Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.     

De novo human leukocyte antigen allosensitization patterns in patients bridged to heart transplantation using left ventricular assist devices

IntroductionWe examined the impact and time course of de novo human leukocyte antigen (HLA) allosensitization following left ventricular assist device (LVAD) implantation.Methods and resultsForty patients had a calculated panel reactive antibody (cPRA) prior to LVAD surgery between January 2014 and December 2018. Of these patients, we retrospectively studied 33 patients who had pre-LVAD cPRA <10%. De novo allosensitization was defined as cPRA ≥10% within 3 months following LVAD surgery, and “persistent allosensitization” was defined as cPRA ≥10% at time of heart transplant or death. One-third (11/33) of our cohort developed de novo allosensitization within 3-months post-LVAD. Median duration of follow-up during LVAD support was 588 days (IQR 337–1071 days), or approximately 19 months. In an adjusted, multivariable analysis, female sex remained associated with de novo allosensitization (adjusted odds ratio [95%CI]: 11 (1.4–85), P = 0.026). De novo allosensitization was subsequently associated with persistent allosensitization (P = 0.024). Both axial-flow and centrifugal-flow LVADs had similar rates of allosensitization. Compared to those with no allosensitization, patients with de novo allosensitization did not appear to have inferior post-transplant outcomes of death or treated rejection.ConclusionIn our single-center experience, one-third of patients developed de novo allosensitization which did not appear to associate with inferior post-transplant outcomes. Female sex was associated with de novo allosensitization.     

Outcome of patients surviving to heart transplantation after being mechanically bridged for more than 100 days.

OBJECTIVE: The effect of long-term mechanical support on subsequent heart transplantation is still debated. METHODS: We report the outcome of 41 patients (42 +/- 12 years) bridged with left ventricular assist devices (VAD; 28 Novacor, 9 HeartMate, 2 Thoratec, and 2 DeBakey) for >100 days (218 +/- 76 days) between April 1994 and March 2000). We compared follow-up with 146 patients (55 +/- 13 years) who underwent heart transplantation during the same time without prior long-term mechanical support. RESULTS: Thirty-two of the 41 patients (78%) underwent heart transplantation, 9 patients (22%) died of multi-organ (n = 5), cardiac (n = 2), or cerebral failure (n = 2). Thirty-day post-transplant mortality includes 5 cases (3 graft failures). Within the following 2 years, another 5 patients expired, 2 of cardiac failure/sudden death. Currently, 21 of 41 patients (51%) are still alive 10 to 77 months (41 +/- 22 months) after heart transplantation (1 patient was lost for follow-up). One-year and 5-year survival rates were compared with the control group (VAD vs control, 1-year survival was 75% vs 74% and 5-year survival was 60% vs 66%). Fifteen patients are doing well in New York Heart Association Class I), and 6 are NYHA Class II despite normal left ventricular ejection fraction. Episodes of moderate acute rejection (International Society for Heart and Lung Transplantation Grade 3) occurred in 10 patients (1.3 episodes per patient), not significantly different from that of the control group (1.2 episodes per patient). Scintigraphy showed regional myocardial ischemia/transplant vasculopathy in 4 patients, and coronary angiography detected the same in 2. One patient has undergone successful retransplantation. Two patients had increased right ventricular pressure. Six patients had impaired kidney function, and 3 had impaired liver function. Seven patients experienced cytomegalovirus infection. CONCLUSIONS: Our data indicate that patients who underwent heart transplantation after long-term mechanical support have a similar survival rate and comparable cardiac morbidity associated with acute rejection episodes.     

Early and midterm risk of coronary allograft vasculopathy in patients bridged to orthotopic heart transplantation with ventricular assist devices

