Donation After Circulatory Determined Death Research Articles

Graft function and incidence of cardiac allograft vasculopathy in donation after circulatory-determined death heart transplant recipients

Experience in donation after circulatory-determined death (DCD) heart transplantation (HTx) is expanding. There is limited information on the functional outcomes of DCD HTx recipients. We sought to evaluate functional outcomes in our cohort of DCD recipients. We performed a single-center, retrospective, observational cohort study comparing outcomes in consecutive DCD and donation after brain death (DBD) HTx recipients between 2015 and 2019. Primary outcome was allograft function by echocardiography at 12 and 24 months. Secondary outcomes included incidence of cardiac allograft vasculopathy, treated rejection, renal function, and survival. Seventy-seven DCD and 153 DBD recipients were included. There was no difference in left ventricular ejection fraction at 12 months (59% vs 59%, P = .57) and 24 months (58% vs 58%, P = .87). There was no significant difference in right ventricular function at 12 and 24 months. Unadjusted survival between DCD and DBD recipients at 5 years (85.7% DCD and 81% DBD recipients; P = .45) was similar. There were no significant differences in incidence of cardiac allograft vasculopathy (odds ratio 1.59, P = .21, 95% confidence interval 0.77-3.3) or treated rejection (odds ratio 0.60, P = .12, 95% confidence interval 0.32-1.15) between DBD and DCD recipients. Post-transplant renal function was similar at 1 and 2 years. In conclusion, cardiac allografts from DCD donors perform similarly to a contemporary population of DBD allografts in the medium term.

CARC18: Donor Heart Refusal Following Circulatory Death: An Analysis Of UNOS Refusal Codes

Purpose: Due to the severe shortage of donor hearts, many patients with end-stage cardiac disease die before receiving potentially lifesaving transplantation. In the past, heart donation was restricted to donation after brain death (DBD). Utilizing hearts following controlled donation after circulatory determined death (DCD) is a promising development that could significantly increase the number of hearts available for transplantation. Recent studies demonstrate that survival following transplantation of controlled DCD hearts achieves results similar to transplantation using DBD hearts. Currently, the majority of DCD hearts are discarded because most do not meet the strict criteria required for controlled DCD. Of those that meet controlled DCD criteria, the majority are still refused by the recipient institutions. We sought to explore this discrepancy and characterize the reasons that institutions refuse hearts that appear to meet controlled DCD criteria. Methods: All United Network for Organ Sharing (UNOS) refusal codes used for both DCD and DBD donors in the United States for the years 2021 and 2022 were compiled and analyzed. Rates of donor heart refusal were compared using a Z-test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to characterize the basis for DCD heart refusal. Results: During the study period 83.3% (2,578/3,094) of potential DCD hearts were declined for transplantation, while 35.5% (3,770/10,610) of potential DBD hearts were declined (p<0.01). Specifically, in 2022 refusal code data demonstrated that DCD hearts were more likely to be declined due to prolonged warm ischemic time than DBD hearts (OR 2.781; 95% CI, 4.253-1.818; p<0.01) and more likely to be declined due to organ preservation concerns (OR 1.612; 95% CI, 2.044-1.272; p<0.01). The most frequently used refusal code for DCD hearts was neurological function. In 2022, 29% (24,989/86,196) of all DCD refusals were attributed to neurological function, presumably because retained neurological function prolonged the period of warm ischemia. Conclusion: The high DCD refusal rates do not appear to align with previous publications showing that results following transplantation of controlled DCD hearts are similar to DBD. Further analysis of transplant recipient team criteria that result in DCD heart refusal should be considered. Understanding and addressing the specific reasons for refusal may substantially increase the number of donor hearts available for transplantation.

