Scarcity Of Donors Research Articles

Patient selection for heart transplant: balancing risk.

Heart failure incidence continues to rise despite a relatively static number of available donor hearts. Selecting an appropriate heart transplant candidate requires evaluation of numerous factors to balance patient benefit while maximizing the utility of scarce donor hearts. Recent research has provided new insights into refining recipient risk assessment, providing additional tools to further define and balance risk when considering heart transplantation. Recent publications have developed models to assist in risk stratifying potential heart transplant recipients based on cardiac and noncardiac factors. These studies provide additional tools to assist clinicians in balancing individual risk and benefit of heart transplantation in the context of a limited donor organ supply. The primary goal of heart transplantation is to improve survival and maximize quality of life. To meet this goal, a careful assessment of patient-specific risks is essential. The optimal approach to patient selection relies on integrating recent prognostication models with a multifactorial assessment of established clinical characteristics, comorbidities and psychosocial factors.

402.1: Towards a GMP-Compliant Protocol for the Differentiation of Human Pluripotent Stem Cells to Beta-like Cells for the Treatment of Type 1 Diabetes

Background: β-cell replacement therapy by allogeneic pancreas or islet transplantation is a promising approach for patients with type 1 diabetes. However, there is a scarcity of organ donors. The generation of insulin-producing pancreatic β-cells from human pluripotent stem cells (hPSC) in vitro would provide an unlimited cell source for drug discovery and cell replacement therapy for diabetes. Here we aim to generate β-cells under GMP (Good Manufacturing Practice)-compliant conditions that can be used for clinical application. Methods: We applied a modified seven-stage (30-day) differentiation protocol to generate hPSC-derived insulin-producing β-like cells in a 3D microwell culture system. Next, in order to scale up the production of hPSC-derived β-cells, we adapted the protocol to spinner flask culture. Differentiation was assessed by qPCR, immunocytochemistry and flowcytometry for stage-specific marker expression. β-cell function was evaluated in vitro by GSIS (Glucose-Stimulated Insulin Secretion), and in vivo by intraperitoneal glucose tolerance tests after transplantation of stage-7 cell clusters in immunodeficient mice and human C-peptide secretion was determined by ELISA. Results: In the microwell set-up, cells acquired a definitive endoderm phenotype at stage 1 (day 3), characterized by expression of SOX17 (87.2% ± 4.6; n=5), FOXA2 (82.8% ± 4.6; n=3), co-expression of c-KIT and CXCR4 (93.3% ± 5.6; n=4), and silencing of pluripotency marker OCT4 (2.8% ± 6; n=5). At the end of stage 4 (day 12), pancreatic progenitor cells were identified by the co-expression of PDX1/NKX6.1 (46.7% ± 3.5; n=3). Finally, at the end of stage 7 (day 30), C-peptide-positive β-like cells (49.5% ± 10.5; n=3) and glucagon-positive α-like cells (18.4%± 6.1; n=3) were present. The stimulation index upon exposure to glucose was 4.4 ± 3.1(n=5). Following transplantation of day-30 clusters into mice, stimulated human C-peptide levels reached 46 pmol/L (n=21), 70.5 pmol/L (n=19) and 327.4 pmol/L (n=11) at day 14, 28 and 60 respectively, indicating further maturation of the cells in vivo after transplantation. Next, we scaled up the cell culture in disposable spinner flasks, and obtained comparable differentiation efficiency. Conclusion: We can generate functional hPSCs-derived β-like cells in GMP-compliant conditions in vitro. We will apply these protocols on a clinical-grade PSC line that is currently in expansion (banking) in the GMP facility of our institute. hPSCs-derived β-like cells are a promising future alternative to donor islets for the treatment of type 1 diabetes.

Patients with kidney failure who cannot access dialysis in rural and remote areas of Canada should be prioritized for kidney transplantation.

