Trasplante cardíaco

Transplantation. 2025 Jun 24. doi: 10.1097/TP.0000000000005435. Online ahead of print.

ABSTRACT

The rising prevalence of heart failure, global donor heart shortages, and limitations of current assist devices have driven innovation in bioartificial hearts (BAHs) and cardiac constructs. This systematic review aims to give an overview of new developments in BAHs, engineered myocardium, and biohybrid ventricular assist devices research, evaluating their clinical readiness and outcomes while addressing strengths and limitations. Significant variability in study designs and outcomes highlights both advancements and ongoing challenges in this field. Although the development of BAHs and larger cardiac tissue constructs remains in preclinical stages, progress has been achieved in the development of cardiac patches, with 2 approved for clinical use. Several critical challenges continue to hinder the successful clinical translation of bioengineered cardiac solutions. Achieving meaningful myocardial contraction remains a complex task, as well as ensuring adequate vascularization and electrical integration. Biocompatibility limits the progression of bioengineered cardiac constructs toward clinical applications. Innovations in 3-dimensional bioprinting, shape-memory materials, adhesives, microfabrication techniques, and soft and stretchable bioelectronics are driving advancements in this field. However, outcomes regarding hemodynamic performance of BAHs or constructs are marginal at best. Cardiac patches show promising results in preclinical studies, with the paracrine effect of the patches being the most plausible explanation of these results. Importantly, from very little clinical experience thus far, we cannot conclude that cardiac patches have any beneficial effects nor that they are safe. The path toward developing a fully functional BAH or even parts of a functional myocardium appears to be long, complex, and perhaps even unattainable.

PMID:40561089 | DOI:10.1097/TP.0000000000005435

Cell Transplant. 2025 Jan-Dec;34:9636897251348566. doi: 10.1177/09636897251348566. Epub 2025 Jun 25.

ABSTRACT

Mesenchymal stem cells (MSCs) are considered to be effective treatments for various diseases, and a wide variety of clinical studies have been performed worldwide. However, substantial obstacles remain before they can be approved and disseminated as treatments. A major bottleneck is the elucidation of their mechanisms of action, and the molecules that are essential for their efficacy have not been fully characterized. In this paper, I review the studies that attempted to identify the key mediators of MSCs that are involved in their effects on disease using in vivo models. More specifically, studies are discussed in which reductions in the efficacy of MSCs in animal models of disease were induced by the absence of key mediators. The target diseases were lung, joint, cerebral nerve, or cardiac diseases and graft-versus-host disease (GVHD). The following molecules were identified and are discussed herein: TSG-6, VEGF, KGF, HGF, claudin-4, ANXA1, MANF, PYCR1, integrin β1, PDGFRβ, type-II collagen, CD151, TIMP3, TGF-β1, BDNF, COX-2, Botch, IL-1β, CTRP3, CXCR4, miR-34c, FSTL1, IDO, iNOS, IFNγR1, PGES, Chi3l1, and IL-6. These are key mediators of the efficacy of MSCs in vivo.

PMID:40560652 | PMC:PMC12198582 | DOI:10.1177/09636897251348566

J Cardiovasc Dev Dis. 2025 May 29;12(6):205. doi: 10.3390/jcdd12060205.

ABSTRACT

INTRODUCTION: Pediatric heart transplantation (HTX) remains the only therapeutic option for end-stage heart failure not amenable to conventional surgical or catheter interventions. We reviewed our pediatric HTX outcomes according to primary diagnosis.

PATIENTS AND METHODS: Sixty-two patients underwent HTX between 01/2007 and 12/2022. Patients were divided into congenital heart disease (CHD, n = 20) and cardiomyopathy (CMP, n = 42) groups. All potential variables relevant to patient recovery and long-term survival with endpoints of retransplantation or death were analyzed.

