Front Oncol. 2025 Sep 3;15:1320679. doi: 10.3389/fonc.2025.1320679. eCollection 2025.
ABSTRACT
Situs inversus totalis (SIT) is a rare congenital anatomical variation. This case report describes the first instance of a patient with both lung and esophageal cancer along with SIT. Additionally, it presents the first successful radical radiation therapy for esophageal carcinoma with SIT. The patient underwent a left upper lobectomy with lymph node dissection using video-assisted thoracic surgery (VATS) for lung cancer in 2021 and radical radiotherapy for esophageal cancer in 2023.
PMID:40969271 | PMC:PMC12440748 | DOI:10.3389/fonc.2025.1320679
Clin Exp Pediatr. 2025 Sep 19. doi: 10.3345/cep.2025.00836. Online ahead of print.
ABSTRACT
BACKGROUND: Open cardiac surgery involving cardiopulmonary bypass (CPB) triggers a systemic inflammatory response that significantly affects clinical outcomes. However, the dynamics and specific roles of cytokine release after CPB in the pediatric population remain unclear.
PURPOSE: To evaluate the dynamics of cytokine levels and their association with low cardiac output syndrome (LCOS)-related outcomes.
METHODS: A prospective observational cohort study was conducted of 32 children who underwent elective open cardiac surgery with CPB at Songklanagarind Hospital, Thailand. Levels of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were analyzed preoperatively and immediately (T0), 6, 12, and 24 hours after intensive care unit admission. LCOS-related outcomes were defined with at least two of the following criteria being met within 24 hours postoperative: clinical and laboratory parameters, vasopressor-inotropic score ≥20, ejection fraction <50% on echocardiography; and requirement for a serious postoperative intervention. Statistical analyses utilized linear mixed models and multivariate logistic regression to identify the independent predictors of LCOS.
RESULTS: The mean patient age was 34.8±34.4 months; 56.2 % were male. Roughly one-third (37.5%) had a history of previous cardiac surgery, while one-quarter (28.3%) had a Risk Adjustment for Congenital Heart Surgery score ≥3. LCOS-related outcomes occurred in 37.5% of patients. IL- 6, IL-8, and TNF-α levels differed significantly between patients with and without LCOS outcomes. An increase in IL-8 of >56 pg/mL from baseline to T0 showed the strongest association with LCOS (odds ratio, 37.34; 95% confidence interval, 4.53-836.53).
CONCLUSION: An elevated postoperative IL-8 level is a robust predictor of LCOS-related outcomes in pediatric patients undergoing cardiac surgery. These findings emphasize the importance of monitoring cytokine dynamics to guide interventions and improve patient outcomes.
PMID:40968612 | DOI:10.3345/cep.2025.00836
JACC Case Rep. 2025 Sep 17;30(28):105094. doi: 10.1016/j.jaccas.2025.105094.
ABSTRACT
BACKGROUND: The LAMPOON (laceration of the anterior mitral leaflet to prevent outflow obstruction) procedure is an innovative transcatheter technique designed to prevent left ventricular outflow tract obstruction during transcatheter mitral valve interventions.
CASE SUMMARY: A 14-year-old male patient with a history of infective endocarditis, previously treated with surgical aortic valve replacement and mitral annuloplasty, presented with severe mitral regurgitation and decompensated heart failure. Owing to prohibitive surgical risk, a transcatheter mitral valve-in-ring replacement (TMViR) was performed with adjunctive LAMPOON to prevent left ventricular outflow tract obstruction. This is to our knowledge the first reported pediatric case of TMViR facilitated by LAMPOON. The procedure was technically successful, and the patient recovered without major complications.
DISCUSSION: This case highlights a novel application of LAMPOON in the pediatric population. Given the absence of surgical options, this approach offers a life-saving, minimally invasive alternative and expands the role of structural interventions in children with complex valvular disease.
TAKE-HOME MESSAGES: LAMPOON can enable safe TMViR in high-risk pediatric patients. Successful outcomes require careful planning, imaging, and multidisciplinary coordination.
PMID:40973330 | PMC:PMC12478498 | DOI:10.1016/j.jaccas.2025.105094
Front Immunol. 2025 Sep 3;16:1652294. doi: 10.3389/fimmu.2025.1652294. eCollection 2025.