KEY POINTS Kidney transplantation costs less than dialysis[1][1] and is associated with improved survival and quality of life[2][2] for patients with kidney failure. In Canada, systems for allocating kidney transplants from deceased donors typically aim to maximize the utility of scarce donor organs

Rapid and Safe T Cell Immune Reconstitution By T Cell Progenitor Injection Following Haploidentical Transplantation for Severe Combined Immunodeficiency (SCID)

Severe Combined Immunodeficiencies (SCID) are defined by a complete absence of T lymphocytes in the blood and lymphoid organs, with variable defects in other WBC subsets depending on the gene defect. From a clinical perspective SCIDs are characterized by early development of life-threatening infections accounting for early death if untreated. The treatment of choice is allogeneic HSCT with very high success rates if a HLA identical sibling (MRD) or unrelated donor (MUD) is used. However, due to the scarcity of matched-related donors, SCID can benefit from haploidentical HSCT. In contrast to the continuous improvement of HLA compatible donor transplantations, no significant improvements have been obtained over the last twenty years for haploidentical HSCT. The profound immunodeficiency during the first months following haploidentical HSCT exposes patients to opportunistic viral, bacterial and fungal infections, which account for approximately 30-40% of the transplant related mortality (TRM). The rapid restoration of the T-cell compartment is the main aim of stem cell therapy in this setting. To this end we have recently set up a phase I/II clinical trial (ClinicalTrials.gov Identifier: NCT03879876) aiming to accelerate the immune reconstitution by injection of ex vivo generated Human T lymphoid progenitors (ProTcell TM) following haploidentical HSCT. T cell progenitors in this trial are generated in vitro within 7 days from mobilized peripheral blood (mPB) CD34 + hematopoietic stem and precursor cells (HSPCs) using our Notch ligand Delta-like 4 GMP culture platform so called SMART Immune's SMART101 product.This open-label, non-randomized study evaluates safety and efficacy of the SMART101 injection following CD34 + selected, haploidentical HSCT in SCID patients and is designed as a dose-escalation study comprising 6 doses of the SMART101 product obtained from the patient's haploidentical stem cell graft. The aim of this protocol is to define the highest efficacy dose without any toxicity.The conditioning regimen is based on Busulfan and Fludarabine according to IE-WP/EBMT guidelines with upfront administration of ATG to prevent graft rejection. Tight monitoring of ATG serum levels is applied in order to assure injection of SMART101 when ATG is below the lymphotoxicity threshold.Here we report the results of the first two SCID patients. P1 presented a homozygous Artemis deficiency. At diagnosis he had an ALC of 341/µl, with complete absence of T cells (CD3 + < 4/µl, CD4 + < 1/µl, CD8 + < 2/µl) and B cells (CD19 + 0/µl). NK cells were present in the normal range for age (CD16 +CD56 + 331/µl).In the absence of an HLA compatible donor, the patient's father was chosen as haploidentical stem cell donor.P1 received upfront ATG (5 mg /kg total dose), Busulfan (AUC of 16058 microM.min) and Fludarabine (160 mg/m²). He received Defibrotide prophylaxis from D0 until D+21, as well as Ursodeoxycholic acid until D+80. The CD34 + immunoselected graft contained 1.04 x 10 8 nucleated cells/kg with 24.15 x10 6 CD34 + cells/kg and 4000 CD3 + cells/kg on D0. After ATG monitoring 0.12x10 6 Smart101 cells were administered at D+14 post- HSCT.In the follow-up P1 didn't develop any acute or chronic SAEs, no acute or chronic GVHD, and no infection. He was discharged at D+121 post HSCT.The day +100 post transplantation CD4 + cell count/microliter exceeded 10 times the CD4 + count of our historical cohort of RAG1/2 or Artemis deficient patients transplanted with haploidentical HSCT alone following the same conditioning regimen.At 6 months post HSCT this difference remains important (851 versus 300 CD4 + cells/µl); Ig replacement therapy could be stopped as early as 9 months post transplantation and vaccinations have been started. At last follow up; almost 14 months post HSCT P1 is alive and well.P2 had an undefined molecular SCID diagnosis. She has been treated with the same conditioning regimen and received the second dose of 0.2x10 6 CD7 + cells, but unfortunately died from severe VOD emphasizing the need to replace chemotherapy with less toxic myeloablative agents.The preliminary results obtained after injection of Human T lymphoid progenitors in P1 are encouraging. While deserving confirmation in larger numbers of patients they could represent an important step forward in improving the outcome of haploidentical HSCT for SCID. DisclosuresCavazzana: Smart Immune: Other: co-founder.

