Are heart valves from donors over 65 years of age morphologically suitable for transplantation?

Since there is no upper age limit for general organ donation, unlike heart valve donation, and since a quarter of all organ donors are 65 years and older, we examined whether the heart valves from these donors are suitable as allografts. In the period 1999–2004 the aortic valve and pulmonary valve of 100 organ donors above 65 years of age were examined to establish whether they would have been suitable as valve grafts. To compare the valve grafts above and below the age limit of 65 years, we used data on the aortic and pulmonary valves of 380 organ donors below the age limit in the same time period. Examination of the 200 heart valves showed that – just like valves from donors below the age limit – 100 of them would have met the medical quality standards for transplantation, which discriminate among optimal, suitable and unsuitable tissue morphology. The morphological suitability of the aortic valves decreases rapidly during the 4th decade of life and near to the age limit only 6% of them are accepted as grafts. The rate of potentially acceptable aortic valve grafts from organ donors aged over 65 years of 15% is also small. By contrast, the pulmonary valves are not affected by age-related tissue changes that might reduce their transplantability. The predominant majority (85%) of potential pulmonary valve grafts from organ donors over 65 years of age fulfilled the acceptance criteria, half of them (48%) even showing good tissue quality. In light of these results the age limit was raised to 70 years in 2005.     

脑死亡诱发肺损伤机制及治疗进展

肺移植是终末期肺疾病的最终治疗方案.供体短缺是肺移植所面临的主要问题.目前,脑死亡供体是肺移植供体的重要来源.然而,脑死亡过程会诱发急性肺损伤并且加重肺缺血再灌注损伤.脑死亡肺损伤机制主要包括三个方面:血流动力学的剧烈改变、全身炎症改变、神经内分泌的改变.其肺损伤表现于肺间质水肿、血浆外漏和肺泡出血,造成肺水肿等.深入探索脑死亡肺损伤的机制,将对治疗及实施肺保护提供有力的依据.     

Banking of the human heart valves and the arteries at the European homograft bank (EHB) – Overview of a 14-year activity in this International Association in Brussels<Superscript>*</Superscript>

Processing of the human heart valves and arteries has been carried out at the European Homograft Bank (EHB) in Brussels since 1989 and 1991, respectively. Heart valve donors of 0–65 years were classified in (1) Beating heart donors (BHD), of which recipients of heart transplantation (RHT) and multiorgan donors (MOD) after brain death, and (2) non-beating heart donors (NBHD) with warm ischaemic time (WIT) of less then 6 h. Past history of the donors has been checked for malignant and chronic diseases, as well as biology for transmissible and infectious diseases. Perfect collaboration has been established with the transplant coordinators and transplant teams of the implanting centres. Dissection, decontamination, cryopreservation and storing in fluid nitrogen has been carried out in accordance with the Belgian and European Standards of cardiovascular allografts. During this period, a total of 2.828 hearts, 28 predissected valves and 616 batches of arteries arrived in the EHB. 3.537 valves and 1.137 different arteries were accepted for implantation. The main reasons for tissue rejection were morphology, contamination and cuts during the tissue retrieval or dissection. A huge network of different hospitals in Belgium and elsewhere in Europe and Switzerland were included in this process. Pulmonary allografts were not sent for implantation in the left ventricular outflow tract after 1998, since the early and mid-term results after 76 implantations were disappointing. The number of implanted aortic and pulmonary allografts remains stable from year to year, however the number of the allografts used for Ross operation is still increasing. Since the results of the follow up were disappointing, we still only require the implantation and immediate postoperative results, whereas the follow-up information only for specific study purposes. This revised version was published online in July 2006 with corrections to the Cover Date.     

Are all tissue donors recognised? A cohort study in three Dutch hospitals

Nowadays, the demand for tissue transplantation has significantly increased. To optimize donor recruitment, the potential availability of tissue donors has to be evaluated. In 2011 we conducted a cohort study in three Dutch hospitals in the Netherlands. The potential amount of eligible tissue donors found, based on medical records in these hospitals is compared to the physician’s donation form report. In total 1,342 patient records were analysed. From these records, the donation officers considered 484 patients as a potential tissue donor (36.1 %). Despite the absence of contra-indication, the physician did not recognise 25 % (n = 123/484) of potential tissue donors. Physicians’ lack of sufficient knowledge of tissue donation was the main cause of adequately identifying tissue donors. A higher percentage of tissue donors in these Dutch hospitals should be feasible through creating awareness and education regarding tissue donation.     

