Background Acute type A aortic dissection (ATAAD) is the most frequent acute aortic disease with high mortality. To date, a comprehensive metabolic characterization of the human ATAAD ascending aorta remains elusive. Methods We used large-scale targeted metabolomics on ascending aortas obtained from patients with ATAAD, patients with ascending thoracic aortic aneurysm (ATAA), and healthy donors to quantify the 1,349 metabolites. By integrating with transcriptomics and mass spectrometry imaging (MSI) analysis, we further visualized the spatial distribution of the key ATAAD-altered metabolic network. Findings Quantitative profiling revealed distinct hydrophilic metabolite and glycerophospholipid profiles in ascending aortas from patients with ATAAD (n = 20), which remarkably differed from those in patients with ATAA (n = 20) and healthy controls (n = 20). Various metabolites in purine, pyrimidine, and amino acid metabolic pathways were found to be specifically and significantly altered in the ascending aorta of ATAAD. MSI analysis indicated that those differentiated metabolites were mainly enriched in the tunica media and intima. Two key ATAAD-altered metabolites—hypoxanthine and pyroglutamic acid—were selected as proof-of-concept candidates. In a prospective ATAAD cohort (n = 196), circulating levels of both metabolites correlated positively with adverse clinical outcomes. Functional studies confirmed they promote aortic dissection by impairing vascular smooth muscle and endothelial cell functions. Conclusions Our study presents the first large-scale quantitative and spatial metabolic atlas of the human ATAAD ascending aorta, highlighting key metabolic disturbances with potential as risk markers and therapeutic targets for acute aortic diseases. Funding This work was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project and the Beijing Natural Science Foundation.

OBJECTIVES:This study aimed to investigate the associations of biological age (BA) acceleration and genetic risk with the incidence of abdominal aortic aneurysm (AAA), and to evaluate the extent to which BA acceleration mediates the impact of a healthy lifestyle on AAA risk. DESIGN:A large prospective cohort study. SETTING AND PARTICIPANTS:This study included 279,944 participants from the UK Biobank. METHODS:Two validated measures of BA, Klemera-Doubal Method Biological Age (KDM-BA) and PhenoAge, were estimated using clinical biomarkers. BA acceleration was calculated as the residual from regressing BA on chronological age. A polygenic risk score (PRS) was constructed based on AAA-associated genetic variants, and a healthy lifestyle score was derived from key behavioral factors. Cox proportional hazards models were used to assess the independent and joint associations of BA acceleration, PRS, and lifestyle score with AAA risk. Interaction and mediation analyses were also conducted. RESULTS:Among the 279,944 participants, 1305 developed AAA over a mean follow-up of 15.5 years. Acceleration in both KDM-BA (HR, 1.89; 95% CI, 1.49-2.41) and PhenoAge (HR, 2.65; 95% CI, 2.21-3.17) was significantly positively associated with an increased risk of AAA. Significant interaction and joint effects were observed between genetic risk and BA acceleration. Compared with individuals with low genetic risk and low BA acceleration, those with both high PRS and high BA acceleration, particularly PhenoAge acceleration, had the highest risk of AAA (HR, 7.14; 95% CI, 5.64-8.46). Furthermore, a higher healthy lifestyle score was inversely associated with AAA risk, with approximately 7% of this association mediated through reduced BA acceleration. CONCLUSIONS:Both BA acceleration and genetic predisposition were significant risk factors for AAA, highlighting their potential utility in guiding precision prevention strategies and targeted interventions.

OBJECTIVE:Acute type A aortic dissection during pregnancy with situs inversus totalis is exceptionally rare. METHODS:We report a 27-year-old woman at 24 weeks of gestation who underwent emergency ascending aortic and total arch replacement with frozen elephant trunk implantation. RESULTS:Fetal demise occurred on postoperative day 1, but the mother recovered without neurological deficit and remained well at 10-year follow-up. CONCLUSIONS:This case demonstrates the feasibility of complex arch repair in mirror-image anatomy and highlights the importance of individualized operative planning and multidisciplinary maternal-fetal management in experienced aortic centres.

