Trasplante cardíaco

Eur Heart J Case Rep. 2025 Sep 16;9(10):ytaf448. doi: 10.1093/ehjcr/ytaf448. eCollection 2025 Oct.

ABSTRACT

BACKGROUND: Severe aortic insufficiency (AI) after catheter ablation (CA) for ventricular tachycardias (VTs) via a retrograde aortic (RA) approach in patients with left ventricular assist devices (LVADs) has not been reported and is not well recognized.

CASE SUMMARY: A 59-year-old man with dilated cardiomyopathy underwent LVAD implantation as a bridge to transplantation. After 6 months, the drug-resistant VTs increased, and CA was performed via the RA approach since echocardiography showed that the aortic valve was still occasionally open with only trivial AI. After mapping and ablation of the left ventricle (LV), the VTs were acutely suppressed. However, the patient was readmitted to our hospital 8 days later with worsening heart failure. The AI had progressed from trivial to severe and did not improve despite medical therapy; therefore, a surgical aortic valvuloplasty was performed. Since then, the heart failure has resolved for 12 months without AI.

DISCUSSION: This is the first report of a patient with an LVAD who underwent CA via an RA approach for VTs and subsequently developed heart failure due to severe AI that required open-heart surgery. In patients with LVADs, aortic valves may be prone to catheter-induced deformation or injury, and continuous aspiration of the LV by LVADs can lead to significant AI, requiring open-heart surgery. This study demonstrated a real case in which it was important to consider these potential risks when selecting the LV approach as well as during and after the procedures via an RA approach, especially in patients with LVADs.

PMID:41050537 | PMC:PMC12495030 | DOI:10.1093/ehjcr/ytaf448

Eur Heart J Case Rep. 2025 Sep 19;9(10):ytaf478. doi: 10.1093/ehjcr/ytaf478. eCollection 2025 Oct.

ABSTRACT

BACKGROUND: Post-infarction ventricular septal defect (VSD) is a rare but life-threatening complication of myocardial infarction, in severe cases needing heart transplantation. The Aeson Total Artificial Heart (TAH), a bioprosthetic device designed to replace both ventricles, offers an alternative for patients unsuitable for conventional therapies.

CASE SUMMARY: A 69-year-old male presented in cardiogenic shock following an inferior wall ST-elevation myocardial infarction complicated by a large VSD. Initial support included extracorporeal life system. Surgical repair was unfeasible due to the defect's size and proximity to the atrioventricular valve, leaving insufficient rim for septal reconstruction. Total artificial heart implantation was the only viable option, used as bridge-to-decision therapy given the patient's advanced age. Post-operative recovery was prolonged, but the patient was successfully transferred to an inpatient rehabilitation facility, where structured physiotherapy, endurance, resistance, and mobility training led to significant functional improvement. Close collaboration with a mechanical circulatory support perfusionist resolved recurring TAH alarms related to intraventricular pressure and communication issues adapting the diuretic and antihypertensive medication. The patient was discharged home in stable condition, achieving substantial physical recovery and independence in managing the device.

DISCUSSION: The Aeson TAH proved to be a safe and effective therapy, in particular, as bridge-to-decision therapy in this complex case of post-infarction VSD. Inpatient cardiac rehabilitation played a pivotal role in optimizing physical recovery, managing device-related challenges, and preparing the early transition to an independent living. This case highlights the potential of advanced bioprosthetic solutions and the benefits of a structured rehabilitation system in managing severe cardiac conditions. Further research is needed to evaluate the long-term outcomes and broader applicability of the Aeson TAH.

PMID:41050533 | PMC:PMC12495036 | DOI:10.1093/ehjcr/ytaf478

iScience. 2025 Aug 27;28(9):113449. doi: 10.1016/j.isci.2025.113449. eCollection 2025 Sep 19.