Cardiac allografts: a 24-year South African experience

The history of using homologous cardiac valves dates back more than 30 years. Through the years emphasis was placed on the optimization of graft retrieval, preservation techniques and clinical application. A cardiac homograft valve bank was established at the Department of Cardiothoracic Surgery, University of the Free State, Bloemfontein in 1982. A retrospective analysis was performed on all allograft data since 1984. Since the first valve was successfully procured and transplanted in 1984, 2,540 aortic and pulmonary homografts were harvested from 1,792 donors, of which 1,545 [989 (64%) aortic and 556 (36%) pulmonary] were released for clinical use. Valves were discarded for various reasons, the main reasons being Human Immunodeficiency Virus (32.4%), Hepatitis B (9.6%) and venereal diseases (8.9%). The mean donor age was 26.98 years with a male predominance of 1,368 males versus 424 females. The average ischemic time was 33 h mainly due to medico-legal autopsies exceeding the desired 24 h time limit. The valves were disinfected in an antibiotic cocktail of Mefoxin, Piperacillin, Amikacin and Amphotericin B prior to cryopreservation. The surgical procedures utilizing the majority of homografts were aortic valve replacements (42.9%), aortic root replacements (19.3%) and right ventricular-pulmonary artery conduits (33.3%). The bank also supplied 23 other centers with homografts (402 aortic and 301 pulmonary). The Bloemfontein bank has established itself over the years as a viable and functional cardiac homograft bank. However, with increasing activity in the procurement arena and widened applications in the operating room the role of the homograft seems assured but availability still remains a major concern.     

Transplantation of Pulmonary Valve Using a Mouse Model of Heterotopic Heart Transplantation

Tissue engineered heart valves, especially decellularized valves, are starting to gain momentum in clinical use of reconstructive surgery with mixed results. However, the cellular and molecular mechanisms of the neotissue development, valve thickening, and stenosis development are not researched extensively. To answer the above questions, we developed a murine heterotopic heart valve transplantation model. A heart valve was harvested from a valve donor mouse and transplanted to a heart donor mouse. The heart with a new valve was transplanted heterotopically to a recipient mouse. The transplanted heart showed its own heartbeat, independent of the recipient’s heartbeat. The blood flow was quantified using a high frequency ultrasound system with a pulsed wave Doppler. The flow through the implanted pulmonary valve showed forward flow with minimal regurgitation and the peak flow was close to 100 mm/sec. This murine model of heart valve transplantation is highly versatile, so it can be modified and adapted to provide different hemodynamic environments and/or can be used with various transgenic mice to study neotissue development in a tissue engineered heart valve.     

Age-Dependent Changes in Geometry,Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves

There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation–but more pronounced in aortic valves–the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.     

Evaluation of the autopsy report before releasing musculoskeletal tissue donors; what is the benefit?

EU directive 2006/17/EC requires that all available medical information, including the autopsy report, is evaluated before releasing tissues for transplantation. The study objective was to investigate whether evaluation of autopsy results of musculoskeletal tissue donors contributes to safety and availability of transplantable tissues. The files of all donors of whom musculoskeletal tissues were retrieved by BIS in 2006 were reviewed for death cause and autopsy results. Of 84 donors musculoskeletal tissues were retrieved. In 47 donors autopsy was performed (56.0%). The groups with and without autopsy were similar in sex, age, length, and weight. In one donor no autopsy results were evaluated, since the donor was already rejected because of positive blood tests. In 13 donors (28.1%) death causes before autopsy were unknown. In 12 of these donors a death cause could be established after autopsy. In nine of the donors with a clear suspected death cause (27.3%), the death cause after autopsy differed from the suspected death cause. Four donors with autopsy (8.7%) had a general contraindication for donation, a (possible) sepsis in three and a persisting unknown death cause in one. Eight donors (17.4%) had musculoskeletal-specific contraindications, i.e. local infections. In conclusion, in 26.1% of the donors with autopsy, general or musculoskeletal-specific contraindications for donation were found. Furthermore, performance of autopsies enlarges the potential donor pool, since death causes can be established in almost all autopsies done in case of an unknown death cause. Therefore, evaluation of autopsy results improves the safety and quantity of tissues for transplantation.     