Abstract 13053: Cardiac Allograft Vasculopathy Following Donation After Circulatory-Determined Death Heart Transplantation

Introduction: Cardiac allograft vasculopathy (CAV) remains a major problem for heart transplant (HTx) recipients, limiting their long-term survival. Our centre has performed the world’s largest series of donation after circulatory-determined death (DCD) HTx. Five-year survival is equivalent to donation after brainstem-determined death (DBD) HTx. However, there is no information on CAV in DCD HTx recipients. We sought to evaluate the incidence of CAV in our cohort of DCD HTx recipients. Methods: All DCD HTx recipients at our centre between February 2015 and December 2019 who had undergone CAV screening were included. They were compared with all DBD recipients during the same period who had undergone CAV screening. Angiograms were retrospectively assigned an ISHLT CAV grade by two independent observers. Results: Thirty-six DCD and 70 DBD HTx recipients were included in the study. Median time to first imaging of coronary arteries was 621 days and 572 days for DCD and DBD cohorts respectively. There was a higher proportion of male donors in the DCD cohort (p= 0.03) but no other significant differences between donor baseline characteristics. DCD recipients had a lower median pre-transplant pulmonary vascular resistance (p=0.03) but there were no other significant differences in recipient baseline characteristics. The two cohorts had similar rates of pre-operative durable LVAD use, post-transplant mechanical circulatory support and post-transplant immunosuppression regimes. There was no significant difference in the rates of CAV between the DBD and DCD groups (p=0.41) (Figure 1). When adjusted for standard risk factors for development of CAV (including donor factors, CMV status and rejection) there remained no significant difference between rates of CAV between groups (OR 1.48, p=0.41, 95% CI 0.58-3.78). Conclusions: DCD HTx recipients have similar rates of CAV when compared to a contemporary population of DBD HTx recipients.

Ex vivo perfusion of the donor heart: Preliminary experience in high-risk transplantations

The number of heart transplantations (HTs) has decreased in France since 2017 (-5%/year) despite a stable rate of patients referred on the waiting list. Ex vivo heart perfusion (EVHP) is an innovative approach for organ preservation, reducing graft ischaemic time and facilitating continuous organ monitoring before transplantation. To report our preliminary experience of seven donor hearts preserved with EVHP, including the first heart resuscitated after circulatory-determined death in France. Seven hearts were procured from donation after brain death (DBD) for HT or donation after circulatory-determined death (DCD) for research purposes (Protocol PFS20-004, Agence de la Biomédecine, La Plaine Saint-Denis, France). All grafts were preserved using the Organ Care System® (TransMedics Inc., Andover, MA, USA) for normothermic EVHP. Perfusion parameters were adjusted to achieve stable or decreasing arterial lactate trend consistent with suitability for organ transplantation. Indications for EVHP were assessment of a marginal graft in four cases, prolonged preservation in two cases (anticipated duration for retrieval of recipient's heart>3hours) and resuscitation after circulatory-determined death in one case. Median duration of EVHP was 270 (interquartile range 216-343) minutes. five were transplanted, with a median ex situ preservation time (ischaemic time+EVHP time) of 334 (interquartile range 326-444) minutes. The two other grafts were discarded for HT. Three recipients had extracorporeal life support after HT, and presented complete cardiac recovery within a week after HT. One patient died at day 11 because of septic shock. The 3-month survival rate was 75% among recipients. Three months after HT, the left ventricular ejection fraction was>60% in all cases. EVHP enabled safe prolonged preservation and assessment of marginal grafts. This approach provides an opportunity to expand the donor pool by resuscitating grafts from donors with extended criteria, including controlled DCD.

Emergency medical staffs\u2019 knowledge and attitude about organ donation after circulatory determined death (DCD) and its related factors

BackgroundAdverse attitudes and insufficient knowledge about organ donation after Circulatory Determined Death (DCD) among emergency staff can have important consequences for the proper identification of potential DCD donors. This is aided by the constant application of donation after Circulatory Determined Death policies, and the relative strength of support for this type of donation. Therefore, this study was conducted to investigate the awareness and attitude of emergency personnel about organ donation after Circulatory Determined Death.MethodsThis descriptive study was carried out with the participation of 49 physicians and 145 nurses working in the emergency departments of educational and medical centers of Tabriz University of Medical Sciences. Nurses were selected by simple random sampling, and all physicians working in the emergency departments were included in the study. The questionnaire of Knowledge and Attitude regarding Organ Donation after Circulatory Determined Death designed by Rodrigue et al. was used. Data were analyzed using descriptive statistics and independent samples t-test, one-way ANOVA, and chi-square test.ResultsMost of the nurses (62.8%) and physicians (66.7%) had a high level of knowledge about organ donation after circulatory determined death. The mean attitude score was 101.84 (SD: 9.88) out of 170 for nurses and 106.53 (SD: 11.77) for physicians. Physicians who carried organ donation cards had a more positive attitude toward organ donation after circulatory determined death.ConclusionAccording to this study findings, knowledge and attitude of the emergency staff about organ donation was both high and positive. It is recommended to devise necessary guidelines for organ donation in Iranian emergency departments to assist in the training of colleagues in organ donation ensuring no necessary measures are missed. The results of this study would support the development of guidelines for the successful introduction of DCD in Iran.