To evaluate the impact of Bentall-de Bono (BD) versus modified Bentall-de Bono (MBD) procedures on patient survival and long-term clinical outcomes. We reviewed 1,478 patients who underwent Bentall procedures between 2003 and 2022. Patients were initially stratified into two groups based on surgical technique: the BD group (n = 1,274), and the MBD group (n = 204). To mitigate baseline imbalances and selection bias, a 1:1 propensity score matching analysis was performed, yielding 202 matched pairs. Long-term survival was assessed using Kaplan-Meier analysis. Stroke was analyzed as an exploratory secondary cerebrovascular outcome. Predictors of mortality were identified via multivariable Cox proportional hazards regression. In the matched cohort, the median follow-up was 5.98 (interquartile range: 3.53–9.84) years. Kaplan-Meier analysis demonstrated comparable 10-year survival rates between the BD and MBD groups (90.9

IntroductionDisrupted rest-activity rhythm (RAR), an accelerometer-derived measure of the strength and temporal organization of daily behavioral rhythms, has been linked to multiple adverse health outcomes. Given that the development of abdominal aortic aneurysm (AAA) involves chronic inflammation, extracellular matrix degradation, and vascular smooth muscle cell dysfunction, attenuated rest-activity rhythms (RAR) may be associated with AAA risk. However, prospective evidence on this association remains limited.MethodsThe primary analysis included 78,282 UK Biobank participants who completed accelerometer monitoring between 2013 and 2015. Thirteen parametric and nonparametric RAR parameters were derived. Cox proportional hazards models estimated associations between RAR parameters and AAA incidence, as well as potential interactions and joint effects with other risk factors. Causal mediation analysis examined the mediating role of inflammatory markers. An XGBoost-based survival model evaluated variable importance, and SHapley Additive exPlanations (SHAP) interpreted feature contributions.ResultsDuring a mean follow-up of 10.1 years, 229 AAA cases were recorded. Lower RAR parameters, particularly relative amplitude (RA), M10, amplitude, and mesor, were significantly associated with higher AAA risk [lowest vs. highest tertile HRs: RA 1.49 (95% CI 1.03–2.15); M10 1.51 (1.05–2.18); amplitude 1.58 (1.09–2.30); mesor 1.46 (1.04–2.14)]. Although no significant interactions were observed, individuals with weaker RAR combined with current smoking or high polygenic risk had markedly increased AAA risk. Mediation analysis indicated that neutrophil and monocyte counts explained about 5–6% of the RAR-AAA association. In the XGBoost model, beyond age, male sex, and PRS as dominant predictors, mesor, RA, and M10 emerged as meaningful contributors to AAA risk prediction.ConclusionAccelerometer-derived RAR parameters are strongly associated with the risk of developing AAA. Integrating RAR measures with genetic and traditional risk factors may improve risk stratification and provide novel insights for preventive strategies against AAA.

Background: Calcified aortic valve disease (CAVD) is a prevalent valvular disorder in the elderly and a major cause of aortic stenosis. Surgical and transcatheter aortic valve replacement remain the primary treatments for advanced CAVD; however, effective pharmacological therapies to prevent or slow disease progression are lacking. Therefore, there is an urgent need to explore potential novel candidate biomarkers and therapeutic targets. Methods: In this study, transcriptomic data from multiple independent datasets were integrated to comprehensively characterize the transcriptional profile of CAVD. Feature genes were identified using complementary machine learning approaches, followed by functional pathway enrichment and protein-protein interaction (PPI) network analyses to uncover novel candidate genes associated with CAVD. Single-cell RNA sequencing (sc-RNA-Seq) data were further analyzed using pseudotime trajectory analysis to explore transcriptional dynamics during valve interstitial cells' (VICs) osteogenic progression. Quantitative PCR and Western blot analyses of human calcified aortic valve tissues were used for validation. Results: A total of 119 CAVD-associated genes were identified, primarily involved in ossification, extracellular matrix organization, and cell-substrate adhesion. Among these, the ossification-associated genes BAMBI, HAND2, and MYOC exhibited potential discriminatory power between CAVD and control samples, with notable downregulation in calcified valves. Pseudotime analysis showed that the expression of these genes gradually decreased along the transcriptional trajectory associated with osteogenic differentiation. In addition, the analysis of relative immune signatures revealed negative correlations between these genes and multiple immune signatures. Conclusions: This study identifies novel candidate genes underlying CAVD pathogenesis and highlights BAMBI, HAND2, and MYOC as potential biomarkers and therapeutic targets, providing new insights into disease mechanisms and opportunities for novel interventions.