BACKGROUND: Coronary transplant vasculopathy (CAV) has been associated with both immunologic and nonimmunologic factors. The impact of preoperative ventricular assist device (VAD) support on the development of CAV has not been studied. To examine this, we obtained posttransplant coronary angiograms from a group of patients bridged with VAD and compared them to post transplant coronary angiograms of a non-VAD cohort. METHODS: Adult patients undergoing orthotopic heart transplant between 1996-2000 were retrospectively studied and divided into VAD and non-VAD patients. Coronary angiograms were retrospectively reviewed and severity of coronary vasculopathy was categorized as trivial, mild, moderate, or severe. Other variables studied included recipient and donor demographics, cytotoxic panel reactive antibodies (PRA) against T-cell targets and flow cytometric crossmatching against donor T lymphocytes. RESULTS: There was no significant difference between groups regarding demographics. However, VAD patients had a sixfold greater chance of having a T-cell PRA >10% at the time of transplant (p < 0.05), and a fourfold greater chance of having a positive cross match when compared to non-VAD patients (p < 0.05). There was no significant difference in the degree of CAV between groups. Normal coronary anatomy was present in 76% of VAD patients and 64% of non-VAD patients (p = 0.37). These results were similar at 2- and 3-year follow-up (76 vs. 74% and 80 vs. 62%, respectively). CONCLUSION: Preoperative VAD use is associated with increased sensitization; however, these patients develop CAV at the same rate as those not bridged with a VAD.     

Predictors of survival in patients bridged to transplantation with the thoratec VAD device: a single-center retrospective study on more than 100 patients.

BACKGROUND: Careful patient selection markedly influences the outcome of patients who undergo mechanical circulatory support. Therefore, we tried to evaluate predictors of survival after implantation of the Thoratec ventricular assist device (VAD). METHODS: Between October 1992 and January 2000, 104 patients (86 men, 18 women, aged 11 to 69 years) received the Thoratec VAD as a bridge to transplant. A total of 51 patients required left ventricular support (LVAD), 50 patients required biventricular support (BVAD), and 3 patients required total artificial heart implantation. We performed univariate analysis of 25 parameters with regard to their effect on survival and then applied a multivariate analysis to evaluate those factors that turned out to be marginally significant. We performed all analysis for the total collective as well as for the LVAD and BVAD sub-group. RESULTS: The BVAD patients tended to have worse outcomes than did LVAD patients. We found no significant predictors of survival in either sub-group. In the total collective, however, we found the following pre-implant conditions were independent risk factors for survival after VAD implantation: patient age > 60 years (odds ratio [OR] 3.87, confidence interval [CI] 1.39 to 10.76), pre-implant ventilation (OR, 6.76; CI 2.42 to 18.84), and increased pre-implant total bilirubin (OR, 1.42; CL, 1.19 to 1.69). CONCLUSIONS: Transplant candidates on inotropic support should be considered for bridging to transplant as soon as bilirubin values start to increase or before respiratory function deteriorates and ventilation becomes necessary. In elderly patients, careful patient selection, particularly considering potential risk factors, might favorably affect their outcomes.     

肝移植术后腹腔积液的危险因素分析

目的对肝移植术后腹腔积液并发症进行原因分析，了解其危险因素，从而指导肝移植术后腹腔积液的预防和治疗。 方法回顾性分析2015年1月至2016年12月中山市人民医院47例肝移植患者临床资料，根据术后腹腔积液发生情况，分为腹腔积液组（24例）和无腹腔积液组（23例），采用单因素分析、Logistic多元回归分析以及ROC曲线分析肝移植术后发生腹腔积液的危险因素以及敏感度、特异度。 结果Logistic回归分析显示，术后第1天白蛋白（ALB）水平、供体胆碱酯酶（ChE）、脑死亡时间是肝移植术后腹腔积液的危险因素（P=0.017、0.044、0.035）。术后第1天ALB水平每增加评分一级、供体ChE每增加1 U、脑死亡时间增加1 h，患者术后腹腔积液风险分别增加6.531、1.000、1.052倍。ROC曲线分析发现，供体ChE的最佳截断值为5 142 U/L，判断术后腹腔积液发生风险敏感度为79.2%，特异度为56.5%，曲线下面积为0.676（P=0.039，95% CI：0.520~0.832）；供体脑死亡时间截断值为21.5 h，判断术后腹腔积液发生风险敏感度为62.5%，特异度为73.9%，曲线下面积为0.674（P=0.041，95% CI：0.520~0.828）。 结论提高术后第1天ALB水平，选择相对低ChE水平供体及减少供体脑死亡后等待时间可降低肝移植术后腹腔积液发生风险。     

Risk factors for lymphoproliferative disorders after liver transplantation in adults: an analysis of 480 patients

