Donor Hearts Research Articles

Pediatric donor heart acceptance practices in the United States: What is really being considered?

Recent studies demonstrate high offer decline and organ non-utilization rates are associated with increased pediatric heart transplant waitlist mortality. We sought to determine which donor, candidate, and offer specific variables most importantly influenced these decisions using only data available at the time of each offer. Retrospective review of pediatric (<18 years) heart donor offers made to pediatric candidates in the United States between 2010 and 2020. In addition to standard donor, candidate, and offer data available in UNOS, we extracted objective and qualitative valvar and myocardial function data from all available donor echocardiogram reports. During the study period, 5625 pediatric donor hearts produced 30 156 offers to 4905 unique candidates, of which 88.7% of all offers were declined and 39.2% of organs were not utilized by pediatric waitlisted candidates. Of the 60.8% utilized hearts, 89.7% had a 'cumulatively' normal echocardiogram at the time of offer acceptance; 62.9% of hearts not utilized for a pediatric candidate also had a cumulatively normal final echocardiogram. Random forest and logistic regression modeling demonstrated good predictive performance (AUROC ≥0.83) of likelihood to accept when utilizing donor, candidate, and offer specific variables. SHAP variable importance scores demonstrated number of prior offer declines and candidate institution's prior year acceptance rates as the two most important variables influencing offer decisions. Behavioral economics appear to play a significant role in pediatric heart transplant candidate institutions' acceptance practices, even when considering the arguably healthier pediatric donor population. Removal of prior institution's decisions from DonorNet may help increase donor utilization.

Heart transplantation surgery in children and young adults with congenital heart disease

BackgroundPediatric cardiac transplantation remains a surgical challenge as a variety of cardiac and vessel malformation are present in patients with congenital heart disease (CHD). Despite limited availability and acceptability of donor hearts, the number of heart transplantations remains on a stable level with improved survival and quality of life.ObservationAs treatment options for CHD continue to improve and the chances of survival increase, more adult CHD patients are listed for transplantation. This review focuses on the clinical challenges and modified techniques of pediatric heart transplantations.ConclusionNot only knowledge of the exact anatomy, but above all careful planning, interdisciplinary cooperation and surgical experience are prerequisites for surgical success.

Donor Heart Preservation: Current Knowledge and the New Era of Machine Perfusion

Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.

Diagnostics of combined hereditary cardiovascular pathology in a teenager

Dilated cardiomyopathy is one of the leading causes of heart failure in children with a variety of clinical characteristics. A 12-year-old patient with dilated cardiomyopathy and heterozygous familial hypercholesterolemia, who underwent surgical treatment for implantation of the Abbott HeartMate III Left Ventricular Assist Device as a bridge to donor heart transplantation, is presented. Establishing an accurate diagnosis in the presented observation became possible thanks to the use of a modern molecular genetic method — whole genome DNA testing by next generation sequencing (NGS). The description of this case will help expand the range of possible clinical manifestations of dilated cardiomyopathy and reminds us of the importance of dynamic monitoring of children with cardiac arrhythmias.

Acceptance, Awareness, Attitude, and Practices Toward Heart Transplantation: A Saudi Based Survey.

