial valves explain why it has an increased resistance to cusps oscillation in comparison with porcine. The mathematical model in this paper is the first flutter analytical theory focused on heart valves. It can assist in new bioprosthesis projects that can be more resistant to oscillations and early fatigue failure.

In vitro comparative assessment of decellularized bovine pericardial patches and commercial bioprosthetic heart valves

Notwithstanding their wide exploitation, biological prosthetic heart valves are characterized by limited durability (10–15 years). The treatment of biological tissues with chemical crosslinking agents such as glutaraldehyde accounts for the enhanced risk of structural deterioration associated with the early failure of bioprosthetic valves. To overcome the shortcomings of the currently available solutions, adoption of decellularized biological tissues of animal origin has emerged as a promising approach. The present study aims to assess in vitro cardiovascular scaffolds composed of bovine pericardium decellularized with the novel TRITDOC (TRIton-X100 and TauroDeOxyCholic acid) procedure. The effects of the treatment have been assessed by means of histological, biomolecular, cellular, biochemical and biomechanical analyses. The TRITDOC procedure grants the complete decellularization of bovine pericardial scaffolds while preserving the extracellular matrix architecture and the biomechanical properties. With a dedicated ELISA test, the TRITDOC procedure has been proven to ensure the complete removal of the alphaGal antigen, responsible for hyperacute rejection and for long-term deterioration of xenogenic biomaterials. Static seeding of the acellular pericardial patches with human adipose-derived stem cells resulted in an evenly repopulated scaffold without signs of calcification. The in vitro cyto-/immuno-compatibility response of the TRITDOC-bovine pericardium was compared with glutaraldehyde-treated xenogenic pericardium collected from two bioprosthetic devices currently used in clinical practice: PERIMOUNT MAGNA and TRIFECTATM. TRITDOC-bovine pericardium exhibited lower complement activation, lower cytotoxicity and a lower tendency to secrete pro-inflammatory cytokines compared to the tested commercial bioprostheses. Therefore, TRITDOC-decellularized pericardium could be considered as possible candidate material for the production of prosthetic heart valves.

Novel imaging strategies for the detection of prosthetic heart valve obstruction and endocarditis.

Prosthetic heart valve (PHV) dysfunction remains difficult to recognise correctly by two-dimensional (2D) transthoracic and transoesophageal echocardiography (TTE/TEE). ECG-triggered multidetector-row computed tomography (MDCT), 18-fluorine-fluorodesoxyglucose positron emission tomography including low-dose CT (FDG-PET) and three-dimensional transoesophageal echocardiography (3D-TEE) may have additional value. This paper reviews the role of these novel imaging tools in the field of PHV obstruction and endocarditis.For acquired PHV obstruction, MDCT is of additional value in mechanical PHVs to differentiate pannus from thrombus as well as to dynamically study leaflet motion and opening/closing angles. For biological PHV obstruction, additional imaging is not beneficial as it does not change patient management. When performed on top of 2D-TTE/TEE, MDCT has additional value for the detection of both vegetations and pseudoaneurysms/abscesses in PHV endocarditis. FDG-PET has no complementary value for the detection of vegetations; however, it appears more sensitive in the early detection of pseudoaneurysms/abscesses. Furthermore, FDG-PET enables the detection of metastatic and primary extra-cardiac infections. Evidence for the additional value of 3D-TEE is scarce.As clinical implications are major, clinicians should have a low threshold to perform additional MDCT in acquired mechanical PHV obstruction. For suspected PHV endocarditis, both FDG-PET and MDCT have complementary value.

T Cell Response in Patients with Implanted Biological and Mechanical Prosthetic Heart Valves.

The study was aimed at assessing T cell subsets of peripheral blood from recipients of long-term functioning (more than 60 months) biological and mechanical heart valve prostheses. The absolute and relative number of CD4 and CD8 T cell subsets was analyzed: naïve (N, CD45RA+CD62L+), central memory (CM, CD45RA−CD62L+), effector memory (EM, CD45RA−CD62L−), and terminally differentiated CD45RA-positive effector memory (TEMRA, CD45RA+CD62L−) in 25 persons with biological and 7 with mechanical prosthesis compared with 48 apparently healthy volunteers. The relative and absolute number of central memory and naïve CD3+CD8+ in patients with biological prosthesis was decreased (p < 0.001). Meanwhile the number of CD45RA+CD62L−CD3+CD8+ and CD3+CD4+ was increased (p < 0.001). Patients with mechanical prosthesis had increased absolute and relative number of CD45RA+CD62L−CD3+CD8+ cells (p = 0.006). Also the relative number of CD3+CD4+ cells was reduced (p = 0.04). We assume that altered composition of T cell subsets points at development of xenograft rejection reaction against both mechanical and biological heart valve prostheses.

