Heart transplantation (HT) is an effective technique for patients in the end stage of heart failure. Unfortunately, its use is limited by a shortage of donor hearts, resulting in a waitlist mortality rate exceeding 30% per year. Most heart donors are patients whose circulatory function remains intact after the diagnosis of brain death, known as donation after brain death (DBD). Recently, another type of donor, where donation occurs after circulatory death, known as controlled DCD, has become available. These donors suffer irreversible brain damage but do not meet the criteria for brain death, meaning their lives are sustained by mechanical respiratory and circulatory support. The decision to withdraw this support is made independently of their potential as organ donors. In DCD, death is diagnosed after a specific period following the cessation of spontaneous breathing and circulation, without natural resumption. The required period for confirming death varies by different agencies and governing bodies overseeing organ donation.

In recent years in the United States, the increase in DCD has significantly raised the number of kidney, liver, pancreas, and lung transplants, representing about one-quarter of all donors. However, its utilization in heart transplantation has been limited due to technical and ethical reasons, with recent reintroduction aimed at expanding donor availability.

To examine the use and outcomes of heart transplants in these cases, a nationwide study was conducted using the United Network for Organ Sharing (UNOS) database. A total of 266 adult patients who received DCD heart transplants were identified and compared with 5,998 DBD transplants, using a propensity score–adjusted model for group balancing. Cardiopulmonary transplants were excluded from the study. During the period from December 2019 to December 2021, the monthly percentage of DCD HT increased significantly from 2.5% to 6.8% (p < 0.001). Twenty-two centers performed these transplants, ranging from 1 to 75 transplants per center. Four centers accounted for 70% of the national volume. Recipients of hearts from DCD donors demonstrated greater clinical stability compared to DBD recipients (80.4% vs. 41.1% in status 3-6, respectively; p < 0.001). Additionally, recipients of DCD hearts were more likely to have type O blood (58.3% vs. 39.9%; p < 0.001) and to have waited longer after being listed (55 days vs. 32 days; p = 0.003). No significant differences were found in six-month survival between the two groups, with a survival rate of 92.1% for DBD transplants and 92.6% for DCD transplants. Outcomes in propensity score–matched patients were similar, except for higher rates of treated acute rejection in DCD transplants prior to discharge (14.4% vs. 8.8%; p = 0.01). Furthermore, the outcomes of DCD heart recipients did not differ based on procurement and preservation techniques used, with outcomes remaining consistent between simple retrieval and normothermic regional perfusion (NRP).

According to the study authors, DCD HT is comparable to DBD transplantation in terms of short-term survival. Furthermore, broader implementation of this donation technique could significantly enhance organ availability for transplantation.

COMMENTARY:

The history of DCD HT began in 2004, but it was not until 2015 that the first series was published in Australia using a protocol for rapid surgical heart explant and subsequent preservation in an ex situ perfusion device (Organ Care System® [OCS®] by Transmedics®). The United Kingdom also developed a similar protocol, with the option to perform NRP after diagnosing the donor’s death, using an extracorporeal membrane oxygenation (ECMO) device. In both series, short- and long-term survival was comparable to DBD HT series. Subsequently, other groups published cases of DCD HT using a modified protocol involving peripheral cannulation before donor death, NRP, and static cold preservation after explantation without using an ex situ perfusion device, also yielding excellent results.

This American registry suggests that six-month survival rates and in-hospital adverse events are similar for DCD and DBD HT. These figures align with results from previous registries in the United Kingdom and Australia. Although patients selected for DCD transplantation had lower baseline risk, were younger, and had better ejection fraction than DBD patients in the study by Chen et al., after propensity score adjustment, both heart donation techniques achieved similar short-term survival. This supports the theory that the warm ischemic period experienced in DCD does not significantly impact post-transplant outcomes when donors and recipients are properly selected. However, for the first time, a higher rate of treated acute rejection before discharge in DCD transplants is reported. The lack of information on pretransplant sensitization status and other relevant data prevents full validation of these findings.

In practice, two techniques are currently used to retrieve DCD hearts for transplantation: simple retrieval and NRP, both with static cold or ex situ perfusion preservation using the OCS® device. Evidence on which method is superior is limited. The ongoing US DCD Heart Trial only uses simple retrieval with ex situ perfusion. European centers that used NRP achieved 100% short-term survival, though with primary graft dysfunction between 12-60%. In the UK, one-year survival was 100% with NRP compared to 91% with simple retrieval. In the OCS Heart EXPAND study, which uses the OCS® system after DBD donation, 30-day and six-month survival rates were 94.7% and 88%, respectively. In the study by Chen et al., while no significant differences were observed, NRP had a lower organ rejection rate compared to simple retrieval. Remaining outcomes were similar with both techniques.

The findings of this registry are of critical importance, reinforcing and confirming that DCD HT, along with other published registries in Europe and Australia, constitutes a viable alternative with outcomes comparable to DBD HT. Nonetheless, this study has some limitations, including a follow-up period for transplanted patients that is too short to draw conclusions on long-term outcomes. Additionally, there is no information on times between asystole and reperfusion, which could be a key factor in post-surgical outcomes. Exact total ischemia times are also unknown, as some organs were perfused with an ex situ perfusion platform, which cannot be considered true ischemia. Lastly, for classification purposes, it was assumed that those patients with intervals of less than 15 minutes between death and aortic clamping had undergone simple retrieval, while the rest underwent NRP, though this assumption is not precise.

In Spain, a national DCD HT protocol has recently been established, endorsed by the Standing Commission for Transplant of the Interterritorial Council of the National Health System. This protocol primarily involves peripheral ante mortem cannulation, NRP, and static cold preservation prior to implantation. The first DCD HT using this protocol was performed in Spain in January 2020, and since then, more than 60 DCD HTs have been carried out across 12 different Spanish centers, adding to the over 295 procedures conducted in six European countries. Initial published results support the positive DCD outcomes described in this article. Additionally, the NRP cardiac preservation technique used in DCD in Spain offers numerous advantages, such as reducing ischemia-reperfusion injury and enabling multiple organ preservation simultaneously, avoiding costly ex situ preservation techniques. Furthermore, it allows for elective organ retrieval and evaluation before extraction.

It is believed that DCD HT could increase transplant activity by 10-15% in Spain, making it a real and viable alternative to meet the growing global demand for organs. Optimism is the hope that leads toward achievements, and in this case, with this new cardiac donor modality, we can say that hope is becoming reality.

REFERENCE
Chen Q, Emerson D, Megna D, Osho A, Roach A, Chan J, et al. Heart transplantation using donation after circulatory death in the United States. J Thorac Cardiovasc Surg. 2023 May;165(5):1849-1860.e6. doi: 10.1016/j.jtcvs.2022.05.005.