The awareness of brain death and heart donation (HD) among the Saudi population remains limited, coupled with negative attitudes toward heart donation, resulting in a significant gap between the demand for donor hearts and the available supply. This study aimed to comprehensively understand the current perceptions, attitudes, and practices of the Saudi population regarding HD, as well as identify the obstacles. The ultimate goal was to strengthen the local donor pool. A cross-sectional study was conducted from March to May 2023, employing a self-administered internet survey. The survey collected demographic information, assessed awareness, attitudes, and practices related to HD, and was completed by 1820 participants from various regions in Saudi Arabia. Data was analyzed using SPSS version 25 (SPSS Inc., Chicago, Illinois, USA). Chi-square test, Independent-samples t-test, one way analysis of variance test (ANOVA) and Spearman correlation coefficient was performed with the significance level set at p < 0.05. A significant portion of the population (out of 1820 participants) lacked organ donation cards and were uncertain about the registration process. Participants displayed a moderate level of knowledge about HD, with roughly half holding unfavorable attitudes toward HD. A considerable percentage of participants 62.0% were unwilling to register as heart donors, but a majority (79.9%) were willing to contribute by disseminating information about HD. The study identified significant associations between knowledge scores and several factors, including age (p = 0.002), career (p = 0.000), possession of an organ donation card (p = 0.000), and a history of transplantation or organ donation among relatives (p = 0.000). A significant relationship was observed between attitude scores and several factors, including career (p = 0.001), Saudi region (p = 0.025), possession of an organ donation card (p = 0.000), and a history of transplantation or organ donation among relatives (p = 0.000). The study highlights the urgent need for increased awareness to bolster the number of local heart donors. The involvement of healthcare professionals and social campaigns is essential to enhance public knowledge and potentially boost the willingness of individuals to become donors.

Heart transplantation : Current situation

Heart transplantation is the gold-standard in the treatment of terminal heart failure. The shortage of donor hearts represents the major obstacle in patient care and necessitates the creation of waiting lists and allocation algorithms. The Transplantation Act regulates donor heart allocation according to the urgency and the prospects of success. Donor hearts can be implanted following the classical biatrial or the modern bicaval valve implantation technique with a slightly lower spectrum of complications. Modern mechanical perfusion systems enable extended transport times. After heart transplantation rejection reactions must be controlled by an individually adjusted immunosuppression to guarantee long-term survival with as few complications as possible.

Donor heart preconditioning during orthotopic transplantation

Background. To date, there are about 500 patients in the heart transplant waiting list in Ukraine. The study included 20 donors for orthotopic heart transplantation. Their average age was 32.3 years. The study evaluated the preparation of the donor heart in terms of its protection against ischemia-reperfusion injury during transplantation and the effect of donor heart preconditioning in a recipient after orthotopic heart transplantation. Тhe purpose was to evaluate the effectiveness of donor heart preconditioning for increasing myocardial resistance to ischemia-reperfusion injury and its preparation for orthotopic transplantation. Materials and methods. The work is based on the results of 20 donors who were diagnosed with brain death and authorized for the use of transplantation of human anatomical materials. Then changes in the main biochemical parameters (lactate, troponin, acid-base balance, creatinine clearance, blood glucose) and the functional state of systemic hemodynamics (blood pressure, heart rate, central venous pressure, ejection fraction, cardiac index) were analyzed at the time of donor heart explantation. Results. It was found that in 100 % of donors, norepinephrine was used for inotropic support, in 40 % — dobutamine and in 25 % — dopamine. Lactate levels were higher than normal in 75 % of cases and troponin levels were increased in all donors, indicating a possible microcirculatory dysfunction that led to a deterioration in donor preconditioning and enhanced ischemia-reperfusion injury to the transplant. According to the correlation coefficient between time and cardiac index, there was a tendency to the deterioration in the donor’s condition depending on the time of making a decision about heart transplantation before heart explantation. Conclusions. The study showed that in 100 % of donors, norepinephrine was used for inotropic support — more often than dobutamine or dopamine. Lactate levels were higher than normal in 75 % of donors and troponin levels were increased in all donors, indicating a possible microcirculatory dysfunction that led to a deterioration in donor preconditioning and increased ischemia-reperfusion injury to the transplant. According to the correlation coefficient between time indicators and cardiac index, it is noted that the longer the time of authorization for orthotopic heart transplantation, the greater the deterioration in the donor’s condition, which is expressed in a decreased myocardial contractility. Based on the correlation coefficient between time indicators and troponin, it was concluded that the growth of troponin complexes was observed with an increase in the time of making a decision for obtaining permission to transplant human anatomical materials, which indicated the onset of ischemic changes in the myocardium.

