Donor Selection for Heart Transplantation in 2025

Abstract

The number of candidates on the waiting list for heart transplant (HT) continues to far outweigh the number of available organs, and the donor heart non-use rate in the USA remains significantly higher than that of other regions such as Europe. While predicting outcomes in HT remains challenging, our overall understanding of the factors that play a role in post-HT outcomes continues to grow. We observe that many donor risk factors that are deemed “high-risk” do not necessarily always adversely affect post-HT outcomes, but are in fact nuanced and interact with other donor and recipient risk factors. The field of HT continues to evolve, with ongoing development of technologies for organ preservation during transport, expansion of the practice of donation after circulatory death, and proposed changes to organ allocation policy. As such, the field must continue to refine its processes for donor selection and risk prediction in HT.

Introduction

“Do the best you can until you know better. Then when you know better, do better.”

Maya Angelou

Heart transplantation (HT) provides the best long-term quality of life and survival for patients with end-stage heart failure. However, the number of patients awaiting HT far exceeds the number of hearts available for transplantation, and this discrepancy is growing (1) (Figure 1), despite numerous changes in the field, including acceptance of hepatitis C-positive donors, the opioid epidemic in the USA, development of donation after circulatory death practices, and evolutions in HT waitlisting and organ allocation for multiorgan transplants, among others. As a result, it is critically important that donor hearts, a limited resource, are maximally utilized and not squandered. HT clinicians are tasked with the difficult responsibility of evaluating the quality of donor hearts for potential recipients. For this task, clinicians are equipped with only a modest body of evidence; the donor selection process remains largely dependent on small retrospective analyses, anecdotal information, and personal clinical experience (2,3). This has led to high rates of donor heart non-use, particularly in the United States. In Europe, the donor non-use rate is approximately 20-30% (4,5), while in the U.S., this number approaches 60-65% (4,6-8). Donor heart “non-use” refers to a decision to not recover an organ from a potential donor. In this review, we aim to: 1) highlight which donor factors do, or do not, adversely affect short- and long-term post-HT outcomes, 2) examine the rapidly expanding practice of HT via donation after circulatory death (DCD), and 3) review areas for future research as the field continues to grow and develop. We performed a scoping review of all English-language published articles, with an emphasis on work that had been published within the last 5 to 10 years. We have summarized general consensus recommendations combined with decades of clinical experience in this field.

Figure 1.

Numbers of patients on the United States heart transplant waiting list versus those transplanted between 2000 – 2023

(based on data made available by Organ Procurement & Transplantation Network at https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/)

Predicting Risk in Donor Selection for Heart Transplantation

When matching a donor to a recipient in HT, the goal is to select a donor that will maximize survival of the recipient. However, given the large number of donor and surgical variables that can affect post-transplant outcomes, it is no surprise that evaluation of donor quality and prediction of risk based on donor factors remains challenging. In one study, it was found that donor sequence number, defined as the number of times a donor organ was declined before it was ultimately transplanted, had no correlation with 1- and 5-year recipient survival, highlighting not only the significant variability in donor acceptance practices, but also that the overall understanding of which donor organ characteristics confer risk remains incomplete (9). To date, attempts to predict risk of outcomes such as mortality or re-transplantation within 1-year post-HT have been largely unsuccessful (10,11). Existing risk prediction scores suffer from low sensitivity and specificity, poor ability to discriminate between high- and low-risk patients, and lack of capacity to stratify risk of these outcomes (11).

Part of the reason that risk prediction based on donor characteristics in HT remains so challenging is that the degree of risk conferred by different donor characteristics can vary. Factors such as donor age, left ventricular hypertrophy (LVH), left ventricular dysfunction, and coronary artery disease impart risk on a continuum, rather than in a binary, “yes/no” fashion. Furthermore, interactions between risk factors can be variable and synergistic, rather than just additive. For example, an older donor with LVH with short travel distance between donor and recipient centers may be deemed acceptable, but addition of a 5-hour ischemic time could make that same donor undesirable. There does not yet exist an algorithm with the ability to compute exact risk for donors with multiple risk factors that accounts for the differing effects of multiple, concomitant risk factors.

