EJHaem. 2025 Oct 6;6(5):e70161. doi: 10.1002/jha2.70161. eCollection 2025 Oct.
ABSTRACT
A Sickle Cell Anemia patient with severe ventricular arrhythmia and left ventricular dysfunction achieved rapid, complete cardiac recovery after haplo-identical stem cell transplantation, raising questions about SCA cardiac pathophysiology and highlighting the potential for reversible cardiac complications following curative treatment. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.
PMID:41058956 | PMC:PMC12498570 | DOI:10.1002/jha2.70161
Transplant Direct. 2025 Oct 3;11(11):e1858. doi: 10.1097/TXD.0000000000001858. eCollection 2025 Nov.
ABSTRACT
BACKGROUND: Donation after circulatory death (DCD) is the major contributor to the growth in deceased organ donation in the United States. Normothermic regional perfusion (NRP) and ex situ machine perfusion (es-MP) have been vital for improving organ assessment and preservation in DCD donor organs. The procurement procedure and storage strategy for noncardiac donors were determined by liver transplant centers in the early era of machine perfusion in the United States. In this study, we analyzed the landscape of liver utilization from noncardiac DCD donors in the United States during the early era of machine perfusion.
METHODS: All adult (18 y and older) DCD donors in the United States for which the heart was not used for transplantation from October 1, 2020, to December 31, 2023, were compared using procurement technique (NRP versus super rapid recovery [SRR]) and storage strategy (ex situ machine perfusion [es-MP] versus static cold storage).
RESULTS: One hundred fifty-six livers were transplanted from 284 NRP donors (55% utilization) versus 2497 liver transplants from 9132 SRR donors (27% utilization). Es-MP was used in 19% (n = 30) of liver NRP cases versus 28% (n = 695) of liver SRR cases. Eight hundred fifty-one liver grafts (32%) were exposed to NRP, es-MP, or both.
CONCLUSIONS: Given the variation in liver graft management, further research needs to be conducted on the optimal strategies for using technologies such as NRP and es-MP in liver transplantation in the United States; better data collection is necessary to support this research and additional strategies are required to increase access to machine perfusion on a national level are needed.
PMID:41058935 | PMC:PMC12499658 | DOI:10.1097/TXD.0000000000001858
Innovations (Phila). 2025 Oct 7:15569845251375442. doi: 10.1177/15569845251375442. Online ahead of print.
ABSTRACT
Despite efforts to improve donor heart allocation policies, geographic disparities, logistical challenges and patient criteria limit organ availability. However, recent surgical innovations offer potential solutions. These include partial heart transplantation and xenotransplantation. Partial heart transplantation is a new procedure with the potential to address several clinical challenges in treating congenital heart defects. Cardiac xenotransplantation involves the transplantation of genetically modified porcine hearts into humans, offering a potential solution to the shortage of donor organs. Although immunologic barriers and ethical concerns remain, ongoing research aims to mitigate the risks and optimize outcomes, providing hope for patients in need. These innovative surgical approaches offer promising avenues for addressing the critical shortage of donor hearts and with ongoing research, may hold the potential to revolutionize heart transplantation, and improve outcomes for patients facing terminal heart failure.
PMID:41058154 | DOI:10.1177/15569845251375442
Pediatr Transplant. 2025 Nov;29(7):e70204. doi: 10.1111/petr.70204.
ABSTRACT
BACKGROUND: In 2020, the Organ Procurement and Transplantation Network authorized the creation of a National Heart Review Board for Pediatrics along with a guidance document. The purpose of this study was to evaluate the utilization of exception requests and approval rates after the implementation of the new review board.
METHODS: This was a retrospective review of 1A and 1B exception requests between June 2021 and January 2023. Exception request narratives were reviewed to determine if the request followed guidance and then analyzed the frequency of those approved by diagnosis.
RESULTS: There were 591 exception requests submitted for 419 candidates with an overall approval rate of 91%. Only 55% of the exceptions followed the guidance, but of those, 97% were approved. Exceptions submitted that did not follow the guidance had a lower approval rate of 85%. 1A exception requests that followed the guidance were significantly more likely to be approved than those that did not (97% vs. 62%, respectively, p < 0.05). For 1B requests, approval rates did not differ between requests that followed the guidance and those that did not (98% vs. 95%, respectively, p = 0.15). Candidates with single ventricle congenital heart disease made up 59% of 1B exception requests. There is no 1B exception guidance for candidates with dilated or hypertrophic cardiomyopathy; however, requests were still submitted and 95% were approved.
