RESUMEN
The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart.
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Miocitos Cardíacos/citología , Células Endoteliales/citología , Corazón/fisiología , Humanos , Antígenos Comunes de Leucocito/metabolismo , Mesodermo/citología , Miocardio/citología , Poliploidía , Datación RadiométricaRESUMEN
More than 1000 donated aortic and pulmonary valves from predominantly European tissue banks were centrally decellularized and delivered to hospitals in Europe and Japan. Here, we report on the processing and quality controls before, during and after the decellularization of these allografts. Our experiences show that all tissue establishments, which provide native cardiovascular allografts for decellularization, meet comparably high-quality standards, regardless of their national origin. A total of 84% of all received allografts could be released as cell-free allografts. By far the most frequent reasons for rejection were non-release of the donor by the tissue establishment or severe contaminations of the native tissue donation. Only in 2% of all cases the specification for freedom from cells was not fulfilled, indicating that decellularization of human heart valves is a safe process with a very low discard ratio. In clinical use, cell-free cardiovascular allografts have been shown to be advantageous over conventional heart valve replacements, at least in young adults. These results open the discussion on the future gold standard and funding of this innovative therapeutic option for heart valve replacement.
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Válvulas Cardíacas , Válvula Pulmonar , Adulto Joven , Humanos , Trasplante Homólogo , Donantes de Tejidos , Control de CalidadRESUMEN
Homograft heart valves may have significant advantages and are preferred for the repair of congenital valve malformations, especially in young women of childbearing age, athletes and in patients with active endocarditis. A growing problem, however, is the mismatch between tissue donation and the increasing demand. The aim of this paper is to describe the initiation process of a homograft procurement program to attenuate the shortage of organs. A comprehensive description of the infrastructure and procedural steps required to initiate a cardiac and vascular tissue donation program combined with a prospective follow-up of all homografts explanted at our institution. Between January 2020 and May 2022, 28 hearts and 12 pulmonary bifurcations were harvested at our institution and delivered to the European homograft bank. Twenty-seven valves (19 pulmonary valves, 8 aortic valves) were processed and allocated for implantation. The reasons for discarding a graft were either contamination (n = 14), or morphology (n = 13) or leaflet damage (n = 2). Five homografts (3 PV, 2 AV) have been cryopreserved and stored while awaiting allocation. One pulmonary homograft with a leaflet cut was retrieved by bicuspidization technique and awaits allocation, as a highly requested small diameter graft. The implementation of a tissue donation program in cooperation with a homograft bank can be achieved with reasonable additional efforts at a transplant center with an in-house cardiac surgery department. Challenging situations with a potential risk of tissue injury during procurement include re-operation, harvesting by a non-specialist surgeon and prior central cannulation for mechanical circulatory support.
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Procedimientos Quirúrgicos Cardíacos , Donantes de Tejidos , Humanos , Femenino , Estudios Prospectivos , Trasplante Homólogo , Criopreservación , AloinjertosRESUMEN
For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.
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Cardiopatías Congénitas , Válvula Pulmonar , Humanos , Bovinos , Animales , Lactante , Adolescente , Niño , Válvula Pulmonar/trasplante , Venas Yugulares/trasplante , Resultado del Tratamiento , Cardiopatías Congénitas/cirugía , Aloinjertos , Estudios RetrospectivosRESUMEN
Vascular tissue banking has been carried out in Brussels for over 30 years in compliance with EU and Swiss tissue banking regulations. A total of 2.765 vascular tissue donations were performed in Belgian, French, Netherlands and Suisse transplant centres: 547(20%), 1.013(37%) and 1.205(43%) during the first, second and third periods, respectively. 85% and 18% increase in donations during the second and third decades compared to previous one, were remarkable. Of the 7.066 evaluated vascular tissues, 2.407(227, 921 and 1.259) were discarded (34.1%), whereas 4.659(523, 1.861 and 2.275) accepted (65.9%) during the respective period. Of the 92 donated veins, 44(47.8%) were discarded and 48(52.2%) accepted. Allografts available for clinical application were stored in vapours of liquid nitrogen. A total of 4.636 allografts were delivered and transplanted for cases of infection (58%), critical limb ischaemia (16%) and congenital cardiac surgery (15%). Thirty veins were implanted. The progressive increases in donations of 20%, 37% and 43% and in transplantations of 20.8%, 34.6% and 45% during the first, second and third periods, respectively, were remarkable. Complications were reported after transplantation and these included acute rejection of two femoral arteries one month after transplantation. We conclude that the donation and transplantation of cryopreserved vascular allografts was stable with a progressive increase over time. Allografts were used predominantly for the treatment of infection, limb salvage for critical ischaemia and for neonates and infants with congenital cardiac malformation. Immune related rejection was observed. This should be a subject of future investigation.
