Cardiomyopathy classification remains challenging due to their extraordinary clinical, morphological, and genetic heterogeneity. As diagnostic technologies evolve, so too must the frameworks by which we conceptualize and communicate these diseases. Since the 2008 ESC morphofunctional classification and the genotype-phenotype integrated MOGE(S) system proposed in 2013, substantial advances in imaging and genetics have prompted a revised 2023 ESC phenotype-first model. The five current phenotypes-dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and non-dilated left ventricular cardiomyopathy (NDLVC)-capture major morphological expressions but display extensive overlap, especially among DCM, ARVC, and NDLVC. This overlap underscores the need for dynamic, multiparametric diagnostic pathways and individualized interpretation.

The widespread use of coronary computed tomography (CT) to exclude significant coronary stenoses and, more broadly, to achieve a more accurate assessment of cardiovascular risk through the evaluation of atherosclerosis has gained momentum in recent years, largely driven by growing criticism of the traditional ischaemia-centred paradigm. The SCOT-HEART studies were among the first large randomized trials to promote the use of coronary CT in patients presenting with angina. The information provided by coronary CT translated into improved clinical outcomes through the adoption of more aggressive medical therapy, particularly lipid-lowering treatment, which was selectively prescribed to patients with evidence of atherosclerosis. The results of the SCOT-HEART 2 primary prevention trial are eagerly awaited and may further influence clinical practice. Finally, photon-counting CT, representing the latest technological advance, together with the application of artificial intelligence-based image analysis algorithms, may constitute an additional step forward in the use of CT imaging.

Despite major advancements in liver transplantation, graft dysfunction remains a key challenge for long-term success. The use of extended criteria donors, including donation after circulatory death, grafts with prolonged warm ischemia, steatotic grafts, and older donors, is often associated with delayed function or primary non-function. These risk factors must be accounted for when tailoring intraoperative and postoperative strategies. Intraoperatively, maintaining adequate hepatic perfusion, typically requiring mean arterial pressures above 55 millimeters of mercury through careful titration of vasopressors and fluids, is essential. Various monitoring modalities can support perfusion optimization. To minimize microcirculatory injury, anesthetic management can be optimized, and advanced microcirculation-monitoring tools such as videomicroscopy, contrast-enhanced ultrasound, and laser speckle contrast imaging should be considered. Additionally, ischemic preconditioning and postconditioning may help reduce postoperative graft dysfunction. Routine use of ultrasound in the postoperative period allows for early detection and treatment of vascular complications such as thrombosis or hepatic outflow obstruction. Use of machine perfusion and normothermic regional perfusion during organ procurement can help to ameliorate microcirculatory problems and improve the survival of extended criteria donors. This expert opinion paper outlines key aspects of hepatic graft monitoring and management aimed at improving outcomes in liver transplantation.

Atherosclerosis and Alzheimer's Disease are two significant health concerns characterised by overlapping pathophysiological mechanisms, including chronic inflammation, oxidative stress, and lipid metabolism dysregulation. Impaired vascular integrity in atherosclerosis enhances the accumulation of Aβ plaque in the brain by reducing cerebral perfusion and compromising the clearance of Aβ. This review examines the shared pathways linking these conditions, emphasizing the role of the NLRP3 inflammasome, Receptor for Advanced Glycation End Products, and the apolipoprotein E4 allele in exacerbating vascular dysfunction that promotes neurodegeneration. The interplay between these factors underscores the potential of targeting these common pathways as a therapeutic strategy for both diseases. In preclinical studies, emerging treatments, NLRP3 inflammasome inhibitors like MCC950 and CY-09, show promise in mitigating both arterial plaque formation and neuronal amyloid deposition, while innovative microRNA-based therapies targeting miR-146a and miR-155 offer novel approaches to reduce inflammatory responses. Additionally, modulation of lipid metabolism through liver X receptor agonists like T0901317 and cholesteryl ester transfer protein inhibitors, including Anacetrapib, offers potential dual benefits for cardiovascular and neurological health. However, challenges such as restricted BBB permeability, genetic and sex variability, and limited long-term clinical evidence continue to constrain the effectiveness of dual-targeted therapeutic approaches. Future perspectives suggest integrating multi-- modal therapies that combine anti-inflammatory, lipid-regulatory, and antioxidant strategies to effectively address these interrelated diseases. Advancements in molecular biology and imaging techniques may facilitate the development of personalised medicine approaches, ultimately improving outcomes for patients suffering from both atherosclerosis and Alzheimer's Disease.