CONCLUSION: Most status 1A exceptions being granted followed the guidance document from OPTN. While the greatest number of requests for 1B exceptions were for single ventricle physiology candidates, many exceptions outside the guidance are being sought and granted.
PMID:41058036 | DOI:10.1111/petr.70204
Pediatr Transplant. 2025 Nov;29(7):e70203. doi: 10.1111/petr.70203.
ABSTRACT
BACKGROUND: Screening for social needs has become increasingly common across healthcare settings. While pediatric programs across the United States have successfully implemented social needs in a clinic setting, the ability to connect families with a positive screen to needed resources is not entirely clear. Through this quality improvement initiative, we sought to universally screen for social needs and refer all families with a positive screen to community resources.
METHODS: Social needs screening was conducted within a pediatric heart transplant clinic in the Western USA. The clinic team devised two separate resource referral pathways: high-risk needs (addressed by social worker) and low-risk needs (referred to Unite Us). Referral outcomes of interest were resource identification and resource connection, with the social worker pathway demonstrating higher effectiveness.
RESULTS: Social needs screening identified 66 active needs among 28 of the 86 families screened. Team members were unable to identify a community resource for almost half of the identified needs (n = 30, 44.8%), most often because a resource was not found (n = 23). Of the 59 needs addressed, the clinic team was able to connect families to resources for 24 needs. Overall, families were connected to resources for 36.4% of all identified needs.
CONCLUSIONS: Screening for social needs revealed a high degree of social need. However, referral to resources was hampered by two key barriers-lack of available resources and lack of local program follow-up. When resources were identified, the in-person support and referral pathway was more effective than remote support.
PMID:41058021 | DOI:10.1111/petr.70203
J Transl Med. 2025 Oct 7;23(1):1060. doi: 10.1186/s12967-025-07099-6.
ABSTRACT
Global cerebral ischemia (GCI) caused by impaired blood flow to the brain-typically following cardiac arrest or traumatic brain injury-remains the leading cause of coma and disorders of consciousness (DoC). In certain cases, the recovery potential of these patients may be significantly underestimated. Historically, these patients were often given little hope for recovery, particularly due to longstanding, outdated dogmatic views such as the presumed absence of adult neurogenesis. However, recent advances suggest that we have been discounting ongoing mental activity in comatose patients; additionally, emerging evidence shows that some patients in coma retain the capacity for communication through non-traditional means. The authors believe that the exponential progress in the field and the increase of our understanding in neurophysiology, regenerative medicine, and the biology of cellular senescence now makes it plausible to initiate experimental interventions that offer a realistic chance of reversing disorders of consciousness. The proposed strategy involves a two-step therapeutic paradigm: first the use of senolytic approaches to remove senescent cells and reduce neuroinflammatory burden ("clear the debris"); second, stimulation of neural regeneration through stem cell therapies, combined with electrophysiologic/pharmacological stimulation. The authors propose, that this integrated approach offers a novel treatment paradigm to address the previously insurmountable challenge of coma reversal.
PMID:41057934 | DOI:10.1186/s12967-025-07099-6
BMC Med Genomics. 2025 Oct 7;18(1):151. doi: 10.1186/s12920-025-02231-3.
ABSTRACT
BACKGROUND: The intrapatient variability (IPV) of tacrolimus (Tac) has gradually become a new index for the prognosis of organ transplantation. The gene polymorphism is involved in the pharmacokinetic process of Tac. The aim of this study was to investigate the effects of genetic polymorphisms on Tac IPV and other clinical outcomes in heart transplant recipients during the early post-transplantation period.
METHODS: Our study retrospectively collected the clinical data and genotyping results of 48 heart transplant recipients. SPSS (21.0) and Graphpad Prism (8.0) were used to analyze the effect of gene polymorphism on Tac concentration (C0) and clinical outcome.
