Heart transplantation is the replacement of a failing heart with a heart from a suitable donor.[1] After a decline between 1993 and 2004, heart transplant volumes reported to the International Society of Heart and Lung Transplantion (ISHLT) Transplant Registry have been steadily increasing, especially in recent years, and reached an all-time high in 2016 at a total of 5832 heart transplants from 346 centers.[2]
Heart transplantation (HTx) has become the preferred therapy for select patients, with a 1-year survival of almost 90% and a conditional half-life (the time at which 50% of patients who survived the first year are still alive) of 13 years.[3] See the image below.
View Image
Completed operation. Note suture lines on now-implanted heart.
Indications for heart transplantation
Heart transplantation is generally reserved for patients with end-stage congestive heart failure (CHF) who are estimated to have less than 1 year to live without the transplant and who are not candidates for or have not been helped by conventional medical therapy. Because of the poor condition of their heart, most heart transplantation candidates are excluded from other surgical options. Specific indications for a transplant include the following:
Dilated cardiomyopathy
Ischemic cardiomyopathy
Congenital heart disease for which no conventional therapy exists or for which conventional therapy has failed
Ejection fraction of less than 20%
Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted
Pulmonary vascular resistance of less than 2 Wood units
Age younger than 65 years
Ability to comply with medical follow-up care
Workup
Evaluation of the heart transplant candidate includes laboratory tests, imaging studies, and other tests as appropriate.
Laboratory studies
Virus: Including hepatitis viruses, human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV); used to determine past exposure and currently active disease
Fungus and tuberculosis (TB): Used to determine past exposure and to predict reactivation
Prostate-specific antigen (PSA): If elevated, initiate appropriate evaluation and therapy before completing the evaluation for transplantation
Papanicolaou test: Results should be negative before listing for transplantation
Complete blood count (CBC): With differential, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and a complete chemistry profile (including liver panel, lipid profile, and urinalysis)
Blood typing and screening, panel-reactive antibody (PRA) testing, and tissue typing: Used to determine the immunologic suitability of the patient for transplantation and donor matching
Imaging studies
Coronary arteriography: Performed in cases of cardiomyopathy to determine if the cause of the cardiac dysfunction may be amenable to conventional therapies
Echocardiography: Used to determine the cardiac ejection fraction and to monitor the cardiac function of patients on the transplantation waiting list
Posteroanterior and lateral chest radiographs: Used to screen for other thoracic pathologies that may preclude transplantation.
Bilateral mammograms: Should reveal no abnormalities before listing for transplantation
Cardiac and pulmonary evaluation
Maximal venous oxygen consumption (MVO2): Used to assess overall cardiac function and as a predictor of the severity of congestive heart failure and survival
Right- and left-heart catheterization: Used to determine if the disease process is reversible or treatable by more conventional therapy
Pulmonary vascular resistance: Patients with fixed resistances above 4 Wood units are not candidates for heart transplantation
Biopsy
Endomyocardial biopsy of the potential candidate is not routinely performed. The procedure may be considered if a systemic process involving the heart is thought to be the cause of the cardiomyopathy.
Perform biopsies of appropriate areas if the patient exhibits symptoms of systemic disease. Biopsies are used to determine the extent and activity of the disease process. Systemic disease processes are a contraindication to cardiac transplantation.
Transplantation procedures
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. A cardiac allograft can be sewn in either a heterotopic or an orthotopic position.
Heterotopic heart transplantation
Heterotopic transplantation is an excellent technique for patients with severe pulmonary hypertension. Inherent problems with the technique, however, include pulmonary compression of the recipient, difficulty obtaining an endomyocardial biopsy, and the need for anticoagulation.
