List For Transplantation Research Articles

Clinical outcome after complete response with immunotherapy in hepatocellular carcinoma.

573 Background: Immunotherapy has shown great efficacy in hepatocellular carcinoma (HCC). No clear consensus exists on when to stop the immune checkpoint inhibitor (ICI) after complete response (CR), and clinical course after stopping ICI remains unknown. Methods: We identified 138 HCC patients who received ICI at Cedars-Sinai Medical Center and Mayo Clinic Rochester from 2016-2023. Modified Response Evaluation Criteria In Solid Tumors (mRECIST) was used to assess treatment response. We further described the clinical course of patients who achieved CR after ICI discontinuation, including cancer recurrence, subsequent treatment, liver transplantation (LT) listing and outcomes. Results: The median age at ICI initiation was 68 years; 79% were male; 55.9% were white; 51.5% were BCLC stage C. 9.4% CRs, 25.4% partial responses, 39.9% stable diseases, and 25.4% progressive disease. Hepatitis C etiology was associated with higher likelihood of CR (P=0.005). Among 13 patients who achieved CR, 10 stopped ICI (60% for LT evaluation, 40% for toxicity). After stopping ICI, 40% had recurrence (Table). 3 patients underwent local therapy for recurrent HCC within Milan criteria and 1 patient restarted ICI for recurrence beyond Milan criteria. Among CR patients, 9 patients underwent LT evaluation after stopping ICI and 7 patients were waitlisted. After listing, 3 dropouts were observed, due to recurrent HCC beyond Milan criteria, sepsis leading to death, and personal preference. 4 patients underwent LT. 2 patients underwent local therapy before LT for recurrent HCC (Table). All transplanted patients had the last dose of ICI more than 1 year before LT (12, 21, 24, and 29 months). On explanted livers, 2 patients had no residual viable tumor and 2 patients had residual HCC within Milan criteria. 1 patient developed acute cellular rejection and was treated with immunosuppressants and maintained stable graft function. None had graft loss or evidence of HCC recurrence in the follow-up period at 8, 20, 28, and 51 months. Conclusions: Immunotherapy demonstrated excellent effects on a subset of HCC patients, including 9.4% who achieved CR. After stopping ICI, 40% had cancer recurrence but 3 out of 4 were within Milan criteria. 4 underwent successful LTs (2.9%) with excellent post LT outcome. Larger prospective data is needed to establish a protocol for ICI use, especially to determine the optimal timing for ICI discontinuation after CR. BCLC at ICI initiation ICI cycles before stopping, ICI Recurrence after last ICI (days) Within Milan at recurrence Treatment(s) received after recurrence and outcomes OS (days) Patient 1 B 7, Nivolumab 730 No Nivolumab. Died from GI bleeding 1065 Patient 2 B 64, Atezo/Bev 149 Yes TACE with CR, followed by LT without recurrence. 1203 Patient 3 A 8, Nivolumab 1393 Yes Y90 with CR. No recurrence. 1984 Patient 4 C NA, Pembrolizumab 407 Yes TACE and MWA with CR, followed by LT without recurrence. 1722

Association of a Liver Allocation Policy Change With Domestic Travel for Liver Transplantation.

In 2020, liver allocation policy in the United States was changed to allow for broader organ sharing, which was hypothesized to reduce patient incentives to travel for transplant. Our objective was to describe patterns of travel for domestic liver transplant pre- and post-acuity circle (AC) implementation. Incident adult liver transplant listings between August 16, 2016, and February 3, 2020 (pre-AC) or June 13, 2020, and December 3, 2023 (post-AC) were obtained from the Scientific Registry of Transplant Recipients. We used previously defined geographic catchment areas to classify patients as (1) no travel, (2) travel to a neighboring region, and (3) travel beyond a neighboring region. We used multinomial logistic regression to identify characteristics associated with travel and cause-specific hazards modeling to estimate the association between travel and time to deceased donor transplant, stratified by model for end-stage liver disease (MELD) score and AC era. Among 83 033 liver candidates, 76% were listed in their home region. Black race, lower educational attainment, increased neighborhood social deprivation, and Medicaid were significantly associated with decreased odds of traveling beyond a neighboring region. After AC, traveling beyond a neighboring region was associated with an increased hazard of transplant for patients with a MELD score <15 (cause-specific hazard ratio [csHR]: 1.25; 95% confidence interval [CI], 1.11-1.40), MELD score 15-24 (csHR: 1.19; 95% CI, 1.07-1.31), and MELD score 25-34 (csHR: 1.15; 95% CI, 1.01-1.32). Travel frequency, geographic patterns of travel, and characteristics associated with travel were largely unchanged after AC. Changes to allocation policy alone may not equalize patient means or desire to travel for transplant care.