To investigate the role of CD34-high endothelial cells (CD34hi_ECs) and fibroblast growth factor-2 (FGF2) signaling in the pathological vasa vasorum angiogenesis and inflammatory progression of Takayasu arteritis (TAK). Single-cell RNA sequencing (scRNA-seq) and immunohistochemical analyses of aortic walls from three TAK patients and three controls were performed to evaluate CD34hi_ECs and FGF2 expression. Serum cytokines from 48 TAK patients and 24 healthy controls were measured by cytometric bead array. ScRNA-seq of human aortic tissues revealed a marked expansion of CD34hi_ECs in TAK lesions (97.6

BACKGROUND:Abdominal aortic aneurysm (AAA) is typically asymptomatic until rupture, and established risk factors do not fully explain its occurrence. Whether social isolation, loneliness, polygenic susceptibility, and systemic inflammation jointly influence AAA risk remains unclear. METHODS:We included 356,181 White British participants from the UK Biobank free of AAA at baseline. Social isolation and loneliness indices were derived from questionnaires. A genome-wide polygenic risk score (PRS) for AAA was constructed using PRS-CS and grouped into tertiles. The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) were calculated from baseline blood counts. Incident AAA was identified through linked hospital, primary care, mortality, and self-report records. Cox models estimated hazard ratios (HRs), and mediation analyses quantified the proportion of the social isolation-AAA association explained by inflammatory indices. RESULTS:Over 15.6 years of follow-up, 1727 AAA events occurred. A social isolation index ≥2 was associated with higher AAA risk (HR 1.23; 95% CI 1.05-1.46), and each 1-SD increase corresponded to ~11% higher risk; loneliness was not associated with AAA. Although statistical interactions were non-significant, individuals with both high PRS and high social isolation had fourfold higher risk than those with low PRS and no isolation. SIRI, but not SII, was independently associated with AAA (HR 1.24; 95% CI 1.06-1.46) and mediated ~5% of the association. CONCLUSIONS:Social isolation, particularly in genetically susceptible individuals, identifies a population at substantially elevated AAA risk, partly via systemic immune-inflammatory activation, and may represent a modifiable target for prevention.

BACKGROUND AND AIMS:While surgical left atrial appendage occlusion (SLAAO) reduces stroke in atrial fibrillation (AF) patients, its efficacy in patients without pre-operative AF but with CHA₂DS₂-VASc ≥2 remains uncertain despite their high post-operative AF risk (15-54%). The aim of this study was to evaluate whether prophylactic SLAAO reduces post-operative thrombo-embolic events in valvular surgery patients. METHODS:The OPINION was a multicentre, open-label, randomized, superiority trial conducted at three cardiac surgery centres in China. Eligible non-AF patients with CHA₂DS₂-VASc ≥2 and an indication for valve repair or replacement due to mitral or aortic valve lesions were randomly assigned (1:1) to undergo SLAAO (intervention arm) or not undergo SLAAO (control arm) during surgery. The primary outcome was a composite of ischaemic stroke, transient ischaemic attack (TIA), or cardiovascular mortality assessed at 1 year. The primary analysis was done in the intention-to-treat population. RESULTS:Between April 2021 and June 2024, a total of 2157 patients were enrolled and randomized. After exclusion of 39 patients who withdrew informed consent, 2118 participants were included in the intention-to-treat population (1062 in the SLAAO group and 1056 in the control group). Baseline characteristics were well-balanced between the SLAAO group and control group (mean age 55.5 [11.4] vs 55.6 [11.5] years, P = .65; female 32.9% vs 32.3%, P = .78; CHA2DS2-VASc score 2.88 [0.98] vs 2.87 [0.96], P = .83; median EuroSCORE II 1.58% [1.42%] vs 1.56% [1.28%], P = .74). The 1-year primary endpoint occurred in 73 (6.9%) patients in the SLAAO group and in 87 (8.2%) patients in the control group (hazard ratio 0.83; 95% confidence interval 0.61-1.14; P = .25). CONCLUSIONS:For valvular surgery patients with CHA₂DS₂-VASc scores ≥2 but no pre-operative AF, routine prophylactic left atrial appendage closure did not significantly reduce the incidence of the primary composite endpoint (ischaemic stroke, TIA, and cardiovascular mortality) at 1-year follow-up. TRIAL REGISTRATION:ChiCTR.org registry ChiCTR2100042238.

