Non-atherosclerotic coronary artery disease (N-ACAD) is a group of conditions affecting the coronary arteries that can result in sudden cardiac death. This group of conditions can be categorized into structural anomalies, such as collagenopathies, and functional anomalies, such as inflammatory vasculopathies, based on the pathological mechanism. The epidemiology of N-ACAD varies according to the genetic condition involved; however, these disorders are thought to represent a significant proportion of sudden cardiac deaths among young individuals, especially those with a family history of inherited cardiovascular diseases. In collagenopathies, the causes of N-ACAD are genetic, involving pathogenic mutations in several genes responsible for encoding the structural proteins of the vascular wall. Conversely, in vasculitis, etiology is multifactorial, encompassing genetic, immune, environmental, and infectious contributors that influence inflammatory processes. Notably, pathogenic variants may result in arterial dissection, aneurysm formation, rupture, and, ultimately, sudden cardiac death. When the cause of death remains unexplained following a standard post-mortem examination, the case is classified as a sudden unexplained death. In such circumstances, a post-mortem genetic investigation-referred to as a molecular autopsy-is of key importance for identifying potential inherited cardiac conditions and assessing the genetic risk within the deceased’s family, with the aim of preventing future cases of sudden cardiac death. In this literature review, we focus on the role of pathogenic variants in the pathogenesis of non-atherosclerotic coronary artery disease associated with sudden cardiac death in the young.

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening form of heart failure that occurs in late pregnancy or the early postpartum period in previously healthy women. Characterized by left ventricular (LV) dysfunction and reduced LV ejection fraction (LVEF), PPCM shares pathophysiological features with other forms of dilated cardiomyopathy but presents unique challenges due to its association with pregnancy-related hormonal and vascular changes. While the exact etiology remains incompletely understood, oxidative stress, prolactin cleavage, inflammation, and genetic predisposition have been implicated in its pathogenesis. Diagnosis relies on echocardiographic evidence of systolic dysfunction in the absence of other identifiable causes of heart failure. Management strategies focus on optimizing heart failure therapy while considering the safety of both mother and fetus when treatment is initiated during pregnancy. Bromocriptine, an inhibitor of prolactin secretion, has emerged as a promising therapy, but its widespread use remains under investigation. Most patients experience significant recovery of cardiac function within six months postpartum; however, a subset progresses to chronic heart failure, transplantation, or death. This systematic review provides an in-depth analysis of current knowledge on the epidemiology, diagnostic challenges, and evolving therapeutic strategies for PPCM.

Artificial intelligence (AI) has been revolutionizing invasive cardiology in recent years, with respect to diagnostic accuracy, procedural success, and long-term patient outcomes. Advanced machine learning (ML) and deep learning algorithms facilitate automated image analysis, risk stratification, and personalized intervention planning, paving the way for precision medicine. AI-based technologies, such as coronary computed tomography angiography, intravascular ultrasound, and optical coherence tomography, enable precise plaque definition and quantification that goes beyond classical subjective methods. AI-based quantitative computed tomography and radiomics-based approaches have demonstrated strong correlations with invasive standards such as NIRS-IVUS, effectively identifying lipid-rich plaques and predicting acute coronary events. AI is also refining risk stratification models, significantly improving predictive capabilities compared to traditional methods, thus enabling personalized therapeutic interventions in real time. In interventional cardiology, the integration of real-time AI with fluoroscopy significantly improves procedural decision making while reducing procedure time, radiation exposure, and operator variability. Additionally, AI-assisted predictive analytics facilitate comprehensive risk assessment, optimizing treatment strategies by accurately identifying patients at the highest risk of major adverse cardiovascular events. ML algorithms improve image analysis by automating plaque characterization, thus facilitating clinical decision making and procedural optimization. In the future, AI-based applications, such as AI-guided catheter navigation, could further transform PCI, opening new possibilities for innovation and optimization. Despite these advances, challenges remain regarding data standardization, algorithmic interpretability, regulatory compliance, and ethical concerns about data privacy and potential bias. This review will explore the risks and potential benefits of this unprecedented evolution.

Cardiac computed tomography (CT) is an important tool in the management of patients with aortic root and ascending aorta dilatation. It complements echocardiography by providing high-resolution, three-dimensional images that enhance the assessment of aortic anatomy and help to determine the optimal timing for surgical intervention. Beyond preoperative planning, CT also plays an important role in postoperative surveillance by enabling early detection of changes or complications. Accurate imaging is essential for successful surgical outcomes, particularly given the complex structure of the aortic root and its relationship with the base of the left ventricle. Advances in CT technology, including improvements in spatial and temporal resolution, now allow surgeons to obtain highly detailed, accurate images of the aortic root, which are critical for planning aortic valve-sparing procedures. These detailed images provide a clearer picture of the root’s anatomy and structural components, thereby supporting more informed and precise surgical decision making. Intraoperative decision making based solely on surgical experience may always yield optimal results. This is because the aortic root is not under physiological stress during surgery, and outcomes may vary depending on the surgeon’s level of experience. These factors can influence the success of the procedure. This review highlights the growing importance of cardiac CT in the preoperative planning of complex aortic root surgeries. By providing clear, detailed anatomical data, CT enables surgeons to develop more individualized surgical strategies, ultimately improving outcomes and supporting personalized care for patients with aortic root aneurysms.

