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Heart transplantation is the primary therapeutic option for patients with end-stage heart failure. The shortage of donors has been the main limiting factor for the increasing quantity of heart transplantation. With persistent updating and introduction of novel technologies, the donor pool has been increasingly expanded, such as using the heart from older donors, donors infected with hepatitis C virus, donors dying from drug overdose or donation after cardiac death (DCD) donors, etc. Meantime, the proportion of recipients with advanced age, multiple organ dysfunction, mechanical circulatory support and human leukocyte antigen antibody sensitization has been significantly increased in recent years. The shortage of donors, complication of recipients' conditions, individualized management of immunosuppressive therapy and prevention and treatment of long-term cardiac allograft vasculopathy are all challenges in the field of heart transplantation. In this article, novel progresses on donor pool expansion, improving the quality of recipients, strengthening the diagnosis and treatment of rejection, and preventing cardiac allograft vasculopathy were reviewed, aiming to prolong the survival and enhance the quality of life of patients with end-stage heart failure on the waiting list or underwent heart transplantation.
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Objective To summarize the incidence of cardiac allograft vasculopathy (CAV) after heart transplantation and the effect on the long-term survival of recipients. Methods Clinical data of 1 006 heart transplant recipients were retrospectively analyzed. Of 48 CAV patients, 4 cases were not included in this analysis due to lack of imaging evidence. A total of 1 002 recipients were divided into the CAV group (n=44) and non-CAV group (n=958) according to the incidence of CAV. The incidence of CAV was summarized. Clinical data of all patients were statistically compared between two groups. Imaging diagnosis, coronary artery disease, drug treatment and complications, postoperative survival and causes of death of CAV patients were analyzed. Results Among 1 006 heart transplant recipients, 48 cases (4.77%) developed CAV. Compared with the non-CAV group, the proportion of preoperative smoking history, preoperative hypertension history, coronary artery disease and perioperative infection was significantly higher in the CAV group (all P < 0.05). Among 44 patients diagnosed with CAV by imaging examination, 24 cases were diagnosed with CAV by coronary CT angiography (CTA), 4 cases by coronary angiography (CAG), and 16 cases by coronary CTA combined with CAG. Among 44 patients, the proportion of grade Ⅰ CAV was 45% (20/44), 30% (13/44) for grade Ⅱ CAV and 25% (11/44) for grade Ⅲ CAV, respectively. All patients received long-term use of statins after operation, and 20 patients were given with antiplatelet drugs. Among 44 CAV patients, 11 patients underwent percutaneous coronary intervention, 6 cases received repeated heart transplantation, and 8 patients died. Kaplan-Meier survival analysis demonstrated that there was no significant difference in the long-term survival rate between the CAV and non-CAV groups (P > 0.05), whereas the survival rate of patients tended to decline after the diagnosis of CAV (at postoperative 6-7 years). The long-term survival rates of patients with grade Ⅰ, grade Ⅱ and grade Ⅲ CAV showed no significant difference (P > 0.05). Even for patients with grade Ⅰ CAV, the long-term survival rate tended to decline. Conclusions CAV is a common and intractable complication following heart transplantation, and the long-term survival rate of patients after the diagnosis of CAV tended to decline. Deepening understanding of CAV, prompt prevention, diagnosis and treatment should be delivered to improve the long-term survival rate of patients after heart transplantation.
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The pathology of liver allograft biopsy is not only essential for the evaluation of liver donor, but also for the diagnosis and differential diagnosis of posttransplantation complications. With the development of liver transplantation in clinical practice, relevant studies of the pathological diagnosis of liver allograft complications have been deepened. Banff classification on liver allograft pathology have been gradually established within the international community. In China, pathological studies related to liver allograft pathology have been steadily carried out, and the pathological diagnostic basis of liver allograft pathology suitable for the clinical practice of liver transplantation in China has been gradually formed. This article reviews the history of Banff liver allograft pathology and major pathological lesions of liver allograft complications, aiming to provide reference for implementing pathological diagnosis of liver allograft pathology in China, assisting clinical diagnosis and targeted treatment of complications after liver transplantation, and further improving the survival of liver allograft and recipients.
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Antibody-mediated rejection (AMR), also known as humoral rejection, is an immune injury caused by rejection involved with multiple humoral immune effectors, such as antibodies and complements, etc. AMR plays a pivotal role in hyperacute, acute and chronic rejection. In this article, the basic definition of AMR, the research progress and major achievements on AMR pathology according to Banff classification on allograft pathology (Banff classification), and main pathological characteristics of AMR in renal allograft were reviewed, aiming to provide reference for accurate diagnosis and timely treatment of AMR, and guarantee the long-term survival of renal graft and recipients.