Plasma GlycA, a Glycoprotein Marker of Chronic Inflammation, and All-Cause Mortality in Cirrhotic Patients and Liver Transplant Recipients.

Low-grade chronic inflammation may impact liver disease. We investigated the extent to which circulating GlycA, a glycoprotein biomarker of low-grade inflammation, and high-sensitivity C-reactive protein (hs-CRP) are altered in patients with cirrhosis and liver transplant recipients (LTRs) and examined their associations with all-cause mortality. Plasma GlycA (nuclear magnetic resonance spectroscopy) and hs-CRP (nephelometry) were assessed in 129 patients with cirrhosis on the waiting list for liver transplantation and 367 LTRs (TransplantLines cohort study; NCT03272841) and compared with 4837 participants from the population-based PREVEND cohort. GlycA levels were lower, while hs-CRP levels were higher in patients with cirrhosis compared to PREVEND participants (p < 0.001). Notably, GlycA increased, but hs-CRP decreased after transplantation. In LTRs, both GlycA and hs-CRP levels were higher than in PREVEND participants (p < 0.001). Survival was impaired in patients with cirrhosis and LTRs with the highest GlycA and the highest hs-CRP tertiles. In Cox regression analysis, GlycA remained associated with mortality in cirrhotic patients after adjusting for potential confounders and for hs-CRP (HR per 1-SD increment: 2.34 [95% CI 1.07-5.13]), while the association with hs-CRP after adjusting was lost. In LTRs, both GlycA and hs-CRP were also associated with mortality (adjusted HR: 1.60 [95% CI: 1.2-2.14] and 1.64 [95% CI: 1.08-2.51], respectively) but not independent of each other. GlycA increases while hs-CRP decreases after liver transplantation. Both inflammatory markers may be associated with all-cause mortality in cirrhotic patients and LTRs, while the association for GlycA seems at least as strong as that for hs-CRP.

Comparing mental health and substance use disorders in patients receiving durable VADs versus transplants: A TriNetX database analysis.

Ventricular assist device (VAD) and cardiac transplant patients experience significant strain on their physical and mental wellbeing postoperatively. Mental health and substance use disorders (MHDs and SUDs) have substantial effects on the quality of life and compliance of transplant and VAD patients. In this study, we compare and characterize MHDs and SUDs between VAD and cardiac allograft patients and transplant list patients with and without VADs. This study compares the incidence of MHDs and SUDs between VAD and cardiac transplant patients. Cohorts were defined using ICD-10 codes in TriNetX, a large public database. Patient characteristics were matched by using propensity score matching. Incidence was analyzed using the log-rank test. Statistical significance was set at p < 0.05. Survival analysis showed a statistically significant impact of adjustment disorder, nicotine dependence, and mood disorder in VAD patients as compared to cardiac allograft recipients. Depression and opioid use disorder had a significantly higher incidence in post-transplant patients compared to their VAD counterparts. Survival analysis showed that PTSD and mood disorder had a statistically significant effect on the patients waiting on transplant wait list without VADs as compared to those with VADs. MHDs and SUDs have profound implications on quality of life, survival, and medication compliance. The incidence of MHDs and SUDs differed between VAD versus cardiac transplant patients as well as the patients on the transplant waitlist with and without VADs. Mental health resources should be tailored to address risk factors that may be unique to each group of patients.

Delisting From Liver Transplant List for Improvement and Recompensation Among Decompensated Patients at One Year.