Dynamic regulation of anti-oxidation following donation repairing after circulatory determined death renal transplantation with prolonged non-heart-beating time.

Donation after circulatory-determined death (DCD) is an important part of renal transplantation. Therefore, DCD renal transplantation animal model should be established to study the mechanism of organ injury. Here, we established a stable DCD rat renal transplantation model and investigated the dynamic regulation of graft self-repairing and antioxidant capacities with different non-heart-beating times (NHBTs). Male Sprague-Dawley rats were randomly divided into four groups with the NHBT of the donors from 0 to 15, 30, and 45 minutes. Recipients in long NHBT groups had a significantly lower survival rate and poorer graft function than those in short NHBT groups. Grafts from the 15-minute and 30-minute NHBT groups showed light and severe injury respectively at an early stage after transplantation and recovered within 7 days after transplantation, whereas the self-repairing of the grafts in the 45-minute NHBT group was delayed. The expressions of proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) were dependent on NHBT. The expression of antioxidant proteins paralleled graft recovery. In conclusion, the recipients can up-regulate antioxidant capacity to enhance graft self-repairing in DCD renal transplantation. Prolonged NHBT can delay the self-repairing and antioxidation of grafts.

A 5-year single-center early experience of heart transplantation from donation after circulatory-determined death donors

In an effort to address the increasing demand for heart transplantation within the United Kingdom (UK), we established a clinical program of heart transplantation from donation after circulatory-determined death (DCD) donors in 2015. After 5 years, we report the clinical early outcomes and impact of the program. This is a single-center, retrospective, matched, observational cohort study comparing outcomes of hearts transplanted from DCD donors from March 1, 2015 to February 29, 2020 with those from matched donation after brain death (DBD) donors at Royal Papworth Hospital (RPH) (Cambridge, UK). DCD hearts were either retrieved using thoracoabdominal normothermic regional perfusion or the direct procurement and perfusion technique. All DBD hearts were procured using standard cold static storage. The primary outcomes were recipient 30-day and 1-year survival. During the 5-year study, DCD heart donation increased overall heart transplant activity by 48% (79 for DCD and 164 for DBD). There was no difference in survival at 30days (97% for DCD vs 99% for DBD, p = 1.00) or 1 year (91% for DCD vs 89% for DBD, p = 0.72). There was no difference in the length of stay in the intensive care unit (7 for DCD vs 6 for DBD days, p = 0.24) or in the hospital (24 for DCD vs 25 for DBD days, p = 0.84). DCD heart donation increased overall heart transplant activity at RPH by 48%, with no difference in 30-day or 1-year survival in comparison with conventional DBD heart transplantations. DCD heart donation is set to make a dramatic difference in the number of patients who can benefit from heart transplantation.

Successful Combined Heart-Lung Transplant from a Donation after Circulatory Determined Death (DCD) Donor

