心脏移植术后多普勒超声引导下的心内膜心肌活检

目的 评估心脏移植术后在多普勒超声引导下行心内膜心肌活检的应用价值。方法 在心脏移植术后不同时期对8例心脏移植患者共行16次(每例2次)多普勒超声引导下的心内膜心肌活检，活检取材在手术室进行，取材部位为右心室靠近心尖处以及室间隔的右心室面。结果 8例患者中，3例分别于术后第18个月、第24个月和第32个月发生急性排斥反应，其他患者病理诊断为轻度慢性排斥反应。16次取材，无一例发生并发症。结论 在多普勒超声引导下行心内膜心肌活检可以节省费用，减少X线的照射，是一种可行、安全、有效的新方法。     

心脏移植后的移植心冠状动脉血管病与急性排斥反应一例

目的 探讨移植心冠状动脉血管病与急性排斥反应的早期诊断。方法 对1例扩张型心肌病患者施行同种原位心脏移植术。术后定期随访，观察项目有：临床表现，血液生化，标准十二导联心电图，超声心动图，心内膜心肌活检，冠状动脉造影术。结果 术后5-6个月，患者出现乏力，活动后胸闷，心悸，发热等全身或心脏非特异性症状，并有持续存在的窦性心动过速，左心室射血分数（EF）降低，右心房内径增大，室间隔增厚，持续三尖瓣返流，外周血白细胞持续升高，增加免疫抑制剂用量后症状好转或消失，术后9个月，冠状动脉造影显示典型的冠状动脉血管病改变，以左前降支及其中，远段分支血管弥漫性狭窄病变为甚，心内膜心肌活检显示典型的急性排斥反应改变（I-A型）。结论 心脏移植术后系列超声心动图和心电图检查可作为早期移植心冠状动脉血管病和急性排斥反应的无创性检测方法。心内膜心肌活检和冠状动脉造影为确诊手段。     

经胸多普勒超声引导下心内膜心肌活检在心脏移植术后随访中的应用

经皮穿刺、右心室取材的心内膜心肌活检最早是由Caves等在1973年应用于临床，现在已成为诊断心脏移植术后排斥反应的标准检查方法。心内膜心肌活检通常是在DSA室X线透视下进行，患者和操作者均要暴露在放射线下，而且1次检查的费用在1万元左右，因此也限制了心肌活检在临床上的应用。经胸多普勒超声引导下心内膜心肌活检是一种检测心脏移植后排斥反应的新方法，     

巴利昔单抗联合三联免疫抑制方案预防心脏移植后急性排斥反应

目的 评价巴利昔单抗联合常规三联免疫抑制方案预防心脏移植后排斥反应的临床效果及安全性.方法 2004年6月至2011年1月接受心脏移植的受者共214例.所有受者均在术前1h和术后4d时各应用1次巴利昔单抗,剂量为20 mg/次,三联免疫抑制方案为环孢素A(CsA)+吗替麦考酚酯(MMF)+皮质激素.术后采用心内膜活检诊断排斥反应,并按照国际心肺移植协会(ISHLT)的分级标准评价急性排斥反应的严重程度.术后对受者随访1年,收集心内膜活检及发生排斥反应的资料,观察术后并发症的发生情况及死亡情况.结果 受者接受心内膜活检的时间为术后(20.1±7.3) d(1～60 d),结果显示,Ⅰa 级63例(29.4％),Ⅰb 级8例(3.7％),Ⅱ级12例(5.6％);术后1年,143例受者接受心内膜活检,结果显示,Ⅰa 级29例(20.3％),Ⅰb 级1例(0.7％)及Ⅱ级11例(7.7％).住院期间,共有5例受者死亡,死亡原因包括移植心脏功能衰竭3例,多器官功能衰竭1例及猝死1例;出院后至术后1年内,有2例受者死亡,死亡原因包括严重排斥反应1例和多器官功能衰竭1例.术后1个月内,发生感染7例(3.3％),发生急性肾功能不全11例(5.1％),无受者发生肝功能衰竭.结论 应用巴利昔单抗联合常规三联免疫抑制方案是预防心脏移植术后早期急性排斥反应安全、有效的方式.     

