Trasplante cardíaco

J Cardiothorac Vasc Anesth. 2025 May 18:S1053-0770(25)00413-6. doi: 10.1053/j.jvca.2025.05.031. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess concordance between Hemochron Response (ACTr) and the three-activator device Hemochron Signature Elite (ACTe) in adult cardiac surgery patients. To evaluate the correlation between ACTe and anti-Xa values.

DESIGN: Multicenter, prospective observational study.

SETTING: University hospitals.

PARTICIPANTS: Thirty-five elective adult cardiac surgery patients.

INTERVENTIONS: Patients received 300 IU/kg of unfractionated heparin (UFH) before cardiopulmonary bypass (CPB), as recommended by guidelines. ACTe was the reference device, with ACTe target ≥ 450 seconds required to establish adequate anticoagulation during CPB. Otherwise, an additional 100 IU/kg UFH was administered, up to a maximum cumulative dose of 500 IU/kg. Blood samples for ACTe and ACTr and samples for anti-Xa activity were collected simultaneously at baseline and after each UFH administration. The analyses included Pearson correlation, linear regression, and the Bland-Altman test.

MEASUREMENTS AND MAIN RESULTS: Thirty-five patients were enrolled (71% male, median age 68 years). After 300 IU/kg UFH, 13 (37%) patients required a second heparin dose due to ACTe less than 450 seconds despite ACTr ≥ 450 seconds and 5 (14%) due to ACT less than 450 seconds with both devices. Following the second UFH administration, 10/18 (55%) patients still did not reach the target ACTe despite an ACTr ≥ 450 seconds, requiring a third UFH administration. ACTe and ACTr showed no correlation (r = 0.157, p = 0.369). Linear regression analysis demonstrated limited agreement (R2 = 0.025). Bland-Altman analysis indicated a mean bias of -20.7% (95% CI -75.28% to +35.5%), with ACTe underestimating ACTr. The predicted ACTe, corresponding to an ACTr threshold of 450 seconds, was 357 seconds. Anti-Xa levels always exceeded 4 IU/mL, confirming adequate anticoagulation in all cases and were positively correlated to ACTe (r = 0.587, p < 0.001). Predicted ACTe interval corresponding to anti-Xa levels of 4 IU/mL was 263 to 515 seconds.

CONCLUSIONS: ACTe and ACTr showed no correlation. Switching devices without adjusting ACT thresholds leads to unnecessary UFH redosing, despite adequate anticoagulation as measured by anti-Xa levels.

PMID:40555631 | DOI:10.1053/j.jvca.2025.05.031

Transplant Proc. 2025 Jun 23:S0041-1345(25)00305-7. doi: 10.1016/j.transproceed.2025.05.030. Online ahead of print.

ABSTRACT

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic option for hematologic malignancies. However, it is associated with severe complications, including graft-versus-host disease (GVHD). While GVHD is widely recognized for its impact on various organs, its role in the development of heart failure (HF) remains insufficiently understood. This study investigates the association between GVHD and HF following allo-HSCT, focusing on identifying key risk factors contributing to HF development.

METHODS: A retrospective cohort study was conducted on 220 patients who underwent allo-HSCT between 2005 and 2024. HF was defined by clinical criteria and left ventricular ejection fraction. The association of GVHD severity (acute and chronic), inflammatory markers (tumor necrosis factor-alpha, interleukin-6), and cardiac biomarkers (B-type natriuretic peptide) with HF was analyzed. Multivariate logistic regression was performed to identify independent predictors of HF.

RESULTS: Patients with HF demonstrated significantly lower left ventricular ejection fraction (33.92% ± 6.73% vs 61.51% ± 6.18%, P = .021) and higher levels of B-type natriuretic peptide (393.29 ± 71.29 ng/L vs 307.92 ± 76.28 ng/L, P = .042), tumor necrosis factor-alpha (80.3 ± 20.4 pg/mL vs 40.2 ± 10.1 pg/mL, P < .001), and interleukin-6 (65.1 ± 15.7 pg/mL vs 25.4 ± 8.6 pg/mL, P < .001) compared to controls. Severe acute GVHD (Grade ≥III) significantly increased the risk of HF (odds ratio = 3.5, P < .001). Patients with multiple GVHD-related complications had a 3.6-fold higher likelihood of HF development (P < .01). Echocardiographic findings revealed significant cardiac remodeling in HF patients, with increased left ventricular end-diastolic diameter (68.76 ± 7.23 mm vs 44.18 ± 7.16 mm, P = .004) and left ventricular posterior wall thickness (12.18 ± 4.32 mm vs 4.46 ± 2.19 mm, P = .002). Additionally, HF patients experienced more severe transplant-related complications, including infections (29.0% vs 10.6%, P = .041) and hemorrhagic cystitis (23.4% vs 7.1%, P = .027). Mortality was significantly higher in the HF group (86.0% vs 41.6%, P < .001), with infection (71.0%) and HF (21.5%) being the leading causes of death. GVHD significantly heightens the risk of HF after allo-HSCT.