The increase in the average age of the population leads to an inevitable increase in demand for coronary intervention in elderly patients with more comorbidities, often carriers of coronary calcifications. Calcific lesions present a major challenge in Percutaneous Coronary Interventions, often requiring debulking techniques for successful lesion preparation. In some cases, the combined use of “dedicated” devices is essential. Some imaging-based algorithms have been established to guide the stepwise treatment of severe angiographic calcification by evaluating the calcium burden in terms of its circumferential extension, length, and thickness. Mild angiographic calcifications do not require an atherectomy strategy. Moderate and severe angiographic calcifications generally require debulking techniques. Currently, practice guidelines recommend the use of rotational atherectomy to prepare heavily calcified lesions that cannot be crossed using a balloon or adequately dilated before planned stenting (bailout situations). However, the evaluation of the plaques, as well as the characteristics of the patient, should be considered when choosing the most appropriate debulking system, and sometimes a combination of different techniques may be necessary. Therefore, understanding the various debulking systems and the possible combinations of these can be crucial for optimizing the procedural outcome.

Aim: To study the clinical effects and long-term outcomes of radiofrequency renal denervation (RDN) in patients with true resistant arterial hypertension, type 2 diabetes mellitus, and coronary artery disease after completed myocardial revascularization.

Methods: 75 patients were randomized into RDN and control groups (1:1.5). RDN was performed via femoral access using a Spyral catheter (Medtronic, USA). The primary endpoint was the change in blood pressure (BP). Secondary endpoints were: the development of cardiovascular and cerebral complications, changes in laboratory and instrumental parameters, changes in antihypertensive medication, late lumen loss (LLL) in the stented segments [measured by computer-assisted quantitative coronary angiography analysis (QCA)], and the frequency of de novo stenosis.

Results: In the RDN group, there was a significant decrease in both office (o) and average daily (ad) systolic (S) and diastolic (D) BP (oSBP: -8 mmHg; oDBP: -6 mmHg; adSBP: -11 mmHg; adDBP: -8 mmHg - P < 0.05); decreased activity of plasma renin Δ-2.44 ng/mL/h; concentrations of angiotensin I Δ -1.27 ng/mL and aldosterone Δ -13 pg/mL - P < 0.05); decrease in fasting glycemia (Δ -2.73 mmol/l - P < 0.05), HbA1c (Δ -1% - P < 0.05) and the level of insulin resistance according to HOMA-IR index (Δ -1.78 - P < 0.05), as well as a decrease in the concentration of C-reactive peptide in the blood (Δ -1.84 mg/L - P < 0.05). No significant dynamics of these indicators were recorded in the control group. The effectiveness of RDN was highest in the cohorts of obese patients - OR 1.31 (95%CI: 1.17-1.44), patients with obstructive sleep apnea syndrome - OR 1.73 (95%CI: 1.23-2.26) and tachycardia - OR 2.02 (95%CI: 1.69-3.10); P < 0.001 in all cases. The incidence of major adverse cardiovascular events (26.7% in the RDN group; 24.4% in the control group), the average LLL (24.7% in the RDN group; 28.1% in the control group), and the incidence of de novo stenosis (23.3% in the RDN group; 22.2% in the control group) did not differ between the groups.

Conclusion: The use of RDN in the cohort of comorbid patients is safe and enables better control of modifiable risk factors of progression of resistant arterial hypertension and type 2 diabetes mellitus due to an improvement of BP, carbohydrate metabolism parameters, regulatory factors of the renin-angiotensin-aldosterone system (RAAS), and factors of the systemic inflammatory response.

Aim: We measured the left-to-right ventricular volume ratio (LRVR) in a large cohort of patients with transfusion-dependent thalassemia (TDT) and assessed its cross-sectional correlations and its prognostic value in predicting heart failure (HF) and all-cause mortality.

Methods: 1,481 TDT patients underwent cardiovascular magnetic resonance for assessment of biventricular volumes and ejection fractions (cine images) and myocardial iron overload (T2* technique) and for detection of replacement myocardial fibrosis (late gadolinium enhancement-LGE images). The LRVR was defined as the ratio between the left ventricular (LV) and right ventricular (RV) end-diastolic volume indexes.

Results: 1160 (78.3%) patients had normal ventricular symmetry, 220 (14.9%) LV dominant asymmetry (LRVR > 118%), and 101 (6.8%) RV dominant asymmetry (LRVR < 89%).

Cardiac iron levels and LGE were comparable among the three groups. LV dominance was associated with reduced LV function. RV dominance was correlated with aging, reduced RV function, and a history of arrhythmias.