Intraoperative support during lung transplantation.

The role of intraoperative mechanical support during lung transplantation (LTx) is essential to provide a safe hemodynamic and ventilatory status during critical intraoperative events. This hemodynamic and ventilatory stability is vital to minimize the odds of suboptimal outcomes, especially considering that, due to the scarcity of donors and the fact that more and more patients with significant comorbidities are being considered for this therapy, a more aggressive approach is often needed by the transplant centers. Hence, the attenuation of any potential injury that can happen during this complex event is paramount. While a thorough assessment of the donor and optimization of postoperative care is pursued, certainly protective intraoperative management would also contribute to better outcomes. Understanding each patient’s underlying anatomy and cardiopulmonary physiology, associated with awareness of critical events during a complicated procedure like LTx, is essential for a precise indication and safe use of support. Cardiopulmonary bypass (CPB) and veno-arterial extracorporeal membrane oxygenation (VA ECMO) have been the most common approaches used, with the latter gaining popularity more recently and we have used VA ECMO exclusively for the last decade. New technologies certainly contributed to more liberal use of VA ECMO intraoperatively, enabling a protecting and physiologic environment for the newly implanted grafts. In this setting, potential prophylactic use for lung protection during a critical period is also considered.

The unnoticed truth: Patients on the heart transplantation waiting list are becoming cachexic

Heart transplantation is a major lifesaving surgery practiced globally on daily basis. The scarcity of donors has led to long waiting lists for the surgery. Both physiology and psychology of patients are affected severely during this period. The nutritional status is known to be correlated with postoperative outcomes. The aim of this study was to investigate the significance of the weight loss of patients by comparing their weights and ideal body weights. The data of 259 patients were used in this study and unpaired t-test was applied to the patient groups. The weight difference of the patient population was found as extremely significant (p&lt;0.0001). The results demonstrated that the weight difference of female patient group was very significant (p=0.0012) and the male patient group was extremely significant (p&lt;0.0001). The weight difference of young patients (18-34 years) was not significant (0.7309), middle aged patients (35-64 years) was extremely significant (p&lt;0.0001) and elderly patients (65 years and above) was not significant (p=0.3540). Therefore, weight change is prominent in most of the patients who are on heart transplantation waiting list. Employment of a dietitian or nutrition specialist to transplant multidisciplinary teams is advised, to minimize patient cachexia.

Intraperitoneal administration of human "Neo-Islets", 3-D organoids of mesenchymal stromal and pancreatic islet cells, normalizes blood glucose levels in streptozotocin-diabetic NOD/SCID mice: Significance for clinical trials.

Globally, individuals with autoimmune Type 1 diabetes mellitus (T1DM) continue to depend for survival on insulin injections. While pancreas and intrahepatic pancreatic islet transplants can produce insulin-independence and ameliorate serious complications, both therapies depend on potentially toxic anti-rejection drugs. Furthermore, the scarcity of pancreas donors and islet transplant failures limit the general availability of such interventions. Recently, fetal and induced Pluripotent Stem Cells have been successfully differentiated to generate insulin producing β-like cells that generate euglycemia in diabetic mice. However, their clinical use still depends on anti-rejection drugs or immune-isolating encapsulation systems. We reported recently that allogeneic “Neo-Islets” (NI), 3-D organoids of Mesenchymal Stromal and Islet Cells are immune protected and permanently correct autoimmune diabetes in NOD mice by omental engraftment and endocrine cell redifferentiation. This new “endocrine pancreas” delivers islet hormones physiologically into the hepatic portal vein. Furthermore, treatment of insulin-dependent dogs with allogeneic canine NIs (ongoing FDA-approved Pilot Study) consistently improved glycemic control without the need for antirejection drugs. As there remains a critical need for curative therapies of T1DM, we engineered human NIs and tested their ability, after i.p. administration, to reestablish euglycemia in streptozotocin (STZ)-diabetic NOD/SCID mice. This diabetes model reproduces, in part, the clinical situation in which recipients of allogeneic biotherapies must take potent anti-rejection drugs that similarly create a life-long immune-compromised status. The present study demonstrates that human NI therapy (2x10e5/kg bw NIs/mouse) of STZ-diabetic NOD/SCID mice (n = 6), compared to controls (n = 6) significantly improved glycemic control, and most importantly, that a second dose given to the initial group normalized blood glucose levels long-term. Conclusion: Despite the limitations of the utilized diabetic NOD/SCID mouse model, the obtained data show that human NIs are curative, an observation that has high translational relevance and significantly supports the planned conduct of clinical trials with human NIs.