ABSTRACT
INTRODUCTION: Currently, chronic immune rejection of bioprosthetic heart valves (BHVs) is considered among the key players in the development of structural valve degeneration (SVD). However, the relative contribution of leukocyte infiltration and cyclic mechanical loading into the SVD in bioprosthetic mitral valves (BMVs) and bioprosthetic tricuspid valves (BTVs, experiencing lower hemodynamic load due to the right heart's pressure environment) remains unclear.
METHODS: Here we performed an investigation of BMVs and BTVs which have been pairwise-excised from 4 patients during the BHV replacement because of BMV failure. The amount of valvular calcification was measured by multislice computed tomography and quantified using Pydicom script. Immune cell infiltration and lipid deposition in sectioned leaflets were evaluated by hematoxylin and eosin and Oil Red O staining, respectively; the semi-quantitative analysis of whole slide images was conducted by QuPath and Fiji software. In addition, we conducted an ultrastructural examination of BHVs by backscattered scanning electron microscopy after epoxy resin embedding (EM-BSEM technique).
RESULTS AND DISCUSSION: All BMVs had a significant extent of lipid deposition, hemorrhages, and tears, which eventually led to its mechanical incompetence. Strikingly, BMVs had less amount of immune cell infiltration as compared with BTVs. These results indicate that mechanical fatigue prevails over immune cell infiltration in driving the development of SVD.
PMID:40969748 | PMC:PMC12440782 | DOI:10.3389/fimmu.2025.1652294
Open Heart. 2025 Sep 17;12(2):e003453. doi: 10.1136/openhrt-2025-003453.
ABSTRACT
INTRODUCTION: An evidence-based selection between fractional flow reserve (FFR) and optical coherence tomography (OCT) to drive percutaneous coronary intervention is still lacking.
METHODS: Patients enrolled in the Fractional Flow Reserve vs. Optical Coherence Tomography to Guide Revascularization of Intermediate Coronary Stenoses (FORZA) trial and in the OCT-Features Of moRphology, coMposItion anD instABility of culprit and not culprit coronary pLaquE in ACS patient (OCT-FORMIDABLE) registry were included. Target vessel revascularisation (TVR) and major adverse cardiac events (MACE), a composite endpoint of cardiac death, myocardial infarction (MI) and TVR were considered as coprimary endpoints. Phenomapping with clustering was performed: incidence of outcomes according to FFR and OCT was explored.
RESULTS: 405 patients were treated according to OCT and 405 to FFR. Three different clusters were identified. 48% of the patients were included in the first cluster, presenting mainly with stable angina and a relevant burden of risk factors (cardiovascular risk factors, CVRFs). 21% of the patients were included in the second cluster, presenting with ST segment elevation MI (STEMI) and with low rates of CVRFs. 31% of the patients, being admitted mostly for non-STEMI (NSTEMI) and with high rates of CVRFs, were included in the third cluster. FFR and OCT performed similarly in terms of MACE and TVR in the first cluster. In the second cluster, rates of MACE were lower in the OCT arm (3% vs 12%, p 0.04), mainly driven by TVR (2% vs 6%, p 0.18). In the third cluster, rates of TVR were significantly reduced in the OCT arm (6% vs 14%, p 0.037) with a neutral impact on MACE (12% vs 15%, p 0.71).
CONCLUSIONS: Compared with a functional assessment, an OCT-based approach reduces revascularisation in patients with STEMI/NSTEMI, while FFR proved non-inferior for patients with stable angina.
PMID:40967674 | PMC:PMC12458727 | DOI:10.1136/openhrt-2025-003453
BMJ Open. 2025 Sep 17;15(9):e092482. doi: 10.1136/bmjopen-2024-092482.
ABSTRACT
INTRODUCTION: Treatment expectations are a key mechanism of placebo effects in clinical trials. In a previous study (PSY-HEART-I), preoperative expectation optimisation improved quality of life 6 months postcardiac surgery. However, barriers such as travel distance, staffing shortages and COVID-19 limited participation. This study evaluates the feasibility and acceptability of iEXPECT, a brief internet-based intervention designed to optimise expectations before heart surgery.