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T cell-mediated rejection (TCMR) is one of the main mechanisms of rejection in organ transplantation, which is also the most common type of acute rejection.Based on Banff classification on allograft pathology (Banff classification) in 2019, TCMR can be divided into acute TCMR (aTCMR) and chronic active TCMR (caTCMR) according to the characteristics of immune lesions.In this article, the basic definition of TCMR, the research progress on TCMR pathology according to Banff classification for renal allograft, and the basic pathological changes and diagnostic grading of TCMR were reviewed, aiming to provide evidence for early identification, diagnosis and treatment of TCMR and prevent the progression of TCMR into caTCMR, thereby guarantying the long-term survival of both the renal allograft and recipient.
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Allogeneic heart transplantation (HTx) is the primary treatment for patients with end-stage heart failure. Nevertheless, the long-term complication of cardiac allograft vasculopathy (CAV) after HTx is the main factor affecting the long-term survival of the recipients. Up to now, there is no effective methods to prevent and treat CAV. This article reviews the pathological manifestations of CAV, immunological factors of CAV and other risk factors of CAV, aiming to provide novel ideas and understanding for CAV research.
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BACKGROUND: The aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients. METHODS: A total of 1190 EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions, acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy was diagnosed by computed tomography coronary angiography. Clinical information, including the patients’ survival was retrieved by a review of medical records. RESULTS: Eighty-eight patients (75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellular rejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patient sdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesions from transplantation was longer than that of acute cellular rejections. We found a significant association between Quilty lesions and cardiac allograft vasculopathy. No significant relationship was found between Quilty lesions and the patients’ survival. CONCLUSIONS: Quilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection.
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Humains , Allogreffes , Biopsie , Coronarographie , Transplantation cardiaque , Coeur , Dossiers médicauxRésumé
Objective Allograft Vasculopathy(AV), which limits the function and long-term survival of transplanted organs, it is the most urgent problem need to be solved in the field of organ transplantation.Traditional vascular anastomosis requires excellent microsurgical techniques, it is difficult to carry out.To explore a simple and feasible AV model can provide ideas for clinical research.Methods We make vessel cannulas by using vein detained needles, pulling the thoracic aorta of donor rat in vessel cannula, both ends turned over and fixed,and then transplant it in recipient rat abdominal aorta.1, 4 and 8 weeks after transplantation, we take out of the transplanted arteries, HE stain, to observe the histomorphology and measurement the vascular intimal thickness.Results 38 of the 40 recipient rats healthy survival to the detection time points, the legs and tail can move freely, defecating and urinating normally.It is found that transplanted arteries concentric circles thickening, its histomorphology just like the AV by using HE staining.Conclutions The method of rats artery transplantation is simple and feasible, significantly shorten the time of abdominal aortic blocking, reduce surgical trauma, can improve the success rate and the reproducibility of operation.
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Objective To understand the pathological role of nitric oxide synthase 2 (NOS2) in rat allograft vascular lesions and the effects of triptolide.Methods The abdominal aorta transplantation between Wistar and SD rats was used as an animal model.Three groups were set up..the same genome group (group A),the allogeneic control group (group B),and the isogene Triptolide group (group C).The grafts were removed at 7th,28th,and 56th day after surgery.The transplant artery intima thickness was measured.The irnmunohistochemical staining was applied to observe the NOS2 expression in the vascular tissue layers.The integral optical density value in each group was calculated.Results The arterial intima of transplants at 28th and 56th day postoperation was thickened,and that was thickest in group C among the three groups (P＜0.05).There was significant difference in intima thickness and integral optical density between group C with groups A and B (P＜ 0.05).The expression of NOS2 was strongest in group B,and that in group C was significantly weaker than that in group B (P ＜ 0.05).Conclusion Triptolide is capable of slowing down the progression of graft vascular disease by inhibiting the expression of NOS2.