RESULTS: CHD patients underwent HTX after significantly more multiple major cardiac surgeries per patient (2.5 [0-5]) than CMP patients (0.5 [0-2], p < 0.01), without notable allosensitization. Post-HTX recovery was longer in CHD (mean mechanical ventilation 7 vs. 3 days, p = 0.001), likely due to longer surgical time (468 vs. 375 min, p = 0.037). There were no significant differences in the frequency of rejections between the two groups (4/20 vs. 9/42). Midterm survival was slightly better (85/70% p = NS) in CMP (median follow-up 44.5 [0-177] months).

CONCLUSION: Our study confirmed good short- and long-term outcomes of pediatric HTX in both CMP and CHD. The longer postoperative recovery in CHD did not lead to higher mortality. No higher pretransplant hypersensitization was observed, possibly explaining the lack of difference in the number and severity of rejections.

PMID:40558640 | PMC:PMC12194210 | DOI:10.3390/jcdd12060205

Curr Opin Cardiol. 2025 Jun 23. doi: 10.1097/HCO.0000000000001238. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: There are several multifactorial risk assessment tools used to predict mortality in patients with pulmonary arterial hypertension (PAH). These tools are also used to guide clinical decision-making including changes in therapy and referrals for transplantation. While the prominent driver of morbidity and mortality in PAH is right ventricular failure, most available risk assessment tools do not include parameters specific to right ventricular structure or function. Several cardiac imaging parameters are known to be associated with survival and may enhance the predictive ability of existing risk scores.

RECENT FINDINGS: This review compiles the existing literature surrounding the improved predictive power of existing risk assessment tools when combined with echocardiographic and cardiac magnetic resonance imaging findings. The review also discusses scenarios in which imaging findings may influence clinical decision making outside of risk scores.

SUMMARY: Decision making in PAH is complex and multifaceted. Cardiac imaging is an important component in the management of PAH and should be considered carefully and in conjunction with existing risk assessment tools.

PMID:40557914 | DOI:10.1097/HCO.0000000000001238

ESC Heart Fail. 2025 Jun 25. doi: 10.1002/ehf2.15353. Online ahead of print.

ABSTRACT

AIMS: Following HeartMate 3 (HM3) LVAD implantation, acute right heart failure necessitating temporary right ventricular assist device (tRVAD) support has not been extensively described. We examined clinical outcomes in patients with HM3 LVAD stratified by the need for tRVAD support.

METHODS AND RESULTS: This was a single-centre, retrospective study of patients who underwent primary HM3 implantation from 2018 to 2022. Patients were placed on tRVAD (concomitant or delayed) support due to clinical deterioration. The primary outcome was 1-year all-cause mortality following HM3 implantation using competing risk analysis with heart transplantation acting as the competing event. A matched cohort analysis was also performed to evaluate the primary outcome of patients with and without tRVAD support. Secondary outcomes included an analysis of risk of LVAD-related adverse events stratified by the presence of tRVAD. Of the 192 patients (median age 60 [49-68] years, 74% male, 37% white), 51 (26%) required tRVAD support. Compared with those with HM3 alone, the tRVAD group had a higher percentage of INTERMACS profile 1 or 2 (49% vs. 27%, P = 0.0005) and had higher rates of pre-operative VA-ECMO (28% vs. 5%, P < 0.0001). The tRVAD group had a higher 1-year all-cause mortality (33% vs. 3%, adjusted HR [95%CI]: 32.4 [9.51-110], P < 0.0001) compared with the HM3 alone group. In-hospital mortality for patients with tRVAD was 26% compared with 1% in patients with HM3 alone (P < 0.0001). In the matched cohort analysis, significantly higher risk of both stroke (HR [95% CI]: 5.75 [1.55-21.3], P = 0.009) and dialysis (HR [95% CI]: 13.4 (3.96-45.5), P < 0.0001) was observed in the tRVAD cohort. Compared with concomitant tRVAD support, the delayed tRVAD group did not have a significantly higher risk of adverse events.

CONCLUSIONS: In this large single-centre experience, patients undergoing HM3 LVAD requiring tRVAD support had significantly higher risks of adverse clinical outcomes.