心脏移植术后排斥反应的三种无创免疫监测技术的应用

目的 研究心肌内心电图、组织多普勒超声及外周血多基因表达等三种无创监测技术在心脏移植术后排斥反应监测中的安全性和有效性.方法 2004年6月至2011年6月,103例终末期心脏病患者接受了心脏移植手术,术后使用心肌内心电图、组织多普勒超声、外周血多基因表达等三种无创监测技术监测排斥反应.术后1、3、12个月,或发生临床排斥症状,或以上无创监测技术结果高度怀疑排斥反应时常规进行心肌活检.根据心肌活检结果将受者分组,进行组织多普勒超声监测,使用实时荧光定量逆转录聚合酶链技术检测活检证实排斥反应者的外周血单核细胞中16个相关基因的表达.结果 心肌内心电图监测排斥反应的敏感度为92.9％,特异性为99.2％,阳性预见率为70.0％,阴性预见率为99.8％.常规超声仅在心脏功能明显降低时发现异常.组织多普勒技术监测时,Ⅰ级、Ⅱ级及Ⅲ级排斥反应各组与正常对照组各参数比较,均明显降低(P＜0.05);Ⅱ级及Ⅲ级组与0级、Ⅰ级组比较,舒张早期运动速度峰值(Em)、收缩期运动速度峰值(Sm)、舒张早期时间(Tem)显著减少(P＜0.05).发生排斥反应时,7个目的基因的表达出现显著变化,其中整联蛋白α4、他克莫司结合蛋白和白细胞介素1受体Ⅱ型的表达上调,血小板因子4、整联蛋白αM、转化生长因子β1和Ras同源物基因家族成员U的表达下降.结论 心肌内心电图的阴性预见率较高,可作为无创、方便、安全的排斥反应监测技术,并可避免多次活检;常规超声技术监测排斥反应的敏感度较低,组织多普勒超声技术的相关性更好,其中Em、舒张晚期运动速度峰值(Am)、Tem、Sm、收缩早期时间(Tsm)是早期检测急性排斥反应的敏感指标;监测多种排斥反应相关基因的整体变化趋势,可为机体免疫状态评估提供有价值的参考.这几种无创监测技术在监测心脏移植排斥反应方面均具有良好的应用前景.     

心脏移植后经胸超声引导下的颈内静脉径路心内膜心肌活检

经皮穿刺于右心室取材的心内膜心肌活检[1]现在已成为诊断心脏移植术后排斥反应的标准检查方法.我们尝试在最简单的流程,最少的医疗资源消耗,以及对病人产生最小的心理恐惧前提下,开展了经胸超声引导下的颈内静脉径路心内膜心肌活检术.     

原位心脏移植30例临床分析

目的对30例心脏移植进行分析总结。方法30例患者中,24例的原发病为扩张型心肌病,4例为终末期瓣膜性心肌病,1例为终末期缺血性心肌病,1例为病毒性心肌炎行双心室辅助术后1个月。均在体外循环下行原位心脏移植术,3例采用标准心脏移植术式,27例采用双腔静脉吻合心脏移植术式,体外循环时间(75±24)min,主动脉阻断时间(72±8)min。术后采用环孢素A、霉酚酸酯和泼尼松预防排斥反应,根据血环孢素A的浓度调整CsA的用量。术后早期,每天行心肌内心电图及超声心动多普勒监测,以便早期发现急性排斥反应,必要时行心内膜心肌活检。结果30例患者中,术后死亡5例,3例死于低心排,1例死于感染所致的多器官功能衰竭,1例死于出血。术后并发症有低心排、心律失常、三尖瓣返流、右心衰竭、细菌和真菌感染、肾功能异常及血糖升高,上述并发症除导致死亡者外,其余经治疗好转;4例发生急性排斥反应,给予甲泼尼龙冲击治疗,并调整免疫抑制剂的用量后排斥反应逆转。结论术后并发症的预防和及时正确的处理,是心脏移植成功的关键,尤其是对感染、急性排斥反应、右心功能不全及肾功能异常的预防和处理。     

心脏移植术后的免疫抑制治疗与排斥反应的监测

目的：探讨心脏移植术后排斥反应的监测指标及免疫抑制治疗效果,方法：对4例原位心脏移植患者术后给予他克莫司（FK506）,霉酚酸酯（MMF）及泼尼松组成的新三联进行免疫抑制治疗,同时进行急性排斥反应的监测,结果：死亡1例,存活3例,该3例未发生急性排斥反应,且生活质量良好,由FK506,MMF及泼尼松组成的新三联免疫抑制效果良好,结论：FK506,MMF及泼尼松的免疫抑制效果肯定,副作用少,排斥反应监测应把无创性检查与心内膜活检有机地结合起来。     

