medRxiv [Preprint]. 2025 Mar 5:2025.03.04.25323391. doi: 10.1101/2025.03.04.25323391.
ABSTRACT
BACKGROUND: Antibody-mediated rejection (AMR) remains the major risk factor for allograft loss across all solid organ transplantation. Unfortunately, its diagnosis relies on biopsy, an invasive gold standard that often sample unaffected allograft tissue leading to missed diagnosis. Plasma donor-derived cell-free DNA (dd-cfDNA) is noninvasive biomarker that has high sensitivity but low specificity for AMR diagnosis. This proof-of-concept study assessed the utility of cell-free chromatin immunoprecipitation (cfChIP) as a surrogate for gene expression to detect cardiac AMR and the associated pathobiology.
METHODS: The discovery GRAfT multicenter cohort of heart transplant patients ( NCT02423070 ) identified AMR, acute cellular rejection (ACR), and stable controls based on biopsy and dd-cfDNA results. Plasma cfChIP-sequencing was performed to identify peaks, associated genes and pathobiological pathways. Plasma from an external cohort (GTD, NCT01985412 ) was also analyzed to verify pathways identified. Digital droplet PCR (ddPCR) assays targeting differential regions were constructed to test the diagnostic performance of cfDNA to detect AMR/ACR from stable controls (rejection-specific assays) or AMR from ACR (AMR-specific assays).
RESULTS: The cohort included 21 AMR, 28 ACR, and 45 stable controls from GRAfT and GTD, and 23 healthy controls. cfChIP detected expected active genes, including housekeeping genes and gene targets of transplant immunosuppressive drugs but not inactive genes. Unsupervised clustering of the discovery GRAfT cohort assigned 95% of samples correctly as AMR, ACR or stable control. Differential analysis identified pathobiological pathways of AMR such as neutrophil degranulation and complement activation. The pathways were consistent in GTD samples. Rejection-specific assays detected AMR/ACR from controls with AUC of 0.78 - 0.95. AMR-specific assays detected AMR from ACR with AUC of 0.71 - 0.85, sensitivities of 0.73 - 0.94 and specificities of 0.73 - 0.80.
CONCLUSION: This study provides valuable preliminary data supporting the use of cfChIP to detect AMR and the associated pathobiological pathways.
PMID:40568656 | PMC:PMC12191110 | DOI:10.1101/2025.03.04.25323391
Cardiovasc Ther. 2025 Jun 18;2025:9910333. doi: 10.1155/cdr/9910333. eCollection 2025.
ABSTRACT
Background and Aims: Trimethylamine-N-oxide (TMAO) is recognized as a novel marker and mediator of atherosclerotic cardiovascular disease (ASCVD). Endothelial progenitor cells (EPCs) are crucial for maintaining vascular homeostasis. Impaired EPC numbers and function correlate with increased adverse cardiovascular events. The aim of this study was to decipher the effect of TMAO on late EPCs (LEPCs) and its underlying molecular mechanism. Methods and Results: In vitro migration and tubulogenic capacities of LEPCs were attenuated by TMAO in a dose-dependent manner, accompanied by inhibition of manganese superoxide dismutase (MnSOD) and mitochondrial damage. TMAO-induced mitochondrial damage provoked proinflammatory responses (increased levels of IL-6, IL-1b, ICAM-1, E-sel, and TNF-α) and autophagic cell death (confirmed by western blot immunofluorescent staining and transmission electron microscopy) in LEPCs. Overexpression of MnSOD through adenovirus transfection reversed TMAO-related LEPCs dysfunction. To study the effect of TMAO on LEPC-mediated vascular repair in vivo, a hind limb ischemia model was established in nude mice, and LEPCs were injected in the ischemic hind limb. Laser Doppler imaging of mouse ischemic hindlimbs at 21 days indicated that TMAO treatment inhibited LEPCs-mediated blood flow recovery, which was restored by MnSOD overexpression. Immunohistology analyses further revealed consistent alterations in capillary density determined by CD31 staining. Conclusions: TMAO induces mitochondrial damage in LEPCs via MnSOD suppression, which leads to cell dysfunction, proinflammatory activation, and autophagic cell death in vitro and impaired LEPCs-mediated revascularization in vivo. Overexpression of MnSOD restores TMAO-induced LEPCs dysfunction and further enhances LEPC-mediated revascularization in the ischemic hind limbs in nude mice.
