INTRODUCTION — Cardiac transplantation requires a system for donor matching, selection, and management as well as allocation of the limited supply of donor organs. In the United States, if a patient is accepted as a candidate for cardiac transplantation, that patient is registered with the United Network for Organ Sharing (UNOS), a private organization that is contracted to the federal government and which is responsible for the fair and equitable distribution of donor organs. This topic will focus on the waitlist prioritization of transplant candidates in the United States, including the 2018 modification of the UNOS allocation system. Treatment of refractory heart failure (HF) in transplant candidates, as well as indications for and prognosis after cardiac transplantation, are discussed separately. (See "Management of refractory heart failure with reduced ejection fraction" and "Heart transplantation in adults: Indications and contraindications" and "Heart transplantation in adults: Prognosis".)

IMPACT OF DONOR ORGAN SHORTAGE — The ongoing organ donor shortage limits the number of heart transplants that can be performed and thus impacts pretransplant waitlist mortality. The Registry of the International Society for Heart and Lung Transplantation reported 5149 heart transplants performed worldwide from July 1, 2016, to June 30, 2017 [1,2]. This is probably an underestimate (estimated as approximately 75 percent of worldwide transplant activity), as reporting to the registry is voluntary outside of the United States. In the United States, where reporting to the United Network for Organ Sharing (UNOS) has been mandatory for the past two decades, the number of heart transplants performed increased to 3191 in 2016 from 2884 in 2015 [3]. The majority of centers perform between 10 and 19 heart transplants per year [1].

The number of cardiac transplant centers increased to 302 during January 2016 to June 2017 from 295 in 2015. The ongoing organ donor shortage has been the major limitation to the growth of this therapy. Due to this critical organ shortage, the recipient selection process and donor allocation system have involved both clinical and ethical issues.

The donor organ shortage is a limiting factor in being able to reduce pretransplant waitlist mortality rates. The Scientific Registry of Transplant Recipients reports that waitlist mortality is standardized to 100 patient-years. This estimate is derived from the total patients on the waitlist, the total days the patients were alive on the list during the observational period, and the number of patients who died during that period. The calculated mortality rate is then the number of patients who died divided by the total number of days to yield a mortality rate per one patient-day, which is then multiplied by 36,500 to yield mortality per 100 waitlist-years.

Pretransplant waitlist mortality rates have generally declined since 2005, due to changes in organ allocation and improved survival in transplant candidates with the use of ventricular assist devices (VADs). In the interval between 2005-2006 and 2015-2016, pretransplant mortality on the waitlist declined from 14.6 to 9.7 deaths per 100 waitlist-years [4]. Declines occurred in all age groups. Pretransplant mortality declined among Status 1A and 1B candidates [5], which was the goal of the status changes implemented in 2006. The most striking decline in pretransplant mortality was in those candidates supported with VADs at the time of listing, from 43.2 to 8.0 deaths per 100 waitlist-years [5] . This was lower than the pretransplant mortality among candidates without VADs (10.4 deaths per 100 waitlist-years). However, status 7 (ie, inactive) candidates had consistent increases in pretransplant mortality over the past 10 years, rising from 16.4 deaths in 2005 to 2006 to 25.3 deaths per 100 waitlist-years in 2015 to 2016. Wide variation in pretransplant mortality by donor service areas have persisted, ranging from 3.4 to 19.9 deaths per 100 waitlist-years.

DONOR SELECTION — Cardiac donor selection involves identification and evaluation of potential organ donors to determine which patients meet the criteria for cardiac donation.

Identification of potential organ donors — A potential organ donor is typically a mechanically ventilated patient in an intensive care unit (ICU) with severe neurological devastation who has sustained brain death (donation after brain death [DBD]) or cardiac death (donation after cardiac death [DCD]). Nearly all heart donations are DBD and there has been very limited experience with DCD. The identification, evaluation, and management of potential organ donors are discussed separately. (See "Evaluation of the potential deceased organ donor (adult)" and "Management of the deceased organ donor" and 'Strategies to expand donor organ supply' below.)

