Circulatory Death Heart Transplantation Research Articles

Outcomes of Donation After Circulatory Death Heart Transplantation Using Normothermic Regional Perfusion

BackgroundDonation after circulatory death (DCD) with cardiopulmonary bypass for thoracoabdominal normothermic regional perfusion (TA-NRP) has led to increased use of donor hearts. Rejection rates and long-term survival outcomes are not known. MethodsA single-center retrospective cohort review of patients who underwent DCD heart transplantation from January 2020 to December 2023 was performed. Donor and recipient characteristics, operative characteristics, and posttransplantation outcomes were analyzed. Subgroup analysis comparing co-localized vs distant donors and recipients was performed. The primary end point was 1-year survival. Secondary end points included incidences of primary graft dysfunction (PGD), cardiac allograft vasculopathy (CAV), rejection rate, and overall mortality. Our TA-NRP protocol has remained the same, consisting of sternotomy, ligation of aortic arch vessels, establishment of cardiopulmonary bypass, reintubation, resuscitation of the heart, and cold static storage during transport. ResultsIn total, 32 recipients underwent DCD heart transplantation, including 26 isolated hearts, 3 heart-lungs, and 3 heart-kidneys. The median age was 56 years for recipients and 39 years for donors; 21 donors and recipients were co-localized, whereas 11 were distant. One-year survival was 100%. Two patients required mechanical circulatory support for PGD. Four patients experienced grade 2R acute cellular rejection. Five patients had grade 1 CAV at 1 year. On subgroup analysis, distant donors and recipients had longer warm (47 vs 30 minutes; P < .005) and cold (213 vs 76 minutes; P < .005) ischemia times, without any other differences. ConclusionsOutcomes after DCD heart transplantation using TA-NRP remain encouraging with acceptable rates of rejection, PGD, CAV, and survival at 1 year.

The Rapidly Evolving Landscape of DCD Heart Transplantation.

To summarise current international clinical outcomes from donation after circulatory death heart transplantation (DCD-HT); discuss procurement strategies, their impact on outcomes and overall organ procurement; and identify novel approaches and future areas for research in DCD-HT. Globally, DCD-HT survival outcomes (regardless of procurement strategy) are comparable to heart transplantation from brain dead donors (BDD). Experience with normothermic machine perfusion sees improvement in rates of primary graft dysfunction. Techniques have evolved to reduce cold ischaemic exposure to directly procured DCD hearts, though controlled periods of cold ischaemia can likely be tolerated. There is interest in hypothermic machine perfusion (HMP) for directly procured DCD hearts, with promising early results. Survival outcomes are firmly established to be equivalent between BDD and DCD-HT. Procurement strategy (direct procurement vs. regional perfusion) remains a source of debate. Methods to improve allograft warm ischaemic tolerance are of interest and will be key to the uptake of HMP for directly procured DCD hearts.

Direct Procurement with Machine Perfusion and Normothermic Regional Perfusion in Donation after Circulatory Death Heart Transplantation

ObjectiveDonation after circulatory death (DCD) heart transplants have increased in US with DPP and TA-NRP techniques. There remains a paucity of data examining DPP and TA-NRP outcomes. The purpose of this study was to investigate the impact of DCD technique on post-transplant outcomes compared to DBD donors. MethodsAdult patients undergoing heart transplantation between December 1, 2019, and June 30, 2023 were identified in the UNOS registry. DPP and TA-NRP cohorts were detected using time of death to aortic cross-clamp of 30 minutes. Categorical variables were compared using chi-square or Fisher exact tests, while continuous variables were compared using Mann-Whitney U tests. Propensity score matching was performed using a 1:3 match. 1-year survival was analyzed using log-rank test and Cox proportional hazard regression model. ResultsDuring the study period, there were 7338 DBD and 419 DCD heart transplants. At 1-year, there was no difference in survival between unmatched (p=0.13) and matched (p=0.36) DBD and DCD recipients. There was an increase in acute rejection and rejection requiring treatment in DCD compared to DBD in the matched cohort. 134 TA-NRP and 242 DPP transplants occurred. 1-year survival and post-transplant outcomes were similar in DPP and TA-NRP. TA-NRP functional warm ischemia times increased significantly during the study period. ConclusionsIn a matched cohort, DCD heart recipients experience increased acute rejection, both treated and non-treated, compared to DBD. Despite differences in the techniques, and likely functional warm ischemic times, acute rejection, survival, and other secondary outcomes are similar between DPP and TA-NRP.

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.

Donation After Circulatory Death Heart Transplantation—Where Do We Go From Here?

Donation After Circulatory Death Heart Transplantation—Where Do We Go From Here?

(233) - Donation After Circulatory Death Heart Transplantation - Withdrawal Practices and Location Matter!

