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The temporal trends of ST-elevation myocardial infarction mortality according to infarct size and location: insights from the UK National MINAP registry from 2005 to 2019

http:www.cardiocirugia.sld.cu - Lun, 09/22/2025 - 10:00

Eur Heart J Open. 2025 Aug 20;5(5):oeaf111. doi: 10.1093/ehjopen/oeaf111. eCollection 2025 Sep.

ABSTRACT

AIMS: Myocardial infarction size is associated with mortality in ST-elevation myocardial infarction (STEMI). With advances in primary percutaneous coronary intervention (PPCI) and medical therapy, whether this relationship has changed over time is unclear.

METHODS AND RESULTS: Patients with STEMI in the UK from 2005 to 2019 were included from the national AMI MINAP registry, with mortality linkage to 2021. Primary outcomes were all-cause mortality at 30 days and 1 year according to infarct size, using Cox regression models. Infarct size was stratified by Tertiles (T1-3) of peak troponin level (T1, smallest; T3, largest), across the early (2005-09), middle (2010-14), and late (2015-19) periods. Subgroup analyses assessed the relationship according to infarct location (anterior vs. non-anterior). A total of 177 214 STEMI patients were included. Adjusted 30-day mortality risk according to infarct size was highest in the early period (aHR: 1.32, 1.21-1.45, P < 0.001), compared to middle (1.12, 1.04-1.20, P = 0.002) and late study periods (1.05, 0.96-1.14, P = 0.299). The relationship between infarct size and 30-day mortality was significant for patients with anterior STEMI in early (1.39, 1.22-1.57, P < 0.001) but not middle or late periods, while remained significant for non-anterior infarction until the late period (early, 1.28, 1.13-1.45, P < 0.001; middle, 1.17, 1.06-1.29, P = 0.002; late, 1.09, 0.96-1.24, P = 0.180).

CONCLUSION: We observed an independent relationship between infarct size and STEMI mortality, strongest between 2005 and 2009, which reduced over time, becoming non-significant in the 2015-19 period. This association diminished more rapidly for patients with anterior STEMIs. These findings underscore the potential role of contemporary revascularization, systems of care, and guideline-directed medical therapy in reducing STEMI-related mortality.

PMID:40980717 | PMC:PMC12448480 | DOI:10.1093/ehjopen/oeaf111

Categorías:

What role for cardiac imaging in chronic coronary syndromes: review of the literature in light of the latest recommendations

http:www.cardiocirugia.sld.cu - Lun, 09/22/2025 - 10:00

Eur Heart J Imaging Methods Pract. 2025 Aug 20;3(2):qyaf112. doi: 10.1093/ehjimp/qyaf112. eCollection 2025 Jul.

ABSTRACT

The 2019 ESC guidelines redefined stable coronary artery disease as chronic coronary syndrome (CCS), highlighting the dynamic nature of this disease. This condition is characterized by the gradual accumulation of atherosclerotic plaques in the epicardial coronary arteries. CCS can result in myocardial ischaemia due to supply-demand mismatch, often triggered by physical or emotional stress. The clinical course may be abruptly interrupted by plaque rupture or erosion, leading to acute coronary syndromes. Revolutionary advances in non-invasive imaging have transformed the chronic coronary syndrome diagnosis algorithm and management. Coronary computed tomography angiography provides detailed anatomical insights, identifying high-risk plaques with features like low attenuation and positive remodelling, as evidenced by SCOT-HEART, which reported reduced coronary events (HR: 0.59, P = 0.004). Stress echocardiography may detect ischaemia-induced wall motion abnormalities (sensitivity, 85-95%), while cardiovascular magnetic resonance is paramount in functional assessment, offering 81-86% sensitivity/specificity and detecting microvascular dysfunction via perfusion and late gadolinium enhancement. Nuclear imaging (SPECT/PET) enhances ischaemia detection, with PET's myocardial flow reserve improving prognostic accuracy (sensitivity 90%, specificity 88%). AI-driven innovations, such as CT-derived fractional flow reserve, automate plaque quantification and may reduce in the future unnecessary invasive angiographies by 19-25% (P = 0.01), while dynamic CT myocardial perfusion integrates anatomical and hemodynamic data, boosting diagnostic accuracy (87%). These advancements enable precise risk stratification and a personalized multimodal imaging approach, based on pre-test likelihood. It also increases the risk of unsustainable costs for society, repeated radiation exposure throughout a patient's life, and raises the question of actual limited benefits from revascularization in low-risk patients.

PMID:40978762 | PMC:PMC12448739 | DOI:10.1093/ehjimp/qyaf112

Categorías:

Melt electrowritten medium chain length polyhydroxyalkanoate cardiac patches for Post-MI cardiac regeneration

Terapia celular - Lun, 09/22/2025 - 10:00

Mater Today Bio. 2025 Aug 29;34:102256. doi: 10.1016/j.mtbio.2025.102256. eCollection 2025 Oct.