ABSTRACT

Hepatic mitochondrial maladaptation features the transition from metabolic dysfunction-associated steatotic liver disease (MASLD) to Steatohepatitis (MASH) up to fibrosis/cirrhosis. However, it is still unexplored whether mitochondrial alterations also affect adipose tissue, muscle and heart during disease progression. C57Bl/6 mice were fed an AMLN diet to recapitulate the human MASLD spectrum. In the liver, TEM depicted a progressive morphologic dysfunction of mitochondria, which appeared swollen in MASH, with disorganized cristae/matrix loss in MASH-fibrosis. The mitophagy pathway was reduced in MASH-fibrosis, thus explaining the accumulation of damaged mitochondria, whereas mitochondrial complexes activities alongside OXPHOS protein levels and ATP production were dampened across the disease in liver, adipose, muscle, and cardiac tissues. Finally, the release of cell-free circulating mitochondrial DNA into the bloodstream reflected tissue mitochondrial impairment. In sum, we demonstrated that alterations in mitochondrial morphology, life cycle, and activity feature all disease stages in the liver but also in other tissues engaged in MASLD evolution.

PMID:41050429 | PMC:PMC12495477 | DOI:10.1016/j.isci.2025.113449

Acta Clin Croat. 2024 Dec;63(3-4):611-618. doi: 10.20471/acc.2024.63.03-04.20.

ABSTRACT

The aim of the study was to determine major adverse cardiac events (MACE) related to the percutaneous coronary intervention (PCI) on saphenous vein graft (SVG) with a second-generation drug eluting stents in patients with previous coronary artery bypass graft (CABG). The research was conducted as a unicenter retrospective observational study which analyzed consecutive patients of both genders who had PCI on SVG from January 1, 2016 until June 30, 2019. The aim was to investigate the occurrence of MACE defined as development of periprocedural myocardial infarction, acute heart failure in the first 24 hours after PCI, unstable angina after PCI, periprocedural stroke, contrast induced nephropathy, death, acute/subacute/late stent thrombosis, and target lesion revascularization. The study included 97 consecutive patients. MACE was recorded in 20.6% of patients, more often in patients with thrombolysis in myocardial infarction grade flow ≤2. High thrombus burden (HTB) was detected in 44.3% of patients and it significantly contributed to the development of MACE. In conclusion, PCI on SVG is a highly challenging procedure, especially in patients with an acute coronary syndrome. In patients who have HTB recorded in SVG, the usage of thrombus aspiration and distal protection device can reduce the frequency of no-reflow phenomenon and consequential MACE.

PMID:41050241 | PMC:PMC12490448 | DOI:10.20471/acc.2024.63.03-04.20

JHLT Open. 2025 Sep 5;10:100383. doi: 10.1016/j.jhlto.2025.100383. eCollection 2025 Nov.

ABSTRACT

BACKGROUND: Donation-after-circulatory-death (DCD) heart procurement is enlarging the donor pool, yet its safety in adults with congenital heart disease (ACHD) is uncertain. We compared early (90-day) and mid-term (3-year) graft outcomes after DCD versus donation-after-brain-death (DBD) heart transplantation in ACHD recipients.

METHODS: Using the United Network for Organ Sharing registry (1 January 2018 - 1 April 2025), we identified adults (≥18 y) with ACHD undergoing isolated heart transplantation. Retransplants and multiorgan procedures were excluded. The primary endpoint was graft failure (death or retransplant). Survival was analysed with Kaplan-Meier curves, multivariable Cox models, and 1:1 nearest-neighbor propensity-score matching (caliper = 0.25 SD) adjusting for donor and recipient age, sex, body-mass index, renal and hepatic function, support devices, listing status, prior sternotomy, and regional ACHD center volume.