Finally, risk prediction cannot be isolated to donor characteristics alone, as recipient characteristics also interact with donor risk factors and contribute to outcomes. For example, recipients with a left ventricular assist device, who will be undergoing a second sternotomy, may be expected to experience more bleeding complications or longer transplant surgeries, so younger donors may be preferred to mitigate overall risk. These types of nuances in donor/recipient matching have largely been based on personal experience. They have not been quantified, and this further limits current risk prediction algorithms.

Comparing Organ Utilization and Donor Selection in the U.S. Versus Europe

Donor selection practices in Europe differ from those in North America. In one study that examined transplanted patients from the ISHLT registry, a “donor utilization score” was developed to predict the likelihood of a donor heart being accepted for transplantation; this score incorporated various donor characteristics, including donor age, sex, history of cardiotoxin abuse, several lab values, and comorbidities (4). It was found that acceptance of “higher-risk” donor hearts was significantly more frequent in Europe than in North America (4). This has led to a considerably lower donor non-use rate in Europe (5). Indeed, the mean European donor age is higher than that of the US, with European centers transplanting over 40% of donor hearts over the age of 60 years, and American centers only utilizing 3.2% of donor hearts at this age range (4,5).

Furthermore, one analysis comparing donor selection practices between the USA and Europe using data from The Eurotransplant Registry and the Scientific Registry for Transplant Recipients (SRTR), found that European centers were more likely than American centers to utilize organs from donors with obesity, smoking history, hypertension, diabetes, and alcohol abuse history (5). In addition, it was found in the same study that over time, donor utilization rates for donors with each of these risk factors increased in Europe, while over the same period of time, they decreased in the US (5). Given this, the overall size of the transplant waiting list in the Eurotransplant system over the past 10 years has remained stable at approximately 1,100 patients, and the number of transplants performed annually has also been consistent at roughly 600 per year (12). However, the increased donor utilization in Europe does come at a cost: transplant recipients in Europe demonstrate lower freedom from graft failure and increased post-HT mortality compared to recipients in USA (4,5).

The differences in practices between the USA and Europe likely partly relate to variations in regulatory oversight. In the USA, each transplant program’s post-HT outcomes are scrutinized; if the observed vs expected death rate hazard ratio for a program is consistently above a set threshold, that program may be flagged and closed (13). This emphasis may contribute to lower donor acceptance rates and thus fewer hearts transplanted (13,14). In 2022, the United Network for Organ Sharing (UNOS) made adjustments to its program performance metrics (14,15). Regardless, the system is in stark contrast to that of Europe, where a similar penalty for suboptimal outcomes does not exist. Hence, in Europe, the trend in practice has been on the side of accepting marginal donors to increase potential lives saved. Given the importance of maximizing utility from the precious limited resource of donor hearts for HT, it is time to consider broadening our definition of “acceptable” donor organs, and to be more aggressive with donor acceptance practices.

Donor Characteristics That Affect Post-Transplant Outcomes

HT clinicians must utilize the existing body of evidence, largely based on analysis of single donor factors, in the evaluation of a donor heart (Central Illustration). The donor factors that are known to have a significant impact on recipient post-transplant outcomes include donor age, donor-recipient size mismatch, donor left ventricular hypertrophy, and donor coronary artery disease (Table 1). Those factors are discussed in detail below.

Central Illustration.

Components of decision making in donor selection for heart transplantation

CAD = coronary artery disease, DBD = donation after brain death, DCD = donation after circulatory death, EF = ejection fraction, LVH = left ventricular hypertrophy, MCS = mechanical circulatory support, NRP = normothermic regional perfusion

Table 1.