The mean follow-up time was 4.82 ± 2.06 years. HF death occurred in 15 (1.01%) patients. The risk for HF death was significantly higher in the group with RV dominant asymmetry compared to that with normal ventricular symmetry (hazard ratio, HR = 6.07). All-cause death occurred in 42 (2.8%) patients. RV dominant asymmetry was associated with a significantly increased risk of all-cause mortality compared to normal ventricular symmetry [hazard ratios (HR) = 3.57] and LV dominant asymmetry (HR = 6.17). RV dominance remained associated with an increased risk of HF and all-cause mortality even after adjusting for other risk factors such as cardiac iron, LGE, or biventricular ejection fractions.

Conclusion: The LRVR may play a significant role in enhancing death risk stratification in TDT.

Endothelial dysfunction is a pivotal factor in the pathogenesis of atherosclerosis, driving plaque formation, inflammation, and thrombosis. This review synthesizes classical mechanisms and emerging perspectives on endothelial dysfunction, emphasizing its role in atherogenesis. Traditional contributors, including lifestyle factors, lipid dysregulation, shear stress, and nitric oxide (NO) deficiency, are discussed alongside novel insights from single-cell RNA sequencing, metabolomics, and intercellular communication. scRNA-seq has unveiled endothelial cell (EC) heterogeneity and endothelial-to-mesenchymal transition (EndMT) as critical contributors to plaque instability. Metabolites such as trimethylamine N-oxide (TMAO) and homocysteine derivatives exacerbate endothelial injury, while gut microbiome interactions further modulate disease progression. Exosome-mediated crosstalk between ECs, immune cells, and vascular smooth muscle cells (VSMCs) highlights new pathways in vascular inflammation and remodeling. Current pharmacotherapies, such as lipid-lowering and anti-inflammatory drugs, improve endothelial function, and emerging strategies like nanotechnology and exosome-based therapies show promise as well. Integrating classical and novel approaches could enhance our understanding of endothelial biology and lead to targeted therapies, addressing atherosclerosis-related diseases.

Reimplantation using a Valsalva graft is a well-established and validated technique for valve-sparing root replacement with sinus reconstruction. In 2014, Modine and collegues et al. proposed a modification to the standard procedure in which the aortic valve is resuspended by simply attaching the tops of the commissures to the neo-sinutubular junction. This approach eliminates the need for continuous in-graft suturing of the aortic wall remnants. However, a major concern with this technique is the creation of a gap between the commissures and the graft, along with concentrated diastolic hemodynamic stress at the suture sites securing the commissural posts. Recently, we introduced an enhancement to the modine modification by securing the commissural posts more firmly to the Valsalva graft using longitudinal pledgeted sutures placed within the interleaflet triangles. Early short-term outcomes of this approach called the simplified reimplantation appear promising. The aim of this commentary is to describe the simplified reimplantation technique, evaluate its potential advantages over the Modine modification and define its appropriate indications.

Atherosclerosis is one of the key problems of modern society. A growing body of evidence suggests that atherosclerosis is not only a metabolic but also an immune disease with local and systemic mechanisms. Dyslipidemia, local disturbances in vascular hemodynamics, and inflammation in the vascular wall involving various immune and non-immune cells such as endothelial and smooth muscle cells, are thought to be important for the development of atherosclerosis. In this context, there is a growing clinical and research interest in the possibility of therapeutically targeting different immune mechanisms. The aim of the current review is to discuss recent advances in understanding the immune mechanisms of atherogenesis and the challenges and prospects for immunotherapy of atherosclerosis.

Ischemic stroke is a devastating global public health problem and the leading cause of acute death and chronic disability. Despite being the diagnostic cornerstone, limitations in neuroimaging, including availability, cost, and therapeutic window, have rekindled interest in biomarker-based approaches. Biomarkers will be employed to facilitate the eventual prediction, early diagnosis, and prognosis of strokes, as well as to inform person-centered medicine. This review summarizes recent advances in the search for biomarkers related to inflammatory, endothelial, metabolic, and neuroaxonal pathways. Interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), endothelial microparticles (EMP), and homocysteine serve as predictive biomarkers corresponding to vascular risk and inflammatory priming. Glial fibrillary acidic protein (GFAP), D-dimer, and neuron-specific enolase (NSE) are diagnostic markers that can already subtype stroke and estimate lesion burden. Prognostic biomarkers, such as serum neurofilament light chain (sNfL), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), and growth differentiation factor 15 (GDF-15), are associated with infarct size and long-term outcomes. The -omic sciences (genomic, proteomic, and metabolomic) have discovered defined molecular signatures and panels with high specificity to describe heterogeneity in stroke. Cerebrospinal fluid (CSF) biomarkers and newer imaging modalities, such as those provided through positron emission tomography/computed tomography (PET/CT), offer valuable adjuncts to blood biomarkers in the diagnosis of conditions. Translational potential is hindered by heterogeneity in the transcriptional landscape.

