Disclosure
The success of a cardiac transplantation program depends on the careful scrutiny and selection of potential deceased donors. The growing discrepancy between the donor supply and the burgeoning recipient demand requires a screening process tailored to specific needs of the recipient. This flexible clinical approach widens the potential therapeutic benefit and promotes the efficient use of donor organs with minimal wasting of this scarce commodity. Potential allografts must meet specific criteria for brain death. Although some organ procurement organizations (OPOs) rely on consent documented on driver's licenses, donors' families or their next of kin generally must provide permission for organ donation. In certain instances, the coroner must consent to release the body for organ donation. Only when these criteria are met can regional OPOs activate the allocation system. This system is based on the urgency status of the recipient, the proximity of the donor and the recipient, and the time the recipient has been on the waiting list. The Uniform Anatomic Gift Act of 1968 established the voluntary basis of organ donation. The Uniform Brain Death Act (1978) and the Uniform Determination of Death Act (1980) established the legislation on which the diagnosis of brain death is made. The United Network for Organ Sharing (UNOS) was created in 1986 to coordinate equitable organ allocation. The formal declaration of brain death and written informed consent must be documented in the patient's medical record before organ donation can occur. Hospitals are now required to report all deaths to the OPO to maximize the recovery of transplantable organs to meet the escalating demand. Some countries have enacted presumed consent legislation to enable organ recovery to proceed automatically in individuals who are brain dead if wishes to the contrary were not expressed before their death.
Legal criteria for brain death The criterion for brain death, that is, absent cortical and brainstem function, must be fulfilled according to accepted medical standards. Clinical states that might temporarily alter these findings must be absent. Comatose states that must be ruled out include systemic hypothermia (<32.2°C), drug (eg, barbiturate) overdose, shock, metabolic or endocrinologic derangements, and electrolyte or acid-base disorders. If the definitive diagnosis is difficult to establish on the basis of clinical findings, electroencephalography, cerebral angiography, or radionuclide study of cortical blood flow is useful in confirming brain death. The use of anencephalic neonates as organ donors is periodically proposed. Such proposals challenge the current definition of brain death and stimulate debate and controversy. These neonates represent a relatively small cohort of potential donors for neonatal cardiac recipients and have a negligible effect on the supply of donor organs. Clinical criteria for brain death Clinical criteria for brain death include the following:
Cause of death In patients who become cardiac donors in urban United States, the usual mechanism of brain death is penetrating or blunt head trauma. Most deaths in these patients are secondary to motor vehicle accidents, gunshot wounds to the head, or closed head trauma. Intracranial bleeding, drug poisonings, asphyxia, intracranial neoplasms, and cold-water drowning are other causes.
Phases of donor selection Donor selection involves 3 phases: primary screening, secondary screening, and definitive screening. The OPO performs the primary screening. Pertinent demographic information is collected about the potential donor. This information includes the donor's age, height, weight, sex, ABO blood group, mechanism of death, hospital course, and routine laboratory and serologic data. After brain death is verified and informed consent obtained, potential recipients are identified by using a computerized database. Secondary screening involves notification of the team at the recipient's hospital, which consisting of a transplant coordinator and cardiac surgeon or cardiologist. The team scrutinizes the potential donor's medical history, clinical and hemodynamic status, complete blood counts, Gram stain and culture results, arterial blood gas levels, chest radiograph, ECG, echocardiogram (obtained during resting or dobutamine stress testing), and cineangiogram. The team identifies potential absolute or relative contraindications to donation and coordinates the donor's clinical treatment. Adverse issues are always considered in relation to the clinical needs of the potential recipient. The team may be dispatched to the donor's hospital to complete this formal evaluation and stabilize the donor's condition if problems are present or anticipated. The final phase or definitive screening occurs at the time of recovery. On his or her arrival at the donor hospital, the cardiothoracic surgeon examines the patient and reviews his or her medical record, chest radiograph, ECG, echocardiogram, and cineangiogram. Once in the operating room, the surgeon directly inspects the heart, looking for signs of myocardial contusion, infarction, and ventricular dysfunction. The great arteries are palpated for thrills and examined for signs of valvular dysfunction or intracardiac shunts. The coronary arteries are palpated for plaques and gross calcifications, which are potential harbingers of underlying atherosclerotic occlusive disease. Minicatheterization can be performed by directly measuring the pressures of the cardiac chamber, aortic, and main pulmonary artery. If necessary, oximetry can be performed to evaluate intracardiac shunts. The recipient hospital is notified of the findings in the field, and recovery can proceed if indicated (see Criteria for accepting donor allografts). Recovery usually involves several organs and surgical teams from different hospitals. The cardiothoracic surgeon coordinates the surgical treatment of the patient and the sequence of organ retrieval with the other teams. Criteria for excluding donor allografts Criteria for excluding donor allografts include the following:
Criteria for accepting donor allografts
Criteria for accepting donor allografts include the following:
ABO blood group matching
A minimum prerequisite for allograft survival is ABO compatibility. However, the Toronto group recently demonstrated successful outcomes violating this traditional biologic barrier in neonatal orthotopic heart transplantation. Crossing this biologic barrier results in lethal hyperacute rejection caused by preformed donor-specific antibodies in the recipient. Recipients at additional risk for hyperacute rejection are patients with a history of exposure to multiple transfusions; these include multiparous women, recipients of multiple transfusions, patients with long-term ventricular assist devices because of preformed anti–human leukocyte antigen (HLA) antibodies, and infants with congenital heart disease and a history of multiple operations (including previous transplantation). Prospective lymphocyte crossmatching is advised when the level of recipient preformed antibodies (PRAs) is 15% or higher.