Timeline of Post-Transplant Effects of Traditional Donor Risk Factors

	Early (≤ 30 days)	Intermediate (≤ 1 year)	Late (≥ 3-5 years)
Donor Age	PGD, mortality	Mortality	Mortality at all time points, even up to 10 years post-transplant
Low Predicted Heart Mass	PGD, mortality	Mortality	Mortality
Ischemic Time	PGD
Donor Hyperoxia (FiO2 > 40%)	PGD
Donor Coronary Artery Disease	Mortality		Cardiac allograft vasculopathy, cardiovascular death and major adverse cardiovascular events
Donor Tobacco Smoking			Mortality, cardiac allograft vasculopathy
Donation after Circulatory Death	Risk of ECMO requirement (although not observed with normothermic regional perfusion)

PGD = primary graft dysfunction

Donor Age

It has repeatedly been shown that higher donor age, especially greater than 45 years, correlates with worse post-HT outcomes, including increased risk of primary graft dysfunction (PGD), increased risk of primary graft failure within one year, and increased mortality, even after controlling for presence of atherosclerosis or recipient age (2,10,16-19). However, acceptable donor outcomes have been reported using older donors aged 50 and above (20); there appears to be an upper age threshold for acceptable outcomes at age 65 (21).

Size Matching

Predicted heart mass (PHM) is the optimal metric for size matching and is also strongly predictive of post-transplant outcomes (22). PHM is a metric that estimates heart mass based on the age, sex, weight, and height of the donor or recipient (23). These values for both the donor and recipient are entered into normative equations derived from the Multi-ethnic Study of Atherosclerosis (MESA), and then the ratios of donor-to-recipient values are assessed (donor /recipient PHM). Donor undersizing is present when the donor /recipient PHM is < 0.98, and donor oversizing is present when the donor /recipient PHM is ≥ 1.04. Severe undersizing of the donor heart (PHM < 0.86) leads to increased mortality at 1 year post-HT and is also predictive of development of PGD (22), particularly in patients with obesity or increased pulmonary vascular resistance (24). The exact lower threshold for acceptability of donor/recipient size match by PHM is unclear, as values as low as 0.8 appear to be acceptable, especially for recipients without increased pulmonary vascular resistance (25). Alternative metrics for size matching, including weight, height, and BMI, have not been found to be predictive of post-transplant outcomes (26). As such, the use of PHM for donor-recipient size matching in HT has been adopted in the most recent ISHLT guidelines for management of HT candidates (27); a PHM calculator has been incorporated into the UNOS website (28).

A potential alternative to PHM may be a physiologic analysis whereby organ utilization is based on whether or not calculated cardiac output (CO) of the donor organ would be adequate for the intended recipient – this approach led to similar outcomes at 1 and 6 months between undersized, size-matched, and oversized HT recipients (26,29). A separate analysis similarly found that incorporation of donor cardiac index in addition to PHM, particularly for undersized hearts, can be more effective in distinguishing acceptable donor hearts and increasing organ acceptance (30).

Left Ventricular Hypertrophy

The presence of severe donor left ventricular hypertrophy (LVH), with interventricular septum measurement of > 1.5 cm, appears to interact with other donor characteristics (31). In combination with older donor age of > 50 years or longer ischemic time of > 240 minutes, the presence of LVH confers greater risk of 1-year mortality (32). However, this trend does not persist in donors with younger age or lower ischemic time. In an analysis of the UNOS database for HT recipients between 2006 and 2010, donor LVH was classified as none (< 1.1 cm), mild (1.1 – 1.3 cm), or moderate to severe (> 1.4 cm), and it was found that there was no difference in 1- and 3-year mortality between the groups. However, this study also found that in donors of older age > 55 years and long ischemic time > 240 minutes, the presence of moderate to severe LVH correlates with increased mortality (33). Thus, LVH in and of itself is not predictive of, or a risk factor for, worse outcomes, but interacts with other risk factors. It has been found that in HT recipients of donors with mild or moderate LVH, there may actually be regression of interventricular septum and posterior wall thickness over time (34). More specifically, it is likely that in donors with LVH due to edema from cardiopulmonary resuscitation, there is a greater chance of observing wall thickness regression, while LVH due to hypertension, for example, may be less likely to regress. Thus, in donors with LVH, further assessment of the cause of LVH, and of the presence of additional risk factors and relevant characteristics, should be evaluated.