RESULTS: Among 726 ACHD transplants, 61 (8.4%) used DCD grafts and 665 (91.6%) used DBD grafts. Baseline clinical characteristics were similar, although DCD grafts had longer ischemic times (median 5.3 h vs 3.8 h, p < 0.001) and more frequent exvivo perfusion (65% vs 5.8%). Unadjusted 90-day and 3-year graft survival were lower after DCD (log-rank p = 0.009 and 0.040, respectively). On multivariable analysis, DCD procurement remained an independent risk factor for graft failure at 90 days (HR 2.56, 95% CI 1.23-5.17) and 3 years (HR 2.11, 95% CI 1.03-3.50).Propensity-matched analysis (n = 148) confirmed inferior 90-day survival for DCD recipients (log-rank p = 0.020). Post-operative morbidity and length of stay did not differ between groups.

CONCLUSIONS: In the early US experience, ACHD recipients of DCD hearts experienced significantly worse short- and mid-term graft survival than those receiving DBD hearts, despite comparable peri-operative morbidity. Until preservation strategies further mitigate warm-ischemic injury, careful candidate selection is warranted when allocating DCD grafts to complex ACHD patients.

PMID:41049570 | PMC:PMC12495479 | DOI:10.1016/j.jhlto.2025.100383

JHLT Open. 2025 Sep 4;10:100384. doi: 10.1016/j.jhlto.2025.100384. eCollection 2025 Nov.

ABSTRACT

Living allogenic valve transplantation (LAVT) refers to transplantation of viable human heart valves in an orthotopic or heterotopic fashion and has recently garnered significant interest for children in need of a living, growing, regenerating valve replacement option. However, at present, there is no standardized approach for establishing and implementing such a program. We provide a practical, step-by-step blueprint of the operational, administrative and regulatory requirements needed to establish an LAVT program based on our center's experience.

PMID:41049569 | PMC:PMC12489827 | DOI:10.1016/j.jhlto.2025.100384

Int J Med Sci. 2025 Sep 3;22(15):3946-3957. doi: 10.7150/ijms.118408. eCollection 2025.

ABSTRACT

Heart failure remains one of the leading causes of morbidity and mortality worldwide. Conventional treatment strategies, while beneficial, face numerous limitations. Drug therapies may lead to resistance, while device-based treatments such as LVAD and ICD carry risks of infection, bleeding, device failure, and high costs. For end-stage heart failure, heart transplantation is further constrained by donor shortages and immune rejection. In contrast, cell-based therapies have emerged as a promising alternative. Recent studies have highlighted the critical role of the epicardium and epicardium-derived cells (EPDCs) in cardiac regeneration. These cells contribute to heart repair through multiple mechanisms, including direct cell therapy, the development of epicardium-based biomaterials, and integration with gene therapy approaches. This review outlines the anatomical structure and biological functions of the epicardium, explores the regenerative potential of the epicardium and EPDCs, and evaluates their application in heart failure treatment. Furthermore, it discusses the translational potential and current challenges associated with epicardial-based therapies, offering novel insights and strategies for heart failure management.

PMID:41049437 | PMC:PMC12492376 | DOI:10.7150/ijms.118408

MedComm (2020). 2025 Oct 4;6(10):e70407. doi: 10.1002/mco2.70407. eCollection 2025 Oct.

ABSTRACT

The substantial loss of cardiomyocytes resulting from myocardial infarction leads to pathological remodeling of the heart and the onset of heart failure. Promoting heart regeneration is therefore a critical therapeutic goal for repairing damaged cardiac tissue. Over the past two decades, the utilization of cardiac stem cells for heart regeneration has emerged as a focal point of research. However, the related mechanisms and efficacy remain constrained by poor integration and survival. Concurrently, genetic lineage tracing has definitively shown that the adult mammalian heart lacks significant endogenous stem cells. It is now widely accepted that heart regeneration primarily arises from the proliferation of pre-existing adult cardiomyocytes. This review systematically summarizes the physiological and microenvironmental changes during the developmental process of cardiomyocytes, elucidates the intrinsic and extrinsic molecular biological mechanisms that regulate cardiomyocyte proliferation, and discusses exogenous cell transplantation therapy, potentially endogenous pharmacological and genetic approaches, as well as promising bioengineering and cross-disciplinary methods. By synthesizing these multifaceted advances, this review aims to clarify important issues that require further elucidation in this field, thereby advancing the depth of research on heart regeneration and its clinical translational applications.

