Lack of evidence for the involvement of non-canonical pyroptosis in a mouse model of thoracic aortic dissection.

Clinicopathologic study of inflammatory diseases of the aorta: A single-center experience.

Noteworthy in Cardiothoracic Surgery 2025 highlights several of the most influential trials and emerging trends shaping cardiothoracic surgical practice. In structural heart disease, new randomized data have expanded consideration of transcatheter aortic valve replacement to asymptomatic patients while reinforcing the importance of longer-term durability and lifetime valve management in lower-risk populations. In heart transplantation, advances in minimally invasive and robotic techniques, alongside growing international experience with donation after circulatory death, underscore both the promise of innovation and the need for disciplined management of ischemic and preservation times. Endovascular management of complex thoracic aortic disease continues to evolve with broader use of branched devices. In thoracic oncology, practice changing trials support a shift towards perioperative chemotherapy and immunotherapy for resectable esophageal, gastroesophageal junction, and lung cancers, redefining surgical timing, coordination, and multidisciplinary care. Finally, continued adoption of minimally invasive and robotic approaches reflects a broader trend toward reducing surgical morbidity while maintaining oncologic and transplant outcomes.

The aim of this systematic review and meta-analysis was to investigate the changes in aortic stiffness before (pre) and after endovascular aortic repair (ER) for thoracic and abdominal aortic disease, along with the associated changes in left ventricular function. PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched. Two independent reviewers screened and selected eligible studies, and RevMan 5.4 was used for the statistical analysis. A total of 28 studies (including 2227 participants) were included. Abdominal aortic aneurysms (AAA) patients had higher pulse wave velocity (PWV) than volunteer participants (Mean difference [MD]:2.08; 95% confidence interval (CI): 0.54-3.62, I2 = 94%, p = 0.008). The PWV increased after ER (MD 1.22; 95%CI: 0.54-1.91, I2 = 86%, p < 0.001) and subgroup analysis of thoracic endovascular aortic repair (TEVAR, MD: 1.51; 95%CI: 0.83-2.19, I2 = 9%, p < 0.001) and endovascular aneurysm repair (EVAR, MD:1.29; 95%CI: 0.39-2.20, I2 = 90%, p = 0.005) showed similar results. Pooled analysis also showed that the left ventricular mass index (LVMI) increased after ER (MD:5.35; 95%CI: 1.16-9.54, I2 = 24%, p = 0.01), while no significant change was observed in left ventricular ejection fraction (MD:0.08; 95%CI: -0.63-0.79, I2 = 0%, p = 0.82). Patients with AAA have significantly higher PWV than age-matched controls. Endovascular repair may be associated with left ventricular structural remodeling, as reflected by changes in LVMI, while no significant effect on LVEF was observed. These adverse remodeling processes may merit consideration during follow-up. Further high-quality studies are needed to confirm these findings and to clarify strategies for reducing aortic stiffness.

Transformative Advances in Vascular Surgery: Five Decades of Innovation in the Management of Aortic, Carotid, and Peripheral Arterial Disease.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that affects cardiovascular, musculoskeletal, and ocular tissues, with premature death often resulting from dissection of the thoracic aorta. MFS results from pathogenic variants in FBN1, which encodes fibrillin-1, a glycoprotein that promotes elastic fiber organization and stability and contributes to smooth muscle cell mechano-sensing of extracellular matrix. It has been 35 years since the discovery that FBN1 variants cause MFS, yet understanding links between a variant and thoracic aortic disease remains incomplete and definitive treatments remain wanting. We review advances in understanding disease progression in the aorta in MFS from perspectives of genetics, histology, mechanobiology, and biomechanics, with a focus on mouse models that include further genetic modifications to assess factors contributing to disease progression as well as effects of pharmacological treatments. This monogenic disease results in hundreds of differentially expressed genes in the aorta, many cell specific, that should be delineated as protective compensations, pathologic consequences, or neutral changes, and therapies should promote beneficial compensations and prevent detrimental consequences. Given the complexity of aortic disease in MFS, data-informed and data-driven computational models promise to help integrate multimodal data and increase understanding of molecular and cellular changes that drive disease progression, with a goal of improved therapies that prevent disease progression.