CONCLUSIONS: These findings underscore the necessity for proactive cardiovascular monitoring and targeted therapeutic interventions in GVHD patients to prevent the development of HF.

PMID:40555592 | DOI:10.1016/j.transproceed.2025.05.030

J Card Fail. 2025 Jun 17:S1071-9164(25)00251-9. doi: 10.1016/j.cardfail.2025.05.015. Online ahead of print.

ABSTRACT

BACKGROUND: The impact of amiodarone on severe primary graft dysfunction (PGD) and vasoactive inotropic scores (VIS) following heart transplantation (HT) is unclear.

METHODS AND RESULTS: We investigated these relationships through a retrospective study of 183 consecutive patients > 18 years old who underwent isolated HT at our center from 2018-2023. Data for amiodarone use in the 6 months pre-HT were recorded (duration, cumulative dose, use at HT, last dose pre-HT). Of the 69 patients in the amiodarone cohort, 37 were considered to be on amiodarone at time of transplant. The primary endpoint was severe PGD as defined by International Society of Heart and Lung Transplantation (ISHLT) criteria. Post-HT VIS were calculated as defined by ISHLT.

CONCLUSIONS: Amiodarone was not associated with severe PGD (p = 0.67), and there was no difference in post-transplant VIS based on amiodarone exposure (20 [19.6] vs 16.3 [13.8], p=0.122, Figure 1). This study supports similar hemodynamic profiles post-HT regardless of amiodarone use.

PMID:40553932 | DOI:10.1016/j.cardfail.2025.05.015

Proc Natl Acad Sci U S A. 2025 Jul;122(26):e2424534122. doi: 10.1073/pnas.2424534122. Epub 2025 Jun 24.

ABSTRACT

Tissue fibrosis is commonly associated with organ malfunction and is strongly associated with the development of chronic rejection, cardiovascular diseases, and other chronic diseases. Fibrosis also contributes to immune exclusion in tumor tissues. Targeting fibrosis might be a strategy for prolonging allograft survival while suppressing cancer development. Here, single-cell transcriptomes of human and mouse heart allografts showed that macrophages accumulated in grafts with fibrosis were reprogrammed via histone methylation regulated by Setdb1, an H3K9 methyltransferase. Myeloid-specific deletion of Setdb1 prolonged heart allograft survival but reversed immune exclusion in tumor tissues. Interestingly, myeloid-specific Setdb1-knockout led to lower fibrosis in heart allografts and tumor tissues in mice. Our single-cell sequencing data showed that Setdb1 ablation impaired Fn1+ and SPP1+ profibrogenic macrophage reprogramming. Mechanistically, Fn1, which was induced by the CCR2-Creb/Setdb1 axis, upregulated the expression of genes related to fibrosis in fibroblasts and macrophages via ITGA5 and PIRA receptors. Blocking the interaction between FN1 and these receptors inhibited fibrosis in allograft and tumor tissues. Our results reveal a target, histone methylation in macrophages, for the treatment of fibrosis-related disease.

PMID:40553495 | DOI:10.1073/pnas.2424534122

Scand Cardiovasc J. 2025 Jun 24:1-11. doi: 10.1080/14017431.2025.2525098. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim was to resuscitate and evaluate hearts ex vivo after 22 minutes of cardiac arrest with the goal of increasing the number of usable hearts from controlled donation after circulatory death (cDCD).

DESIGN: Eight pigs (39-61 kg) underwent 22 minutes of ventricular fibrillation, after which the heart was first perfused in vivo for three minutes with an oxygenated, erythrocyte-containing cardioplegic preservation solution. The heart was then explanted and perfused ex vivo with the same solution for three hours at 18 °C in a transportable heart preservation system. Functional evaluation was performed ex vivo (n = 7), while one heart underwent orthotopic transplantation and was monitored for 24 hours.