PMID:41049268 | PMC:PMC12495452 | DOI:10.1002/mco2.70407

Expert Rev Mol Diagn. 2025 Oct 6. doi: 10.1080/14737159.2025.2570245. Online ahead of print.

ABSTRACT

INTRODUCTION: Calcifying carotid artery atheromas (CCAAs) identified on standard dental panoramic radiographs (DPRs) have been presented as potential disease markers for cardiovascular disease (CVD). CCAAs are further linked to several systemic disease processes (i.e. diabetes) that are also associated with periodontitis. The active matrix metalloproteinase-8 (aMMP-8) mouthrinse point-of-care-test has been multiply globally validated for periodontitis disease diagnostics. Calprotectin can inhibit matrix metalloproteinases and also exert significant anti-microbial activities. Recently, calprotectin has been suggested as a potential biomarker of endovascular inflammation.

AREAS COVERED: This special report considers a combination of mouthrinse aMMP-8 and calprotectin in periodontitis disease diagnostics at the dentist's office for simultaneously identifying at-risk patients of diabetes and CVD reviewing recent PubMed indexed findings comparing disease diagnostics by aMMP-8 and calprotectin individually and combined.

EXPERT OPINION: By combining CCAA-DPRs analysis with oral fluid mouthrinse aMMP-8 and calprotectin lateral-flow immunoassays as point-of-care/chair-side testing's, especially by the polynomial-algorithm-machine-learning technology (including computer vision), can provide a modern noninvasive, safe, economical diagnostic AI-tool. This tool can be utilized for on-line real-time screening of the interlinked processes involving stroke-, CVD-, diabetic- and periodontal disease cascades. Accordingly, identified at-risk patients are then referred for necessary medical and dental interventions.

PMID:41048171 | DOI:10.1080/14737159.2025.2570245

Kardiol Pol. 2025 Oct 6. doi: 10.33963/v.phj.108921. Online ahead of print.

NO ABSTRACT

PMID:41048077 | DOI:10.33963/v.phj.108921

Circ Genom Precis Med. 2025 Oct 6:e005192. doi: 10.1161/CIRCGEN.125.005192. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.

METHODS: We performed single-nucleus RNA sequencing on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.

RESULTS: We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes exhibiting stressed myocardium gene signatures and underlying pathways associated with cardiac hypertrophy; cardiac fibroblasts exhibited activation signatures and compared with adult patients, exhibited heightened downstream processes associated with fibrosis and a unique, myofibroblast-like cluster with increased metabolic stress and antiapoptotic properties. We noted depletion of tissue-resident macrophages and increased vascular remodeling in endothelial cells in pediatric HCM.

CONCLUSIONS: Our analysis provides the first single-nucleus analysis focused on end-stage pediatric HCM. Fibroblast-mediated cellular processes were the most prominent in pediatric HCM, which had more downstream processes associated with fibrosis than did adult HCM.

PMID:41048033 | DOI:10.1161/CIRCGEN.125.005192

Curr Cardiol Rev. 2025 Oct 2. doi: 10.2174/011573403X394902250911111958. Online ahead of print.

ABSTRACT

INTRODUCTION: Sex-based differences in outcomes among patients with heart failure with reduced ejection fraction (HFrEF) treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) remain underexplored. This study aimed to evaluate sex-specific differences in cardiovascular outcomes in patients with HFrEF receiving SGLT2 inhibitors alongside guidelinedirected medical therapy (GDMT).

METHODS: We conducted a retrospective cohort study using the TriNetX global research network. Adults with HFrEF treated with SGLT2is and GDMT were stratified by sex. Propensity score matching (PSM) was used to balance baseline demographics, comorbidities, medications, and laboratory data. Primary outcomes were all-cause mortality and acute heart failure (HF) events; secondary outcomes included hospitalizations, arrhythmias, renal outcomes, and advanced therapies.