Common Complications and Cardiopulmonary Resuscitation in Patients with Left Ventricular Assist Devices: A Narrative Review.

Heart failure remains a major global burden regarding patients' morbidity and mortality and health system organization, logistics, and costs. Despite continual advances in pharmacological and resynchronization device therapy, it is currently well accepted that heart transplantation and mechanical circulatory support represent a cornerstone in the management of advanced forms of this disease, with the latter becoming an increasingly accepted treatment modality due to the ongoing shortage of available donor hearts in an ever-increasing pool of patients. Mechanical circulatory support strategies have seen tremendous advances in recent years, especially in terms of pump technology improvements, indication for use, surgical techniques for device implantation, exchange and explantation, and postoperative patient management, but not in the field of treatment of critically ill patients and those undergoing cardiac arrest. This contemporary review aims to summarize the collected knowledge of this topic with an emphasis on complications in patients with left ventricular assist devices, their treatment, and establishing a clear-cut algorithm and the latest recommendations regarding out-of-hospital or emergency department management of cardiac arrest in this patient population.

Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats

BackgroundHeart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes. The inhibition of cathepsin C (CatC) has been shown to block NE-related protease activation. We hypothesized that the CatC inhibitor BI-9740 improves graft function after HTX.MethodsIn a rat model of HTX, the recipient Lewis rats were orally administered with either a placebo (n = 12) or BI-9740 (n = 11, 20 mg/kg) once daily for 12 days. Donor hearts from untreated Lewis rats were explanted, preserved in a cardioplegic solution, and subsequently heterotopically implanted. In vivo left-ventricular (LV) graft function was assessed after 1 h of reperfusion. The proteolytic activity of neutrophil serine proteases was determined in bone marrow lysates from BI-9740-treated and control rats. Additionally, myocardial morphological changes were examined, and heart samples underwent immunohistochemistry and western blot analysis.ResultsThe NE-related proteolytic activity in bone marrow cell lysates was markedly decreased in the BI-9740-treated rats compared to those of the placebo group. Histopathological lesions, elevated CatC and myeloperoxidase-positive cell infiltration, and nitrotyrosine immunoreactivity with an increased number of poly(ADP-ribose) polymerase (PARP)-1-positive cells were lowered in the hearts of animals treated with BI-9740 compared to placebo groups. Regarding the functional parameters of the implanted graft, improvements were observed in both systolic function (LV systolic pressure 110 ± 6 vs 74 ± 6 mmHg; dP/dtmax 2782 ± 149 vs 2076 ± 167 mmHg/s, LV developed pressure, at an intraventricular volume of 200 µl, p < 0.05) and diastolic function in the hearts of BI-9740 treated animals compared with those receiving the only placebo. Furthermore, the administration of BI-9740 resulted in a shorter graft re-beating time compared to the placebo group. However, this study did not provide evidence of DNA fragmentation, the generation of both superoxide anions and hydrogen peroxide, correlating with the absence of protein alterations related to apoptosis, as evidenced by western blot in grafts after HTX.ConclusionsWe provided experimental evidence that pharmacological inhibition of CatC improves graft function following HTX in rats.

Abstract 16780: Single Cell Profiles of Human Heart Failure and Myocardial Diseases

Background: Heart failure represents the end-stage of a range of diseases which adversely impact the heart muscle. The extent by which cellular and molecular mechanisms differ between myocardial diseases in heart failure remains incompletely understood. Methods: We performed isolation and droplet-based RNA-sequencing of 394 247 single nuclei from 103 explanted hearts from transplant and ventricular assist device recipients and 7 unused donor hearts without heart disease. After sample and nuclei level quality control, doublet removal and sample integration; principal component analysis and shared nearest neighbor clustering were used to identify distinct cell populations. Cell type composition and transcriptomic profiles were compared across donor hearts and 10 myocardial diseases (hypertrophic, dilated, ischemic, restrictive, arrythmogenic and non-compaction cardiomyopathy; rheumatic and congenital heart disease; cardiac amyloidosis and graft rejection; n=1-45/group). Results: We identified and manually annotated 14 distinct cell populations that were present across controls and myocardial diseases, including transcriptionally diverse subgroups of cardiomyocytes, endothelial cells and pericytes. Compared to controls, we observed disease-specific differences in cell populations with regards to composition, heterogeneity, and specific transcriptional profiles. Conclusions: Our results reveal differences in single cell profiles of individual heart muscle diseases compared to controls without heart disease.