RESULTS: The seven hearts evaluated ex vivo easily pumped twice the cardiac output measured in vivo. The transplanted heart maintained normal blood pressure, blood gases, and urine output throughout the 24-hour observation period. At the end of this period the aortic pressure was 104/80 mmHg with a heart rate of 129 beats per minute. Intravenous administration of 20, 40, and 100 µg adrenaline resulted in an aortic pressures of 238/171, 284/196, and 287/201 mmHg with corresponding heart rates of 162, 188, and 223 beats per minute.

CONCLUSION: Hearts exposed to 22 minutes of cardiac arrest were successfully resuscitated ex vivo and demonstrated adequate function when evaluated.

PMID:40553492 | DOI:10.1080/14017431.2025.2525098

Clin Transplant. 2025 Jul;39(7):e70213. doi: 10.1111/ctr.70213.

ABSTRACT

INTRODUCTION: The impact of empiric intraoperative vancomycin and piperacillin-tazobactam (VPT) compared to vancomycin and cefepime (VC) on AKI is equivocal, and renal recovery and infection outcomes have not been studied in this context. Further, this has not been studied in patients undergoing orthotopic heart transplantation (OHT).

METHODS: We performed a single-center prospective study in patients undergoing OHT (n = 120), with a change in intraoperative microbial coverage from VPT to VC. Primary outcomes included AKI rates and stage. Secondary outcomes included renal recovery rates, bloodstream bacterial infections, rates of enterococcal infection, ESRD (end-stage renal disease), change in eGFR, and mortality at 12 months post-OHT.

RESULTS: Rates of all stages of AKI were similar between groups (p = 0.769), and the majority of AKI in both groups were Stage 1. 27.1% of patients in the pre-intervention arm and 25.0% in the post-intervention arm had a Stage 3 AKI (p = 0.798). Rates of recovery from AKI at 7 days showed a trend toward improved recovery in patients receiving VC compared to VPT (65.1%, 46.7%, p = 0.056), but recovery from RRT at 7 days and recovery from RRT at hospital discharge were not statistically significant between groups (p = 0.140, p = 0.659). Rates of bloodstream infection were similar following the change in empiric antimicrobials (2.08%, 4.17%; p = 0.53), and rates of wound infection were similar following this change (4.2%, 1.4%; p = 0.56). There was no increase in enterococcal infections.

CONCLUSION: In patients undergoing OHT and receiving empiric antimicrobial therapy, change from VPT to VC did not affect the incidence or severity of AKI, renal recovery, or infection rates.

PMID:40552693 | PMC:PMC12186467 | DOI:10.1111/ctr.70213

Clin Transplant. 2025 Jul;39(7):e70217. doi: 10.1111/ctr.70217.

ABSTRACT

INTRODUCTION: Primary graft dysfunction (PGD) is a significant barrier to survival in lung transplant (LTx) recipients. PGD in patients with systemic sclerosis (SSc) remains especially underrepresented in research.

METHODS: We investigated 92 SSc recipients (mean age 51 years ± 10) who underwent bilateral LTx between 2007 and 2020. PGD was defined as grade 3 PGD at 72 h post-LTx. A comprehensive set of CT image features was automatically computed from recipient chest CT scans using deep learning algorithms. Volumetric analysis of recipients' lungs and chest cavity was used to estimate lung-size matching. Four machine learning (ML) algorithms were developed to predict PGD, including multivariate logistic regression, support vector machine (SVM), random forest classifier (RFC), and multilayer perceptron (MLP).

RESULTS: PGD was significantly associated with BMI >30 kg/m2 (p = 0.009), African American race (p = 0.011), lower Preop FEV1 (p = 0.002) and FVC (p = 0.004), longer waitlist time (p = 0.014), higher lung allocation score (LAS) (p = 0.028), and interstitial lung disease (p = 0.050). From CT analysis, PGD was significantly associated with decreased lung volume (p < 0.001), increased heart-chest cavity volume ratio (p < 0.001), epicardial (p = 0.033) and total heart (p = 0.049) adipose tissue, and five cardiopulmonary features (p < 0.050). Oversized donor allografts estimated using CT analysis were significantly associated with PGD (p < 0.050). The MLP model achieved a maximum AUROC of 0.85 (95% CI: 0.81-0.88) in predicting PGD with four features: Preop FEV1, heart-chest cavity volume ratio, waitlist time, and donor to recipient chest cavity volume ratio.