Coronary Artery Disease

The presence of multivessel coronary artery disease (CAD) increases the risk of mortality five-fold (35). CAD with lesions of > 50% stenosis is associated with a two-fold increased risk of a composite of cardiovascular death, nonfatal major adverse cardiac events, and hospital admissions for graft dysfunction not related to rejection (36). Multiple analyses have also demonstrated that donor-transmitted atherosclerotic disease is associated with accelerated increases in plaque volume at 1 year post-HT, and higher incidence of cardiac allograft vasculopathy (CAV) at 3 years post-HT (37,38). There remains a need for further data to better understand whether percutaneous coronary interventions for donor-transmitted CAD leads to any improvement in overall outcomes.

Recommendations for obtaining a coronary angiogram to assess for donor CAD are variable by age, geographic region, and risk factors. In general, coronary angiograms may be considered for donors of older age (above 40 years for men and 45 years for women per UNOS guidelines), presence of comorbidities such as hypertension, diabetes, or obesity, and history of tobacco smoking or cocaine/methamphetamine use (10,27). Despite these guidelines, there remains a lack of strong evidence behind recommendations for coronary angiography for donor evaluation.

“High-Risk” Donor Hearts – How Risky Are They?

In one analysis of the UNOS database, degree of donor and recipient risk were both quantified, and subsequent post-transplant outcomes were examined; it was found that high-risk donors paired with high-risk recipients led to the highest incidence of graft failure at 1 year, while a pairing of low-risk donors and recipients led to the lowest 1-year incidence of graft failure. High-risk donors paired with low-risk recipients led to less graft failure than low-risk donor/high-risk recipient pairings (4), potentially suggesting that the definition of high-risk donors may require re-examination. Indeed, numerous analyses and increased use of “extended-criteria” donors, who have characteristics perceived to confer higher risk of morbidity and mortality post-transplant, actually have not been clearly shown to negatively impact outcomes. The most frequent reasons for decline of a donor heart include female gender, presence of LV dysfunction, LVH, positive troponin levels, and CAD, among various other factors (9,31,39). Below, we discuss the findings from contemporary literature on these and other donor characteristics that are commonly labeled “high-risk.”

LV Dysfunction

Reduced LV function on an echocardiogram of the donor heart is one of the most common reasons for decline of a donor heart, accounting for 20-25% of rejected offers (40,41). It is critically important for HT clinicians to recognize that LV dysfunction is not infrequent in donors due to the sympathetic nervous system activation concomitant with brain death, and is frequently reversible. Khush et al. found that 13% of potential donor hearts showed reduced ejection fraction (26), but that 58% of these demonstrated recovery of function within approximately 24 hours, and that 1-year survival in HT recipients with donors with LV dysfunction was similar to that of HT recipients with donors with normal LV function (40). Another study that examined outcomes over 15 years of follow-up found that long-term survival was also equivalent between recipients of normal donor hearts and those of hearts with mildly reduced LV function (42). Frequently, reduced ejection fraction in younger donors is more likely to recover. Dobutamine stress echocardiography may be performed for further evaluation of LV dysfunction – improvement in wall motion may predict an overall improvement in LVEF post-HT (10,43).