Orthotopic heart transplantation
Orthotopic heart transplantation is performed with either of the following techniques:
Shumway-Lower technique: This method is simpler and saves perhaps 10-15 minutes of ischemic time
Bicaval anastomosis: One advantage of the bicaval method is that, by avoiding a large right atrium, the surgeon can maintain better atrial transport; another claimed advantage of this technique is a lower reported incidence of tricuspid regurgitation
Immunosuppressive therapy
Immunosuppression is started soon after surgery. Several regimens can be used, including pretransplantation induction therapy and simple postoperative maintenance therapy; the choice of regimen depends on the training and experience of the transplant center.[4, 5]
Most maintenance immunosuppressive protocols after HTx use a 3-drug regimen consisting of a calcineurin inhibitor (CNI) (cyclosporine or tacrolimus), an antimetabolite agent (mycophenolate mofetil or azathioprine), and tapering doses of corticosteroids over the first year post-transplantation.[3]
Complications
Posttransplant complications can include the following:
Bleeding from suture lines
Hyperacute rejection
Infection
Psychiatric disturbances from steroid therapy
Cardiac rejection
Allograft vascular diseaseatient education
For patient education resources, see the Heart Transplant Directory.
Heart transplantation is generally reserved for patients with end-stage chronic heart failure (CHF) who are estimated to have less than 1 year to live without the transplant and who are not candidates for, or have not been helped by, conventional medical therapy. In addition, most candidates are excluded from other surgical options because of the poor condition of the heart.
Candidacy determination and evaluation are key components of the process, as are 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.[6]
Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.[7] Evaluation demonstrates ejection fractions of less than 25%. Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken.
Interim therapy can include oral agents as well as inotropic support. Mechanical support with the intra-aortic balloon pump (IABP) or implantable assist devices may be appropriate in some patients as a bridge to transplantation.[8, 9, 10] However, mechanical support does not improve waiting list survival in adult patients with congenital heart disease.[11]
The annual frequency of heart transplantation is about 1% of the general population with heart failure (both candidates and noncandidates). Improved medical management of CHF has decreased the candidate population; however, organ availability remains an issue.[12, 13] Further information on organ availability and waiting lists is available from the United Network for Organ Sharing.
The disease processes that necessitate cardiac transplantation can be divided into the following categories:
Dilated cardiomyopathy (54%) - This often has an unclear origin
Ischemic cardiomyopathy (45%) - This percentage is rising because of the increase in coronary artery disease (CAD) in younger age groups
Congenital heart disease and other diseases not amenable to surgical correction (1%)
The pathophysiology of cardiomyopathy that may necessitate cardiac replacement depends on 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; however, the small-vessel disease is progressive and thus causes 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 a dilated cardiomyopathy is still unclear. Mechanical dilatation and disruption of energy stores appear to play roles.
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-side function is directly dependent on the ischemic time before 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 has 2 primary 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. It 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; endomyocardial biopsy is of little value in this context.
CAD is a late pathologic process common to all cardiac allografts, characterized by myointimal hyperplasia of small and medium-sized vessels. The lesions are diffuse and may appear any time from 3 months to several years after implantation. The inciting causes are unclear, though cytomegalovirus (CMV) infection and chronic rejection have been implicated. The mechanism of the process is thought to depend on growth-factor production in the allograft initiated by circulating lymphocytes. Currently, there is no treatment other than retransplantation.
The general indications for cardiac transplantation include deteriorating cardiac function and a prognosis of less than 1 year to live. Specific indications include the following:
Dilated cardiomyopathy
Ischemic cardiomyopathy
Congenital heart disease for which no conventional therapy exists or for which conventional therapy has failed
Ejection fraction less than 20%
Intractable angina or malignant cardiac arrhythmias for which conventional therapy has been exhausted
Pulmonary vascular resistance of less than 2 Wood units
Age younger than 65 years
Ability to comply with medical follow-up care
The 2016 International Society for Heart Lung Transplantation updated criteria for heart transplantation are as follows[14, 15] :
Heart failure prognosis scores should be performed along with cardiopulmonary exercise testing to determine prognosis and guide listing for transplantation for ambulatory patients. An estimated 1-yr survival of < 80%, as calculated by the Seattle Heart Failure Model (SHFM), or a Heart Failure Survival Score (HFSS) in the high/medium risk range should be considered as reasonable cut points for listing
Patients should not be listed solely on the criteria of heart failure survival prognostic scores
Right heart catheterization (RHC) should be performed on all adult candidates in preparation for listing for cardiac transplantation and periodically until transplantation.