Evaluation of potential donors

General approach — The initial survey of potential organ donors includes confirmation of brain death or circulatory determination of death and verification of consent for donation by the next of kin. Identification of brain death and circulatory determination of death is discussed separately. (See "Evaluation of the potential deceased organ donor (adult)".)

The required general information on potential organ donors includes ABO blood type, demographic information, comorbidities (including substance abuse history and mechanism of death), and identification of the need for cardiopulmonary resuscitation (and if needed, the duration of resuscitation) [6]. Additional information required from potential heart donors includes identification of any needed inotropic support, determination of hemodynamic stability, presence of thoracic trauma, cardiac troponin levels, electrocardiogram (ECG), echocardiogram, and coronary angiography, if indicated. Many procurement agencies now make long-distance review of echocardiograms and coronary angiograms available on many donors over protected websites.

Echocardiography should be performed promptly in potential organ donors. If the ejection fraction is estimated at less than 45 percent, or the patient is requiring inotropic support, serial echocardiography may be required to assess changes in cardiac function. The precise timing of echocardiography is controversial. The most important echocardiographic information is obtained once normovolemia has been achieved [7]. Therefore, it is reasonable to repeat an echocardiogram after volume repletion if the first study was abnormal and was performed when the donor was hypovolemic.

Coronary angiography is indicated for older donors (>40 years old) or for younger donors with risk factors for premature coronary artery disease [7].

Other aspects of deceased organ donor management are discussed separately. (See "Management of the deceased organ donor".)

COVID-19 pandemic — Additional considerations apply during the coronavirus disease 2019 (COVID-19) pandemic. Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from donor to heart transplant recipient has not been documented but is theoretically possible. Donor screening for SARS-CoV-2 is recommended, consistent with guidance from the International Society for Heart and Lung Transplantation regarding the SARS CoV-2 pandemic [8]. (See "COVID-19: Issues related to solid organ transplantation", section on 'Donor screening'.)

●Donors should be screened for exposure to and symptoms and signs of COVID-19. A donor with exposure to a confirmed or probable case of COVID-19 within the past 14 days should be declined or deferred, as the donor may be in an incubation phase. A donor with a clinical syndrome consistent with COVID-19, regardless of known exposure, should be declined or deferred. Since a thoracic computed tomography scan may show signs of SARS-CoV-2 infection before development of symptoms or a positive reverse-transcriptase polymerase chain reaction (RT-PCR), such testing should be considered for donor assessment if there are adequate local resources, including provisions for nosocomial infection control.

●Donors should also be screened for SARS-CoV-2 infection by RT-PCR on respiratory tract samples (nasopharyngeal/oropharyngeal swab, sputum/tracheal aspirate, or bronchoalveolar lavage; the last two approaches are more sensitive methods). Transplantation is avoided from PCR-positive donors.

Criteria for cardiac donors — Criteria for acceptability for donor hearts include normal right and left ventricular (LV) function, absence of coronary artery and valvular disease, absence of cardiac contusion, match with the recipient's size and blood type, and if sensitized, to an acceptable human leukocyte antigens (HLA) profile.

Traditionally, a cardiac donor was required to meet all of the following selection criteria: age <55 years old, no history of chest trauma or cardiac disease, no prolonged hypotension or hypoxemia, appropriate hemodynamics (ie, mean arterial pressure >60 mmHg and central venous pressure 8 to 12 mmHg), inotropic support less than 10 mg/kg/min (dopamine or dobutamine), normal ECG, normal echocardiogram, normal coronary angiography (if indicated based on the donor age and history), and negative viral serology (including hepatitis B surface antigen, hepatitis C virus, and human immunodeficiency virus) [6].

Some standard criteria for donor hearts may be relaxed on an individual basis in an effort to meet the needs of recipients. For example, given the safety and efficacy of direct-acting anti-viral therapies for hepatitis C virus (HCV), the use of HCV positive donors for cardiac transplantation is under investigation as a potential means of expanding the donor pool [9,10]. (See "Infection in the solid organ transplant recipient", section on 'HIV, HTLV, and hepatitis viruses'.)