CONCLUSION: CT-derived features are significantly associated with PGD, and models incorporating these features can predict PGD in SSc recipients.

PMID:40552679 | DOI:10.1111/ctr.70217

Artif Organs. 2025 Jun 24. doi: 10.1111/aor.15035. Online ahead of print.

NO ABSTRACT

PMID:40552484 | DOI:10.1111/aor.15035

Future Cardiol. 2025 Jun 24:1-6. doi: 10.1080/14796678.2025.2521993. Online ahead of print.

ABSTRACT

Xenotransplantation is a promising advancement in the field of transplantation that could eliminate deaths on the waitlist and provide an unlimited supply of on-demand organs for those in need of this life-saving therapy. The results of preclinical studies in orthotopic heart xenotransplantation have shown that non-human primate models can consistently survive 9 months post-transplant. However, early clinical results in orthotopic heart xenotransplantation have been subpar compared to traditional orthotopic heart transplantation as the longest surviving patient survived for 60 days with a complicated postoperative course. Partial heart xenotransplantation could serve as an earlier clinical use case of xenotransplantation products due to the many advantages of the neonate and infant population for xenotransplantation as well as the unique immunogenicity of heart valves which is significantly lower than that of whole hearts. The adoption of partial heart xenotransplantation would allow more children to realize the benefits of a valve that tolerates somatic growth without the need for serial reoperation.

PMID:40552429 | DOI:10.1080/14796678.2025.2521993

Front Oncol. 2025 Jun 9;15:1568169. doi: 10.3389/fonc.2025.1568169. eCollection 2025.

ABSTRACT

Acquired aplastic anemia (AA) is a bone marrow failure syndrome characterized by pancytopenia and decreased hematopoietic stem and progenitor cells (HSPCs) in the bone marrow, it can be either congenital or acquired, predominantly affecting adolescents and the elderly, with higher incidence in Asia compared to Europe and America. Current treatment options include allogeneic hematopoietic stem cell transplantation or immunosuppressive agents, yet proximately a third of patients fail to reach long-term survival. AA is primarily driven by immune-mediated destruction of HSPCs, initiated by self-activated T cells. Early stages feature a Th1 response, which later shifts to Th17 and effector memory CD8+ T cells. Key cytokines including interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) play crucial roles in this immune dysregulation, influencing HSPCs and contributing to bone marrow failure. Furthermore, bone marrow macrophages (MΦ), particularly M1 subtype, are implicated in AA via the TNF-α/TNF-α receptor pathway, leading to T cell activating and subsequent HSPC damage. Interestingly, MΦ with high expression of IL-27Ra have been demonstrated to contribute to HSPC destruction in AA murine models. Beyond their role in thrombosis, platelets also participate in immune regulation. Some studies suggest that platelet may modulate T cell responses through mechanisms such as Akt-PGC1α-TFAM pathway or PF4-mediated activity, which could play a role in AA. However, direct evidence connecting platelet regulation to T cell-mediated HSPC damage is limited, and current research has largely focuses on CD8+ T cells. Moving forward, it is essential to investigate the interactions between platelets, CD4+ T cells, and mitochondrial energy metabolism. In this review, we propose that platelet-derived factors such as PF4 and TGFβ may activate mitochondrial pathways, influencing T cell activation and leading to HSPC destruction in AA. This hypothesis could provide new insights into the molecular mechanisms of AA and pave the way for novel therapeutic strategies (Highlight).

PMID:40552264 | PMC:PMC12183292 | DOI:10.3389/fonc.2025.1568169

Xenotransplantation. 2025 May-Jun;32(3):e70058. doi: 10.1111/xen.70058.

ABSTRACT

INTRODUCTION: Xenotransplantation has emerged as a promising solution to organ shortage, generating numerous publications. However, no studies have analyzed the research dynamics of xenotransplantation research. We aimed to systematically assess xenotransplantation publication activity.

METHODS: A systematic literature search was conducted up to November 22, 2024. Studies on xenotransplantation of solid organs and islets of Langerhans from animals to humans, or perfusion with human blood or its derivatives were included. Publication information, publishing journal, publication type, organ, donor species, and topics studied were extracted.