PMID:40557852 | DOI:10.1002/ehf2.15353

Int J Artif Organs. 2025 Jun 25:3913988251351116. doi: 10.1177/03913988251351116. Online ahead of print.

ABSTRACT

BACKGROUND: Ongoing donor-organ shortage has limited transplantation making LVADs an effective alternative therapy for patients with end-stage heart failure. When LVAD-associated complications arise device exchange is a feasible and safe alternative. This study addresses the factors that impact survival post-LVAD exchange.

METHODS: Our decoded database was constructed retrospectively. Surgical details, device features, and re-intervention information were studied. The primary outcome was mortality. Kaplan-Meier estimators were used for post-pump exchange survival analysis. Pairwise log-rank tests compare the survivals between different groups within each variable. p-Value <0.05 was considered significant. Backward-stepwise regression was used to construct the multivariable model using a subset of variables, retaining only variables with a p-value <0.1. Hazard ratios, their 95% confidence intervals, and p-values of the significant variables were reported.

RESULTS: Analysis of factors impacting survival post-pump exchange study showed a poor survival probability of only primary midline-sternotomy/redo (p = 0.005). Multivariable analysis showed that bridging with ECMO was protective with a hazard ratio of 0.16 (0.03-0.86, p = 0.03).

CONCLUSIONS: The overall survival probability is 50% at 4 years post-pump exchange. This study highlights the differences in post-exchange outcomes depending on the device types and surgical approaches used. LVAD exchange for device-related complications can be performed in high-risk patients as a viable alternative to heart transplantation in the setting of the current heart allocation prioritization systems.

PMID:40557755 | DOI:10.1177/03913988251351116

Clin Transplant. 2025 Jul;39(7):e70193. doi: 10.1111/ctr.70193.

ABSTRACT

BACKGROUND: Days alive and out of the hospital (DAOH) is an increasingly used patient-centered outcome in studies of patients with heart failure, but has not been well studied in heart transplantation (HT). We sought to examine predictors of DAOH at 1-year post-discharge from HT in a diverse population at a large volume HT center.

METHODS: Adult recipients who underwent HT between January 1, 2005 and December 31, 2022 at our institution were included. Baseline demographics were collected as well as psychosocial factors including primary insurance, education, primary language, and socioeconomic status (SES) index as determined by the American Community Survey using patient zip code data. The primary outcome was DAOH at 1 year from HT, accounting for hospital readmissions and time spent in rehabilitation facilities. For patients who died on index admission, DAOH was considered 0.

RESULTS: A total of 1141 patients (26% female, 16% Hispanic, 24% Black) were included in the primary analysis. Seventy-two patients (6.3%) died during the index HT hospitalization. Mean DAOH was 306 (± 87) days. Among those who survived to hospital discharge, 56% were readmitted at least once in the first year after HT. After adjustment for clinical and psychosocial variables, older age, chronic kidney disease, post-2018 allocation change, and greater length of stay at the index hospitalization were associated with significantly fewer DAOH.

CONCLUSIONS: The integration of patient-centered metrics such as DAOH should be a continued priority in our transplant community as it may better convey health-related quality of life.

PMID:40557739 | DOI:10.1111/ctr.70193

Circ Arrhythm Electrophysiol. 2025 Jun 25:e013670. doi: 10.1161/CIRCEP.124.013670. Online ahead of print.

ABSTRACT

BACKGROUND: Differences in cardiac sarcoidosis between racial groups remain understudied. Therefore, this study aims to explore race differences in patients with cardiac sarcoidosis.

METHODS: We analyzed data from the Cardiac Sarcoidosis Consortium, an international registry including over 25 centers. The primary clinical outcome was a composite end point of all-cause mortality, left ventricular assist device implantation, heart transplantation, or implantable cardioverter defibrillator therapy.