METHODS AND ANALYSIS: In this three-arm, multicentre randomised controlled trial, 160 patients undergoing elective coronary artery bypass graft surgery are randomised to: (a) standard of care (SOC); (b) SOC plus iEXPECT with phone-based guidance (iEXPECT enhanced) or (c) SOC plus iEXPECT with email-based guidance (iEXPECT limited). The intervention includes four 20 min online modules addressing surgical benefits, side effects and coping strategies. Modules are accompanied by personalised guidance provided through feedback on each module via email or telephone (three before surgery, three booster sessions at 6, 12 and 18 weeks postsurgery). Assessments occur at baseline (5-21 days before surgery), preoperatively (day before surgery), 7 days postsurgery and 6 months later. Primary feasibility outcomes include recruitment (≥1 participant/week/centre), retention (≥49% completing 6-month follow-up including biomarkers) and engagement (≥75% completing ≥1 presurgery module). Acceptability is measured by self-reported enjoyment, usefulness and impact, with acceptance defined as mean scores >3.4 (5-point Likert scale) and CSQ-I ratings. Secondary outcomes include psychological measures, inflammatory markers and heart rate variability.
ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committees of Philipps University Marburg (AZ 229/23 BO) and the University of Giessen (AZ 186/23). All participants provide written informed consent. Results will be shared via publications, conferences and public outreach with relevant consumer advocacy groups.
TRIAL REGISTRATION NUMBER: DRKS00033284.
PMID:40967648 | PMC:PMC12458749 | DOI:10.1136/bmjopen-2024-092482
Ann Vasc Surg. 2025 Sep 16:S0890-5096(25)00600-4. doi: 10.1016/j.avsg.2025.08.052. Online ahead of print.
ABSTRACT
BACKGROUND: Carotid artery stenosis is a significant cause of ischemic stroke. Transcarotid artery revascularization (TCAR), a newer technique utilizing dynamic flow reversal, has emerged as a potentially safer alternative to transfemoral carotid artery stenting (TFCAS). This systematic review and meta-analysis aimed to compare TCAR and TFCAS in patients undergoing carotid revascularization.
METHODS: We searched PubMed, Cochrane CENTRAL, Scopus, and Web of Science through June 2025 for comparative studies evaluating TCAR vs TFCAS. Primary outcomes included 30-day and in-hospital mortality, stroke, and composite stroke/death. Secondary outcomes assessed myocardial infarction (MI), transient ischemic attack (TIA), procedural times, and periprocedural complications. Risk ratios (RRs) and mean differences (MDs) were pooled using random-effects models.
RESULTS: Thirteen studies involving 142,032 patients were included in the analysis. TCAR significantly reduced 30-day mortality (RR 0.45; p<0.001), in-hospital mortality (RR 0.45; p<0.001), 30-day stroke (RR 0.66; p<0.001), and composite 30-day stroke/death (RR 0.57; p<0.001). TIA (RR 0.72; p<0.001) and stroke/TIA (RR 0.66; p<0.001) were also lower with TCAR. MI rates were similar overall, though asymptomatic patients had a higher 30-day MI risk with TCAR. TCAR reduced reperfusion injury (RR 0.38; p<0.001) and hospital stay length (RR 0.76; p<0.001), but had slightly longer operative times. Long-term data from two large cohorts confirmed TCAR's durable stroke risk reduction up to 3 years.
CONCLUSION: This meta-analysis of current observational data demonstrates that TCAR is associated with superior perioperative outcomes compared to TFCAS, with significantly lower rates of stroke and death. These findings support TCAR as a preferred endovascular treatment for eligible patients with carotid artery stenosis.
PMID:40967268 | DOI:10.1016/j.avsg.2025.08.052
Sichuan Da Xue Xue Bao Yi Xue Ban. 2025 May 20;56(3):840-845. doi: 10.12182/20250560104.
ABSTRACT
OBJECTIVE: To study the effect of the transbrachial artery approach on the success rate of puncture, revascularization time, and postprocedural complications in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI).
METHODS: The clinical data of 324 patients with STEMI who underwent PCI between September 2020 and May 2024 at our hospital were retrospectively analyzed. According to the different approaches, the patients were divided into a brachial artery group (127 cases) and a radial artery group (197 cases). Their procedural parameters (X-ray exposure time, contrast agent dosage, puncture time, puncture success rate, and revascularization time) and hospital length-of-stay, cardiac function indicators, including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI), before surgery and 3 months after PCI, and the incidence of complications were compared between the two groups of patients. Furthermore, a difference-in-differences method was adopted for the logistic model to evaluate the effects of different approaches.