Data are limited regarding etiology-specific trends for delisting and recompensation for liver disease improvement among liver transplantation (LT)-listed candidates in the United States. A retrospective cohort (2002-2022) using United Network of Organ Sharing database examined etiology-specific trends for delisting and recompensation due to liver disease improvement among candidates listed for LT. Of 120,451 listings in adults, 34,444 (2002-2008), 38,296 (2009-2015), 47,711 (2016-2022) were analyzed. A total of 7,196 (6.2%) were delisted for liver disease improvement, with 5.6%, 7.2%, and 5.3% in 3 respective time periods, Armitage trend P < 0.001. Delisting for improvement of liver disease was 8.1%, 5.8%, 4.0%, 3.9%, and 3.1% among listings for alcohol-associated liver disease (ALD n = 41,647), hepatitis C virus infection (HCV n = 38,797), autoimmune (n = 12,131), metabolic-associated steatohepatitis (MASH n = 22,162), hepatitis B virus infection (HBV n = 3,027), and metabolic liver disease (MLD n = 2,687), respectively. One thousand one hundred twenty-two (15.6% or 0.9%) were delisted for improvement at 1 year with cumulative incidence competing for waitlist mortality and receipt of LT of 1.18, 1.17, 0.64, 0.59, 0.50, and 0.34 for ALD, HBV, HCV, MASH, MLD, and autoimmune, respectively. In a fine and gray model, compared with metabolic, subhazard ratio (95% confidence interval) on delisting at 1 year was 3.47 (31.6-3.81) and 3.44 (2.96-3.99), P < 0.001, for ALD and for HBV, respectively. Of 7,196 delisting for improvement, 567 of 5,750 (9.9%) decompensated at listing had recompensation, 19.5% for HBV, 16.6% for MLD and autoimmune, 9.9% ALD, 8.6% for HCV, and 6.9% for MASH. In a logistic regression model among delisted candidates for improved liver disease, HBV vs MASH etiology was associated with recompensation, 2.37 (1.40-4.03), P < 0.001. ALD and HBV are most frequent etiologies for delisting due to liver disease improvement. About 10% of delisted patients develop recompensation, with HBV etiology most likely to recompensate. Models and biomarkers are needed to identify these candidates for optimal use of deceased donor livers.

Non-invasive predictors of the first episode of bleeding from esophageal varices in patients with liver cirrhosis awaiting transplantation

Background. To date, various non-invasive techniques or tests have been proposed that can identify a high risk of bleeding from esophageal varices. Despite a significant number of studies revealing the presence of venous varices as a likely factor for the development of bleeding due to their rupture, data on predictors of the first episode of bleeding are few and often contradictory.Objective. To determine non-invasive independent predictors of the first episode of bleeding in patients waiting for liver transplantation.Material and methods. A comparative retrospective study was conducted in 729 patients with decompensated cirrhosis who were on the waiting list for liver transplantation. We analyzed demographic, clinical and laboratory parameters, MELD-Na, Child-Turcotte-Pugh scores, FIB-4 Index, APRI, AST/ALT ratio; we determined the liver stiffness, spleen diameter, studied the liver stiffness-spleen diameter to platelet ratio risk score (LSPS model), platelet count/spleen diameter ratio in the groups of patients with the first episode of bleeding (n=334) and without it (n=395). The accumulated risks in the compared groups were assessed using a model of proportional hazards (Cox regression) in univariate and multivariate analysis.Results. During 48 months of follow-up from the time of patient placement on the liver transplant waiting list, primary bleeding events developed in 45.8%. The risk of developing the first episode of bleeding progressively increased with LSPS &gt;3.5 and reached maximum values in patients awaiting liver transplantation within 48 months of inclusion in the waiting list, while with LSPS &lt;3.5 the risk was minimal.Conclusion. Independent non-invasive predictors of the first episode of bleeding are a high level of AST, a high fibrosis index (FIB-4), a decrease in the ratio of platelet count/spleen diameter and a high LSPS value. Their application in clinical practice will improve the results of dispensary and screening examinations of patients with portal hypertension.

Role of continuous renal replacement therapy in management of the preliver transplant patient.