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Bancos de Tejidos , Obtención de Tejidos y Órganos , Lactante , Recién Nacido , Humanos , Europa (Continente) , Trasplante Homólogo , Aloinjertos , CriopreservaciónRESUMEN
OBJECTIVE: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VICp) mesenchymal-like phenotype was confirmed by CD90+/CD73+/CD44+ expression and multipotent-like differentiation ability. When VICp were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VICp and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VICp-conditioned media and confirmed at the mRNA level in VICp compared with control VIC. Conditioned media from VICp induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VICp involvement in angiogenesis by a VEGF-A dependent mechanism. CONCLUSIONS: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VICp in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
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Estenosis de la Válvula Aórtica/metabolismo , Válvula Aórtica/metabolismo , Válvula Aórtica/patología , Calcinosis/metabolismo , Diferenciación Celular , Linaje de la Célula , Células Progenitoras Endoteliales/metabolismo , Neovascularización Patológica , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Estenosis de la Válvula Aórtica/patología , Calcinosis/patología , Estudios de Casos y Controles , Células Cultivadas , Técnicas de Cocultivo , Células Progenitoras Endoteliales/patología , Células Progenitoras Endoteliales/trasplante , Femenino , Humanos , Masculino , Ratones Desnudos , Persona de Mediana Edad , Osteogénesis , Comunicación Paracrina , Fenotipo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
For over 30 years, our TE has processed, controlled for quality and distributed cryopreserved allograft valves for human application. We present a review of this activity and future perspectives of cardiovascular tissue banking. The donor age and medical/behavioral history are in compliance with the regulations of the EUMS. Allograft morphology and function are evaluated in a class A cleanroom. Tests for viral/bacterial infection, histological control of structure/infection/malignancy and control-rate cryopreservation are performed. A total of 7562 hearts were sent to our TE, whereas 7290 valves (pulmonary, aortic and mitral) were transplanted. The donations increased over time: 1934, 2566 and 3062 hearts were donated during the first, second and third decades (increases of 32.7 and 19.3% during the second and third decades). Likewise, there was a significant increase in transplantations with 2050, 2550 and 2690 valves implanted during the first, second and third decades (24.4 and 5.5% increase during the second and third decades). A total of 4475 pulmonary (61.4%), 2760 aortic (37.9%) and 55 mitral valves (0.7%) were transplanted. Outstanding long-term results in adults and evidence of immune-related deterioration of allografts in neonates and infants were demonstrated. Decellularization was suggested as a solution. One hundred pulmonary and 180 aortic valves were sent for transplantation after decellularization for the ESPOIR and ARISE clinical trials and beyond. The donation and transplantation activity increased progressively. Although cryopreserved valves represent the best substitute for diseased valves, accelerated failure appears after implantation in neonates and infants. The implementation of new technologies, such as decellularization, as a standard procedure for treatment of allograft valves will offer further improvements in allograft quality and increase of durability.
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Válvula Aórtica , Criopreservación , Adulto , Europa (Continente) , Válvulas Cardíacas , Humanos , Lactante , Recién Nacido , Bancos de Tejidos , Trasplante HomólogoRESUMEN
Despite the wide choice of commercial heart valve prostheses, cryopreserved semilunar allograft heart valves (C-AHV) are required, and successfully transplanted in selected groups of patients. The expiration limit (EL) criteria have not been defined yet. Most Tissue Establishments (TE) use the EL of 5 years. From physiological, functional, and surgical point of view, the morphology and mechanical properties of aortic and pulmonary roots represent basic features limiting the EL of C-AHV. The aim of this work was to review methods of AHV tissue structural analysis and mechanical testing from the perspective of suitability for EL validation studies. Microscopic structure analysis of great arterial wall and semilunar leaflets tissue should clearly demonstrate cells as well as the extracellular matrix components by highly reproducible and specific histological staining procedures. Quantitative morphometry using stereological grids has proved to be effective, as the exact statistics was feasible. From mechanical testing methods, tensile test was the most suitable. Young's moduli of elasticity, ultimate stress and strain were shown to represent most important AHV tissue mechanical characteristics, suitable for exact statistical analysis. C-AHV are prepared by many different protocols, so as each TE has to work out own EL for C-AHV.