Three-dimensional transesophageal echocardiography (3D TEE) has become an indispensable tool for the anatomical and functional assessment of the aortic valve (AV). Accurately identifying the degree of regurgitation or stenosis is critical for therapeutic decision making; 3D TEE provides comprehensive morphological and functional descriptions, which have been improved by the introduction of new analytic methods. This review examines the development of 3D echocardiography in evaluating AV disorders, emphasizing its advantages over conventional 2D imaging. 3D TEE improves the accuracy of measures crucial to surgical planning and prosthesis selection, enabling real-time visualization of valve shape and dynamics. The widespread adoption of 3D echocardiography will contribute to improving the treatment of AV diseases as technology advances, thereby opening new horizons for more patient-tailored therapeutic strategies.

Robotic coronary artery bypass grafting (CABG) has emerged as a minimally invasive alternative to traditional open-heart surgery, offering reduced surgical trauma and faster recovery. Techniques include robotic-assisted minimally invasive direct coronary artery bypass (RA-MIDCAB), where the internal thoracic artery is harvested robotically and anastomosed via mini-thoracotomy, and totally endoscopic CABG (TECAB), which avoids thoracotomy altogether. Hybrid coronary revascularization, combining robotic left internal thoracic artery-left anterior descending (LITA-LAD) grafting with percutaneous coronary intervention, provides a patient-specific strategy for multivessel disease. While off-pump approaches reduce recovery time, on-pump techniques remain valuable in complex cases and are mainly performed at expert centers. Despite promising outcomes, such as low mortality, short hospital stays, and high graft patency, widespread adoption remains limited due to high costs and technical complexity. Mastering the technique and performing more advanced procedures like TECAB require a long learning curve. Proficiency improves with experience, typically after 10-50 cases, while full mastery may require hundreds of procedures. Most centers now favor RA-MIDCAB over TECAB, which remains limited to a few high-volume institutions. Recent advances in robotic platforms, including systems from Intuitive Surgical, Medtronic, CMR Surgical, and others, promise improved ergonomics, precision, and cost-efficiency. Features like haptic feedback, eye-tracking, and remote operation are advancing robotic surgery into a new era, though challenges persist in training and accessibility. As robotic systems continue to evolve and integrate artificial intelligence and telesurgical capabilities, broader adoption may become feasible, particularly when combined with hybrid revascularization strategies in selected patients.

For decades, coronary angiography has been the gold standard for identifying and evaluating culprit and non-culprit coronary lesions in acute coronary syndromes (ACS). However, angiography provides limited information on plaque composition and cannot assess the functional significance of lesions. To address these limitations, several invasive methods have been introduced and are now used in clinical practice, including intravascular imaging (IVI) and fractional flow reserve (FFR). Studies have compared FFR-guided complete revascularization with culprit-only revascularization, as well as FFR-guided versus angiography-guided revascularization in both ACS and stable angina. However, clinical trials in ACS have produced contradictory results: some studies indicate that FFR is feasible, safe, and associated with reduced major adverse cardiac events (MACE), while others are less conclusive. IVI has been evaluated in fewer ACS-specific studies, but initial findings are promising. Moreover, a novel strategy has emerged: preemptive stenting of high-risk, hemodynamically non-significant plaques identified by IVI to prevent future MACE. Nevertheless, the limited and sometimes contradictory data highlight the need for further research to determine the optimal diagnostic and treatment strategies for coronary lesions in patients with ACS.

Aim: To develop a functional classification of extrasystoles (ES) based on cardiac biomechanics, arterial hemodynamics and kinetics, and the associated risk of arterial vascular events.

Materials and methods: This monocentric, prospective study included 634 patients with ≥ 700 ES per 24 h. The control group consisted of 106 patients with < 700 ES per 24 h. The main group was divided into two subgroups, A and B, according to the identified ES variant, categorized by the timing of ES ventricular systole within the cardiac cycle, independent of the ectopic focus location. Standard instrumental and laboratory assessments were performed. The prospective follow-up period was one year, with evaluations at 6 and 12 months. The composite endpoint was the occurrence of ischemic vascular events.

Results: Patients with ≥ 700 ES per 24 h had a significantly higher incidence of arterial vascular complications within 1 year, particularly those in subgroup A. The first postextrasystolic wave was characterized by an increase in hemodynamic parameters, especially in early ES occurring before the transmitral blood flow peak (E wave) on echocardiography.

Conclusions: Considering the impact on hemodynamics and the differences in ischemic vascular event rates (including cerebral ischemic events, myocardial infarction, and embolic events in other vascular territories), ES can reasonably be classified based on the timing of ventricular systole within the cardiac cycle: ES with ventricular systole occurring before the transmitral blood flow peak, and ES with ventricular systole occurring after the transmitral blood flow peak.