Abstract 18197: Relationship Between Donor Ejection Fraction and Left Ventricular Wall Thickness With Mortality Among Heart Transplants Recipients

Introduction: Limited availability of donor hearts contributes to significant mortality in patients waitlisted for heart transplantation (HTx). Donor hearts with reduced ejection fraction (EF) and left ventricular hypertrophy are considered to adversely affect long term HTX outcomes and are rejected. Objective: To determine the relationship of donor’s EF and left ventricular wall thickness (LVWT) with mortality in HTx recipients. Method: Retrospective analysis from The United Network for Organ Sharing (UNOS) registry. Adult HTx recipients with donor's EF and LVWT recorded from 2006 to 2022 were included. Study sample was grouped into four groups (Group 1 EF&gt;50% &amp; LVWT&lt;1.4cm, group 2 EF≤50% &amp; LVWT&lt;1.4cm, group 3 EF&gt;50% &amp; LVWT≥1.4cm, and group 4 EF≤50% &amp; LVWT≥1.4cm) according to donor characteristics. Primary end point: mortality (30 days, 1 year, and 5 years). Results: 21,012 patients were included, in which 19,205(91.4%) were in group 1, 898(4.3%) in group 2, 867(4.1%) in group 3, and 42(0.2%) in group 4. There were significant differences in baseline characteristics between the groups (Table 1). Unadjusted mortality was 6.3%, 6.0%, 6.0%, and 2.4% (p=0.86) at 30 days; 16.2%, 13.5%, 16.8%, and 7.3% (p=0.08) at 1 year; and 32.2%, 29.2%, 35.4%, and 29.0% (p=0.18) at 5 years, respectively (Table 1 and Figure 1). Neither adjusted mortality was different across the groups (Table 2). Conclusion: There were no significant differences in recipient mortality in different groups based on donor EF and LVWT. Expanding the donor selection criteria would allow for increase in the donor pool and assist in decreasing the mortality, while on the wait list for HTx.

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.

Abstract 13912: Insights From a Multi-Center Consortium for HCV-Viremic Donor Heart Transplant: Outcomes Are Excellent Across Regimens Often Without Major Changes to Statin or PPI

Introduction: With the availability of pangenotypic direct-acting antivirals (DAA) for facile, curative treatment of hepatitis C virus (HCV) infections, HCV-viremic donors are utilized regularly to partially address the shortage of suitable organs for heart transplant (HT). This multi-center, retrospective registry characterized HT outcomes from HCV-positive donors. Methods: Of 138 isolated HT recipients from 8 sites across the US, the most common DAAs were the pangenotypic antiviral combinations sofosbuvir-velpatasvir (SOF/VEL, n=39) and glecaprevir-pibrentasvir (GLE/PIB, n=76); these 115 cases were analyzed in terms of primary graft dysfunction (PGD), episodes of rejection ≥ pAMR1 and/or Grade 2R, post-transplant infection, sustained virologic response at 12 weeks post-treatment (SVR12), and survival up to 1 year. Results: Comparing these two most common pangenotypic regimens, HT recipients differed in their listing status (p&lt;0.001), hospital stay length (p=0.04), time until HCV+ (p=0.01), DAA payor (p=0.01), induction therapy (p=0.03) and statin therapy (p=0.01). A concurrent open-label trial accounted for up to 13/39 SOF/VEL patients, partially accounting for differences in DAA payor. Despite potential interactions, statin and proton pump inhibitor (PPI) therapy typically continued uninterrupted with minimal dose adjustment. Both treatment groups showed 100% cure (SVR12) of donor-derived HCV. Although not powered for comparative effectiveness of DAA agents, there were no significant differences in study outcomes. SOF/VEL and GLE/PIB-treated patients demonstrated 97% and 96% survival at 1 year, respectively. Conclusions: As utilized to achieve cure of HT donor-derived HCV, two pangenotypic DAA regimens are safe and feasible, with coverage accessed across a variety of DAA payors. SVR12 can be achieved often without major modifications to PPIs or statins with either pangenotypic DAA regimen (with pravastatin most commonly utilized).