The value of autopsy and other histological examinations for the safety of tissue transplantation

Directive 2006/17/EC requires that all available medical information, including autopsy reports, is evaluated before releasing tissues for transplantation. The aim of this study was to investigate whether evaluation of results of autopsy and other histological examinations contributes to the safety of tissue transplantation. From the files of all deceased Dutch donors, from whom tissues were retrieved in a 6-month period, results of autopsy and other histological examinations (remnant heart after valve donation and biopsies obtained during retrieval) were evaluated for contraindications for transplantation. Of 758 donors at least one tissue was considered suitable for transplantation at initial assessment. 637 Donors donated corneas, 256 skin, 177 heart valves and 61 musculoskeletal tissues. On 220 donors (29.0%) autopsy was done. Of seven donors no autopsy results were requested, since a contraindication was detected earlier in the medical screening. In 19 donors with autopsy (8.9%) general or tissue-specific contraindications were detected. There were no differences in distribution of detected contraindications among donors who donated different tissues. For 136 donors (17.9%) results of histological examinations other than autopsy were available; results of examination of remnant hearts for all, brain autopsy for two (0.3%) and retrieval biopsy for four donors (0.5%). Contraindications were detected in nine of these donors with histology results other than autopsy (6.6%). For 402 donors (53%) no histological examinations were done. Evaluation of results of autopsy and other histological examinations improves the safety of tissue transplantation for all types of tissues. In donors without autopsy alternative histological examinations can contribute to enhance the safety of tissue transplantation.     

Differences in accumulation of elements in human cardiac valves

To elucidate changes of human cardiac valves with aging, the authors determined age-related changes of element contents in the four human cardiac valves by inductively coupled plasma-atomic emission spectrometry and attempted to examine the relationships in the element contents among the four cardiac valves. The subjects consisted of 10 men and 15 women, ranging in age from 65 to 102 yr. The accumulation of calcium and phosphorus was the highest in the aortic valve, and decreased in the order mitral, pulmonary, and tricuspid valves. The contents of calcium and phosphorus in the aortic valves corresponded to about 12 and 19 times the amounts of those in the tricuspid valves, in which the contents were very low. The contents of calcium and phosphorus in the aortic valves were about 2.5-fold the amounts of those in the mitral valves. An examination was attempted to determine whether or not there were relationships in element contents among the four cardiac valves. As for the aortic and mitral valves, there were no relationships in the contents of calcium and phosphorus between them, but there were relationships in the contents of sulfur and magnesium between them. Three out of 24 cases contained high contents of calcium and phosphorus in both the mitral and aortic valves, whereas 16 out of 24 cases contained high contents of calcium and phosphorus in the aortic valves alone, without the high contents in the mitral valves. Likewise, there were no relationships in the element contents, such as calcium, phosphorus, sulfur, and magnesium, between the mitral and pulmonary valves or between the mitral and tricuspid valves. It is suggested that the accumulation of calcium and phosphorus in the cardiac valve occurs independent of the other cardiac valves.     

老年瓣膜病患者瓣膜置换术术后死亡原因分析

目的:分析老年瓣膜病在瓣膜置换术后的死亡原因,为降低术后死亡率提供科学依据。方法:回顾分析我院以瓣膜置换术治疗的329例老年瓣膜病变患者的资料,对比分析生存患者和死亡患者之间的差异,总结瓣膜置换术后患者死亡的危险因素。结果:心脏瓣膜置换术后死亡率8.51%,单因素分析发现年龄、心功能分级、置换瓣膜数、LAD、LVEF、LVEDD、CPB时间、主动脉阻断时间、置换瓣膜数目与术后死亡有关联(P0.05),Logistic回归分析发现高龄、心功能差、LVEED、CPB为死亡独立危险因素(P0.05)。结论:高龄、心功能差、LVEED过度增大、CPB过长均是瓣膜置换术后的老年瓣膜病患者死亡的独立危险因素,建议临床在诊治中加以警惕。     

Factors associated with outcome of renal transplantation.

