Text B Cardiac Transplantation

Advanced or end－stage heart failure is an increasingly frequent sequela as progressively more effective palliation for the earlier stages of heart disease and prevention of sudden death associated with heart disease become more widely recognized and employed．1 When patients with end－stage or refractory heart failure are identified，the physician is faced with the decision of advising compassionate end－of－life care or choosing to recommend extraordinary life－extending measures．For the occasional patient who is relatively young and without serious comorbidities，the latter may represent a reasonable option．

Surgical techniques for orthotopic transplantation of the heart were devised in the 1960s and taken into the clinical arena in 1967．The procedure did not gain widespread clinical acceptance until the introduction of“modern”and more effective immunosuppression in the early 1980s．By the 1990s the demand for transplantable hearts met，and then exceeded，the available donor supply and leveled off at about 4，000heart transplants annually worldwide， according to data from the Registry of the International Society for Heart and Lung Transplantation（ISHLT）．Subsequently heart transplant activity in the United States has remained stable at 2，200 per year，but worldwide activity reported to this Registry has decreased some．This apparent decline in numbers may be a result of the fact that reporting is legally mandated in the United States，but not elsewhere，and several countries have started their own databases．

Surgical Technique

Donor and recipient hearts are excised in virtually identical operations with incisions made across the atria and atrial septum at the midatrial level （leaving the posterior walls of the atria in place）and across the great vessels just above the semilunar valves．2 The donor heart is generally“harvested”in an anatomically identical manner by a separate surgical team and transported from the donor hospital in a bag of iced saline solution and then is reanastomosed into the waiting recipient in the orthotopic or normal anatomic position．The only change in surgical technique since this method was first described has been a movement in recent years to move the right atrial anastomosis back to the level of the superior and inferior vena cavae in order to better preserve right atrial geometry and prevent atrial arrhythmias．Both methods of implantation leave the recipient with a surgically denervated heart that does not respond to any direct sympathetic or parasympathetic stimuli but does respond to circulating catecholamines．The physiologic responses of the denervated heart to the demands of exercise are atypical but quite adequate to carry on normal physical activity．

Donor Allocation System

In the United States the allocation of donor organs is accomplished under the supervision of the United Network for Organ Sharing（UNOS），aprivate organization under contract to the federal government．The United States is divided geographically into eleven regions for donor heart allocation．Allocation of donor hearts within a region is decided according to a system of priority that takes into account：（1）the severity of illness，（2）geographic distance from the donor，and（3）patient time on the waiting list．A physiologic limit of 3 h of“ischemic”（out of body）time for hearts precludes a national sharing of hearts． This allocation system design is reissued annually and is responsive to input from a variety of constituencies，including donor families and transplant professionals．3

At the current time，highest priority according to severity of illness is assigned to patients requiring hospitalization at the transplant center forⅣinotropic support with a pulmonary artery catheter in place for hemodynamic monitoring or to patients requiring mechanical circulatory support［i．e．intra－aortic balloon pump（IABP），right or left ventricular assist device（RVAD， LVAD），extracorporeal membrane oxygenation（ECMO），or mechanical ventilation］．Second highest priority is given to patients requiring ongoing inotropic support，but without a pulmonary artery catheter in place．All other patients have priority according to their time on the waiting list，and matching is achieved only according to ABO blood group compatibility and gross body size compatibility，although some patients who are“pre－sensitized”and have preexisting anti－HLA antibodies（commonly multiparous women or patients previously multiply transfused）undergo prospective crossmatching with the donor．

Indications／Contraindications

Heart failure is an increasingly common cause of death，particularly in the elderly．Most patients，who reach what has recently been categorized as stage D，or refractory end－stage heart failure，are appropriately treated with compassionate end－of－life care．A subset of such patients who are younger and without significant comorbidities can be considered as candidates for heart transplantation．Exact criteria vary in different centers but generally take into consideration the patient's physiologic age and the existence of comorbidities such as peripheral or cerebrovascular disease，obesity，diabetes，cancer，or chronic infection．

