Agregador de feeds

Apoptosis. 2025 Oct 5. doi: 10.1007/s10495-025-02192-z. Online ahead of print.

ABSTRACT

Myocardial ischemia-reperfusion (I/R) injury remains a major challenge in cardiovascular interventions. Although conventional reperfusion therapies restore coronary blood flow, they can often exacerbate myocardial damage. In recent years, ferroptosis, a novel form of regulated cell death characterized by iron-dependent lipid peroxidation, has emerged as a pivotal contributor to myocardial I/R injury. Unlike apoptosis and necrosis, ferroptosis is driven by the accumulation of reactive iron and the peroxidation of membrane phospholipids enriched with polyunsaturated fatty acids (PUFAs), processes that are tightly regulated by lipid metabolism. However, the precise mechanisms linking lipid metabolic reprogramming to ferroptosis during myocardial I/R injury remain incompletely understood. To address this gap, this review systematically examines the interplay between lipid metabolism and ferroptosis in myocardial I/R injury. We highlight the roles of fatty acid uptake, β-oxidation, phospholipid remodeling, cholesterol metabolism, and mitochondria-lipid droplet interactions in forming a deleterious cycle of metabolic disruption, oxidative stress, and membrane damage. Key regulators, such as acyl-CoA synthetase long-chain family member 4 (ACSL4), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and cluster of differentiation 36 (CD36), are emphasized for their roles in contributing to ferroptotic vulnerability. Moreover, the review also explores the protective roles of short-chain fatty acids (SCFAs) and 7-dehydrocholesterol (7-DHC) as emerging anti-ferroptotic agents. Novel yet understudied mechanisms with therapeutic potential are also discussed, including Rab8a-PLIN5-mediated lipid droplet trafficking and 7-DHC reductase (DHCR7) deficiency-induced 7-DHC accumulation. Collectively, this review provides a comprehensive framework for understanding the lipid metabolism-ferroptosis axis in myocardial I/R injury, offering insights for future mechanistic studies and clinical translation.

PMID:41047443 | DOI:10.1007/s10495-025-02192-z

Am J Cardiol. 2025 Oct 3:S0002-9149(25)00556-9. doi: 10.1016/j.amjcard.2025.09.008. Online ahead of print.

ABSTRACT

Surgical revascularization is still considered the gold standard for patients with complex coronary artery disease and left ventricular dysfunction. The advent of Impella has sparked growing interest, yet current evidence on its efficacy remains inconclusive. All studies reporting outcomes beyond 30 days outcomes of pPCI with any Impella device were included. Pooled effect of estimated outcomes was calculated according to a random-effect model with generic inverse variance weighting. Primary endpoint was all-cause mortality. Secondary outcomes were myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. Six studies globally encompassing 1,581 patients were included in the quantitative analysis. Median age was 70 years old (IQR 69 to 72) with a median left ventricular ejection fraction (LVEF) of 27 % (SD ± 6) and a SYNTAX SCORE of 31 (IQR 29 to 35). Impella 2.5 was the most common micro axial flow pump used to support high-risk PCI. All-cause of death was observed in 13.4% (95% CI: 10.4 to 16.4) of patients at 6 months median follow-up. Myocardial infarction occurred in 5.8% (95% CI 3.4 to 8.1) of patients, repeat revascularization in 9.1% (95% CI: 4.8 to 13.3) of patients, stroke in 1.6% (IQR 1.2 to 2.1) of patients and, finally, heart failure rehospitalization in 8.4% (95% CI 3.3 to 13.6) of patients. In conclusion, for high-risk patients, PCI with the Impella device represented a viable strategy with an acceptable risk profile when surgical revascularization is not an option, and a poor prognosis is predicted.

PMID:41046995 | DOI:10.1016/j.amjcard.2025.09.008

Tissue Cell. 2025 Sep 29;98:103163. doi: 10.1016/j.tice.2025.103163. Online ahead of print.

ABSTRACT

BACKGROUND: (STL) is an extensively used anti-depressant drug that has been reported to induce organ damage including cardiac impairments. Nepetin (NEP) is a naturally derived flavonoid which exhibits excellent biological as well as pharmacological properties.

METHODOLOGY: This research investigation explored the cardioprotective ability of NEP to counter STL induced cardiotoxicity in Sprague Dawley rats. Thirty-six male Sprague Dawley rats were categorized into control, STL (20 mg/kg), STL (20 mg/kg) + NEP (10 mg/kg), and NEP (10 mg/kg) alone treated group.