The use of flow cytometry to define the risk of hyperacute rejection and plasmapheresis and IVIG therapy in the peritransplantation period has improved the treatment of these high-risk recipients. To date, the limited organ preservation window has precluded the use of prospective human HLA matching, which may be associated with improved long-term allograft survival in other solid-organ transplantations.
Age of the donor
Over the 30-year history of heart transplantation, the strict age criteria for the donor have gradually been relaxed. This liberalization is partly related to the increasing use of angiography and dobutamine stress echocardiography to detect occult coronary artery occlusive disease in relatively old donors and partly related to mounting pressures to expand the organ pool because of the epidemic of end-stage heart failure. Coronary angiography permits transplantation teams to identify important occlusive disease of the coronary artery and, in certain isolated instances, to perform surgical or catheter-based perioperative revascularization. So far, this strategy is promising in the early and intermediate follow-up stages.
The physiologic age of an allograft is more relevant than its chronologic age. Hearts from all donors are considered on a case-by-case basis, depending on the age and medical needs of the potential recipients. In the author's program, no chronologic age criteria are used for donor cardiac allografts. Although recent findings from the multi-institutional database of the International Society for Heart and Lung Transplantation (ISHLT) indicate increased mortality and graft failure rates in recipients of allografts from donors older than 40 years, this outcome has not been observed in selected large, single-institutional experiences. Thus far, at the author's institution, use of older donor hearts has not increased the risk of accelerated vasculopathy of the cardiac allograft.
Malignancy
Active extracranial malignancy in donors who are brain dead is an absolute contraindication to donation because of the potential for donor-transmitted malignancy. Recipients of donor hearts from patients who had primary brain malignancies with low metastatic potential have done well after transplantation. However, these donor hearts should not be used if existing ventriculostomies or other decompressive or extirpative procedures have breached the brain-blood barrier and increased the potential for systemic seeding. Cardiac allografts from individuals thought to be cured of a previously treated malignancy (>5-y survival without clinical or laboratory evidence of residual or recurrent disease) may be cautiously considered for transplantation on a case-by-case basis. |
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Organ transplantation is an efficient means of transmitting certain diseases. Therefore, critical evaluation of a potential donor is essential to prevent transmission of life-threatening infection with the cardiac allograft. One can divide the infections into 3 groups: (1) active viral infection (eg, HIV, HBV, or HCV infection); (2) latent infection with cytomegalovirus (CMV) or Toxoplasma species that can be reactivated after transplantation, with a potential for systemic dissemination in the absence of preventive strategies; and (3) active infection of the allograft with bacteria, fungi, and certain viruses associated with terminal illness or preceding clinical illness. HIV infection The rate of transmission of HIV infection from HIV-positive donors whose organs are inadvertently transplanted approaches 100%, and infection uniformly results in the death of the recipients. Therefore, organs from donors with a positive antibody-screening results for HIV infection are rejected unless subsequent tests confirm that the initial result is false-positive. Recent screening for HIV p24 antigen (the core structural protein of the HIV virus) may be used to detect false-negative HIV serologic findings (see Routine serologic screening of the organ donor). HBV infection HBV transmission can occur in heart-transplantation populations. Within 30-60 days of exposure, hepatitis B surface antigen (HBsAg) may be detected in the sera of inoculated patients. Hemolysis of a donor blood sample may lead to false-positive HBsAg screening results. Heart recipients who have positive anti-HBsAb findings (secondary to immunization or natural immunity) are considered candidates for HBV-positive donors at some transplantation centers. Table 1 summarizes the risks related to the transmission of HBV infection according to donor serologic test results. Table 1. Donor-Organ Serologic Patterns and the Risk of Hepatitis B Transmission to Heart Allograft Recipients
Note.—Anti-HBs = antibody to HBsAg; anti-HBc = total hepatitis B core antibody. HCV infection About half of anti-HCV–positive patients have hepatitis C viremia, as detected by means of polymerase chain reaction (PCR) analysis of the blood. All donors with positive PCR results can transmit HCV to allograft recipients. The risk of HCV transmission from a donor who has the anti-HCV antibody (PCR negative) is indeterminate. PCR testing is usually performed retrospectively in heart donors, given the short preservation window. About 50% of those who receive cardiac allografts with positive findings for anti-HCV antibody have detectable levels of the anti-HCV antibody. Half of these (25%) have hepatitis C viremia, as detected with PCR analysis. In time, 35% of patients who receive a heart from a donor who has positive anti-HCV antibody findings may develop liver disease. Routine serologic screening of the organ donor
Routine serologic screening of the organ donor should include tests for the following:
Bacteriology and sepsis
Donor infection is evaluated with blood culture bacteriologic findings, the presence and duration of catheter and intravenous line use, and the nature of the infection before decisions about donor acceptability are made. The removal of the offending foreign body and the administration of appropriate antibiotics may suffice to ensure suitability of the organ for donation.