Results

A registry organized by the ISHLT has tracked worldwide and United States survival rates after heart transplantation since 1982．The most recent update reveals 83％and 76％survival 1 and 3 years posttransplant，or a posttransplant“half－life”of 9．3 years．The quality of life in these patients is generally excellent，with well over 90％of patients in the registry returning to normal and unrestricted function following transplantation．

Immunosuppression

Medical regimens employed to provide suppression of the normal immune response to a solid organ allograft vary from center to center and are in a constant state of evolution as more effective agents with improved side－effect profiles and less toxicity are introduced．4 All currently used regimens are nonspecific，providing general hyporeactivity to foreign antigens rather than donor－specific hyporeactivity as well as the attendant，and unwanted，susceptibility to infections and malignancy．Most cardiac transplant programs currently use a three－drug regimen including a calcineurin inhibitor（cyclosporine or tacrolimus），an inhibitor of T cell proliferation or differentiation（azathioprine，mycophenolate mofetil，or sirolimus），and at least a short initial course of glucocorticoids． Many programs also include an initial“induction”course of polyclonal or monoclonal anti－T cell antibodies in the perioperative period to decrease the frequency or severity of early posttransplant rejection．Most recently introduced have been monoclonal antibodies（daclizumab and basiliximab）， which block the interleukin2 receptor and may provide prevention of allograft rejection without additional global immunosuppression．

Diagnosis of cardiac allograft rejection is usually made with the use of endomyocardial biopsy，either done on a surveillance basis or in response to clinical deterioration．Biopsy surveillance is performed on a regular basis in most programs for the first year postoperatively and for the first 5 years in many programs． Therapy consists of augmentation of immunosuppression，the intensity and duration of which is dictated by the severity of the rejection．Diagnosis of cardiac allograft rejection is usually made with the use of endomyocardial biopsy，either done on a surveillance basis or in response to clinical deterioration．

Late Posttransplant Management Issues

Increasing numbers of heart transplant patients are surviving for years following transplantation and constitute a population of patients with a number of long－term management issues．

Allograft coronary artery disease．Despite usually having young donor hearts，cardiac allograft recipients are prone to develop coronary artery disease （CAD）．This CAD is generally a diffuse，concentric，and longitudinal process that is quite different from“ordinary”atherosclerotic CAD，which is more focal and often eccentric．The underlying etiology is most likely primarily immunologic injury of the vascular endothelium，but a variety of risk factors influence its existence and progression and include nonimmunologic factors such as dyslipidemia，diabetes，and cytomegalovirus（CMV）infection．It is hoped that newer and improved immunosuppressive modalities will reduce the incidence and impact of these devastating complications，which currently account for the majority of late posttransplant deaths．Thus far the newer immunosuppressive agents mycophenolate mofetil and the mammalian target of rapamycin（m TOR）inhibitors sirolimus and everolimus have been shown to be associated with short－term lesser incidence and extent of coronary intimal thickening；in anecdotal reports institution of sirolimus was associated with some reversal of the disease．The use of statins has also been shown to be associated with a reduced incidence of this vasculopathy，and these drugs are now almost universally used in transplant recipients unless contraindicated． Palliation of the disease with percutaneous interventions is probably safe and effective in the short term，although the disease often advances relentlessly． Because of the denervated status of the organ，patients rarely experience angina pectoris，even with advanced stages of the disease．

Retransplantation is the only definitive form of therapy for advanced allograft CAD，but the scarcity of donor hearts makes the decision to pursue retransplantation a difficult one in an individual patient，as well as a difficult ethical issue．