PMID:40568449 | PMC:PMC12197513 | DOI:10.1155/cdr/9910333
JHLT Open. 2025 May 26;9:100289. doi: 10.1016/j.jhlto.2025.100289. eCollection 2025 Aug.
ABSTRACT
INTRODUCTION: Donation after circulatory death (DCD) with thoracoabdominal normothermic regional perfusion (TA-NRP) has been increasingly used to procure cardiac allografts; however, concerns persist regarding its impact on lung allografts. We present our institution's experience with DCD TA-NRP and donation after brain death (DBD) lung transplants, comparing outcomes between the two techniques.
METHODS: All lung transplants recovered with DBD or DCD TA-NRP performed between October 2022 and December 2024 were included. DCD TA-NRP procured lungs were retrieved using a lung protective strategy including early reintubation and pulmonary venting as previously described. The primary outcome was survival, with secondary outcomes of primary graft dysfunction (PGD) and pulmonary-related mortality.
RESULTS: There were 85 DBD and 23 DCD TA-NRP lung transplants performed in the study period. Overall survival was not significantly different by Kaplan-Meier curve (p = 0.49), with 1-year absolute survival of 81.6% for DCD TA-NRP, with only one pulmonary-related mortality, and 89.4% for DBD, with six pulmonary-related mortalities. PGD grade 3 rates were not statistically different at postoperative day (POD) 0 (47.8% DCD TA-NRP vs 35.2% DBD, p = 0.27), POD 1 (21.7% vs 10.6%, p = 0.16), POD2 (8.7% vs 11.7%, p = 0.68), and POD3 (13.0% vs 11.8%, p = 0.87). Other intraoperative and postoperative outcomes were not significantly different.
CONCLUSION: Lung transplantation outcomes were not significantly different between lung grafts recovered by DCD TA-NRP and DBD. This early data suggests TA-NRP may not adversely impact DCD lung allografts during procurement.
PMID:40568346 | PMC:PMC12192336 | DOI:10.1016/j.jhlto.2025.100289
Mayo Clin Proc Innov Qual Outcomes. 2025 Jun 11;9(4):100634. doi: 10.1016/j.mayocpiqo.2025.100634. eCollection 2025 Aug.
ABSTRACT
OBJECTIVE: To evaluate temporal associations of cancer with subsequent incident atrial fibrillation (AF) and temporal associations of AF with subsequent incident cancer, within 3, 3 to 12, and >12 months after index diagnosis.
PATIENTS AND METHODS: We included 13,748 community-dwelling adults (mean age, 54 years) in the Atherosclerosis Risk in Communities study without cancer or AF histories at baseline (follow-up between January 1, 1987, and December 31, 2019). Atrial fibrillation was ascertained from electrocardiograms at study visits and health records. Cancer was ascertained via linkage with state registries and health records. We estimated associations of cancer with AF risk and AF with cancer risk by time since diagnosis using Cox regression, adjusting for shared risk factors and other cardiovascular diseases.
RESULTS: In 3909 adults, cancer was diagnosed before AF. Atrial fibrillation risk was the highest within 3 months after cancer diagnosis (hazard ratio [HR], 11.71; 95% CI, 9.52-14.41), followed by 3 to 12 months (HR, 2.07; 95% CI, 1.54-2.80) and >12 months (HR, 1.46; 95% CI, 1.29-1.64). In 1973 adults, AF was diagnosed before cancer. Cancer risk was the highest within 3 months of AF diagnosis (HR, 2.24; 95% CI, 1.47-3.41), followed by 3 to 12 months (HR, 1.28; 95% CI, 0.91-1.80) and >12 months (HR, 1.09; 95% CI, 0.91-1.29).
CONCLUSION: In adult cancer patients, AF risk is the highest within 3 months after diagnosis and remains significantly elevated throughout survivorship but could be due to detection bias. Cancer risk is strongest within 3 months of AF diagnosis but significantly attenuated over time, suggesting detection bias and reverse causation.