Abstract 19190: The Impact of Donor Age on Long-Term Survival After Heart Transplantation: A Modern Analysis of the Unos Database

Introduction: Despite innovations in organ procurement and preservation, heart transplantation (HT) remains challenged with paucity of donor organs. Data is limited regarding the influence of donor age on long term outcomes of HT. Hypothesis: Our aim was to investigate the impact of donor age on long-term survival of transplant recipients between the past two decades. We hypothesized that the probability of survival has increased significantly over the most recent decade with significant increases in survivability for donor hearts aged 55+ years. Methods: The UNOS heart transplant registry was used to analyze survival of heart transplant patients between 2000-2009 (N= 10178) and 2010-2019 (N=20990). These were further separated into three donor age groups: 18-34, 35-54, and over 55 years. Kaplan-Meier survival curves were generated over a 10-year period. Log-ranked statistical testing was used to test the survival curves for significance. Results: Between 2000-2009, 5895 (58%) HT were performed from donors aged 18-34, 3862 (38%) HT from ages 35-54, and 422 (4%) HT from age 55+ group. The chance of 10-year survival was 62%, 52% and 40% respectively.In the 2010-2019 era, there were 12993 (62%) HT performed from donors aged 18-34, 7363 (35%) from ages 35-54, and 634 (3%) from age 55+ group. The 10-year survival was 81%, 77% and 73% respectively.In the donor group age 55+, there was significant difference (p&lt;0.0001) between the head trauma and cerebrovascular cause of death prior to 2010, but no difference in the new era. Conclusions: Our study of the UNOS database finds that the donor age of transplanted hearts significantly impacted long-term survival during 2000-2009. These significant differences carry for transplants from 2010-2019, however, we find that long-term survivability for all donor groups increased to over 70%. The largest increase was observed for donor hearts 55+ years where the chance of 10-year survival improved from 40% before 2010 to 73% after 2010.

Abstract 14896: Age is a Predictor of In-Hospital Mortality for Left Ventricular Assist Device: Implication in Post-2018 Donor Heart Allocation System

Background: The introduction of the new heart allocation system in 2018 has significantly changed the landscape of heart transplantation and trends of durable left ventricular assist device (LVAD) utilization. Although the quality of durable LVAD has improved, the impact of age on in-hospital mortality for LVAD implantation remains unknown under the new allocation system. Objective: We aimed to investigate the influence of age on the outcome following the LVAD implantation under the new heart allocation system. Method: We utilized the National Inpatient Sample to investigate patients who underwent LVAD implantation between 2019 and 2020. The primary endpoint was in-hospital mortality following LVAD implantation, stratified by different age groups. We also investigated independent predictors of in-hospital mortality. Result: A total of 7,375 patients underwent LVAD implantation between January 2019 and December 2020. Among these patients, individuals aged 18-49, 50-59, 60-69, and over 70 years old accounted for 26%, 26%, 31%, and 17%, respectively. In-hospital mortality rates in the aforementioned age groups were 7%, 6%, 12%, and 17%, respectively. Notably, the age groups of 60-69 and over 70 compared to age &lt;59 exhibited independent predictors of mortality, with an adjusted odds ratio (aOR) of 1.99 (p=0.02; 95% confidence interval [CI), 1.12-3.57) and 2.88 (p=0.002; 95% CI 1.45-5.71), respectively. Charlson Comorbidity Index (aOR, 1.39; p=0.02; 95% CI, 1.05-1.84) was also associated with increased risks of mortality. Conclusion: Our findings indicate that individuals over 60 years-old or with higher Charlson Comorbidity Index face a higher risk of in-hospital mortality following LVAD implantation.