Highlight the importance of acute kidney injury (AKI) among liver transplant candidates, its importance of survival and the vital role of continuous renal replacement therapy (CRRT) as a supportive therapy. Kidney dysfunction is common in the preliver transplant patient. Early recognition, broad diagnostic work up, and therapeutic interventions are vital in minimizing morbidity and mortality in this critically ill group of patients. Liver dysfunction can impact kidney function in multiple ways, leading to worsening of clinical illness. High mortality and poor prognosis in those with AKI without CRRT and Liver Transplant are highlighted. Etiology of AKI may not be as important as is the potential for liver transplant (LT) listing in offering CRRT. Non eligibility for a LT does not by default imply non eligibility for CRRT. Multidisciplinary approach should be adopted among those with a need for CRRT in the setting of end-stage liver disease. Goals of care conversations are key, in evaluating the role of CRRT in this group of individuals as they have a very high risk of mortality.

Clinical Management and Transplant Considerations in Pediatric Pulmonary Hypertension Due to Left Heart Disease: A Scientific Statement From the American Heart Association.

Children with left heart disease are at risk for developing pulmonary hypertension, initially secondary to pulmonary venous hypertension that can progress to include elevated pulmonary vascular resistance, known as combined pre- and postcapillary pulmonary hypertension. Elevated pulmonary vascular resistance may pose a risk to the right ventricle of a newly transplanted heart because of increased afterload and is an important consideration for heart transplant eligibility. However, the epidemiology, pathophysiology, optimal diagnostic and treatment approaches, and thresholds for pulmonary vascular resistance in pulmonary hypertension associated with left heart disease remain unclear because of lack of evidence, particularly in pediatrics. The result is heterogeneity with respect to hemodynamic assessment, use of pulmonary vasodilator therapies, and heart transplant listing. This scientific statement aims to synthesize the available data and highlight areas of general consensus as well as important knowledge gaps.

Ensuring equity in psychosocial risk assessment for solid organ transplantation: a review.

This review summarizes the different instruments for evaluating the psychosocial health of transplant candidates, the evidence demonstrating how these instruments relate to probability of transplant waitlisting and transplant outcomes, and the critical knowledge gaps that exist in the causal pathway between psychosocial health and clinical transplant trajectory. The current literature reveals that psychosocial assessments are a common reason for racial and ethnic minorities to be denied access to the transplant list. Given evidence that a lack of clinician consensus exists regarding the definition of, importance of, and reproducibility of psychosocial support evaluations, this facet of the holistic evaluation process may create a unique challenge for already vulnerable patient populations. Though recent evidence shows that psychosocial evaluation scores predict select transplant outcomes, these findings remain inconsistent. Multiple instruments for psychosocial transplant evaluation exist, though the utility of these instruments remains uncertain. As equity becomes an increasingly urgent priority for the transplant system, rigorous interrogation of the causal pathway between psychosocial health and transplant longevity is still needed.

A gift of life, not immortality: Evaluation of a strategy of heart transplant listing in the older patient with advanced heart failure

Patients 65 years of age or older represent the fastest-growing demographic group added to the U.S. heart transplant (HT) list. While post-HT outcomes appear acceptable, immortal time bias is introduced if adverse outcomes that occur while waiting for HT are not considered. Recent durable left ventricular assist device (dLVAD) technological innovations have engendered the question of whether this patient subgroup would achieve equivalent survival from a strategy of primary dLVAD implant as opposed to HT listing. We identified adults ≥65 years of age listed for HT between 2018-2021, excluding persons with dLVAD support and/or multi-organ listing. Among 1176 patients, 2-year survival from HT listing was 78.4 ± 1.2%, similar to the 71% to 75% reported in The Society of Thoracic Surgeons (STS) Intermacs National Database for older adults. Linkage of the Scientific Registry of Transplant Recipients with STS Intermacs would enable comparative effectiveness analyses of surgical heart failure therapeutic strategies in high-risk patient cohorts.

Circulating Citrate Is Reversibly Elevated in Patients with End-Stage Liver Disease: Association with All-Cause Mortality.