RESULTS: Of 2944 publications, 706 met inclusion criteria: 41.2% original articles, 41.1% reviews, 14.2% publications without original data, 1.6% case reports, 1.3% research letters, 0.6% systematic reviews/meta-analyses. Publication activity displayed two peaks: in the 1990s, driven by the gene editing advancements, and in the early 2020s, following the first pig-to-human transplantation. The top five publishing countries were the USA with (48.2%), Germany (10.2%), UK (5.4%), Sweden (4.8%), and China (4.2%). Xenotransplantation journal accounted for 19.7% of publications, transplantation journals for 27.6%, and general medical journals for 5.4%. Islets of Langerhans were studied in 23.1% of studies, and the most studied organs were heart (21.2%), followed by kidney (17.1%), liver (12.2%), and lung (6.2%). The most represented thematic groups were rejection, immune mechanisms, overall challenges, gene editing, current research, and prospects.

CONCLUSION: This first systematic assessment of xenotransplantation research highlights its growing global interest and evolving focus areas. The low proportion of publications with original data underscores the need for more original research. Limited representation in general medical journals highlights the importance of engaging a broader audience as clinical trials approach.

PMID:40551623 | DOI:10.1111/xen.70058

BMC Nephrol. 2025 Jun 23;26(1):290. doi: 10.1186/s12882-025-04264-3.

ABSTRACT

BACKGROUND: Chronic kidney disease represents an immunocompromising condition and a cause of a lower vaccine efficacy, even in patients undergoing maintenance dialysis. Recent SARS-CoV-2 outbreaks have prompted clinicians to better understand the underlying mechanisms and establish more suitable vaccination schedules.

METHODS: In a single-center, retrospective, observational study of patients undergoing maintenance dialysis in France, we studied the factors associated with the intensity of the humoral response to a SARS-CoV-2 vaccine in this population, including specific dialysis-related variables.

RESULTS: After having received three doses of SARS-CoV-2 mRNA vaccine, a cohort of 80 patients was divided into low-responders (28 patients with an anti-SARS-CoV-2 antibody level of 50-1830 AU/mL) and responders (52 patients with an antibody level > 1830 AU/mL). We found that chronic heart failure (p < 0.00001), higher performance status (p = 0.004), hypoalbuminemia (p < 0.001), lymphopenia (p = 0.003), Rhesus status positivity (p = 0.02), and absence of response to a hepatitis B virus vaccine (p = 0.02) were associated with a poor response to a third dose of SARS-CoV-2 vaccine. In contrast, none of the dialysis-related variables were associated with the vaccine response. In multivariate logistic regression, chronic heart failure (p < 0.0001) and hypoalbuminemia (p = 0.0004) remained associated with a lower humoral response to SARS-CoV-2 vaccine.

CONCLUSIONS: Our results showed that chronic heart failure and hypoalbuminemia were factors associated with a poor humoral response after three doses of SARS-CoV-2 vaccine. However, we found no association between specific dialysis-related variables and the anti-SARS-CoV-2 antibody titer.

PMID:40551111 | PMC:PMC12186387 | DOI:10.1186/s12882-025-04264-3

Medicine (Baltimore). 2025 Jun 20;104(25):e43043. doi: 10.1097/MD.0000000000043043.

ABSTRACT

RATIONALE: Heart transplantation (HT) represents the optimal treatment for patients with end-stage heart disease. However, it is prone to numerous postoperative complications, among which cardio-renal syndrome (CRS) is particularly serious and carries a high mortality rate. Continuous renal replacement therapy is an essential supportive treatment for these patients, but its efficacy is highly dependent on precise nursing management. Currently, there are few reports on the care of CRS complicating HT both domestically and internationally. This case is presented in this report to provide reference for clinical work.

PATIENT CONCERNS: This report details the case of a 31-year-old man who underwent an in situ HT due to dilated cardiomyopathy with class IV cardiac function. Following the operation, he developed CRS, which led to oliguria, rapid deterioration of renal function, and cardiac failure.

DIAGNOSES: Cardiorenal syndrome, chronic kidney disease stage 4, post-dilated cardiomyopathy surgery, HT status, heart function class IV (NYHA classification).