Biomarker Levels – Troponin

The use of donor serum biomarker levels to predict post-HT outcomes has been of limited utility as well. Frequently, elevated donor troponin levels may lead to decline of a donor heart, but it has been shown in multiple analyses that donor troponin levels are not associated with recipient survival, either in the short or long term (44-46). One caveat to this is that if the donor troponin level continues to rise, proceeding with transplantation should be avoided, given that whatever process may be contributing to a rising troponin would continue post-transplant. Donor electrocardiogram abnormalities are also associated with increased likelihood of donor organ non-use, but do not appear to be associated with decreased graft survival (47).

Sex Mismatch

An additional donor characteristic that frequently leads to donor heart non-use is female donor gender, particularly for male recipients. Early studies had demonstrated that transplantation of female donor hearts into male recipients was associated with increased mortality (48,49). However, subsequent analyses showed that donor gender does not negatively impact post-HT outcomes as long as the organ is appropriately size-matched using PHM which accounts for the difference in heart size by sex (22).

Donor Cardiotoxin Abuse

Donor cardiotoxin abuse, such as tobacco, alcohol, and cocaine use, also tend to be of concern when evaluating donor organs, and lead to significant donor organ non-use, particularly for donors above the age of 19 years (6). However, multiple studies have demonstrated that use of organs from donors with a history of cocaine use does not adversely impact post-HT survival (50-52), and donor history of heavy alcohol use also does not adversely impact outcomes (50,51), With regard to donor smoking history, an analysis of patients transplanted between 2005 and 2016 from the ISHLT Registry suggested that donor history of heavy, chronic smoking does lead to an increased incidence of CAV, rejection, graft failure, and decreased 5-year survival compared to donors without a history of smoking (53); however an analysis of the UNOS database for patients transplanted between 2004 and 2015 reported no difference in survival between recipients transplanted with hearts from donors with and without a history of smoking (51). Limitations of the UNOS database for analysis of risks of donor smoking include lack of granular donor smoking history data and significant amounts of missing data. A multi-center prospective analysis of European and American heart transplant recipients between 2004 and 2016 had identified donor tobacco consumption as one of 4 major predictors for development of CAV within 10 years post-transplant (54). Thus, additional risk factors, history, and coronary angiography should be carefully reviewed when evaluating donors with a history of tobacco smoking.

Chronic Infections - Hepatitis C Seropositivity, Human Immunodeficiency Virus (HIV)

With the advent of direct-acting antiviral therapies, post-HT survival from hepatitis C-positive donors is similar to that from non-HCV-infected donors (55,56). In addition, HT of HIV-positive donors to HIV-positive recipients have also been performed (57).

Medical Comorbidities

Donor comorbidities such as hypertension and diabetes mellitus commonly lead to non-use of donor hearts. Hypertension may be a concern due to its association with LVH, but it has been shown that in donors with LVH, history of hypertension is not associated with worse 1-year survival or higher rates of CAV and rejection compared with donors without a history of hypertension (58). An UNOS analysis of patients transplanted between 2000 and 2010 suggested that donor history of diabetes is not associated with increased mortality (59), and a more recent analysis of the UNOS database for patients transplanted between 2010 and 2021 suggested that duration of diabetes in donors does not significantly impact 5-year post-HT survival rates (60). However, many patients with insulin dependence or long duration of diabetes are evaluated with coronary angiograms prior to a decision being made on whether or not to proceed with transplant, which may lead to bias in these retrospective analyses. Thus, in donors with diabetes, donor age, duration of diabetes, and comorbid risk factors for CAD ought to be considered.