Circulating citrate may serve as a proxy for mitochondrial dysfunction which plays a role in the progression of end-stage liver disease (ESLD). This study aimed to determine the extent of alterations in circulating citrate in patients with ESLD, and examined its association with all-cause mortality among ESLD patients while on the waiting list for liver transplantation. Plasma citrate levels were measured using nuclear magnetic resonance spectroscopy in 129 ESLD patients (TransplantLines cohort study; NCT03272841) and compared to levels in 4837 participants of the community-dwelling PREVEND cohort. Plasma citrate levels were 40% higher in ESLD patients compared to PREVEND participants (p < 0.001). In a subset of 30 ESLD patients, citrate decreased following liver transplantation (p < 0.001), resulting in levels that were slightly lower than those observed in PREVEND participants. In multivariable analysis, plasma citrate levels were positively associated with Child-Turcotte-Pugh classification and inversely associated with estimated glomerular filtration rate (both p < 0.05). Survival was significantly reduced in ESLD patients in the highest citrate tertile (log-rank p = 0.037). Elevated citrate levels were associated with an increased risk of all-cause mortality in ESLD patients (HR per 1 Ln SD increment: 1.65 [95% CI: 1.03-2.63], p = 0.037). This association was suggested to be particularly present in men (HR: 2.04 [95% CI: 1.08-3.85], p = 0.027). In conclusion, plasma citrate levels are elevated in ESLD patients and decrease following liver transplantation. Moreover, elevated plasma citrate levels may be associated with increased all-cause mortality in ESLD patients, likely more pronounced in men.

Results of regional care for patients with cirrhosis of the liver in the outcome of viral hepatitis C in the era of direct-acting antiviral drugs

Objective: to assess the effect of antiviral therapy on the clinical course and survival in patients with cirrhosis of the liver in the outcome of chronic viral hepatitis C.Materials and methods: a retrospective analysis of the medical histories of 325 patients with cirrhosis of the liver in the outcome of chronic viral hepatitis C, who were on the waiting list for liver transplantation from 2014 to 2024. The patients were divided into 2 groups: patients who received antiviral therapy (n=273), and patients who did not receive antiviral therapy (n=52).Results: in the group of patients who received antiviral therapy, 219 (80.2%) patients were alive at the time of the diagnosis, including 57 (20.8%) people achieved liver function compensation and were excluded from the waiting list for liver transplantation; 42 (15.3%) patients underwent liver transplantation. The dynamics of clinical and laboratory indicators in patients from this group improved. In the group of patients who did not receive antiviral therapy, 2 (3.8%) patients were alive at the time of the examination, none of the patients had achieved liver function recompensation. The dynamics of clinical and laboratory indicators in patients of this group worsened.Conclusion: antiviral therapy has a positive effect on the survival of patients with cirrhosis of the liver in the outcome of chronic viral hepatitis C, as well as on the clinical course and laboratory parameters, which necessitates the earliest possible implementation of this therapy. Clinical and laboratory monitoring of these patients is also needed to prevent re-infection with viral hepatitis C, early detection of decompensation of liver function, and the occurrence of hepatocellular carcinoma.

Subgroup differences in public attitudes, preferences and self-reported behaviour related to deceased organ donation before and after the introduction of the ‘soft’ opt-out consent system in England: mixed-methods study

BackgroundIn the UK, over 7,000 people are on the waiting list for an organ transplant and there are inequalities in need, access and waiting time for organs, with notable differences between minority ethnic groups. In May 2020, England changed the law and introduced a ‘soft’ opt-out system of consent to organ donation with a view to increase consent rates. We aimed to learn more about the impact of the law change on attitudes and views likely to be relevant to consent to deceased organ donation between different population subgroups.MethodsMixed-methods design involving latent class analysis of data from twelve repeated cross-sectional surveys undertaken from 2015 to 2021 (n = 19,011); analysis of the law change survey dataset collected quarterly from 2018 to 2022 (n = 45,439); and interviews with purposively selected members of the public (n = 30) with a focus on minority perspectives.ResultsSupport for the principle of deceased organ donation remained high and stable in the general population (80%) but was 20% lower among ethnic minorities. From 2018 to 2022, an average of 58% of the general population was aware of the law change; this was lower among minority ethnic groups (31%). We identified four population subgroups (supportive donors (24% of the population); unengaged donors (22%); uncommitted donors (46%); and unsupportive donors (9%)). Interview themes included the challenges of discussing organ donation decisions, balancing autonomy with respecting family relationships, targeted misinformation, frustrations at the lack of consensus between community leaders, limited understanding of what happens during the end-of-life care leading to organ donation, and how this aligns with cultural values and preferences.ConclusionImplementation of the law change has not been associated to date with any change in public attitudes and preferences likely to influence consent overall or in minority ethnic groups in England. Uncommitted donors may benefit from encouragement to express their organ donation decision, and unengaged donors from attempts to address mis/information, confusion, and uncertainty. Interventions to raise the consent rate need to take account of the significant role of the family as well as wider community influences on attitudes, preferences and decision-making, particularly among certain minority (ethnic) groups.