ABSTRACT

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold promise in averting the development of heart failure with reduced ejection fraction (HFrEF) following myocardial infarction (MI) by potentially regenerating the infarcted myocardium and restoring left ventricular contractility. However, challenges remain regarding the structural and functional maturation states of these cells, as well as their retention and integration into the myocardium. Here, we developed a novel three-dimensional cardiac patch and evaluated its potential to instigate cardiac regeneration. For the first time, melt electrowriting (MEW) was utilised to fabricate reproducible, structurally anisotropic, and handleable scaffolds from high molecular weight, medium chain-length polyhydroxyalkanoates (MCL-PHAs). These MEW-PHA scaffolds maintained hPSC-CMs, facilitating their rapid structural maturation and functional improvement in vitro. Different combinations of hPSC-derived cardiovascular cells were seeded onto the MEW-PHA scaffolds and stacked to create synchronously beating, multi-scaffold cardiac patches. These were well-accepted in a murine MI model without capsule formation. Notably, cardiac patches containing hPSC-derived cardiac microvascular-like endothelial cells (hPSC-CMVECs) initiated vascular regeneration within the infarcted myocardium. This novel advancement enabled the reproducible fabrication of high molecular weight MCL-PHA-based MEW cardiac patches that matured hPSC-CMs and promoted vascular regeneration, offering potential for future improvement in post-MI cardiac function through enhanced hPSC-CM retention.

PMID:40977832 | PMC:PMC12446554 | DOI:10.1016/j.mtbio.2025.102256

Categorías: Terapia celular

Benefit of Icosapent Ethyl Across Types and Sizes of Myocardial Infarction in REDUCE-IT

Protección miocárdica - Lun, 09/22/2025 - 10:00

Eur J Prev Cardiol. 2025 Sep 22:zwaf602. doi: 10.1093/eurjpc/zwaf602. Online ahead of print.

ABSTRACT

AIMS: We studied the efficacy and safety of icosapent ethyl (IPE) 4g daily in reducing the risk of myocardial infarction (MI) across different MI subtypes and sizes, among REDUCE-IT high-risk patients with hypertriglyceridemia.

METHODS: REDUCE-IT was a phase 3b, double-blind multicenter trial. Patients with established CVD or diabetes who were treated with statins and had moderate hypertriglyceridemia were randomized to receive IPE 4g daily or placebo. The current analysis focused on MI subtypes (fatal MI, nonfatal MI, ST-segment elevation MI (STEMI), non-STEMI (NSTEMI)), as well as MI size (measured by multiples of troponin upper limit of normal) and MI-related complications. Safety outcomes included treatment emergent adverse events (TEAEs), bleeding, atrial fibrillation, and flutter.

RESULTS: At 5.7 years follow-up, MI incidence was lower with IPE compared with placebo (8.6% vs 12.0%), hazard ratio (HR) 0.69 (95% CI 0.58-0.81, P<0.0001). STEMI incidence was lower with IPE (2.7% vs 3.9%, HR 0.60, 95% CI 0.44-0.81, P=0.0008), as was NSTEMI incidence (5.9% vs 7.8%, HR 0.73, 95% CI 0.60-0.89, P=0.001). Fatal and nonfatal MIs were reduced with IPE (HR 0.55, 95% CI 0.30-1.01, P=0.05 and HR 0.70, 95% CI 0.59-0.82, P<0.0001, respectively). Stratification by size revealed IPE reduced most MIs, but the protective effect was higher for larger MIs (P<0.0001). Further analyses showed benefits in MI-related outcomes, including reductions in spontaneous MI and MI-related complications. Among patients who developed MI, safety outcomes showed no significant increase in serious bleeding, atrial fibrillation or flutter, or adverse events with IPE.

CONCLUSION: IPE significantly reduced MI across most subtypes and sizes in statin-treated patients with elevated triglycerides at increased cardiovascular risk.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01492361.

PMID:40982548 | DOI:10.1093/eurjpc/zwaf602

The Nrf Family and Its Cardioprotective Potential: Mechanisms, Functions, and Therapeutic Perspectives

Protección miocárdica - Lun, 09/22/2025 - 10:00

Drug Des Devel Ther. 2025 Sep 15;19:8339-8373. doi: 10.2147/DDDT.S547848. eCollection 2025.

