You are in: eMedicine Specialties > Transplantation > Surgery Heart TransplantationArticle Last Updated: Feb 9, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Mary C Mancini, MD, PhD, Director of Cardiothoracic Transplantation, Professor, Department of Surgery, Louisiana State University Health Sciences Center Mary C Mancini is a member of the following medical societies: American Heart Association, American Medical Association, American Thoracic Society, Association for Academic Surgery, Association for Surgical Education, International College of Surgeons, International Society for Heart and Lung Transplantation, New York Academy of Sciences, Phi Beta Kappa, and Southern Thoracic Surgical Association Coauthor(s): Deepak M Gangahar, MBBS, MD, Professor, Department of Surgery, Chief, Section of Cardiovascular and Thoracic Surgery, Surgical Director, Heart Transplant and VAD Services, University of Nebraska Medical Center Editors: Richard Thurer, MD, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Miami School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Shreekanth V Karwande, MBBS, Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center; Michael E Zevitz, MD, Assistant Professor of Medicine, Finch University of the Health Sciences, The Chicago Medical School; Consulting Staff, Private Practice; John Geibel, MD, DSc, MA, Professor, Department of Surgery, Section of Gastrointestinal Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital Author and Editor Disclosure Synonyms and related keywords: cardiac replacement, cardiac transplantation, cardiac allograft, cardiopulmonary bypass, cyclosporine, intra-aortic balloon pump, implantable assist devices, coronary artery angioplasty, coronary artery bypass surgery, CABG, valve repair, allografts, xenografts, end-stage congestive heart failure, CHF, ischemic cardiomyopathy, angina, pulmonary disease, malignant cardiac arrhythmias, coronary artery disease, CAD, congenital heart disease, CHD, cytomegalovirus, CMV, rejection, organ donors, organ donation INTRODUCTIONSection 2 of 12
  Cardiac transplantation is a widely accepted therapy for the treatment of end-stage congestive heart failure. Most candidates for cardiac transplantation have not been helped by conventional medical therapy and are excluded from other surgical options because of the poor condition of the heart. About 45% of the candidates have ischemic cardiomyopathy; however, this percentage is rising because of the increase in coronary artery disease in younger age groups. Of the candidates, 54% have some form of dilated cardiomyopathy, which often has an unclear origin. The remaining 1% of candidates fall into the category of other diseases, including congenital heart disease, that are not amenable to surgical correction. Candidacy determination and evaluation are key components of the process, as is postoperative follow-up care and immunosuppression management. Proper execution of these steps can culminate in an extremely satisfying outcome for both the physician and patient. History of the ProcedureChristian Barnard performed the first successful heart transplant in a human in 1967 in South Africa. The origins of the procedure date to 1905, when Alexis Carrel transplanted a puppy's heart into the neck of a dog. Because of the lack of immunosuppression, the experiment was unsuccessful; however, the work spurred numerous investigations that culminated in the success the procedure has today. Early investigators included Frank C. Mann of the Mayo Clinic, V.P. Demikov of the Soviet Union, and Marcus Wong. These early efforts in transplantation were thwarted by the infancy of cardiopulmonary bypass and a lack of understanding of the immune system. As knowledge in these areas advanced, so did the field of cardiac transplantation. The clinical use of cyclosporine as an immunosuppressant revolutionized the field of cardiac transplantation in 1983. Recipient survival rates improved, thus producing an explosive increase in the number of transplant centers offering cardiac transplantation. The remaining limiting factor was the number of available organ donors. ProblemCardiac transplantation is the procedure by which the failing heart is replaced with another heart from a suitable donor. The procedure is generally reserved for patients with end-stage congestive heart failure with a prognosis of less than a year to live without the transplant and who are not candidates for conventional medical therapy or have not been helped by conventional medical therapy. As of this writing, approximately 3,109 individuals are waiting for hearts. In 2004, about 1,800 heart transplants were performed nationwide. Clearly, one issue surrounding the transplantation process is the availability of organs for this lifesaving procedure. FrequencyThe annual frequency of the procedure is about 1% of the general population with heart failure, both candidates and noncandidates. EtiologyThe disease processes that require cardiac transplantation can be divided into the following categories:
PathophysiologyThe pathophysiology of cardiomyopathy that may require cardiac replacement is dependent upon the primary disease process. Chronic ischemic conditions precipitate myocardial cell damage, with progressive enlargement of the myocyte followed by cell death and scarring. The condition can be treated with angioplasty or bypass procedures; however, the small-vessel disease is progressive in nature, resulting in progressive loss of myocardial tissue. This eventually results in significant functional loss and progressive cardiac dilatation. The pathologic process involved in the functional deterioration of the dilated cardiomyopathy is still unclear. Mechanical dilatation and disruption of energy stores appear to play a role. The pathophysiology of the transplanted heart is unique. The denervation of the organ makes it dependent on its intrinsic rate. As a result of the lack of neuronal input, some left ventricular hypertrophy results. The right-sided function is directly dependent upon the ischemic time incurred prior to reimplantation and the adequacy of preservation. The right ventricle is easily damaged and may initially function as a passive conduit until recovery occurs. The rejection process that can occur in the allograft is primarily of 2 forms, cellular and humoral. Cellular rejection is the classic form of rejection and is characterized by perivascular infiltration of lymphocytes with subsequent myocyte damage and necrosis if left untreated. Humoral rejection is much more difficult to characterize and diagnose. Humoral rejection is thought to be a generalized antibody response initiated by several unknown factors. The antibody deposition into the myocardium results in global cardiac dysfunction. This diagnosis is generally made on the basis of clinical suspicion and exclusion because endomyocardial biopsy is of little value. Coronary artery disease is a late pathologic process common to all cardiac allografts. The pathology is characterized by myointimal hyperplasia of the small- and medium-sized vessels. The lesions are diffuse in nature. The lesions may appear any time from 3 months to several years after implantation. The inciting causes are still unclear, though cytomegalovirus (CMV) infection and chronic rejection have been implicated. The mechanism of the process is thought to be dependent upon growth-factor production in the allograft initiated by circulating lymphocytes. Currently, the process has no treatment other than retransplantation. ClinicalCandidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III or IV symptoms. Evaluation demonstrates ejection fractions of less than 25%. Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken. The interim therapy can include oral agents as well as inotropic support. Mechanical support with the intra-aortic balloon pump or implantable assist devices may be appropriate in some patients as a bridge to transplantation. INDICATIONSSection 3 of 12
The general indications for cardiac transplantation include deteriorating cardiac function and having a prognosis of less than 1 year to live. Specific indications
RELEVANT ANATOMYSection 4 of 12
During the cardiac transplantation procedure, the ventricles are excised, leaving the great vessels, right atrium, and left atrium of the recipient. The donor heart is then sewn to these areas (see Images 1-3). A recent trend has been to revert to bicaval anastomoses rather than right atrial anastomoses in an attempt to decrease the incidence of postoperative tricuspid insufficiency. In the transplantation process, the sinoatrial nodes of the donor and recipient remain intact, and both are present within the recipient. For approximately 3 weeks after surgery, the electrocardiogram demonstrates 2 P waves; however, the heart rate and electrical activity of the new heart are purely dependent on the intrinsic electrical system of the heart and not on the neurological input from the recipient. CONTRAINDICATIONSSection 5 of 12
WORKUPSection 6 of 12
Lab Studies
Imaging Studies
Other Tests
Diagnostic Procedures
TREATMENTSection 7 of 12