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

Abstract 4137107: The Impact of Race in the Evaluation Process for Advanced Heart Failure Therapies

Introduction: Racial and socioeconomic disparities in heart failure therapy and heart transplantation have been well described. Potential racial disparities during the evaluation process for advanced heart failure (AHF) therapies is not well understood. We examined whether there were differences by race in the evaluation process for heart transplantation or left ventricular assist device (LVAD) implantation. Methods: Adult patients who underwent heart transplant or LVAD evaluation between May 1, 2014 – Dec 31, 2022 at the University of North Carolina Medical Center were included. Logistic regression models assessed whether approval for heart transplant listing or LVAD implantation differed by race. The multivariate model adjusted for demographic and clinical characteristics, LVEF, RV function, and substance use. Secondary outcomes assessed included the time between critical points in the evaluation process: first clinical encounter with an AHF specialist, evaluation initiation, and final decision. Results: The study cohort included 611 patients (304 non-Hispanic Black patients, 307 non-Hispanic White patients). Black patients were younger than White patients (52.4 vs. 60.7 years), less male-predominant (65.5% vs. 81.4%), with less ischemic cardiomyopathy (16.8% vs. 58.3%, all p&lt;0.05). There was no significant difference in approval for advanced therapies between Black and White patients (unadjusted OR [95% CI]: 1.24 [0.90-1.72]; adjusted OR 0.98 [0.64-1.48]). Male sex was associated with a higher likelihood of approval for AHF therapies (adjusted OR 1.55 [1.02-2.36]). Age (OR 0.98 [0.96-0.99]) and creatinine (OR 0.66 [0.53-0.82]) were associated with a lower likelihood of approval for AHF therapies. Black patients had a significantly longer time interval from the first AHF specialist encounter to the initiation of evaluation for AHF therapies (median 45.5 vs. 14 days, p &lt;0.01), and from the initiation of the evaluation process to the final decision (25.5 vs. 14 days, p &lt;0.01). Conclusions: Male patients had a greater approval rate for advanced heart failure therapies. Black and white patients did not have significantly different approval rates for LVAD implantation or listing for heart transplantation. However, the evaluation process was longer for black patients. Further work is needed to investigate which factors contribute to these racial and sex differences in the evaluation and approval process for advanced heart failure therapies.

Comprehensive Characterization of Anti-HLA and Non-HLA Antibodies in Patients on Kidney Transplant Waiting List and Evaluation of Their Impact on Alloimmunization Risk and Dialysis Treatment.

Alloimmunization remains a major obstacle to successful kidney transplantation, mainly due to the formation of anti-HLA antibodies. In recent years, non-HLA antibodies have emerged as additional immunologic factors that can potentially contribute to graft rejection. The aim of this study was to investigate the prevalence and specificity of both anti-HLA and non-HLA antibodies in patients with end-stage renal disease on a waiting list for kidney transplantation. Serum samples from 74 patients were analyzed using complement-dependent cytotoxicity and solid-phase assays. IgG anti-HLA antibodies were identified in 43.2% of participants, while IgG non-HLA antibodies were detected in 91.9%. The most frequent non-HLA antibodies included anti-ENO1 (28.4%), anti-FIBR1 (23.0%) and anti-PRKCZ (23.0%). A significant difference was found between the number of distinct IgG anti-HLA and IgG non-HLA antibody specificities. However, no significant correlation was found between the number of IgG non-HLA antibody specificities and previous alloimmunization events or dialysis treatments. These results suggest that non-HLA antibodies, although often overlooked, can sometimes play a critical role in transplant outcomes. Routine testing for non-HLA antibodies, in addition to mandatory anti-HLA antibody screening and identification, could improve immunologic risk assessment in transplant patients and post-transplant care.

Donor Selection for Heart Transplantation in 2024.