超声心动图在原位心脏移植后监测急性排斥反应上的应用

原位心脏移植术后对供心的排斥反应是不可避免的,而心脏的急性排斥常是造成病人突然死亡的最重要的原因,因此早期发现,及时处理,终止急性排斥反应于早期阶段是提高术后成活率的重要保证。当前对心脏排斥反应的诊断最可靠方法是心内膜活检,但由于此项技术有一定的难度和要求一定     

抗体介导的排斥反应所致的移植心脏组织病理学变化的观察

目的 研究心脏移植术后移植心中抗体介导的排斥反应(AMR)的发生情况及其组织病理学特征.方法 2003年1月至2007年12月接受心脏移植的受者10例.术后受者移植心功能异常时,以及术后1个月、3个月、1年、2年和3年时进行移植心心内膜心肌活检(EMB),共取得17份活检组织样本,进行常规病理学和C4d免疫组织化学染色.依据2004年国际心脏和肺移植学会(ISHLT)的病理学诊断体系以及移植心AMR诊断体系进行病理学诊断.C4d免疫组织化学染色结果以0至+++予以分级.结果 10例17次EMB中,1次样本不合格,余16次EMB中,7例次诊断为C4d阳性AMR,3例4次诊断为急性细胞性排斥反应,2例次诊断为Quilty损伤.7例次AMR中,1例合并急性细胞性排斥反应,余6例次均为单独发生.10例受者中,1例移植后20个月死亡,尸体解剖检查诊断为慢性排斥反应合并AMR和急性细胞性排斥反应(ISHLT分级3级).其移植心AMR组织学特征为局灶性至广泛性心肌间毛细血管内皮C4d阳性沉积.结论 AMR是心脏移植术后主要的并发症之一,EMB及其C4d免疫组织化学染色是早期诊断AMR的有效方法.     

Interpretation of endomyocardial biopsy after heart transplantation. Potentially confusing factors

Histological examination of the myocardium by endomyocardial biopsy is a standard method of monitoring the presence of acute rejection in the transplanted heart. The histopathological consequences of the biopsy procedure itself have been investigated in non-transplanted hearts in the baboon. Organization of thrombus, necrosis of myocytes adjacent to the biopsy site, and mononuclear cells (including T lymphocytes) surrounding the biopsy site appear after biopsy; should a subsequent biopsy be taken from this area, these appearances may be confused with the appearances associated with acute or resolving cardiac rejection. This problem has been encountered in the clinical transplant programme. Observations on the myocardial histopathological changes resulting from brain death and from parasitic infestation, both of which may also lead to confusion in the interpretation of endomyocardial biopsies, are also presented. Awareness of these factors in patients with heart transplants should lead to caution in the interpretation of the histopathological features and may avoid unnecessary extra immunosuppression early after transplantation. Observations indicate that endomyocardial biopsy should not be the sole method of monitoring for the development of acute rejection.     

Acute septal myocardial infarction diagnosed by endomyocardial biopsy in a heart transplant recipient.

We describe an unusual case of acute septal myocardial infarction in a heart transplant recipient. The clinical presentation was most suggestive of acute rejection; the correct diagnosis was first made by endomyocardial biopsy and was then verified by coronary angiography. Acute myocardial infarction should be included in the differential diagnosis of acute rejection after heart transplantation and included among the possible diagnoses made by endomyocardial biopsy in these patients.     

Role of routine endomyocardial biopsy to monitor late rejection after heart transplantation.

Endomycardial biopsy remains the standard used to monitor rejection after heart transplantation. There is, however, no consensus as to how often surveillance endomyocardial biopsy should be carried out after heart transplantation. We have analyzed 131 patients undergoing orthotopic heart transplantation during the first 4 years of the transplant program at St. Vincent's Hospital. The majority of endomyocardial biopsies that showed acute rejection occurred in the first 3 months after transplantation; after 9 months only 2.5% of endomyocardial biopsies performed showed rejection. Of those patients with rejection, 47% had symptoms. Seven patients experienced late rejection and all made a good recovery with normal cardiac function. We conclude that the incidence of acute rejection decreases significantly more than 3 months after-transplantation; after 9 months only 2.5% of endomyocardial biopsies will show rejection. Of these, 47% will be associated with symptoms. On the basis of experience, we believe that in our own unit, endomyocardial biopsy more than 9 months after transplantation seems unwarranted unless clinically indicated.     