PMID:40568232 | PMC:PMC12192571 | DOI:10.1016/j.mayocpiqo.2025.100634
SAGE Open Med. 2025 Jun 24;13:20503121251348420. doi: 10.1177/20503121251348420. eCollection 2025.
ABSTRACT
OBJECTIVES: Ruxolitinib is used to treat myelofibrosis, polycythemia vera, and steroid-refractory graft-versus-host disease following allogeneic stem cell transplantation. This study aimed to determine the association between ruxolitinib and adverse events by evaluating case reports published between January 2014 and March 2024 in the Japanese Adverse Drug Event Report database.
METHODS: The signals for the ruxolitinib-adverse event association were identified using propensity score-adjusted reporting odds ratio analysis. Data obtained from the drug-gene interaction, drug signature, search tool for chemical interactions, and interaction reference index databases were used to construct a drug-gene interaction network. Functional and pathway enrichment analyses were performed using the Disease Ontology Semantic and Enrichment and ReactomePA R packages.
RESULTS: The propensity score-adjusted reporting odds ratio for ruxolitinib-associated adverse events was as follows: anemia, 18.49 (95% confidence interval (CI): 16.15-21.16); myelosuppression, 4.70 (95% CI: 3.54-6.24); pancytopenia, 1.97 (95% CI: 1.23-3.16); cardiac failure, 2.29 (95% CI: 1.60-3.28); hepatic function abnormal, 1.60 (95% CI: 1.15-2.23); herpes zoster, 6.40 (95% CI: 4.35-9.41); pneumonia, 2.96 (95% CI: 2.35-3.73); renal impairment, 1.34 (95% CI: 0.94-1.90); sepsis, 5.14 (95% CI: 3.75-7.05); interstitial lung disease, 0.33 (95% CI: 0.21-0.52); deep vein thrombosis, 0.32 (95% CI: 0.07-1.44); hemorrhage, 1.99 (95% CI: 1.05-3.75). We also assessed 3015 human genes that directly or indirectly interact with ruxolitinib. The molecular complex detection plug-in of Cytoscape was used to detect 24 clusters. Several genes were enriched in the biological processes of "anemia" and "bacterial infections," identified as significant ruxolitinib-related disease terms.
CONCLUSIONS: This retrospective analysis using the Japanese Adverse Drug Event Report database indicated potential associations between ruxolitinib and adverse events, including anemia and bacterial infections. Future research should explore the underlying pharmacological mechanisms using functional enrichment analysis of ruxolitinib-associated genes related to blood toxicity and bacterial infections.
PMID:40567936 | PMC:PMC12188073 | DOI:10.1177/20503121251348420
Plast Reconstr Surg Glob Open. 2025 Jun 25;13(6):e6916. doi: 10.1097/GOX.0000000000006916. eCollection 2025 Jun.
ABSTRACT
Pediatric heart transplantation can present with many obstacles, including size mismatch of the donor heart with the thoracic cavity of the recipient. For the patient to have vitality, they may need to have surgical interventions to address these conditions. We investigate the case of a 23-month-old infant who underwent orthotopic heart transplantation for nonischemic dilated cardiomyopathy. Given the large size of the donor heart relative to the infant, a subsequent modified thoracoplasty was performed to allow for chest wall closure. This report provides potential surgical techniques that can be taken and follows the patient for a 25-year time span.
PMID:40567426 | PMC:PMC12190079 | DOI:10.1097/GOX.0000000000006916
Circ Res. 2025 Jun 26. doi: 10.1161/CIRCRESAHA.124.326030. Online ahead of print.
ABSTRACT
BACKGROUND: Sipa1 (signal-induced proliferation-associated gene 1) is known as a specific Rap1 GTPase-activating protein that negatively regulates Rap1 signaling. Although Sipa1 has been extensively studied in cancer research, its role in the wound-healing response after myocardial infarction (MI) remains unexplored.