The Role of Plasma Transfusion in Pre-Hospital Haemostatic Resuscitation.

Traumatic haemorrhage remains a major cause of preventable death and early haemostatic resuscitation is now a mainstay of treatment internationally. Recently, 2 randomized control trials (RCTs) - PAMPer (Prehospital Air Medical Plasma) and COMBAT (Control of Major Bleeding After Trauma), evaluating the effect of pre-hospital use of plasma on mortality provided conflicting results, raising important questions on the role of plasma resuscitation in pre-hospital environment. Both PAMPer (n=501 patients) and COMBAT (n=144 patients) trials were pragmatic RCTs that evaluated the effect of pre-hospital plasma transfusion (two units) versus standard of care on 28/30 days mortality in trauma patients who presented with clinical signs of haemorrhagic shock (defined as hypotension or tachycardia). The PAMPer trial showed that plasma transfusion reduced 30-day mortality compared with standard of care (23% vs 33%, 95% confidence interval -18.6; -1.0%; P=0.03), while COMBAT trial showed no difference in 28-day survival. The post-hoc analyses of the 2 trials have suggested that the benefit of pre-hospital plasma transfusion may be greater for patients who are coagulopathic, have blunt injury and have a transport time from the scene of injury to the hospital of >20 minutes. In this review we evaluate strengths and limitations of the two trials and their differences and similarities, which may explain the conflicting results, as well as provide directions for future trials to better define the target population that would most benefit from pre-hospital plasma resuscitation. Further, considering the logistical challenges of carrying any blood components on an aircraft, cost/safety of plasma, and the scarcity of universal blood group donors, there is a need for a health economic evaluation of pre-hospital plasma transfusion in trauma patients, prior to this intervention becoming universal.

Emerging roles of left ventricular assist device therapy as bridge to transplant in an Asian city with scarce heart transplant donor.

BackgroundLeft ventricular assist device (LVAD) has been increasingly used in patients with advanced heart failure. This study aimed to assess the impact of implementation of LVAD therapy on heart transplantation (HTx) service in Hong Kong (HK).MethodsLVAD program was started in 2010 in HK and patients who had been put on HTx waiting list since the start of HTx program in HK from 1992 to 2020 were included for analysis. Survival on HTx waiting list between pre-LVAD era 1992–2009 and post-LVAD era 2010–2020 were analyzed by Kaplan-Meier method and compared by log-rank test. Multivariate analysis by time-dependent Cox-proportional hazard model was used to identify independent predictors of HTx waiting list mortality.ResultsA total of 478 heart transplant listing episodes involving 457 patients were included for analysis. There were 232 heart transplantations (HTxs), including one re-transplantation, during the study period. There were 110 patients who received LVAD as bridge to transplantation (BTT) and 30 of them had undergone subsequent HTx. The 1-, 2- and 3-year survival on waiting list were 82.3%, 61.7% and 43.0% respectively in the pre-LVAD era (n=178), while the 1-, 2- and 3-year survival were significantly improved at 85.7%, 81.8% and 78% respectively in the post-LVAD era (n=300), (P=0.003). Time-dependent multivariate analysis revealed that LVAD support was independently associated with significant reduction of waiting list mortality [odds ratio (OR): 0.21; 95% confidence interval (CI): 0.10–0.44, P<0.001]. There was no significant difference when comparing survival after LVAD as BTT and survival after HTx up to 8 years (76.1% vs. 72% at 8 years respectively, P=0.732).ConclusionsWaiting list survival improved in the post-LVAD era driven by the implementation of LVAD service. Long-term survival for LVAD recipients as BTT were comparable to heart transplant recipients in HK.