Prediction of acute cardiac rejection using radionuclide techniques

Radionuclide scanning of the donor left ventricle using technetium-99m-labelled red cells was used to monitor acute rejection after heterotopic heart transplantation and compared with histopathological evidence of rejection obtained at examination of an endomyocardial biopsy specimen. The ejection fraction and end-diastolic, end-systolic and stroke volumes were calculated at each examination; an equation was derived from these data to predict the degree of acute rejection, using histopathological examination of endomyocardial biopsy specimens as criteria of the presence and severity of rejection. A highly significant multiple correlation between radionuclide scanning parameters and endomyocardial biopsy was found. The advantages of non-invasive radionuclide scanning over the invasive procedure of endomyocardial biopsy are discussed.     

Induction immunosuppression with basiliximab in heart transplantation

After clinical heart transplantation (HT), it is crucial to use appropriate immunosuppressive agents to prevent rejection. The use of basiliximab or rabbit anti-thymocyte globulin (RATG) for induction therapy has significantly reduced the incidence of acute rejection episodes after kidney transplantation. In this study we sought to examine the effects of basiliximab after HT. From June 2006 to July 2007, we performed 43 HT including patients 18-65 years old undergoing primary HT who were included in this study of basiliximab induction (20 mg intravenous [iv] on days 0 and 4). Cyclosporine and everolimus were given with basiliximab induction. All others received RATG induction (1.5-2.5 mg/kg iv infusion on days 0, 1, and 2) followed by cyclosporine or tacrolimus combined with mycophenolate mofetil. All patients underwent the same operative procedure, steroid-tapering protocol, and postoperative care with protocol endomyocardial biopsy. Basiliximab was well-tolerated and easy to use. There was only 1 operative mortality; the patient died of sepsis due to Enterobacter cloacae. All others survived the operation and are alive and in good health with a 2-year survival rate of 92.86%. No severe adverse events were noted during the first postoperative month. No acute rejection ≥ grade 2R or rejection associated with hemodynamic compromise was noted during the whole course. Basiliximab as induction immunosuppressant was simple, safe, and effective after HT.     

Chronic rejection of a transplanted heart

Three cases of chronic rejection occurring 7.5, 10, and 24 months after transplantation of the heart are analysed. The clinical features of chronic rejection in the late-term periods after transplantation of the heart are discussed. The problems of clinical diagnosis of chronic rejection, the role of endomyocardial biopsy and disorders of lipid metabolism are dealt with. Tactics of saving the patient are recommended. The authors substantiate the necessity for heart retransplantation and, in the absence of a donor's heart, for two-stage transplantation of the heart through an artificial heart or a biventricular approach by means of artificial heart ventricles.     

Non‐invasive graft monitoring after heart transplantation: rationale to reduce the number of endomyocardial biopsies

Abstract The endomyocardial biopsy is invasive, reduces quality of life and cannot be repeated daily. Initial studies on noninvasive cardiac graft monitoring have been presented recently. During the heart transplant procedure, we implanted wideband telemetric pacemakers and fractally coated, epimyocardial electrodes. On biopsy days and during each follow‐up, intramyocardial electrogram sequences were obtained. The maximum T‐slew rate from the ventricular evoked response (VER) was automatically calculated and compared to the biopsy results (n = 331, ISHLT grading). The VER T‐slew rate was significantly lower during rejection grade 2 or higher. The negative predictive value to exclude rejection was 98%. Using a single threshold diagnosis model, 74% of the biopsies could have been avoided. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after heart transplantation     

Intermediate term results of infant orthotopic cardiac transplantation from two centers

Orthotopic cardiac transplantation has become established for selected infants with severe forms of congenital heart disease. This study reviews the combined experience and intermediate term results of infants undergoing orthotopic cardiac transplantation from Children's Memorial Hospital, Chicago, and Kosair Children's Hospital, Louisville. From June 1986 through December 1989, 20 orthotopic cardiac transplantations were performed in 19 patients. Sixteen patients had variants of hypoplastic left heart syndrome. One infant had anomalous origin of the left coronary artery with severe ischemic cardiomyopathy. Two infants had aortic stenosis with endocardial fibroelastosis, and one had extracorporeal membrane oxygenation as a bridge to transplantation. Immunosuppression included cyclosporine, azathioprine (Imuran), and corticosteroids with an effort to wean the patients from steroids by 6 months to 2 years. Three early deaths resulted--from technical errors in two patients and from hyperacute rejection in one patient at 3 days. Four late deaths have occurred. Two patients died at 2 and 13 months of acute rejection. One patient died at 15 months of acute rejection after retransplantation. One patient died at 7 months of respiratory syncytial viral pneumonia. The remaining 12 patients are surviving 5 to 47 months (means 20 months) after orthotopic cardiac transplantation. Rejection surveillance in the first 6 months is by clinical signs supplemented by echocardiography, electrocardiography, and cell cycle analysis; endomyocardial biopsy is used after 6 months of age. For the cumulative series, 24 episodes of suspected rejection have been treated during 277 at-risk patient months with intravenous methylprednisolone (Solu-Medrol) (n = 18) and monoclonal antibody (OKT3) (n = 6), for an incidence of 1.04 episodes of rejection per patient per year. Serious posttransplantation infections including endocarditis, catheter sepsis, meningitis, and colonic perforation were successfully treated in four patients. Subjectively, their quality of life is excellent as shown by normal growth and developmental milestones and a low hospital readmission rate (1.4 episodes per patient per year). These encouraging intermediate term results warrant continued application of infant orthotopic cardiac transplantation for severe forms of congenital heart disease.     

Acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system.

BACKGROUND: A cascade of inflammatory reactions characterize acute vascular rejection after heart transplantation. This study was undertaken to test the hypothesis that acute vascular rejection is associated with up-regulation of vitronectin receptor (alphavbeta3), increased expression of tissue factor, and activation of the extracellular matrix metalloproteinase induction system. METHODS: Acute vascular rejection developed in 14 heart transplant recipients within 2 weeks of transplantation, confirmed by immunofluorescence (AVR group). We compared these patients with 10 transplant recipients who had no evidence of acute vascular rejection or peritransplant ischemic injury (control group). We evaluated endomyocardial biopsy specimens for alphavbeta3, tissue factor, and extracellular matrix metalloproteinase inducer (EMMPRIN). RESULTS: Compared with the control group, the AVR group demonstrated evidence of significantly increased expression of alphavbeta3 (1.9-fold, p < 0.001), tissue factor (1.8-fold, p < 0.001), and EMMPRIN (1.5-fold, p < 0.001). All patients in the AVR group received plasmapheresis; 11 of 14 patients had evidence of ischemic necrosis on biopsy specimens, and 3 of 14 patients experienced hemodynamic compromise and graft dysfunction and died within 3 weeks of transplant. Another patient died at 10 months after transplant. CONCLUSIONS: Acute vascular rejection is associated with up-regulation of alphavbeta3, tissue factor, and activation of the matrix metalloproteinase induction system, which may contribute to the lethal morbidity associated with this disease.     

Sustained elevated concentrations of cardiac troponin T during acute allograft rejection after heart transplantation in children

BACKGROUND: The diagnosis of acute rejection after heart transplantation is made on the basis of endomyocardial biopsy. In children, where the method may be associated with complications, a noninvasive alternative would be desirable. We evaluated the myocardial damage marker cardiac troponin T (cTnT) as a marker of rejection in children who have undergone heart transplantation. METHODS: Peripheral venous blood was collected in 124 endomyocardial biopsies in 14 children who had undergone heart transplantation (1-20 years of age). Serum levels of cTnT were compared with histologic rejection according to the International Society of Heart and Lung Transplantation (ISHLT) (grades 0-4). RESULTS: Seven children experienced nine episodes of acute rejection. During rejection, cTnT increased from 0.05+/-0.07 (mean+/-SD) microg/L to 0.26+/-0.27 microg/L and remained elevated 7 and 30 days thereafter (0.10+/-0.11 and 0.36+/-0.38 microg/L, respectively) before returning to normal after 50 to 430 days. In surveillance biopsies, cTnT displayed considerable variation at all rejection grades: ISHLT grade 0, median 0.03 microg/L (range 0.01-2.04 microg/L); ISHLT grade 1, median 0.06 microg/L (range 0.01-0.67 microg/L); ISHLT grade 2, median 0.10 microg/L (range 0.01-1.42 microg/L); and ISHLT grade 3, median 0.17 microg/L (range 0.01-0.93 microg/L). A receiver operating characteristics analysis for cTnT versus rejection grade revealed an area under the curve of 0.69, indicating a moderate predictive value for cTnT. However, a cutoff of 0.015 microg/L yielded a specificity of only 36%, with a sensitivity of 89%, whereas a cutoff of 0.1 microg/L resulted in sensitivity and specificity of 53% and 77%, respectively. CONCLUSIONS: Cardiac troponin T increased and remained elevated for at least 1 month during acute rejection. The diagnostic power of a single cTnT measurement was not sufficient to replace endomyocardial biopsy.