Circulatory Death Research Articles

The Association Between the Origin of the Donation After Circulatory Death Liver Recovery Team and Graft Survival: A National Study

Background. Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary. Methods. We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure. Results. Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT. Conclusions. This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.

Racial Equity in Family Approach for Patients Medically Suitable for Deceased Organ Donation.

To conduct a contemporary analysis of the association between family approach of medically suitable potential organ donors and race/ethnicity. Retrospective review of data collected prospectively by Organ Procurement Organizations (OPOs). Ten OPOs representing eight regions of the Organ Procurement and Transplantation Network and 26% of all deceased donor organs recovered in the United States. All hospitalized patients on mechanical ventilation and referred to OPOs as potential donors from January 1, 2018, to December 31, 2022. None. OPOs provided data on referral year, race, sex, donor registration status, screening determination, donation medical suitability, donation type (brain death, circulatory death), and family approach. We evaluated factors associated with family approach to discuss donation using descriptive statistics and multivariable logistic models. Of 255,429 total cases, 138,622 (54%) were screened-in for further evaluation, with variation by race/ethnicity (50% White, 60% Black, 69% Hispanic, and 60% Asian). Among those screened-in, 31,253 (23%) were medically suitable for donation, with modest variation by race/ethnicity (22% White, 26% Black, 23% Hispanic, and 21% Asian). Family approach rate by OPOs of medically suitable cases was 94% (n = 29,315), which did not vary by race/ethnicity (94% White, 93% Black, 95% Hispanic, and 95% Asian). Family approach by OPOs was lower for circulatory death (95%) vs. brain death (97%) cases but showed minimal differences in approach rate based on race/ethnicity between medically suitable patients with different death pathways. In contrast, donor registration status of medically suitable potential donors was highly variable by race/ethnicity (37% overall; 45% White, 21% Black, 29% Hispanic, and 25% Asian). Multivariable models indicated no significant difference of family approach between White and Black (odds ratio [OR], 1.09; 95% CI, 0.95-1.24) or Asian (OR, 1.23; 95% CI, 0.95-1.60) patients. Findings indicate racial equity in OPO family approach rates among patients who were medically suitable for organ donation.

Innovations in Liver Preservation Techniques for Transplants from Donors after Circulatory Death: A Special Focus on Transplant Oncology.

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia-reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion-NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia-reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence.

Islet-after-kidney transplantation versus kidney alone in kidney transplant recipients with type 1 diabetes (KAIAK): a population-based target trial emulation in France

Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes. In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis. Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36). In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide. Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté.

Advancements in Donation after Circulatory Death Heart Procurement and Preservation: A Comprehensive Review of Recent Innovations.

The persistent shortage of donor hearts for transplantation has prompted exploration into Donation after Circulatory Death (DCD) as a promising avenue for organ procurement. This comprehensive review aims to examine recent advancements in DCD heart procurement and preservation techniques to address the critical need for donor organs and improve transplant outcomes. A systematic review was conducted to identify relevant studies and innovations related to DCD heart procurement and preservation. Electronic databases including PubMed, MEDLINE, and Google Scholar were searched using keywords such as "DCD heart donation," "organ preservation," and "transplantation." Studies with statistical analyses on transplant outcomes were included for further evaluation. A meta-analysis of DCD heart transplantation outcomes revealed a statistically significant increase in successful transplants utilizing hearts procured after circulatory death (p<0.05). Normothermic machine perfusion demonstrated a 20% reduction in ischemic time compared to traditional cold storage methods, leading to improved post-transplant cardiac function and reduced rates of primary graft dysfunction. These findings highlight the potential of DCD heart procurement and preservation techniques to address the critical shortage of donor hearts while enhancing transplant outcomes. Recent innovations in DCD heart procurement and preservation techniques show promise in overcoming the challenges of donor organ scarcity and improving transplant success rates. Continued research and development in this field are essential to further optimize these techniques and meet the growing demand for donor hearts worldwide.

Potential organ donors during two years at the second largest hospital in Norway.