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Válvula Aórtica , Criopreservación , Aloinjertos , Aorta , Válvula Aórtica/cirugía , Módulo de Elasticidad , HumanosRESUMEN
To present our validation study of the BD BACTEC FX blood culture system for sterility testing of cardiovascular tissues aimed for human application. For operational qualification, we performed temperature mapping of the system, vacuum test using non-inoculated BACTEC vials, and growth promotion tests by injecting contaminant strains into aerobic and anaerobic bottles. For performance qualification, negative control, assessment of method suitability, evaluation of sensitivity limits, control of neutralization of antibiotics in biopsy samples from allografts and tissue toxicity effects, were performed. Tissue samples and transport/cryopreservation solutions were homogenized in GentleMACS Dissociator and injected into BACTEC Plus aerobic and anaerobic vials for incubation at 35 °C for 14 days. Tissues were spiked with aerobic and anaerobic bacteria and fungi. Growth of contaminants appeared in all aerobic and anaerobic vials for Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa; in anaerobic vials for Cutibacterium (Propionibacterium) acnes and Clostridium sporogenes; and only in aerobic vials for Candida albicans and Aspergillus brasiliensis. The majority of bacterial strains were detected within two days (59-100%), exceptionally between 3 and 14 days. In contrast, fungal contaminations were detected within 2, 3-6, 7-10 and after 10 days of incubation in 33.3, 71.6, 96.6 and 99.9% of cases,respectively. Uninhibited growth appeared in the tissue biopsies and homogenized tissues with and without antibiotics and in other solutions. BD BACTEC blood culture system with GentleMACS Dissociator is a rapid and efficient tool for detection of contamination in cardio-vascular tissues aimed for human application.
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Cultivo de Sangre , Infertilidad , Aloinjertos , Aspergillus , Clostridium , Medios de Cultivo , Válvulas Cardíacas , HumanosRESUMEN
OBJECTIVE: Infective endocarditis remains a severe complication associated with a high morbidity and mortality in patients after heart valve replacement. Exploration of the pathogenesis is of high demand and we, therefore, present a competent model that allows studying bacterial adherence and the role of plasma fibrinogen in this process using a new in-house designed low-volume flow chamber. Three cardiac graft tissues used for pulmonary valve replacement have been tested under shear conditions to investigate the impact of surface composition on the adhesion events. METHODS: Tissue pieces of cryopreserved homograft (non-decellularised), decellularised homograft and bovine pericardium patch were investigated for fibrinogen binding. Adherence of Staphylococcus aureus to these graft tissues was studied quantitatively under flow conditions in our newly fabricated chamber based on a parallel plates' modality. The method of counting colony-forming units was reliable and reproducible to assess the propensity of different graft materials for bacterial attachment under shear. RESULTS: Bacterial perfusions over all plasma-precoated tissues identified cryopreserved homograft with the lowest affinity for S. aureus compared to decellularised homograft presenting a significantly higher bacterial adhesion (p < 0.05), which was linked to a more avid fibrinogen binding (p < 0.01). Bovine pericardial patch, as a reference tissue in this study, was confirmed to be the most susceptible tissue graft for the bacterial adhesion, which was in line with our previous work. CONCLUSION: The two studied homograft tissues showed different levels of bacterial attachment, which might be postulated by the involvement of fibrinogen in the adhesion mechanism(s) shown previously for bovine tissues.