Accurate characterization of coronary atherosclerotic plaque and individualized cardiovascular risk assessment remain active challenges in clinical and interventional cardiology. In recent times, Artificial Intelligence (AI) has emerged as a powerful new tool able to support clinicians in determining diagnoses and prognoses from coronary imaging. This commentary focuses on the current applications of AI in coronary plaque imaging, particularly on coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS), and optical coherence tomography (OCT), evaluating its role in identifying high-risk plaque features and predicting future adverse cardiovascular events. We discuss limitations of conventional assessment methods, illustrating how AI algorithms can improve reproducibility, reduce operator dependence, and examine current evidence from registries and clinical studies. Furthermore, some key challenges remain to be addressed, including data quality, model generalizability, clinical integration, and regulatory concerns. We argue that AI’s promise lies not in replacing clinical expertise, but in empowering coronary risk stratification and characterization. Ongoing validation and clinician-AI collaboration will be essential to ensure meaningful patient outcomes.

Calcified coronary nodules (CCNs) represent a distinct and under-recognized form of coronary artery calcification with significant implications for percutaneous coronary intervention (PCI). Unlike superficial or sheet-like calcifications, CCNs are characterized by protruding, irregular calcium deposits that disrupt luminal integrity, promote thrombus formation, and hinder optimal stent expansion. They have been implicated in acute coronary syndromes (ACS), in-stent restenosis (ISR), and PCI failure, yet they are underappreciated on angiography. This review provides a comprehensive overview of the pathophysiology, diagnostic modalities, and interventional challenges associated with CCNs. Intravascular imaging, particularly optical coherence tomography (OCT) and intravascular ultrasound (IVUS), plays a crucial role in distinguishing nodular from concentric or superficial calcium, thereby guiding appropriate lesion preparation strategies. It also facilitates differentiation between eruptive and non-eruptive nodules, which exhibit distinct prognostic and therapeutic characteristics. Various calcium modification techniques-including rotational atherectomy, orbital atherectomy, intravascular lithotripsy, and scoring/cutting balloons-offer specific advantages and limitations in treating nodular calcium. We also discuss evolving interventional strategies to optimize PCI outcomes and note that restenosis rates with covered stents are unacceptably high, making them unsuitable as a treatment option. Finally, we highlight the need for further research into hybrid calcium modification techniques and long-term PCI outcomes in patients with CCNs. Coronary artery bypass grafting remains a viable alternative.

Our commentary addresses the issues raised with two manuscripts published in the Special Issue of the Journal edited by Professor de Paulis about the surgical approach to the aortic root. It is unquestionable that appropriate surgical treatment requires a detailed understanding of the underlying anatomy. In the first article, Professor de Paulis et al. show the anatomical precision that can now be achieved using computed tomography. In the second article, the same group shows how an appreciation of this anatomy dictates their surgical approach. In our commentary, we highlight that the terms used in the two manuscripts indicate that the confusion identified in a questionnaire organized in 2012 about terminological issues remains unresolved, in particular regarding the definition of the enigmatic valvar “annulus”. We provide anatomical illustrations that demonstrate the ongoing problems. We also emphasize that bisecting planes of the root, rather than off-center cuts, should be used when taking the measurements of the components of the root that help the surgeon make the optimal repair. We finish by stressing the need for equal specificity in the words used to describe the components, pointing out that “cusp” is inadequate as a synonym for the valvar leaflets, especially since more often the valvar sinuses are described as “cusps”.

Diabetic cardiomyopathy (DCM) is a serious complication of diabetic mellitus that occurs independently of other known cardiac diseases and is associated with significant morbidity and mortality. Microvascular injury plays a central role in the pathogenesis of DCM, contributing to its hallmark features, such as cardiac contractile dysfunction and myocardial fibrosis. Current evidence points to endothelial dysfunction (ED) as the key contributor to the development of microvascular injury. Chronic hyperglycemia, hyperinsulinemia, and insulin resistance progressively promote ED, characterized by alterations in gene expression, shifts in endothelial cell (EC) subpopulation dynamics, and dysregulated crosstalk between EC and other cardiac cell types. Ultimately, these changes result in microvascular impairments such as chronic inflammation, EC loss leading to microvascular rarefaction, endothelial-to-mesenchymal transition (EndoMT) promoting myocardial fibrosis, and loss of vasodilatory function. If left uncorrected, these impairments will progress to contractile dysfunction and widespread myocardial fibrosis, manifesting as systolic heart failure. Over the past decade, single-cell RNA sequencing (scRNA-seq) has allowed for the transcriptional profiling of individual cells, enabling the identification of distinct subpopulations within the same cell type and providing deeper insights into cellular crosstalk under both normal and disease conditions. Although research on DCM using scRNA-seq remains an emerging field, studies have identified distinct EC subpopulations, their gene expression profiles, and their contributions to DCM pathogenesis. Moreover, scRNA-seq has revealed dysregulated interactions between ECs and other cardiac cell types in DCM. The expanding application of scRNA-seq holds significant promise for mapping EC subpopulation dynamics and communication pathways in DCM, which may ultimately support the development of novel EC-targeted therapeutic strategies against ED in this condition.