(233) - Donation After Circulatory Death Heart Transplantation - Withdrawal Practices and Location Matter!

(517) - Donation After Circulatory Death Heart Transplantation with Ex-Vivo Perfusion: Is It Ready for Prime Time?

(517) - Donation After Circulatory Death Heart Transplantation with Ex-Vivo Perfusion: Is It Ready for Prime Time?

(429) - Early Cardiac and Renal Complication Risk in Donor After Circulatory Death Heart Transplantation

(429) - Early Cardiac and Renal Complication Risk in Donor After Circulatory Death Heart Transplantation

(238) - Role of Traditional Cardiac Biomarkers in Donation After Circulatory Death Heart Transplantation

(238) - Role of Traditional Cardiac Biomarkers in Donation After Circulatory Death Heart Transplantation

Can we safely expand the donation after circulatory death donor heart pool by extending the donor age limit?

ObjectiveThis study evaluates the impact of donor age on outcomes following donation after circulatory death heart transplantation. MethodsThe United Network for Organ Sharing registry was queried to analyze adult recipients who underwent isolated donation after circulatory heart transplantation from January 1, 2019, to September 30, 2023. The cohort was stratified into 2 groups according to donor age, where advanced donor age was defined as 40 years or more. Outcomes were 90-day and 1-year post-transplant survival. Propensity score matching was performed. Subgroup analysis was performed to evaluate the effects of recipient age on 90-day survival among the recipients with advanced-age donors. ResultsA total of 994 recipients were included in the study period, and 161 patients (17.1%) received allografts from advanced-age donors. During the study period, the annual incidence of donation after circulatory heart transplantation with advanced-age donors substantially increased. The recipients with advanced-age donors had similar 90-day and 1-year post-transplant survivals compared with the recipients with younger donors. The comparable 90-day survival persisted in a propensity score–matched comparison. In the subgroup analysis among the recipients with advanced-age donors, the recipients aged 60 years or more had significantly reduced 90-day survival compared with the recipients aged less than 60 years. ConclusionsThe use of appropriately selected donation after circulatory donors aged 40 years or more has similar survival compared with that of younger donors. With careful candidate risk stratification and selection, consideration of using donation after circulatory donors aged more than 40 years may further ameliorate ongoing organ shortage with comparable early post-transplant outcomes.

Financial impact of donation after circulatory death heart transplantation: A single-center analysis.

Clinical success of donation after circulatory death (DCD) heart transplantation is leading to growing adoption of this technique. In comparison to procurement from a brain-dead donor, DCD requires additional resources. The economic impact of DCD heart transplantation from the hospital perspective is not well known. We compared the financial data of patients who received DCD allografts to those who received a DBD organ at our institution from January 1, 2021 to December 31, 2022. We also compared the cost of ex-situ machine perfusion to in-situ organ perfusion employed during DCD recovery. We performed 58 DBD and 22 DCD heart-alone transplantations during the study period. Out of 22 DCD grafts, 16 were recovered with thoracoabdominal normothermic regional perfusion (TA-NRP) and six with direct procurement followed by normothermic machine perfusion (DP-NMP). The contribution margin per case for DBD versus DCD was $234,362 and $235,440 (P=.72). The direct costs did not significantly differ between the two groups ($171,949 and 186,250; P=.49). In comparing the two methods of procuring hearts from DCD donors, the direct cost of TA-NRP was $155,955 in comparison to $223,399 for DP-NMP (P=.21). This difference translated into a clinically meaningful but not statistically significant greater contribution margin for TA-NRP ($242, 657vs. $175,768; P=.34). Our data showed that the adoption of DCD procurement did not have a negative financial impact on the contribution margin in our institution. Programs considering starting DCD heart transplantation, and those who are currently performing DCD procurement should evaluate their own financial situation.

Effects of ketone body 3-hydroxybutyrate on cardiac and mitochondrial function during donation after circulatory death heart transplantation

Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia–reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer’s acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function.

Outcomes Of Donor Circulatory Death Heart Transplantation In Recipients With Durable Left Ventricular Assist Device

Outcomes Of Donor Circulatory Death Heart Transplantation In Recipients With Durable Left Ventricular Assist Device

Abstract 13887: Longitudinal Trends in Donor and Recipient Risk Profile, and Clinical Outcomes, for Donation After Circulatory Death Heart Transplantation