RESULTS: The CYP3A5 rs15524 AA genotype has a higher trough concentrations/dose (C0/D) value than G allele carriers, and CYP3A7 rs776744 CC genotype has a higher C0/D value than T allele carriers. Patients with The CYP3A5 rs15524 and CYP3A7 rs776744 mutants had a higher IPV. One year after heart transplantation, the mortality of wild-type and mutant CYP3A5 rs15524 patients due to rejection was 0 vs. 10.7% (P = 0.255). The mortality caused by rejection in wild-type patients and mutant patients of CYP3A7 rs776744 was 4.5% vs. 7.7% (p = 0.564).
CONCLUSIONS: Genetic polymorphisms of CYP3A5 rs15524 and CYP3A7 rs776744 affect tacrolimus metabolism in heart transplant recipients, significantly affecting Tac C0/D during the early postoperative period. In addition, gene polymorphism may be related to Tac IPV and clinical outcome in patients with early heart transplantation.
PMID:41057866 | DOI:10.1186/s12920-025-02231-3
Biomaterials. 2025 Oct 3;327:123762. doi: 10.1016/j.biomaterials.2025.123762. Online ahead of print.
ABSTRACT
Cardiac transplantation is the preferred treatment option for patients with chronic heart failure. However, acute rejection remains as a the significant challenge that leads to cardiac allograft dysfunction, resulting from immune system activation and reactive oxygen species (ROS) production by inflammatory cells. Current immunosuppressive regimens have limitations, such as systemic administration, toxicity, and inefficient inhibition of B cells, macrophages, and natural killer (NK) cells. Targeted immunosuppressant delivery via nanomaterials is a promising approach for sustained release within allografts, significantly enhancing drug efficiency. Manganese dioxide (MnO2) possesses the characteristics of chemotaxis towards inflammatory sites, scavenging ROS, and facilitating drug transport. In this study, tacrolimus (FK506)-loaded MnO2 nanoparticles (NPs) are synthesized via in-situ polymerization, using polydopamine (PDA) as an intermediate. The resulting FK506@MnO2/PDA NPs exhibit excellent safety and cytocompatibility. This targeted delivery system significantly increases FK506 accumulation in murine cardiac allografts, effectively mitigating acute rejection and prolonging allograft survival. Furthermore, the mechanism by which FK506@MnO2/PDA NPs alleviate acute rejection is investigated, validating that FK506 release inhibits T-cell activation while modulating the inflammatory environment by reducing oxidative stress and scavenging ROS. Fluorescence imaging demonstrates that FK506@MnO2/PDA NPs exhibit prolonged retention and more pronounced accumulation in cardiac allografts compared with free FK506. This study presents a novel strategy for immunosuppressive therapy following cardiac transplantation, potentially improving allograft prognosis.
PMID:41056839 | DOI:10.1016/j.biomaterials.2025.123762
Eur Heart J Cardiovasc Imaging. 2025 Oct 7:jeaf287. doi: 10.1093/ehjci/jeaf287. Online ahead of print.
ABSTRACT
AIMS: While pre-defined reference shapes have been used to assess morphological changes in the left ventricle, standardized methods for evaluating right ventricular (RV) remodeling are lacking. This study aimed to develop and test a new 3D echocardiography (3DE)-based method for quantifying RV shape in a large cohort of healthy individuals and across various disease states.
METHODS AND RESULTS: 3DE-derived RV mesh models were reconstructed in 1043 healthy subjects from the World Alliance of Societies of Echocardiography (WASE) study and in 581 patients with severe aortic stenosis (AS), heart failure with reduced ejection fraction (HFrEF), post-heart transplantation (HTX), severe primary mitral regurgitation (MR), atrial secondary tricuspid regurgitation (A-STR), tetralogy of Fallot (TOF) and pulmonary hypertension (PH). To assess global RV shape, hemi-sphericity volume ratio (HSVR) and hemi-conicity angle (HCA) were calculated, where a higher HSVR and a more acute HCA reflect more spherical and conical shapes, respectively. In the WASE population, females had more spherical RVs, whereas males had more conical RVs (p=0.028). Considering age, younger females had more conical RVs, while older individuals in both sexes showed spherical remodeling (p<0.05). Comparing disease groups with WASE controls, MR, HFrEF, and A-STR patients had more spherical RVs compared to controls (both p<0.001), while PH and TOF patients showed conical remodeling (both p<0.001). In A-STR, a more conical remodeling was associated with adverse clinical outcomes.