After left ventricular assist device (LVAD), reevaluation of hemodynamics should be done after 3-6 mo to ascertain reversibility of pulmonary hypertension
Pre-transplant body mass index (BMI) > 35 kg/m2 is associated with a worse outcome after cardiac transplantation; for such obese patients, it is reasonable to recommend weight loss to achieve a BMI of ≤35 kg/m2 before listing for cardiac transplantation.
It is reasonable to consider the presence of irreversible renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 ml/min/1.73 m2) as a relative contraindication for heart transplantation alone.
Clinically severe symptomatic cerebrovascular disease may be considered a contraindication to transplantation
Assessment of frailty (3 of 5 possible symptoms, including unintentional weight loss of ≥10 lb within the past year, muscle loss, fatigue, slow walking speed, and low levels of physical activity) could be considered when assessing candidacy
Use of mechanical circulatory support should be considered for patients with potentially reversible or treatable comorbidities, such as cancer, obesity, renal failure, tobacco use, and pharmacologically irreversible pulmonary hypertension, with subsequent reevaluation to establish candidacy
Any patient for whom social supports are deemed insufficient to achieve compliant care in the outpatient setting may be regarded as having a relative contraindication to transplant. The benefit of heart transplantation in patients with severe cognitive-behavioral disabilities or dementia (eg, self-injurious behavior, inability to ever understand and cooperate with medical care) has not been established and has the potential for harm; therefore, heart transplantation cannot be recommended for this subgroup of patients
Retransplantation is indicated for those patients who develop significant cardiac allograft vasculopathy (CAV) with refractory cardiac allograft dysfunction, without evidence of ongoing rejection
Contraindications for heart transplantation include the following:
Age older than 65 years - This is a relative contraindication; patients who are older than 65 years are evaluated on an individual basis
Fixed pulmonary vascular resistance of greater than 4 Wood units
Active systemic infection
Active systemic disease such as collagen-vascular disease or sickle cell disease
Active malignancy - Patients with prior malignancies who have demonstrated a 3- to 5-year disease-free interval may be considered, depending on the tumor type and the evaluating program
An ongoing history of substance abuse (eg, alcohol, drugs, tobacco)
Psychosocial instability
Inability to comply with medical follow-up care[16]
The 1-year survival rate after cardiac transplantation is almost 90%, and the conditional half-life (the time at which 50% of patients who survived the first year are still alive) is 13 years.[3] After transplantation, adult patients with congenital heart disease have high 30-day mortality but better late survival.[11] The functional status of the recipient after the procedure is generally excellent, depending on the his or her level of motivation.
In patients with severe biventricular failure who received pneumatic biventricular assist devices as a bridge to transplant, the 1-year actuarial survival rate was 89%, compared with 92% in patients without a ventricular assist device.[17]
Hypertension, diabetes mellitus, and obesity are associated with exponential increases in postoperative mortality rates. Heart transplant recipients with all three of these metabolic risk factors were found to have a 63% increased mortality compared to patients without any of the risk factors.[18]
Arnaoutakis et al found that high-risk patients had better 1-year survival rates at high-volume centers (ie, centers that perform more than 15 procedures per year) than at lower-volume centers (79% vs 64%, respectively). These differences dissipated among lower-risk patients. Based on these findings, the authors recommended that all high-risk heart transplantation procedures be performed at higher-volume centers.[19]
The future of cardiac transplantation will be determined by the outcomes of several issues. One is the ongoing shortage of donor organs. In Europe, waiting time has tripled since 2000 and now exceeds one year. In order to address this shortage, the median age of donors has increased from 30 to almost 45 years. Even hearts from donors aged >60 years are commonly used, with outcomes only slightly inferior to that of hearts from young donors.[20]
Novel technological solutions for organ preservation, such a warm machine perfusion that allows some degree of ex‐vivo evaluation of the organ and better control of the cold ischaemia time, could potentially allow better utilization rates of marginal donor hearts.[20] The use of highly selected hearts from circulatory death donors has contributed to the increase the number of heart transplants while achieving short‐term outcomes comparable to traditional brain-dead donors.[21]
Shortage of donor organs has also fueled a search for alternative therapies for the failing heart. Such therapies include artificial assist devices, dual-chamber pacing, new drug interventions, and genetic therapy.[22] These efforts have proven to be successful in reducing the need for transplantation. Research in the area of xenografts continues.[23, 24]
Another issue is the prevention of allograft vascular disease, which remains a paramount challenge. The pathology of allograft vascular disease is clearly multifactorial in origin, making the research and therapy equally complex. Resolution of this issue will prolong graft survival and lives.