Although single-cell studies have profiled diseased aorta, mechanisms driving aortic dissection (AD) remain largely elusive owing to limited cohorts. Here, we integrate single-cell and spatial transcriptomic data from 110 thoracic aortic samples (80 individuals; control, aneurysm, dissection; 767018 high-quality cells) to generate a comprehensive thoracic-aorta cellular-molecular atlas. We identify an elastin-rich fibroblast subset (Fibro_C1_FBN1+; FBN1, MFAP5, LOX) that declines with age and is markedly depleted in AD, linking fibroblast loss to increased aortic wall vulnerability and dissection risk. Vascular smooth muscle cells (vSMCs) undergo ENO1-driven glycolytic reprogramming under hypoxia, lose contractility and adopt a synthetic, MIF-secreting phenotype that engages macrophage receptors to promote macrophage recruitment and pro-inflammatory polarization, leading aggregated macrophages to upregulate proteolytic and fibrinolytic pathways and thereby accelerate extracellular-matrix degradation. In vitro and in vivo, ENO1 knockdown inhibits vSMC switching, reduces macrophage inflammation, and slows AD progression. This stromal-immune axis suggests potential therapeutic targets in AD.

Aortic fistulas represent rare but life-threatening communications between the aorta and the adjacent structures, most commonly the gastrointestinal tract. They are classified as primary, arising spontaneously in the setting of a native, diseased aorta, or secondary to prior aortic surgery or endovascular repair. Clinical presentation is often variable and nonspecific-ranging from gastrointestinal bleeding, sepsis, abdominal pain to hemodynamic collapse-making imaging pivotal for diagnosis. Computed tomography angiography is the preferred imaging modality. Imaging features such as visualization of the fistula tract and active contrast extravasation into the fistulized hollow organ are definitive signs of aortic fistulas, but are rarely encountered. On the contrary, nonspecific indirect imaging features such as loss of fat planes and/or ectopic foci of gas are more frequently seen. Prompt recognition of these indirect imaging features is crucial, as delayed diagnosis significantly increases mortality. This review article summarizes the types, clinical features, and imaging findings of aortic fistulas, emphasizing the radiologist's pivotal role in timely detection and management of aortic fistulas.

The prevalence and clinical correlates of extra-aortic vascular disease in Marfan syndrome remain incompletely defined, and current surveillance strategies primarily target the thoracic aorta. We conducted a multicentre retrospective cohort study of 783 patients with Marfan syndrome across three tertiary centres, with systematic chart and imaging adjudication to define aneurysm and dissection distribution. Extra-aortic aneurysms were identified in 32% of patients, most commonly involving the iliac, carotid and subclavian arteries. Extra-aortic dissections occurred in 5.2%. Extra-aortic aneurysms clustered strongly with markers of advanced aortic disease, including abdominal aortic aneurysm (adjusted OR 3.48), prior aortic dissection (OR 3.39) and extra-aortic dissection (OR 4.44), as well as age >40 years and male sex. Genetic confirmation status was not associated with extra-aortic aneurysm presence. Extra-aortic vascular involvement is common in Marfan syndrome and closely linked to advanced aortic pathology. These findings support risk-stratified vascular imaging beyond the thoracic aorta in higher-risk patients.