CONCLUSION: The proposed 3DE method comprehensively characterizes RV geometry, demonstrating demographic variation in healthy individuals and disease-specific alterations in patients, with important prognostic implications.
PMID:41056461 | DOI:10.1093/ehjci/jeaf287
Eur Heart J. 2025 Oct 7:ehaf710. doi: 10.1093/eurheartj/ehaf710. Online ahead of print.
ABSTRACT
This clinical consensus statement, developed by the Heart Failure Association of the European Society of Cardiology, offers a detailed review of the non-specific management of transthyretin amyloid cardiomyopathy (ATTR-CM). This progressive and often fatal condition is increasingly recognized as a major contributor to heart failure. This document provides advice on symptom management and enhancing quality of life, with a focus on volume management, neurohormonal modulation, and tailored use of diuretics and other supportive therapies that address the distinct pathophysiology of ATTR-CM. It also explores advanced treatment modalities such as heart transplantation and mechanical circulatory support, which play crucial roles in managing advanced stages of the disease. Furthermore, it addresses the management of aortic stenosis in the context of ATTR-CM, advising transcatheter aortic valve replacement as the preferred treatment for these patients. The advice provided in this document relies primarily on expert opinion and retrospective studies due to a notable lack of randomized clinical trials, which underscores a critical research gap and the pressing need for evidence-based treatment protocols.
PMID:41055898 | DOI:10.1093/eurheartj/ehaf710
JACC Case Rep. 2025 Oct 7:105596. doi: 10.1016/j.jaccas.2025.105596. Online ahead of print.
ABSTRACT
BACKGROUND: Implantation of two HeartMate 3 devices in a total artificial heart configuration, known as the HeartMate 6 (HM6) approach, can be used to manage severe biventricular heart failure in a patient who is not eligible for transplantation.
CASE SUMMARY: We report a case in which a young patient presented with heart failure of unknown etiology. She was initially considered a transplant candidate but then was delisted due to allosensitization and a stroke. HM6 implantation was successfully completed.
DISCUSSION: We discuss considerations for perioperative care in patients with HM6 implantation.
TAKE-HOME MESSAGE: HM6 implantation can be used to manage severe biventricular heart failure in patients who are not candidates for heart transplant.
PMID:41055626 | DOI:10.1016/j.jaccas.2025.105596
JACC Case Rep. 2025 Oct 7:105601. doi: 10.1016/j.jaccas.2025.105601. Online ahead of print.
ABSTRACT
BACKGROUND: Cardiac sarcoidosis (CS) is a rare but clinically significant condition in heart transplant recipients.
CASE SUMMARY: A 64-year-old woman with nonischemic cardiomyopathy and heart transplant presented with exertional dyspnea and new reduction in left ventricular ejection fraction. Endomyocardial biopsy, donor-specific antibodies, and imaging were concerning for antibody-mediated rejection versus CS. Empiric treatment for antibody-mediated rejection was initiated, but her left ventricular ejection fraction remained unchanged. Native heart explant was reviewed and was consistent with CS. Methotrexate was started, with clinical and radiographic improvement.
DISCUSSION: Owing to its patchy nature, CS can be difficult to diagnose on biopsy, but cardiac imaging can assist. Heart transplant recipients with known CS have similar outcomes to transplant recipients without CS if they take low-dose steroids indefinitely.
TAKE-HOME MESSAGE: The explanted heart should be extensively examined for CS in transplant recipients; if found, clinicians should prescribe CS-effective therapy indefinitely to prevent recurrence.
PMID:41055622 | DOI:10.1016/j.jaccas.2025.105601
Nat Rev Cardiol. 2025 Oct 6. doi: 10.1038/s41569-025-01220-4. Online ahead of print.