For patients with end stage heart failure and fixed pulmonary hypertension, combined heart-lung transplantation offers the only possibility of survival with a return to a normal quality of life. Unfortunately, due to the severe scarcity of donation after brain death (DBD) organs it is rarely performed. We present the first successful combined heart lung transplant from a DCD donor. A 24-year-old male born with transposition of the great arteries, pulmonary stenosis and a ventricular septal defect (VSD) was operated in childhood with the arterial switch operation and closure of VSD. He continued to suffer with pulmonary hypertension in childhood treated with pulmonary vasodilators. He was referred to our institute in decompensated heart failure and listed for combined heart and lung transplantation, (table 1). After 3 months on the urgent list with no suitable DBD donor offers, the possibility of DCD transplantation was discussed. He matched for a DCD heart-lung bloc 109 days after his original listing and 17 days after listing for a DCD organ. The donor was a 29 year old male motorcyclist who suffered a 30 minute hypoxic cardiac arrest following a road traffic accident (table 1). The potential donor was treated for Staphylococcus aureus pneumonia and was ventilated for 12 days in ITU until futility was declared. Death was declared 219 minutes following withdrawal with a functional warm ischaemic time of 41 minutes. The heart heart and lungs were removed en bloc and perfused together on an in house modified Transmedics OCS lung device for 8 hours 2 minutes. Post transplant the recipient weaned off cardiopulmonary bypass without difficulty. He was discharged home in the 7th post-operative week and remains well at home 3 months following his transplant. DCD heart-lung transplantation has the potential for the increasing number of young adult congenital heart failure patients bridged through childhood with palliative surgical procedures in urgent need of transplantation.

Establishing a heart transplant programme using donation after circulatory-determined death donors: a United Kingdom based single-centre experience.

Demand for heart transplant donors worldwide continues to outstrip supply. Transplanting hearts following donation after circulatory-determined death (DCD) is increasingly recognized as a safe and effective alternative. As the fourth centre worldwide to have established such a programme, our goal was to present our initial experience. This was a single-centre retrospective observational study. All DCD hearts were retrieved using direct procurement and perfusion. Continuous normothermic perfusion of the procured heart was then established on the TransMedics® Organ Care System. The primary outcome of this study was the 30-day survival rate. Between May 2017 and December 2018, 8 DCD hearts were procured and 7 were subsequently implanted, including in 2 patients who had left ventricular assist devices explanted. During the same time period, 30 patients received donation after brainstem death heart transplants. Therefore, the DCD heart transplant programme led to a 23% increase in transplant activity. The median donation warm ischaemic time was 34 min [interquartile range (IQR) 31-39 min]. The median functional warm ischaemic time was 28 min (IQR 25-30 min). The median time spent by the organ on the Organ Care System was 263 min (IQR 242-296 min). The overall 30-day survival rate was 100% and the 90-day survival rate was 86%. Postoperative extracorporeal membrane oxygenation was required in 3/7 (43%). DCD heart transplants can lead to a 23% increase in heart transplant activity and should be adopted by more institutions across the world. Already established transplant programmes with good early outcomes can start such a programme safely.

The Impact of DCD Heart Transplantation on the Waiting List: A Single Centre Experience

Purpose Heart transplantation from donation after circulatory determined death (DCD) has been practiced at our institution since March 2015 and has markedly increased our transplant activity. In this observational study , we explored the impact of DCD heart transplantation on waiting time for heart transplantation, need for mechanical circulatory support and waiting list mortality. Methods We interrogated our local transplant database for all patients listed for heart transplantation to include a period from March 2012 to March 2018. The first era (pre-DCD) included all patients listed in the 3 years before the introduction of DCD and the second era (DCD) included all patients listed in the 3 years after the introduction of DCD. To account for variances in the urgency listing process over the period, analyses were performed on cumulative waiting times. Results The introduction of DCD heart transplantation was associated with increased heart transplant numbers, compared with the preceding three years. There was a significant increased probability of being transplanted on the waiting list in the DCD period compared with the pre-DCD period. The waiting list mortality rate (deaths per 100 patient-years) was similar for the two periods, suggesting that the patients had a similar risk profile. There was a significant reduction in mean waiting time associated with a significant reduction in death/need for MCS on the waiting list in the DCD era. Competing risk analysis was performed to compare time to transplant and death whilst on the waiting list in the pre-DCD vs the DCD era (transplant, p Conclusion In the three years after introduction of DCD heart transplantation, we have seen an increase in heart transplant activity and a reduction in the waiting time for heart transplantation. It appears that DCD heart transplantation may have the potential to reduce waiting list mortality and the need for mechanical circulatory support by increasing the pool of donor hearts that are available for transplantation.

