Search Results (222)

Patients with thoracic aortic disease (TAD) frequently seek advice on the safety of commercial air travel. Despite the clinical relevance of this question, robust evidence is virtually absent, and current recommendations rely largely on expert opinion. This Viewpoint discusses the physiological effects of flights, reviews the limited available evidence, and proposes a pragmatic, risk-based approach for clinicians counselling patients with TAD. Full article

Background: Heritable thoracic aortic disease (HTAD) encompass a heterogeneous spectrum of conditions characterized by increased susceptibility to developing thoracic aortic aneurysm and life-threatening complications, including aortic dissection and rupture. Despite distinct underlying mechanisms involving extracellular matrix integrity, vascular smooth muscle cell function, and dysregulation of signaling pathways, these disorders converge on a shared vulnerability of the aortic wall. Although acute events typically occur in adulthood, the disease process often begins early in life, making HTAD highly relevant in pediatric practice, where early recognition and longitudinal management are essential. Aims: This narrative review provides a biology- and genetics-oriented, translational complement to current consensus recommendations, framing pediatric HTAD as a developmentally shaped disorder of the aortic wall in which genotype increasingly informs diagnosis, surveillance, and treatment. Methods: Relevant studies were identified through a comprehensive PubMed search, with particular focus on pathogenic mechanisms, current clinical guidelines, follow-up strategies and emerging genetic perspectives. Results: Genetic testing is emerging as a key tool for the management of HTAD, although its clinical utility remains limited by provisional genotype–phenotype correlations and inconclusive results. Current risk stratification is still mainly based on aortic diameter surveillance, while pharmacological strategies are predominantly extrapolated from Marfan syndrome trials, highlighting important gaps in evidence. Conclusions: Genetic advances are expanding management opportunities in HTAD, but their clinical translation remains challenging. Disease-specific risk models integrating genetic and clinical data may improve individualized risk stratification, treatment strategies and clinical outcomes. Full article

Heritable thoracic aortic diseases (HTADs) comprise a genetically heterogeneous group of disorders predisposing patients to thoracic aortic aneurysm and dissection, yet current medical therapies remain limited to slowing disease progression rather than preventing aortic wall failure. Although pathogenic variants affect diverse genes encoding extracellular matrix (ECM) components, smooth muscle contractile proteins, and signaling molecules, these defects converge on disruption of the mechanobiological systems that maintain aortic wall integrity. The thoracic aorta functions as a mechanically integrated tissue in which endothelial cells, vascular smooth muscle cells, fibroblasts, immune cells and ECM continuously sense and respond to pulsatile biomechanical forces. Genetic perturbations affecting ECM architecture, contractile force generation, or growth factor signaling alter force transmission across this multicellular network, leading to maladaptive mechanotransduction, cellular phenotypic modulation, and progressive aneurysm formation. Using Marfan syndrome as a paradigmatic ECM-driven aortic disease, this review synthesizes current understanding of how altered biomechanics, biochemical signaling and immune responses reshape intercellular communication and activate disease-associated signaling pathways, including dysregulated TGF-β, nitric oxide, angiotensin receptor, calcium-dependent, and metabolic signaling. We highlight how single-cell transcriptomic analyses have elaborated changes in different cell-level functions including, ECM degradation, iron homeostasis, circadian/stress responses. Changes in iron metabolism in different cell types in the aorta suggest possible coordinated metabolic changes in aneurysm progression. These mechanistic insights enable the identification of cell-type–specific pathogenic programs and therapeutic discovery through systems-level approaches. We highlight the translational opportunities and challenges emerging from mouse models and human studies, emphasizing that therapeutic efficacy depends not only on pathway selection but also on disease stage, cellular context, and timing of intervention. Together, these findings support a model in which HTAD progression reflects dynamic, multicellular failure of mechanobiological homeostasis and provide a framework for the development of more precise, mechanism-based therapies. Full article