ABSTRACT
The growing epidemics of metabolic-dysfunction-associated steatotic liver disease, type 2 diabetes mellitus, obesity and cardiovascular disease are inextricably linked. Cardiovascular-liver-metabolic (CLM) diseases coexist and interact to constitute a synergy of epidemics (a syndemic), with shared mechanisms and socioeconomic influences. The goal of this Review is to construct this complex public-health issue into a unified framework, using epidemiological data to illustrate the current burden of disease and the trends in the CLM syndemic and to make projections for the future. We also discuss the challenges of promoting CLM health and the need for shared solutions. The proposed micro-meso-macro framework integrates strategies to improve risk prediction and precision prevention and to disentangle the competing risks within the CLM construct (micro), while keeping communities at the heart of CLM health promotion by ensuring access to healthy foods, healthy environments and metabolic interventions (meso). In addition, we propose interventions to eliminate inequities in the social and commercial determinants of health, from communities to healthcare systems (macro). Thus, multisystem interventions could address the trajectories of the CLM disease epidemics simultaneously.
PMID:41053364 | DOI:10.1038/s41569-025-01220-4
Cardiovasc Res. 2025 Oct 6:cvaf179. doi: 10.1093/cvr/cvaf179. Online ahead of print.
ABSTRACT
Anthracycline cardiotoxicity is a severe chemotherapeutic side effect that can lead to heart failure in cancer patients and survivors. Chronomodulated chemotherapy is a promising preventive strategy that encompasses the adjustment of anthracycline administration time to the circadian rhythms (24-hour rhythms) of the body. Circadian rhythms play a major role in cardiovascular physiology and disease and may lead to a time-dependent variation in cardiac sensitivity to anthracyclines. In this review, all available evidence on the topic of chronomodulated anthracyclines for cardiotoxicity reduction and/or oncological efficacy enhancement is summarized. In total, 3 in vitro studies, 12 animal studies, and 9 clinical studies were included. Potential mechanistic explanations involved 24-hour variation in oxidative stress regulation, DNA damage repair, and systemic or intracellular pharmacokinetics. We identified a hypothesized optimal time frame from 3 to 11 AM for anthracycline administration in humans, based on extrapolation of findings in animal studies.
PMID:41052913 | DOI:10.1093/cvr/cvaf179
Diabetes Res Clin Pract. 2025 Oct 4;229:112931. doi: 10.1016/j.diabres.2025.112931. Online ahead of print.
ABSTRACT
AIMS: Following up on a prior placebo-controlled trial (NCT03889236), we examined the effects of an oral glycocalyx-mimetic supplement and a fasting-mimicking diet (FMD) on three urinary peptidomic-based classifiers, which indicate future heart failure (HF2), coronary artery disease (CAD160), and chronic kidney disease (CKD273) risk in South-Asian Surinamese adults with type 2 diabetes mellitus.
METHODS: Forty-four participants were randomly allocated to one of three 12-week interventions: daily glycocalyx-mimetic capsules (n = 18), placebo (n = 14), or a five-day FMD repeated every four weeks (n = 12). Baseline and week-12 urine were profiled via capillary electrophoresis-mass spectrometry (CE-MS). The pre-validated support vector machine (SVM) classifiers (HF2, CAD160, CKD273) produced risk scores that were evaluated through paired t-tests for each group. Peptide-level changes were analyzed using paired Wilcoxon signed-rank tests, and all p-values were Benjamini-Hochberg corrected (α = 0.05).
RESULTS: Glycocalyx-mimetic supplementation significantly reduced HF2 scores (mean Δ = -0.58, 95 % CI -0.83 to -0.33, adjusted p < 0.001) and altered the abundance of 17 peptides, primarily decreasing collagen-derived fragments, suggesting improved extracellular-matrix turnover. The risk scores for CAD160 and CKD273 remained unchanged. FMD and placebo did not produce any meaningful changes in classifier scores.
CONCLUSIONS: In this cohort, glycocalyx-mimetic supplementation improved the urinary peptidomic signature associated with heart-failure risk, whereas an FMD did not. Urinary peptidomics offers a sensitive molecular method for monitoring the effects of (dietary) interventions.
PMID:41052726 | DOI:10.1016/j.diabres.2025.112931
Transpl Immunol. 2025 Oct 4:102308. doi: 10.1016/j.trim.2025.102308. Online ahead of print.
ABSTRACT
BACKGROUND: Kidney transplant recipients experience heightened systemic inflammation, and biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), and high-sensitivity CRP (hsCRP) have been proposed as prognostic indicators.
OBJECTIVE: This meta-analysis evaluates the associations between IL-6, CRP, and hsCRP levels and all-cause mortality, cardiovascular events, and graft dysfunction in kidney transplant recipients.