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Endocarditis Bacteriana , Trasplante de Corazón , Aloinjertos , Animales , Bovinos , Endocarditis Bacteriana/cirugía , Fibrinógeno , Humanos , Staphylococcus aureus , Donantes de TejidosRESUMEN
The European Blood Alliance (EBA) Tissue and Cells annual benchmarking exercise identified that in 2014, the heart valve (HV) discard rate in tissue establishments (TEs) run by EBA members was between 19 and 65%. Given this significant discard rate, a decision was taken to carry out a worldwide data-gathering exercise to assess the processing methodology in different TEs. In collaboration with the Foundation of European Tissue Banks, a questionnaire asking for the details on HV processing was sent to TEs worldwide. Nineteen questionnaires were received back from 15 European TEs and 4 non-European TEs. The data provided confirmed a significant discard rate of HVs with 43-50% of aortic valves and 20-32% of pulmonary valves being discarded in 2015. The causes of HV discard varied, with microbiology contamination, anatomical and medical reasons being the main causes. This data-gathering exercise highlighted significant variations in practice in different TEs including how donor suitability is assessed, critical timings for heart retrieval and processing, heart rinsing, HV decontamination protocols and methods of microbiological testing. To reduce the discard rates, there are several aspects of HV banking that could be validated and standardised. Here, we report the findings of this data-gathering exercise. We consider this a first step that will help lead to standardising HV banking.
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Descontaminación/estadística & datos numéricos , Válvulas Cardíacas/microbiología , Válvulas Cardíacas/trasplante , Bancos de Tejidos/normas , Europa (Continente) , Humanos , Encuestas y Cuestionarios , Donantes de Tejidos , Trasplante HomólogoRESUMEN
The performance of many laboratories can be evaluated by participation in external quality assessment (EQA) schemes. EQA allows for comparison of a laboratory's performance with a source outside the laboratory-either a peer group of laboratories or a reference laboratory. Such EQA schemes do not exist in tissue banking despite the fact that tissue establishments (TE) perform very complex procedures. This paper describes the first ever EQA scheme in the field specifically assessing microbiological aspects in heart valve (HV) banking. Twenty-two TEs participated. Three HV tissue samples were sent to each participating TE-two contaminated with non-pathogenic micro-organisms and a third negative control. The aims were to isolate and identify the micro-organisms present and then to successfully decontaminate the HV tissue using the routine standard operating procedures of the TE. Eight of the TEs were able to isolate and identify all contaminating micro-organisms present, and of these, five also successfully decontaminated the tissue; 13 TEs failed to establish the identity of one or more of the contaminants; five TEs appear to have introduced contamination during the processing or testing of the tissue; and eight failed to successfully decontaminate the HV tissue. This initiative provides TEs with an international benchmark for tissue product microbiology testing. It has identified significant variation in practice and in the ability of different TEs to identify the presence of contamination. There is now work ongoing with the aim of setting up a regular EQA scheme for HV banking.
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Bacterias/aislamiento & purificación , Técnicas de Laboratorio Clínico/normas , Descontaminación/normas , Válvulas Cardíacas/microbiología , Técnicas Microbiológicas/normas , Control de Calidad , Bancos de Tejidos/normas , Benchmarking , Válvulas Cardíacas/trasplante , Humanos , Agencias Internacionales , Trasplante de TejidosRESUMEN
BACKGROUND: Bacteria are the pathogens most frequently transmitted through substances of human origin (SoHO). The European Centre for Disease Prevention and Control (ECDC) organized an expert consultation, with the objective of developing a priority list of bacterial pathogens transmissible via SoHO. The list will be used to further assess risks and determine appropriate preventive measures. STUDY DESIGN AND METHODS: The 14 most frequently SoHO-transmitted bacteria identified through a scoping literature review were then prioritized during an expert workshop through a methodology based on multicriteria decision analysis. The selection of the prioritization method was based upon an ECDC framework for best practices in conducting risk-ranking exercises. Three transmission pathways, blood and blood components, tissues and cells, and organs, were considered in the ranking exercise. RESULTS: According to the ranking score (RS), bacteria were organized within each SoHO pathway into one of four risk tiers: Tier 1 (RS ≥ 0.70), Tier 2 (RS = 0.60-0.69), Tier 3 (RS = 0.40-0.59), or Tier 4 (RS < 0.40). The most consistently identified pathogens in the highest risk Tiers 1 and 2 of all three pathways were: Staphylococcus aureus, Klebsiella spp., Escherichia coli, ß-hemolytic streptococci, Pseudomonas spp., and Acinetobacter spp. CONCLUSION: Six bacteria were defined as being of the highest priority in respect of the threat to the safety of SoHO and will be the subject of subsequent in-depth risk assessments to be conducted by ECDC to identify measures to mitigate the risk posed by these bacteria.