RESULTS: NEP intoxication significantly suppressed the expression of Notch 1, JAG1, DDL4, HES1, and HEY2 while escalating the levels of ROS and MDA. Besides, STL administration increased intraventricular septal thickness during IVSd and IVSs, promoted the internal diameter of left ventricular as well as elevated ESV as while reducing PWs and PWd, LVEF, and LVFS in echocardiographic examination. The enzymatic activities of HO-1, SOD, GPx, GSR, GST, CAT, and contents of GSH were reduced while the levels of CPK, ProBNP, troponin-T, CK-MB, LDH, C-reactive protein, BNP, and troponin-I were promoted after STL intoxication. Moreover, the levels of COX-2, IL-6, TNF-α, NF- κB, and IL-1β were elevated after STL exposure. Histopathological analysis showed abnormal cardiac architecture following the administration of STL. Importantly, NEP therapy significantly conferred cardio-protection via regulating redox state, reactivating Notch signaling, suppressing inflammatory responses, and improving histopathological alterations. Moreover, echocardiographic parameters were also found normal after NEP supplementation. These findings highlight the cardioprotective role of NEP in mitigating anti-depressant drugs induced cardiotoxicity.

CONCLUSION: NEP confers cardio-protection against STL-induced cardiotoxicity via regulating oxidative stress, notch signaling, inflammation and cardiac function markers. These findings suggest this compound a promising therapy to mitigate anti-depressant drug-induced cardiac damage.

PMID:41046804 | DOI:10.1016/j.tice.2025.103163

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

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

Am Heart J. 2025 Oct 2:107284. doi: 10.1016/j.ahj.2025.107284. Online ahead of print.

ABSTRACT

Complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease reduces major adverse cardiac events (MACE) compared with incomplete revascularization, although whether survival is improved is uncertain. For this systematic review and meta-analysis, all randomized trials of complete vs. incomplete revascularization in patients with acute MI without cardiogenic shock were identified from PubMed, Scopus, Web of Science, and Cochrane Library databases from inception to December 31, 2024. The primary and major secondary endpoints were MACE and all-cause mortality derived from reconstructed time-to-event individual-patient-data from published Kaplan-Meier curves. Additional outcomes included cardiovascular mortality, MI, and unplanned repeat revascularizations. Outcomes were expressed as hazard ratios with 95% confidence intervals. This study was registered with the PROSPERO (number, CRD42023415428). A total of nine randomized trials with 9,658 patients (86.8% with STEMI) were identified among whom 4,671 (48.4%) patients had complete revascularization. Patients with complete revascularization had a lower 5-year risk of MACE (HR: 0.59, 95% CI: 0.54 to 0.66, p<0.001) compared with incomplete revascularization. Complete revascularization was also associated with lower 5-year risks of all-cause mortality (HR: 0.64, 95% CI: 0.56 to 0.72, p<0.001), cardiovascular mortality (HR: 0.82, 95% CI: 0.71 to 0.95, p=0.008), MI (HR: 0.69, 95% CI: 0.55 to 0.87, p<0.001), and unplanned repeat revascularizations (HR: 0.62, 95% CI: 0.54 to 0.71, p<0.001). Complete revascularization results in lower risks of all-cause and cardiovascular mortality, MI, unplanned repeat revascularizations and MACE in patients with acute MI and multivessel disease. These results support current guidelines recommending CR in hemodynamically stable patients with STEMI, emphasizing that this approach may improve survival.

PMID:41046115 | DOI:10.1016/j.ahj.2025.107284

J Vasc Surg. 2025 Oct 2:S0741-5214(25)01778-1. doi: 10.1016/j.jvs.2025.09.044. Online ahead of print.

ABSTRACT

BACKGROUND: Beyond patient factors, recent evidence has suggested that institutional characteristics may contribute to persistent racial disparities in carotid revascularization following acute ischemic stroke. Minority-serving hospitals (MSH) care for a disproportionately high number of historically underserved populations and thus may contribute to observed disparities.

METHODS: All adults (≥ 18 years) admitted for acute ischemic stroke due to carotid artery stenosis were identified in the 2016-2021 Nationwide Inpatient Sample. Patients with missing key data, elective status or admitted to hospitals performing ≤5 carotid revascularization procedures per year (≤5th percentile), were excluded. Carotid revascularization comprised of endarterectomy or stenting. The outcomes of interest were receipt of carotid revascularization, in-hospital mortality, myocardial infarction (MI), and a composite of both measures (death/MI), along with postoperative length of stay, hospitalization costs, and non-home discharge. Multivariable regression models were developed to evaluate the association of MSH with outcomes of interest.