METHODS: A comprehensive search of PubMed, Web of Science, Scopus, Ovid MEDLINE, and the Cochrane Library until October 11, 2024, identified eligible studies reporting associations between IL-6, CRP, or hsCRP and clinical outcomes in adult kidney transplant recipients.
RESULTS: The systematic review included 40 studies, with 18 meeting criteria for meta-analysis. Elevated IL-6 was associated with a higher risk of graft dysfunction (HR 1.53, 95 % CI 1.28-1.83; I2 = 0 %) and all-cause mortality (HR 1.66, 95 % CI 1.05-2.61; I2 = 97.2 %), but not cardiovascular events. CRP was associated with all-cause mortality (HR 2.07, 95 % CI 1.59-2.70; I2 = 0 %) and cardiovascular events (HR 6.89, 95 % CI 2.52-18.85; I2 = 0 %), but not cardiovascular mortality or graft dysfunction. Elevated hsCRP was associated with all-cause mortality (HR 1.29, 95 % CI 1.15-1.44; I2 = 61 %), but not with cardiovascular events or graft dysfunction.
CONCLUSIONS: Among kidney transplant recipients, elevated levels of IL-6, CRP, and hsCRP were significantly associated with increased all-cause mortality, though the association of IL-6 with all-cause mortality showed substantial heterogeneity and should be interpreted with caution. IL-6 also emerged as a predictor of graft dysfunction, while CRP demonstrated a strong association with cardiovascular events. These findings highlight the potential role of inflammatory biomarkers, particularly IL-6 and CRP, in post-transplant risk stratification; however, further studies are needed to establish causality and clarify their clinical utility.
PMID:41052640 | DOI:10.1016/j.trim.2025.102308
Ultrasound J. 2025 Oct 6;17(1):46. doi: 10.1186/s13089-025-00448-y.
ABSTRACT
BACKGROUND: Pulsus alternans (PA) is an intriguing phenomenon and a clinically rare entity. Accurately assessing cardiac function in patients with PA remains challenging. This study aims to investigate the myocardial mechanical characteristics and non-invasive hemodynamic profiles of PA patients using multiple echocardiographic imaging modalities.
METHODS: Clinical and echocardiographic data were retrospectively analysed from 16 patients diagnosed with PA by echocardiography at our hospital between January 2021 and May 2025. In this study, the characteristics of PA were elaborated by multiple echocardiographic methods, and the non-invasive hemodynamic profile was determined by pulse-wave Doppler.
RESULTS: Sixteen patients were enrolled. Seven were classified as NYHA class III and six as class IV. Elevated levels of NT-proBNP and hs-cTNT were observed in most patients. Follow-up ranged from 1 to 44 months, and five patients experienced adverse outcomes, including heart transplantation, rehospitalisation, and death. Within this cohort, three patients exhibited biventricular PA, while 13 patients presented with left ventricular (LV) PA. Key hemodynamic parameters varied significantly: LVOT-VTIstrong beat ranged from 11.3 cm to 29.2 cm, LVOT-VTIweak beat from 6.8 cm to 22.1 cm, and the variation rate between strong and weak beats (∆LVOT-VTI) ranged from 19 to 52%. Global longitudinal strain (GLS) was significantly reduced in 14 patients (range: - 1.2% to - 10.4%), while peak strain dispersion (PSD) increased (range: 47 ms to 117.5 ms). Two patients were excluded from strain analysis due to suboptimal imaging. Hemodynamic parameters (LVOT-VTIstrong beat, LVOT-VTIweak beat and ∆LVOT-VTI) showed strong correlations with GLS in PA patients (r = 0.806, P = 0.001; r = 0.642, P = 0.018 and r = 0.611, P = 0.027, respectively). NT-proBNP was significantly positively related to adverse outcomes in PA patients (r = 0.669, P = 0.012).
CONCLUSION: Echocardiography is essential for evaluating cardiac function in patients with PA. This study used multiple echocardiographic methods to delineate the characteristics of this intriguing clinical phenomenon. Non-invasive hemodynamic parameters are potentially important for prognosis assessment, and myocardial strain assessment provides valuable insights into myocardial mechanical features. A comprehensive analysis using multimodality imaging is crucial for accurately identifying this disease, potentially enhancing the understanding of the pathophysiological mechanism of PA.