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of organ transplantation that leads to death in more than 50% of cases. The aim of this work was to identify specific risk factors for lymphoproliferative disorders after liver transplantation in adults. METHODS: A total of 480 consecutive patients who underwent transplantation between 1986 and 1997 were studied (323 men, 157 women; mean age: 49.8+/-10.4 years). Demographics, the indication for transplantation, the immunosuppressive regimens, the incidence of rejection episodes, and Epstein-Barr virus infection were analyzed. Univariate and multivariate analysis were used to identify factors predictive of PTLD. RESULTS: Sixteen cases of PTLD (3.3%) occurred at a median of 5.5 (range, 1-39) months after liver transplantation. All 16 cases occurred in patients with evidence of exposure to Epstein-Barr virus before transplantation. In multivariate analysis, the use of antilymphocyte antibodies (P=0.007, relative risk [RR]=4.2, 95% confidence interval [CI]=1.5-11.7), age older than 50 years (P=0.037, RR=3.5, 95% CI=0.95-13.0), liver transplantation for hepatitis C virus cirrhosis (P=0.015, RR=8.7, 95% CI=1-78.3), and liver transplantation for alcoholic cirrhosis (P=0.015, RR=9.6, 95% CI=1.2-77.2) were independently associated with the onset of PTLD. CONCLUSION: Liver transplantation for hepatitis C virus-related and alcoholic cirrhosis and age older than 50 years are three additional risk factors for lymphoproliferative disorder independent of the use of antilymphocyte antibodies. The use of antilymphocyte antibodies after liver transplantation should be avoided in these categories of patients, especially those older than 50 years.     

肝移植术后应用利奈唑胺对血小板的影响

目的分析肝移植术后应用利奈唑胺的不良反应及对患者预后的影响,评价其发生血小板减少的风险及治疗的有效性和安全性。方法选取2007年9月至2009年6月在本院肝移植中心行肝移植的患者85例,采取随机、对照的方法分为利奈唑胺组和万古霉素组,以治疗前、治疗后第3天、第5天、第7天、治疗结束以及治疗结束后第7天等6个时间点,分别从临床特征、血小板计数、发生血小板减少患者的累计发生率、临床疗效和细菌学检查结果等方面进行对比分析。结果随着用药时间的延长,两组患者平均血小板数量无减少的趋势,利奈唑胺组用药前及治疗结束后血小板计数分别为（71.25±11.01）×109/L和（86.74±11.60）×109/L;万古霉素组用药前及治疗结束后分别为（62.0±19.11）×109/L和（85.2±12.73）×109/L,两组差异无统计学意义;用药前后发生血小板减少的患者累计发生率两组的差异无统计学意义（利奈唑胺组2.3%,万古霉素组2.5%）,其中利奈唑胺组45%的患者血小板计数无明显变化或增加,万古霉素组47%的患者血小板计数无明显变化或增加。通过临床疗效及细菌学疗效对比,利奈唑胺组和万古霉素组的有效性差异也无统计学意义。其中临床疗效的有效率分别为90.9%和92.5%,细菌学疗效的有效率分别为91.8%和92.8%。结论与万古霉素相比,在肝移植术后发生革兰阳性球菌的患者中使用利奈唑胺并不会引起血小板的减少,其安全性及有效性与万古霉素相似。     

Risk of colorectal neoplasia in patients with solid organ transplantation

The incidence of colorectal adenomas and advanced neoplasia in the transplant population has not been well characterized. The aim of this study was to determine whether or not there was an increased incidence of colorectal adenomas and advanced neoplasia in solid organ transplantation (SOT) recipients compared with an average-risk population. We reviewed 360 patients with solid organ transplants who underwent colonoscopy between February 1995 and July 2008, and 360 age- and gender-matched patients in an average-risk population. The mean duration from transplantation to colonoscopy in the SOT group was 40.4 ± 34.0 months. Ninety-three (25.8%) adenomas were detected in the SOT group, while 98 (27.2%) adenomas were detected in the control group (p = 0.763). There was a statistically significant difference (p < 0.0001) in the number of patients with advanced neoplasia in the SOT group (24 patients [6.7%]) compared with the control group (3 patients [0.8%]). The independent risk factors of advanced neoplasia were old age (odds ratio [OR], 1.067; 95% CI, 1.019-1.118) and transplantation (OR, 6.069; 95% CI, 1.455-25.314). In summary, there was a significant increase in the incidence of advanced colorectal neoplasia in SOT recipients. The reason for this finding is unclear, and studies with a larger number of patients are needed to further evaluate this group.