Malignancy．The occurrence of an increased incidence of malignancy is a well－recognized sequela of any program of chronic immunosuppression，and organ transplantation is no exception．Lymphoproliferative disorders are among the most frequent posttransplant complications and，in most cases，seem to be driven by the Epstein－Barr virus．Effective therapy includes reduction of immunosuppression（a clear“double－edged sword”in the setting of a life－sustaining organ），antiviral agents，and traditional chemo－and radio－therapy．Most recently，specific antilymphocyte（CD20）therapy has shown great promise． Cutaneous malignancies（both basal cell and squamous cell carcinomas）also occur with increased frequency in transplant recipients and can pursue very aggressive courses．The role of decreasing immunosuppression for treatment of these cancers is much less clear．

Infections．The use of currently available nonspecific immunosuppressive modalities to prevent allograft rejection naturally results in an increased susceptibility to infectious complications in transplant recipients．5 Although their incidence has decreased since the introduction of cyclosporine，infections with unusual and opportunistic organisms remain the major cause of death during the first postoperative year and remain a threat to the chronically immunosuppressed patient throughout life．Effective therapy depends on careful surveillance for early signs and symptoms of opportunistic infection and an extremely aggressive approach to obtaining a specific diagnosis as well as expertise in recognizing the more common clinical presentations of CMV， Aspergillus，and other opportunistic infectious agents．

（1，620 words）

New words and phrases

palliation［pælɪ'eɪʃən］n． （痛苦的）减轻

orthotopic［ɒðə'tɒpɪk］a． 正位的，原位的

donor［'dəʊnə］n． （器官等的）供者

recipient［rɪ'sɪpɪənt］n． 接受者

semilunar［,semɪ'ljuːnə］a． 半月形的

vena［'viːnə］n． 静脉

denervate［diː'nзːveɪt］v． 切除……的神经支配

parasympathetic［'pærə,sɪmpə'θetɪk］a． 副交感神经的n． 副交感神经；副交感神经系统

inotropic［,ɪnə'trɒpɪk］a． 影响肌（肉）收缩力的，变力的

antibody［'æntɪ,bɒdɪ］n． 抗体

multiparous［mʌl'tɪpərəs］a． 多产的；经产的

allograft［'æləɡrɑːft］n． 同种异体移植物

hyporeactivity［'haɪpə,rɪæk'tɪvɪtɪ］n． 极度不活跃

susceptibility［sə,septə'bɪlətɪ］n． 敏感性

calcineurin n． 钙调磷酸酶

proliferation［,prəlɪfə'reɪʃən］n． 增殖

azathioprine［,æzə'θaɪəpriːn］n． 硫唑嘌呤（一种免疫抑制剂）

mycophenolate mofetil 吗替麦考酚酯，麦考酚酸酯

sirolimus n． 西罗莫司（一种免疫抑制剂）

glucocorticoid［,ɡluːkəʊ'kɔːtɪkɒɪd］n． 糖皮质激素

polyclonal［,pɒlɪ'kləʊnəl］a． 多克隆的

monoclonal［,mɒnə'kləʊnəl］a． 单克隆的

daclizumab n． 达克珠单抗

basiliximab n． 巴利昔单抗

interleukin 2 白细胞介素2

deterioration［dɪ,tɪərɪə'reɪʃən］n． 恶化

cytomegalovirus（CMV） 巨细胞病毒

［'saɪtəʊ,meɡələʊ'vaɪərəs］n．

rapamycin n． 雷帕霉素

everolimus n． 依维莫司

vasculopathy［,væskjuː'lɑːpəθɪ］n． 血管病变

lymphoproliferative［,lɪmfəʊprəʊ'lɪfərətɪv］a． 淋巴组织增生的

antiviral［æntɪ'vaɪərəl］a． 抗病毒的

antilymphocyte［,æntɪ'lɪmfəsaɪt］a． 抗淋巴细胞的

cutaneous［kjuː'teɪnɪəs］a． 皮肤的

Aspergillus［,æspə'dʒɪləs］n． 曲霉菌属，曲霉属

Notes

1．Advanced or end－stage heart failure is an increasingly frequent sequela as progressively more effective palliation for the earlier stages of heart disease and prevention of sudden death associated with heart disease become more widely recognized and employed．