Оценка провоспалительного статуса реципиентов биологических протезов клапанов сердца

Оценка провоспалительного статуса реципиентов биологических протезов клапанов сердца

Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H2O and CO2. Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid.

Cardiac imaging of prosthetic valve dysfunction by transesophageal echocardiography

Surgical implantation of a mechanical or biological prosthetic heart valve (PHV) with original structure and hemodynamics is conventional treatment of valvular heart disease. All kinds of prosthetic valves are stenotic comparing with native valves. They should be imagined by being aware of their specific properties. PHV diseases (PHVD) describes situations like obstruction, thromboembolism and regurgitation which also have characteristic images. Determining the cause and severity of PHVD is mandatory for selection of treatment method. Knowledge about PHVD and correct usage of cardiac imaging methods facilitate diagnosis. Most helpful diagnostic test for PHVD is transesophageal echocardiography (TEE). The aim of this review is to describe TEE in PHVD, TEE imaging characteristics of some special PHVD and clinical guidance of TEE in PHV problems.

Diagnostic evaluation of left-sided prosthetic heart valve dysfunction

Prosthetic heart valve (PHV) dysfunction is a rare, but potentially life-threatening, complication. In clinical practice, PHV dysfunction poses a diagnostic dilemma. Echocardiography and fluoroscopy are the imaging techniques of choice and are routinely used in daily practice. However, these techniques sometimes fail to determine the specific cause of PHV dysfunction, which is crucial to the selection of the appropriate treatment strategy. Multidetector-row CT (MDCT) can be of additional value in diagnosing the specific cause of PHV dysfunction and provides valuable complimentary information for surgical planning in case of reoperation. Cardiac magnetic resonance imaging (CMR) has limited value in the evaluation of biological PHV dysfunction. In this Review, we discuss the use of established imaging modalities for the detection of left-sided mechanical and biological PHV dysfunction and discuss the complementary role of MDCT in this context.

Prosthetic heart valve assessment with multidetector-row CT: imaging characteristics of 91 valves in 83 patients

ObjectivesMultidetector CT (MDCT) has shown potential for prosthetic heart valve (PHV) assessment. We assessed the image quality of different PHV types to determine which valves are suitable for MDCT evaluation.MethodsAll ECG-gated CTs performed in our institutions since 2003 were reviewed for the presence of PHVs. After reconstruction in 3 specific PHV planes, image quality of the supravalvular, perivalvular, subvalvular and valvular regions was scored on a four-point scale (1 = non-diagnostic, 2 = moderate, 3 = good and 4 = excellent) by two independent observers.ResultsEighty-four CT examinations (66 cardiac, 18 limited-dose aortic protocols) of 83 patients with a total of 91 PHVs in the aortic (n = 71), mitral (n = 17), pulmonary (n = 1) and tricuspid (n = 2) position were included. CT was performed on a 16-slice (n = 4), 64-slice (n = 28) or 256-slice (n = 52) MDCT system. Median image quality scores for the supra-, peri- and subvalvular regions and valvular detail were (3.5, 3.3, 3.5 and 3.5, respectively) for bileaflet PHV; (3.0, 3.0, 3.5 and 3.0, respectively) for Medtronic Hall PHV; (1.0, 1.0, 1.0 and 1.0, respectively) for Björk-Shiley and Sorin monoleaflet PHV and (3.5, 3.5, 4.0 and 2.0 respectively) for biological PHV.ConclusionCurrently implanted PHVs have good image quality on MDCT and are suitable for MDCT evaluation.