RESULTS: Of the hospitals included in the analysis, 28.9% were classified as MSH. Revascularization rate for these patients significantly increased for both MSH (2016: 16.5%, 2021: 20.5%, nptrend = 0.02) and non-MSH (2016: 20.1%, 2021: 22.0%, nptrend < 0.01), over the study period. Following risk adjustment, treatment at MSH was associated with significantly reduced odds of receiving revascularization (AOR 0.80, CI 0.74-0.87), relative to others. MSH status was linked with similar in-hospital mortality (AOR 1.15, CI 0.96-1.22), but increased odds of MI (AOR 1.17, CI 1.02-1.34) and death/MI (AOR 1.14, CI 1.04 - 1.25). Treatment at these centers was associated with prolonged LOS (β +0.45 days, CI 0.14-0.76) and hospitalization expenditures (β +$5,800, CI 4,510-7,080), along with increased relative risk of non-home discharge (AOR 1.10, CI 1.05 - 1.18) compared to non-MSH. Despite decreased revascularization use for Black and Asian patients across all centers, Hispanic race was linked with reduced odds of revascularization solely at MSH.

CONCLUSION: Providing increased resources to support MSH may be an effective strategy to ensure equal health access to racial/ethnic minority patients. Future studies incorporating hospital quality initiatives targeted for MSH are warranted.

PMID:41046049 | DOI:10.1016/j.jvs.2025.09.044

Am J Cardiol. 2025 Oct 2:S0002-9149(25)00601-0. doi: 10.1016/j.amjcard.2025.09.048. Online ahead of print.

ABSTRACT

OBJECTIVES: Diabetes mellitus (DM) is a known risk factor for cardiac events in patients undergoing percutaneous coronary intervention (PCI). It remains unclear whether specific stent types improve long-term outcomes in this population. This substudy of the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) IX trial compared long-term outcomes in patients with DM with either the polymer-free biolimus A9-coated BioFreedom stent (BF-BES) or the ultra-thin strut, biodegradable polymer sirolimus-eluting Orsiro stent (O-SES).

METHODS: SORTOUT IX was a randomized, non-inferiority trial allocating patients to BF-BES or O-SES. The primary endpoints was target lesion failure (TLF), consisting of cardiac death, target lesion-related myocardial infarction (MI), and target lesion revascularization (TLR), and stent thrombosis within 5 years in patients with DM.

RESULTS: Among 3,151 patients enrolled, 607 (19.3%) had DM (BF-BES: 304; O-SES: 303). At 5-year, TLF was higher for patients with DM than those without DM (19.9% vs. 11.4%, rate ratio (RR) 1.48; 95% confidence interval (CI) 1.15-1.91). In patients with DM, TLF was similar between BF-BES and O-SES (21.7% vs. 18.2%; RR 1.11; 95% CI; 0.76-1.62). Rates of cardiac death, TLR and stent thrombosis did not differ significantly. In-stent restenosis was higher for BF-BES within 1 year (4.6% vs. 1.0%; RR 4.20; 95% CI 1.20-14.7), but not after 5 years (5.9% vs. 10.2%; RR 1.56; 95 % CI 0.85-2.85).

CONCLUSION: In patient with DM undergoing PCI, rates of TLF, cardiac death, target MI, TLR and stent thrombosis did not differ between BF-BES and O-SES after 5 years.

PMID:41045957 | DOI:10.1016/j.amjcard.2025.09.048

Korean Circ J. 2025 Jul 14. doi: 10.4070/kcj.2024.0400. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: CENTUM is a biodegradable everolimus-eluting stent comprising a cobalt-chromium open-cell stent platform. In this prospective trial, we aimed to evaluate the effectiveness and safety of CENTUM™ in a clinical setting.

METHODS: A prospective, single-arm, multi-center observational registry was designed to assess the clinical outcomes after CENTUM implantation in all-comers who underwent percutaneous coronary intervention. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, and target lesion revascularization at 12 months. The secondary endpoints included stent thrombosis and other clinical events (all-cause death, myocardial infarction, stroke, target vessel revascularization, and bleeding).

RESULTS: Total 490 patients were enrolled, and 451 completed the study. The mean age was 67.1 years, and 52.8% of the patients presented with acute coronary syndrome. The primary endpoint was observed in 1.11% of the patients. Definite/probable stent thrombosis was observed in 0.44% of the patients, whereas total clinical events recorded was 4.43%.