ABSTRACT

This review systematically elucidates the molecular mechanisms and therapeutic potential of nuclear factor erythroid 2-related factor (Nrf) family members in the cardiovascular system. As critical components of the CNC-bZIP transcription factor family, the Nrf family (including Nrf-2/NFE2L2, Nrf-1/NFE2L1, and Nrf-3/NFE2L3) orchestrates antioxidant response element (ARE)-dependent gene expression networks, playing pivotal roles in maintaining redox homeostasis, modulating inflammatory responses, improving mitochondrial function, and regulating programmed cell death (apoptosis, autophagy, and pyroptosis). Clinical data have demonstrated that in patients with myocardial infarction, the expression of Nrf-3 gene is significantly upregulated in myocardial cells within the infarcted area. Its high expression is associated with increased in-hospital mortality during the acute phase and accelerated progression of ventricular remodeling. Knockout of the Nrf-3 gene can reduce the acute-phase mortality of myocardial infarction, improve ventricular remodeling, and enhance cardiac function. Additionally, a crossover trial involving 19 participants showed that after 2 months of administration of olive oil by-product pâté tablets, the plasma Nrf-2 level in the subjects increased by 88.9% with concurrent improvement in cardiovascular risk factors. Collectively, these findings confirm the impact of the Nrf family on cardiovascular prognosis and its potential for intervention. Furthermore, we comprehensively analyze the regulatory functions of Nrf members in major cardiovascular pathologies, including myocardial ischemia-reperfusion injury, atherosclerotic plaque formation/stabilization, and heart failure progression. Based on recent advances, we also discuss innovative therapeutic strategies targeting the Nrf pathway, encompassing pharmacological activators, gene/epigenetic therapies, combinatorial approaches, and lifestyle interventions, thereby providing a theoretical framework and novel perspectives for the precision medicine of cardiovascular diseases.

PMID:40980421 | PMC:PMC12448090 | DOI:10.2147/DDDT.S547848

Farrerol ameliorates diabetic cardiomyopathy by inhibiting ferroptosis <em>via</em> miR-29b-3p/SIRT1 signaling pathway in endothelial cells

Protección miocárdica - Lun, 09/22/2025 - 10:00

World J Diabetes. 2025 Sep 15;16(9):109553. doi: 10.4239/wjd.v16.i9.109553.

ABSTRACT

BACKGROUND: Diabetic cardiomyopathy (DCM) is the leading cause of cardiovascular disease-related mortality. Farrerol (FA) possesses anti-inflammatory and antioxidant properties. However, its role in regulating endothelial ferroptosis in DCM remains unknown.

AIM: To investigate the beneficial effects of FA on cardiac microvascular dysfunction in DCM from the perspective of ferroptosis in endothelial cells (ECs).

METHODS: The mice were fed a high-fat diet and injected with streptozotocin to induce DCM. DCM mice were orally administered FA (10 and 40 mg/kg/day) and a tail vein injection of the miR-29b-3p mimic or inhibitor for 24 weeks. Cardiac function and myocardial fibrosis were also analyzed. Cardiac microvascular function was assessed using immunofluorescence and transmission electron microscopy. Ferroptosis was analyzed using RNA sequencing, immunofluorescence, and western blotting.

RESULTS: FA administration improved cardiac function, alleviated myocardial fibrosis, strengthened endothelial barrier function, suppressed endothelial inflammation, and preserved the microvascular structure in DCM mice. This improvement was associated with the inhibition of endothelial ferroptosis and downregulation of miR-29b-3p in ECs. Similar efficacy was observed after tail vein injection of the miR-29b-3p inhibitor. Inhibition of miR-29b-3p in vivo showed an anti-cardiac fibrotic effect by improving microvascular dysfunction and ferroptosis in ECs, whereas overexpression of miR-29b-3p showed the opposite effects in DCM mice. Luciferase reporter assay revealed that miR-29b-3p binds to SIRT1. In cultured ECs, FA reduced high glucose and free fatty acid (HG/FFA)-induced lipid peroxidation and ferroptosis and inhibited endothelial-mediated inflammation. However, the overexpression of miR-29b-3p partially abolished the protective effects of FA against HG/FFA-induced injury in ECs. This finding suggests that the mechanism of action of FA in improving DCM is related to the downregulation of miR-29b-3p and activation of SIRT1 expression.

CONCLUSION: Therefore, FA has a potential therapeutic effect on cardiac microvascular dysfunction by suppressing EC ferroptosis through the miR-29b-3p/SIRT1 axis.

PMID:40980297 | PMC:PMC12444265 | DOI:10.4239/wjd.v16.i9.109553

Activity evaluation of multifunctional H<sub>2</sub>S donors for anti-inflammatory, cardioprotective, and hepatoprotective applications

Protección miocárdica - Lun, 09/22/2025 - 10:00

Front Chem. 2025 Sep 5;13:1643663. doi: 10.3389/fchem.2025.1643663. eCollection 2025.

ABSTRACT

INTRODUCTION: As an important gas signaling molecule, hydrogen sulfide (H2S) exhibits therapeutic potential in inflammatory and oxidative stress-related diseases. This study developed and evaluated novel H2S donor derivatives based on the phenylphosphonothioic dichloride scaffold.

METHODS: Derivatives were synthesized based on the phenylphosphonothioic dichloride scaffold. Compound 3b-1 was selected for its high H2S release capacity and favorable safety profile. Its anti-inflammatory activity was evaluated by measuring inhibition of TNF-α, TNF-β, and nitrite. Hepatoprotective effects were assessed in an H2O2-induced injury model using oxidative stress markers (MDA, SOD, GSH) and HSC activation. Cardioprotective effects were examined in an LPS-induced model by analyzing mitochondrial membrane potential, cardiac markers (LDH, CK-MB), and oxidative balance.