METHODS: To investigate the role of endogenous Sipa1 in MI, we performed permanent left anterior descending artery ligation in both Sipa1 knockout mice and their control littermates. Bone marrow transplantation, flow cytometry, cell sorting, and transcriptomic analysis were conducted to identify the cellular source of Sipa1 in the infarcted heart. The role of cardiac fibroblast-derived Sipa1 during MI was examined using Sipa1 deletion approaches, specifically in cardiac fibroblasts, in vivo and in vitro.
RESULTS: Mice deficient in Sipa1 exhibited improved post-MI survival and cardiac function, along with attenuated expression of inflammatory mediators and diminished accumulation of Ly6Chigh monocytes and CCR (C-C chemokine receptor) 2+ macrophages in the infarcted heart. Although Sipa1 was broadly expressed in the heart, cardiac fibroblasts were responsible for the Sipa1-induced deleterious phenotype as demonstrated by cardiac fibroblast-specific Sipa1 conditional knockout mice, which averted excessive inflammation and adverse cardiac remodeling following MI. Mechanistically, Sipa1 promotes the production of CCL (C-C chemokine ligand) 2, CCL7, and GM-CSF (granulocyte/macrophage colony-stimulating factor) in the cardiac fibroblasts early after MI via a noncanonical RasGRP2-Ras-JNK signaling pathway, irrespective of canonical Rap1, thereby facilitating the accumulation and activation of inflammatory monocytes and macrophages.
CONCLUSIONS: These results identify a previously unknown fibroblast-myeloid axis characterized by Sipa1, which initiates excessive inflammation and leads to poor outcomes after MI. Targeting Sipa1 offers a potential novel therapeutic strategy to optimize post-MI wound-healing response, thereby preventing the development of chronic ischemic heart failure.
PMID:40567222 | DOI:10.1161/CIRCRESAHA.124.326030
Circ Heart Fail. 2025 Jun 26:e012835. doi: 10.1161/CIRCHEARTFAILURE.125.012835. Online ahead of print.
ABSTRACT
BACKGROUND: The use of donation after circulatory death (DCD) donors for heart transplantation (HT) is increasing in the United States. Whether sex differences exist in DCD HT utilization and outcomes is unknown.
METHODS: Adults listed for HT at DCD centers between January 1, 2019 (first US DCD HT) and September 15, 2023, in the Organ Procurement and Transplantation Network Registry were included. Differences in listing for DCD HT by sex were investigated using multivariable logistic regression. The impact of listing for DCD HT (modeled as a time-varying covariate) on waitlist outcomes including the rate of HT waitlist removal for death or clinical deterioration was assessed using multivariable competing risk analyses. Annual trends in DCD HT and 2-year survival after DCD HT by sex were also investigated.
RESULTS: A total of 9807 individuals were listed at DCD centers during the study period. Listing for DCD HT was less common among women after multivariable adjustment (odds ratio, 0.84 [95% CI, 0.76-0.92]; P<0.001). Listing for DCD HT was associated with an adjusted increased rate of HT (hazard ratio, 1.85 [95% CI, 1.75-1.95]; P<0.001) and a lower risk of waitlist removal for death or clinical deterioration (hazard ratio, 0.57 [95% CI, 0.45-0.73]; P<0.001) for both men and women; these protective effects were not different between sexes (interaction terms: transplant, P=0.55; delisting, P=0.91). During the study period, women made up 26% to 29% of donation after brain death transplants, but only 18% to 20% of DCD transplants. Survival at 2 years after DCD HT was similar between sexes (87% for women and 88% for men; log-rank P=0.37).
CONCLUSIONS: Women were less likely to be listed for DCD HT and makeup proportionally less DCD transplants compared with men. Being listed for DCD HT improved waitlist outcomes in both sexes. One-year survival after DCD HT was similar by sex. As DCD HT expands, additional measures to ensure equitable access are imperative.
PMID:40567220 | DOI:10.1161/CIRCHEARTFAILURE.125.012835
World J Pediatr Congenit Heart Surg. 2025 Jun 26:21501351251345790. doi: 10.1177/21501351251345790. Online ahead of print.