Combined oral anticoagulant and antiplatelet treatment: need for an evidence-based approach

Oral anticoagulants and antiplatelets are used in the longterm treatment and prevention of thromboembolic diseases. For more than 50 years, vitamin K antagonists (VKA), i.e. warfarin, acenocoumarol, and phenprocoumon, have been the only available oral anticoagulants. New oral anticoagulant drugs will soon be available: those at a more advanced stage of development are a direct thrombin inhibitor (dabigatran etexilate) and two direct factor Xa inhibitors (rivaroxaban and apixaban). Antiplatelet drugs interfere with some steps in the activation process, including adhesion, release, and/or aggregation. Aspirin and thienopyridines (ticlopidine and clopidogrel) are the currently used drugs, but new molecules are coming. VKA are used in the primary and secondary prevention of venous thromboembolism, in the prophylaxis of cardioembolic events in patients with mechanical or biological prosthetic heart valves, in patients with atrial fibrillation, and in some other ischemic myocardial diseases; antiplatelets are used mainly to prevent and/or to treat myocardial infarction, stroke, and peripheral arterial diseases. Combined anticoagulant‐antiplatelet treatment has been attempted in order to increase the efficacy of the antithrombotic treatment in some clinical conditions. Moreover, one patient already on anticoagulant treatment may develop also the indication for antiplatelet treatment, or vice versa. For both anticoagulants and antiplatelets, the efficacy in treating and preventing thromboembolic diseases cannot be dissociated from an increased risk of bleeding; therefore, the combination of these drugs can be not only more effective, but also more dangerous, and should be considered with caution. Overall, the evidence of benefit of combined treatment is limited, and the increased risk of bleeding is proven. However, combined anticoagulant and antiplatelet treatment is frequently prescribed in clinical practice: an aggressive therapeutic approach seems currently to be more attractive and popular than an evidence-based one. Sometimes it may be difficult to assess

Electrospun Bioresorbable Heart Valve Scaffold for Tissue Engineering

Currently marketed mechanical or biological prosthetic heart valves are regarded as valid substitutes for native heart valves suffering from degenerative pathologies. These devices require strict follow-up due to dysfunctions or post-surgical complications. Potential drawbacks of these medical devices are calcification, tearing of the cusps, thromboembolism and hemolysis. In this context, a tissue engineering approach offers a promising alternative scenario. In this paper, a trileaflet poly(epsilon-caprolactone) (PCL) heart valve scaffold prototype has been manufactured by electrospinning technique using a custom-made rotating target. Process parameters were selected in order to achieve suitable microstructure and mechanical performance. The electrospun heart valve prototype was functionally characterized by means of a pulse duplicator in order to evaluate the mechanical/hydraulic response to the imposed testing conditions. Leaflets synchronously opened in the ejection phase and the proper apposition of the leaflets prevented high leakage volumes in the diastolic phase. This preliminary study suggests a successful perspective for the proposed approach in designing a novel tissue engineered bioresorbable heart valve.

Prosthetic Heart Valves and Pregnancy

In patients with prosthetic heart valves (PHV), pregnancy is associated with the risks of warfarin embryopathy in patients with mechanical PHV and of structural valve deterioration (SVD), both early and late, in patients with biological PHV. ### Warfarin The use of warfarin, particularly between the 6th and 12th weeks of pregnancy, is associated with an embryopathy, “warfarin embryopathy,”1,2 which is characterized by nasal hypoplasia and/or stippled epiphyses.3 Uncommon features, including central nervous system and eye abnormalities, may be due to warfarin exposure during the second and third trimester.3 There is a wide range of the reported incidence of warfarin embryopathy (Table 1).3–18 Ten studies comprising 427 pregnancies reported the incidence was zero (Table 1). From the patient’s point of view, the incidence per live birth may be more important; four recent (between 1994 and 99) studies reported an incidence of 3/189 (1.6%) live births7,9,17,18 (Table 1). One group has shown that the risk of warfarin embryopathy was extremely low in the 33 women who needed ≤5 mg of warfarin to maintain an adequate INR.14,18 View this table: TABLE 1. Incidence of Warfarin Embryopathy The incidence of warfarin embryopathy will be lower with use of IV unfractionated heparin in the first 3 months (especially between the 6th to 12th weeks) of pregnancy; one review concluded that this strategy “eliminated the risk.”19 IV unfractionated heparin use in the last 2 weeks of pregnancy is associated with a reduced risk of hemorrhage during delivery and the neonatal period in the mother, as well as in the baby, because warfarin crosses the placenta, and therefore, the fetus/baby is anticoagulated. To reduce the latter complication, some have suggested elective caesarian section in the 38th week of pregnancy.17,18 An earlier study reported the incidence of abortion and stillbirths in these patients was …