PMID:41051648 | PMC:PMC12500491 | DOI:10.1186/s13089-025-00448-y
Clin Transplant. 2025 Oct;39(10):e70336. doi: 10.1111/ctr.70336.
ABSTRACT
BACKGROUND: Transplant teams may be better prepared to entertain DCD offers with a priori prediction of prolonged warm ischemia time (WIT) and deploy perfusion strategies (PS) to mitigate the risk of WIT.
METHODS: All potential adult Maastricht-III DCDs in one Organ Procurement Organization from January 2016 to July 2024 were reviewed. Data were obtained from UNOS DonorNet. Cases with missing variables were excluded. The most recent clinical values prior to withdrawal of life support treatment (WLST) were utilized. Logistic regression assessed the likelihood of DCD progression within 30 min after WLST.
RESULTS: From a total of 748 potential DCDs, 350 were assessed after exclusion criteria. One hundred and seventy-one (49%) progressed within 30 min. Forty percent (n = 140) of the sample was used for training and 60% (n = 160) for validation. Potassium (OR: 3.01; 95% CI: [1.39, 6.5], p = 0.005), sodium (OR: 1.23; 95% CI: [1.01, 1.50], p = 0.036); body mass index (OR: 1.68; 95% CI: [1.39, 2.03], p = 0.0001) and heart rate (OR: 1.54; 95% CI: [1.24, 1.92], p = 0.0001) positively correlated with progression. Age (OR: 0.71; 95% CI: [0.58, 0.86], p = 0.0006); presence of pupillary reflexes (OR: 0.81; 95% CI:[0.68, 0.92], p = 0.007); presence of corneal reflexes (OR: 0.27; 95% CI: [0.22, 0.34], p = 0.001); and presence of overbreathing the ventilator (OR: 0.39; 95% CI: [0.32, 0.48], p = 0.001) negatively correlated with progression. Discrimination was excellent (NPV 89%; PPV 88%).
CONCLUSIONS: DonorNet variables predict progression to circulatory death within 30 min. If there is an indication that a DCD will not progress within a 30-min threshold, then early discussion of PS may decrease the risk of a dry run.
PMID:41051386 | DOI:10.1111/ctr.70336
Interdiscip Cardiovasc Thorac Surg. 2025 Oct 6:ivaf239. doi: 10.1093/icvts/ivaf239. Online ahead of print.
ABSTRACT
We report Europe's longest documented heart perfusion using the Transmedics Organ Care System (OCS) during a heart transplantation. A 55-year-old patient with end-stage heart failure received a donor heart after 536 min (8 h 55 min) of OCS perfusion and a total out-of-body time of 676 min (11 h 16 min). Due to adverse weather, air transport was not possible, necessitating an extended ground-based journey. Despite initial vasospasm, perfusion parameters remained stable. The heart demonstrated immediate post-transplant function without need of mechanical support. This case demonstrates the potential of the OCS to extend preservation times beyond conventional limits, increasing access to viable donor organs and optimizing transplantation outcomes.
PMID:41051264 | DOI:10.1093/icvts/ivaf239
Front Immunol. 2025 Sep 19;16:1685682. doi: 10.3389/fimmu.2025.1685682. eCollection 2025.
ABSTRACT
Xenotransplantation has experienced major clinical advancements over the past three years. Yet, despite potent immunosuppressive regimens combining B-cell depleting therapies, T cell activation blockade, complement inhibition, and high-dose steroids, signs of antibody-mediated and cellular rejection were seen in the few pig-to human heart and kidney xenotransplants. Considering the recent success of chimeric antigen receptor T cell therapies in severe refractory autoimmune diseases, there are windows for opportunities to develop novel approaches to reduce the burden of immunosuppression. In this line, regulatory T cell (Treg) therapy is an attractive strategy, as Tregs could be genetically modified to recognize pig organs. In this brief review, we summarize the lessons learned from Tregs therapies in allotransplantation, update on the recent development in Treg research for xenotransplantation, and discuss future perspectives of humanizing pigs with human leukocyte antigens to promote tolerance using engineered Tregs.
PMID:41050672 | PMC:PMC12491223 | DOI:10.3389/fimmu.2025.1685682