Medical therapyClosely monitor the heart transplant candidate for signs of clinical deterioration during the waiting period for a suitable donor organ. Administer standard therapy for congestive heart failure, and offer the patient the alternative of participating in experimental clinical trials because this does not preclude listing for transplantation. Close contact with the transplant center must be maintained, keeping the consultants informed of ongoing medical and social issues pertaining to the candidate. In the event of clinical deterioration, the transplant center may deem it appropriate to admit the patient for evaluation for implantation of an artificial cardiac assist device and/or an upgrade on the waiting list. At times, the candidate may deteriorate to the point that transplantation is no longer an option. Carefully discuss these issues with the treating physicians, the patient, and the family. Surgical therapyThe applicability of cardiac transplantation is limited by the availability of suitable donors. All potential donors have succumbed to brain death secondary to some catastrophic event. The underlying pathology of the donor, including cardiac contusion, cocaine use, cardiac pathology, or social history, often precludes donation. Because of the short preservation time tolerated by the heart (4-6 h), procurement distances are limited. Potential heart donors must meet brain death criteria and be free of cardiac pathology. Examination by echocardiography remains the best initial screening mechanism for potential donors. A normal ejection fraction (>50%) with normal valvular structure and function and an absence of left ventricular hypertrophy (as determined by echocardiography) are indicators of an excellent heart for transplantation. Minimal abnormalities detected by echocardiography, such as trivial tricuspid or mitral regurgitation, marginal left ventricular hypertrophy, or reduced ejection fraction, may also be indicators of an acceptable organ for transplantation, depending on the history of the donor and the condition of the recipient. In instances in which the recipient is in extremis, a less-than-ideal donor heart may be accepted in order to save the patient's life. Donors who have a significant smoking history must be screened for coronary artery disease with cardiac catheterization. Current donor criteria include age younger than 65 years, normal cardiac function, and no coronary artery disease. Once these criteria are met, donor and potential recipients are matched according to blood group (ABO) compatibility and size. The final decision regarding the suitability of the donor heart can be made only by direct inspection by an experienced surgeon. A median sternotomy incision is performed to allow for inspection of the heart. Care is taken to assess the organ for potential contusions and overall function. The heart is flushed with cold cardioplegia solution, removed, and placed into cold sterile electrolyte solution for transport. The recipient operation is performed using cardiopulmonary bypass. The recipient heart is removed, and the donor heart is inserted in its place. The left atrial anastomosis is performed, followed by the right atrium and the great vessels. Intraoperative detailsSee Images 1-3. While preparing a graft for transplantation, the authors look for a patent foramen ovale. If present, it is closed. Over the last few years, many centers have started to perform tricuspid valve annuloplasty of the graft as prophylaxis against development of tricuspid regurgitation in the postoperative period. In some series, the rate of moderate-to-severe tricuspid regurgitation is reported to be as high as 50% at 5 years. A cardiac allograft can be sewn in a heterotopic or orthotopic position. The authors rarely perform heterotopic heart transplants (see Image 4) because of the inherent problems (eg, pulmonary compression of the recipient, difficulty obtaining endomyocardial biopsy, need for anticoagulation); however, it is an excellent technique for patients with severe pulmonary hypertension. Orthotopic heart transplantation is performed with either the classic Shumway-Lower technique or as a bicaval anastomosis (see Images 5-6). The former method is simpler and saves perhaps 10-15 minutes of ischemic time. The latter method is advantageous in that, by avoiding a large right atrium, the surgeon is able to maintain better atrial transport. Another claimed advantage is a lower reported incidence of tricuspid regurgitation with the bicaval technique. Additionally, when the ischemic time of the allograft is too long because of transportation or surgical extraction of the recipient heart/ventricular assist device, the donor heart can be better preserved by continuous cold retrograde blood cardioplegia through the coronary sinus. Of course, topical cooling of the graft continues to be the primary means of graft preservation. The incidence of tricuspid regurgitation is reported to be as high as 47-98% following heart transplantation (Chan, 2001). Some centers have now begun to prophylactically perform tricuspid annuloplasty on donor grafts before performing the transplantation (McGee, 2004). Postoperative detailsThe patient is maintained on a combination of pressor agents while the donor heart regains energy stores. The ionized calcium level of the patient is carefully monitored and replaced with