RESULTS: After PSM, 17,408 male and 17,408 female patients were analyzed. Male patients had lower odds of acute HF events (aOR: 0.949; 95% CI: 0.909-0.991), all-cause hospitalizations (aOR: 0.933; 95% CI: 0.895-0.973), and renal failure (aOR: 0.915; 95% CI: 0.870-0.962). No significant differences were observed in all-cause mortality (aOR: 1.003; 95% CI: 0.926-1.087) or heart transplantation, although LVAD use was more frequent in males (aOR: 1.416; 95% CI: 1.053-1.905).

DISCUSSION: The findings highlighted potential sex-based disparities in outcomes for patients with HFrEF on SGLT2is. Differential prescribing patterns, comorbidity burden, or timing of therapy initiation may contribute to observed differences.

CONCLUSION: Among HFrEF patients treated with SGLT2is, males experienced lower risks of HF events, hospitalizations, and renal failure compared to females, despite similar mortality. Further research is needed to understand and address sex-specific disparities in HFrEF management.

PMID:41047672 | DOI:10.2174/011573403X394902250911111958

BMC Biomed Eng. 2025 Oct 6;7(1):14. doi: 10.1186/s42490-025-00101-8.

ABSTRACT

BACKGROUND: Continuous cardiac output (CCO) monitoring using pulmonary artery (PA) thermodilution and newly introduced beat-to-beat cardiac output (CO) monitoring technologies exhibits different response time delays. These differences can hinder accurate comparisons of their trending abilities. To address this, we applied moving average processing to the beat-to-beat CO monitor data to evaluate its effect on trending assessment accuracy. This study aimed to confirm the effectiveness of moving average processing for such comparisons.

RESULTS: This was a single-center, retrospective, observational study conducted at a 916-bed university hospital. A total of 20 patients undergoing kidney transplantation were included. We analyzed the trending ability of arterial pressure cardiac index (APCI) and estimated continuous cardiac index (esCCI) relative to continuous cardiac index (CCI) derived from PA thermodilution. Trending ability was assessed using a Polar plot and Bland-Altman analyses. A wide range of moving average windows (0–60 min) was applied to APCI and esCCI. The polar concordance rate at 30° exceeded 92% for moving average windows between 20 and 30 min, with APCI peaking between 21 and 27 min. These improvements reflected both time-shifting and filtering effects of the moving average process.

CONCLUSIONS: Moving average processing over 20 to 30 min significantly enhanced concordance between esCCI and reference CCI, with APCI demonstrating similarly high concordance in the same time window. This approach effectively compensates for differences in response time delays between CO monitoring modalities, enabling more accurate assessment of trending ability.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42490-025-00101-8.

PMID:41047412 | PMC:PMC12498450 | DOI:10.1186/s42490-025-00101-8

BMJ Open. 2025 Oct 5;15(10):e103841. doi: 10.1136/bmjopen-2025-103841.

ABSTRACT

INTRODUCTION: Chronic pain is a common health condition that significantly impacts the quality of life of those affected, affecting one in five people in Canada. The prevalence of this condition tends to increase with age, making it a major health issue given the ageing population. However, its management remains inadequate and requires significant mobilisation of healthcare professionals as well as the development of multiple therapeutic solutions. Among these, non-pharmacological interventions such as hypnosis and virtual reality have proven effective. Nevertheless, while the existing literature seems promising, it presents methodological limitations. Therefore, this study aims to assess the effectiveness of an intervention combining virtual reality and hypnosis in an ageing population suffering from a widespread chronic pain condition, that is, hand arthritis.