The number of candidates on the waiting list for heart transplantation (HT) continues to far outweigh the number of available organs, and the donor heart nonuse rate in the United States remains significantly higher than that of other regions such as Europe. Although predicting outcomes in HT remains challenging, our overall understanding of the factors that play a role in post-HT outcomes continues to grow. We observe that many donor risk factors that are deemed "high-risk" do not necessarily always adversely affect post-HT outcomes, but are in fact nuanced and interact with other donor and recipient risk factors. The field of HT continues to evolve, with ongoing development of technologies for organ preservation during transport, expansion of the practice of donation after circulatory death, and proposed changes to organ allocation policy. As such, the field must continue to refine its processes for donor selection and risk prediction in HT.

The ASK trial: a randomised controlled feasibility trial and process evaluation of a complex multicomponent intervention to improve AccesS to living-donor Kidney transplantation

Background Following identification of barriers to living-donor kidney transplantation, and subsequent development of a multicomponent intervention, we undertook a feasibility trial of the intervention. Trial design Two-arm, parallel group, pragmatic, individually-randomised, controlled, feasibility trial, comparing the new intervention with usual care, with a mixed-methods parallel process evaluation. Based at two UK hospitals. Participants Individuals were eligible if ≥18 years old, active on the kidney transplant waiting list or had been referred for transplant listing without a contraindication to transplantation. Individuals with a living-donor undergoing surgical assessment were excluded. Intervention i) A meeting between a home educator for a dedicated discussion about living-donor kidney transplantation, living kidney donation and potential donors; ii) A standardized letter from a healthcare professional to a candidate’s potential donors; iii) A home-based education and family engagement session undertaken by a living kidney donor and a nurse specialist. Objective To establish the acceptability and feasibility i) of delivering the developed intervention in existing care pathways, and ii) of undertaking a randomised controlled trial of the intervention. Primary outcomes Recruitment and retention. Randomisation Participants were randomly allocated 1:1 to i) the intervention or ii) usual care, stratified by site. Minimisation was used to ensure balance in sex, age group, and socioeconomic strata, with probability weighting of 0.8. Results 183 people were invited to participate. 62 people (34% recruitment) were randomised. 62/62 (100%) completed nurse assessed follow-up at 6 weeks. 51/62 (82%) completed follow-up questionnaires. 3/30 (10%) in the usual care arm and 9/32 (28%) in the intervention arm had individuals ask to be tested for living kidney donation following recruitment to the trial. Conclusions Intervention and trial delivery are feasible and acceptable. Findings have informed the design of an effectiveness and cost-effectiveness trial. Trial registration ISRCTN Registry ISRCTN10989132 https://doi.org/10.1186/ISRCTN10989132. The trial was registered on 6/11/2020.

Nexilin-related cardiomyopathy (NEXN-CMP) - an island's perspective

Abstract Introduction The phenotypic features of Nexilin related cardiomyopathies (NEXN-CMP) are poorly understood and under-reported. A better understanding of the genotype-phenotype association is paramount. Objectives The main objective of this study was to investigate the causative role and phenotypic expression of the NEXN gene in the Maltese Islands. Methodology Probands and relatives referred for a cardiac gene panel were evaluated. Subjects harbouring NEXN variants were identified. Those finally classified as having NEXN-CMP were evaluated for the purpose of this study. Results Out of 444 probands (confirmed or suspected cardiomyopathy), 12 probands were labelled with NEXN-CMP. This equates to a prevalence of 2.7% in the local cardiomyopathy pool, substantially higher to what has been previously reported. Genetic testing identified 19 individuals (probands [n=15] and relatives [n=4]) all harbouring the same novel frameshift variant: NEXN c.1589_1590del p.(Arg530LysfsTer3), classified as likely pathogenic according to ACMG criteria. Three (15.8%) harboured a second pathogenic variant (n=2 MYH7, n=1 TTN). Another 3 were not clinically affected (n=1 FH of SCD, n=2 first degree relatives of NEXN-CMP probands). These individuals were excluded from further analysis. The NEXN-CMP cohort (n=13) consisted of a dominant male (68.8%) population (54±22 years at presentation, 7.7% athletes, 12 families). Most were probands (n=12/13). DCM was the dominant phenotype (n=8, 61.5%) followed by HNDLVC (n=3, 23.1%) and HCM (n=2, 15.4%). One infantile DCM was homozygous for the NEXN variant. Symptoms were the most frequent method of presentation (n=6, 46.2%), followed by a FH of SCD and/or cardiomyopathy (n=3, 23.1%), abnormal echocardiogram (n=2 15.4%), OHCA (n=1, 7.7%) and inutero diagnosis (n=1, 7.7%). A FH of SCD was present in a third (n=4/12, 33.3%). The ECG was abnormal in the majority (n=10/11, 90.9%). Most patients had a LBBB (6/11, 54.5%) followed by inferolateral TWI (n=3, 27.3%), ventricular arrhythmias/high-grade AVB (n=1, 9.1% each). NEXN-CMP appears to be a left dominant cardiomyopathy. LV dilation and reduced LVEF were present in 84.6%. Non-ischaemic scar was present in 3/8 cases (37.5%), 2 had a ring-like pattern. RV morphology and function was normal in all cases. Tachyarrhythmias were frequently observed (n=4/6, 66.7%) during holter monitoring or exercise testing (n=2 NSVTs, n=1 VEs, n=1 SVEs). A fourth (n=3/11, 27.3%) were implanted with an electrophysiological device. No significant predictors for device implantation were identified at univariate analysis. One patient is on the transplant list (infantile DCM). Conclusion The prevalence of NEXN-CMP in Malta appears higher than previously reported (2.7%), possibly because of a founder mutation. DCM and HCM are the dominant presenting phenotypes, frequently associated with symptoms, an abnormal ECG, a FH of SCD and LV dilatation/dysfunction.