Donor Risk Factors for PGD and Mitigation Approaches

PGD is an important early complication of HT, defined as dysfunction of the LV and/or RV, diagnosed within 24 hours of completion of HT surgery, and with no other discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications (61). Severe PGD is a major contributor to early mortality (death within one year of HT), and various donor factors have been identified as risk factors for PGD (16,62). Ischemic time has been established as major risk factor for PGD (31). While ischemic time is not a donor factor per se, it is indirectly related to the donor in that it is primarily a factor of the travel distance between the donor and the recipient. It has been suggested that the time should not exceed 240 minutes to avoid complications such as PGD and decreased survival (10,27). However, as technologies for donor heart preservation evolve, it is possible that there may be more flexibility around guidelines for ischemic time (Table 2). The traditional gold standard for heart preservation has been static cold storage in a cooler filled with crushed ice, with the organ placed in 3 bags, the innermost of which contains preservation solution. The advent of technologies such as Organ Care System (OCS) (Transmedics, Andover, MA, U.S.A), which keeps the heart in a near-physiologic state perfused with oxygen- and nutrient-rich blood, SherpaPack (Paragonix Technologies, Waltham, MA, U.S.A), and XVIVO (XVIVO Perfusion Ab, Gothenburg, Sweden), which both maintain the organ between 4 and 8°C, may allow for transportation of organs across greater distances with less ischemic injury. Analyses comparing these technologies to standard cold storage methods have demonstrated similar post-HT outcomes, with comparable long and short-term survival, rejection, CAV, and decreased severe PGD, despite longer ischemic times (63-65). In addition, examination of these technologies with extended-criteria donor hearts also showed acceptable outcomes with similar survival rates as controls and low rates of severe PGD (66-68). Thus, these technologies have allowed for HT across greater distances between donor and recipient without increasing ischemia of the donor organ (69), and have allowed for increased acceptance of organs from donors with more high-risk characteristics.

Table 2.

Comparison of different organ preservation systems

Preservation Method	How it Works	Pros/Cons	Trials (if applicable)
Static Cold Storage	Organ placed in preservation solution and 3 bags, and placed in a cooler with crushed ice	- inexpensive, simple - limited preservation time due to ischemic injury - risk of uneven cooling and cold injury	N/A
SherpaPack	Sterile, pressure-controlled device that maintains temperature between 4-8 °C	- decreased risk of cold injury - allows longer ischemic times - more expensive than ice	GUARDIAN Registry Studies
Organ Care System (OCS)	Extracorporeal perfusion system that keeps heart around physiologic temperature in oxygen and nutrient rich solution	- decreased cold ischemia time - superior outcomes for longer ischemic times and extended criteria hearts - allows monitoring of several cardiac parameters - most expensive and resource/personnel-intensive option	- PROCEED II trial - OCS Heart EXPAND trials

Novel Donor Risk Factors for PGD

Donor hyperoxia, with donor fraction of inspired oxygen (FiO₂) of 40% or greater, is associated with higher risk of severe PGD (70). Specifically, it was found that if FiO₂ was ≥ 40% during organ recovery, and if FiO₂ was increasing during the period before organ recovery (including during referral and authorization for organ donation and at time of organ allocation), there was a particularly increased risk of severe PGD (70).

Finally, recipient allosensitization, as marked by elevated calculated panel reactive antibody value, is associated with increased risk of post-transplant PGD, CAV, and mortality (71). Moreover, recipient allosensitization remains an important factor that can limit donor acceptability for a sensitized recipient (72). The development of virtual crossmatching, which obviated the need for physical testing of compatibility between recipient and donor cells, has allowed for greater ease in matching donors to sensitized recipients (73). Furthermore, development of strategies for desensitization and for management of patients transplanted across a positive crossmatch has also allowed for ways to expand the donor pool for sensitized patients (73,74). Donor selection for sensitized patients should include a careful evaluation of which donor specific antibodies are being crossed, the strength of those antibodies, and whether or not those antibodies are likely to cause “killing” of graft cells (i.e. C1q assay positivity).

Donation after Circulatory Death

The use of donation after circulatory death donors (DCD) (Figure 2) is increasing in the field of HT. In DCD, organs are procured after circulatory arrest. DCD organ procurement involves an agonal phase, where the donor is in the process of dying and blood pressure is low, so all organs are potentially ischemic, termed a “warm ischemic time.” It had initially been suggested that the warm ischemic time should not exceed 30 minutes due to risk of PGD, but a study from Spain, where serial biopsies were obtained during DCD organ recovery, found that evidence of biologic deterioration was not seen until 10 minutes after death had been declared (75). After circulatory arrest, there is a “stand-off” period of 2-5 minutes before death is officially declared and the organs can be procured (76). Use of this method has increased transplant numbers by approximately 30% (77).