RESULTS: A total of 619 patients were included in the study (362 White, 193 Black, and 64 other races). Black patients were diagnosed with cardiac sarcoidosis at a younger age (50.5±11.8 versus 53.7±10.5 years old; P=0.010) compared with White patients. Left ventricular ejection fraction was significantly lower in Black patients (44.6±15.4 versus 48.3±14.0; P=0.008). In addition, extracardiac involvement in the lungs (80.3% versus 72.7%; P=0.046), skin (22.8% versus 12.4%; p=0.002), and eyes (13.5% versus 5.5%; P=0.001) was more prevalent in Black patients. Patients had significantly higher rates of hypertension (69.9% versus 50.6%; P<0.001), diabetes (37.8% versus 21.0%; P<0.001), smoking (40.9% versus 26.8%; P<0.001), chronic obstructive pulmonary disease or emphysema (15.5% versus 4.1%; P<0.001), and chronic kidney disease (25.9% versus 12.4%; P<0.001). The treatment patterns including glucocorticoid (71% versus 74.3%; P=0.4), glucocorticoid-sparing (53.4% versus 59.9%; P=0.14), and implantable cardioverter defibrillator or cardiac resynchronization implantation (75.6% versus 73.8%; P=0.63), were similar. No significant differences were found in the primary outcome (29.5% in Black versus 28.5% in White; P=0.79). Subgroup analysis of the primary outcome also revealed no significant differences in both the left ventricular ejection fraction >35% group (24.1% in Black versus 25.9% in White; P=0.72) and the left ventricular ejection fraction ≤35% group (51% versus 42.5%; P=0.35).

CONCLUSIONS: Black patients with cardiac sarcoidosis exhibited significantly higher rates of lung, skin, and eye involvement and comorbidities, but had similar cardiac clinical outcomes and all-cause mortality compared with White patients. Nonetheless, ascertainment bias cannot be excluded.

PMID:40557494 | DOI:10.1161/CIRCEP.124.013670

Ann Surg Open. 2025 Jun 13;6(2):e582. doi: 10.1097/AS9.0000000000000582. eCollection 2025 Jun.

ABSTRACT

OBJECTIVE: To assess the outcomes of a pair of kidneys from a single donor used for simultaneous heart-kidney transplantation (SHKT) or kidney after heart transplantation (KAH).

BACKGROUND: An Increase in kidney dysfunction among heart transplant candidates has led to an increased need for SHKT and KAH. The risk of early kidney graft loss and mortality is higher in SHKT compared with kidney-alone recipients.

METHODS: Among adult kidney transplant recipients from Oct 2014 to Oct 2022, outcomes were compared between paired kidney-alone vs SHKT and kidney-alone vs KAH. Paired kidney models were used to mitigate differences among donor risk factors. Differential graft years were calculated using restricted mean survival analysis.

RESULTS: A total of 1220 pairs of kidney-alone and SHKT recipients and 441 pairs of kidney-alone and KAH recipients were identified. Among the paired donor kidneys, graft survival was significantly lower in SHKT recipients compared with kidney-alone recipients at 1-year post-transplant (96.1% vs 89.3%; P < 0.001) and at 3-year post-transplant (83.9% vs 78.8%; P < 0.001). This resulted in lower mean graft years [SHKT (3.98 years, standard error = 0.06) vs kidney-alone (4.55 years, standard error = 0.04); P < 0.001] and an additional loss of 57 kidney graft years per 100 transplants (P < 0.01) during the study period. There was no difference in graft survival of paired kidneys in kidney-alone vs KAH recipients with additional loss of 17 kidney graft years per 100 transplants (P = 0.20).

CONCLUSIONS: Optimal recipient selection for kidney after heart transplant under the new safety-net policy may help mitigate the significant risk of kidney graft failure among SHKT recipients.

PMID:40557359 | PMC:PMC12185088 | DOI:10.1097/AS9.0000000000000582

J Investig Med. 2025 Jun 24:10815589251355173. doi: 10.1177/10815589251355173. Online ahead of print.

