Donation After Circulatory Death Hearts Research Articles

Utilization and outcomes of expanded criteria donors in adults with congenital heart disease

BackgroundUse of donation after circulatory death(DCD) and hepatitis C virus(HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease(ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. MethodsUsing the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016-09/30/2023 for the HCV analysis and between 12/01/2019-09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs. HCV-) and DCD (vs. brain death[DBD]) transplants, we compared perioperative outcomes and post-transplant survival. ResultsOf 1,436 ACHD candidates from 01/01/2016-09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019-09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016-09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019-09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs. HCV-) and DCD (vs. DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. ConclusionsACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs.

Heart Transplantation After Donation After Circulatory Death: Early United States Experience

BackgroundGiven the renewed interest in heart transplantation after donation after circulatory death (DCD), a contemporary analysis of trends and longer-term survival is warranted. MethodsAdult heart transplant recipients (December 2019-September 2023) were identified in the Organ Procurement and Transplantation Network. Recipients were stratified as donation after brain death (DBD) or DCD. DCD procurements were further classified as direct procurement and perfusion (DCD-DPP) or normothermic regional perfusion (DCD-NRP), based on the declaration of death to cross-clamp interval (≥40 minutes DCD-NRP). The main outcome was posttransplant survival at 1 and 3 years. ResultsOf 11,625 transplantations, 792 (7%) involved DCD allografts (249 DCD-NRP, 543 DCD-DPP). The proportion of transplants involving DCD allografts significantly increased from 2% (December 2019) to 11% (January-September 2023, P < .001). Upon adjusted analysis, 1-year posttransplant survival was similar for DBD vs DCD-DPP (hazard ratio [HR], 1.00; 95% CI, 0.66-1.66) or DCD-NRP (HR, 0.92; 95% CI, 0.49-1.72). This remained true at 3 years for DCD-DPP (HR, 1.07; 95% CI, 0.77-1.48) and DCD-NRP (HR, 1.04; 95% CI, 0.62-1.73). Incidence of postoperative stroke, dialysis, acute graft rejection, and primary graft dysfunction were similar across groups. Across various strata of recipient risk and center volume, survival was equivalent between the DBD and DCD cohorts. ConclusionsRates of DCD heart transplantation continue to rise. Across various recipient risk and center volume categories, DCD and DBD recipients show comparable posttransplant survival up to 3 years. These findings encourage broader use of such donors in attempts to expand the organ pool.

Normothermic Ex Vivo Heart Perfusion With Exosomes From Human Umbilical Cord Mesenchymal Stem Cells Improves Graft Function in Donation After Circulatory Death Hearts.

This study aimed to investigate the cardioprotective effect of exosomes derived from human umbilical cord mesenchymal stem cells on donation after circulatory death (DCD) hearts preserved with normothermic ex vivo heart perfusion (EVHP) in a rat heart transplantation model. Thirty-two male Lewis rats were divided into 2 groups: the control group and the exosome group. The donor-heart rats were subjected to the DCD procedure by suffering a 15-min warm ischemia injury, subsequently preserved with EVHP for 90 min, and then transplanted into recipients via abdominal heterotopic heart transplantation. Vehicle or exosome was added into the perfusate of normothermic EVHP in the control or exosome group. We evaluated left ventricular graft function, myocardial inflammation, and myocardial apoptosis of the donor heart 1.5 h after heart transplantation. Furthermore, we investigate the alternation of myocardial gene expression in the donor hearts between both groups by transcriptome sequencing. The treatment with exosome significantly enhanced cardiac function through increasing left ventricular developed pressure, dp/dtmax, and dp/dtmin of DCD hearts at 90 min after heart transplantation compared with the control group. The myocardial cells in the exosome group exhibited an orderly arrangement without obvious edema. Furthermore, exosome added into perfusate in the exosome group significantly attenuated the level of inflammatory response and apoptosis. Transcriptome sequencing and RT-qPCR showed the phosphoinositide 3-kinase/protein kinase B pathway was activated after exosome treatment. Normothermic EVHP combined with exosome can be a promising and novel DCD heart preservation strategy, alleviating myocardial ischemia-reperfusion injury in the DCD heart.

Metabolic Considerations in Direct Procurement and Perfusion Protocols with DCD Heart Transplantation.