Sex-related disparities affect diagnosis, referral, and prognosis of aortic valvular diseases. Contemporary US data on transcatheter aortic valve implantation (TAVI) by sex are limited. To characterize 10-year trends in TAVI use, periprocedural complications, and long-term outcomes among Medicare beneficiaries, stratified by sex. This nationwide, retrospective, population-based cohort study used US Medicare claims data from fee-for-service beneficiaries discharged after TAVI from January 1, 2013, to December 31, 2022. The median follow-up time was 2.19 (IQR, 0.94-3.79) years. Exclusions included patients who had concomitant valve surgery, infective endocarditis, valve-in-valve TAVI, transapical TAVI, TAVI for pure aortic insufficiency, or later conversion to Medicare Advantage. Analyses were conducted between October 1, 2024, and April 1, 2025. TAVI. The primary outcome was all-cause mortality. Secondary outcomes included periprocedural mortality, vascular complications, acute kidney injury, major or life-threatening bleeding, stroke, acute myocardial infarction (AMI), permanent pacemaker implantation (PPI), and hospitalization for heart failure (HF). Adjusted odds ratios (AORs) and hazard ratios (AHRs) with 95% CIs were estimated. The study included 314 123 patients (141 233 women [45.0%] and 172 890 men [55.0%]). Women were older than men (mean [SD] age, female: 80.3 [7.8] years; male: 79.4 [7.7] years; standardized mean difference, 12%). The proportion of female patients who underwent TAVI declined from 47.6% in 2013 to 43.6% in 2022 (P < .001). Compared with men, women had higher periprocedural mortality (2.5% vs 2.2%; AOR, 1.20 [95% CI, 1.14-1.26]), vascular complications (5.8% vs 3.6%; AOR, 1.65 [95% CI, 1.60-1.71]), and bleeding (10.4% vs 6.8%; AOR, 1.67 [95% CI, 1.62-1.71]) but less PPI (16.9% vs 20.0%; AOR, 0.81 [95% CI, 0.79-0.82]). Long-term mortality was lower in female patients (AHR, 0.92; 95% CI, 0.91-0.93), although their risks of HF hospitalization, AMI, stroke, and bleeding were higher. Among Medicare beneficiaries, women constituted a progressively declining proportion of patients treated with TAVI, experienced more periprocedural complications, and demonstrated modestly better long-term survival compared with men. Further work is needed to understand factors influencing these trends and to refine sex-specific strategies for optimal outcomes.

To diagnose undiagnosed heritable thoracic aortic disease (HTAD) using targeted next-generation sequencing technology on human aorta tissue obtained from a single-centre biobank. From May 2016 to November 2021, 622 patients undergoing surgical repair for thoracic aortic aneurysm or acute aortic syndrome donated blood or tissue samples to the research biobank. A total of 134 aortic tissue samples were retrieved from patients suspected of HTAD. The inclusion criteria were (1) family history, (2) age ≤ 45, (3) annuloaortic ectasia, (4) bicuspid aortic valve, (5) patent ductus arteriosus, (6) polycystic kidney disease, or (7) patients previously classified as variant of uncertain significance by germline sequencing (n = 17). Exclusion criteria included patients previously classified as likely pathogenic or pathogenic by germline sequencing. The targeted panel included 96 genes. A total of 29 variants were identified including FBN1, MYH11, COL11A1, SMAD3, SMAD6, ACTA2, COL3A1, FLNA, PKD2, THSD4, ACVRL1, and FBN2. A total of 27 patients (20.1%) had variants with 2 patients having digenic variants. Clinical data were combined with genetic data, and finally, 17 patients (12.7%) were additionally diagnosed with HTAD. Genomic data analysis of human aortic tissue allowed for additional diagnoses of undiagnosed HTAD, contributing to resolving discrepancies between clinical and genomic data. Considering the surgical treatment of HTAD, human aortic tissue can be a valuable resource for genomic analysis.

Dysregulated proteolysis is implicated in thoracic (thoracic aortic aneurysm [TAA]) and abdominal aortic aneurysm (AAA) pathogenesis, but proteolytic landscapes (degradomes) of aneurysmal and normal aorta and contributions of individual proteases remain undefined. Here, a proteome-wide approach was used to define and compare TAA and AAA degradomes and uncover the specific role in aortic remodeling of 2 proteases consistently identified in the aneurysms, CMA1 (mast cell chymase) and MMP9 (matrix metalloprotease 9). The mass spectrometry-based N-terminomics strategy, terminal amine isotopic labeling of substrates, was applied to Marfan syndrome TAAs (n=5), AAAs (n=16), and nondiseased thoracic aorta (n=4), and abdominal aorta (n=4) in a forward degradomics application, that is, to define substrate and protease degradomes. 8-plex iTRAQ terminal amine isotopic labeling of substrates was used for quantitative comparison of the tissue cohorts. Cleavage sites of CMA1 and MMP9 were sought by reverse degradomics, that is, digestion of aortic proteins with these proteases, followed by terminal amine isotopic labeling of substrates. CMA1 and MMP9 proteolysis of biglycan was further resolved using amino-terminal oriented mass spectrometry of substrates. We experimentally annotated 20 885 proteolytically derived peptides and identified 129 proteases in the aortic tissues. Quantitative substrate degradome comparisons identified specific differentially modulated pathways and networks in TAAs and AAAs. Reverse degradomics elucidated >300 CMA1 and MMP9 substrate cleavage sites, of which many, including orthogonally validated biglycan cleavages, occurred in the disease degradomes. Unbiased forward degradomics of the aortic wall from TAA, AAA, and nondiseased tissue provides a systems biology view of aortic wall breakdown and a new resource for its hitherto occult proteolytic landscape, demonstrating widespread extracellular matrix remodeling with disproportionate impact on proteoglycans. The findings provided insights into aortic aneurysm pathways and disease biomarkers and suggest involvement of numerous proteases. Mapping of specific proteolytic contributions of CMA1 and MMP9 illustrates a strategy for defining the activities of all proteases involved in aortic disease.