CONCLUSIONS: CENTUM was effective and safe at 12 months in all patients who underwent percutaneous coronary intervention. Our findings support the broader application of CENTUM in patients with coronary artery disease.

TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0009898.

PMID:41044739 | DOI:10.4070/kcj.2024.0400

Korean Circ J. 2025 Aug 21. doi: 10.4070/kcj.2025.0103. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The optimal grafting strategy for ischemic cardiomyopathy (ICMP) remains uncertain despite the growing heart failure population undergoing coronary artery bypass grafting (CABG). This study sought to explore the outcomes of CABG in ICMP patients according to the number of inflow sources.

METHODS: A total of 447 patients with an ejection fraction (EF) of ≤35% who underwent isolated CABG from 2009 to 2020 were analyzed. Patients were categorized into either a single inflow source group (single group, n=203), in which unilateral in situ internal thoracic artery (ITA) served as the sole inflow, or a multiple inflow source group (multiple group, n=244), utilizing additional inflow sources from the aorta or contralateral ITA. The primary outcome was all-cause mortality, analyzed after adjustment using the inverse-probability-of-treatment-weighting method.

RESULTS: There were no differences in the early outcomes between 2 groups. After adjustment, the single group exhibited significantly worse survival compared to the multiple group during a median follow-up of 5.3-years (adjusted hazard ratio, 1.88; 95% confidence interval, 1.26-2.80; p=0.001), particularly in the subgroup of patients without a recent myocardial infarction within 1 month (p=0.005) and those with an EF of ≥25% (p=0.007). At the last follow-up echocardiography (>6 months), the multiple group showed a significantly higher postoperative EF (p=0.009) and a smaller left ventricular end-systolic dimension (p=0.027) compared to the single group, which had not shown significant differences preoperatively.

CONCLUSIONS: In ICMP patients, CABG using multiple inflow sources was associated with improved outcomes, particularly in those without recent or profound myocardial injury.

PMID:41044726 | DOI:10.4070/kcj.2025.0103

Histochem Cell Biol. 2025 Oct 4;163(1):94. doi: 10.1007/s00418-025-02426-w.

ABSTRACT

Coenzyme Q10 (CoQ10) is an antioxidant known for its potential protective effects against various types of cardiac injury. The aim of this study was to determine the protective effects of CoQ10 on cardiomyocytes, telocytes and progenitor cells in rats with isoproterenol (ISO)-induced cardiotoxicity. A total of 60 Sprague-Dawley rats were divided into six groups (n = 10): Group I: control, Group II: saline control, Group III: oil control, Group IV: ISO, Group V: CoQ10, Group VI: ISO and CoQ10. Isoproterenol was administered intraperitoneally at a dose of 85 mg/kg twice on the eighth and ninth days, and CoQ10 was administered by oral gavage at a daily dose of 20 mg/kg. Heart tissue samples were collected and analysed at the end of the study. CoQ10 reduced ISO-induced cardiac degeneration, necrosis, inflammatory infiltration and fibrosis. The stimulation of cell cycle activators such as histone H3 and proliferating cell nuclear antigen (PCNA) was found to play a role in the repair of cardiac injury in the cardiomyocytes known to be postmitotic. An increase in c-Kit and CD34 stem cells was seen with the beneficial effect of CoQ10 (P < 0.05). The presence of telocytes, which play an important role in cardiac regeneration, was visualised by double CD34-c-Kit and CD34-vimentin immunofluorescence staining. The results indicate that CoQ10, through its antioxidant effect, ameliorates cardiac lesions caused by ISO, induces a limited number of cell cycle activators in cardiomyocytes and interstitial cells and has a positive effect on the increase of progenitor cells in the heart.

PMID:41046280 | DOI:10.1007/s00418-025-02426-w

Histochem Cell Biol. 2025 Oct 4;163(1):94. doi: 10.1007/s00418-025-02426-w.