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Infecciones Bacterianas/transmisión , Medición de Riesgo/métodos , Infecciones Bacterianas/microbiología , Técnicas de Apoyo para la Decisión , Europa (Continente) , Prioridades en Salud , HumanosRESUMEN
BACKGROUND: Segmental replacement of the esophagus (SRE) is challenging. Allogenic aorta (AA) has shown promising remodeling abilities when used as an esophageal substitute. The aim of this study was to evaluate the feasibility and results of esophageal replacement with fascial flap-wrapped AA segments in a novel rabbit model. MATERIALS AND METHODS: Seven Geant des Flandres rabbits and one New Zealand rabbit served as thoracic aorta donors, and 25 New Zealand rabbits were used as recipients. One to 3 wk before esophageal replacement either cryopreserved or fresh thoracic aortic segments were wrapped in thoracic wall fascia to generate revascularization. In an attempt to optimize the model, step-by-step modifications concerning perioperative and postoperative management of the recipients were made as results accumulated. Microscopic evaluation was focused on the viability of aortic segments and neoangiogenesis originating from the fascia. RESULTS: Survival after SRE was poor. Most recipients died within 1 wk, mainly from upper digestive tract hypomotility. Microscopically, AAs were severely necrosed. In one recipient sacrificed on day 16, the edges of the graft became evanescent. In these areas, esophageal reepithelialization directly covered the fascia, in which unexpected smooth muscle cells were found, suggestive of the first stages of esophageal remodeling of the graft. CONCLUSIONS: Results for SRE using fascial-wrapped AAs in rabbits were disappointing. The transposition of this approach to larger animals might result in longer survival, increasing the possibility for more complete graft remodeling.
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Aorta Torácica/trasplante , Trastornos de la Motilidad Esofágica/mortalidad , Esófago/cirugía , Fascia/trasplante , Colgajos Quirúrgicos , Procedimientos Quirúrgicos Vasculares/mortalidad , Implantes Absorbibles , Animales , Profilaxis Antibiótica , Tamaño Corporal , Trastornos de la Motilidad Esofágica/etiología , Estudios de Factibilidad , Femenino , Masculino , Modelos Animales , Conejos , Siliconas , Stents , Dehiscencia de la Herida Operatoria/prevención & control , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
The use of arterial homograft is indicated especially in case of prosthetic graft infections after bypass surgery. We report the case of a patient who experienced the loss of a cryopreserved femoral artery caused by an acute rejection. This homograft had to be explanted 1 month after implantation because of an acute aneurysmal deterioration. Histology of the explanted artery showed inflammatory cells infiltration, pseudoaneurysms and necrosis. It was then replaced by a second cryopreserved femoral artery which is currently well tolerated. This first case of acute rejection of a cryopreserved artery, to our knowledge, raises again the question of the immunogenicity of cryopreserved homografts. The case report is followed by a brief discussion.