Over the past few decades, advances in physiological monitoring, imaging technologies, and artificial intelligence (AI) have greatly improved the diagnosis and treatment of cardiovascular diseases. However, traditional diagnostic methods have limitations, particularly in dynamic assessment and personalized care. Digital Twin technology offers a solution by creating virtual replicas of physical entities, enabling precise disease prediction and personalized interventions. This review introduces the concept of the digital vessel, a patient-specific cardiovascular digital twin that integrates imaging data, physiological signals, and AI-driven simulations. We define its core framework, summarize advances in image analysis, computational modeling, and predictive AI, and compare digital vessel models with conventional diagnostic tools in terms of data input, individualization, feedback, and scalability. Finally, we outline key challenges, including data integration, computational cost, clinical validation, and regulatory issues, and propose future research directions. By consolidating current knowledge, this review positions the digital vessel as a pathway toward precision diagnosis and personalized cardiovascular care.

Vascular diseases-including atherosclerosis, essential hypertension, pulmonary arterial hypertension, aortic dissection, and aneurysms-share core pathological mechanisms including endothelial dysfunction, inflammation-oxidative stress cascades, and aberrant activation of vascular smooth muscle cells (VSMCs). This review focuses on these four disorders as classic case studies to elucidate the multifaceted roles of extracellular vesicles (EVs) in vascular pathophysiology. Emerging evidence highlights that autoimmune-mediated vascular wall injury exacerbates these common pathogenic pathways in a subset of patients. EVs, nanoscale mediators endogenously produced by cells, are increasingly recognized for their multifaceted roles in vascular pathophysiology. They act not only as carriers of pathological signals [e.g., proteins such as cytokines, autoantigens, and proteases, as well as nucleic acids such as microRNAs (miRNAs)], but also as regulators of immune homeostasis. Beyond their well-documented function as miRNA transporters, EVs are now understood to serve as critical shuttles for functional proteins, including cytokines, growth factors, proteases, and even functional receptors. These cargoes can directly activate signaling pathways in recipient cells, thereby driving both vascular pathogenesis and repair processes. Furthermore, EVs also hold innovative platforms for targeted therapeutic delivery. This review examines the mechanistic roles of EVs in vascular disease therapy, explores current engineering strategies to enhance their therapeutic potential, and discusses the challenges and future prospects of their clinical translation.

Aim: This study aims to investigate the mechanisms by which vascular endothelial cells regulate the immune microenvironment in scleroderma.

Methods: Two public single-cell RNA sequencing (scRNA-seq) datasets (GSE264508 and GSE138669) from the Gene Expression Omnibus (GEO) database were analyzed, including skin samples from localized and systemic scleroderma patients. Seurat was used for data processing and clustering, CellChat for cell communication analysis, Monocle2 for pseudotime analysis, scMetabolism for metabolic profiling, and TwoSampleMR to identify potential causal genes based on expression quantitative trait loci (eQTL) data.

Results: We identified distinct EC subtypes and found enhanced communication between ECs and myeloid cells in scleroderma, indicating an active role in immune regulation. ECs remodeled the immune microenvironment via multiple ligand-receptor pairs. Increased oxidative phosphorylation in early-stage ECs was linked to immune activation. Pseudotime analysis revealed dynamic differentiation, and Mendelian randomization identified COX4I1 as a potential pathogenic and therapeutic target.

Conclusion: This study provides a comprehensive single-cell atlas of ECs in scleroderma, highlighting their immunometabolic plasticity and crosstalk with immune cells. The findings suggest that ECs are active participants in the early pathogenesis of skin fibrosis and support COX4I1 as a potential therapeutic target.

The “young-to-aged” paradigm represents a long existing postulation that rejuvenation in aged individuals can be achieved by replacing components such as cells, tissues, or organs with young counterparts. While highly publicized human plasma exchange trials show conflicting results, preclinical studies in mice demonstrate promising yet partial functional rejuvenation, including enhanced mitochondrial metabolism, reduced neurodegeneration, and revitalized stem cells via transfer of young biological components (e.g., plasma and microbiota). Importantly, certain critical studies have demonstrated that the “young-to-aged” paradigm could achieve partial cardiovascular rejuvenation in murine models. For instance, exposure to young plasma represses cardiac hypertrophy, while exposure to young microbiota alleviates vascular dysfunction and systemic inflammation. However, significant challenges still persist, including ethical concerns, the irreversibility of aging beyond certain thresholds, and senescence propagation of young donor transplants due to aged recipient environments. This paradigm faces immense scientific and ethical hurdles, raising profound questions about feasibility and identity.

Aim: Intracranial aneurysms pose significant challenges in diagnosis and treatment, emphasizing the need for accurate segmentation methods to assist clinicians in their management. In this paper, we present a novel approach for segmenting intracranial aneurysms using three-dimensional time-of-flight magnetic resonance angiography (TOF-MRA) images and the no-new-U-net framework. We aim to improve segmentation accuracy and efficiency through the integration of hybrid loss functions and additional vessel information.