A third issue is the question of recipient selection and listing status, which 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.
The final issue is financial. In this era of cost containment in health care, the escalating costs of heart transplantation raises the questions of who should pay for the therapy and whether the procedure should be available on demand.
Evaluation of the heart transplant candidate includes laboratory tests, imaging studies, and other tests as appropriate.
Closely 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 (CHF), and offer the patient the alternative of participating in experimental clinical trials; such participation does not preclude listing for transplantation. Maintain close contact with the transplant center, 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 so that he or she can be evaluated for implantation of an artificial cardiac assist device, an upgrade on the waiting list, or both. At times, the candidate may deteriorate to the point where transplantation is no longer an option. Carefully discuss these issues with the treating physicians, the patient, and the family.
A hepatitis panel can serve as a screen, provided that no active antigenicity exists. Patients who are carriers of the disease or who have active disease are not considered candidates for heart transplantation. Hepatitis C positivity remains controversial with respect to thoracic transplantation and is addressed on a center-to-center basis. A large multicenter cohort study found that pretransplant hepatitis C positivity was associated with decreased survival at a mean follow-up of 5.6 years after transplantation.[25]
The patient must not be infected with HIV. HIV positivity remains a contraindication to transplantation.
Testing for other viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV), is used to determine past exposure and currently active disease. Past exposure indicates a risk of reactivation; appropriate prophylaxis should be instituted after the procedure. Treat active disease before considering transplantation. Recipients whose test results are negative for CMV are generally given CMV immune globulin. Immunize patients whose test results are negative for other viral agents during the evaluation period.
Perform fungal serologic testing and tuberculosis (TB) skin testing, paying particular attention to environmental exposure. These studies are used to determine past exposure and to predict reactivation. Patients with positive TB skin test results are usually treated before being placed on the transplantation list.
If the prostate-specific antigen (PSA) study results are positive, initiate appropriate evaluation and therapy before completing the evaluation for transplantation.
Papanicolaou test results should be negative before listing for transplantation. If the results are positive, undertake appropriate referral for evaluation and therapy before proceeding with the evaluation for transplantation.
Perform a complete blood count (CBC) with differential, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and complete chemistry profile (including liver panel, lipid profile, and urinalysis). Results of these tests should be essentially normal. Any abnormalities must be assessed before proceeding with the evaluation.
Blood typing and screening, panel-reactive antibody (PRA) testing, and tissue typing are used to determine the immunologic suitability of the patient for transplantation and donor matching.
In the case of cardiomyopathy, coronary arteriography is performed to determine if the cause of the cardiac dysfunction may be amenable to conventional therapies such as coronary artery angioplasty, coronary artery bypass grafting (CABG), or valvular repair.
Echocardiography is used to determine the cardiac ejection fraction and to monitor the cardiac function of patients on the transplantation waiting list. Ejection fractions of 25% or less are indicative of poor long-term survival rates.
Posteroanterior and lateral chest radiographs are used to screen for other thoracic pathologies that may preclude transplantation.
Bilateral mammograms should reveal no abnormalities before listing for transplantation. If abnormalities are found, undertake appropriate referral for evaluation and therapy before proceeding further with the evaluation for transplantation.
Pulmonary function tests are performed to assess overall pulmonary function. Severe untreatable pulmonary disease is a contraindication to the procedure.
Maximal venous oxygen consumption (MVO2) is used to assess overall cardiac function and is used as a predictor of the severity of congestive heart failure and survival. An MVO2 value of less than 15 ml/dl/min is a poor prognostic indicator for 1-year survival in the patient awaiting cardiac transplantation.
Cardiopulmonary evaluation includes right- and left-heart catheterization to determine if the disease process is reversible or treatable by more conventional therapy. Careful evaluation of pulmonary vascular resistance is essential. Patients with fixed resistances above 4 Wood units are not candidates for the procedure.
