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For end-stage heart failure patients who have failed medical therapy.
Heart transplant has emerged as the preferred therapy for select patients with advanced heart failure, with a one-year survival of 90% and half life of 13 years.
Estimated 30-70,000 Americans each year could benefit from cardiac replacement.
Average annually 4500 performed in the U.S.
Brain death is the current ethical standard for when a heart donation can be allowed.
Brain death frequently precipitates systemic heart derangements that negatively affect organ donation, resulting in fewer than half of donor hearts being deemed usable for transplantation.
In hemodynamically unstable brain dead, potential heart donors, IV thyroxine, does not significantly result in more hearts being transplanted than with saline infusions (Dhar R).
Xenografts from other species and artificial hearts are two less successful alternatives to allografts.
A surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease when other medical or surgical treatments have failed.
The annual frequency of heart transplantation is about 1% of the general population with heart failure.
The most common procedure is to take a functioning heart, with or without transplanting one or both lungs at the same time, from a recently deceased organ donor and implanting it into the patient.
Risk adjusted survival at 6 months after transplantation with a donor heart that has been reanimated and assessed with the use of extracorporeal non-ischemic perfusion after circulatory death is not inferior to that after standard care transplantation with a donor heart that has been preserved with the use of cold storage after brain death (Schroeder JN).
About 3200 transplants a performed annually.
During heart transplant, the vagus nerve is severed, and this removes parasympathetic activity over the myocardium.
Median post transplant survival was approximately 11 years.
Currently, survival rates after heart transplant surgery are about 85% at 1 year.
Post-operation survival averages 15 years.
In a large study of transplant eligible patients-77% five-year survival occurred among transplant recipients and was 33% among those who did not undergo heart transplantation, with a survival benefit of 44% (Parker et al).
The difference between transplant recipient mortality and waiting list mortality over five years varies from 30-55% across transplant centers.
Survival decreases each additional year after surgery by 3% to 4%.
Median waiting time is longer than 9 months.
Candidates are classified according to the supportive therapy prescribed by their transplant center.
It is a life-saving treatment intended to improve the quality, and hopefully also both the overall total duration of time and the extent of time afterwards in a more active state, of life for the recipients.
Allotransplantation is the technical term for a transplant from a non-genetically identical individual of the same species.
For patients with end-stage cardiomyopathy there is an actual survival of 80% at 1 year and 75% at 3 years.
The patient’s own heart is usually removed and replaced with the donor heart: orthotopic procedure.
Less commonly, the recipient’s diseased heart is left in place to support the donor heart and is ref2241ed to as a heterotopic transplant procedure.
Acute allograft rejection can be associated with hemodynamic abnormalities, irreversible graft injury and death.
About one quarter of heart transplant recipients have a refjection episode requiring treatment during the first year of transplantation (Taylor DO).
Death from infection related to immunosuppression is the leading cause of death in the year after transplantation.
Death from rejection during the first year is only 2%, while the incidence of histologic rejection is 50-75%.
Acute rejection causes 12% of deaths between 1 month and 1 year after transplantation (Taylor DO).
In selected patients aged 60 years and older results in survival comparable to younger patients.
Older patients have a lower risk of rejection but an increased risk of cancer.
There is no noninvasive marker for rejection and pateints must undergo serial endomyocardial biopsies to monitor for rejection.
Most patients with histological changes of rejection have no changes in allograft function, and the histologic findings can be reversed with increasing immunosuppressive therapy.
Thirty day mortality about 6%.
Risk of cerebrovascular events in heart transplant patients is 10 fold higher than in age-matched healthy patients.
Cardiac allograft vasculopthy is the leading cause of late heart failure and death and it is caused by major histocompatibility complex class I and class II antigens on the endothelium of the allografts by recipient T lymphocytes.
The cardiac allograft vasculopthy is a result of inflammation leading to activation of macrophages and proliferation of smooth muscle cells.
The immune rejection results in denuding of the endothelium secondary to peri-transplantation ischemia and reprofusion injury and cellular immunity, with disruption of the endothelial lining.
Hearts from donors with infection with hepatitis C result in risk of transmission of HCV and high rates of liver enzyme abnormalities.
Receipt of a heart from an HCV positive donor associated with increased mortality early following transplantation and neither the recipient’s age or HCV status alters this finding.
Heart donor HCV positivity associated with accelerated coronary artery disease in heart transplant recipients.
The procedure by which the failing heart is replaced with another heart from a suitable donor.
Generally reserved for end-stage congestive heart failure in patients 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.
Candidates generally present with New York Heart Association (NYHA) class III (moderate) symptoms or class IV (severe) symptoms.
Work up reveals ejection fractions of less than 25%.
Attempts are made to stabilize the cardiac condition while the evaluation process is undertaken include oral agents as well as inotropic support.
Mechanical support with the intra-aortic balloon pump or implantable assist devices may be required as a bridge to transplantation.
The annual frequency of heart transplantation is about 1% of the general population with heart failure.
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.
The prognosis for heart transplant patients following the orthotopic procedure has increased.