INTERVENTIONS: This includes implementing a personalized continuous renal replacement therapy (CRRT) program and providing excellent CRRT care; closely monitoring for rejection and the side effects of immunosuppressants; and offering comprehensive psychological support.

OUTCOMES: After undergoing CRRT for 5 weeks, the patient's 24-hour urine volume, glomerular filtration rate, and N-terminal brain natriuretic peptide precursor levels stabilized, leading to discharge with improved renal function.

LESSONS: The key to a favorable renal function prognosis is the use of CRRT for precise volume management. Careful management of internal jugular vein catheterization is crucial for preventing infections in post-heart transplant patients. Additionally, monitoring the side effects of immunosuppressive drugs and signs of rejection are essential nursing points for patients with cardiorenal syndrome. Providing psychological care in various forms to patients and their families can help improve disease outcomes and ensure long-term efficacy after transplantation.

PMID:40550023 | PMC:PMC12187291 | DOI:10.1097/MD.0000000000043043

J Vis Exp. 2025 Jun 6;(220). doi: 10.3791/68090.

ABSTRACT

The number of advanced heart failure patients who can receive a heart transplant is limited by a shortage of suitable organ donors. In efforts to expand the donor pool, alternative donation and procurement methods have been developed, including heart transplantation following donation after circulatory death (DCD HT). While short-term survival following DCD HT is non-inferior to heart transplantation with brain-dead donors, there may be an increased rate of primary graft dysfunction (PGD) associated with DCD HT allografts. The underlying etiology of PGD is multifactorial and incompletely understood. For DCD HT allografts, the period of warm ischemic injury during DCD procurement is a potential risk factor for PGD to which brain death allografts are not exposed. The functional warm ischemic time thus may be an important driver of PGD in DCD HT. However, the mechanisms underlying PGD in this clinical scenario are poorly understood at the molecular level. The work presented herein aims to describe the development and validation of a high-fidelity non-survival porcine model of DCD orthotopic heart transplantation. We hypothesize that the use of this translational large animal model is critical to elucidate molecular mechanisms contributing to PGD, as well as to investigate interventions designed to optimize allograft preservation and early performance. This model replicates the perioperative and surgical approach used in DCD HT clinically, with modifications to account for porcine anatomy and physiology. The development of this large animal surgical model will not only provide mechanistic insights into the development of PGD but also can be modified to enhance translational research efforts aimed at improving organ recovery following DCD HT.

PMID:40549678 | DOI:10.3791/68090

Mol Biol Rep. 2025 Jun 23;52(1):623. doi: 10.1007/s11033-025-10729-3.

ABSTRACT

Recently, immunogene therapy has been of great interest in cardiovascular diseases. In this regard, various immune checkpoint inhibitors (ICIs) are identified to have a crucial role in regulating inflammatory responses. The T-cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3, CD366), a relatively newly discovered group of molecules with a conserved structure, has emerged as a critical immune checkpoint with significant regulatory roles in cardiovascular inflammation and atherosclerosis. This prospective review explores the importance of TIM-3 in modulating immune responses relevant to ischemic heart diseases (IHD), highlighting its interactions with inflammatory pathways such as Toll-like receptor-4 (TLR-4). TIM-3, predominantly expressed on T cells, dendritic cells, and monocytes, acts as an inhibitory receptor that quenches pro-inflammatory signaling, particularly upon binding to ligands like galectin-9. Noteworthy, recent evidence suggests that TIM-3 deficiency or dysregulation can exacerbate inflammatory cascades, contributing to the progression of IHD and related complications. Here, the therapeutic potential of targeting TIM-3 for the management of IHD, especially in the settings of systemic inflammation and post-operative complications, has been discussed. By elucidating the molecular mechanisms and translational prospects of TIM-3 modulation, this work proposes new avenues for immunotherapeutic intervention in cardiovascular disease and post-operative SIRS, warranting further research in clinical trials.

PMID:40549173 | DOI:10.1007/s11033-025-10729-3

ASAIO J. 2025 Jun 23. doi: 10.1097/MAT.0000000000002487. Online ahead of print.