The impact of donor factors on survival after cardiac transplantation is discussed separately. (See "Heart transplantation in adults: Prognosis", section on 'Donor factors'.)

Strategies to expand donor organ supply — Potential strategies to expand the supply of donor organs include technologic advances for extending the time limit for organ transport, accepting some DCD, as well as individualized relaxation of traditional criteria for transplantation, as discussed above. (See 'Criteria for cardiac donors' above.)

A portable heart perfusion system is under investigation as a potential technology for extending the time limits of organ transport and increasing donor supply. The only system that has been studied clinically for human cardiac allograft preservation is the Transmedics Organ Care System, which provides normothermic blood-based perfusion of the beating donor heart [11]. In the PROCEED trial, 130 patients receiving standard donor organs were randomly assigned to usual cold preservation or normothermic machine perfusion. There were comparable 30-day patient and graft survival rates in the two groups [12]. This trial has been followed by the EXPAND trial, in which donors with high-risk factors (such as older age, presence of LV hypertrophy, and LV ejection fraction between 40 to 50 percent) are being randomly assigned to cold versus warm preservation. The potential advantages of this system include increasing the number of donors (potentially including resuscitated metabolically abnormal donors) and extending safe transport times, thus easing the logistics of transplant surgery, and potentially being able to pretreat patients with cytoprotective and immune-modulatory agents [11]. Disadvantages include its expense and the work intensive nature of the technology.

Resuscitating organs is a key component in the evaluation and potential use of DCD. For hearts, this involves resuscitating and then excising a donor heart after cardiac arrest. Case series in Australia and England have demonstrated the potential utility of using this type of cardiac donor [13].

ALLOCATION

Donor allocation system — A donor allocation system is required to fairly and efficiently distribute the limited supply of donor hearts. Many allocation systems exist in North America and Europe [14]. Generally, the criteria for organ allocation are dependent on the urgency of the candidate's status and the geographic distance between donor and recipient.

In the United States, in an effort to ensure equitable distribution of donor hearts, the United Network for Organ Sharing (UNOS), a private organization under contract to the federal government, has created and regularly updates an organ allocation system (administered via the Organ Procurement and Transplantation Network [OPTN]) [15]. This system delineates prioritization rules that take into account the clinical severity of illness, time accrued on the waitlist, blood type compatibility, and geographic distance. With heart procurement, the duration of predicted ischemic time for the donor heart is a limiting factor in organ retrieval, with ischemic times greater than four hours associated with a higher rate of primary graft failure.

This allocation system is regularly reviewed and revised with input from various sectors, including transplant professionals, organ recipients, and donor families. The system prior to October 2018 was a three-tier system with UNOS Statuses 1A, 1B, and 2. The last previous major change to this allocation system occurred in July 2006 when Status 1A and 1B patients in Zone A (concentric circle encompassing the first 500 nautical miles [NM]) were prioritized over local Status 2 candidates [15]. Despite efforts to develop equal sharing of a scarce resource, there continues to be great variability in the median time to transplant, which is highly dependent on location (ie, UNOS regions). Median time to heart transplantation in adults in 2009 ranged from 1.1 to 12.4 months, depending on the donor service area [16].

In March of 2000, UNOS adopted the policy known as the "final rule," mandating that organ donors should be allocated to the sickest candidates such that acuity of care takes precedence over geographic factors. As of 2018, there are 58 local donor service areas in 11 UNOS regions. Donor service areas have been used as the initial zone of allocation. However, this unit may not always serve the sickest candidates, and thus there is a shift in UNOS policy favoring broader sharing.