ABSTRACT
Congenital sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly with an incidence ranging from 0.1% to 3.5% of all congenital heart disease. Sinus of Valsalva aneurysm involving more than one sinus of Valsalva is very rare and dangerous. Valve-sparing root replacement is a safe and effective procedure that preserves growth potential for the aortic valve and has some benefits compared with valve replacement. There are limited data on valve-sparing operations in neonates and young children. In this case report, we present the surgical correction of an isolated, unruptured, multiple SVA in a 1.4-year-old child using the Yacoub II valve-sparing procedure.
PMID:40567013 | DOI:10.1177/21501351251345790
Perm J. 2025 Jun 26:1-9. doi: 10.7812/TPP/25.041. Online ahead of print.
ABSTRACT
INTRODUCTION: Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi and can remain clinically silent for decades. The objectives of this study were to quantify the prevalence of CD within the membership of Kaiser Permanente Northern California, to describe the demographic and clinical characteristics of patients with CD, and to report their adverse cardiovascular outcomes.
METHODS: In this cohort study from 2006 to 2022, the authors identified patients with CD by screening the electronic medical record for International Classification of Diseases, 9th Revision and 10th Revision codes. The authors obtained demographic, medical history, electrocardiographic, echocardiographic, and pharmacy data. Adverse outcomes, including all-cause mortality, heart failure hospitalization, and heart transplantation, were identified by database programming and confirmed by manual chart review.
RESULTS: There were 53 cases of CD in total, and 75% of patients self-identified as Hispanic. The mean age was 49 years old, and 45% were female. Dyslipidemia (45%) and hypertension (32%) were common comorbidities. A total of 7 patients (13%) had a left ventricular ejection fraction < 45%. During the follow-up period, adverse outcomes included 4 cardiovascular deaths, 5 heart failure hospitalizations, and 4 heart transplantations. The prevalence of diagnosed CD in the Kaiser Permanente Northern California population has risen from 0.22 per 100,000 persons from 2006 to 2010 to 0.70 per 100,000 persons from 2018 to 2022.
DISCUSSION: The prevalence of diagnosed CD in Kaiser Permanente Northern California increased during the study period, and patients with CD frequently had poor cardiovascular outcomes, likely due to the patients presenting with advanced disease.
CONCLUSION: Systematic screening and awareness are likely to facilitate early diagnosis and improve treatment to avoid chronic complications of CD.
PMID:40566857 | DOI:10.7812/TPP/25.041
J Clin Med. 2025 Jun 12;14(12):4195. doi: 10.3390/jcm14124195.
ABSTRACT
Objectives: This study aims to describe the experience of using ECMO on various patients who require ECMO support during the entire perioperative period of lung transplantation. ECMO has several roles: it can bridge patients to transplantation, improve lung graft function in case of primary graft dysfunction after transplantation, improve left ventricle function after transplantation in patients with primary pulmonary hypertension, and manage COVID-19 patients who are awaiting LuTx or undergoing LTx. Methods: We present 6-year results from a high-volume lung transplant center (219 cases/6 years, >50 cases/2022). We used ECMO in 56 cases (25.6%) of all lung transplants between 2018 and 2023. Results: The one-year survival rate of patients transplanted on ECMO was 85.7%. We applied all advanced ECMO techniques, such as bridging to transplantation on ECMO (n = 15, early survival 66.7%) and left ventricular conditioning after LuTx with VA-ECMO (n = 12, 60-day and one-year survival 85.1% and 53%, respectively). We also bridged patients with COVID-19 to transplantation and transplanted them from ECMO (n = 9, early survival 55%). Conclusions: This article shows possible applications of ECMO therapy for various indications in lung transplant patients and, along with data from other publications, it demonstrates that ECMO can improve survival and outcomes for patients with respiratory failure, primary pulmonary hypertension, and COVID-19. The COVID-19 pandemic highlighted new utilization of ECMO, demonstrating its usefulness and importance in critical care medicine. Further research into capabilities of the ECMO system may expand the knowledge about its role in lung transplantation and future treatments.
PMID:40565939 | PMC:PMC12194707 | DOI:10.3390/jcm14124195
J Clin Med. 2025 Jun 9;14(12):4083. doi: 10.3390/jcm14124083.