METHODS AND ANALYSIS: This study will be a single-centre randomised clinical trial. Participants will be randomly assigned to one of two conditions: one receiving an intervention combining virtual reality and hypnosis, and the other receiving only virtual reality. The effectiveness of the intervention on current perceived pain before and after the intervention (primary outcome) will be evaluated. Secondary outcomes will include anxiety and depressive symptoms, quality of life, relaxation and fatigue. Exploratory analyses will also be conducted to contribute to the emerging literature by examining physiological variables such as heart rate variability, respiratory rate and electrodermal activity during the intervention, and their relationship with primary and secondary outcomes.

ETHICS AND DISSEMINATION: The project was approved by the Research Ethical Committee of the Hospital Maisonneuve-Rosemont (Project no 2024-3539). Participants will be asked to provide written consent for their participation. Results from this study will be shared through peer-reviewed publications, as well as oral and poster presentations at scientific events. The protocol for this study was preregistered on Open Science Framework and raw anonymised data will be available on this platform (https://osf.io/vbh72/?view_only=1d17c5708f894faab6669d85e1fde75d).

TRIAL REGISTRATION NUMBER: NCT06833905.

PMID:41047257 | DOI:10.1136/bmjopen-2025-103841

J Heart Lung Transplant. 2025 Oct 3:S1053-2498(25)02306-X. doi: 10.1016/j.healun.2025.09.019. Online ahead of print.

ABSTRACT

BACKGROUND: This study evaluates the impact of low diastolic blood pressure and resultant coronary hypoperfusion during the agonal phase on outcomes following donation after circulatory death (DCD) heart transplantation.

METHODS: The UNOS registry was queried to analyze adult recipients of isolated DCD heart transplants between 1/1/2019-9/30/2023. Recipients were stratified based on the proportion of the agonal phase with coronary hypoperfusion, defined as diastolic blood pressure <40 mmHg. Using threshold regression, coronary hypoperfusion was classified as extensive (>20% of the agonal phase) or limited (≤20% of the agonal phase). The primary outcome was 1-year post-transplant survival. Risk adjustment was performed using multivariable Cox regression and 1:1 propensity score-matching.

RESULTS: Among 696 recipients of DCD hearts, 105 (15.1%) received hearts with limited coronary hypoperfusion during the agonal phase. The extensive coronary hypoperfusion group had a nominally shorter median agonal phase duration than the limited coronary hypoperfusion group (19 vs. 21 minutes, p=0.17). The recipients with extensive coronary hypoperfusion had significantly reduced 1-year post-transplant survival than those with limited coronary hypoperfusion (91.1% vs. 97.1%, p=0.039). These findings persisted in both multivariable Cox regression and propensity score-matched analyses.

CONCLUSION: Extensive coronary hypoperfusion during the agonal phase in DCD donor hearts is associated with reduced post-transplant survival, even when the total agonal period is short. These findings suggest that the impact of the agonal phase is determined not only by its duration but also by the extent of allograft malperfusion, highlighting the need to reconsider rigid time-based criteria for DCD heart acceptance and utilization.

PMID:41047011 | DOI:10.1016/j.healun.2025.09.019

J Clin Apher. 2025 Oct;40(5):e70061. doi: 10.1002/jca.70061.

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) is a last resort treatment for children with cardio-respiratory failure. Some of these patients will develop thrombocytopenia-associated multiple organ failure (TAMOF), which is sometimes managed with therapeutic plasma exchange (TPE). Our objective is to describe critically ill children on ECMO who underwent TPE for TAMOF. We conducted a single-center retrospective case series of seven children with congenital cardiac disease, requiring ECMO, diagnosed with TAMOF, and treated with TPE between 12/2023 and 6/2024. A centrifugation-based apheresis instrument was used to process 1.5 total blood volume. One packed red blood cell was used to prime the apheresis circuit. Systemic bivalirudin was used for anticoagulation. Seven patients (median age: 55 days, median weight: 4.0 kg, median bypass time: 172 min, 100% VA ECMO, 85% central cannulation, 100% bivalirudin) underwent a total of 30 TPE sessions. The median number of sessions per patient was 3, with a median time to first session of 27.3 h after cannulation. Plasma was used as the replacement fluid in all sessions, with a median volume of 168 mL/kg. The median platelet count increased from 45 × 109/L (38; 54) pre-TPE to 64 (IQR: 45; 75, p < 0.001) post-TPE, despite no platelet transfusions during TPE. The modified organ severity index decreased significantly from 13 to 12 (p < 0.001). The mortality rate was 71%. TPE may improve platelet counts and reduce organ severity scores in critically ill children with TAMOF on ECMO.