A primary complication of atherosclerosis(AS) is characterized by chronic inflammatory and mitochondrial dysfunction, both of which play critical roles in the disease's progression. This study aims to investigate the regulatory role of mascRNA in mediating the hypoxia-induced phenotypic transition of vascular smooth muscle cells (VSMCs).

An AS model was established, and the aortic plaque area was assessed by Oil Red O staining. Human VSMCs were divided into five groups: normoxia, hypoxiainduced, negative control (pGV-NC), mascRNA overexpression (pGV-mascRNA), and inhibitor-treated. Quantitative PCR (qPCR) was utilized to detect the expression of mascRNA, vWF, and MMP2. Western blotting was performed to detect the expression of phenotypic transformation-related proteins.

In high-fat diet (HFD)-fed mice, the expression of mascRNA was significantly decreased in the aortas (P < 0.05). Hypoxia led to a reduction in mascRNA levels, an upregulation of synthetic markers, and increased reactive oxygen species (ROS) in VSMCs. Overexpression of mascRNA suppressed VSMC migration and proliferation, enhanced mitophagy, and inhibited the PI3K-AKT pathway. Our study has been the first to demonstrate mascRNA play a crucial role in VSMC phenotypic transformation and functions via regulation of mitophagy. These findings highlight mascRNA's role in AS development and provide a theoretical basis for its clinical applications, but in vivo experiments are called for to validate its anti-AS effect.

MascRNA suppressed hypoxia-induced phenotypic transformation of VSMCs, potentially through the modulation of the PI3K-AKT signaling pathway and the enhancement of mitochondrial autophagy. These findings indicate a prospective therapeutic application of mascRNA in AS.

Atrial fibrillation (AF) is a complex cardiac arrhythmia that substantially compromises survival and quality of life. Patients with AF are predisposed to a substantially elevated risk of systemic embolism, including ischemic stroke. Clinical risk-stratification tools guide the initiation of oral anticoagulation (OAC) to mitigate these thromboembolic complications. However, chronic OAC is inherently associated with bleeding complications, some of which may be life-threatening. Historically, maintenance of OAC has remained the clinical standard even after successful catheter ablation and subsequent restoration of sinus rhythm. Given that the procedural efficacy of ablation has improved in recent years, the need for lifelong anticoagulation in patients without documented recurrences is increasingly questioned. Findings from recent randomized controlled trials - OCEAN and ALONE-AF - provide a new perspective on this clinical paradigm. Here, we integrated available data concerning this topic, with the goal of providing input into the ongoing debate. This review compares data from these landmark trials in the context of previous literature. Although current evidence supports discontinuation of OAC after successful catheter ablation, such data should be interpreted with caution due to the presence of high-risk cohorts and the persistent influence of the underlying atrial substrate. This review also analyzes clinical and imaging factors that identify high-risk patients who may be unsuitable for OAC discontinuation. We discuss the utility of left atrium functional assessment via speckle-tracking echocardiography. Furthermore, we examine strategies for high-fidelity rhythm surveillance and methods for managing subclinical recurrences. Finally, we summarize current evidence and propose directions for future research in personalized antithrombotic therapy.

Acute aortic dissection (AAD) is a life-threatening emergency without established effective monitoring biomarkers. This study aimed to explore biomarkers to optimize the diagnosis of AAD. AAD related genes were screened by spatial transcriptomics experiments, and their encoded proteins were validated in aortic tissues. We measured plasma levels of candidate proteins in 302 participants (173 AAD cases, 129 controls), finding higher PTMA, ADAMTS8, and CD36 in AAD. Case-control analysis revealed that elevated levels of those proteins along with D-dimer, increased systolic blood pressure (SBP), height and smoking history were risk factors for AAD. A multi-marker score comprising D-dimer, ADAMTS8, height, SBP, and age was developed for AAD diagnosis, achieving an AUC of 0.921 (95%CI 0.889-0.952), with 77.5% sensitivity and 96.5% specificity. We further validated the diagnostic performance of the multi-marker score in an independent validation set including healthy controls and patients with chest pain. Our findings indicate that PTMA, ADAMTS8, and CD36 are potential biomarkers associated with AAD. The multi-marker score effectively discriminates AAD from both healthy controls and non-AAD acute chest pain conditions, and may serve as a rapid, cost-effective auxiliary diagnostic tool.