ABSTRACT
This review provides an in-depth analysis of argatroban as an alternative anticoagulant in cardiac surgery, with a focus on its use in patients with heparin-induced thrombocytopenia (HIT). We examine argatroban's pharmacokinetics and dosing regimens and the challenges associated with cosnventional monitoring methods-such as activated clotting time (ACT) and activated partial thromboplastin time (aPTT)-to evaluate its safety and effectiveness in high-risk surgical settings. Drawing on data from multiple case reports and series, our review highlights both the potential benefits and limitations of argatroban, including complications such as clot formation in extracorporeal circulation systems and prolonged postoperative coagulopathy. In addition to the literature review, we present a detailed clinical case of urgent HeartMate 3 left ventricular assist device implantation in a patient with advanced heart failure and active HIT. In this case, despite targeting an ACT above 400 s, intraoperative complications such as clot formation in the heart-lung machine and difficulty achieving hemostasis highlight the need for improved monitoring and dosing protocols. Our findings call for refined anticoagulation strategies and advanced monitoring techniques to optimize argatroban use in cardiac surgery, offering valuable insights for clinicians managing complex scenarios where conventional heparin therapy is contraindicated.
PMID:40565829 | PMC:PMC12194504 | DOI:10.3390/jcm14124083
Bioengineering (Basel). 2025 Jun 16;12(6):657. doi: 10.3390/bioengineering12060657.
ABSTRACT
Stem-cell-based therapies rely on the transplantation of stem cells or stem-cell-derived organotypic cells into injured tissues in order to improve or restore tissue function that has been impaired by various diseases. The potential of induced pluripotent stem cells has created many applications in the field of cell therapy, for example. Some applications, for example, those in cardiac cell therapy, suffer from low or very low efficiencies of cell engraftment. Therefore, magnetic cell targeting can be discussed as a method for capturing superparamagnetic nanoparticle-labelled cells in the tissue. Here, we employ superparamagnetic iron oxide nanoparticles (SPIONs) for the intracellular magnetic loading of mesenchymal stem cells (MSCs). In addition, we test a novel strategy of labelling MSCs with ferromagnetic particles. The adhesion assays demonstrate a faster adhesion kinetic of SPIONs-loaded MSC spheroids when a magnetic field was applied, resulting in >50% spheroid adhesion after 30 min. Clustering of cells inside the magnetic field is a second potential mechanism of magnetic cell retention and >80% of cells were found to be aggregated in clusters when placed in a magnetic field for 10 min. SPIONs-loaded and ferromagnetic-particle-loaded cells performed equally in the cell clustering assay. In conclusion, the clustering of SPION-labelled cells explains the observation that magnetic targeting reaches maximal efficiency in vivo after only 10 min of magnetic field application. This has significant implications for magnetic-targeting-assisted stem cell and cell replacement therapies.
PMID:40564473 | PMC:PMC12189464 | DOI:10.3390/bioengineering12060657
Biomedicines. 2025 May 29;13(6):1335. doi: 10.3390/biomedicines13061335.
ABSTRACT
Background: Right ventricular primary graft dysfunction (RV-PGD) is a rare but serious complication following heart transplantation, associated with a high morbidity and mortality. Temporary mechanical circulatory support is indicated when patients fail to respond to pharmacological therapy. This study aimed to evaluate the outcomes of patients with RV-PGD who received RV mechanical support with the Impella RP Flex device at our institution. Methods: Medical records of patients with RV-PGD supported by the Impella RP Flex device between December 2022 and March 2024 were reviewed retrospectively to assess survival, procedural complications, duration of support, and end organ dysfunction. Results: Of the 20 patients reviewed, 5 met the inclusion criteria. All five patients demonstrated recovery of RV function after a mean support duration of 8.6 ± 3.05 days. One pump showed transient evidence of biologic material ingestion during a weaning trial. No cases of tricuspid valve injury were observed. The most common complications were hemolysis, bleeding, and acute kidney dysfunction, with all patients requiring hemodialysis. Conclusions: Impella RP Flex support is safe and effective for managing primary and isolated RV-PGD without the need for additional blood oxygenation. However, bleeding complications requiring intervention remain a significant concern, and further evaluation of renal recovery is warranted.