Other allocation systems are used in other countries and geographic areas. European allocation groups include Eurotransplant, which is responsible for the allocation of organs in Austria, Belgium, Germany, Luxemburg, the Netherlands, and Slovenia; Scandiatransplant, a Nordic exchange organization that covers five countries; Balttransplant, which operates in Estonia, Latvia, and Lithuania; and United Kingdom Transplant, which allocates organs in England and Ireland. Spain, France, and Canada all have separate allocation systems.

US heart allocation policy — The current heart allocation system has been in effect since October 18, 2018 [17]. The goals of the new allocation system are to reduce waitlist mortality; reduce the number of exemptions to high priority statuses (1A and 1B), which had become problematic; define objective criteria for the statuses based on physiologic measures rather than therapeutic interventions; and modify geographic distribution to ensure fair allocation of organs to the sickest candidates. The criteria assigns priority to certain non-dischargeable mechanical support devices (non-dischargeable devices are those that are not US Food and Drug Administration (FDA) approved for use outside a hospital). The table lists approved dischargeable and non-dischargeable mechanical support devices (table 1).

As of October 18, 2018, the prior three-tier system (ie, Statuses 1A, 1B, and 2) was upgraded to a six-tier system (table 2). The prior Status 1A is now divided into three levels: new Statuses 1, 2, and 3. The new Status 4 is similar to the prior Status 1B and was expanded to include candidates not usually responsive to inotropic or mechanical support (including those with congenital heart disease, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and those requiring cardiac retransplantation). Status 5 is a new tier identifying combined organ candidates (ie, on the waitlist for at least one other organ at the same hospital). Status 6 (previously Status 2) is for all remaining active candidates.

Transition of time accumulated prior to the new allocation system will be performed such that a patient who was previously Status 1A due to a device malfunction will become a new Status 3 with the time accrued from the prior 1A listing. If a patient was previously Status 1A for mechanical circulatory support (MCS) device for ventricular tachycardia (VT)/ventricular fibrillation (VF), then that patient becomes Status 1 with accrued time from the prior 1A Status.

As of January 9, 2020, the use of donor service areas (DSAs) was eliminated for thoracic organ allocation [18]. Distances for heart allocation now range from 250 nautical miles (NM) to the nation (the United States) and are based upon the status of the patient and the blood type match with the donor. As an example, for adult Status 1 or 2 with primary or secondary blood type match, the initial distance is broadened to 500 NM (versus 250 NM for status 3 with primary or secondary blood type match).

To qualify for each status, candidates must meet specific criteria, which were designed to create similar profiles of risk for each status. These criteria are outlined in the OPTN policy statement, and some are quite complex (table 3). For example, to qualify for Status 1 listing for use of venous-arterial extracorporeal membrane oxygenation (VA-ECMO), the patient will need documentation of systolic blood pressure below 90 mmHg, cardiac index <1.8 L/min/m² off inotropes (or <2 L/min/m² on inotropes), and pulmonary capillary wedge pressure (PCWP) >15 mmHg prior to initiation of VA-ECMO. If these values were not available seven days prior to initiation of VA-ECMO, the patient will need documentation of cardiopulmonary resuscitation, systolic blood pressure <70 mmHg, lactate >4 mmol/L, or aspartate transaminase/alanine transaminase >1000 units/L 24 hours prior to initiation of VA-ECMO. An additional example of the complexity of the criteria to qualify can be seen for the Status 1 criterion of mechanical device with VT or VF. The patient must not be a candidate for ablation and must have had at least three episodes of VT/VF separated by at least one hour.

Exception process — Transplant programs may request an exception to qualify a candidate for adult Tiers 1 to 4. For any exception request, the Regional Review Board will examine retrospectively objective medical criteria that show the heart candidate has an urgency and potential for benefit comparable to that of other candidates at the requested status. For exceptions, OPTN policy requires that candidates for Tiers 1 to 3 be admitted to the transplant program's hospital for the duration of the exception approval. The Review Board cannot approve exceptions for candidates in any of those statuses if the candidate is not admitted to his or her transplant program's hospital. Hospital admission is not required for adult Status 4 or Status 4 exceptions.