Impact of mitral transcatheter edge-to-edge repair in patients with advanced heart failure evaluated for heart transplantation

Abstract Background Heart transplantation is sometimes the only therapeutic option in patients with advanced heart failure (HF), impaired ventricular function and significant functional or secondary mitral regurgitation (MR). The shortage of organs and the limitations of the recipient make it necessary to consider other therapeutic alternatives in these patients, such as mitral transcatheter edge-to-edge repair (M-TEER). The MitraBridge registry has recently been published in which they analyze the potential effect of M-TEER in patients with advanced HF and moderate-severe MI who are candidates for heart transplantation (mean age 59 years, left ventricular ejection fraction (LVEF) 27%); after a mean follow-up of 24 months, complete in 82.4%, they report an overall survival of 78.5%, a combined event-free survival of 47%, with a 6.5 % need for urgent transplantation and an HF hospitalization rate after M-TEER of 44/100 patient-years. The aim of our study is to assess the impact of M-TEER on mortality and the combined events of death, HF rehospitalization and the need for urgent transplantation or a ventricular assistance device in patients with moderate-severe functional MI and advanced HF who have also been evaluated for cardiac transplantation in our hospital. Methods This is a retrospective analysis of a prospective registry. Of the patients treated by M-TEER for severe MI, we selected those with advanced HF (defined as LVEF≤35%, and/or advanced functional class (NYHA III-IV)) who had also been evaluated as possible candidates for inclusion in the heart transplant list. Results From November 2011 to December 2023, 191 patients were treated by M-TEER, of whom 38 patients met the established criteria (median age 59 years [48-65], 31 (81%) males, mean LVEF was 26 ± 6%). All patients had at least one previous hospitalization for HF and optimal medical treatment according to guidelines; the rest of the baseline clinical characteristics are listed in Table 1. During the follow-up after M-TEER, with a median of 34 months [7-70], the probability of overall survival at 2 years was 75.6%. The combined endpoint of death, need for urgent transplantation or a ventricular assist device, and rehospitalization for heart failure occurred in 26 patients with a 2-year event-free survival probability of 48% (Figure 1). Five patients (13%) were transplanted, one (2.6%) urgently. Prior to M-TEER therapy, the rate of HF hospitalization was 108 hospitalizations/100 patient-years, which was significantly reduced after the procedure to 33 hospitalizations/100 patient-years (rate ratio 0.31 [95% CI 0.21-0.45, p&amp;lt;0.0005]). Conclusions In patients with advanced HF and severe functional MR who are candidates for cardiac transplantation, M-TEER is an effective therapeutic alternative, achieving a survival rate of more than three-quarters of the patients at 2 years of follow-up, a significant reduction in HF hospitalizations, and a low rate of need for cardiac transplantation.