Figure 2.

Illustrations of (a) the direct procurement and preservation method of donation after circulatory death organ procurement and (b) the normothermic regional perfusion process

In one analysis of DCD donation from the United Kingdom between September 2020 and February 2022, 50 DCD heart transplants were compared with 179 donation after brain death (DBD) heart transplants, 30-day and 90-day survival were the same between the DCD and DBD groups (78). However post-HT ECMO was required in 40% of patients in the DCD group, compared with 16% in the DBD group (78). There was an increase in heart transplantation in the UK by 28% due to adoption of the DCD technique (78). Another analysis of DCD transplants in Australia between July 2014 and April 2018 demonstrated similarly comparable survival outcomes up to 4 years post-HT, but also demonstrated higher post-HT ECMO use, with 35% of DCD patients and only 10% of DBD patients requiring ECMO support (76). A randomized study of 90 DCD and 90 DBD patients showed that risk-adjusted survival at 6 months was 94% in the DCD group vs 90% in the DBD group, although there was an increased incidence of moderate to severe or severe PGD in the DCD group (79). More recently, a retrospective analysis of DCD and DBD HTs at Vanderbilt University Medical Center revealed similar survival and rates of PGD, rejection, and CAV at 1 year, between the two groups (80).

In these studies, DCD donors are generally more likely to be male (78,79), younger (79,80), and to be transplanted in recipients of a lower urgency status on the waiting list (78-80). One major reason for DCD organ non-utilization in these studies was elevated or rising lactate levels (76,79), although it has subsequently been shown that lactate profiles do not reliably predict post-transplant outcomes such as MCS requirement (81). It remains unclear which factors to monitor during organ procurement to better predict outcomes in DCD transplantation, as assessments of heart rate, rhythm, coronary flow rate, and aortic pressure have also not been correlated with post-HT outcomes (77). The emergence of DCD HT has led to decreased waitlist times, particular for patients with lower-urgency status on the waiting list; post-transplant outcomes have remained largely unchanged (82). However, DCD organ recovery can be resource-intensive (78) and cost may be prohibitive for smaller centers without access to sufficient financial and labor resources. It is likely that DCD may lead to an increased concentration of HTs in larger transplant centers; the possible impact on smaller HT centers is currently unknown.

Organ Reperfusion in DCD

In DCD HT, the method for organ procurement that was initially utilized in early studies was termed direct procurement and preservation (DPP) (Figure 2a). In DPP, after the organ is recovered from the donor, it is directly placed on the OCS system and re-perfused ex situ (77). More recently, an alternative method for in situ re-perfusion has come into practice, called normothermic regional perfusion (NRP) (Figure 2b). With this method, after declaration of death, median sternotomy is performed, aortic arch arteries are occluded (to prevent cerebral blood flow), and systemic circulation is restored to allow re-perfusion of thoraco-abdominal organs; use of this method allows for decreased warm ischemic time; assessment of the heart in situ, prior to organ recovery; and significantly decreased costs of DCD transplantation (77). In liver and kidney transplantation, this method has been shown to lead to fewer post-transplant complications, decreased graft loss and dysfunction, and better overall survival (77). In HT, the use of NRP further increases the amount of overall transplantation by 23% (77). Post-transplant survival using NRP after DCD was similar to that of DBD transplantation at 30 days, 1 year, and 5 years, per a retrospective multicenter analysis (77); there were similar 1-year findings in a more recent retrospective analysis of DCD vs DBD HT at Vanderbilt University (80). Interestingly, post-transplant ECMO requirement was not increased compared to DBD when using NRP for DCD organ procurement (77). When using NRP, transport of the organ can be done using perfusion systems like OCS, or static cold storage.