Stem cells' centrosomes: How can organelles identified 130 years ago contribute to the future of regenerative medicine?

At the core of regenerative medicine lies the expectation of repair or replacement of damaged tissues or whole organs. Donor scarcity and transplant rejection are major obstacles, and exactly the obstacles that stem cell‐based therapy promises to overcome. These therapies demand a comprehensive understanding of the asymmetric division of stem cells, i.e. their ability to produce cells with identical potency or differentiated cells. It is believed that with better understanding, researchers will be able to direct stem cell differentiation. Here, we describe extraordinary advances in manipulating stem cell fate that show that we need to focus on the centrosome and the centrosome-derived primary cilium. This belief comes from the fact that this organelle is the vehicle that coordinates the asymmetric division of stem cells. This is supported by studies that report the significant role of the centrosome/cilium in orchestrating signaling pathways that dictate stem cell fate. We anticipate that there is sufficient evidence to place this organelle at the center of efforts that will shape the future of regenerative medicine.

Liver Transplantation in Patients with Acute-onChronic Liver Failure: Challenging the Limits

Acute-on-chronic liver failure (ACLF) is one of the main causes of death on the waiting list. Liver transplantation (LT) is the only curative treatment for patients with ACLF and therefore it should be considered in all cases. However, the applicability of LT in patients with ACLF is challenging, given the scarcity of donors and the high short-term mortality of these patients. Organ allocation has traditionally been prioritised according to the model for end-stage liver disease (MELD) system. However, the accuracy of MELD score is limited in patients with ACLF. In this article, the authors review the outcomes of patients with ACLF before and after LT, highlighting its clinical course, the feasibility of LT in the sickest patients, the role of the organ allocation system, and possible indicators of futility.

Cost-effectiveness and system-wide impact of using Hepatitis C-viremic donors for heart transplant

The advent of direct-acting antiviral therapy for Hepatitis C (HCV) has made using HCV-viremic donors a viable strategy to address the donor shortage in heart transplantation. We employed a large-scale simulation to evaluate the impact and cost-effectiveness of using HCV-viremic donors for heart transplant. We simulated detailed histories from time of listing until death for the real-world cohort of all adults listed for heart transplant in the United States from July 2014 to June 2019 (n=19,346). This population was imputed using historical data and captures "real-world" heterogeneity in geographic and clinical characteristics. We estimated the impact of an intervention in which all candidates accept HCV+ potential donors (n=472) on transplant volume, waitlist outcomes, and lifetime costs and quality-adjusted life years (QALYs). The intervention produced 232 more transplants, 132 fewer delistings due to deterioration, and 50 fewer waitlist deaths within this 5-year cohort and reduced wait times by 3% to 11% (varying by priority status). The intervention was cost-effective, adding an average of 0.08 QALYs per patient at a cost of $124 million ($81,892 per QALY). DAA therapy and HCV care combined account for 11% this cost, with the remainder due to higher costs of transplant procedures and routine post-transplant care. The impact on transplant volume varied by blood type and region and was correlated with donor-to-candidate ratio (ρ=0.71). Transplanting HCV+ donor hearts is likely to be cost-effective and improve waitlist outcomes, particularly in regions and subgroups experiencing high donor scarcity.

Using Two Compatible Donor Polymers Boosts the Efficiency of Ternary Organic Solar Cells to 17.7%

The use of ternary organic semiconducting blends is recognized as an effective strategy to boost the performance of polymer solar cells (PSCs) by increasing the photocurrent while minimizing voltage losses. Yet, the scarcity of suitable donors with a deep highest occupied molecular orbital (HOMO) level poses a challenge in extending this strategy to ternary systems based on two polymers. Here, we address this challenge by the synthesis of a new donor polymer (PM7-Si), which is akin to the well-known PM6 but has a deeper HOMO level. PM7-Si is utilized as the third component to enhance the performance of the best-in-class binary system of PM6:BTP-eC9, leading to simultaneous improvements in the efficiency (17.7%), open-circuit voltage (0.864 V), and fill factor (77.6%). These decisively enhanced features are attributed to the efficient carrier transport, improved stacking order, and morphology. Our results highlight the use of two polymer donors as a promising strategy toward high-performance ternary PSCs.