Survival: 1 year: 88.0% (males), 86.2% (females) 3 years: 79.3% (males), 77.2% (females) 5 years: 73.2% (males), 69.0% (females)
Men receiving female hearts have a 15% increase in the risk of adjusted cumulative mortality over five years compared to men receiving a male heart
Indications for heart transplantation:
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.
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.
Requirements include:
Pulmonary vascular resistance of less than 2 Wood units.
Age younger than 65 years
Ability to comply with medical follow-up care.
Evaluation includes laboratory tests, and imaging studies.
Laboratory studies include: hepatitis viruses, human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV); used to determine past exposure and currently active disease.
Tests to determine past exposure and to predict reactivation to TB, and fungal disease.
Evaluation of elevated PSA, if present.
Papanicolaou test should be negative before considering transplantation in younger women.
Complete blood count (CBC), bleeding and clotting studies, complete chemistry profile and urinalysis
Blood typing and screening, panel-reactive antibody, and tissue typing. to determine the immunologic suitability of the patient for transplantation and donor matching
Coronary arteriography is performed in cases of cardiomyopathy to determine if the cause of the cardiac dysfunction.
Echocardiography helps determine the cardiac ejection fraction and to monitor the cardiac function.
CXRs 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 include maximal venous oxygen consumption (MVO 2) 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.
Patients with fixed pulmonary vascular resistances above 4 Wood units are not candidates for heart transplantation.
Endomyocardial biopsy of the potential candidate is not routinely performed.
Biopsies are used to determine the extent and activity of the underlying disease process, as a systemic disease processes are a contraindication to cardiac transplantation.
During the procedure, the ventricles are excised, leaving the great vessels, right atrium, and left atrium of the recipient to which the donor heart is then sewn.
The graft can be sewn in either a heterotopic or an orthotopic position.
Immunosuppression is started soon after surgery.
Posttransplant complications can include the following: Bleeding
Hyperacute rejection
Infection
Psychiatric disturbances from steroid therapy
Cardiac rejection
Allograft vascular disease
Cardiac transplantation can be utilized into the following categories:
Dilated cardiomyopathy (54%)?
Ischemic cardiomyopathy (45%).
Congenital heart disease and other diseases not amenable to surgical correction.
Cardiomyopathy may necessitate transplantation.
Transplantation results in denervation of the heart and makes it dependent on its intrinsic rate.
The lack of neuronal input, results in ventricular hypertrophy
The right-side heart function is dependent on the ischemic time before reimplantation and the adequacy of its preservation.
The right ventricle is easily damaged in transplantation.
Initially after transplant the right ventricle may function as a passive conduit until recovery occurs.
The rejection process has 2 primary forms, cellular and humoral.
Cellular rejection is characterized by perivascular infiltration of lymphocytes with subsequent myocyte damage and necrosis if left untreated.
Humoral rejection is thought to be an antibody response with antibody deposition into the myocardium resulting in global cardiac dysfunction.
This diagnosis of humoral rejection generally is 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.
The CAD lesions are diffuse and may appear any time from 3 months to several years after implantation.
CAD may be due to CMV infection and chronic rejection.
Heart failure prognosis scores are performed along with cardiopulmonary exercise testing to determine prognosis and guide listing for transplantation for ambulatory patients.
An estimated 1-yr survival of <80%, or high/medium risk range are considered as reasonable cut points for listing.
Right heart catheterization (RHC) is performed on all candidates in preparation for listing for cardiac transplantation and periodically until transplantation .
Reevaluation of hemodynamics should be done after 3-6 mo to ascertain reversibility of pulmonary hypertension
BMI >35 kg/m 2 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/m 2 before listing for cardiac transplantation.
The presence of irreversible renal dysfunction is a relative contraindication for heart transplantation.
Severe symptomatic cerebrovascular disease may be considered a contraindication to transplantation.
Frailty, weight loss of ≥10 lb within the past year, muscle loss, fatigue, slow walking speed, and low levels of physical activity should be considered when assessing candidacy
Patients who could not be compliant with care in the outpatient setting may be regarded as having a relative contraindication to transplant.
Heart transplantation in patients with cognitive-behavioral disabilities or dementia cannot be recommended for this subgroup of patients.
Contraindications for heart transplantation include:
Age greater than 65 years
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
An ongoing history of substance abuse.
Psychosocial instability.
Inability to comply with medical follow-up care.
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.
After transplantation, adult patients with congenital heart disease have high 30-day mortality but better late survival.
In patients with severe biventricular failure who received pneumatic biventricular assist devices as a bridge to transplant, the 1-year actuarial survival rate is 89%, compared with 92% in patients without a ventricular assist device.
Hypertension, diabetes mellitus, and obesity are associated with 63% increases in postoperative mortality rates. c compared to to individuals without such risks.
High-risk patients had better 1-year survival rates at high-volume centers than at lower volume centers (79% vs 64%, respectively).
It Is recommended that all high-risk heart transplantation procedures be performed at higher-volume centers.
In the event of clinical deterioration, the transplant center may deem it appropriate that the patient be evaluated for implantation of an artificial cardiac assist device, an upgrade on the waiting list, or both, or cancel the transplant.