PMID:41046521 | DOI:10.1002/jca.70061

Bone Marrow Transplant. 2025 Oct 4. doi: 10.1038/s41409-025-02721-z. Online ahead of print.

ABSTRACT

Belumosudil is approved after failure of ≥2 lines of therapy in chronic graft-versus-host disease cGVHD. However, real-world data is limited. We conducted a retrospective analysis of 67 patients with steroid-refractory or dependent (SR/SD) cGVHD. At baseline, most patients had advanced multi-organ cGVHD. The 6- and 12-month overall response rate (ORR) was 61%. However, a subset of patients achieved deeper responses with ongoing therapy at 12 months. The 6-month failure-free survival (FFS) was 75% (95%CI: 65-86) whereas the 12-month FFS was 66% (95%CI: 55-78). A low incidence of drug-related grade ≥3 toxicities was observed. A cohort of patients with immune function analysis showed gradual improvement in immune subsets at 1-year post-treatment. The combined bel-rux cohort (n = 14) showed a 6- and 12-month ORR of 64% and 57%, respectively. Overall, belumosudil was associated with high treatment response and survival outcomes. Notably, deeper responses were observed with ongoing therapy, and it was overall well tolerated. In a cohort of patients, immune cell populations had preserved to improved values throughout treatment. Patients who received bel-rux demonstrated efficacy and safety as well. Overall, our real-world study indicates similar findings to the clinical trial and supports the use of belumosudil in cGVHD.

PMID:41046308 | DOI:10.1038/s41409-025-02721-z

Eur Urol Focus. 2025 Oct 3:S2405-4569(25)00251-2. doi: 10.1016/j.euf.2025.08.005. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Although cardiovascular toxicity from modern systemic treatments in metastatic hormone-sensitive prostate cancer (mHSPC) remains a concern, real-world data are limited. We aimed to characterise patients treated for mHSPC across multiple large cohorts and estimate cardiovascular adverse event (AE) risks.

METHODS: Leveraging PIONEER's Big Data platform, with databases standardised using the Observational Medical Outcomes Partnership model, we defined cohorts and calculated the incidence rates of AEs per 1000 person-years. The time to first event was assessed via a Kaplan-Meier analysis, and the mean cumulative function (MCF) was estimated for recurrent events. Analyses were stratified by therapy and database.

KEY FINDINGS AND LIMITATIONS: We included 90 087 mHSPC patients from five databases, treated with androgen deprivation therapy (ADT) + androgen receptor pathway inhibitor (ARPI) + docetaxel (DOC) (n = 3743), ADT + ARPI (n = 13 588), ADT + DOC (n = 16 287), or ADT alone (n = 56 469). The distribution of age (63.5-73.7 yr) and comorbidities varied between databases (eg, for hypertension 22-79%). Diabetes was reported in up to 33%, heart failure in 17%, obesity in 25%, and kidney impairment in 26% of men. The highest incidence rates of AEs were as follows: 115 cases (ADT) for acute cardiac events, 403 (ADT + ARPI) for cerebral events, 214 (ADT + ARPI) for thromboembolism, 34 (ADT) for chronic heart failure, and 143 (ADT + ARPI + DOC) for hypertension. The 3-yr acute cardiac event-free survival rate ranged from 79% to 97%, and the 3-yr MCF for acute cardiac events was up to 0.33. Limitations include the retrospective nature and a lack of AE grading.

CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study highlights important heterogeneity in real-world, observational mHSPC data. The included patients demonstrated a substantial comorbidity burden, often exceeding that reported in clinical trials, alongside a high rate of cardiovascular AEs.

PMID:41046191 | DOI:10.1016/j.euf.2025.08.005

J Heart Lung Transplant. 2025 Oct 2:S1053-2498(25)02313-7. doi: 10.1016/j.healun.2025.09.023. Online ahead of print.

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is prioritized in Korea's heart transplant (HTx) allocation system to reduce waitlist mortality, but post-transplant outcomes remain a concern. We compared post-transplant outcomes among HTx recipients bridged with ECMO, left ventricular assist device (LVAD), or without mechanical circulatory support (non-MCS).

METHODS: We retrospectively analyzed 1,021 adult HTx recipients enrolled in the Korean Organ Transplant Registry (2014-2023). Patients were categorized according to bridging strategy at transplantation (ECMO n=357, LVAD n=137, non-MCS n=527). Outcomes included primary graft dysfunction (PGD), in-hospital mortality, any treated rejection, coronary allograft vasculopathy, infection requiring hospitalization, and post-transplant mortality.

RESULTS: ECMO bridging was associated with significantly higher risks of severe PGD (adjusted HR 3.68 vs non-MCS; 2.23 vs LVAD). In-hospital mortality was highest in ECMO recipients (17.9%) compared with LVAD-bridged (4.4%) and non-MCS recipients (4.4%) (p<0.001). Kaplan-Meier analysis demonstrated significantly lower survival in the ECMO group at 90 days (83.2% vs. 94.8% vs. 95.0%) and 1 year (77.5% vs. 89.0% vs. 92.5%) (log-rank p<0.0001). However, in 6-month landmark analyses, survival was similar across groups. Among ECMO recipients, those who died within 6 months had a markedly higher prevalence of pre-transplant dialysis (66.7% vs. 34.7%, p<0.001). The incidence of treated rejection and CAV did not differ significantly among the three groups.

CONCLUSIONS: Direct ECMO bridging is associated with worse early post-transplant outcomes, primarily driven by severe PGD and early mortality, underscoring the need for careful candidate selection. LVAD bridging provided outcomes comparable to non-MCS and may offer a bridge-to-candidacy strategy for selected ECMO patients.

PMID:41046003 | DOI:10.1016/j.healun.2025.09.023

ESC Heart Fail. 2025 Oct 4. doi: 10.1002/ehf2.15437. Online ahead of print.

ABSTRACT

Heart failure (HF) is a progressive condition marked by recurrent episodes of symptom exacerbation, leading to worsening cardiac function, increased hospitalization and mortality risk. Worsening HF (WHF) and advanced HF (AdvHF) represent two distinct stages in this progression, each with unique clinical features and therapeutic needs. WHF is characterized by a deterioration of pre-existing symptoms requiring intensified treatment, such as diuretic escalation, which often reflects disease progression. Conversely, AdvHF involves severe cardiac dysfunction with persistent symptoms despite optimal medical management, requiring advanced interventions such as inotropic support or heart transplant. Although both stages share some pathophysiological and clinical features, they differ significantly in haemodynamic profiles, disease severity and response to treatment. This review argues that recognizing the transition from WHF to AdvHF is a pivotal issue in patient care. We explore the distinct natural histories, clinical presentations and diagnostic markers of WHF and AdvHF to provide a framework for earlier, more targeted interventions aimed at altering the disease trajectory and preventing the decline associated with the advanced stage. While WHF symptoms are typically reversible with appropriate interventions, AdvHF represents the end stage of HF with often irreversible dysfunction and multi-organ involvement. A clearer understanding and standardized definition of these phenotypes are essential for improving patient outcomes and guiding future clinical research.

PMID:41045229 | DOI:10.1002/ehf2.15437