First to 50: Early Outcomes Following Heart Transplantation at Royal Papworth Hospital from Donation after Circulatory Determined Death (DCD) Donors

Purpose The demand for heart transplantation has increased by 162% in the United Kingdom over the last decade. In an attempt to address both wait list mortality and prolonged waiting times, a programme of DCD heart transplantation was implemented at Royal Papworth Hospital in March 2015. We report the early outcomes of the first 50 DCD heart transplants and compare them to a matched cohort of donation after brain death (DBD) heart transplants. Methods DCD hearts were retrieved either by; Normothermic Regional Perfusion followed by ex-situ heart perfusion (NRP-ESHP), NRP followed by cold storage (NRP-CS) or Direct Procurement and Perfusion using ESHP alone (DPP-ESHP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation whilst DPP hearts were removed directly. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics was used as a comparison group. All DBD hearts were transported using static cold storage. Outcome measures for this study included 30 day survival as well post transplant inotrope dependence, mechanical support, initial cardiac performance, ventilator duration, intensive care duration and length of hospital stay. Results From 1st March 1 2015 to 10th October 50 DCD heart transplants were performed at our institute. Sixteen DCD hearts were transplanted following (NRP-ESHP), 32 hearts following (DPP-ESHP) and 2 hearts following (NRP-CS). The 30-day survival post transplant was 100% in both DCD and DBD groups. All other outcome variables were comparable between groups with the exception of Dopamine reliance post transplant, table 1. Values are median (IQR) or n (%) Conclusion After 50 DCD heart transplants, the results continue to show that DCD heart transplantation can be performed safely with comparable early outcomes to those achieved with DBD heart transplantation.

Lung donation after circulatory determined death: a single-centre experience.

Donor organ utilization and shortage remain the major limitations to the opportunity of a lung transplantation (LTx). Donation after circulatory determined death (DCD) has been adopted as a source of additional organs worldwide. However, concerns about organ quality and ischaemia-reperfusion injury have limited its application. The aim of this study was to retrospectively analyse a single-centre experience in the DCD LTx and compare early and mid-term outcomes with those from a standard donation after brain death (DBD). During the 6-year study period, 186 LTxs were performed: 147 bilateral LTxs (79%) and 39 single LTxs (21%). Of these, 23 recipients received organs retrieved from DCD donors (12.4%). No differences were found between the 2 groups of recipients except for age and cystic fibrosis as an underlying disease. No differences in terms of duration of mechanical ventilation, incidence of postoperative extracorporeal membrane oxygenation support, intensive care unit stay, hospital length of stay, airway anastomotic complications, incidence and grade of rejection and freedom from bronchiolitis obliterans syndrome were demonstrated. There was a non-statistically significant trend towards older age in the DCD group. Actuarial survival in the subgroup of bilateral LTx at 1 year and 5 years was 75% and 51% for the DCD group and 82% and 61% for the DBD group, respectively (P = 0.12). Short- and medium-term outcomes after the DCD LTx are comparable with those achieved after transplantation from the DBD donors, despite a tendency to use DCD lungs for older recipients. Therefore, the DCD LTx is a clinical option that can be used with favourable results to expand the lung donor pool.

One Year- Outcomes Following Heart Transplantation from Donation After Circulatory Determined Death (DCD) Donors

One Year- Outcomes Following Heart Transplantation from Donation After Circulatory Determined Death (DCD) Donors

Human heart transplantation from donation after circulatory-determined death donors using normothermic regional perfusion and cold storage

Heart transplantation from donation after circulatory-determined-death (DCD) donors is emerging as an additional avenue to increase heart transplant activity. Previous methods of DCD heart retrieval include direct procurement and cold storage, direct procurement, and machine perfusion and normothermic regional perfusion, followed by machine perfusion during transportation. Herein we report a further technique resulting in successful DCD heart transplantation utilizing normothermic regional perfusion and permitting functional assessment followed by cold storage.

Heart transplantation from donation after circulatory determined death.