ABSTRACT

Coenzyme Q10 (CoQ10) is an antioxidant known for its potential protective effects against various types of cardiac injury. The aim of this study was to determine the protective effects of CoQ10 on cardiomyocytes, telocytes and progenitor cells in rats with isoproterenol (ISO)-induced cardiotoxicity. A total of 60 Sprague-Dawley rats were divided into six groups (n = 10): Group I: control, Group II: saline control, Group III: oil control, Group IV: ISO, Group V: CoQ10, Group VI: ISO and CoQ10. Isoproterenol was administered intraperitoneally at a dose of 85 mg/kg twice on the eighth and ninth days, and CoQ10 was administered by oral gavage at a daily dose of 20 mg/kg. Heart tissue samples were collected and analysed at the end of the study. CoQ10 reduced ISO-induced cardiac degeneration, necrosis, inflammatory infiltration and fibrosis. The stimulation of cell cycle activators such as histone H3 and proliferating cell nuclear antigen (PCNA) was found to play a role in the repair of cardiac injury in the cardiomyocytes known to be postmitotic. An increase in c-Kit and CD34 stem cells was seen with the beneficial effect of CoQ10 (P < 0.05). The presence of telocytes, which play an important role in cardiac regeneration, was visualised by double CD34-c-Kit and CD34-vimentin immunofluorescence staining. The results indicate that CoQ10, through its antioxidant effect, ameliorates cardiac lesions caused by ISO, induces a limited number of cell cycle activators in cardiomyocytes and interstitial cells and has a positive effect on the increase of progenitor cells in the heart.

PMID:41046280 | DOI:10.1007/s00418-025-02426-w

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

Am J Hematol. 2025 Oct 4. doi: 10.1002/ajh.70074. Online ahead of print.

ABSTRACT

Viscoelastic testing (VET) has evolved significantly since its inception in the mid-20th century, when it was first developed to guide transfusion strategies in trauma and surgical patients. Initially, VET technologies such as TEG and ROTEM assessed clot formation by measuring the mechanical resistance of a pin or piston within a blood sample. Recent advances have introduced automated, cartridge-based systems and novel detection methods-including resonance frequency and ultrasound-based sonorheometry-these new systems allow for more precise, rapid, and user-friendly assessment of clot dynamics at the point of care. VET is now indicated for a wide range of clinical scenarios where complex coagulopathy is anticipated, including trauma, cardiac surgery, liver transplantation, obstetric hemorrhage, and hematologic disorders such as DIC. Its use is expanding into new populations, including pediatric cardiac surgery, patients with inflammatory bowel disease, and those with COVID-19. However, VET remains limited in its ability to reliably detect therapeutic anticoagulants and certain congenital bleeding disorders, such as von Willebrand disease and deficiencies of protein C, S, and antithrombin. Technical limitations, including potential discrepancies between in vitro and in vivo clot formation, and lack of FDA approval for pediatric use have imposed implementation barriers to centers interested in pediatric VET. Looking forward, the integration of VET data with electronic medical records, the development of predictive models, artificial intelligence, and continued innovation in platelet function assessment and detection technologies are poised to enhance the clinical utility of VET. As guidelines and evidence continue to evolve, VET is positioned to become an increasingly important tool for real-time, individualized management of coagulopathy in diverse patient populations.

PMID:41045051 | DOI:10.1002/ajh.70074

Ann Thorac Surg. 2025 Oct 2:S0003-4975(25)00907-5. doi: 10.1016/j.athoracsur.2025.08.061. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical outcomes in neonates with complex congenital heart disease (CHD) and pulmonary over-circulation (POC) initially palliated with pulmonary flow reducers (PFR) were evaluated.

METHODS: Retrospective study between Jan 2020 - 2024. Eleven neonates underwent PFR palliation. Fenestrated Medtronic microvascular plugs™ (PFR) were delivered into branch pulmonary artery (PA). Target surgical procedure (TSP) involved the removal of PFR and biventricular (BiV) repair (9) or single ventricle (SV) palliation (2).

RESULTS: Patients were deemed high risk based on prematurity (5), early gestational age (5), heterotaxy (1), hypoxic-ischemic encephalopathy (1), chromosomal abnormality (4), or complex intracardiac anatomy (4). Median age and weight at PFR implantation (PFRI): 48 days (IQR 16-85) and 2.8 kg (IQR 1.7-3.4), respectively. Median PFRI time: 84 days (IQR 33-202). Weight gain following PFRI, 20.31 versus 3.75 g/day prior. Complications of PFRI included POC in 2 patients [bilateral PFR migration (1) and embolization (1)], excessive flow restriction (1), PFR release failure (1), and malposition (1). All patients were bridged to TSP. Devices were surgically removed without need for PA reconstruction needed. There was 1 in-hospital mortality following targeted surgery with 9/11 patients achieving 1-year survival. One-year echocardiographic follow-up showed 3/22 PAs with mild stenosis.

CONCLUSIONS: Outcomes of high-risk neonates with complex CHD and POC are good following PFR palliation. Removal of PFR is feasible without PA stenosis.

PMID:41046011 | DOI:10.1016/j.athoracsur.2025.08.061