Background Preoperative coagulation dysfunction is a common complication among patients with acute type A aortic dissection (ATAAD). However, evidence regarding its association with prolonged mechanical ventilation (PMV) following emergency surgery remains limited. Methods Clinical data from 793 patients with ATAAD were retrospectively collected. Patients were stratified into two groups according to preoperative coagulation function indicators. Logistic regression and nomogram analyses were conducted to assess the relationship between coagulopathy and PMV in patients with ATAAD. Results Patients with coagulation dysfunction demonstrated a longer awakening time [9.0 (5.50, 14.0) h versus 7.50 (4.0, 13.0) h, P = 0.015], a higher incidence of PMV [243 (35.5%) versus 28 (25.7%), P = 0.044], a higher incidence of postoperative acute kidney injury (AKI) [382 (55.8%) versus 39 (35.8%), P < 0.001], and a greater requirement for continuous renal replacement therapy (CRRT) [60 (8.8%) versus 3 (2.8%), P = 0.031]. Multivariable logistic regression analysis indicated that PMV was significantly associated with age, duration of surgery, duration of cardiopulmonary bypass (CPB), preoperative lactic acid, creatinine, and fibrin degradation products (FDPs). Subgroup analysis further demonstrated that patients with preoperative FDP levels >15.27 μg/mL experienced poorer early postoperative outcomes. Conclusion Preoperative coagulopathy was associated with PMV in patients with ATAAD. These findings underscore the clinical relevance of coagulation dysfunction in preoperative risk stratification for ATAAD.

Gastrointestinal bleeding is a clinically important complication after emergency surgery for acute type A aortic dissection. Dedicated postoperative risk-stratification tools for this high-risk population remain limited. We aimed to develop and internally validate an early postoperative prediction model for gastrointestinal bleeding after acute type A aortic dissection repair and to compare logistic regression with commonly used machine-learning classifiers. We conducted a single-centre retrospective cohort study of 1,345 consecutive patients who underwent emergency acute type A aortic dissection repair between 5 December 2017 and 4 August 2022. Comprehensive clinical data, laboratory findings, imaging results, operative variables, transfusion data, and postoperative outcomes were collected. The cohort was divided into training and validation sets at a 70:30 ratio using stratified sampling. Candidate predictors were screened using least absolute shrinkage and selection operator logistic regression, and a clinically interpretable five-variable logistic regression model was developed. Model performance was assessed by discrimination, calibration, decision-curve analysis, repeated-split analysis, temporal validation, and comparison with tuned machine-learning classifiers. Overall, 108 patients (8.0