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Objective To investigate the feasibility of using ultrasound‐mediated destruction of microbubbles ( US+ MB) to enhance the transplantation of endothelial progenitor cells ( EPCs) to confer chronic allograft vasculopathy (CAV) .Methods Bone marrow derived mononuclear cells were isolated and induced in vitro . The abdominal aorta transplantation was performed . Four groups were divided:control group without treatment (group A) ,injection with saline (group B) ,injection with EPCs (group C) ,group D ( US+MB+EPCs) was injected with EPCs and US was applied to MB prior to the infusion . All rats were killed during 8 weeks after transplantation to enable histological examination;SDF‐1α expression was detected by immunohistochemistry ,the expression of SDF‐1αand TNF‐αin the grafted aortas were detected with RT‐PCR . Results When 8 weeks after EPCs transplantation ,there was a significant improvement in aortic intima of Group D compared with Group B and C ,respectively ( P <0 .05) . In addition ,treatment of Group D significantly increased the expression of SDF‐1αand reduced the expression of TNF‐αin the grafted aortas . Conclusions US‐mediated MB destruction prior to EPCs transplantation into the grafted aortas can improves the effectiveness of endothelial repair and delay the progress of CAV .
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Cardiac allograft vasculopathy is one of the most important causes of poor long-term survival after heart transplantation. The condition tends to be diffuse, usually affecting the mid-to-distal portions of the coronary artery. Reperfusion therapy is ineffective. Everolimus, an inhibitor of proliferation signaling, has been reported to prevent development of the condition; however, the efficacy thereof has not yet been fully accepted. The only definitive treatment for cardiac allograft vasculopathy is retransplantation. Herein, we describe the case of a 15-year-old boy who underwent heart retransplantation because of rapidly progressive cardiac allograft vasculopathy.
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Adolescent , Humains , Mâle , Allogreffes , Vaisseaux coronaires , Évérolimus , Transplantation cardiaque , Coeur , ReperfusionRésumé
The aim of this study was to describe in more detail the predisposition, natural course, and clinical impact of post-transplantation diabetes mellitus (PTDM) after heart transplantation (HT). The characteristics and clinical outcomes of 54 patients with PTDM were compared with those of 140 patients without PTDM. The mean age of PTDM patients was significantly higher than controls (48.9 +/- 9.3 vs 38.6 +/- 13.3 yr, respectively, P = 0.001), and ischemic heart disease was a more common indication of HT (20.4% [11/54] vs 7.1% [10/140], respectively, P = 0.008). In multivariate analysis, only recipient age (odds ratio, 1.80; 95% confidence interval, 1.35-2.40; P = 0.001) was associated with PTDM development. In 18 patients (33%), PTDM was reversed during the follow-up period, and the reversal of PTDM was critically dependent on the time taken to develop PTDM (1.9 +/- 1.0 months in the reversed group vs 14.5 +/- 25.3 months in the maintained group, P = 0.005). The 5-yr incidence of late infection (after 6 months) was higher in the PTDM group than in the control group (30.4% +/- 7.1% vs 15.4% +/- 3.3%, respectively, P = 0.031). However, the 5-yr overall survival rate was not different (92.9% +/- 4.1% vs 85.8% +/- 3.2%, respectively, P = 0.220). In conclusion, PTDM after HT is reversible in one-third of patients and is not a critical factor in patient survival after HT.
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Études de cohortes , Diabète/épidémiologie , Études de suivi , Transplantation cardiaque/effets indésirables , Hémoglobine glyquée/analyse , Incidence , Infections/étiologie , Enregistrements , Taux de survie , Transplantation homologue , Résultat thérapeutiqueRésumé
Objective Allograft vasculopathy (AV), feature of chronic rejection, is a major serious long-term post-operation complication in organ transplantation. The accurate mechanisms for AV have not been definitively established, but extensive basic and clinical studies demonstrate AV is triggered by immune reaction and nonimmunologic factors, and also possibly attributed to the metabolism of branched-chain amino acids (BCAA). Methods The transplanted hearts from Lewis to Sprague-Dawely rats served as allografts and those from Lewis to Lewis rats as isografts based on Ono 's model. The differential proteins in transplanted hearts were separated by comparative proteomic technique, and some enzymes which regulated the metabolism of BCAA were identified and validated.Results All transplanted hearts at second week postoperation were characterized by lumen loss (total area-luminal area/total area) in coronary artery, but more predominant at 8th week. All samples from the left ventricles were analyzed by proteomic techniques and the subunits E1 a, E1β and E3 of branched-chain α-ketoacid dehydrogenase (BCKDH) complex were decreased in the heart allografts.Immunohistological detection also showed the expression of BCKDH was reduced not only in the cardiac muscle but also more significantly in blool vessels with cardiac allograft vasculopathy (CAV).BCAA concentrations were increased in the cardiac allografts, but there was no difference in the serum. Conclusion These findings suggest that the catabolic pathways of the BCAA may be inhibited owing to the reduced expression of BCKDH complex, and elevated intracellular concentrations of leucine. The vascular smooth muscle cell and cardiac muscle cell proliferation is stimulated via mTOR-dependent and mTOR-independent pathways, which is associated with the formation of myocardial hypertrophy and AV in the heart allografts.