RESULTS: Compound 3b-1 showed the highest H2S release capacity and inhibited TNF-α (86%), TNF-β (82%), and nitrite (67%). In the hepatocyte model, it reduced MDA (79%), enhanced SOD (49%) and GSH (76%), and suppressed HSC activation (55%). In the myocardial model, 3b-1 attenuated mitochondrial membrane potential dissipation, decreased LDH (34%) and CK-MB (24%), and restored GSH activity (73%) while reducing MDA (48%).

DISCUSSION: The phosphorus-sulfur scaffold-based H2S donor 3b-1 demonstrates synergistic anti-inflammatory, antioxidant, and organ-protective effects, highlighting its promise as a drug candidate for treating inflammation- and oxidative stress-related disorders.

PMID:40979186 | PMC:PMC12447644 | DOI:10.3389/fchem.2025.1643663

Hyperoside alleviates myocardial ischemia-reperfusion injury in heart transplantation by promoting mitochondrial fusion via activating the Stat3-Tom70-Opa1 pathway

Protección miocárdica - Lun, 09/22/2025 - 10:00

Front Pharmacol. 2025 Sep 4;16:1566674. doi: 10.3389/fphar.2025.1566674. eCollection 2025.

ABSTRACT

BACKGROUND: Myocardial ischemia-reperfusion injury (IRI) is the major cause of primary graft dysfunction in heart transplantation, which is characterized by mitochondrial dysfunction. Hyperoside is a bioactive compound that has been reported to have pharmacological potential for cardiac and mitochondrial protection. Here, we investigated the protective effect of hyperoside during myocardial IRI and identified the underlying mechanisms.

METHODS: In this study, we established IRI in an in vivo murine heterotopic heart transplantation model and an in vitro hypoxia-reoxygenation cell model. Inflammatory responses, oxidative stress level, mitochondrial function, and cardiomyocyte apoptosis were evaluated.

RESULTS: We found that hyperoside pretreatment alleviated through reducing MDA content, LDH activity, TUNEL positive cells, serum cTnI level, Bax protein expression and the level of inflammatory cytokines, and increasing SOD activity and Bcl-2 protein expression. Furthermore, hyperoside pretreatment improved Opa1-mediated mitochondrial fusion, upregulated mitochondrial ATP content and downregulated NADP+/NADPH and GSSG/GSH ratios. Opa1 inhibitor blunted the protective effects of hyperoside. Mechanistically, Co-immunoprecipitation experiments showed the binding property between Tom70 and Opa1, siRNA knockdown, AAV-mediated loss-of-function and gain-of-function approaches suggested that hyperoside-promoted Opa1-mediated mitochondrial fusion required the upregulation of Tom70.

CONCLUSION: Collectively, we demonstrated for the first time that hyperoside administration alleviates myocardial IRI by promoting Opa1-mediated mitochondrial fusion in vivo and in vitro. The Tom70-Opa1 pathway was essential for cardioprotective effects of hyperoside treatment. The results in our study indicated that hyperoside or promotion of mitochondrial fusion might be a new potential option for the prevention and treatment of IRI in heart transplantation.

PMID:40978492 | PMC:PMC12443569 | DOI:10.3389/fphar.2025.1566674

miR-21 regulates LPS-induced apoptosis and inflammatory injury in rat cardiomyocytes by targeting PLD1 and STAT3

Protección miocárdica - Lun, 09/22/2025 - 10:00

Pol J Pathol. 2025;76(2):131-140. doi: 10.5114/pjp.2025.153974.

ABSTRACT

This study aims to elucidate the role and molecular mechanism of microRNA-21 (miR-21) in LPS-induced inflammatory injury in H9c2 cardiomyocytes. H9c2 cardiomyocytes were treated with lipopolysaccharide (LPS) to establish an in vitro model. The expression of miR-21 was quantified using RT-qPCR, while protein levels were assessed via Western blot analysis. The impact of miR-21 on inflamma-tory response, cell proliferation, and apoptosis in LPS-treated H9c2 cells was evalu-ated using ELISA, CCK-8/EdU assays, and flow cytometry. TargetScan predictions and dual-luciferase reporter assays were employed to identify potential miR-21 tar-gets. The regulatory effects of miR-21 on inflammation, proliferation, and apop-tosis in cells were further examined following transfection with phospholipase D1 (PLD1) overexpression constructs or signal transducer and activator of transcription 3 (STAT3) activation. The expression levels of miR-21, PLD1, and p-STAT3 were significantly elevated in LPS-treated H9c2 cells. Knockdown of miR-21 markedly inhibited the LPS-induced inflammatory response, enhanced cell proliferation, and reduced apoptosis in H9c2 cells. PLD1 and STAT3 were confirmed as direct targets of miR-21. Overexpression of PLD1 or activation of STAT3 significantly reversed the protective effects of miR-21 downregulation in LPS-treated H9c2 cells. Downregu-lation of miR-21 protects cardiomyocytes against LPS-induced inflammatory injury and apoptosis by inhibiting PLD1 expression and STAT3 phosphorylation.