calcium chloride because the function of the denervated heart is initially extremely dependent on circulating calcium ions. The acid-base status of the patient is also carefully monitored and corrected. Immunosuppression is started soon after surgery. Several regimens can be used, including pretransplantation induction therapy or simply postoperative maintenance therapy. The choice of regimen is dependent upon the training and experience of the transplant center. Once stabilized, the patient is rapidly weaned from the ventilator and the pressors. The posttransplant hospital stay can be as short as 5 days, depending upon the condition of the recipient prior to surgery. Follow-upAfter transplant, endomyocardial biopsies are performed to assess for allograft rejection. These may be performed as frequently as every week for the first month, with the frequency decreasing over time. Follow-up visits are frequent for the first month because regulation of immunosuppression is being adjusted during this time. The frequency of visits gradually diminishes until the patient is generally seen on an annual basis. Certain centers perform coronary angiography annually after transplantation to monitor the patient for the development of allograft vascular disease. For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education articles Heart and Lung Transplant and Congestive Heart Failure. COMPLICATIONSSection 8 of 12
Complications after transplantation include bleeding from the suture lines. This is a rare occurrence but may require reexploration in the early postoperative period. Hyperacute rejection can occur immediately after blood flow is restored to the allograft and up to 1 week after surgery despite therapeutic immunosuppression. Infection is the primary concern in transplant patients. Preventive measures should be instituted. During the early posttransplant course, bacterial infections are of primary concern. Fungal infections can appear if the patient is diabetic or overimmunosuppressed. Prophylaxis for Pneumocystis carinii is universally administered, as is therapy for CMV infection. Maintain vigilance for other uncommon infectious processes including Listeria, Legionella, Chlamydia, and Nocardia infections. Psychiatric disturbances from steroid therapy can occur in the immediate posttransplant period. These disturbances may be predicted from the pretransplantation psychiatric evaluation and thus averted. Cardiac rejection is to be expected and should be detected by endomyocardial biopsy. Depending upon the severity of the incident, the process can be treated with steroid therapy alone, polyclonal antibody therapy, or monoclonal antibody therapy. Allograft vascular disease is the main cause of late graft failure and death. The coronary arteries develop a progressive concentric myointimal hyperplasia. This hyperplasia can develop as early as 3 months after transplantation. The cause of the process is unclear. However, CMV infection and recurrent rejection episodes are thought to be associated with the cause. Current research indicates that the initial ischemia/reperfusion injury of the allograft coupled with repeated rejection episodes might contribute to the process. The only available therapy is retransplantation. The process can sometimes be treated by stenting of the diseased vessels. OUTCOME AND PROGNOSISSection 9 of 12
The 1-year survival rate after cardiac transplantation is as high as 81.8%, with a 5-year survival rate of 69.8%. A significant number of recipients survive more than 10 years after the procedure. The functional status of the recipient after the procedure is generally excellent, depending upon the motivation of the individual. FUTURE AND CONTROVERSIESSection 10 of 12
The future of cardiac transplantation rests upon several issues. The ongoing shortage of donor organs has fueled a search for alternative therapies for the failing heart. These therapies include artificial assist devices, dual-chamber pacing, new drug interventions, and genetic therapy. Research in the area of xenografts continues. The prevention of allograft vascular disease remains a paramount challenge. This pathology is clearly multifactorial in origin, making the research and therapy equally complex. Resolution of this issue will prolong graft survival and lives. The question of recipient selection and listing status continues to pose medical and ethical dilemmas. If the donor situation were not an issue, then the listing of potential recipients would not be troublesome. Finally, in this era of cost containment in health care, the escalating costs of this advanced therapy raises the interesting questions of who should pay for the therapy and whether it should be available on demand. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
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