PMID:40564056 | PMC:PMC12190657 | DOI:10.3390/biomedicines13061335
Pediatr Transplant. 2025 Aug;29(5):e70123. doi: 10.1111/petr.70123.
ABSTRACT
BACKGROUND: Partial heart transplantation (PHT) is a promising procedure for pediatric patients with irreparable semilunar valve disease. Current immunosuppression regimens mirror orthotopic heart transplant (OHT) protocols. However, semilunar valves may have immune privilege, making true immunosuppressive requirements unclear. This study examines the effect of rejection on semilunar valves in OHT to inform immunosuppression strategies for PHT.
METHODS: We conducted a single-center retrospective case-control study of pediatric OHT recipients from 2008 to 2023. Patients were grouped by the presence or absence of rejection episodes, with further stratification by rejection severity. Semilunar valve function was assessed via echocardiography at baseline, during, and after rejection episodes. Subgroup analysis was performed based on rejection severity and age at transplant (< 1 year of age).
RESULTS: Of 113 eligible OHT recipients, 57 had ≥ 1 rejection episodes (32 high-grade). Baseline valve function was comparable between rejection and non-rejection groups. After a 3.8-year median follow-up, there were no significant differences in aortic or pulmonary valve gradients or in the prevalence of clinically significant regurgitation between groups. Paired analysis during rejection demonstrated no change in valve function compared to pre-rejection assessment. Similar findings were observed in infants transplanted < 1 year of age.
CONCLUSIONS: Over a median follow up of nearly 4 years, semilunar valve function in pediatric OHT recipients remained clinically unaffected by rejection, even in high-grade cases and among younger patients. These findings support the hypothesis of semilunar valve immune privilege and suggest that intensive immunosuppression may not be necessary to preserve valve function after PHT.
PMID:40563161 | PMC:PMC12198430 | DOI:10.1111/petr.70123
BMJ Open. 2025 Jun 25;15(6):e100553. doi: 10.1136/bmjopen-2025-100553.
ABSTRACT
INTRODUCTION: Ischaemia-reperfusion (I/R) injury remains a major challenge in heart transplantation, with mortality risk increasing significantly when allograft ischaemic time exceeds 4 hours. Non-ischaemic heart preservation (NIHP), using continuous hypothermic perfusion, has shown promise in preliminary studies for reducing I/R injury and improving outcomes. This randomised controlled trial aims to compare NIHP with standard static cold storage (SCS) in adult heart transplantation.
METHODS AND ANALYSIS: The trial is a prospective, open-label, multicentre, single-blinded, randomised controlled trial including 66 adult heart transplant recipients across four Swedish hospitals. Participants will be randomised into 1:1 ratio to NIHP or SCS preservation groups and undergo a 12-month follow-up period. The primary outcome is 1-year survival free from acute cellular rejection or retransplantation. Secondary outcomes include quality of life, I/R injury markers, graft function and adverse events. Substudies will evaluate renal function using MRI and continuously monitor physical activity and heart rhythm via wearable devices. Analysis will follow intention-to-treat principles, with time-to-event analysis using Cox proportional hazard models and Kaplan-Meier estimates.
ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority. It will be conducted according to the Declaration of Helsinki and relevant local and international regulations. Results will be published in peer-reviewed journals following Consolidated Standards of Reporting Trials guidelines.
TRIAL REGISTRATION NUMBER: NCT04066127.
PMID:40562558 | PMC:PMC12198846 | DOI:10.1136/bmjopen-2025-100553
Rev Esp Cardiol (Engl Ed). 2025 Jun 23:S1885-5857(25)00190-2. doi: 10.1016/j.rec.2025.04.011. Online ahead of print.