Understanding the genetic regulation of circulating protein levels can provide new insights into disease mechanisms. Here, we present the largest proteogenomic study to date (n = 78,664 participants across 38 studies), identifying >24,000 protein quantitative trait loci (QTLs) associated with 1,116 proteins, acting near to (n = 5,040) or distant (n = 19,698) from the cognate gene. Using machine learning-guided effector gene assignment, we provide genetic evidence for pathways, cell types, and tissues that modulate circulating protein levels, highlighting N-linked glycosylation as an important regulatory pathway. We demonstrate that genetic instruments of protein production/function ("cis") versus modulation ("trans") reveal distinct phenotypic insights. We identify proteins as candidates for drug targets and engagement (e.g., plasma furin and cardiovascular diseases) by comparing cis-based genetic evidence with protein-disease associations. Systematic triangulation of trans-protein QTLs (pQTLs) with genetic and protein associations across many diseases highlights potential drug repurposing opportunities, e.g., tyrosine kinase 2 (TYK2) inhibitors for rheumatoid arthritis. Our multi-cohort meta-analyses generate proteogenomic insights into disease mechanisms and new treatment opportunities.

This study aims to explore the characteristics and differentiation pathways of microglia and macrophages using single-cell transcriptome data from mouse stroke models. The clusters of microglia and macrophages in the middle cerebral artery occlusion model mouse brain were identified using the Seurat package. The signaling pathways were evaluated through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses, while transcription factor activity was analyzed using DecoupleR. Monocle2 was employed to infer the differentiation trajectory of microglia and macrophages, exploring changes in gene expression patterns during their activation process using gene dynamics analysis. Additionally, the self-differential and overlapping subclusters of macrophages and microglia following cerebral ischemia were assessed, and CellChat was used to analyze differences in cell communication. An in vitro oxygen-glucose deprivation model of BV2 microglia was established, and phagocytosis assays and real-time-quantitative PCR were conducted to evaluate the effects of FoxO1 knockdown on the phagocytic ability and inflammatory cytokine production of microglia. Microglia and macrophages showed significant functional changes following ischemic stroke. Microglia enhance their phagocytic capabilities, whereas macrophages exhibited a reduction in phagocytic function. The predominance of microglia in phagocytic and inflammatory pathways is primarily attributed to the differential expression of specific transcription factors, particularly FoxO1. Knockdown of FoxO1 significantly diminished the phagocytic ability of BV2 cells and increased the expression of the inflammatory cytokines CCL2, IFN-γ, and TNF. The transcription factor FoxO1 mediates the functional differences in phagocytosis and inflammatory responses between macrophages and microglia. Activation of FoxO1 can significantly enhance the phagocytic capacity of microglia while simultaneously reducing inflammatory responses, positioning it as a potential new target for the treatment of ischemic stroke.

Single-ventricle congenital heart disease (SV-CHD) is a uniformly lethal condition requiring the Glenn surgery, which as a side effect eliminates arterial pulsatility and contributes to pulmonary vascular complications. In Glenn patients, we quantified pulsatility loss in each dimension of force (flow, pressure, and stretch) using cardiac catheterization and MRI. To model and investigate the individual impact of each dimension of pulsatility loss on the pulmonary vasculature, we applied isolated pulsatile and non-pulsatile mechanical stimuli to pulmonary artery endothelial cells (ECs) in vitro. We found that each dimension of force triggered distinct transcriptional responses, revealing force-specific regulation of structural and signaling pathways. Pulsatile stretch uniquely stimulated EC secretion of PDGFB, a key driver of vascular smooth muscle cell (vSMC) recruitment. In a rat Glenn model, loss of pulsatility led to vascular wall thinning, loss of EC PDGFB, and reduced activation of smooth muscle PDGFBRβ, confirming in vivo relevance. Our findings uncover a mechanistic link between endothelial stretch sensing and PDGFB-mediated EC-vSMC crosstalk, essential for maintaining pulmonary artery architecture. Clinically, these insights suggest that restoring or mimicking pulsatile forces may help preserve vascular integrity and prevent remodeling in patients with SV-CHD.