PMID:40977551 | DOI:10.5114/pjp.2025.153974

Does donor-recipient body mass index ratio influence heart transplantation outcomes??

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

BMC Cardiovasc Disord. 2025 Sep 22;25(1):654. doi: 10.1186/s12872-025-05147-z.

ABSTRACT

BACKGROUND: Obesity is a common risk factor for heart failure, and heart transplantation (HTx) is the treatment of choice for end-stage heart failure. Due to the limited availability of the donor's heart, efforts are made to increase the donor pool on one hand and to find predictors that can impact HTx outcomes on the other hand. These predictors can help improve donor organ allocation and HTx outcomes. This study aims to investigate the impact of the donor-recipient BMI ratio on follow-up mortality and other outcomes after HTx.

METHODS: From 2012 to 2021, 821 patients underwent HTx in our centre. Patients under 18 years, re-transplantation, multiorgan transplantation, and missing recipient and donor BMI data were excluded. The final sample size of 653 patients was divided into three quartile categories based on the donor-recipient (D-R) BMI ratio. D-R BMI ratio < 0.86 (n = 156), D-R BMI ratio 0.86-1.12 (n = 338), and D-R BMI ratio > 1.12 (n = 159). Analysis of variance and chi-square test with post hoc test according to the types of variables were performed to find differences among the groups. Kaplan-Meier survival analysis was used to evaluate survival, and the difference between the curves was checked with the log-rank test. Cox regression analysis was used to adjust for confounders and find independent predictors of mortality.

RESULTS: Some preoperative variables were statistically different between the groups. The D-R BMI ratio did not impact follow-up mortality after adjustment for confounders. The 7-year survival in D-R BMI ratios < 0.86, 0.86-1.12, and > 1.12 was 73%, 68%, and 70% respectively (p = 0.532). There was no significant difference in other postoperative outcomes, including ICU stay, systemic complications, and mechanical circulatory support use, between the groups based on unadjusted analysis.

CONCLUSION: The donor-recipient BMI ratio had no significant impact on post-transplantation mortality. Postoperative outcomes other than survival were also comparable between the groups. These outcomes were observed in a specific D-R BMI ratio range (0.77-1.26), and extreme BMI ratios may have different results. The results of this study support the liberal use of donor and recipient BMI during patient matching, which can decrease the likelihood of potential donor non-use and subsequently increase the donor pool.

PMID:40983895 | PMC:PMC12452006 | DOI:10.1186/s12872-025-05147-z

Categorías: Trasplante cardíaco

Efficacy and safety of direct Oral anticoagulants versus vitamin K antagonist in patients with left ventricular Thrombus: A Meta-analysis of randomized controlled trials

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

J Cardiol. 2025 Sep 20:S0914-5087(25)00242-4. doi: 10.1016/j.jjcc.2025.09.012. Online ahead of print.

ABSTRACT

BACKGROUND: While vitamin K antagonist (VKA) has traditionally been the preferred treatment for left ventricle (LV) thrombus, the comparative efficacy and safety of direct oral anticoagulants (DOACs) with VKA in this setting remain unelucidated.

METHODS: A comprehensive literature search of PubMed and Google Scholar was conducted through May 7, 2025, to identify randomized controlled trials (RCTs) comparing DOACs with VKA in patients with LV thrombus. The primary endpoint was complete resolution of LV thrombus. Secondary endpoints included stroke, systemic embolism, the composite of both stroke and systemic embolism, major bleeding, and all-cause mortality. Both pairwise and network meta-analyses were performed using a random-effects model to synthesize the effect estimates.

RESULTS: Eight RCTs comprising a total of 576 patients were included. Collectively, 88.9 % of the patients treated with DOACs and 81.7 % of those receiving VKA experienced LV thrombus resolution, with a synthesized risk ratio (RR) of 1.01 [95 % confidence interval (CI), 0.94 to 1.07]. No significant differences were observed between the two groups for stroke (RR, 0.75; 95 % CI, 0.25 to 2.19), systemic embolism (RR, 0.21; 95 % CI, 0.01 to 4.58), the composite of stroke and systemic embolism (RR, 0.64; 95 % CI, 0.17 to 2.32), major bleeding (RR, 0.43; 95 % CI, 0.16 to 1.19), or all-cause mortality (RR, 0.92; 95 % CI, 0.36 to 2.31). A network meta-analysis showed no statistically significant differences across the anticoagulants in any clinical endpoint.

CONCLUSION: DOACs showed comparable efficacy and safety to VKA in managing LV thrombus, supporting their potential role as a viable alternative anticoagulation strategy.