Western Norway has the lowest number of actual deceased organ donors per million inhabitants in Norway. We wished to find the total number of potential donors and donor organs during 2 years at Haukeland University Hospital, the largest hospital in the region, and evaluate where and why potential donors were lost. We evaluated all patients who died at Haukeland University Hospital in 2018-19. We checked if intensive care patients, filling the criteria as organ donors after brain death, became donors, and the reasons why potential donors were lost. We also estimated the number of potential donors after circulatory death. We checked if patients transferred from the intensive care units and patients never admitted to intensive care were potential donors. Location, gender, age, and possible number of organs were registered. Of 1453 in-hospital deaths, 20 brain-dead patients became actual donors. One brain-dead and two other potential donors, one of them discharged to a bed ward, were not evaluated at the intensive care units. Relatives refused in five patients. Three fulfilled the Norwegian criteria from 2021 as organ donors after circulatory death. Ten potential donors after brain death were never admitted to intensive care and died on neurological or neurosurgical wards. If all potential organ donors were realised, the number of donors would double. The number of transplanted organs would increase less, as organs used per donor would drop from 3.50 to 2.90. Our study cannot explain the low number of donors in our region compared with the rest of Norway. If all potential donations were implemented, the number of actual donors would double. Patients dying outside the intensive care units represent the largest potential source for extra donors, maximally increasing the number of donors by 42%, high-quality livers 44% and kidneys 18%. Introducing organ donation after circulatory death may increase the number of donors by 15% and the number of high-quality livers and kidneys by 12%.

Circulating factors, in both donor and ex-vivo heart perfusion, correlate with heart recovery in a pig model of DCD

BackgroundHeart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. MethodsCirculatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. ResultsCirculating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min. ConclusionsIn heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.

The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.

Early outcomes in heart transplantation using donation after circulatory death donors in patients bridged with durable left ventricular assist devices

ObjectiveDonation after circulatory death heart transplantation potentially increases donor allografts, especially for patients with lower listing status. We assessed the outcomes of donation after circulatory death heart transplantation in patients bridged with durable left ventricular assist devices. MethodsThe United Network for Organ Sharing database was queried for adult heart transplants using donation after circulatory death donors from 2019 to 2022. Patients were stratified between those with durable left ventricular assist devices and those with intra-aortic balloon pump, inotropic, or no bridging support (control group). Primary outcome was 1-year mortality. Secondary end points were hospital length of stay, stroke, pacemaker implantation, dialysis, and acute rejection before discharge. ResultsA total of 160 left ventricular assist device recipients and 311 control recipients met study inclusion criteria. Recipients bridged with left ventricular assist devices were younger (55 vs 58 years, P < .001) with lower body mass index (28.3 vs 30.3, P < .001), longer waitlist times (112 vs 34 days, P < .001), longer out of body times (5.7 vs 4.6 hours, P < .001), and less frequent normothermic regional perfusion (31% vs 40%, P = .049). Patients with left ventricular assist devices commonly underwent transplantation at United Network for Organ Sharing status 3 and 4 (92%), whereas control patients underwent transplantation at status 2 (27%), status 3 (10%), status 4 (30%), or status 6 (30%). Kaplan–Meier analysis showed no difference in 1-year mortality between groups (P = .34). However, acute rejection was higher in the unadjusted left ventricular assist device cohort (26% vs 13%, P < .001). On multivariable logistic regression, left ventricular assist device was an independent predictor of acute rejection (odds ratio, 2.21, 95% CI, 1.32-3.69, P = .002). ConclusionsDurable left ventricular assist devices may be associated with a higher risk of developing an early inflammatory response in donation after circulatory death heart transplantation; however, 1-year survival was similar between groups.

Transplantation Outcomes in Hepatitis C Virus-Positive Donor Hearts After Circulatory Death

Although the use of hepatitis C virus (HCV)-positive hearts has been shown to be safe and effective among donors with donation after brain death (DBD), it remains unknown whether such organs recovered after circulatory death (DCD) have similar outcomes. In contradistinction to recovery from DBD using cold static organ storage, DCD procurement processes typically use normothermic-perfusion transport strategies that necessitate the use of a large volume of donor blood and involve exposure to temperatures oscillating between cold to dominantly normothermic conditions. We performed a retrospective analysis of United Network for Organ Sharing (UNOS) registry data in the United States and found that clinical outcomes do not differ with respect to rates of treated allograft rejection, early and 1-year survival. Ideally, the organ-recovery source should not result in a bias in organ-offer acceptance from HCV-positive donors, although long-term outcome data are yet unavailable.