ABSTRACT

Although durable mechanical circulatory support (MCS) has been promising in supporting advanced heart failure patients, device hemocompatibility-related complications remain a major concern compared with heart transplantation. We investigated the blood damage potential of the three most recent clinically available, implantable MCS devices and compared their biocompatibility performance. One axial pump (HeartMate II) and two centrifugal pumps (HeartMate 3 and BrioVAD) were chosen for this study. In vitro experiments with healthy human blood and computational fluid dynamics simulations were performed to compare high-mechanical shear-induced blood trauma in these devices. Regions of higher shear stresses were identified. Power-law relations between shear stress and blood damage were implemented to assess hemolysis, platelet activation, and platelet receptor shedding of key functional receptors (glycoprotein [GP] Ibα, and GPVI) caused by these devices. HeartMate II caused the most severe blood trauma among these three devices, producing an order of magnitude larger values for hemolysis and platelet activation compared with HeartMate 3 and BrioVAD. Also, HeartMate II consistently exhibited the highest levels of receptor shedding, approximately double those caused by the HeartMate 3 and BrioVAD. The HeartMate 3 and BrioVAD centrifugal pumps showed similar performance in terms of blood damage.

PMID:40548579 | DOI:10.1097/MAT.0000000000002487

Exp Clin Transplant. 2025 May;23(5):317-327. doi: 10.6002/ect.2025.0089.

ABSTRACT

OBJECTIVES: Donation after circulatory death offers a promising solution to expand the thoracic organ donor pool, yet its application remains limited because of warm ischemia and technical barriers, especially in uncontrolled donation after circulatory death. We aimed to evaluate a pulsatile normothermic car-diopulmonary bypass-based strategy for thoracic organ recovery of uncontrolled donors after circulatory death and the effects of this strategy on graft function and recipient outcomes.

MATERIALS AND METHODS: In this prospective single-center study, we studied thoracic organs recovered from uncontrolled donors after circulatory death after ≥60 minutes of unsuccessful cardiopulmonary resuscitation. After heparinization and pharmacologic optimization, donors underwent median sternotomy and were connected to a cardiopulmonary bypass circuit with pulsatile flow. Organ assessment was performed in vivo. Donor, graft, and recipient functional data were recorded, with follow-up results studied through at least 1 year.

RESULTS: Forty-two donors were included. All hearts (n = 42) and 40 lungs (from 84 donors) were successfully transplanted. Despite prolonged cardiopulmonary resuscitation, no graft failure or recipient mortality occurred. One year survival for both heart and lung recipients was 100%. Heart grafts showed progressive improvement in functional status, including left ventricular ejection fraction, lactate levels, and New York Heart Association classification; lungs demonstrated sustained gains in gas exchange, pulmonary function tests, and 6-minute walk distance. Mild primary graft dysfunction (grade 1-2) occurred in 10% of lung recipients (all unilateral transplants). Pericardial effusion increased, likely because of trauma before procurement, but resolved without effects on function.

CONCLUSIONS: Pulsatile normothermic cardiopulmonary bypass enables successful procurement of thoracic organs from uncontrolled donors after circulatory death with excellent outcomes. This low-cost physiological approach may offer a viable strategy to expand availability of donors in resource-limited settings.

PMID:40548529 | DOI:10.6002/ect.2025.0089

Infect Control Hosp Epidemiol. 2025 Jun 23:1-8. doi: 10.1017/ice.2025.10217. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the mitigation strategies for a Candida auris outbreak in a cardiothoracic transplant intensive care unit (CTICU) and its implications for infection prevention practices.

DESIGN: Retrospective cohort study from July 2023 to February 2024.

SETTING: A large academic medical center.

METHODS: A multidisciplinary team convened to conduct the outbreak investigation and develop mitigation strategies in the CTICU.

RESULTS: From July 2023 to February 2024, 34 possible hospital-onset cases of C. auris were identified in our CTICU. Whole-genome sequencing and phylogenetic analysis based on pairwise single nucleotide polymorphism (WG-SNP) distance revealed two distinct outbreak clusters. Of the 34 patients, 11 (32.3%) were solid organ transplant recipients and 12 (35.3%) had a mechanical circulatory support device. Of the cohort, only 11/34 (32.3%) had prior exposure to high-risk healthcare facilities within six months prior to admission, as follows: acute inpatient rehabilitation facilities (AIRs) (n = 5, 14.7%), skilled nursing facilities (SNFs) (n = 3, 8.8%), and long-term acute care hospitals (LTACHs) (n = 3, 8.8%). The cohort had a median of 22.0 antibiotic-days prior to their positive results. Five (14.7%) patients had C. auris candidemia, three of whom expired likely due to infection. Infection Prevention (IP) interventions addressed several modes of transmission, including healthcare personnel hands, shared patient equipment, and the environment.