PMID:40983289 | DOI:10.1016/j.jjcc.2025.09.012

Categorías: Trasplante cardíaco

Clinical Significance of C4d Positivity Within the First Month after Heart Transplantation in Detecting Antibody-Mediated Rejection on Endomyocardial Biopsies

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

Cardiovasc Pathol. 2025 Sep 20:107783. doi: 10.1016/j.carpath.2025.107783. Online ahead of print.

ABSTRACT

BACKGROUND: The pathologic definition for antibody-mediated rejection (AMR) includes both histopathological and immunopathological components. C4d is the most validated diagnostic marker for immunopathologic AMR; however, the clinical significance of early C4d positivity (≤1 month post-transplant) on endomyocardial biopsies (EMBs) is unknown.

METHODS: Patients who had ≥1 episode of C4d-positive EMB within the first month after heart transplantation were selected, the coexistence with acute cellular rejection (ACR) and the correlations of C4d positivity with histopathologic features of AMR, clinical graft dysfunction, presence of donor specific antibodies (DSAs), and clinical outcomes were examined.

RESULTS: 112 EMBs from 46 patients were qualified and included in the study. 19 patients had single C4d-positive EMB whereas 27 patients developed multiple (2-4) episodes of C4d positivity within the first month. 40% of C4d-positive EMBs showed concurrent ACR (26 with G1R, 6 with G2R). The C4d positivity correlated well with the histopathologic AMR, with 73% of C4d-positive EMBs showing all or partial histologic features of AMR. Only 29% of the C4d-positive EMBs were associated with clinical graft dysfunction, indicating that most early C4d-positive EMBs were clinically asymptomatic. DSAs were found positive in 28 patients (61%), with preformed DSAs being more common than de novo DSAs. Although no cardiac allograft vasculopathy was observed from any patient, two pediatric patients died of AMR shortly after transplantation whereas three adult patients passed away mostly because of infection.

CONCLUSION: Heart recipients with C4d-positive EMBs within the first month post-transplant were mainly clinical asymptomatic, combined considerations including clinical, pathological, and serological evaluation should be conducted for the best management of AMR.

PMID:40983256 | DOI:10.1016/j.carpath.2025.107783

Categorías: Trasplante cardíaco

Reanimation-less Rapid Recovery of a Donor Heart After Circulatory Death With Prolonged 8-Hour Ischemic Time

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

J Heart Lung Transplant. 2025 Sep 20:S1053-2498(25)02276-4. doi: 10.1016/j.healun.2025.09.009. Online ahead of print.

ABSTRACT

Cardiac allografts from donation after circulatory death (DCD) donors have helped increase the donor pool for heart transplantation. Techniques that reanimate the heart, such as ex situ perfusion or thoracoabdominal normothermic regional perfusion (TA-NRP), are typically employed. We recently described a novel method for the "reanimation-less" rapid recovery of DCD hearts for transplantation. Here, we highlight using our rapid recovery with extended ultra-oxygenation preservation (REUP) technique combined with 10C static cold storage to recover an older donor allograft (45 years of age) with a prolonged 8-hour ischemic time (477 minutes). The recipient underwent successful heart transplantation with subsequent normal biventricular function and excellent postoperative outcomes out to 8 months following surgery.

PMID:40983135 | DOI:10.1016/j.healun.2025.09.009

Categorías: Trasplante cardíaco

Cardiovascular Therapeutic Applications of the Human Amnion: Membrane, Cells, and Beyond

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

J Cardiovasc Pharmacol Ther. 2025 Jan-Dec;30:10742484251380914. doi: 10.1177/10742484251380914. Epub 2025 Sep 22.

ABSTRACT

BackgroundThe therapeutic potential of the human amnion has been known since the early twentieth century. Subsequent study has revealed the further therapeutic potential of all elements of the amnion-membrane, cells, fluid-in the treatment of cardiac disease.Materials and MethodsA systematic review was performed utilizing PubMed/MEDLINE and Embase with search terms including "amniotic fluid," "cardiovascular disease," "cardiac disease," "amnion," "amniotic membrane," and "heart." Results were reviewed by each author to ensure inclusion of all relevant articles. Animal studies were included for evaluation of existing preclinical models, and the few available clinical studies of amniotic products were included.ResultsPreclinical studies addressing organ function, assessment, and enhancement of cardiac performance in response to injury, and regenerative potential are included, as are the few clinical studies utilizing amniotic products for the treatment of cardiac disease. Therapeutic approaches include reduction of inflammation, immunomodulation, and the promotion of myocardial regeneration via cellular therapy to target the most common mechanisms underlying myocardial injury.ConclusionsThe components of the human amnion have anti-inflammatory, immunomodulatory, and pro-differentiation abilities which lend the ability to attenuate myocardial ischemia-reperfusion injury, temper cardiac fibrosis, and promote activation of progenitor cells to induce regeneration. Preclinical studies have focused heavily on cellular therapy, but clinical experience has yielded little success. The acellular components of the amnion have fueled more recent investigation and represent a new source of enthusiasm for clinical translation of amniotic products in the treatment of cardiac disease.