Ethical Considerations

Several ethical questions have been raised concerning the practices of DCD transplantation and NRP re-perfusion. One of these is how long to wait for a patient to pass away after withdrawal of life support. Currently, practices regarding this question are inconsistent and highly variable. For example, in many centers, the maximum length of this “warm ischemic time” has been capped at 30 minutes (75-77,79), but in the analysis of DCD in the UK, a maximum time of 2 hours had been allowed between withdrawal of support and circulatory arrest (78). In addition, with regard to the NRP method, concerns have been expressed about the risk of re-introducing circulation to the brain, despite clamping of the aortic arch to prevent this; while data are limited, one analysis examining brain circulation found no brain blood flow during the NRP process (83).

New Developments on the Horizon in Heart Transplantation

In March 2024, the Organ Procurement and Transplantation Network (OPTN) announced plans to change the heart allocation process (84). The plan is to transition from a “classification-based” system, in which various transplant candidate attributes are evaluated in sequence in order to assign an available organ to a recipient, to a “continuous distribution” system in which all relevant candidate factors are considered together in a points-based system. The ultimate goals of this transition would be more equitable distribution of donor organs and improved overall outcomes. One registry-based observational analysis of adult heart transplant candidates in the US listed between 2019 and 2022 compared the current 6-tier rank system with a continuous distribution system. It was found that the continuous system outperformed the tiered system in effectively ranking waitlisted candidates by medical urgency (85). This policy has not yet been established, and as of yet, weights still need to be assigned to different risk factors in order to create a system for calculating points.

Conclusions and Future Directions

As the field of heart transplantation continues to progress, our understanding of relevant factors in donor selection continues to evolve (Figure 3). However, clinicians’ understanding of donor risk factors ultimately must be placed in the context of their incentives. If the emphasis lies on lives saved, then a nuanced understanding of the incremental risks of older donors or donors with a history of cardiotoxin abuse, for example, carries different meaning than in a system where programs compete on the basis of post-HT outcomes. For urgent status patients on the transplant waiting list, a slightly reduced 1-year survival from a higher-risk donor is still better than the extremely low 1-year survival associated with remaining on the waiting list. The time has come to reconsider priorities in the field, and increase donor acceptance in order to improve heart failure outcomes and maximize the benefits that can be derived from HT. Development and expansion of DCD has also further broadened the donor pool and opened avenues for increased life-saving transplants. There will be a need for further analysis to determine what donor characteristics are optimal in DCD transplantation, how they differ from donor characteristics that are relevant in DBD transplantation, and how this method impacts long term HT outcomes. In addition, as AI-based technologies continue to grow and develop, use of AI for analysis of medical images such as echocardiograms and coronary angiograms for donor hearts may alter the way risk factors like donor CAD, reduced LVEF, and LVH are examined. Furthermore, use of AI may be helpful in successful development of a comprehensive risk-prediction algorithm that accounts for varying effects of different donor risk factors and that incorporates recipient characteristics' interactions with donor risk factors. All these factors will also need to be assessed in the context of upcoming changes to the heart allocation policies.

Figure 3. Donor risk evaluation algorithm.

CAD = coronary artery disease; LV = left ventricular; PHM = predicted heart mass

Highlights:

• Donor selection for heart transplantation remains highly subjective and variable between transplant centers and around the world

• Numerous factors affect donor selection, and the exact risk associated with various donor characteristics is difficult to predict

• The development of novel organ preservation technologies and donation after circulatory death have broadened donor organ availability and utilization

• As discussions about ethics and organ allocation policies continue to evolve, donor selection processes may continue to change as well

Abbreviations:

CAD

coronary artery disease

CAV

cardiac allograft vasculopathy

DCD

donation after circulatory death

HT

heart transplantation

PGD

primary graft dysfunction

PHM

predicted heart mass