Heart transplantation with donation after circulatory death (DCD) provides excellent patient outcomes and increases donor heart availability. However, unlike conventional grafts obtained through donation after brain death, DCD cardiac grafts are not only exposed to warm, unprotected ischemia, but also to a potentially damaging pre-ischemic phase after withdrawal of life-sustaining therapy (WLST). In this review, we aim to bring together knowledge about changes in cardiac energy metabolism and its regulation that occur in DCD donors during WLST, circulatory arrest, and following the onset of warm ischemia. Acute metabolic, hemodynamic, and biochemical changes in the DCD donor expose hearts to high circulating catecholamines, hypoxia, and warm ischemia, all of which can negatively impact the heart. Further metabolic changes and cellular damage occur with reperfusion. The altered energy substrate availability prior to organ procurement likely plays an important role in graft quality and post-ischemic cardiac recovery. These aspects should, therefore, be considered in clinical protocols, as well as in pre-clinical DCD models. Notably, interventions prior to graft procurement are limited for ethical reasons in DCD donors; thus, it is important to understand these mechanisms to optimize conditions during initial reperfusion in concert with graft evaluation and re-evaluation for the purpose of tailoring and adjusting therapies and ensuring optimal graft quality for transplantation.

Outcomes of Heart Transplantation From Donation After Circulatory Death: An Up-to-Date Systematic Meta-analysis.

Donation after circulatory death (DCD) heart transplantation (HTx) significantly expands the donor pool and reduces waitlist mortality. However, high-level evidence-based data on its safety and effectiveness are lacking. This meta-analysis aimed to compare the outcomes between DCD and donation after brain death (DBD) HTxs. Databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, were systematically searched for randomized controlled trials and observational studies reporting the outcomes of DCD and DBD HTxs published from 2014 onward. The data were pooled using random-effects models. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the summary measures for categorical outcomes and mean differences were used for continuous outcomes. Twelve eligible studies were included in the meta-analysis. DCD HTx was associated with lower 1-y mortality rate (DCD 8.13% versus DBD 10.24%; RR = 0.75; 95% CI, 0.59-0.96; P = 0.02) and 5-y mortality rate (DCD 14.61% versus DBD 20.57%; RR = 0.72; 95% CI, 0.54-0.97; P = 0.03) compared with DBD HTx. Using the current DCD criteria, HTx emerges as a promising alternative to DBD transplantation. The safety and feasibility of DCD hearts deserve further exploration and investigation.

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.

Impact of Hemoglobin Level in Ex Vivo Heart Perfusion on Donation After Circulatory Death Hearts: A Juvenile Porcine Experimental Model.

Ex vivo heart perfusion (EVHP) of donation after circulatory death (DCD) hearts has become an effective strategy in adults; however, the small circulating volume in pediatrics poses the challenge of a low-hemoglobin (Hb) perfusate. We aimed to determine the impact of perfusate Hb levels during EVHP on DCD hearts using a juvenile porcine model. Sixteen DCD piglet hearts (11-14 kg) were reperfused for 4 h in unloaded mode followed by working mode. Metabolism, cardiac function, and cell damage were compared between the low-Hb (Hb, 5.0-5.9 g/dL; n = 8) and control (Hb, 7.5-8.4 g/dL; n = 8) groups. Between-group differences were evaluated using 2-sample t-tests or Fisher's Exact tests. During unloaded mode, the low-Hb group showed lower myocardial oxygen consumption (P < 0.001), a higher arterial lactate level (P = 0.001), and worse systolic ventricular function (P < 0.001). During working mode, the low-Hb group had a lower cardiac output (mean, 71% versus 106% of normal cardiac output, P = 0.010) and a higher arterial lactate level (P = 0.031). Adjusted cardiac troponin-I (P = 0.112) did not differ between the groups. Morphological myocyte injury in the left ventricle was more severe in the low-Hb group (P = 0.028). Low-Hb perfusate with inadequate oxygen delivery induced anaerobic metabolism, resulting in suboptimal DCD heart recovery and declined cardiac function. Arranging an optimal perfusate is crucial to organ protection, and further endeavors to refine the priming volume of EVHP or the transfusion strategy are required.

HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.