Fifty years since the first successful human heart transplant from a non-heart beating donor, this concept of heart transplantation from donation after circulatory determined death (DCD) promises to be one of the most exciting developments in heart transplantation. Heart transplantation has established itself as the best therapeutic option for patients with end-stage heart failure, with the opportunity to provide these patients with a near-normal quality of life. However, this treatment is severely limited by the availability of suitable donor hearts. In recent times, heart transplantation has been limited to using donor hearts from donors following brain stem death. The use of donor hearts from DCD had been thought to be associated with high risk and poor outcomes until recent developments in organ perfusion and retrieval techniques have shown that this valuable resource may provide an answer to the global shortage of suitable donor hearts. With established DCD heart transplant programmes reporting encouraging results, this technique has been shown to be comparable to the current gold standard of donation after brain death (DBD) heart transplantation.

Outcome after heart transplantation from donation after circulatory-determined death donors

The requirement for heart transplantation is increasing, vastly outgrowing the supply of hearts available from donation after brain death (DBD) donors. Transplanting hearts after donation after circulatory-determined death (DCD) may be a viable additive alternative to DBD donors. This study compared outcomes from the largest single-center experience of DCD heart transplantation against matched DBD heart transplants. DCD hearts were retrieved using normothermic regional perfusion (NRP) or direct procurement and perfusion (DPP). During NRP, perfusion was restored to the arrested heart within the donor with the exclusion of the cerebral circulation, whereas DPP hearts were removed directly. All hearts were maintained on machine perfusion during transportation. A retrospective cohort of DBD heart transplants, matched for donor and recipient characteristics, was used as a comparison group. The primary outcome measure of this study (set by the United Kingdom regulatory body) was 90-day survival. There were 28 DCD heart transplants performed during the 25-month study period. Survival at 90 days was not significantly different between DCD and matched DBD transplant recipients (DCD, 92%; DBD, 96%; p = 1.0). Hospital length of stay, treated rejection episodes, allograft function, and 1-year survival (DCD, 86%; DBD, 88%; p = 0.98) were comparable between groups. The method of retrieval (NRP or DPP) was not associated with a difference in outcome. These results suggest that heart transplantation from DCD heart donation provides comparable short-term outcomes to traditional DBD heart transplants and can serve to increase heart transplant activity in well-selected patients.

Functional assessment and transplantation of the donor heart after circulatory death

After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program. Normothermic regional perfusion (NRP) was used to restore function to the arrested DCD heart within the donor after exclusion of the cerebral circulation. After weaning from support, DCD hearts underwent functional assessment with cardiac-output studies, echocardiography, and pressure-volume loops. In the feasibility phase, hearts were transported perfused before evaluation of function in modified working mode extracorporeally. After the establishment of a reliable assessment technique, hearts with demonstrable good function were then selected for clinical transplantation. NRP was instituted in 13 adult DCD donors, median age of 33 years (interquartile range [IQR], 28-38 years), after a median ischemic time from withdrawal to perfusion of 24 minutes (IQR, 21-29; range, 17-146 minutes). Two of 4 hearts in the feasibility phase were unsuitable for transplantation after functional assessment. Nine DCD hearts were transplanted in the clinical phase, with 100% survival. The median intensive care duration was 5 days (IQR, 4-5 days), with 2 patients requiring mechanical support. There were no episodes of rejection (total, 1,436 patient-days; range, 48-297). During the same period, we performed 20 standard heart transplants using brain-dead donors. NRP allows rapid reperfusion and functional assessment of the DCD donor heart, ensuring only viable hearts are selected for transplantation. This technique minimizes the risk of primary graft dysfunction and maximizes confidence in DCD heart transplantation, realizing a 45% increase in our heart transplant activity.

(761) - Restoring Function to the DCD Human Heart Using ECMO Followed By Transportation and Functional Assessment on the TransMedics Organ Care System

Donation after circulatory determined death (DCD) donor hearts are currently not considered for transplantation as there is no reliable method to assess function following an obligatory warm ischaemic period. We explored the feasibility of in-situ reperfusion of human DCD hearts using extra corporeal membrane oxygenation (ECMO) and compared functional assessment on a modified TransMedics Organ Care System (OCS) in working mode.

(754) - The Potential of Transplanting Hearts From Donation After Circulatory Determined Death (DCD) Donors Within the United Kingdom

(754) - The Potential of Transplanting Hearts From Donation After Circulatory Determined Death (DCD) Donors Within the United Kingdom