CONCLUSION: Our experience suggests that the epidemiology of C. auris may be changing, pointing towards a rising prevalence in acute care settings. IP interventions targeting hand hygiene behavior and promoting centralizing cleaning and disinfection of shared patient equipment may have contributed to outbreak resolution.

PMID:40548370 | DOI:10.1017/ice.2025.10217

Front Oncol. 2025 Jun 6;15:1570981. doi: 10.3389/fonc.2025.1570981. eCollection 2025.

ABSTRACT

BACKGROUND: POEMS syndrome is a rare multisystem disease secondary to plasma cell neoplasm. Due to its rarity, there are no internationally agreed treatment standards, with very limited data to guide management in the relapse setting.

CASE PRESENTATION: We describe a 51-year-old woman with initially presented with fatigue, anorexia, nausea, abdominal distension, and edema of the face and both lower limbs, who was diagnosed with POEMS syndrome accompanied with Raynaud's phenomenon and cardiac involvement. After multiple lines of treatment, including bortezomib, cyclophosphamide, and dexamethasone (VCD), ixazomib, and daratumumab along with dexamethasone (DD), her clinical and laboratory features, and cardiovascular system continued to deteriorate. Then we started carfilzomib and dexamethasone, and the patient achieved a complete response. She did not develop significant cardiac toxicity and peripheral neuropathy. A total of 4 cycles of carfilzomib and dexamethasone were administered monthly, followed by autologous stem cell transplantation (ASCT). After 4 months of follow-up, a complete remission persists, and no significant complications were observed.

CONCLUSION: We report on the first case of relapsed/refractory POEMS syndrome who received carfilzomib and dexamethasone, and achieved very good remission. Carfilzomib may be a safe and effective treatment option for patients with relapsed/refractory POEMS syndrome.

PMID:40548108 | PMC:PMC12179133 | DOI:10.3389/fonc.2025.1570981

Front Immunol. 2025 Jun 6;16:1538046. doi: 10.3389/fimmu.2025.1538046. eCollection 2025.

ABSTRACT

BACKGROUND: Chronic high-altitude hypobaric hypoxia leads to high-altitude heart disease and heart failure. Recent research has indicated that WJMSCs (Wharton's jelly-derived mesenchymal stem cells, WJMSCs) can alleviate ischemic myocardial injury and improve cardiac dysfunction, and macrophage polarization may have been involved. However, few studies have focused on the cardioprotective effects of WJMSCs against HAHI (high-altitude-induced heart injury, HAHI). Here, our research focused on how WJMSCs regulate macrophage polarization impacted myocardial repair in HAHI.

METHODS: C57/BL6J mice were fed for 28 days at a hypobaric chamber that had a comparable altitude of 6000 m, and WJMSCs were injected intravenously before HH (hypobaric hypoxia, HH) exposure. To assess cardiac function, echocardiography was carried out. Blood and heart tissue were collected for subsequent analysis. We simulated anoxic environment in vitro by inducing BMDMs (bone marrow-derived macrophages, BMDMs) with 1% O2, and employed co-culture system to investigate how WJMSCs affect macrophage polarization.

RESULTS: Abnormal myocardial fibrosis and cardiomyocyte apoptosis, cardiac inflammation and dysfunction were exhibited in the Chronic HAHI mouse model. WJMSCs infusion maintained the cardiac structure and function in HAHI mice. Furthermore, WJMSCs infusion was effective in elevating the M2 macrophages proportion and decreasing inflammation in the heart. In vitro studies revealed that hypoxia stimulation elevated the ratio of M1 macrophages in comparison to those in the Control group and coculturing with WJMSCs encouraged the shift of M1 to M2 macrophages. Surprisingly, the anti-inflammatory effects of WJMSCs on M2 polarization were negated with pretreatment of a COX2 (Cyclooxygenase-2, COX2) inhibitor, which could be reversed with PGE2 (prostaglandin E2, PGE2) addition.

CONCLUSIONS: In conclusions, our findings indicated that WJMSCs infusions may enhance M2 macrophage polarization through the COX2-PGE2 pathway, and therefore safeguard against cardiac damage in HAHI mice.

PMID:40547034 | PMC:PMC12180414 | DOI:10.3389/fimmu.2025.1538046