Background: The US rate of Donation after Circulatory Death (DCD) Heart Transplant (HT) increased threefold from 2020 to 2022. While early analyses of DCD HT have suggested similar outcomes compared to donation after brain death HT, this may be the result of a restrictive DCD donor and recipient selection process, intended to minimize risk in the first US DCD HT cohorts. Hypothesis: We hypothesized that risk profiles for DCD HT donors and recipients have increased over time, as DCD HT has rapidly expanded. We sought to identify longitudinal changes in risk profiles for DCD donors and recipients from 2019-2023, and determine if such changes have impacted post-DCD HT clinical outcomes. Methods: We analyzed the UNOS thoracic organ database from December 2019 to March 2023. DCD HT donor and recipient risk characteristics were evaluated over time for significant trend. One-year recipient survival was compared over time. Results: During the study period, 716 DCD HT were performed. Recipients were mostly male (79%), Caucasian (68%), and had mean age of 54 years. Over time, several donor and recipient characteristics were significantly different (Table, Figure). Donors were older, and had increased BMI, creatinine, and agonal phase to cross-clamp time, although overall lower ischemic time. Recipients were more likely to be status 1 or 2, and had increased BMI, waitlist time, creatinine, and CPRA. Donor and recipient comorbidities and mechanical support use were unchanged. Post-HT survival over time was unchanged. Conclusions: Since the first US DCD HT, several donor and recipient risk-factors have increased. These increased risk profiles have not translated into reduced one-year survival.

Longitudinal Trends in Donor and Recipient Risk Profile, and Clinical Outcomes, for Donation After Circulatory Death Heart Transplantation.

Longitudinal Trends in Donor and Recipient Risk Profile, and Clinical Outcomes, for Donation After Circulatory Death Heart Transplantation.

Early national trends of lung allograft use during donation after circulatory death heart procurement in the United States

ObjectiveInnovative technology such as normothermic regional perfusion and the Organ Care System has expanded donation after circulatory death heart transplantation. We wanted to investigate the impact of donation after circulatory death heart procurement in concurrent lung donation and implantation at a national level. MethodsWe reviewed the United Network for Organ Sharing database for heart donation between December 2019 and March 2022. Donation after circulatory death donors were separated from donation after brain death donors and further categorized based on concomitant organ procurement of lung and heart, or heart only. ResultsA total of 8802 heart procurements consisted of 332 donation after circulatory death donors and 8470 donation after brain death donors. Concomitant lung procurement was lower among donation after circulatory death donors (19.3%) than in donation after brain death donors (38.0%, P < .001). The transplant rate of lungs in the setting of concomitant procurement is 13.6% in donation after circulatory death, whereas it is 38% in donation after brain death (P < .001). Of the 121 lungs from 64 donation after circulatory death donors, 22 lungs were retrieved but discarded (32.2%). Normothermic regional perfusion was performed in 37.3% of donation after circulatory death donors, and there was no difference in lung use between normothermic regional perfusion versus direct procurement and perfusion (20.2% and 18.8%). There was also no difference in 1-year survival between normothermic regional perfusion and direct procurement and perfusion. ConclusionsAlthough national use of donation after circulatory death hearts has increased, donation after circulatory death lungs has remained at a steady state. The implantation of lungs after concurrent procurement with the heart remains low, whereas transplantation of donation after circulatory death hearts is greater than 90%. The use of normothermic regional perfusion lungs has been controversial, and we report comparable 1-year outcomes to standard donation after circulatory death lungs. Further studies are warranted to investigate the underlying mechanisms of normothermic regional perfusion on lung function.

The effect of warm ischemia and donor ejection fraction on 30-day mortality after donation after circulatory death heart transplantation: A national database analysis

Donation after circulatory death (DCD) donor hearts recovered using the direct procurement and perfusion method experience variable durations of warm ischemia at the time of procurement (WIP). We used the Organ Procurement and Transplantation Network database to assess the effect of WIP on 30-day mortality after DCD heart transplantation. The analysis evaluated outcomes in 237 recipients of DCD heart transplantation, demonstrating an optimal WIP cut point of <36minutes. Multivariable logistic regression modeling identified donor left ventricular ejection fraction (LVEF) <60% as an independent predictor of 30-day mortality. The area under the receiver operating characteristic curve for predicting 30-day mortality based on WIP ≥36minutes and donor LVEF <60% was 0.90. Based on these findings, we do not recommend proceeding with DCD heart transplantation for patients with WIP ≥36minutes, particularly in donors with LVEF <60%.

(111) Pushing The Boundaries of Donation After Circulatory Death Heart Transplantation - The Australian Experience

(111) Pushing The Boundaries of Donation After Circulatory Death Heart Transplantation - The Australian Experience

(191) Impact of Functional Warm Ischemic Time on Short Term Outcomes in Donation after Circulatory Death Heart Transplantation

(191) Impact of Functional Warm Ischemic Time on Short Term Outcomes in Donation after Circulatory Death Heart Transplantation

(1067) Donation after Circulatory Death Heart Transplantation Reduces Length of Stay and Associated Costs: A Single Center Comparison

(1067) Donation after Circulatory Death Heart Transplantation Reduces Length of Stay and Associated Costs: A Single Center Comparison