Abstract 12968: Atorvastatin for the Treatment of Endocardial Fibroelastosis Formation in a Preclinical Animal Model

Background: Endocardial fibroelastosis (EFE) frequently associated with development of HLHS or critical AS, restricting growth of the left ventricle (LV). The mechanism of EFE formation is the transition from endocardial endothelial cells to mesenchymal cells (EndMT). Regulation of EndMT in cardiac fibrosis is mainly through the TGF-β pathway, and upregulated Krüppel-like factor 2 (KLF2) inhibits the TGF-ß pathway by blocking SMAD2/3. Besides their plasma lipid-lowering effect, statins (e.g. Atorvastatin) directly upregulate KLF2 and are thereby atheroprotective (i.e., inhibit EndMT). The aim was to evaluate whether the upregulation of KLF2 with Atorvastatin inhibits EFE formation. Methods: Heterotopic rat heart transplantation was performed using 2-4 day-old donor hearts into adolescent recipients, which induces LV EFE growth. Atorvastatin (n=7) was administered daily at 3 mg/kg intraperitoneally for two weeks and compared to untreated/vehicle (n=5) controls. At postoperative day 14, LV EFE thickness was determined on Masson’s trichrome-stained slides. Gene expression of KLF2 was analyzed by qRT-PCR and protein expression by Westernblot and quantified via densitometry for SMAD2/3 and collagen. Results: Mean LV EFE thickness was significantly decreased in the Atorvastatin group (22.3±2.5μm) compared to 176.8±22.6μm in the untreated/vehicle-treated group (p&lt;0.0001, A ). KLF2 was significantly upregulated in Atorvastatin treated hearts (p=0.0173, B ). SMAD2/3 and collagen were significantly elevated in the control group, p=0.0014 and p=0.048, respectively ( C, D ). Conclusion: LV growth restriction through EFE formation precludes patients from biventricular repair. Until now, surgical resection has been the only available therapeutic option. With this study, we show that Atorvastatin impedes EFE formation within the LV cavity in neonatal rat hearts through the upregulation of KLF2. Atorvastatin is, therefore a promising therapeutic agent.

Abstract 14918: Apical Cardiomyopathy in a Transplanted Heart

Case description: A 67 year old female presented for annual review to the transplant clinic 4 years post orthotopic heart transplant for nonischemic dilated cardiomyopathy. She was asymptomatic. Her medical history included hypothyroidism, hypertension, osteoporosis, restless leg syndrome and calcineurin inhibitor related complications - CKD 3b, impaired glucose tolerance and a left partial glossectomy with neck dissection for stage 3 SCC of the left lateral tongue. Medications included aspirin, atorvastatin, prednisolone, tacrolimus, septrin and ropinirole. Family history was significant for heart failure in her father. She was a nonsmoker and did not consume alcohol. Physical examination was unremarkable. Diagnostic tests are shown below. Discussion: Apical hypertrophic cardiomyopathy (ApHCM) has rarely been described in post cardiac transplant populations. Characterized by increased left ventricular apical wall thickness, it results in a ‘spade-like’ appearance on imaging and is associated with marked T wave inversion on ECG. ApHCM is associated with progression to heart failure, apical aneurysm, ventricular arrhythmias and increased mortality rates. Patients may be asymptomatic at diagnosis. Regarding screening, criteria exist for the selection of donor hearts pre transplant with caution exercised if LVH &gt;13mm. Causes of non HCM hypertrophy in this population include calcineurin inhibitors, hypertension, obesity and graft versus host disease. Data for treatment for ApHCM is lacking however it follows the path of classical HCM, involving the use of beta and calcium channel blockers to reduce demand ischemia and management of sequelae.