Protection of the coronary arteries during donor heart maintenance is pivotal to improve results and prevent the development of coronary allograft vasculopathy. The effect of hypothermic, oxygenated perfusion (HOP) with the traditional HTK and the novel HTK-N solution on the coronary microvasculature of donation-after-circulatory-death (DCD) hearts is known. However, the effect on the coronary macrovasculature is unknown. Thus, we maintained porcine DCD hearts by HOP with HTK or HTK-N for 4 h, followed by transplantation-equivalent reperfusion with blood for 2 h. Then, we removed the left anterior descending coronary artery (LAD) and compared the endothelial-dependent and -independent vasomotor function of both groups using bradykinin and sodium-nitroprusside (SNP). We also determined the transcriptome of LAD samples using microarrays. The endothelial-dependent relaxation was significantly better after HOP with HTK-N. The endothelial-independent relaxation was comparable between both groups. In total, 257 genes were expressed higher, and 668 genes were expressed lower in the HTK-N group. Upregulated genes/pathways were involved in endothelial and vascular smooth muscle cell preservation and heart development. Downregulated genes were related to ischemia/reperfusion injury, oxidative stress, mitochondrion organization, and immune reaction. The novel HTK-N solution preserves the endothelial function of DCD heart coronary arteries more effectively than traditional HTK.

Transcriptomic Changes in the Myocardium and Coronary Artery of Donation after Circulatory Death Hearts following Ex Vivo Machine Perfusion.

Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine-tryptophane-ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.

NADPH oxidase overexpression and mitochondrial OxPhos impairment are more profound in human hearts donated after circulatory death than brain death.

This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups (n = 6) based on different WITs (20, 40, and 60 min). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 h. Left ventricular biopsies were performed at hours 0, 2, 4, and 6. Cardiac stress [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: 47-kDa protein of phagocyte oxidase (p47phox), 91-kDa glycoprotein of phagocyte oxidase (gp91phox)] and mitochondrial oxidative phosphorylation [OxPhos, complex I (NADH dehydrogenase) subunit of ETC (CI)-complex V (ATP synthase) subunit of ETC (CV)] proteins were measured in cardiac tissue and mitochondria respectively. Modulation of cardiac stress and mitochondrial dysfunction were observed in both DCD and DBD hearts. However, DCD hearts suffered more cardiac stress (overexpressed NADPH oxidase subunits) and diminished mitochondrial OxPhos than DBD hearts. The severity of cardiac stress and impaired oxidative phosphorylation in DCD hearts correlated with the longer WIT and subsequent cold storage time. More drastic changes were evident in DCD hearts with a WIT of 60 min or more. Activation of NADPH oxidase via overproduction of p47phox and gp91phox proteins in cardiac tissue may be responsible for cardiac stress leading to diminished mitochondrial oxidative phosphorylation. These protein changes can be used as biomarkers for myocardium damage and might help assess DCD and DBD heart transplant suitability.NEW & NOTEWORTHY First human DCD heart research studied cardiac stress and mitochondrial dysfunction concerning WIT and the efficacy of del Nido cardioplegia as an organ procurement solution and subsequent cold storage. Mild to moderate cardiac stress and mitochondrial dysfunction were noticed in DCD hearts with WIT 20 and 40 min and cold storage for 4 and 2 h, respectively. These changes can serve as biomarkers, allowing interventions to preserve mitochondria and extend WIT in DCD hearts.

Abstract 16801: Effect of Cyclosporine A on Infarct Size in Rat Hearts Donated After Circulatory Death