RESULTS: There were no statistical differences in the general data between the brachial artery group and the radial artery group. Compared with those of the radial artery group, the revascularization time and length-of-stay of the brachial artery group were shortened, and the success rate of puncture was increased (P < 0.05). There were no significant differences in X-ray exposure time or contrast agent dosage between the two groups. The changes in LVEF, LVFS, LVESVI, and LVEDVI from baseline to 3 months post-PCI were (10.97 ± 7.15)%, (3.29 ± 5.90)%, (22.11 ± 9.30) mL/m2, and (18.13 ± 6.68) mL/m2, respectively, in the brachial artery group, while those in the radial artery group were (10.61 ± 7.13)%, (4.38 ± 6.04)%, (23.13 ± 9.60) mL/m2, and (19.34 ± 7.27) mL/m2, respectively, without statistical differences. Difference-in-differences analysis revealed that there were no statistical differences in the effects of different approaches on LVEF, LVFS, LVESVI, and LVEDVI between the brachial artery group and the radial artery group. During follow-up, no complications, such as coronary perforation, coronary dissection, or stent thrombosis, were observed in either group, and there were no statistical differences in the complication incidence between the two groups.
CONCLUSION: The transbrachial artery approach can shorten the revascularization time and length-of-stay of patients with STEMI treated by PCI. It has a high success rate of puncture and can promote the recovery of postoperative cardiac function without increasing postoperative complications.
PMID:40964121 | PMC:PMC12439660 | DOI:10.12182/20250560104
Catheter Cardiovasc Interv. 2025 Sep 17. doi: 10.1002/ccd.70163. Online ahead of print.
ABSTRACT
Dual antiplatelet therapy (DAPT) is recommended after percutaneous coronary intervention (PCI), though the optimal duration is unclear. DAPT reduces stent thrombosis, repeat myocardial infarction, and cardiovascular death, though at the cost of increased bleeding events. Currently, both European and American guidelines recommend a 6-month duration of DAPT following PCI with drug-eluting stents (DES) for stable coronary disease and a 12-month regimen following PCI for acute coronary syndrome. Recent randomized clinical trials (RCTs) suggest a shorter duration of DAPT may be acceptable. PubMed, EMBASE, and Cochrane databases were queried from inception to June 2025 to identify RCTs comparing short ( ≤ 3 months) with traditional durations of DAPT following PCI with DES and reporting outcomes of interest at 1 year, including major adverse cardiovascular and cerebrovascular events (MACCE) and net adverse clinical events (NACE). Individual endpoints including mortality, cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, significant bleeding, and target vessel revascularization were analyzed. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes with 95% confidence intervals. Thirteen studies met the inclusion criteria, reporting results on 53,421 patients, of whom 26,712 patients were in the short DAPT cohort and 26,719 in the traditional DAPT cohort. Duration of DAPT ranged from 1 to 3 months. Ten studies used P2Y12 inhibitors as the single antiplatelet agent following DAPT, whereas three studies used aspirin. Patients were 76.0% male, mean age 64.0 years, and 64.9% with ACS on presentation. Shorter duration of DAPT significantly decreased NACE (RR: 0.80; [0.71, 0.91], p < 0.001) without impacting MACE (RR: 0.98; [0.89, 1.07], p = 0.64) at 1 year following PCI with DES. A 3-month duration of DAPT demonstrated favorable results over shorter durations, and monotherapy with a high-potency P2Y12 inhibitor was preferable over aspirin or a low-potency P2Y12 inhibitor. In patients who underwent a PCI with DES placement, a 3-month duration of DAPT decreased NACE without impacting other MACCE compared to guideline-directed DAPT durations.
PMID:40963197 | DOI:10.1002/ccd.70163
Cardiol Rev. 2025 Sep 18. doi: 10.1097/CRD.0000000000001046. Online ahead of print.