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Criopreservación , Arteria Femoral/trasplante , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Trombosis/complicaciones , Trombosis/cirugía , Enfermedad Aguda , Adulto , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVES: Decellularized aortic homografts (DAH) were introduced in 2008 as a further option for paediatric aortic valve replacement (AVR). METHODS: Prospective, multicentre follow-up of all paediatric patients receiving DAH for AVR in 8 European centres. RESULTS: A total of 143 DAH were implanted between February 2008 and February 2023 in 137 children (106 male, 74%) with a median age of 10.8 years (interquartile range 6.6-14.6). Eighty-four (59%) had undergone previous cardiac operations and 24 (17%) had undergone previous AVR. The median implanted DAH diameter was 21 mm (interquartile range 19-23). The median operation duration was 348 min (227-439) with a median cardiopulmonary bypass time of 212 min (171-257) and a median cross-clamp time of 135 min (113-164). After a median follow-up of 5.3 years (3.3-7.2, max. 15.2 years), the primary efficacy end-points peak gradient (median 14 mmHg, 9-28) and regurgitation (median 0.5, interquartile range 0-1, grade 0-3) showed good results but an increase over time. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 5 years were 97.8 ± 1.2/88.7 ± 3.3/99.1 ± 0.9/100 and 99.2 ± 0.8%, respectively. Freedom from death/explantation/endocarditis/bleeding/thromboembolism at 10 years were 96.3 ± 1.9/67.1 ± 8.0/93.6 ± 3.9/98.6 ± 1.4 and 86.9 ± 11.6%, respectively. In total, 21 DAH were explanted. Seven were replaced by a mechanical AVR, 1 Ross operation was performed and a re-do DAH was implanted in 13 patients with no redo mortality. The calculated expected adverse events were lower for DAH compared to cryopreserved homograft patients (mean age 8.4 years), and in the same range as for Ross patients (9.2 years) and mechanical AVR (13.0 years). CONCLUSIONS: This large-scale prospective analysis demonstrates excellent mid-term survival using DAH with adverse event rates comparable to paediatric Ross procedures.
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Endocarditis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Tromboembolia , Niño , Humanos , Masculino , Aloinjertos/cirugía , Válvula Aórtica/cirugía , Endocarditis/cirugía , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Reoperación , Resultado del Tratamiento , Femenino , AdolescenteRESUMEN
OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients. METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement. RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9-55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (IQR 93-150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [IQR 5.1-6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively. CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.
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Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Endocarditis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Adulto , Humanos , Masculino , Aloinjertos/cirugía , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Endocarditis/cirugía , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/métodos , Estudios Prospectivos , Reoperación , Datos de Salud Recolectados Rutinariamente , Femenino , Adolescente , Adulto Joven , Persona de Mediana EdadRESUMEN
BACKGROUND: Aortic valve stenosis involves inflammation, excess deposition of a collagen-rich extracellular matrix, and calcification. Recent studies have shown that M1 or inflammatory macrophages derived from infiltrating monocytes promote calcification of valvular interstitial cells, the most prevalent cell type of the aortic valve. We hypothesized that valvular interstitial cells could modulate inflammatory macrophages phenotype. METHODS: We first assessed macrophage phenotype in human aortic valve stenosis and control aortic valves from donors. Then, we examined profibrotic and inflammatory-related gene expression in valves and valvular interstitial cells. Finally, we investigated whether valvular interstitial cells can modify the phenotype of inflammatory macrophages. RESULTS: Circulating monocytes and plasma transforming growth factor beta-1 levels of patients with aortic valve stenosis were significantly higher compared with patients without aortic valve stenosis. Histologic analysis of thickened spongiosa of the aortic valve from patients with aortic valve stenosis showed a high macrophage infiltration but a low matrix metalloproteinase-9 expression compared with control aortic valves. On the other hand, valvular interstitial cell culture of aortic valve stenosis exhibited a profibrotic phenotype with a high expression of transforming growth factor beta-1 and transforming growth factor beta-1/transforming growth factor beta-3 ratio but a decreased expression of the peroxisome proliferator-activated receptor gamma nuclear receptor. Valvular interstitial cell-conditioned media of aortic valve stenosis led to a decrease in enzymatic activity of matrix metalloproteinase-9 and an increase in production of collagen in inflammatory macrophages compared with valvular interstitial cell-conditioned media from control aortic valve donors. CONCLUSIONS: These findings indicate that profibrotic valvular interstitial cells promote the imbalance of extracellular matrix remodeling by reducing matrix metalloproteinase-9 production on inflammatory macrophages that lead to excessive collagen deposition observed in aortic valve stenosis. Further investigation is needed to clarify the role of transforming growth factor beta-1/proliferator-activated receptor gamma nuclear receptor/matrix metalloproteinase-9 in aortic valve stenosis.
RESUMEN
Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate around 0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial. Using retrospective 14C birth dating we analyzed cardiomyocyte renewal in patients with end-stage heart failure. We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18-50 times lower compared to the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart. Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.