Methods: The model was conducted on Aneurysm Detection And SegMentation (ADAM) and Renji Hospital (RENJI) datasets. The TOF-MRA ADAM dataset contains data from 113 cases, where 89 have at least one aneurysm with a median maximum diameter of 3.6 mm and range from 1.0 to 15.9 mm. The RENJI private TOF-MRA dataset comprises 213 cases including both ruptured and unruptured aneurysms with a median maximum diameter of 9.35 mm (range: 1.25-37.58 mm). We optimized the segmentation model by exploring hybrid loss functions that combine distribution-based and region-based losses to effectively delineate intricate aneurysm structures. Additionally, we incorporated vessel information as a region of interest using an automatic vessel segmentation algorithm to enhance the model's focus on critical regions. The model was trained on multi-modality data, including both vessel-enhanced and original images, to capture complementary information and improve segmentation accuracy.

Results: Extensive simulations on both the ADAM dataset and a private RENJI dataset demonstrate the effectiveness of our approach. The best-performing loss function yielded significant improvements in the Dice coefficient (0.72 and 0.54) and Sensitivity (0.69 and 0.53) on the RENJI and ADAM datasets, respectively.

Conclusions: The proposed method offers a promising solution for accurately segmenting intracranial aneurysms, showcasing superior performance compared to existing approaches. By integrating hybrid loss functions and vessel information, we enhance the model's ability to delineate intricate aneurysm structures, contributing to improved diagnosis and treatment planning for patients with intracranial aneurysms.

The role of sex in coronary artery disease (CAD), including its treatment and prognosis, is complex and has been studied for several decades. It is well known that men and women differ physiologically and that the pathophysiology of CAD varies between sexes. Additionally, there are sex differences in outcomes after coronary artery bypass grafting (CABG), with women experiencing worse outcomes than men. A PubMed search was conducted using terms related to differences between men and women with CAD requiring CABG. We will discuss the status of CABG in women with respect to preoperative profile, surgical strategy, short- and long-term outcomes, and quality of life. The leading causes of these differences remain debated. Generally, women are older and have a greater clustering of risk factors at the time of CABG. In particular, short-term outcomes appear worse for women, while studies on long-term outcomes are contradictory. Women also report a worse quality of life after CABG and experience higher rates of depression.

Atherosclerosis (AS) is a chronic inflammatory disease initiated by abnormal subendothelial lipid deposition in blood arteries. Although endothelial dysfunction, lipid homeostasis imbalance, and clonal proliferation of vascular smooth muscle cells are central to classical theories, recent studies have shown that immune cells such as neutrophils, T lymphocytes, and macrophages dynamically infiltrate the plaque microenvironment. This evidence suggests that the immune regulatory network plays a significant role in the pathological process of AS. It should be noted that female patients exhibit distinct clinical phenotypes and pathological characteristics during AS. This sex difference is closely related to changes in sex hormone levels, such as estrogen, as well as to differences in inflammatory responses and metabolic regulation. Studies aiming to control the progression of AS by targeting immune mechanisms unique to women remain in the exploratory stage, and their potential mechanisms of action and regulation have not yet been well clarified. This study will systematically elucidate immune activity and provide a theoretical basis for effective intervention strategies for cardiovascular disease in women, focusing on immunological remodeling and the relationship between sex and immunity in AS.

Vascular aging serves as a key driver of cardiovascular diseases, contributing significantly to the increasing global burden of morbidity and mortality. During vascular aging, stem cell senescence perturbs vascular homeostasis through impaired regeneration, increased oxidative stress, and chronic inflammation. Ultimately, it accelerates the development of vascular pathologies, such as atherosclerosis and aneurysm formation. This review aims to elucidate the roles of senescent vascular stem cells in the progression of vascular aging and also to explore the therapeutic potential of stem cell-based interventions in the management of cardiovascular diseases. It comprehensively includes various stem cell types, as well as their derived substances, elaborating on their roles in vascular aging and repair. Centered on "vascular stem cell senescence", it systematically elucidates the causal relationships among stem cell senescence, vascular homeostasis disruption, and the development of cardiovascular diseases, thereby constructing a focused and coherent mechanistic framework for understanding the pathological process of vascular aging. By integrating cross-system factors, including gut microbiota dysbiosis, renin-angiotensin system dysregulation, and abnormal hemodynamics, this review reveals the multi-system interactions underlying vascular aging. Moreover, it emphasizes translational rigor by not only introducing preclinical advancements but also objectively analyzing technical bottlenecks and clinical limitations, and further pointing out directions for future research. Overall, this review clarifies the roles of senescent vascular stem cells in vascular aging and the therapeutic potential of stem cell-based interventions for cardiovascular diseases, providing valuable references for promoting the clinical translation of stem cell-based strategies in the management of vascular aging-related cardiovascular diseases.