The current landscape of in situ and ex situ machine perfusion utilization for liver grafts from cardiac donation after circulatory death donors in the US

Donation after circulatory death (DCD) is driving the increase in deceased organ donors in the United States. Normothermic regional perfusion (NRP) and ex situ machine perfusion (es-MP) have been instrumental in improving liver transplant outcomes and graft utilization. This study examines the current landscape of liver utilization from cardiac DCD donors in the United States. Using the United Network for Organ Sharing Standard Transplant Analysis and Research file, all adult (≥18 years old) DCD donors in the United States from which the heart was used for transplantation from October 1, 2020, to September 30, 2023, were compared by procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (es-MP versus static cold storage). One hundred eighty-eight livers were transplanted from 309 thoracoabdominal NRP donors (61% utilization) versus 305 (56%) liver transplants from 544 SRR donors. es-MP was used in 20% (n = 38) of NRP cases versus 32% (98) of SRR cases. Of the liver grafts, 281 (59%) were exposed to NRP, es-MP, or both. While there is widespread utilization of machine perfusion, more research is needed to determine optimal graft management strategies, particularly concerning the use of multiple technologies in complementary ways. More complete data collection is necessary at a national level to address these important research questions.

Metabolic Choreography of Energy Substrates During DCD Heart Perfusion.

The number of patients waiting for heart transplant far exceeds the number of hearts available. Donation after circulatory death (DCD) combined with machine perfusion can increase the number of transplantable hearts by as much as 48%. Emerging studies also suggest machine perfusion could enable allograft "reconditioning" to optimize outcomes. However, a detailed understanding of the energetic substrates and metabolic changes during perfusion is lacking. Metabolites were analyzed using 1-dimensional 1H and 2-dimensional 13C-1H heteronuclear spectrum quantum correlation nuclear magnetic resonance spectroscopy on serial perfusate samples (N = 98) from 32 DCD hearts that were successfully transplanted. Wilcoxon signed-rank and Kruskal-Wallis tests were used to test for significant differences in metabolite resonances during perfusion and network analysis was used to uncover altered metabolic pathways. Metabolite differences were observed comparing baseline perfusate to samples from hearts at time points 1-2, 3-4, and 5-6 h of perfusion and all pairwise combinations. Among the most significant changes observed were a steady decrease in fatty acids and succinate and an increase in amino acids, especially alanine, glutamine, and glycine. This core set of metabolites was also altered in a DCD porcine model perfused with a nonblood-based perfusate. Temporal metabolic changes were identified during ex vivo perfusion of DCD hearts. Fatty acids, which are normally the predominant myocardial energy source, are rapidly depleted, while amino acids such as alanine, glutamine, and glycine increase. We also noted depletion of ketone, β-hydroxybutyric acid, which is known to have cardioprotective properties. Collectively, these results suggest a shift in energy substrates and provide a basis to design optimal preservation techniques during perfusion.

Heart and multiple organ transplantation from donation after circulatory death using mobile normothermic regional perfusion and cardiac surgery extra-corporeal membrane oxygenation team out of the hub transplant centre.

Heart and multiple organ transplantation from donation after circulatory death using mobile normothermic regional perfusion and cardiac surgery extra-corporeal membrane oxygenation team out of the hub transplant centre.

Adult cardiac transplantation utilizing donors after circulatory death.

Adult cardiac transplantation utilizing donors after circulatory death.

P.431: Donation after circulatory death: Ethical wrinkles &amp; islamic bioethical considerations.

P.431: Donation after circulatory death: Ethical wrinkles &amp; islamic bioethical considerations.

P.062: Impacts of warm ischemia on myocardial protein phosphorylation after normothermic ex vivo reperfusion of hearts donated after circulatory death in a rat DCD model.

P.062: Impacts of warm ischemia on myocardial protein phosphorylation after normothermic ex vivo reperfusion of hearts donated after circulatory death in a rat DCD model.