ABSTRACT
Introduction and objectives This report presents updated data on heart transplants in Spain, including procedures carried out in 2024. It reviews trends over the past decade (2015-2024) in donor and recipient characteristics, surgical techniques, immunosuppression strategies, and survival rates. Methods Data were drawn from the Spanish heart transplant registry, which is updated annually. The analysis includes 347 transplants performed in 2024, as well as procedures from 2015 to 2023 (n = 2721). Results In 2024, the number of heart transplants increased by 6.8% compared with 2023. There were no significant changes in recipient age or sex, but the proportion of urgent transplants rose to 47.0%. Use of circulatory support devices increased, particularly extracorporeal membrane oxygenation. The average donor age showed a slight increase in 2024, although the long-term trend remained downward. Donation after circulatory death accounted for 29.1% of transplants in 2024. One-year survival rates improved, reaching 85.2% for transplants performed between 2021 and 2023. Conclusions The number of heart transplants continued to grow, nearing historic highs, largely due to the expansion of donation after circulatory death. Improved 1-year survival reflects the maturity of transplant programs, advances in surgical and medical management, and better pretransplant conditions in recipients. Full English text available from: www.revespcardiol.org/en.
PMID:40562161 | DOI:10.1016/j.rec.2025.04.011
J Card Fail. 2025 Jun 23:S1071-9164(25)00284-2. doi: 10.1016/j.cardfail.2025.05.017. Online ahead of print.
ABSTRACT
BACKGROUND: Cytomegalovirus (CMV) infection post heart transplantation (HT) is associated with worse outcomes. Antiviral prophylaxis for at-risk patients is standard of care. Valganciclovir, the most commonly used antiviral, is associated with significant adverse events, particularly leukopenia. Letermovir is a CMV-specific anti-viral with a favorable side effect profile but its efficacy in HT recipients is unclear. This study aims to assess the safety and efficacy of letermovir for CMV prophylaxis in HT recipients.
METHODS: This single-center retrospective analysis included HT recipients at our center from January 2020-September 2023. Patients who were switched to letermovir for CMV prophylaxis for leukopenia/neutropenia on valganciclovir, and 1) remained on letermovir for at least 60 days or 2) developed CMV viremia on letermovir within 60 days of initiation were included. Primary endpoint was incidence of CMV viremia/disease during letermovir therapy. Secondary endpoints included changes in white blood cell (WBC) count, tacrolimus dosing, and clinically significant acute rejection.
RESULTS: Fifty-two patients received letermovir for an average of 8.2 months (range 1 to 35 months). Average time from transplant to letermovir initiation was 9.2 months, (range 0.9 to 77 months). Eight (15.4%) patients developed breakthrough CMV viremia on letermovir with a median viral load of 205 [IQR 142-367.5] copies/mL, and 4 of these patients were converted back to valganciclovir; overall 92.3% of patients completed therapy with letermovir. There were no episodes of suspected or biopsy-proven, CMV disease. Majority of patients (78%) required dose reductions of tacrolimus following letermovir initiation with no episodes of tacrolimus toxicity requiring hospitalization. WBC counts increased, on average, from 2.6 to 5.3 × 103 cells/μL, p <0.001.
CONCLUSIONS: Letermovir holds promise as an effective and safe alternative to valganciclovir for CMV prophylaxis in HT recipients.
PMID:40562091 | DOI:10.1016/j.cardfail.2025.05.017
J Clin Oncol. 2025 Jun 25:JCO2402477. doi: 10.1200/JCO-24-02477. Online ahead of print.
ABSTRACT
In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.
PMID:40561385 | DOI:10.1200/JCO-24-02477
Eur Heart J Qual Care Clin Outcomes. 2025 Jun 25:qcaf052. doi: 10.1093/ehjqcco/qcaf052. Online ahead of print.
ABSTRACT
There is increasing recognition that social determinants of health affect outcomes in individuals with congenital heart disease and cause health disparities. This scientific statement from the European Association of Preventive Cardiology of the European Society of Cardiology provides an outline of the existing disparities from a global perspective in this population. We review the current knowledge on racial and ethnic patterns and the role of deprivation status, food insecurity, built environment, financial strain, psychological health and parental distress and education and literacy in creating inequities. Finally, we provide future directions for policy, research and clinical practice in achieving health equity in the congenital heart disease population.
PMID:40561137 | DOI:10.1093/ehjqcco/qcaf052