PMID:40982306 | DOI:10.1177/10742484251380914

Categorías: Trasplante cardíaco

Pathophysiology and clinical applications of PEEP in acute brain injury

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

Intensive Care Med. 2025 Sep 22. doi: 10.1007/s00134-025-08111-9. Online ahead of print.

ABSTRACT

Mechanical ventilation is a life-sustaining treatment needed in patients with acute brain injury to maintain airway permeability, optimize gas exchange, and prevent secondary brain damage. Positive end-expiratory pressure (PEEP), a key component of mechanical ventilation, helps prevent atelectasis, improve oxygenation, and stabilize alveolar recruitment, offering potential benefits in terms of lung protection. However, neurological tolerance of PEEP can be poor in brain-injured patients. The variability in lung and chest-wall elastance, lung recruitability, cardiac function, and fluid status, as well as the integrity of cerebral autoregulation, further complicates the recommendations for the safe range of PEEP in this patient population. This review aims to explore the physiological effects of PEEP on the brain-heart-lung interplay, focusing on the direct and indirect influences of PEEP on intracranial and cerebral perfusion pressures, as well as cerebral perfusion. We also discuss the need for individualized mechanical ventilation settings to balance the respiratory benefits of PEEP against its potential adverse effects on cerebral perfusion.

PMID:40982016 | DOI:10.1007/s00134-025-08111-9

Categorías: Trasplante cardíaco

Mitral Valve Prolapse and Sudden Cardiac Death-A Puzzle with Missing Pieces: Review of the Literature and Case Report

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

Med Sci (Basel). 2025 Sep 10;13(3):185. doi: 10.3390/medsci13030185.

ABSTRACT

Background: Mitral valve prolapse is a common valvular heart disorder, usually associated with a benign prognosis in the absence of significant mitral regurgitation. However, a subset of patients is at increased risk for complex ventricular arrhythmias and sudden cardiac death. Identifying these high-risk individuals remains a major clinical challenge. Case Summary: We present the case of a 71-year-old female patient with recurrent syncopal episodes, a strong family history of sudden cardiac death, and complex ventricular ectopy. Multimodality imaging revealed bileaflet mitral valve prolapse, severe mitral regurgitation, mitral annular disjunction, and the Pickelhaube sign, with no evidence of myocardial fibrosis on cardiac magnetic resonance imaging. The patient underwent minimally invasive mitral valve repair and received an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death. Follow-up revealed significant reverse cardiac remodeling, marked reduction in arrhythmic burden, and restoration of mitral valve function. Family screening identified mitral annular disjunction in both of her daughters, who were asymptomatic and without arrhythmias. Discussion: Mitral annular disjunction has emerged as a potentially arrhythmogenic substrate, especially in patients with familial clustering, raising the possibility of a genetic predisposition. Risk stratification remains difficult, as no individual clinical, electrocardiographic, or imaging marker has demonstrated consistent predictive value. Surgical correction of mitral valve prolapse with associated mitral annular disjunction may lead to a reduction in arrhythmic risk and promote favorable structural remodeling. Conclusions: This case-based review emphasizes the importance of advanced imaging techniques in the identification and management of high-risk mitral valve prolapse phenotypes. Early surgical intervention and close arrhythmic surveillance may improve outcomes, although further research is necessary to define risk assessment tools and explore the genetic background of arrhythmogenic mitral valve disease.

PMID:40981183 | PMC:PMC12452400 | DOI:10.3390/medsci13030185

Categorías: Trasplante cardíaco

Non-Induction Basiliximab to Facilitate Renal Recovery via Temporary Tacrolimus Cessation in Cardiothoracic Transplant Patients

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

Medicines (Basel). 2025 Aug 28;12(3):22. doi: 10.3390/medicines12030022.

ABSTRACT

Introduction: Reversible and irreversible nephrotoxicity are known complications of tacrolimus. Approaches to reduce the incidence of nephrotoxicity include the reduction or avoidance of tacrolimus but must be weighed against risk of rejection. Infrequently, basiliximab has been used outside of the induction period to facilitate temporary tacrolimus cessation in the setting of acute kidney injury (AKI). Objective: The primary objective of this study was to describe renal recovery after temporary tacrolimus cessation with non-induction basiliximab (NIB) compared to a matched cohort. Methods: We conducted a single-center study of adult cardiothoracic transplant recipients that received basiliximab beyond post-operative day 7 for temporary tacrolimus cessation in the setting of AKI between January 2019 and November 2023 and matched them to acontrol cohort. Results: Twelve patients underwent temporary tacrolimus cessation with NIB. In total, 7 (58%) patients achieved initial renal recovery at tacrolimus resumption compared to 15 (42%) patients in the matched cohort at an equivalent time point. No difference between treated rejection (17% vs. 19%, p = 0.80) or infection (75% vs. 50%, p = 0.32) was observed between tacrolimus cessation and its matched cohort. Conclusions: The use of NIB for tacrolimus cessation can allow for potential renal recovery after an AKI or in patients at risk of AKI. This approach does not appear to significantly increase the risk of rejection but may increase the risk of infection in the long term.