All exception extensions also require Regional Review Board approval. For extension of an exemption, objective criteria must be provided to the Regional Review Board for approval. For example, to extend a candidate in Status 1, Criterion 1, VA-ECMO, the transplant program must provide clarification as to why the candidate cannot be supported by a durable device and objective data that the patient cannot be weaned from ECMO such as hypotension (mean arterial pressure <60 mmHg), cardiac index <2.0 L/min/m², PCWP >15 mmHg, or SvO₂ less than 50 percent measured by central venous catheter.

An analysis by the OPTN Thoracic Committee reviewed the impact of the first year of the new heart allocation system on waitlist characteristics, waitlist mortality, types of mechanical device support, and posttransplant survival [19]. Following implementation of the new allocation system, there has been an increase in the use of short-term mechanical assist devices in listed patients. ECMO use rose from 3.7 percent pre- to 6.5 percent postimplementation, and intraaortic balloon pump counterpulsation use rose from 12 to 27 percent. In contrast, overall use of durable LV assist device (LVAD) support declined from 79 to 61 percent. The number of deaths per 100 patient years was highest in the new Status 1 category, followed by Status 2 and Status 3, indicating that the revisions to the allocation system successfully risk-stratified the sickest patients. For all candidates, there was no change in waitlist mortality with the new system. At the time of transplant, 76 percent of patients were in Status 1, 2, and 3 groups, with 7 percent of patients in Status 1, 46 percent in Status 2, and 23 percent in Status 3. Previously, the corresponding Status 1A included 68 percent of all patients transplanted. With broader geographical organ sharing for Status 1 and 2 candidates, a significant increase in ischemic time from 3.1 to 3.4 hours was observed. Though early reports with incomplete follow-up suggested a significant decline in posttransplant survival [20], the complete dataset reviewed by the Thoracic Committee demonstrated comparable posttransplant survival pre- and postimplementation.

Role of mechanical circulatory support — A growing number of cardiac transplant candidates receive MCS. The 2018 International Society for Heart and Lung Transplantation registry data indicated that about half of transplant recipients during 2009 to June 2017 required MCS (predominantly LVAD; also includes right ventricular assist device, total artificial heart, extracorporeal membrane oxygenation, and intra-aortic balloon pump) as a bridge to transplantation [2]. In large part, the revision of the UNOS allocation system described above was driven by the expanding use of LVADs in bridging patients to transplant [16] and the numerous complications (infection, thrombus, bleeding) that resulted in an excessive number of high priority status exceptions. (See 'Donor allocation system' above.)

As discussed separately, MCS with an LVAD may be used in the following three settings (see "Intermediate- and long-term mechanical circulatory support"):

●Potential candidates for transplantation (with a potentially reversible comorbidity) may require MCS as a bridge to observing whether the comorbidity does reverse and thus deciding whether transplantation is an option. (See "Heart transplantation in adults: Indications and contraindications", section on 'Approach to evaluating contraindications'.)

•Potentially reversible or treatable comorbidities include obesity, tobacco use, renal failure, and some cancers.

•In addition, patients with pharmacologically acutely irreversible pulmonary hypertension who are otherwise candidates for transplantation should receive a three- to six-month trial of MCS to see whether the pulmonary hypertension can improve. (See "Heart transplantation in adults: Indications and contraindications", section on 'Elevated pulmonary vascular resistance'.)

●Candidates for cardiac transplantation may require MCS as a bridge to extend life until a donor becomes available for transplantation.

●Patients with refractory HF who are not candidates for heart transplantation may be candidates for MCS as destination (or permanent support) therapy.

LVAD support is offered to transplant candidates who are rapidly deteriorating despite maximal medical therapy, are developing end-organ damage despite maximal medical therapy, or are inotrope dependent with an anticipated long waitlist time (ie, large size, blood type O recipients). These categories correspond to the Interagency Registry for Mechanically Assisted Circulatory Support Levels 1 to 3 (table 4). Use of the LVAD as a bridge to transplantation requires that LVAD recipients be accepted for cardiac transplantation and thus meet the same inclusion criteria detailed separately. (See "Heart transplantation in adults: Indications and contraindications", section on 'Indications for cardiac transplantation' and "Heart transplantation in adults: Indications and contraindications", section on 'Contraindications'.)