Organs from donors with bacterial meningitis (Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis) may be acceptable after the systemic administration of a broad-spectrum cephalosporin. Donor organs infected with gram-negative organisms such as Klebsiella species, Enterobacter species, Escherichia coli, and Pseudomonas aeruginosa, pose a notable risk for anastomotic rupture of the great vessels secondary to bacterial endocarditis and mycotic aneurysm; infections with these organisms and generally disqualify a cardiac donor. This risk is also reported for infections with Staphylococcus aureus and Bacteroides species.
The presence of an important fungal infection in a donor automatically precludes cardiac organ donation. In the case of donor endocarditis, the extent of local disease, the presence of bacteremia (based on bacteriologic and antibiotic sensitivity findings), and the urgency status of the recipient are factors in the decision to use the graft. Appropriate donor and recipient perioperative antibiotic therapy may prevent inoculation and adverse infectious sequelae.
The basic tenet not to transplant an already infected organ or an organ obtained from a patient with ongoing bacteremia or fungemia promotes safe practice. However, indiscriminate adherence to this premise leads to the waste of some potentially usable grafts. Certain donors are at increased risk for occult sepsis; these include drowning patients, those with burns, and those with ventilator dependency and indwelling lines and catheters for longer than a week.
Hypothermia and ischemia The upper limit for cold ischemia of the heart has historically been 4-6 hours. Present organ-preservation techniques have extended heart preservation to 6-8 hours. This biologic constraint has limited the geographic area from which donor hearts can be harvested for specific transplant centers and the potential benefits of prospective cross matching of potential donor hearts for transplantation. Solid organs other than the heart have been successfully preserved for as long as 2 days by flushing the organs with the University of Wisconsin (UW) solution and by storing them at 0-5°C. This success has lead to the substitution of the UW solution for the Stanford solution in the author's heart transplantation program. Cellularly impermeable agents (eg, lactobionic acid, raffinose, hydroxyethyl starch) prevent cell swelling during cold ischemic storage. The addition of glutathione and adenosine may promote organ recovery by combating the reperfusion injury associated with oxygen free radicals and by stimulating high-energy phosphate replenishment. Standard donor cardiectomy is performed after diastolic arrest and after the empty heart is flushed with a cold UW solution and topical sodium chloride slush. At the author's institution, the current protocol requires infusion of the UW solution (10-12 mL/kg) with a mean aortic root pressure of 60-70 mm Hg for 4-6 minutes. The excised allograft is rinsed in cold UW solution to remove blood, submerged in cold UW solution, and placed in sterile bowel bags for transportation in an ice chest. At the recipient hospital, the donor heart is orthotopically transplanted by using a bicaval technique with a continuous topical endocardial infusion of a cold plasmalyte solution. All allografts are reperfused with leukocyte-depleted aspartate- and glutamate-enriched warm blood during cardioplegia for 4 minutes; this is followed by reperfusion with leukocyte-depleted warm blood before the aortic cross-clamp is released. In the author's experience, use of the UW solution and leukocyte-depleted perfusion reduces the incidence of allograft failure associated with long (>5 h) donor ischemia times. Size matching Guidelines from the Stanford experience established that heart transplantation is safe when the donor-recipient size match is >0.8 in the setting of a normal recipient pulmonary vascular resistance and transpulmonary gradient. A donor is considered marginal if the match is <0.7 or if the body surface areas of the donor and recipient differ by >30%. Before an undersized donor heart is accepted, other variables in both the donor and recipient should be considered. These include the donor ischemia time, the lean body masses, the recipient's pulmonary artery pressures, donor heart hypertrophy, and sex mismatching (particularly when the implantation of an undersized female heart in a male recipient is considered). The goal is to match the donor myocardial mass to the circulatory demands of the recipient. In this context, an estimation of lean body mass is more relevant than the absolute weight, particularly in obese individuals. Most patients with end-stage heart failure have cardiomegaly and can receive a larger donor heart. This is particularly true in neonatal and infant recipients for