Vascular ageing accelerates panvascular diseases such as atherosclerosis, age-related arterial stiffening, pulmonary hypertension and cerebral microvascular dysfunction, yet the causal roles of senescent cells remain uncertain. This review aims to clarify those roles by systematically mapping the technological evolution, functional features and disease-specific applications of senescence reporter mouse models. We categorize senescence reporter mouse models into senescence tracing models and senescence eliminating models, and track three successive generations that progressively increased temporal, spatial and functional specificity. First-generation luciferase lines enabled non-invasive whole-body imaging; second-generation fluorescent reporters delivered single cell resolution; third-generation dual recombinase systems achieved lineage tracing and conditional clearance. In parallel, elimination platforms advanced from global ATTAC (apoptosis through targeted activation of Caspase) and trimodality reporter constructs to cell-type-restricted designs. Across atherosclerosis, arterial stiffening, pulmonary vascular remodeling and cerebral microvascular dysfunction, targeted removal or longitudinal tracking of cyclin-dependent kinase inhibitor 2A, CDKN2A (p16^Ink4a) or cyclin-dependent kinase inhibitor 1A, CDKN1A (p21^Waf1/Cip1) positive cells revealed both shared and tissue-specific pathogenic mechanisms, and provided genetic gold standards for benchmarking senolytic drugs. We highlight remaining gaps, particularly the reliance on single biomarkers (p16, p21, p53) that may miss heterogeneous senescent subsets, and propose integrating multi-omics profiling, artificial intelligence-assisted image analysis and next-generation dual recombinase tools to refine mechanistic insight and enable precise anti-senescence interventions in panvascular disease.

Platelets, produced by megakaryocytes, extend far beyond their traditional roles in hemostasis and thrombosis. Emerging studies indicate that they actively participate in multiple physiological and pathological processes through diverse activities, such as modulating immune responses, facilitating tissue regeneration, and contributing to the remodeling of disease-associated microenvironments. This review systematically summarizes the biological basis of platelets (including generation, activation, release and aging) and analyzes their interaction with hemostasis, inflammation, and injured tissues, providing the foundation for advanced therapy. Building on this foundation, we focus on two dimensions and summarize the advanced progress: (1) Platelet targeting therapeutic strategies, including precise intervention in anti-tumor therapy (inhibiting metastasis and immune evasion), cardiovascular diseases (modulating thrombosis and vascular stenosis), and emergency hemostasis (enhancing coagulation efficiency); (2) Engineering construction and targeted delivery using platelet and the derivatives (e.g., platelet-rich plasma, extracellular vesicles, membranes, and platelet-mimicking materials), which leverage their intrinsic bioactivity and multi-targeting capabilities. By bridging platelet biology to therapeutic innovation, this review serves as a framework for understanding disease mechanisms and developing next-generation targeted therapies.

Cardiovascular diseases (CVDs) pose a significant threat to global public health and are the leading cause of death in women. Basal metabolic rate (BMR), which reflects the minimum energy expenditure required to maintain essential physiological functions at rest, has emerged as a crucial indicator of energy metabolism and a potential predictor of disease risk and health status. This review comprehensively examines the role of BMR in women’s CVDs, exploring its associations with body composition, thyroid function, mitochondrial efficiency, and the autonomic nervous system. It also delves into how BMR influences CVD risk across different physiological stages in women, including the reproductive years, pregnancy, and menopausal transition. Furthermore, this review proposes a diagnostic and therapeutic framework centered on BMR, encompassing precise assessment, pharmacological interventions, lifestyle modifications, and the application of emerging technologies. The aim is to enhance women’s cardiovascular health and reduce premature mortality.

The ascending aortic aneurysm represents a critical clinical concern due to its potential for catastrophic complications. With global demographic shifts toward aging populations, the incidence of ascending aortic aneurysms is projected to rise significantly. This brief perspective examines the evolution of our understanding regarding the natural history of ascending aortic aneurysms and the refinement of surgical intervention criteria over time. We discuss the transition from simplistic diameter-based metrics to multidimensional assessment approaches that consider patient-specific factors, including anatomical variations, biomechanical properties, and genetic predispositions. Recent paradigm shifts, such as the recalibration of diameter thresholds from 5.5 cm to 5.0 cm and the integration of volumetric analysis, highlight the field's progression toward more precise risk stratification. This paper aims to provide clinicians with a contemporary framework for surgical decision-making while identifying promising avenues for further refinement of intervention strategies.

Atherosclerosis remains a major global health challenge with limited therapeutic options for plaque regression. Stem cell therapy and stem cell-derived exosomes represent promising novel strategies for treating this disease. Different types of stem cells demonstrate therapeutic effects by modulating lipid metabolism, reducing inflammation, and improving endothelial function. However, challenges such as poor targeting, low maintenance times, and immunogenicity limit their clinical application. Recent advances focus on engineering these cells and their exosomes to overcome these barriers. Strategies include genetic modification, surface functionalization for targeted delivery, and hybrid nanoparticle design. Engineered exosomes also serve as efficient drug carriers for precise therapy. While clinical trials show potential, further validation of long-term efficacy and safety is needed. Integrating bioengineering with regenerative technology offers a new approach for atherosclerosis treatment.