Abstract Background Ascending thoracic aortic aneurysm (ATAA) is a fatal vascular disease characterized by immune dysregulation. However, the cellular composition, spatial localization, and functional diversity of immune cells in the ATAA microenvironment remain poorly understood. Objective To construct a high‐resolution immune cell atlas of human ATAA and explore the immune‐mediated vascular remodelling mechanisms associated with its progression. Method We conduct high‐throughput single‐cell RNA sequencing (scRNA‐seq) of aortic tissues from eight ATAA patients and nine controls, including six from the GEO database. In the ATAA group, CD45+ cell subpopulations are isolated, and the scRNA‐seq results are integrated with Visium high‐definition spatial transcriptomics analysis to achieve near‐single‐cell resolution cell localization through deconvolution. Advanced cell segmentation algorithms are applied to generate a high‐resolution immune cell atlas of human ATAA. Results A total of 187 163 high‐quality immune cells are identified, encompassing eight major immune cell types. Immune cells are significantly enriched in ATAA tissues compared with the controls. CellChat analysis reveals strong immune cell interactions in ATAA, which may contribute to its occurrence and progression. Conclusion This study presents the first high‐resolution immune cell atlas of human ATAA, offering novel insights into its immune‐mediated vascular remodelling mechanism. Key points What is currently known about this topic? ATAA is a vascular disease characterized by medial degeneration and chronic inflammation. Previous single‐cell transcriptomic studies have revealed the cellular heterogeneity of the aortic wall and identified alterations in the populations of smooth muscle, fibroblasts and endothelial cells. However, the immune landscape of ATAA remains unclear. Recent single‐cell and spatial analyses of aortic dissections and abdominal aortic aneurysms have revealed dynamic immune remodelling involving macrophage polarization, T‐cell activation and cytokine‐driven matrix degradation. Nevertheless, the spatial resolution of immune heterogeneity and cross‐lineage signalling in human ATAA is poorly understood. What is the key research question? This study aimed to determine the cellular composition, spatial distribution and transcriptional reprogramming of immune cell populations in ATAA and to elucidate how the interactions among immune cells lead to inflammation and pathological remodelling of the aortic wall. What is new? Single‐cell RNA sequencing combined with Visium HD spatial transcriptomics can comprehensively characterize the composition, gene expression profiles and spatial localizations of eight types of immune cells in the aortic tissues of the control and ATAA groups at the single‐cell level. Targeting of the interferon, AP1, and NF‐κB pathways is a novel strategy for treating ATAA. The interactions among immune cells have a synergistic effect during ATAA formation, jointly driving immune remodelling. How might this study influence clinical practice? Elucidation of the dynamic differentiation trajectories and gene expression signatures of distinct immune cell populations in normal and ATAA‐affected aortas will enhance our understanding of the immunological mechanisms underlying aneurysm pathogenesis. This knowledge provides a foundation for developing targeted anti‐inflammatory therapeutic strategies for ATAA.

Background: While emergency surgery for acute type A aortic dissection (TAAD) is lifesaving, real-world delays occur. Current risk stratification lacks objective imaging criteria. We aimed to develop a computed tomography angiography (CTA)-based model to predict imminent rupture risk in TAAD. Methods: This retrospective study included 121 consecutive patients with TAAD, diagnosed at Beijing Anzhen Hospital between January 2024 and March 2025. Patients were classified into acute rupture (n=46, 38%) and non-acute (n=75, 62%) groups. The primary endpoint was acute rupture-related death within 14 days of symptom onset, rigorously defined by CTA evidence and/or clinical findings. Clinical and imaging variables were screened using univariable logistic regression, followed by least absolute shrinkage and selection operator (LASSO) regression. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, bootstrap validation, calibration, and decision curve analysis (DCA). Results: The overall acute rupture rate was 38% (46/121). The median age of the cohort was 56 years; 72% were men. Univariable analysis showed that rupture patients had higher inflammatory and ischemic marker levels and were more likely to present with circumferential dissection, aortic sinus entry tear, pericardial effusion, entry tear diameter >20 mm, and ascending aorta diameter >50 mm (all P<0.05). LASSO regression identified aortic sinus entry tear [odds ratio (OR) =23.60; 95% confidence interval (CI): 2.27-245.58; P=0.008] and circumferential aortic dissection (OR =8.27; 95% CI: 1.06-64.65; P=0.044) as independent predictors. The combined ROC curve yielded an area under the curve (AUC) of 0.872 (95% CI: 0.803-0.941) with good calibration and net clinical benefit on DCA. Conclusions: We developed and validated a parsimonious CTA-based prediction model with robust performance for identifying TAAD patients at the highest risk of acute rupture. This tool may aid in urgent triage and reinforce the imperative for expedited surgical intervention when these high-risk imaging features are present.