Introduction: Ischemia-reperfusion injury (IRI) is inherent in heart donation after circulatory death (DCD), hence only hearts with &lt;30 minutes of ischemia are used for transplantation. Mitochondrial permeability-transition pore (MPTP) opening has been implicated in IRI. Cyclosporine A (CyA) is known to inhibit MPTP opening. No data on infarct size reduction with CyA exists in a DCD heart. Hypothesis: CyA given during reperfusion will reduce infarct size in DCD hearts. Methods: Male Sprague-Dawley rats were assigned to either DCD + CyA, DCD + vehicle, or control-beating heart donors (CBD) (n=10 per group). Rats were anesthetized with pentobarbital, intubated and ventilated. Vecuronium and heparin were given for muscle paralysis and anticoagulation respectively. For DCD group, ventilation was terminated (start of anoxia/ischemia time), and hearts procured after 5, 10, 15, 20, 25 minutes. CBD hearts were procured without ischemia. Hearts were then perfused on a Langendorff setup for 90 minutes. Vehicle and CyA groups received DMSO and CyA (2μM) in KH buffer, respectively, for first 15 minutes followed by 75 minutes of KH buffer. Developed pressure (DP) was measured via a balloon tip catheter placed in the left ventricle. Infarct size was measured using triphenyltetrazolium chloride staining. CBD hearts perfused with KH buffer only served as controls. Results: Percent infarct size following 5, 10, 15, 20, and 25 minutes of ischemia was 17.7 ± 4, 19.3 ± 6, 25 ± 4, 27.3 ± 3, and 25.4 ± 11 respectively. CyA given to 25 minutes ischemia group reduced infarct size to 14.7%, corresponding to 6 minutes of ischemia. At 60 minutes CyA treated hearts had higher DP (mmHg) compared to vehicle group (34 ± 13 vs. 51 ± 17, p=0.017 ). Conclusions: CyA given during reperfusion to DCD hearts significantly reduced infarct size and preserved function. CyA use may allow for longer ischemia times during DCD heart procurement.

Cardioprotective effect of Interleukin-11 against warm ischemia-reperfusion injury in a rat heart donor model

Shortage of donor organs for heart transplantation is a worldwide problem. Donation after circulatory death (DCD) has been proposed to expand the donor pool. However, in contrast to the donation after brain death that undergoes immediate cold preservation, warm ischemia and subsequent reperfusion injury are inevitable in DCD. It has been reported that interleukin-11 (IL-11) mitigates ischemia-reperfusion injury in rodent models of myocardial infarction and donation after brain death heart transplantation. We hypothesized that IL-11 also offers benefit to warm ischemia in an experimental model of cardiac transplantation that resembles DCD. The hearts of naïve male Sprague Dawley rats (n = 15/group) were procured, subjected to 25-min warm ischemia, and reperfused for 60 min using Langendorff apparatus. IL-11 or saline was administered intravenously before the procurement, added to maintenance buffer, and infused via perfusion during reperfusion. IL-11 group exhibited significantly better cardiac function post-reperfusion. Severely damaged mitochondria was found in the electron microscopic analysis of control hearts whereas the mitochondrial structure was better preserved in the IL-11 treated hearts. Immunoblot analysis using neonatal rat cardiomyocytes revealed increased signal transducer and activator of transcription 3 (STAT3) phosphorylation at Ser727 after IL-11 treatment, suggesting its role in mitochondrial protection. Consistent with expected activation of mitochondrial respiration by mitochondrial STAT3, immunohistochemical staining demonstrated a higher mitochondrial cytochrome c oxidase subunit 2 expression. In summary, IL-11 protects the heart from warm ischemia reperfusion injury by alleviating mitochondrial injury and could be a viable therapeutic option for DCD heart transplantation.

Outcomes of Heart Transplant Donation After Circulatory Death

BackgroundHeart transplantation using donation after circulatory death (DCD) allografts is increasingly common, expanding the donor pool and reducing transplant wait times. However, data remain limited on clinical outcomes. ObjectivesWe sought to compare 6-month and 1-year clinical outcomes between recipients of DCD hearts, most of them recovered with the use of normothermic regional perfusion (NRP), and recipients of donation after brain death (DBD) hearts. MethodsWe conducted a single-center retrospective observational study of all adult heart-only transplants from January 2020 to January 2023. Recipient and donor data were abstracted from medical records and the United Network for Organ Sharing registry, respectively. Survival analysis and Cox regression were used to compare the groups. ResultsDuring the study period, 385 adults (median age 57.4 years [IQR: 48.0-63.7 years]) underwent heart-only transplantation, including 122 (32%) from DCD donors, 83% of which were recovered with the use of NRP. DCD donors were younger and had fewer comorbidities than DBD donors. DCD recipients were less often hospitalized before transplantation and less likely to require pretransplantation temporary mechanical circulatory support compared with DBD recipients. There were no significant differences between groups in 1-year survival, incidence of severe primary graft dysfunction, treated rejection during the first year, or likelihood of cardiac allograft vasculopathy at 1 year after transplantation. ConclusionsIn the largest single-center comparison of DCD and DBD heart transplantations to date, outcomes among DCD recipients are noninferior to those of DBD recipients. This study adds to the published data supporting DCD donors as a safe means to expand the heart donor pool.