A new semi-automatic endothelial cell seeding technique for biological prosthetic heart valves

Until today, tissue heart valve prostheses have been made with biological dead porcine or bovine tissue. However, the durability of this tissue is limited due to degeneration and calcification. Surface seeding with vital human endothelial cells (EC) could improve valve durability and bio-compatibility. A new seeding technique that includes a newly developed special seeding device is presented here. The aortic valve, including a cylinder of the aortic root, was prepared from a fresh porcine heart taken from the slaughterhouse. Porcine endothelial cells were removed by surface treatment with chemical detergent solutions. A new seeding device with an integrated CO2-incubator was designed. The device is composed of: the seeding chamber (SC), the rotation unit (RU), and the Control Unit (CU). The porcine aortic root cylinder with the valve leaflets is placed into the SC. A matrix of fibronectin is applied to the acellular valve. The SC is then filled with the endothelial cells suspended in modified Dulbecco's eagle medium (DMEM). Under cell culture conditions, the endothelial cell seeding of the tissue valve is established by rotating the valve around two orthogonal axes simultaneously and independently. This is done following the software controlled preset parameters. Using initial endothelial cell seeding concentrations of 6x10(6) endothelial cells/ml DMEM, it was possible to achieve a seeding efficiency of 80-85% within 3-4 hrs. Cell viability tests proved that 90-95% of the seeded endothelial cells are vital after the seeding procedure. This new seeding technique allows the complex warped surface of a tissue heart valve to be covered with vital endothelial cells to form a confluent endothelial cell monolayer.

Antithrombotic Therapy in Patients With Mechanical and Biological Prosthetic Heart Valves

1. Permanent therapy with oral anticoagulants offers the most consistent protection in patients with mechanical heart valves. 2. Antiplatelet agents alone do not consistently protect patients with mechanical prosthetic heart valves, including patients in sinus rhythm with St. Jude Medical valves in the aortic position. 3. Levels of oral anticoagulants that prolong the INR to 2.0 to 3.0 appear satisfactory for patients with St. Jude Medical bileaflet and Medtronic-Hall tilting disk mechanical valves in the aortic position, provided they are in sinus rhythm and the left atrium is not enlarged. Presumably, this is also true for the CarboMedics bileaflet valve, based on the observation of no clinically important difference in the rate of systemic embolism with this valve and the St. Jude Medical bileaflet valve. 4. Levels of oral anticoagulants that prolong the INR to 2.5 to 3.5 are satisfactory for tilting disk valves and bileaflet prosthetic valves in the mitral position. 5. Experience in patients with caged ball valves who had prothrombin time ratios reported in terms of the INR is sparse, because few such valves have been inserted in recent years. The number of surviving patients with caged ball valves continues to decrease. It has been suggested that the most advantageous level of the INR in patients with caged ball or caged disk valves should be as high as 4.0 to 4.9. However, others have shown a high rate of major hemorrhage with an INR that is even somewhat lower, 3.0-4.5. The problem is self-limited, however, because few such valves are being inserted. 6. In patients with mechanical heart valves, aspirin, in addition to oral anticoagulants, has been shown to diminish the frequency of thromboemboli. The risk of bleeding is somewhat increased if the INR is 2.0 to 3.0 or 2.5 to 3.5. However, if the INR is 3.0 to 4.5, the risk of bleeding becomes excessive with aspirin. There are no investigations in which aspirin 80 mg/d in combination with oral anticoagulants was evaluated. 7. Data are insufficient to recommend dipyridamole over low doses of aspirin in combination with warfarin. Whether dipyridamole plus aspirin is more effective than aspirin alone when used with warfarin is undetermined. 8. Patients with bioprosthetic valves in the mitral position as well as patients with bioprosthetic valves in the aortic position may be at risk for thromboemboli during the first 3 months after operation. 9. Among patients with bioprosthetic valves in the mitral position, oral anticoagulants at an INR of 2.0 to 2.3 were as effective as an INR of 2.5 to 4.0 and were associated with fewer bleeding complications during the first 3 months after operation.10. Aspirin may reduce the long-term frequency of thromboembolism in patients with bioprosthetic valves.