Background Thoracic endovascular aortic repair (TEVAR) is a primary treatment for complicated type B aortic dissection (TBAD). However, some patients eventually require open thoracoabdominal aortic replacement (TAAR). Comparative outcomes data for TAAR with vs without prior TEVAR remain limited. Methods In this single-centre retrospective study of 198 patients undergoing TAAR for TBAD, we compared outcomes between those with (n = 60) vs without (n = 138) prior TEVAR. The primary endpoint was a composite of in-hospital death, spinal cord injury, or stroke. Results The composite endpoint was significantly higher in the prior-TEVAR group (25.0% vs 7.3%, P < 0.001). In-hospital mortality was similar (11.7% vs 5.1%, P = 0.173), whereas spinal cord injury (10.0% vs 2.2%, P = 0.040) and cerebral hemorrhage (6.7% vs 0%, P = 0.012) were higher with prior TEVAR. Prior TEVAR independently predicted this composite outcome (odds ratio 3.72, P = 0.006). Patients with prior TEVAR had higher rates of reintubation (8.3% vs 1.5%, P = 0.046), and dialysis-requiring acute kidney injury also trended higher in this group (23.3% vs 12.3%, P = 0.050).Prior TEVAR was an independent predictor for late reintervention (hazard ratio 2.74, P = 0.030). Conclusions Prior TEVAR was associated with increased perioperative morbidity and late reintervention risk in patients undergoing TAAR for TBAD. This association underscores the need for enhanced perioperative management and long-term follow-up in this high-risk cohort.

OBJECTIVE:We seek to evaluate our experience with the management of type A aortic dissection (TAAD) during pregnancy or in the postpartum period over 25 years. METHODS:From 1998 to 2023, our team managed 60 pregnant women (mean age, 31.4 ± 5.0 years) who sustained TAAD at mean of 30.3 ± 8.5 gestational weeks (GWs), including 27 in the third trimester (45.0%) and 13 during the postpartum period (21.7%). Marfan syndrome (MFS) was seen in 39 patients (65.0%) with 13 (21.7%) having a positive family history. Before operation, aortic root diameter averaged 53.6 ± 17.1 mm, which was significantly larger in MFS patients than non-MFS patients (57.0 ± 17.0 mm vs 47.0 ± 15.0 mm, P = .019). Management strategy was based on GWs (ie, surgical versus medical treatment, surgery first, or delivery first). RESULTS:One patient was treated medically (1.7%), and 59 were treated surgically (98.3%). Management strategies were single-stage delivery and aortic repair at a mean of 32.4 ± 4.5 GWs in 29 (48.3%); delivery first at 35 ± 8 GWs in 18 (30%), followed by aortic repair after a median of 6.2 days, and aortic repair first at 18.6 ± 6.3 GWs in 12 (20%), followed by delivery after a median of 9.5 days. Maternal and fetal mortality rates were 100% (1/1) and 100% (1/1), respectively, with medical therapy, 11.1% (2/18) and 11.1% (2/18) with delivery first, 3.4% (1/29) and 22.6% (7/31) with single-stage delivery and aortic repair, and 16.7% (2/12) and 66.7% (8/12) with aortic repair-first strategies. Follow-up was complete in 98.1% (53/54) at a median duration of 6.7 years (interquartile range, 4.8-10.9 years). Five maternal deaths and 2 fetal deaths occurred. Eight patients underwent a total of 10 reoperations. Ten-year maternal and fetal survival rates were 79.3% and 67.7%, respectively. Eight patients (7 with MFS, 87.5%) underwent 10 reoperations at a median of 4.7 years (IQR, 2.1-9.1 years). CONCLUSIONS:For TAAD occurring after 28 GWs, adequate maternal and fetal survival can be achieved with delivery followed by aortic repair, preferably in one stage. Before 28 GWs, maternal survival should be prioritized, given the high uncertainty of fetal survival. Prophylactic aortic repair may be reasonable for women with Marfan syndrome contemplating pregnancy when the root diameter is 45 mm or even smaller.