Procurement Trends, Indications, and Outcomes of Heart-Lung Transplantation in the Contemporary Era.

Evolving trends in organ procurement and technological innovation prompted an investigation into recent trends, indications, and outcomes following combined heart-lung transplantation (HLTx). The United Network for Organ Sharing database was queried for all adult (≥18 years) HLTx performed between July 1, 2013 and June 30, 2023. Patients with previous transplants were excluded. The primary endpoint was the effect of donor, recipient, and transplantation characteristics on 1- and 5-year survival. Secondary analyses included a comparison of HLTx at high- and low-volume centers, an assessment of HLTx following donation after circulatory death (DCD), and an evaluation of HLTx volume over time. Cox proportional-hazards models were used to assess factors associated with mortality. Temporal trends were evaluated with linear regression. After exclusions, 319 patients were analyzed, of whom 5 (1.6%) were DCD. HLTx volume increased from 2013 to 2023 (p<0.001). One- and 5-year survival following HLTx was 84.0% and 59.5%, respectively. One-year survival was higher for patients undergoing HLTx at a high-volume center (88.3%vs. 77.9%; p=0.012). After risk adjustment, extracorporeal membrane oxygenation support 72 h posttransplant and predischarge dialysis were associated with increased 1-year mortality (HR=3.19, 95% CI=1.86-5.49 and HR=3.47, 95% CI=2.17-5.54, respectively) and 5-year mortality (HR=2.901, 95% CI=1.679-5.011 and HR=3.327, 95% CI=2.085-5.311, respectively), but HLTx at a high-volume center was not associated with either. HLTx volume has resurged, with DCD HLTx emerging as a viable procurement strategy. Factors associated with 1- and 5-year survival may be used to guide postoperative management following HLTx.

Myocardial oxygen handling and metabolic function of ex-situ perfused human hearts from circulatory death donors

BackgroundThis study investigated oxygen handling of human hearts donated after circulatory death (DCD) on normothermic ex-situ heart perfusion (ESHP) and evaluated oxygen handling markers as adjuncts to cardiac viability assessment. MethodsThis single-center retrospective study included human DCD heart transplantation procedures using ESHP. Lactate concentrations, blood gas, myocardial oxygen consumption (MVO2), delivery (MDO2) and extraction (MEO2), coronary blood flow (CBF), coronary vascular resistance (CVR), and adenosine infusion were reported over time. Correlation between parameters was assessed, and statistical testing compared patients who did and did not require extracorporeal membrane oxygenation (ECMO) support after transplantation. ResultsLactate concentrations decreased during ESHP in all transplanted hearts (n=25) and increased in 1 rejected heart. Arterial PO2 was 75.2±2.9 kPa, with an arteriovenous ΔPO2 of 44.8±10.4 kPa. Oxygen saturation was 100% in most arterial and venous samples. Average MVO2 was 2.7±0.6 mL·min-1·100·g-1 myocardium, MDO2 98.5±20.4 mL·min-1, and MEO2 8.6±1.8%. Average CVR was 0.025±0.006 mmHg∙min∙mL-1∙100 g-1 and increased over time. ΔPO2 correlated strongly with MVO2 (R=0.797, p<0.001) and lactate trend (R=0.799, p<0.001) in transplanted hearts, without differences compared to the rejected heart with increasing lactate. Adenosine infusion on ESHP was significantly higher in patients requiring ECMO post-transplantation versus non-ECMO cases (11.7 (4.5-21.0) vs. 2.2 (1.5-6.7) mL·h-1, p=0.039). ConclusionsHearts on normothermic ESHP receive excessive MDO2, due to high PO2 and CBF, while the MVO2 is relatively low. Thus, CBF and PO2 can potentially be lowered. Furthermore, ΔPO2 could serve as additional marker of metabolic function under these hyperoxic circumstances. The adenosine infusion rate might predict post-transplantation ECMO requirement.

406.5: Bile levels of keratin 19 from donations after circulatory death are associated with early graft dysfunction.

406.5: Bile levels of keratin 19 from donations after circulatory death are associated with early graft dysfunction.

P.430: Expansion of donation after circulatory death in Asian country.

P.430: Expansion of donation after circulatory death in Asian country.