Endomyocardial biopsy of the potential candidate is not routinely performed. The procedure may be considered if a systemic process involving the heart is thought to be the cause of the cardiomyopathy.
Perform biopsies of appropriate areas if the patient exhibits symptoms of systemic disease. Biopsies are used to determine the extent and activity of the disease process. Systemic disease processes are a contraindication to cardiac transplantation.
After transplantation, 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.[26, 27, 28]
The 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 hours), procurement distances are limited.
Potential heart donors must meet brain death criteria and be free of cardiac pathology. Echocardiographic examination 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 on echocardiography (eg, trivial tricuspid or mitral regurgitation, marginal left ventricular hypertrophy, or reduced ejection fraction) may also be indicators of an acceptable organ, depending on the history of the donor and the condition of the recipient. In instances where 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 (CAD) with cardiac catheterization.
Current donor criteria include age younger than 65 years (though the association between heart transplant survival and donor age may not be a strictly linear one[29] ), normal cardiac function, and absence of CAD. 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 on the basis of direct inspection by an experienced surgeon. A median sternotomy incision is performed to allow 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 by 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.
While preparing a graft for transplantation, the authors look for a patent foramen ovale. If a patent foramen is present, it is closed. Many centers now perform tricuspid valve annuloplasty on donor grafts as prophylaxis against development of tricuspid regurgitation in the postoperative period.[30] The incidence of tricuspid regurgitation after heart transplantation is reported to be as high as 47-98%.[31]
During the cardiac transplantation procedure, the ventricles are excised, leaving the great vessels, right atrium, and left atrium of the recipient (see the first image below). The donor heart is then sewn to these areas (see the second and third images below).
View Image
View of the recipient's chest after the heart is removed, with the patient on cardiopulmonary bypass.
View Image
Suturing of the donor heart. Note that the left atrial anastomosis is performed first.
View Image
Completed operation. Note suture lines on now-implanted heart.
A cardiac allograft can be sewn in either a heterotopic or an orthotopic position. The authors rarely perform heterotopic heart transplants because of the inherent problems (eg, pulmonary compression of the recipient, difficulty obtaining endomyocardial biopsy, need for anticoagulation); however, heterotopic transplantation (see the image below) is an excellent technique for patients with severe pulmonary hypertension.
View Image
Heterotopic transplantation.
Orthotopic heart transplantation is performed either with the classic Shumway-Lower technique or as a bicaval anastomosis (see the images below). Currently, there is a trend toward reverting to bicaval anastomoses rather than right atrial anastomoses in an attempt to decrease the incidence of postoperative tricuspid insufficiency.
View Image
View after cardiectomy, showing cuffs for bicaval anastomosis.
View Image
Completed bicaval transplantation technique.
The Shumway-Lower method is simpler and saves perhaps 10-15 minutes of ischemic time. One advantage of the bicaval method is that, by avoiding a large right atrium, the surgeon can maintain better atrial transport. Another claimed advantage of this technique is a lower reported incidence of tricuspid regurgitation.
An additional advantage of the bicaval technique is that 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.
After the procedure, the patient is maintained on a combination of pressor agents while the donor heart regains energy stores. The patient’s ionized calcium level is carefully monitored and replenished with calcium chloride because the function of the denervated heart initially is 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 and simple postoperative maintenance therapy; the choice of regimen depends on the training and experience of the transplant center.[4, 5] Most maintenance immunosuppressive protocols after HTx use a 3-drug regimen consisting of a calcineurin inhibitor (CNI) (cyclosporine or tacrolimus), an antimetabolite agent (mycophenolate mofetil [MMF] or azathioprine), and tapering doses of corticosteroids over the first year post-transplantation.[3]
Mammalian target of rapamycin (mTOR) inhibitors, sirolimus and everolimus, are relatively recent advances in standard immunosuppression. Both sirolimus and everolimus reduce the incidence of acute rejection and prevent development of cardiac allograft vasculopathy (CAV). When sirolimus is used in heart transplant recipients with significant renal impairment, it permits minimization or complete withdrawal of the CNIs, resulting in improvements in renal function without an increased risk of rejection.[3]
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 on the condition of the recipient before the operation.