Computed tomography angiography (CTA) is the reference standard for comprehensive evaluation of the native aorta, providing simultaneous assessment of luminal, mural, and perivascular structures within a single rapid acquisition. Accurate diagnosis and appropriate management increasingly depend on standardized terminology, consistent anatomic segmentation, and reproducible measurement techniques. This review presents a practical framework for systematic interpretation of adult aortic CTA. Key aspects include detailed anatomic considerations, standardized measurement principles, contemporary acquisition protocols, and structured reporting strategies. The imaging spectrum of the main aortic disease categories-degenerative, congenital, and inflammatory-is reviewed, with emphasis on atherosclerosis, acute aortic syndromes, aneurysmal disease, coarctation, Kommerell diverticulum, and large-vessel vasculitis. Particular attention is given to morphologic patterns, prognostic imaging features, and common diagnostic pitfalls, as well as to terminology that more accurately reflects underlying pathophysiology. By integrating technical recommendations with disease-specific imaging criteria, this review aims to improve diagnostic precision, facilitate longitudinal follow-up, and enhance multidisciplinary communication. A structured approach to aortic CTA interpretation reinforces the central role of radiology in clinical decision-making and risk stratification in patients with aortic disease.

Aorta and coronary artery assessment using high-contrast respiratory motion corrected and ECG-gated 3D T2-prepared GRE MRI with Dixon fat-water separation in patients with and without prior aortic root surgery at 3T.

Animal ex-vivo model for the reproduction of the human ascending aorta.

The 2025 ESC/EACTS Guidelines for valvular heart disease introduce substantial changes in timing and modality of intervention, making a focused appraisal of their surgical implications highly relevant for contemporary cardiac practice. The guidelines formalize imaging-based staging of cardiac damage, lower thresholds for intervention in aortic stenosis and primary mitral regurgitation, and refine age- and risk-stratified allocation of surgery vs. transcatheter therapies across aortic, mitral, and tricuspid disease. They expand indications for transcatheter aortic valve implantation, mitral and tricuspid transcatheter edge-to-edge repair, and transcatheter valve replacement in carefully selected high-risk patients, while strengthening the role of durable surgical valve repair, complex aortic and multivalve procedures, and lifetime valve management strategies. Organizationally, they define and emphasize the importance of Heart Valve Centres and volume-outcome relationships. These guideline recommendations reflect upon contemporary evidence to support thoughtful decision making, encourage earlier intervention, and reinforce the central role of cardiac surgery and cardiology partnerships in achieving best patient outcomes through Heart Valve Centres. Cardiac surgeons should continue advance excellence in valve repair and reconstructive surgery and embrace the complementary role of transcatheter valve therapies.