Myocardial edema, inflammation, and injury in human heart donated after circulatory death are sensitive to warm ischemia and subsequent cold storage

BackgroundSingle-dose del Nido solution was recently used in human donation after circulatory death (DCD) heart procurement. We compared the effect of del Nido cardioplegia on myocardial edema, inflammatory response, and injury in human DCD hearts and human donation after brain death (DBD) hearts with different warm ischemic times (WIT) and subsequent cold saline storage times (CST). MethodsA total of 24 human hearts, including 6 in the DBD group and 18 in the DCD group—were procured for the research study. The DCD group was divided into 3 subgroups based on WIT: 20, 40, and ≥60 minutes. All hearts received 1 L of del Nido cardioplegia before being placed in cold saline for 6 hours. Left ventricular biopsies were performed at 0, 2, 4, and 6 hours. Temporal changes in myocardial edema, inflammatory cytokines (TNF-α, IL-6, and IL-1β), and histopathology injury scores were compared between the DBD and DCD groups. ResultsDCD hearts showed more profound changes in myocardial edema, inflammation, and injury than DBD hearts at baseline and subsequent CST. The DCD heart with WIT of 20 and 40 minutes with CST of 4 and 2 hours, respectively, appeared to have limited myocardial edema, inflammation, and injury. DCD hearts with WIT ≥60 minutes showed severe myocardial edema, inflammation, and injury at baseline and subsequent CST. ConclusionsSingle-dose cold del Nido cardioplegia and subsequent cold normal saline storage can preserve both DCD and DBD hearts. DCD hearts have been shown to be able to tolerate a WIT of 20 minutes and subsequent CST of 4 hours without experiencing significant myocardial edema, inflammation, and injury.

Utilization of Paragonix Sherpapak Cardiac Transport System for the Preservation of Donor Hearts After Circulatory Death

Donation after circulatory death (DCD) heart transplantation is being increasingly adopted by transplant centers. The optimal method of DCD heart preservation during transport after in situ thoracoabdominal normothermic regional perfusion (TA-NRP) is not known. We evaluated our experience with the Paragonix SherpaPak Cardiac Transport System (SCTS) for the transport of DCD cardiac allografts after TA-NRP recovery between January 2021 and December 2022. We collected and evaluated donor characteristics, allograft ischemic intervals, and recipient baseline demographic and clinical variables, and short-term outcomes. Twelve recipients received DCD grafts recovered with TA-NRP and transported in SCTS during the study period. The median age of 10 male and 2 female donors was 32 years (min 15, max 38). The median duration of functional warm ischemia was 12 minutes (min 8, max 22). Hearts were preserved in SCTS for a median of 158 minutes (min 37, max 224). Median recipient age was 61 years (min 28, max 70). Ten recipients (83%) survived to hospital discharge, with one death attributable to graft dysfunction (8%). The median vasoactive-inotropic (VIS) score at 72 hours post-transplantation of the entire cohort was 6 (min 0, max 15). The median length of intensive care unit stay in hospital survivors was 5 days (min 3, max 17) days and hospital stay 17 days (min 9, max 37). The Paragonix SCTS provides efficacious preservation of DCD grafts for ≥3.5 hours. Organs transported with this device showed satisfactory post-transplantation function.

Donation after circulatory death improves probability of heart transplantation in waitlisted candidates and results in post-transplant outcomes similar to those achieved with brain-dead donors