ABSTRACT

Lung transplantation (LTx) is a vital treatment option for patients with end-stage lung diseases, significantly enhancing survival rates and quality of life. Nonetheless, chronic lung allograft dysfunction (CLAD) remains the primary cause of long-term morbidity and mortality in LTx recipients, posing substantial challenges to patient outcomes and healthcare systems. Despite progress in surgical methods and immunosuppressive treatments, CLAD management is complicated by its multifaceted, potentially irreversible nature. This review delves into critical aspects such as short telomere syndrome (STS), innovations in early detection, and adjunctive therapeutic approaches, offering insights into strategies that may extend the survival of LTx recipients. STS exacerbates CLAD by accelerating cellular aging and hindering tissue repair, necessitating a multidisciplinary approach involving pulmonologists, geneticists, hepatologists, and hematologists to devise comprehensive care plans. The review emphasizes dynamic magnetic resonance imaging as a promising tool for early CLAD detection, enhancing patient monitoring capabilities. Additionally, it examines the roles of extracorporeal photopheresis (ECP), total lymphoid irradiation (TLI), and anti-thymocyte globulins as adjunctive therapies, advocating for their inclusion in standard treatment protocols. This could lead to broader adoption and insurance coverage. Furthermore, we attempt to provide a framework to help decide which adjunctive treatments should be pursued based on the available evidence. By assessing these strategies and highlighting the importance of personalized care, this review aims to guide future research and clinical practice, ultimately improving CLAD management in lung transplant recipients.

PMID:40556056 | DOI:10.1177/10815589251355173

J Cardiothorac Surg. 2025 Jun 24;20(1):272. doi: 10.1186/s13019-025-03505-8.

ABSTRACT

OBJECTIVE: To explore the application and effect of aortic annulus reconstruction (AAR) with bovine pericardium during surgical aortic valve replacement (SAVR) for severe calcific aortic stenosis (AS).

METHODS: We retrospectively reviewed 12 patients with severe calcified AS who underwent bovine pericardium aortic annulus reconstruction between January 2021 to December 2023. The average age of the patients was 58 ± 8.8 years. All patients were diagnosed with severe AS, along with aortic valve and annulus calcification, through chest computed tomography (CT) and transthoracic echocardiography (TTE) prior to surgery. After the resection of severely calcified aortic annulus tissue, all patients were given a bovine pericardial patch to repair the annular defect, and five of these patients underwent Y-incision aortic annular enlargement (AAE). The patients were followed up for a duration of 0.5 to 2 years.

RESULTS: A total of 12 patients undergoing SAVR were enrolled, and all received bovine pericardial patches to repair the annular defects, with a mean preoperative indexed effective orifice area (iEOA) of 0.58 ± 0.098 cm²/m². The average extracorporeal circulation time during the operation was 150.83 ± 34.5 min, and the average cross-clamp time was 95.42 ± 17.46 min. Postoperative evaluations indicated that the structural integrity of the valve annulus remained intact, demonstrating hemodynamic stabilization without any recorded fatalities among participants. Compared to preoperative levels, the aortic valve mean gradient (4.67 ± 1.15 vs. 59.67 ± 17.94 mmHg, P < 0.001), peak gradient (13 [10-15.75] vs. 92 [82.25-110.25] mmHg, P < 0.001), mean aortic jet velocity (99.67 ± 15.44 vs. 367.17 ± 58.13 cm/s, P < 0.001), and peak aortic jet velocity (182.25 ± 23.40 vs. 495.67 ± 61.74 cm/s, P < 0.001) significantly decreased after 0.5 years of follow-up. There were no complications such as hemolysis, perivalvular leakage, thrombosis or endocarditis during follow-up.

CONCLUSION: In patients with severe calcified AS, the AAR technique using bovine pericardium during SAVR is safe and effective, with stable hemodynamic performance and satisfactory clinical outcomes.