Heart graft preservation technics and limits: an update and perspectives.

Heart transplantation, the gold standard treatment for end-stage heart failure, is limited by heart graft shortage, justifying expansion of the donor pool. Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard practice, but it is usually limited to 240 min. Prolonged cold ischemia and ischemia-reperfusion injury (IRI) have been recognized as major causes of post-transplant graft failure. Continuous ex situ perfusion is a new approach for donor organ management to expand the donor pool and/or increase the utilization rate. Continuous ex situ machine perfusion (MP) can satisfy the metabolic needs of the myocardium, minimizing irreversible ischemic cell damage and cell death. Several hypothermic or normothermic MP methods have been developed and studied, particularly in the preclinical setting, but whether MP is superior to SCS remains controversial. Other approaches seem to be interesting for extending the pool of heart graft donors, such as blocking the paths of apoptosis and necrosis, extracellular vesicle therapy, or donor heart-specific gene therapy. In this systematic review, we summarize the mechanisms involved in IRI during heart transplantation and existing targeting therapies. We also critically evaluate all available data on continuous ex situ perfusion devices for adult donor hearts, highlighting its therapeutic potential and current limitations and shortcomings.

Disparities in donor heart acceptance between the USA and Europe: clinical implications.

Given limited evidence and lack of consensus on donor acceptance for heart transplant (HT), selection practices vary widely across HT centres in the USA. Similar variation likely exists on a broader scale-across countries and HT systems-but remains largely unexplored. This study characterized differences in heart donor populations and selection practices between the USA and Eurotransplant-a consortium of eight European countries-and their implications for system-wide outcomes. Characteristics of adult reported heart donors and their utilization (the percentage of reported donors accepted for HT) were compared between Eurotransplant (n = 8714) and the USA (n = 60 882) from 2010 to 2020. Predictors of donor acceptance were identified using multivariable logistic regression. Additional analyses estimated the impact of achieving Eurotransplant-level utilization in the USA amongst donors of matched quality, using probability of acceptance as a marker of quality. Eurotransplant reported donors were older with more cardiovascular risk factors but with higher utilization than in the USA (70% vs. 44%). Donor age, smoking history, and diabetes mellitus predicted non-acceptance in the USA and, by a lesser magnitude, in Eurotransplant; donor obesity and hypertension predicted non-acceptance in the USA only. Achieving Eurotransplant-level utilization amongst the top 30%-50% of donors (by quality) would produce an additional 506-930 US HTs annually. Eurotransplant countries exhibit more liberal donor heart acceptance practices than the USA. Adopting similar acceptance practices could help alleviate the scarcity of donor hearts and reduce waitlist morbidity in the USA.

Normothermic ex vivo heart and lung autoperfusion: assessment of functional status and metabolism

Objective: to carry out a comparative study of the efficacy of a 6-hour normothermic ex vivo heart and lung autoperfusion and cold cardioplegia using Bretschneider’s solution (Custodiol®, Germany).Materials and methods. Landrace pigs weighing 50 ± 5 kg at the age of 4–5 months (n = 10) were used as a model for a series of acute experiments. In the experimental group (n = 5), the cardiopulmonary complex was conditioned by autoperfusion for 6 hours. In the control group, the heart pumping function was restored after 6-hour cold cardioplegia using Bretschneider’s solution. The efficiency of graft preservation was assessed by measuring hemodynamic parameters, myocardial contractile function, and myocardial oxygen consumption.Results. After reperfusion and repeated isolation of the working cardiopulmonary complex, cardiac output was 0.63 [0.37; 0.8] L/min and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (p &lt; 0.05). Indicators – global left ventricular stroke work index and preload recruitable stroke work – were significantly higher in the experimental group (p &lt; 0.05).Conclusion. Normothermic autoperfusion is significantly more effective in preserving the morphofunctional status of a donor heart than static cold storage with Bretschneider solution for 6 hours.