ObjectiveTo quantitate the impact of heart donation after circulatory death (DCD) donor utilization on both waitlist and post-transplant outcomes in the United States. MethodsThe United Network for Organ Sharing database was queried to identify all adult waitlisted and transplanted candidates between October 18, 2018, and December 31, 2022. Waitlisted candidates were stratified according to whether they had been approved for donation after brain death (DBD) offers only or also approved for DCD offers. The cumulative incidence of transplantation was compared between the 2 cohorts. In a post-transplant analysis, 1-year post-transplant survival was compared between unmatched and propensity-score-matched cohorts of DBD and DCD recipients. ResultsA total of 14,803 candidates were waitlisted, including 12,287 approved for DBD donors only and 2516 approved for DCD donors. Overall, DCD approval was associated with an increased sub-hazard ratio (HR) for transplantation and a lower sub-HR for delisting owing to death/deterioration after risk adjustment. In a subgroup analysis, candidates with blood type B and status 4 designation received the greatest benefit from DCD approval. A total of 12,238 recipients underwent transplantation, 11,636 with DBD hearts and 602 with DCD hearts. Median waitlist times were significantly shorter for status 3 and status 4 recipients receiving DCD hearts. One-year post-transplant survival was comparable between unmatched and propensity score–matched cohorts of DBD and DCD recipients. ConclusionsThe use of DCD hearts confers a higher probability of transplantation and a lower incidence of death/deterioration while on the waitlist, particularly among certain subpopulations such as status 4 candidates. Importantly, the use of DCD donors results in similar post-transplant survival as DBD donors.

Reality of DCD donor use in pediatric thoracic transplantation in the United States

In the US, the first pediatric donation after circulatory death (DCD) thoracic transplant was done in 2004; however, ethical controversy led to minimal utilization of these donors. The present study was performed to characterize the current state of pediatric DCD heart and lung transplantation (HTx, LTx). Children (<18year old) who underwent HTx or LTx using DCD donors from June 2004 to June 2022 were identified in the United Network for Organ Sharing registry. A total of 14 DCD recipients were identified: 7 (50%) HTx and 7 (50%) LTx. Donor and recipient demographics are described in Table 1. One and 5-year post-transplant survival were as follows: HTx recipients (64% for each) and LTx recipients (86%, 55%). Although often discussed, the national experience with DCD donors for pediatric HTx and LTx remains limited and not being practiced consistently by any pediatric program. Given the critical organ shortage, DCD use in the field of pediatric thoracic transplantation should be strongly considered.

Donor utilization in heart transplant with donation after circulatory death in the United States

Heart transplantation using donation after circulatory death (DCD) was recently adopted in the United States. This study aimed to characterize organ yield from adult (≥18 years) DCD heart donors in the United States using the United Network for Organ Sharing registry. The registry does not identify potential donors who do not progress to circulatory death, and only those who progressed to death were included for analysis. Outcomes included organ recovery from the donor operating room and organ utilization for transplant. Multiple logistic regression was used to identify predictors of heart recovery and utilization. Among 558 DCD procurements, recovery occurred in 89.6%, and 92.5% of recovered hearts were utilized for transplant. Of 506 DCD procurements with available data, 65.0% were classified as direct procurement and perfusion and 35.0% were classified as normothermic regional perfusion (NRP). Logistic regression identified that NRP, shorter agonal time, younger donor age, and highest volume of organ procurement organizations were independently associated with increased odds for heart recovery. NRP independently predicted heart utilization after recovery. DCD heart utilization in the United States is satisfactory and consistent with international experience. NRP procurements have a higher yield for DCD heart transplantation compared with direct procurement and perfusion, which may reflect differences in donor assessment and acceptance criteria.

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%.

Infarct Size With Incremental Global Myocardial Ischemia Times: Cyclosporine A in Donation After Circulatory Death Rat Hearts

We quantified the myocardial infarct size with varying global ischemia durations and studied the benefits of Cyclosporine A (CyA) in reducing cardiac injury in ex vivo and transplanted rat hearts. Infarct size was measured after 15, 20, 25, 30, and 35 minutes of in vivo global ischemia (n=34) and compared with control beating-heart donor (CBD) hearts (n=10). For heart function assessment, donation after circulatory death (DCD) rat hearts (n=20) were procured after 25 minutes of in vivo ischemia and reanimated ex vivo for 90 minutes. Half of the DCD hearts received CyA (0.5 mM) at reanimation. The CBD hearts (n=10) served as controls. A separate group of CBD and DCD (with or without CyA treatment) hearts underwent heterotopic heart transplantation; heart function was measured at 48 hours. Infarct size was 25% with 25 minutes of ischemia and increased significantly with 30 and 35 minutes to 32% and 41%, respectively. CyA treatment decreased infarct size in DCD hearts (15% vs 25%). Heart function in the transplanted DCD hearts was significantly better with CyA treatment and was comparable to CBD hearts. CyA administered at reperfusion limited infarct size in DCD hearts and improved their function in transplanted hearts.