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Objective Stress effect plays an important role in the development of some myocardial diseases. We hypothesized it was important nosogenesis to myocardial damage and cardiac allograft vasculopathy. Methods The transplanted hearts from Lewis to Wister rats served as allografts and from Lewis to Lewis rats as isografts based Ono's model. The differential proteins in the transplanted hearts were separated by comparative proteome, and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and searched by Matrix Science software system.Results All transplanted hearts were characterized by lumen loss [(total vessel area-luminal area)/total vessel area] in the coronary artery 2 weeks after the operation [(2.07%±0.93%) vs. (27.58%±11.14%), P＜0.01], but more predominant after 8 weeks [(2.34%±1.06%) vs. (72.29%±20.57%), P＜0.01]. All samples of the left ventricle were analyzed by proteomic techniques and 37 distinct proteins involving their respective isoforms and subunits were identified. Nine proteins were correlated to endoplasmic reticulum stress effect and myocardial damage, and 2 proteins were verified by Western blot.Conclusion Stress plays an important role in cardiac allograft damage and the development of rat cardiac allograft vasculopathy.
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Objetivo: Evaluar la certeza diagnóstica de la tomografía computarizada multicorte (TCM) en pacientes trasplantados cardiacos para la detección de estenosis coronaria y vasculopatía del injerto cardiaco (VDI) en comparación con la angiografía coronaria (AC) y la ecografía intravascular (EIV), respectivamente. Material y métodos: Diecinueve pacientes trasplantados cardiacos fueron estudiados con angiografía coronaria por TCM entre 7 a 14 días después del cateterismo (AD y EIV). Los estudios se llevaron a cabo con un tomógrafo multicorte de 16 filas. Dos observadores evaluaron en forma ciega los estudios de TCM para la detección de estenosis coronaria >50% y VDI. Resultados: Para la detección de estenosis coronaria >50%, la sensibilidad fue: 80-88% y la especificidad: 98- 99%; para la detección de VDI, 91-96% y 88-98%, respectivamente. Conclusión: En esta serie preliminar, nuestros resultados mostraron que la TCM fue una técnica adecuada para evaluar pacientes trasplantados cardiacos y podría ser una alternativa a la AD y EIV para el seguimiento y control no invasivo de estos pacientes.
Objective: To evaluate the diagnostic accuracy of multidetector computed tomography (MDCT) for detection of luminal stenosis and cardiac allograft vasculopathy in comparison with coronary angiography (CA) and intravascular ultrasound (IVUS) respectively. Material and methods: Nineteen cardiac transplant patients scheduled for follow-up CA were included. MDCT coronary angiography was performed using a 16-row CT scanner within 7-14 days after CA and IVUS. Studies were analyzed by independent readers; two observers evaluated the CT datasets for the presence of coronary artery stenosis >50% and allograft vasculopathy. Results: The sensitivity for detecting >50% luminal stenosis was 80-88% and specificity, 98-99% and for detection of cardiac allograft vasculopathy, the sensitivity was 91-96% and specificity, 88-91%. Conclusion: In this preliminary series, our results indicate that MDCT coronary angiography was capable of detecting both significant coronary stenosis as well as diffuse intimal proliferation. This non-invasive procedure could be an alternative to CA and IVUS in the surveillance of heart transplant patients.
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Chronic complications are situations which limit the long-term utility of cardiac transplantation. The allograft vasculopathy is the most important cause of death at 5 years alter transplantation. Another conditions are systemic arterial hypertension, nephropathies, diabetes mellitus, dyslipidemies and malignant neoplasies. The present manuscript summarizes the characteristics, clinical presentation and therapeutic strategies for this conditions.
Las complicaciones crónicas asociadas al trasplante cardiaco son situaciones que limitan la utilidad a largo plazo de este procedimiento. Dentro de ellas destaca la vasculopatía del injerto que constituye la primera causa de muerte a cinco años del trasplante. Otras situaciones incluyen la hipertensión arterial sistémica, la enfermedad renal, la diabetes mellitus de novo, las dislipidemias y las neoplasias. En el presente trabajo se resumen algunas de las características, causas, presentación clínica y estrategias de manejo de estas situaciones.