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, electrocardiography (ECG) 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, not on the neurologic input from the recipient.
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 the procedure, despite therapeutic immunosuppression. Bridging with mechanical assistance may be advantageous in acute allograft rejection.[32]
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 excessively immunosuppressed. Prophylaxis for Pneumocystis jiroveci is universally administered, as is therapy for cytomegalovirus (CMV) infection. Maintain vigilance for other uncommon infectious processes, including Listeria, Legionella, Chlamydia, and Nocardia infection.[33]
Psychiatric disturbances from steroid therapy can occur in the immediate posttransplant period. These disturbances may be predicted from the pretransplant psychiatric evaluation and thus averted.
Cardiac rejection is to be expected and should be detected by endomyocardial biopsy.[34, 35, 36] Depending on 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. A progressive concentric myointimal hyperplasia develops in the coronary arteries, sometimes 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. Research suggests that the initial ischemia-reperfusion injury, coupled with repeated rejection episodes, might contribute to the process.
Surveillance for allograft vascular disease has traditionally utilized coronary angiography. Miller et al reported that allograft vascular disease can be detected more accurately using noninvasive multiparametric cardiovascular magnetic resonance to assess absolute myocardial blood flow.[37]
The use of mTOR inhibitors, statins, and vitamins C and E have been demonstrated to slow the progression of cardiac allograft vasculopathy but there is no therapy to completely prevent or reverse this significant complication.[3] The process can sometimes be treated by stenting the diseased vessels. Drug-eluting stents appear to be more effective in treating cardiac allograft vasculopathy than bare-metal stents are. Drug-eluting stents reduce target lesion revascularization, as well as rates of cardiac death and nonfatal myocardial infarction.[38]
In pediatric patients, there is a 30% increase in the risk of graft loss within 6 months when the ischemic time is longer than 3.5 hours.[39]
Clinical Context:
Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for various organs.
For children and adults, base dosing on ideal body weight. Maintaining appropriate levels of the drug in the bloodstream is crucial to the maintenance of the allograft. Foods can alter the level of the drug and time of administration. Medication must be taken at the same time every day.
Neoral is the capsular form of cyclosporine, available in 25- and 100-mg capsules. Sandimmune is the liquid form. GENGRAF is the branded generic form, available in 25- and 100-mg capsules.
Clinical Context:
Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is an oral steroid with approximately 5 times the potency of endogenous steroids. Minimal to no oral prednisone should be given for the first 21 days after transplantation unless rejection occurs.
Clinical Context:
Methylprednisolone is an immunosuppressant used to treat autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It is the intravenous (IV) form of prednisone.
Clinical Context:
Tacrolimus suppresses humoral immunity (T-cell activity). It is a calcineurin inhibitor with 2-3 times the potency of cyclosporine. Tacrolimus can be used at lower doses than cyclosporine, but it has severe adverse effects, including renal dysfunction, diabetes, and pancreatitis. Levels are adjusted according to renal function, hepatic function, and adverse effects.
Clinical Context:
Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thus inhibiting their proliferation. It inhibits antibody production.
Clinical Context:
Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity. Antimetabolites are used to block the uptake of vital nutrients needed by the cells. As implied, these drugs affect not only the cells of the immune system but also other cells of the body. The potency of therapy is dose dependent. Azathioprine is not effective treatment for acute rejection episodes but remains an economical choice for long-term immunosuppression.
Clinical Context:
Sirolimus, also known as rapamycin, is a macrocyclic lactone produced by Streptomyces hygroscopicus. It is a potent immunosuppressant that inhibits T-cell activation and proliferation by a mechanism that is distinct from those of all other immunosuppressants. This inhibition suppresses cytokine-driven T-cell proliferation by inhibiting progression from the G1 phase to the S phase in the cell cycle.
Immunosuppression is started soon after surgery. Transplant recipients are maintained on an immunosuppression regimen that includes 1-3 drugs. Generally, the drugs fall into 3 categories: steroids, antimetabolites, and other immunosuppressants.Several regimens can be used, including pretransplantation induction therapy and simple postoperative maintenance therapy; the choice of regimen depends on the training and experience of the transplantation center.[4, 5]
Clinical Context:
Dopamine is a naturally occurring endogenous catecholamine that stimulates beta1-and alpha1-adrenergic and dopaminergic receptors in a dose-dependent fashion. It stimulates the release of norepinephrine.