PMID:40981010 | PMC:PMC12452629 | DOI:10.3390/medicines12030022

Categorías: Trasplante cardíaco

Severe hepatic steatosis contributes to liver dysfunction in non-obese patients with insulin-resistant diabetes mellitus after hematopoietic stem cell transplantation

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

Pediatr Int. 2025 Jan-Dec;67(1):e70192. doi: 10.1111/ped.70192.

ABSTRACT

BACKGROUND: Non-obese survivors of childhood hematopoietic stem cell transplantation (HSCT) often exhibit severe insulin resistance and mild hepatic dysfunction. Although the exact pathophysiology remains unclear, one possible explanation is the increasingly recognized condition known as HSCT-associated partial lipodystrophy. In lipodystrophy, hepatic dysfunction is characterized by fibrosis and severe steatosis, resembling nonalcoholic steatohepatitis. Accordingly, detailed hepatic assessment would improve our overall understanding of the condition. This study aimed to evaluate hepatic dysfunction using a non-invasive method (FibroScan) in patients who developed glucose intolerance post-HSCT.

METHODS: Fourteen non-obese childhood HSCT survivors from two institutions underwent FibroScan. They were classified according to the presence or absence of diabetes mellitus (DM) with insulin resistance (HOMA-IR >2.5 or insulin therapy >1.5 U/kg/day). FibroScan provided controlled attenuation parameter (CAP) for hepatic steatosis and liver stiffness measurements (LSM) for fibrosis. Serum hepatic fibrosis markers (collagen type IV and hyaluronic acid) were also measured.

RESULTS: Seven patients developed insulin-resistant DM while seven had normal glucose/lipid metabolism. All DM patients showed "Dunnigan"-type subcutaneous fat distribution. CAP values were higher in the DM group [307 (261.0-343.5) vs. 237 (216.5-271.0), p = 0.041], as were LSM scores [6.7 (5.9-9.9) vs. 4.1 (3.5-4.7), p = 0.007], indicating more severe steatosis and increased liver stiffness. However, serum hepatic fibrosis markers did not differ significantly.

CONSLUSIONS: Non-obese HSCT survivors with insulin-resistant DM exhibited severe hepatic fat accumulation and progression of liver fibrosis attributable to lipodystrophy. FibroScan may have potential utility for monitoring liver health in this population.

PMID:40980970 | DOI:10.1111/ped.70192

Categorías: Trasplante cardíaco

A New Prognostic Score Based on Cell-Mediated Immunity for Cytomegalovirus Infection After Transplantation

Trasplante cardíaco - Lun, 09/22/2025 - 10:00

Kidney Int Rep. 2025 Jul 8;10(9):3044-3057. doi: 10.1016/j.ekir.2025.06.056. eCollection 2025 Sep.

ABSTRACT

INTRODUCTION: The interferon gamma (IFN-γ) enzyme-linked immunosorbent spot is a highly sensitive immune assay that enables the assessment of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) and can identify at-risk transplant patients of CMV infection; however, its clinical implementation remains elusive.

METHODS: We developed a novel CMV-CMI risk-score based on the standardized T-SPOT.CMV assay against 2 CMV antigens (immediate-early protein 1 [IE-1] and 65 kDa phosphoprotein [pp65]), a biomarker predicting CMV infection, both high viral replication, and disease by performing a pooled analysis of 570 kidney transplants participating in different clinical trials and subsequently validating it in 146 consecutives solid organ transplants (SOT) in an interventional trial. By incorporating clinical variables into the CMV-CMI risk-score, we built an integrative prognostic system quantifying the risk of CMV infection (CMV-PrognosTIC score) using elastic net penalized regression analysis.

RESULTS: In the pooled derivation cohort, whereas specific IE-1/pp65-specific CMV-CMI frequencies independently correlated with high risk of CMV infection (areas under the curve [AUCs]: 0.694, P < 0.0001; 0.719, P < 0.0001, respectively), by combining both responses, 3 CMV-CMI risk-scores appeared, accurately discriminating low-risk (LR) from intermediate-risk (IR) and high-risk (HR) patients (98.7% negative predictive value [NPV], 97.2% sensitivity). Its prospective implementation guiding decision-making in an independent SOT cohort confirmed the very high NPV and sensitivity identifying LR patients. By integrating type of preventive therapy, patient age, and donor (D) and recipient (R) CMV-serostatus to the CMV-CMI risk-score, we generated a global risk-prognostic model showing accurate discrimination and calibration in both derivation (AUC: 0.807) and validation cohorts (AUC: 0.719).

CONCLUSION: We developed a robust CMV-PrognosTIC score to quantify the risk of CMV infection in SOT, which may be readily implemented in clinical transplantation to personalize CMV preventive therapies.

PMID:40980655 | PMC:PMC12446942 | DOI:10.1016/j.ekir.2025.06.056

Categorías: Trasplante cardíaco
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