ABSTRACT
Assessing lesion severity and optimizing percutaneous coronary intervention (PCI) are crucial for improving long-term outcomes in patients with coronary artery disease. Both strategies offer advantages over angiography alone; however, direct comparisons for revascularization decision-making are limited. This study evaluates and compares outcomes of FFR versus intravascular ultrasound (IVUS)-guided PCI strategies. We searched PubMed, Cochrane Central, and ScienceDirect from inception till April 2025. Data for various outcomes were extracted after computing the random-effect model and risk ratio (RR) with a 95% confidence interval (CI). The quality assessment of the included randomized controlled trials and observational studies was conducted using the Cochrane Risk of Bias 2 (ROB-2) and the Newcastle-Ottawa Scale, respectively. Publication bias was assessed visually through funnel plots and statistically through Egger's regression test. We included 5 studies comparing FFR and IVUS in 4714 patients undergoing PCI. The FFR and IVUS groups demonstrated comparable results across all endpoints including major adverse cardiovascular events (RR: 1.05; 95% CI: 0.84-1.30; P = 0.68), all-cause mortality (RR: 0.84; 95% CI: 0.50-1.39; P = 0.49), cardiac death (RR: 1.05; 95% CI: 0.59-1.87; P = 0.87), nonfatal myocardial infarction (RR: 1.31; 95% CI: 0.70-2.44; P = 0.40), and target vessel revascularization (RR: 1.20; 95% CI: 0.78-1.84; P = 0.40). The FFR (either hyperemic or angiography-driven) and IVUS groups showed comparable clinical outcomes in PCI for intermediate coronary lesions. However, FFR adds value with enhanced cost-efficiency and a physiology-driven approach that avoids unnecessary interventions. Selection should depend on patient factors, operator expertise, and institutional resources.
PMID:40963157 | DOI:10.1097/CRD.0000000000001046
Cell Stem Cell. 2025 Oct 2;32(10):1563-1576.e11. doi: 10.1016/j.stem.2025.08.015. Epub 2025 Sep 17.
ABSTRACT
Adult mammalian hearts are non-regenerative, and a majority of studies examining repair and potential regeneration post-myocardial infarction (MI) have focused on cardiomyocyte (CM) proliferation and infarcted zones. Here, we observed aberrantly high expression of lysozyme 2 (Lyz2) in injured mouse hearts at both local injury sites and at remote zones, with sustained Lyz2 expression conspicuous in endocardial cells of non-regenerative hearts. Although traditionally conceptualized as a myeloid marker, we demonstrate that LYZ2 functions as an injury-specific, positive regulator of lysosomal degradation capacity that mediates pathogenic degradation of the extracellular matrix. We observed an anti-apoptotic benefit to CMs upon disrupting LYZ2/LYZ function in mice and in a human endomyocardium experimental model. Harnessing these insights, we show that both Lyz2 knockout (KO) and pharmacological inhibition of lysosomal degradation confer rapid functional recovery in injured non-regenerative hearts. Thus, targeting a remote injury response in a non-CM cell type rapidly promotes post-MI recovery of non-regenerative hearts.
PMID:40967223 | DOI:10.1016/j.stem.2025.08.015
J Pharmacol Exp Ther. 2025 Aug 28;392(10):103681. doi: 10.1016/j.jpet.2025.103681. Online ahead of print.
ABSTRACT
Lornoxicam is traditionally used as an anti-inflammatory and analgesic drug. Recent studies suggest that nonsteroidal anti-inflammatory drugs can influence platelet and coagulation pathways. However, the antithrombotic and cardiopulmonary protective potential of lornoxicam remains unexplored. This study addressed this gap by evaluating lornoxicam's effects on thrombosis, myocardial infarction (MI), and pulmonary embolism (PE) using in silico, in vitro, and in vivo models. Docking analysis with 16 target proteins revealed novel interactions with lornoxicam, suggesting potential antithrombotic and cardiopulmonary benefits of beyond its cyclooxygenase (COX)-mediated actions. AutoDock (version 4.2.6) was used with default parameters and empirical force field (Exhaustiveness: 8). High binding affinities (E-value > -9.0 kcal/mol) were observed for COX-1, glycoprotein IIb/IIIa, antithrombin III, COX-2, and nuclear factor kappa light chain enhancer of activated B cells (NFκB), and molecular dynamics simulations confirmed stable ligand-protein complexes. In arachidonic acid-induced platelet aggregation, lornoxicam showed concentration-dependent inhibition (77.8% at 10 μM, IC50 = 0.61 μM) compared with 94.81% inhibition by aspirin (10 μM). In ADP-induced aggregation assays, inhibition was less pronounced (23.21% at 10 μM, IC50 = 20.6 μM). Lornoxicam significantly prolonged prothrombin time, activated partial thromboplastin time, thrombin time, and clot lysis at 1, 3, and 10 μM concentrations (P < .001 vs saline). The cardioprotective potential of lornoxicam was confirmed via an isoprenaline (ISO)-induced MI model in rats, while its protective effect on PE was assessed using a self-embolus-induced PE rat model. Lornoxicam protected the heart and lung tissues of rats against histological damage and infarction by decreasing oxidative stress and inflammatory responses. This effect was due to reduced expression of NFκB, tumor necrosis factor alpha, COX-2, NOD-like receptor family, pyrin domain containing 3, and platelet-derived growth factor beta (in the lungs), as confirmed via immunohistochemical analysis, ELISA, and reverse-transcription polymerase chain reaction. This study opens a new avenue for the repurposing and prophylactic use of lornoxicam in patients more prone to thrombotic disorders. SIGNIFICANCE STATEMENT: The in silico, in vitro, and in vivo experiments in this study revealed the excellent antithrombotic potential and protective effect of lornoxicam on myocardial infarction and pulmonary embolism, even at lower doses. This study proposes that lornoxicam treatment, just like aspirin, at lower doses could be an appropriate prophylactic option in patients who are more prone to myocardial infarction and pulmonary embolism.