Bilateral lobar lung transplantation and a single lung transplantation using lungs from a single organ donor during coronavirus disease 2019 pandemic.

Bilateral lobar lung transplantation and a single lung transplantation using lungs from a single organ donor during coronavirus disease 2019 pandemic.

Maintaining an adequate sperm donor pool: modifying the medical criteria for sperm donor selection.

The shortage of donor sperm will increase due to greater access by lesbian couples and single women and due to extra rules imposed on sperm donation. Two steps should be distinguished in donor recruitment: an ethical phase where candidates are self-selecting on the basis of ethical rules, and a medical phase where criteria related to quality and safety of the sperm are imposed. The first phase functions as a bottle neck. Candidate donors who reject the ethical rules will not present themselves for donation in clinics and sperm banks. If the ethical rules remain unchanged, the medical rules that apply after the bottle neck should become less stringent if a sufficient number of donors are to be maintained. Lowering the sperm quality standards will lead to more IVF. Although this is regrettable, it will become unavoidable if the scarcity of donors increases.

The Surplus Transplant Lung Allocation System in Italy: An Evaluation of the Allocation Process via Stochastic Modeling.

Background: Lung transplantation is a specialized procedure used to treat chronic end-stage respiratory diseases. Due to the scarcity of lung donors, constructing fair and equitable lung transplant allocation methods is an issue that has been addressed with different strategies worldwide. This work aims to describe how Italy’s “national protocol for the management of surplus organs in all transplant programs” functions through an online app to allocate lung transplants. We have developed two probability models to describe the allocation process among the various transplant centers. An online app was then created. The first model considers conditional probabilities based on a protocol flowchart to compute the probability for each area and transplant center to receive each n-th organ in the period considered. The second probability model is based on the generalization of the binomial distribution to correlated binary variables, which is based on Bahadur’s representation, to compute the cumulative probability for each transplant center to receive at least nth organs. Our results show that the impact of the allocation of a surplus organ depends mostly on the region where the organ was donated. The discrepancies shown by our model may be explained by a discrepancy between the northern and southern regions in relation to the number of organs donated.

Design and Usability Evaluations of a 3D-Printed Implantable Drug Delivery Device for Acute Liver Failure in Preclinical Settings.

Acute liver failure (ALF) requiring liver transplantation is a disease that occurs due to rapid hepatocellular dysfunction. As liver transplantation has various limitations, including donor scarcity, high cost, and immuno-incompatibility, continuous local delivery of biopharmaceuticals to the liver tissue can be a promising ALF treatment option. Here, the in vivo safety and usability of a 3D-printed implantable drug delivery device for effective ALF treatment is evaluated. The implantable reservoir consists of a 3D-printed container and a semipermeable membrane for repeated administrations of drugs, specifically to the liver tissue. The physical stability and function of the 3D-printed reservoir are confirmed by the mechanical properties and in vitro drug release test, respectively. In mice implanted with the reservoir system, mortality, weight changes, clinical signs, hematological and serum biochemical changes, and organ weight changes are not observed, suggesting no foreign body reaction. The usability of the reservoir system is further evaluated using an ALF model of 70% hepatectomized mice treated with N-acetylcysteine through the system, showing cell-specific regeneration and significant liver injury alleviation. Overall, the 3D-printed reservoir system is safe for studying the therapeutic potential of ALF treatment, and it can be used for the delivery of various active pharmaceutical ingredients.

Diminished autonomy and justice in liver transplantation – The price of scarcity?