参考译文：当对早期阶段的心脏病需更有效治疗和对与心脏病有关的猝死需有效预防的认识被广泛接受和普遍应用时，晚期或终末期心力衰竭就成为一种渐趋常见的后遗症。

句中as引导时间状语从句；heart disease是状语从句的主语，become是状语从句的谓语。过去分词短语associated with heart disease做sudden death的后置定语。

2．Donor and recipient hearts are excised in virtually identical operations with incisions made across the atria and atrial septum at the midatrial level （leaving the posterior walls of the atria in place）and across the great vessels just above the semilunar valves．

参考译文：供体心脏和受体心脏的切除几乎是相同的手术操作，即在中间心房水平，从心房到房间隔（心房后壁保留在原位），再穿过半月瓣上方的大血管做切除。

此句中过去分词短语made across the atria and atrial septum．．．and across above the semilunar valves做incisions的后置定语，相当于定语从句which are made across．．．

3．This allocation system design is reissued annually and is responsive to input from a variety of constituencies，including donor families and transplant professionals．

参考译文：每年这一脏器分配制度的调整方案都重新公布，接受并输入包括脏器捐赠家庭和移植专业人员在内的各类新信息。

此句中including donor families and transplant professionals是介词短语做状语，对全句进行补充说明。

4．Medical regimens employed to provide suppression of the normal immune response to a solid organ allograft vary from center to center and are in a constant state of evolution as more effective agents with improved side－effect profiles and less toxicity are introduced．

参考译文：用于抑制实体器官同种移植物正常免疫反应的医疗方案因各移植中心的差异而有所不同，并随着不良反应更少、毒性更小、疗效更好药剂的引进和使用而不断完善。

employed to provide suppression of the normal immune response to a solid organ allograft为过去分词短语做后置定语，修饰主语medical regimens；vary from center to center and are in a constant state of evolution是并列谓语部分。as引导时间状语从句，agents是从句主语，are introduced是从句谓语。

5．The use of currently available nonspecific immunosuppressive modalities to prevent allograft rejection naturally results in an increased susceptibility to infectious complications in transplant recipients．

参考译文：为防止异体移植排斥反应而使用现有的非特异性免疫抑制剂的做法会导致移植受体更易发生感染性并发症。

to prevent allograft rejection naturally是不定式短语做定语，修饰主语the use。

Exercises

Ⅰ．Answer the following questions．

1．Can you state the process of the operations in excising donor and recipient hearts？

2．What kinds of drugs will be used in most cardiac transplant programs？

3．What is the underlying etiology to develop coronary artery disease（CAD）？

4．Is there any effective therapy in lymphoproliferative disorders？What does it include？

5．Based on the passage，what should be paid closely attention to avoid infectious complications？

Ⅱ．Decide whether the following statements are True or False．

1．The donor heart is generally“harvested”in an anatomically identical manner by a separate surgical team and transported from the donor hospital in a bag of iced saline solution and then is reanastomosed into the waiting recipient in the orthotopic or normal anatomic position．

2．Most cardiac transplant programs currently use a three－drug regimen including a calcineurin inhibitor（cyclosporine or tacrolimus），an inhibitor of T cell proliferation or differentiation（azathioprine，mycophenolate mofetil，or sirolimus），and at least a short initial course of glucocorticoids．

3．Diagnosis of cardiac allograft rejection is usually made with the use of endomyocardial biopsy，only done on a surveillance basis．

4．This CAD is generally a diffuse，concentric，and longitudinal process that is quite different from“ordinary”atherosclerotic CAD，which is more focal and often eccentric．

5．Lymphoproliferative disorders are among the most frequent posttransplant complications and，in most cases，must be driven by the Epstein－Barr virus．