In low doses (2-5 μg/kg/min), dopamine acts on dopaminergic receptors in renal and splanchnic vascular beds, causing vasodilatation in these beds. In midrange doses (5-15 μg/kg/min), it acts on beta-adrenergic receptors to increase heart rate and contractility. In high doses (15-20 μg/kg/min), it acts on alpha-adrenergic receptors to increase systemic vascular resistance and raise blood pressure.
Clinical Context:
Dobutamine is a sympathomimetic amine with stronger beta than alpha effects. It increases the inotropic state. Vasopressors augment the coronary and cerebral blood flow during the low-flow state associated with severe hypotension.
Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in hypotensive patients. Higher dosages may cause an increase in heart rate, exacerbating myocardial ischemia.
Clinical Context:
Its alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Its beta2-agonist effects include bronchodilation, chronotropic cardiac activity, and positive inotropic effects.
Clinical Context:
Norepinephrine stimulates beta1- and alpha-adrenergic receptors, increasing cardiac muscle contractility and heart rate, as well as vasoconstriction; this results in systemic blood pressure and coronary blood flow increases. After obtaining a response, the rate of flow should be adjusted and maintained at a low-normal blood pressure, such as 80-100 mm Hg systolic, sufficient to perfuse vital organs.
After the procedure, the patient is maintained on a combination of pressor agents while the donor heart regains energy stores. Once stabilized, the patient is rapidly weaned from the ventilator and the pressors. The chosen combination depends on the training and experience of the center.
Donald M Botta, Jr, MD, Assistant Professor, Department of Surgery, Section of Cardiac Surgery, Surgical Director, Cardiac Transplantation, Director of Mechanical Circulatory Support, Yale University School of Medicine
Disclosure: Nothing to disclose.
Coauthor(s)
Mary C Mancini, MD, PhD, MMM, Surgeon-in-Chief and Director of Cardiothoracic Surgery, Christus Highland
Disclosure: Nothing to disclose.
Chief Editor
John Geibel, MD, MSc, DSc, AGAF, Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow; Fellow of the Royal Society of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
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
Deepak M Gangahar, MBBS, MD is a member of the following medical societies: American College of Cardiology, American College of Chest Physicians, American College of Surgeons, American Medical Association, International Society for Heart and Lung Transplantation, International Society for Minimally Invasive Cardiothoracic Surgery, Nebraska Medical Association, and Society of Thoracic Surgeons
Disclosure: Nothing to disclose.
Shreekanth V Karwande, MBBS Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center
Shreekanth V Karwande, MBBS is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Heart Association, Society of Critical Care Medicine, Society of Thoracic Surgeons, and Western Thoracic Surgical Association
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Richard Thurer, MD B and Donald Carlin Professor of Thoracic Surgical Oncology, University of Miami, Leonard M Miller School of Medicine
Richard Thurer, MD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Medical Association, American Thoracic Society, Florida Medical Association, Society of Surgical Oncology, and Society of Thoracic Surgeons
Disclosure: Nothing to disclose.
References
Griepp RB, Ergin MA. The history of experimental heart transplantation. J Heart Transplant. 1984. 3:145.
Heart Failure Society of America. The Stages of Heart Failure - New York Heart Association (NYHA) Classification. Heart Failure Society of America. Available at https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure#.WbL0RU2ovyN. Accessed: March 21, 2019.
Busks M. Wider Eligibility for Heart Transplantation in New Guidelines. Medscape Medical News. Available at http://www.medscape.com/viewarticle/857149. January 13, 2016; Accessed: February 26, 2016.
McGee E, McCarthy PM, Hoercher KJ, et al. Donor Tricuspid Annuloplasty Reduces Post-Transplant Tricuspid Regurgitation (Abstract 22). The Kaufman Center for Heart Failure, The Cleveland Clinic. International Society for Heart and Lung Transplantation Meeting, San Francisco,. April 21-24, 2004.
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}
){kind=link}