Development status and new challenges of heart transplantation / 器官移植

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.

Cardiac allograft vasculopathy after heart transplantation: summary of a single-center long-term follow-up experience in Fuwai Hospital / 器官移植

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.

Research progress on cardiac allograft vasculopathy / 器官移植

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.

Quilty Lesions in the Endomyocardial Biopsies after Heart Transplantation

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.

Triptolide ameliorates transplant arteriosclerosis in rat aorta allograft by inhibiting the expression of NO synthase / 中华器官移植杂志

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.

Heart Retransplantation to Treat a Case of Refractory Cardiac Allograft Vasculopathy / 대한내과학회지

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.

The Clinical Course and Outcomes of Post-Transplantation Diabetes Mellitus after Heart Transplantation

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.

Endogenous stress contributes to cardiac injury after heart transplantation in rats / 中南大学学报(医学版)

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.