Patient autonomy and distributive justice are fundamental ethical principles that may be at risk in liver transplant units where decisions are dictated by the need to maximise the utility of scarce donor organs. The processes of patient selection, organ allocation and prioritisation on the wait list have evolved in a constrained environment, leading to high levels of complexity and low transparency. Regarding paternalism, opaque listing and allocation criteria, patient factors such as passivity, guilt, chronic illness and sub-clinical encephalopathy are cited as factors that may inhibit patient engagement. Regarding justice, established regional, gender and race based inequities are described. The paradox whereby hepatologists both advocate for individual patients and discharge their duty of stewardship to apportion organs according to larger utilitarian principles is explored. Competing subjective factors such as physicians’ perception of moral responsibility, the qualitative nature of expert medical assessment and institutional or personal loyalty to re-transplantation candidates are described. Realistic limits of self-determination and justice are discussed, and possible future directions in terms of patient involvement proposed.

Ethical and practical dilemmas in cardiac transplantation in infants: a literature review.

The waiting time in infants for a cardiac transplant remains high, due to the scarcity of donors. Consequently, waiting list morbidity and mortality are higher than those in other age groups. Therefore, the decision to list a small infant for cardiac transplantation is seen as an ethical dilemma by most physicians. This review aims to describe outcomes, limitations, and ethical considerations in infant heart transplantation. We used Medline and Embase as data sources. We searched for publications on infant (< 1 year) heart transplantation, bridge-to-transplant and long-term outcomes, and waiting list characteristics from January 2009 to March 2021. Outcome after cardiac transplant in infants is better than that in older children (1-year survival 88%), and complications are less frequent (25% CAV, 10% PTLD). The bridge-to-transplant period in infants is associated with increased mortality (32%) and decreased transplantation rate (43%). This is mainly due to MCS complications or the limited MCS options (with 51% mortality in infancy). Outcomes are worse for infants with CHD or in need of ECMO-support.Conclusion: Infants listed for cardiac transplantation have a high morbidity and mortality, especially in the period between diagnosis and transplantation. For those who receive cardiac transplant, the outlook is encouraging. Unfortunately, despite growing experience in VAD, mortality in children < 10 kg and children with CHD remains high. After transplantation, patients carry a psychological burden and there is a probability of re-transplantation later in life, with decreased outcomes compared to primary transplantation. These considerations are seen as an important ethical dilemma in many centers, when considering cardiac transplantation in infants (< 1 year). What is Known: • For infants, waitlist mortality remains high. In the pediatric population, MCS reduces the waiting list mortality. What is New: • Outcomes after infant cardiac transplantation are better than other age groups; however, MCS options remain limited, with persistently high waiting list mortality. • Future developments in MCS and alternative options to reduce waiting list mortality such as ABO-incompatible transplantation and pulmonary artery banding are encouraging and will improve ethical decision-making when an infant is in need of a cardiac transplant.

COST-EFFECTIVENESS AND SYSTEM-WIDE IMPACT OF USING HEPATITIS C-VIREMIC DONORS FOR HEART TRANSPLANT

Background The advent of direct-acting antiviral therapy for Hepatitis C (HCV) has made using HCV-viremic donors a viable strategy to address the donor shortage in heart transplantation . We employed a large-scale simulation to evaluate the impact and cost-effectiveness of using HCV-viremic donors for heart transplant . Methods We simulated detailed histories from time of listing until death for the real-world cohort of all adults listed for heart transplant in the United States from July 2014 to June 2019 (n = 19,346). This population was imputed using historical data and captures “real-world” heterogeneity in geographic and clinical characteristics. We estimated the impact of an intervention in which all candidates accept HCV+ potential donors (n = 472) on transplant volume, waitlist outcomes, and lifetime costs and quality-adjusted life years (QALYs). Results The intervention produced 232 more transplants, 132 fewer delistings due to deterioration, and 50 fewer waitlist deaths within this 5-year cohort and reduced wait times by 3% to 11% (varying by priority status). The intervention was cost-effective, adding an average of 0.08 QALYs per patient at a cost of $124 million ($81,892 per QALY). DAA therapy and HCV care combined account for 11% this cost, with the remainder due to higher costs of transplant procedures and routine post-transplant care. The impact on transplant volume varied by blood type and region and was correlated with donor-to-candidate ratio (ρ = 0.71). Conclusions Transplanting HCV+ donor hearts is likely to be cost-effective and improve waitlist outcomes, particularly in regions and subgroups experiencing high donor scarcity.