whom size-matched donor organs are more difficult to find. In these recipients, a relatively large discrepancy in size match is generally tolerated, but the removal of recipient costal cartilages may be required to enlarge the mediastinal domain for an oversized allograft. The use of undersized grafts should be avoided whenever possible, particularly in patients with an elevated pulmonary vascular resistance and in those with repeat surgical sternotomy (which increases the likelihood for blood transfusion). Old donor hearts The high prevalence of coronary artery occlusive disease in relatively old donors and its potential effect on the development of cardiac allograft vasculopathy have led the author's group to consider aggressively coronary revascularization (percutaneous transluminal coronary angioplasty [PTCA] or coronary artery bypass grafting [CABG]) in these donor allografts, as clinically indicated. At the author's institution, this strategy has been used in 12 patients since 1994. The recipients had a UNOS status of I, or they were aged 65-70 years with a UNOS status of II. The mean recipient age was 57 years, and the mean donor age was 55 years. Angiograms obtained at the end of the first postoperative year showed vein patency rates of 90% among survivors and a mean left ventricular (LV) ejection fraction of 60% ± 4%. Three in-hospital deaths and 1 late death occurred. If one excludes cases with preexisting donor coronary artery disease, angiographically detectable coronary artery disease was similar in hearts from old (>45 y) and young (<45 y) donors in our series. Ventricular dysfunction Ventricular dysfunction is usually defined as a subnormal echocardiographic ejection fraction, a need for high doses of inotropic agents, and hemodynamic abnormalities. A heart from a donor with a history of cardiac arrest and prolonged ventricular resuscitation or death caused by asphyxia used to be considered unacceptable for transplantation. Experience at the author's institution suggests that donor hearts might be used after arrest if this event predates procurement by a few days, if the heart is optimally resuscitated, and if the recipient is smaller than the donor. Function can often be optimized in donors requiring high-dose inotropic support. Fluid may be replaced to match urine or blood losses, and blood may be transfused to optimize myocardial oxygen delivery to improve donor heart function. Thyroid hormone replacement with triiodothyronine is useful and may reduce the need for pressor support. Despite careful management, the ejection fraction (as determined with echocardiography) may remain below 45%. A heart with such function should be used in either a small recipient with normal pulmonary arterial pressures with status of I or in a recipient on the alternate list. The alternate list is a separate list of recipients who do not normally qualify for cardiac transplantation due to advanced age, comorbidities, or retransplantation. A short donor ischemic time is preferred when such a heart is used. LV hypertrophy Diastolic dysfunction of a hypertrophied heart presents particular concerns. Allografts with donors with LV hypertrophy (LVH) may be used selectively, particularly if no ECG criteria of hypertrophy are present and if the graft ischemia time is short. Caution is advised in donors with a documented history of hypertension. Precise measurement of LV wall thickness with echocardiography is warranted in all potential donors to estimate the severity of LVH and to complement the interpretation of ECGs.
Analyses of transplantation outcomes showed that left ventricular hypertrophy, coexistent coronary artery disease are associated with increased early mortality and an increased hazard risk for acute rejection. Single-institutional analyses revealed that intracranial bleeding, as mechanism of brain death, was associated with adverse outcome. Intracranial bleeding may be a surrogate variable for left ventricular hypertrophy due to long-standing donor hypertension.
Tables 2 and 3 show the approximate costs of organ recovery in southern California according to One Legacy, a transplant donor network that serves southern California. Table 2. OPO Organ-Acquisition Fees for Solid-Organ Allografts in Southern California
Note.—The mean total OPO fee is $20,000 (range, $15,000-40,000). Table 3. Organ-Acquisition Fees for Solid-Organ Allografts in Southern California by Organ
The most important factor restricting widespread heart transplantation in patients with terminal congestive heart failure is the dearth of donor organs. Careful scrutiny of potential donors and judicious matching of organs with the growing number of patients awaiting heart transplantation will optimize the utility of precious and scarce resources.
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