To explore the associations between a number of preoperative risk factors and the failure of renal grafts 99 consecutive patients were followed for up to 7 years after transplantation. The patients had all received their grafts from nonliving donors; the operations were performed at one hospital. Statistical analysis in relation to several outcomes showed that rapidly progressive glomerulonephritis, pre-existing cardiovascular disease, the degree of presensitization to histocompatibility antigens and the donor''s being of blood group B were associated with an increased risk of graft rejection or death after transplantation. The risks of acute and accelerated rejection were associated with different factors, which suggests that distinct pathogenetic processes may be involved. The risk of technical failure was associated with immunologic factors, which suggests the possibility that this outcome was not caused by surgical difficulties alone.     

Influence of GSTO2 (N142D) genetic polymorphism on acute renal rejection

Acute renal allograft rejection remains an important problem following kidney transplantation. Several immunological and non-immunological factors intervene in renal graft rejection. Glutathione S-transferase super family is one of the important enzymes for biotransformation of both exogenous and endogenous xenobiotic compounds such as immunosuppressive drugs. The new class of this family is omega that includes two subunits GSTO1 and GSTO2. In this study 282 samples were collected from renal recipients of Namazi hospital in Shiraz-Iran during 2007–2010 years. Also 300 healthy samples as control group were collected from Shiraz population, included in our study. The primary outcome of this study was defined as biopsy-proven acute rejection during 1 year of renal transplantation. We applied polymerase chain reaction–restriction fragment length polymorphism method for determination of GSTO2 N142D polymorphism. Our result showed no significant association between GSTO2 polymorphism and acute rejection. Also this genetic variant has no significant effect with the risk of end stage renal disease. Cadaveric donor type for acute rejection significantly differed between acute rejection and non acute rejection patients (P = 0.004). The combination effect of donor type and GSTO2 polymorphism indicates DD genotype with cadaver donor type increase risk of acute rejection (OR = 3.82, 95 % CI 1.80–12.37, P = 0.02).     

Proteomic profile of human aortic stenosis: insights into the degenerative process

Degenerative aortic stenosis is the most common worldwide cause of valve replacement. While it shares certain risk factors with coronary artery disease, it is not delayed or reversed by reducing exposure to risk factors (e.g., therapies that lower lipids). Therefore, it is necessary to better understand its pathophysiology for preventive measures to be taken. In this work, aortic valve samples were collected from 20 patients that underwent aortic valve replacement (55% males, mean age of 74 years) and 20 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry, and 35 protein species were clearly increased in aortic valves, including apolipoprotein AI, alpha-1-antitrypsin, serum albumin, lumican, alfa-1-glycoprotein, vimentin, superoxide dismutase Cu-Zn, serum amyloid P-component, glutathione S-transferase-P, fatty acid-binding protein, transthyretin, and fibrinogen gamma. By contrast, 8 protein species were decreased (transgelin, haptoglobin, glutathione peroxidase 3, HSP27, and calreticulin). All of the proteins identified play a significant role in cardiovascular processes, such as fibrosis, homeostasis, and coagulation. The significant changes observed in the abundance of key cardiovascular proteins strongly suggest that they can be involved in the pathogenesis of degenerative aortic stenosis. Further studies are warranted to better understand this process before we can attempt to modulate it.     

Replacement of the Aortic and Mitral Valves Using the Starr-Edwards Ball-Valve Prosthesis: A Report of 50 Cases

The aortic and mitral valves were replaced in 50 patients at the University of Alberta Hospital using the Starr-Edwards ball-valve prosthesis. The basis of the selection of 20 patients for isolated aortic valve replacement and 27 for mitral valve replacement using this type of prosthesis is presented, and the techniques of insertion of the aortic and mitral valve are described in detail. Of the 27 patients in whom the mitral valve was replaced by the Starr-Edwards prosthesis six died within 30 days of surgery and two after discharge from hospital at two and a half and four months, respectively. Left atrial thrombosis was the cause of death in four of these patients. In 20 patients in whom the aortic valve was replaced, four died in hospital and two died more than 30 days after returning home. Three of these six patients died from bleeding—the result of the use of anticoagulants. The difficulty in assessing whether or not anticoagulants are needed following replacement by a Starr-Edwards prosthesis is considered. It is felt, in our present state of knowledge, that anticoagulants should be used following mitral valve replacement but are probably not essential following replacement of the aortic valve. Two patients survived replacement of both aortic and mitral valves and have been followed up 18 months and seven months, respectively.     