PMID:40556029 | PMC:PMC12186314 | DOI:10.1186/s13019-025-03505-8

Cell Death Differ. 2025 Jun 24. doi: 10.1038/s41418-025-01540-5. Online ahead of print.

ABSTRACT

Activation of the intrinsic regenerative potential of adult mammalian hearts by promoting cardiomyocyte proliferation holds great potential in heart repair. CAND1 (Cullin-associated and neddylation-dissociated protein 1) functions as a critical regulator of cellular protein homeostasis by fine-tuning the ubiquitinated degradation of specific abnormally expressed protein substrates. Here, we identified that cardiac-specific transgenic overexpression of CAND1 reduced the infarct size, restored cardiac function, and promoted cardiomyocyte proliferation after myocardial infarction in juvenile (7-day-old) and adult (8-week-old) mice. Conversely, CAND1 deficiency blunted the regenerative capacity of neonatal hearts after apex resection. MS and functional verification demonstrated that CAND1 enhanced the assembly of Cullin1, FBXW11(F-box/WD repeat-containing protein 11), and Mob1b (Mps one binder kinase activator 1b) complexes, and thus promotes the degradation of Mob1b. The ubiquitination of Mob1b occurred at K108 and was linked by K48 of ubiquitin. Mob1b deletion partially rescued the loss of regenerative capacity in neonatal hearts induced by CAND1 deficiency and improved cardiac function in adult mice post-MI. Moreover, CAND1 promoted the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our data demonstrate that CAND1 promotes cardiomyocyte proliferation via FBXW11-mediated K48-linked ubiquitination degradation of Mob1b, and improves heart regeneration after cardiac injury. The findings provide a novel strategy to promote cardiac regeneration and repair. Schematic diagram of the role of CAND1 in regulating ubiquitination and degradation of Mob1b and cardiomyocyte proliferation and heart regeneration. Under CAND1-High condition, CAND1 promotes the incorporation of Cullin1, FBXW11, and Mob1b complexes, and accelerates SCFFBXW11-mediated K48-linked ubiquitination of Mob1b at the K108 site, which leads to the degradation of Mob1b and thus suppresses the Hippo signaling pathway and facilitates cardiomyocyte proliferation and heart regeneration post-MI.

PMID:40555744 | DOI:10.1038/s41418-025-01540-5

Exp Mol Med. 2025 Jun 24. doi: 10.1038/s12276-025-01472-7. Online ahead of print.

ABSTRACT

Barth syndrome (BTHS) is an ultrarare, infantile-onset, X-linked recessive mitochondrial disorder that primarily affects males, owing to mutations in TAFAZZIN, which catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mitochondrial transplantation is a novel technique to treat mitochondrial dysfunction by delivering healthy mitochondria to diseased cells or tissues. Here we explored the possibility of using stem-cell-derived cardiomyocytes as a source of mitochondrial transplantation to treat BTHS. We established induced pluripotent stem (iPS) cells from healthy individuals and from patients with BTHS and differentiated them into cardiomyocytes. The iPS-cell-differentiated cardiomyocytes (CMs) derived from patients with BTHS exhibited less expression of cardiomyocytes markers, such as α-SA, cTnT and cTnI, and smaller cell size than normal iPS-cell-derived CMs. Multielectrode array analysis revealed that BTHS CMs exhibited shorter beat period and longer field potential duration than normal CMs. In addition, mitochondrial morphology and function were impaired and mitophagy was decreased in BTHS CMs compared with normal CMs. Transplantation of mitochondria isolated from normal CMs induced mitophagy in BTHS CMs, mitigated mitochondrial dysfunction and promoted mitochondrial biogenesis. Furthermore, mitochondrial transplantation stimulated cardiac maturation and alleviated cardiac arrhythmia of BTHS CMs. These results suggest that normal CMs are useful for allogeneic transplantation in the treatment of mitochondrial diseases, including BTHS.

PMID:40555742 | DOI:10.1038/s12276-025-01472-7

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