PMID:40967083 | DOI:10.1016/j.jpet.2025.103681
Biochem Biophys Res Commun. 2025 Sep 10;784:152613. doi: 10.1016/j.bbrc.2025.152613. Online ahead of print.
ABSTRACT
Reperfusion injury is a complex pathological process that exacerbates conditions such as myocardial infarction, stroke, and neonatal hypoxic-ischemic encephalopathy (HIE). In HIE, the reoxygenation phase amplifies the initial hypoxic insult by inducing oxidative stress, vascular dysfunction, and neuronal death via apoptosis and ferroptosis. Despite its clinical importance, the multifaceted nature of reperfusion injury poses challenges for experimental modeling and therapeutic screening. Here, we developed and refined a zebrafish hypoxia-reoxygenation platform that recapitulates key features of reperfusion injury associated with neonatal HIE, enabling both mechanistic studies and therapeutic validation with S-nitrosoglutathione (GSNO). Zebrafish larvae at 5 or 6 days post-fertilization (dpf) were subjected to varying hypoxia durations (5-20 min) followed by reoxygenation, with 6 dpf larvae exposed to 15 min hypoxia yielding a reproducible ∼50% survival at 48 h post-reoxygenation, providing an optimal baseline for intervention testing. This platform reproduces core pathophysiological outcomes including reduced survival, impaired motor behavior, neuronal loss, vasoconstriction, and diminished cerebral blood flow. GSNO (5-20 μM) was administered during early reoxygenation to assess dose-dependent effects. Treatment with 15 μM GSNO significantly improved survival, restored behavioral function, and mitigated neuronal and vascular dysfunction. Mechanistic analyses revealed that GSNO reduced caspase-3 expression, malondialdehyde (MDA) levels, and intracellular Fe2+ accumulation. These protective effects likely reflect GSNO's multifaceted mechanisms, including NO-mediated vasodilation, inhibition of apoptotic pathways, augmentation of glutathione to counter oxidative stress, and facilitation of S-nitrosation, a key post-translational modification regulating protein function and cellular signaling. Overall, this work establishes a physiologically relevant zebrafish platform for modeling reperfusion injury in neonatal HIE, demonstrating its utility for therapeutic screening and underscoring GSNO's potential as a multi-target protective agent in this setting.
PMID:40967034 | DOI:10.1016/j.bbrc.2025.152613
Cardiovasc Res. 2025 Sep 12:cvaf133. doi: 10.1093/cvr/cvaf133. Online ahead of print.
NO ABSTRACT
PMID:40966486 | DOI:10.1093/cvr/cvaf133
PLoS One. 2025 Sep 18;20(9):e0332892. doi: 10.1371/journal.pone.0332892. eCollection 2025.
ABSTRACT
BACKGROUND: Heart failure (HF) is a major cardiovascular disease with high mortality worldwide, whose pathophysiology is multifaceted. Hypoxia has emerged as a critical factor contributing to the progression of heart failure. We aimed to examine the expression and functions of LncRNA Kcnq1ot1 in hypoxia-induced cardiomyocytes in the process of HF.
METHODS: H9C2 cell model was simulated by hypoxia treatment. TUNEL, ELISA, Western Blot and qRT-PCR assay were carried out to evaluate cell pyroptosis, inflammation and dysfunction. Subsequently, we identified the direct downstream target of Kcnq1ot1 by bioinformatics analysis, RNA pull-down, double Luciferase reporter gene and other functional experiments.