Allogenic heart valve bank in the Department of Cardiovascular Surgery and Transplantology of Jagiellonian University in Cracow – 23 years experience in the treatment of aortic valve or aortic root diseases.

Allogenic aortic valves are widely used in case of native aortic valve or root disease as well as failed prosthetic valves with great success. At the Department of Cardiovascular Surgery and Transplantology of the Jagiellonian University in Cracow, aortic valve or aortic root replacement with allogenic aortic valve has been performed for 23 years. Allogenic heart valve bank was founded in 1980. In the bank we prepare both aortic allografts for adult cardiac surgical procedures and pulmonary allografts that are mostly used for repair of congenital heart disease.Allogenic aortic valves implantation was usually considered in our clinic for older patients, patients with infective endocarditis of the native or prosthetic valve, young women in reproductive age and patients with Marfan syndrome. Allografts exhibit excellent clinical performance and acceptable durability with no early failure if properly inserted. Between 1980 and 1992, allografts were obtained only from cadavers during routine autopsies. More than 10% of prepared allografts were exported to other cardiac surgery centres in Poland and foreign countries.Aortic valve replacement using allogenic aortic valves can be performed with acceptable mortality and good long-term results. The procedure although surgically more challenging has the advantage of not requiring anticoagulation therapy, hemodynamic performance of the allogenic valve is excellent, it demonstrates freedom from thromboembolism and infective endocarditis. We would like to emphasize the importance and advantages of the fact that allogenic heart valve bank is placed in the department of cardiovascular surgery and it is able to supply the department in heart valve allografts 24 h a day.     

Allograft semilunar cardiac valves processing and cryopreservation – morphology in scanning electron microscope

Objective: The most important factors of long term clinical performance of biological heart valve prostheses are methods of processing and cryopreservation. That is why we decided to evaluate the impact of current Allograft Heart Valves (AHV) Bank protocol on valve tissue morphology. Scanning electron microscope (SEM) is a valuable tool for investigation of biological surfaces. In case of cardiac valves it is especially suitable for detection of fine changes in endothelial covering and underlying layers. Material and methods: “Fresh” aortic and pulmonary AHV samples, harvested from “heart-beating” cadaveric donors, were compared with (1) tissue from AHV obtained from non heart-beating donors, (2) samples stored in 4 °C saline for 24 h, (3) antibiotic treated tissue for 24 h at 37 °C and finally (4) cryopreserved valves, stored in liquid nitrogen (−196 °C) for 6–38 months. All samples were dissected, dried with hexamethyldisilazane (HMDS), gold coated, studied and photographed by SEM (Tesla BS 301). Results: Our alternative method of drying samples by the HMDS method proved to be suitable for thin membranes of human semilunar valves. We were able to detect early changes in the endothelium after harvesting, and denudation of the endothelial covering during preservation with and without freezing. Conclusion: SEM (using HMDS drying) along with other methods may be helpful for the morphological control of processing, cryopreservation and liquid nitrogen storage of AHV. According to the current findings we have to avoid washing of AHV in saline after harvesting.     

CUBN as a novel locus for end-stage renal disease: insights from renal transplantation

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p?=?0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8-9.2] years (longitudinal study) documenting ESRD in transplanted kidneys--graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p?=?0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys.     

Hyperlipidaemia and aortic valve disease

PURPOSE OF REVIEW: Degenerative aortic valve stenosis is a common disease in the elderly, and traditional risk factors for atherosclerotic disease including hyperlipidaemia have been associated with the condition in several studies. This review addresses the role of the various risk factors and the potential for intervention. RECENT FINDINGS: The association of lipid abnormalities such as high lipoprotein(a) levels and the presence of the apolipoprotein E4 allele with aortic stenosis, as well as the presence of several inflammatory markers both in plasma and in surgically excised valves, suggest that the stenotic process is driven by many of the same factors behind atherosclerosis. The aortic valves of animals fed a cholesterol-rich diet exhibit many characteristics in common with the early stages of aortic stenosis. This opens up the potential of retarding the process through intervention strategies. SUMMARY: Hyperlipidaemia is associated with degenerative aortic valve stenosis, and the disease resembles the inflammatory process of atherosclerosis. Randomized controlled clinical trials will be needed to demonstrate the role of lipid intervention in patients with this condition.