Objectives: To investigate the outcomes of thoracoabdominal aortic aneurysm repair (TAAAR) following total arch replacement combined stented elephant trunk implantation (Sun's procedure),and to compare the differences in surgical conditions and surgical outcomes between patients with hereditary aortic disease (HAD) and those without HAD. Methods: This is a retrospective cohort study. A retrospective analysis was conducted on the data of 199 patients who underwent TAAAR following a Sun's procedure at the Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Capital Medical University between July 2009 and January 2024. Among them, 150 were male (75.4%), and 49 were female(24.6%), with an age of (39.3±10.9) years (range: 16 to 66 years). The patients were stratified into the HAD group (n=97) and non-HAD group (n=102). The baseline characteristics, short-term and long-term outcomes were compared between groups using Mann-Whitney U test, independent-samples t-test, χ² test, or Fisher's exact test, as appropriate. Survival analysis was conducted using the Kaplan-Meier method, and the Log-rank test was performed to compare the differences between groups. Results: The operative mortality was 6.5% (13/199) in the entire cohort. The patients in the HAD group had a higher incidence of prior cardiovascular intervention (38.1%(37/97) vs. 21.6%(22/102), χ²=6.55, P=0.011). The interval between Sun's procedure and TAAAR was shorter in the HAD group (M(IQR), 2.2(4.0) years vs. 3.1(6.9) years,Z=-1.98,P=0.048). The non-HAD group had a significantly higher age than the HAD group ((34.7±9.2) years vs. (43.7±10.6) years, t=-6.41, P<0.01). No significant differences were observed between the two groups in operative morality, incidences of postoperative spinal cord injury, renal replacement therapy, or infection (all P>0.05). Median follow-up was 4.7(5.0) years (range: 1 month to 16.2 years) in 94.6% (176/186) patients. The 8-year overall survival rates of the HAD group and the non-HAD group were 78.9% (95%CI: 63.9% to 88.2%) and 88.1% (95%CI: 75.0% to 94.5%), respectively,and the 8-year freedom from reoperation rate were 86.5% (95%CI: 72.2% to 93.7%) and 91.0% (95%CI: 79.2% to 96.3%), respectively, which showed no statistically significant differences (all P>0.05). Conclusion: TAAAR following Sun's procedure is safe and reliable, offering favorable survival rate and low reintervention rate for both TAAA patients with HAD or without HAD.

HighlightsWhat are the main findings?Supplementing with ketone esters significantly reduces the incidence of BAPN-induced TAAD and mortality in mice.β-OHB suppresses vascular smooth muscle cell ferroptosis through GPX4 induction and HO-1 reduction.What are the implications of the main findings?Ketone therapy may serve as an effective preventive strategy for managing aortic pathologies.Targeting ferroptotic cell death of vascular smooth muscle cells in the aortic media might provide a novel therapeutic approach.Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease lacking therapies that target underlying cell death pathways. Ferroptosis, an iron-dependent form of lipid peroxidation-driven cell death, has emerged as a key mechanism in vascular remodeling. We investigated whether exogenous ketosis induced by ketone ester (KE) supplementation can suppress ferroptosis and prevent TAAD. TAAD was induced in C57BL/6 mice using β-aminopropionitrile (BAPN). A subset of these mice received KE [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, 20 g/L] in their drinking water starting on day 15 of the BAPN treatment. Human aortic smooth muscle cells (HASMCs) were treated with the GPX4 inhibitor Ras-Selective Lethal 3 (RSL3) and β-hydroxybutyrate (β-OHB) to investigate ferroptotic markers, lipid peroxidation, and labile iron levels. KE supplementation significantly reduced TAAD incidence (69% → 43%) and improved survival rate (52% → 73%), while preserving aortic structure and reducing elastic fiber fragmentation. Transcriptomic analyses of human TAAD datasets (GSE153434 and GSE52093) and single-cell RNA sequencing data (GSE155468) revealed ferroptosis signatures characterized by decreased GPX4 and increased expression of iron metabolism genes. Mechanistically, KE suppressed BAPN-induced iron accumulation and lipid peroxidation in vivo. In HASMCs, β-OHB inhibited ferroptosis induced by GPX4 inhibition, decreasing lipid peroxidation and labile iron levels. KE restored GPX4 and SLC7A11 expression while suppressing HO-1 in vivo, with effects dependent on Nrf2 signaling in vitro. In summary, ketone ester supplementation protects against TAAD by inhibiting VSMC ferroptosis via GPX4 induction and HO-1 suppression, highlighting a potential therapeutic strategy for aortic disease.

Telomere length in patients with Marfan Syndrome.

104. Short Stature, Tall Risk - The Surgical Management of Aortic Disease in Turner Syndrome