RESULTS: Firstly, Kcnq1ot1 levels was revealed to be upregulated in hypoxia cells than in control cells, and miR-27b-3p showed the opposite trend. And as expected, inhibition of Kcnq1ot1 and overexpression of miR-27b-3p both protected H9C2 against hypoxia-induced pyroptosis, inflammation and dysfunction. Moreover, miR-27b-3p was proved to bind with Kcnq1ot1 and participated in Kcnq1ot1-mediated H9C2 injury under hypoxia by regulating the Wnt3a/β-Catenin/NLRP3 signaling pathway.
CONCLUSIONS: Collectively, our study demonstrated that inhibition of Kcnq1ot1 protected cardiomyocyte against hypoxia-induced injury possibly via sponging miR-27b-3p, which could be useful as biomarkers and therapeutic targets for HF patients.
PMID:40966241 | PMC:PMC12445483 | DOI:10.1371/journal.pone.0332892
Curr Neuropharmacol. 2025 Sep 15. doi: 10.2174/011570159X394212250825051955. Online ahead of print.
ABSTRACT
Myocardial Infarction (MI) is a severe cardiovascular event, causing not only substantial damage to the heart but also potentially exerting a profound impact on brain function through a complex cardiac-brain interaction mechanism. The pathological process of MI encompasses myocardial cell necrosis, inflammatory cell infiltration, and the release of a substantial amount of inflammatory mediators. Through the bloodstream, these myocardial mediators may traverse the Blood-Brain Barrier (BBB), eliciting a neuroinflammatory response that can lead to cognitive dysfunction. This article proposes a critical research direction: investigating whether MI mediates the effects of myocardial- derived mediators on the permeability of the BBB, as well as the potential consequences of these mediators on cognitive functions. This review is aimed at triggering future research to elucidate the underlying mechanisms governing heart-brain interactions after MI in order to facilitate the development of more effective cognitive protection strategies for patients with MI.
PMID:40965068 | DOI:10.2174/011570159X394212250825051955
medRxiv [Preprint]. 2025 Sep 11:2025.08.22.25333921. doi: 10.1101/2025.08.22.25333921.
ABSTRACT
BACKGROUND: ADRB1 and ADRB2, encoding cardiac myocyte β1- and β2-adrenergic receptors (ARs) that mediate pathologic myocardial remodeling in response to chronically increased signaling, contain N-terminus haplotype variants capable of influencing agonist- or biased ligand-induced receptor internalization that uncouples canonical signaling and initiates EGFR/ERK1/2 cardioprotection.
METHODS: In two heart failure (HF) clinical trial genetic substudies we investigated effects of internalizing vs. internalization-resistant ADRB1/ADRB2 haplotypes on clinical or biomarker responses to the biased ligand β-blocker bucindolol vs. placebo or vs. the nonbiased β1-antagonist metoprolol, and in haplotyped isolated human heart preparations we measured ERK1/2 activation in response to these same interventions.
RESULTS: In subjects with ≥3 internalizing ADRB1+ADRB2 haplotypes (6.7% subcohort) placebo treatment was associated with fewer clinical events compared to subjects with internalization-resistant haplotypes (Odds Ratio (OR) 0.28, 95% CI (0.10, 0.82)). In contrast, placebo treatment in subjects with ≥3 internalization-resistant haplotypes (70% subcohort) was associated with more clinical events in comparison to subjects with internalizing haplotype counterparts (OR 1.64 (1.46, 1.84)). Bucindolol treatment was equal to placebo in the ≥3 internalizing subcohort, but was superior to placebo in the internalization-resistant subcohort (bucindolol vs. placebo OR 0.49 (0.41, 0.58)). In subjects with all 4 haplotypes internalization-resistant (25% subcohort), bucindolol vs. placebo reduced time to first event rates by 62.3±17.5% (P <0.01, 1.68±0.34 fold > the all-haplotypes parent population and additive to 1.92±0.58 fold when the ADRB1 haplotype contained Arg389 rather than Gly389). The same bucindolol vs. placebo pattern was observed for NT-proBNP or norepinephrine reduction vs. metoprolol. In these comparisons ADRB2 and ADRB1 haplotypes behaved similarly, and although the haplotypes differed in frequency between Black and non-Black subjects, within haplotypes there were no by-race differences in therapeutic effects. Bucindolol but not metoprolol activated ERK1/2 signaling in isolated ventricular preparations with ≥3 internalization-resistant haplotypes.