Given limited experience with MCS in patients with restrictive or hypertrophic cardiomyopathy, MCS use in such patients is limited to selected cases at experienced centers [21]. (See "Heart transplantation in adults: Indications and contraindications", section on 'Indications for cardiac transplantation'.)

Recipient sensitization and virtual crossmatching — Recipient sensitization (ie, the existence of anti-human leukocyte antigen [HLA] antibodies in the recipient that would lead to a positive crossmatch with some donors) is a growing problem that complicates organ allocation. Traditionally, the sensitized candidate was typically a multiparous woman or a person with some prior transfusions. However, with the emergence of mechanical assist devices, the incidence of allosensitization has risen due to the multiple transfusions frequently required (at the time of implant or during long-term follow-up) by patients receiving these devices. The need for multi-drug, high-dose anticoagulation and the development of acquired von Willebrand disease frequently result in blood loss requiring transfusion during the time patients are bridged to transplant with these devices. The percent of sensitized transplant recipients increased from 5.3 in 1998 to 10.7 in 2009 and close to 20 percent in 2015 [16]. (See "Practical management of long-term mechanical circulatory support devices".)

The development of technology for the detection of specific anti-HLA antibodies (eg, using a Luminex template) has enabled identification of unacceptable donor antigens for particular candidates. This testing, in combination with HLA identification of the donor organ, permits the use of long distance "virtual crossmatching" without the need for on-site crossmatching. This practical approach enlarges the potential donor pool for sensitized patients in the modern era [16].

A strategy of higher prioritization for highly sensitized patients to avoid excessive waiting times and reduce waitlist mortality has been proposed, but has not been adopted by UNOS [21].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Heart transplant (The Basics)")

●Beyond the Basics topics (see "Patient education: Heart transplantation (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●The ongoing organ donor shortage continues to limit the numbers of heart transplants able to be performed and is a limiting factor in being able to reduce pretransplant waitlist mortality rates. However, pretransplant waitlist mortality rates have generally declined since 2005 due to changes in the organ allocation system, and improved survival in transplant candidates supported with ventricular assist devices (VADs) while waiting for a donor. (See 'Impact of donor organ shortage' above.)

●Cardiac donor selection involves identification and evaluation of potential organ donors to determine which patients meet the criteria for cardiac donation. Nearly all heart donations are donation after brain death, but there has been limited experience with donation after cardiac death. (See 'Donor selection' above.)

●Information required from potential heart donors includes identification of any inotropic support, determination of hemodynamic stability, identification of any thoracic trauma, cardiac troponin levels, electrocardiogram, echocardiogram, and coronary angiography, if indicated. (See 'Evaluation of potential donors' above.)

●Criteria for donor hearts are specified to optimize the quality of selected donor hearts and to satisfy the needs for a specific cardiac transplant recipient. Thus some of the standard criteria for donor hearts may be relaxed on an individual basis in an effort to meet the needs of recipients. (See 'Criteria for cardiac donors' above.)

●A donor allocation system is required to fairly and efficiently distribute the limited supply of donor hearts. In the United States, the revised six-tier United Network for Organ Sharing (UNOS) allocation system for heart transplant replaced the prior three-level system in the United States in October 2018. To qualify for each status, transplant candidates are required to meet specified criteria as outlined in the Organ Procurement and Transplantation Network (OPTN) policy statement (table 3).

●In patients with refractory heart failure, mechanical circulatory support may be used as a bridge to cardiac transplantation, a bridge to decision on whether to proceed with cardiac transplantation, or as destination therapy for patients who are not candidates for heart transplantation. (See "Heart transplantation in adults: Indications and contraindications", section on 'Role of mechanical circulatory support' and "Intermediate- and long-term mechanical circulatory support".)