Patients who are carriers of hepatitis or who have active disease are not considered candidates for heart transplantation.
The patient must not be infected with HIV.
Testing for 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, and appropriate prophylaxis should be instituted after the procedure.
Active viral diseases before considering transplantation.
Recipients whose test results are negative for CMV are generally given CMV immune globulin.
Perform fungal serologic testing and tuberculosis (TB) skin testing, 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 elevated , evaluation and therapy are done before completing the evaluation for transplantation.
Papanicolaou test results should be negative before listing for transplantation.
Blood typing and screening, panel-reactive antibody testing, and tissue typing are used to determine the immunologic suitability of the patient for transplantation and donor matching.
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.
Bilateral mammograms should reveal no abnormalities before listing 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 predict severity of congestive heart failure and survival.
A maximal venous oxygen consumption (MVO2) value of less than 15 ml/dl/min is a poor prognostic indicator for 1-year survival in the patient awaiting cardiac transplantation.
Patients with fixed pulmonary vascular resistances above 4 Wood units are not candidates for the procedure.
Endomyocardial biopsy of the potential candidate is not routinely performed.
After transplantation, endomyocardial biopsies are performed to assess for allograft rejection.
All potential donors have succumbed to brain death secondary to some catastrophic event.
An underlying pathology of the donor, often precludes donation.
There is a short preservation time tolerated by the heart of 4-6 hours.
Potential heart donors must be free of cardiac pathology.
Echocardiographic examination with a normal ejection fraction of greater than 50%), with normal valvular structure and function and an absence of left ventricular hypertrophy are indicators of a heart for transplantation.
Current donor criteria include age younger than 65 years, normal cardiac function, and absence of coronary artery disease.
Donor and potential recipients are matched according to blood group (ABO) compatibility and size.
The recipient operation is performed by using cardiopulmonary bypass, with removal of the recipient heart.
The donor heart is inserted in its place, and left atrial anastomosis is performed, followed by the right atrium and the great vessels.
While preparing a graft for transplantation, surgeons look for a patent foramen ovale, and if 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.
The incidence of tricuspid regurgitation after heart transplantation is reported to be as high as 47-98%.
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 transplants are associated with pulmonary compression of the recipient, difficulty obtaining endomyocardial biopsy, need for anticoagulation.
Heterotopic transplantation is an excellent technique for patients with severe pulmonary hypertension.
Orthotopic heart transplantation is performed either with the classic Shumway-Lower technique or as a bicaval anastomosis.
Some patients are less suitable for a heart transplant:
Advanced kidney, lung, or liver disease.
Active cancer if it is likely to impact the survival of the patient
Life-threatening diseases unrelated to heart failure, including acute infection or systemic disease such as systemic lupus erythematosus, sarcoidosis or amyloidosis
Peripheral vascular disease.
High pulmonary vascular resistance .
Relative contraindications to heart transplant:
Insulin-dependent diabetes with organ dysfunction
Recent thromboembolism
Severe obesity
Age over 65 years
Active substance abuse.
Bicaval anastomoses rather than right atrial anastomoses is associated with a decrease the incidence of postoperative tricuspid insufficiency.
Topical cooling of the graft continues to be the primary means of graft preservation.
After the procedure, a combination of pressor agents is temporarily used while the donor heart regains energy stores.
Vasopressors increase 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.
Dopamine is the pref2241ed agent in hypotensive patients.
After the procedure ionized calcium is monitored and replaced with calcium chloride, as the function of the denervated heart initially is dependent on circulating calcium ions.
Immunosuppression therapy is started soon after surgery.
The sinoatrial nodes of the donor and recipient remain intact, so that for approximately 3 weeks after surgery, the EKG demonstrates 2 P waves.
Complications after surgery include bleeding from the suture lines, hyperacute rejection can occur immediately after blood flow is restored to the allograft and up to 1 week after the procedure and Infection.
All patient’s receive. Prophylaxis for CMV and Pneumocystis infection.
Awareness of bacterial, viral and fungal infections and other uncommon infectious processes, including Listeria, Legionella, Chlamydia, and Nocardia infection is maintained.
Cardiac rejection can be detected by endomyocardial biopsy and is treated by steroid therapy, polyclonal antibody therapy, or monoclonal antibody therapy.
The main cause of late graft failure and death is from allograft vascular disease.
Allograft vascular disease results in a progressive concentric myointimal hyperplasia in the coronary arteries.
Myointimal hyperplasia can sometimes develop as early as 3 months after transplantation.
Myointimal hyperplasia is thought to be associated with CMV infection and recurrent rejection episodes.
Therapy available for allograft vascular disease includes retransplantation, and restenting the diseased vessels.
Immunosuppressive therapy is started soon after surgery.
Post-operative complications include infection, sepsis, organ rejection and effects of the immunosuppressive medication.
The risk of rejection persists and the patients are on immunosuppressive drugs for the rest of their life
The surgery death rate is 5–10% .
Transplant recipients are maintained on an immunosuppression regimen that includes 1-3 drugs: steroids, antimetabolites, and other immunosuppressants.