CONCLUSIONS: 1) Both β1- and β2-AR haplotypes regulate therapeutic responses in HF; internalizing species confer protection against clinical events in placebo-treated subjects, while in internalization-resistant haplotypes the biased ligand β-blocker bucindolol but not the non-biased ligand metoprolol is associated with favorable effects. 2) The biased ligand cardioprotective effect may be related to internalization-dependent or -independent ERK1/2 activation.
PMID:40963743 | PMC:PMC12440051 | DOI:10.1101/2025.08.22.25333921
J Perinatol. 2025 Sep 18. doi: 10.1038/s41372-025-02392-0. Online ahead of print.
ABSTRACT
OBJECTIVE: Survival outcomes are shifting in trisomy 18 as cardiac disease is being repaired in infancy reminiscent of trisomy 21. The landscape of prenatal counseling related to cardiac disease and trisomy 18 is unknown.
STUDY DESIGN: A survey was distributed to pediatric cardiologists presenting two scenarios of cardiac disease varying by genetic diagnosis: trisomy 18 vs 21. Respondents were asked if cardiac surgery would be offered and ranked the importance of various factors in decision-making.
RESULT: Sixty three percent described surgery as an option in trisomy 18 compared to 97% in trisomy 21. Genetic diagnosis was most important in trisomy 18 compared to neonatal survival in trisomy 21. Quality of life and survival to discharge were least important in trisomy 18 compared to genetic diagnosis in trisomy 21.
CONCLUSION: Significant variability in prenatal counseling exists for trisomy 18. Indecision may be influenced by the genetic diagnosis, survival, and quality of life.
PMID:40968138 | DOI:10.1038/s41372-025-02392-0
J Cardiothorac Vasc Anesth. 2025 Aug 27:S1053-0770(25)00732-3. doi: 10.1053/j.jvca.2025.08.053. Online ahead of print.
ABSTRACT
BACKGROUND: Perioperative management of congenital heart disease (CHD) surgery presents a unique challenge due to significant pathophysiological alterations, with pulmonary hypertension contributing substantially to morbidity and mortality. Although pulmonary vasodilators and inodilators are commonly used, evidence of their efficacy and safety remains limited.
OBJECTIVES: To evaluate the effectiveness and safety of vasodilators and inodilators in pediatric patients undergoing CHD surgery.
DESIGN: Systematic review with network meta-analysis.
DATA SOURCES: PubMed, CENTRAL, and Embase.
ELIGIBILITY CRITERIA: We included single- or double-blind, parallel-group, randomized controlled trials comparing the perioperative use of vasodilators and inodilators in pediatric CHD surgery. We selected only English-language studies. We excluded crossover, non randomized trials and trials comparing the same drugs in all study arms.
RESULTS: We included 28 randomized controlled trials involving 3118 patients. Intravenous levosimendan ranked highest in decreasing postoperative mortality, although the effect was not statistically significant. Intravenous sildenafil and inhaled nitric oxide (NO) significantly reduced the duration of mechanical ventilation, and inhaled NO also significantly shortened the length of intensive care unit stay. Inhaled iloprost, NO, and enteral sildenafil reduced mean pulmonary artery pressure. No intervention significantly affected the incidence of acute kidney injury.
CONCLUSIONS: Vasodilators and inodilators did not significantly decrease perioperative mortality in pediatric CHD. Some agents, such as intravenous sildenafil and inhaled NO, demonstrated modest benefits of questionable clinical significance regarding duration of mechanical ventilation, intensive care unit stay, and pulmonary pressure. The results are limited by small sample sizes, study heterogeneity, variability in standard care, and risk of bias, requiring cautious interpretation.
REGISTRATION: CRD42024552531.
PMID:40968005 | DOI:10.1053/j.jvca.2025.08.053
Mil Med. 2025 Sep 12:usaf442. doi: 10.1093/milmed/usaf442. Online ahead of print.
ABSTRACT
A 64-year-old male veteran with a history of aortic valve (AV) replacement for severe bicuspid AV regurgitation from infective endocarditis was diagnosed with acute decompensated heart failure. Initial transthoracic echocardiogram evaluation demonstrated a dilated cardiomyopathy with a suspicious mass. Multimodality imaging evaluation, including cardiac computed tomography and cardiac magnetic resonance imaging, confirmed the diagnosis of a Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa. Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa may be a potential congenital abnormality or a rare, life-threatening complication of aortic surgery or infective endocarditis. Recognition via multimodality imaging is essential to ensure adequate treatment.
PMID:40966691 | DOI:10.1093/milmed/usaf442