Background: Thoracic aortic aneurysm (TAA) remains a high-risk vascular condition despite major advances in imaging surveillance, operative repair, and endovascular therapy. Medical management still relies largely on blood pressure control and global cardiovascular risk reduction. Renin–angiotensin–aldosterone system (RAAS) inhibitors are frequently used in TAA, but contemporary data evaluating survival and cardiovascular outcomes in broad TAA populations are limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) have established cardiometabolic benefits, yet their role in TAA has not been well defined. Methods: We performed a retrospective multicenter cohort study of adults with imaging-confirmed TAA diagnosed between 1 January 2018 and 1 January 2026 using a Mayo Clinic electronic data platform encompassing more than 15 million patient records. Primary exposures were documented use of RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors, evaluated individually and in prespecified combination-therapy analyses. Propensity score matching was used to balance demographics, comorbidities, aortic procedural history, and concomitant cardiovascular medications. Primary outcomes were all-cause mortality and major adverse cardiovascular events (MACE) through 60 months. Results: The study included 162,126 patients with TAA. After matching, RAAS inhibitor use was associated with higher 60-month overall survival (88.3% vs. 85.5%; hazard ratio [HR], 0.79; 95% CI, 0.76–0.83; p < 0.001) and MACE-free survival (86.1% vs. 84.2%; HR, 0.87; 95% CI, 0.83–0.91; p < 0.001). GLP-1 RA therapy was associated with higher overall survival (97.5% vs. 92.5%; HR, 0.32; 95% CI, 0.27–0.38; p < 0.001) and MACE-free survival (93.2% vs. 89.3%; HR, 0.62; 95% CI, 0.56–0.70; p < 0.001). SGLT2 inhibitor therapy was similarly associated with higher overall survival (89.8% vs. 81.5%; HR, 0.51; 95% CI, 0.47–0.54; p < 0.001) and MACE-free survival (86.3% vs. 79.1%; HR, 0.62; 95% CI, 0.58–0.66; p < 0.001). Combination therapy with RAAS inhibitors plus either GLP-1 RAs or SGLT2 inhibitors was associated with incremental improvements in overall survival and MACE-free survival compared with GLP-1 RA or SGLT2 inhibitor monotherapy. Conclusions: In this large propensity-matched TAA cohort, RAAS inhibitors, GLP-1 RAs, and SGLT2 inhibitors were each associated with improved survival and fewer major cardiovascular events, with additional benefit observed for RAAS-based combination therapy. These findings support further prospective investigation of integrated cardiometabolic and vascular-targeted therapy in TAA, while underscoring that observational associations should not be interpreted as proof of aneurysm-specific disease modification. Full article

The coexistence of cancer and severe aortic stenosis (AS) is increasing as a result of population aging and substantial improvements in cancer survival. Transcatheter aortic valve implantation (TAVI) has transformed the management of AS; however, patients with active malignancy or a history of cancer remain markedly under-represented in pivotal randomized trials. This under-representation has resulted in persistent uncertainty regarding patient selection, risk stratification, and the expected benefit of TAVI in this growing and clinically heterogeneous population. This review provides a comprehensive and contemporary synthesis of the evidence on TAVI in patients with cancer, integrating cardiovascular (CV), oncologic, and geriatric perspectives. Available data on epidemiological overlap, cancer-specific procedural challenges, and short- and long-term outcomes following TAVI are critically examined, with particular emphasis on distinctions between active cancer and cancer survivorship. Key modifiers of risk and benefit—including prior thoracic radiotherapy, competing thrombotic and bleeding risk, immunosuppression, frailty, sarcopenia, and nutritional status—are discussed in detail. Limitations of conventional surgical risk scores in oncology populations are highlighted, underscoring the need for individualized assessment beyond traditional CV metrics. Across registries and meta-analyses, TAVI is associated with high procedural success and comparable short-term outcomes in patients with and without cancer. Excess mortality observed during mid- and long-term follow-up is driven predominantly by non-CV causes related to malignancy rather than valve-related complications. Importantly, patients with cancer in remission demonstrate outcomes similar to those of non-cancer populations, whereas prognosis in active cancer is strongly influenced by disease stage, biology, and competing risks. Overall, cancer diagnosis alone should not preclude consideration of TAVI. Optimal management requires multidisciplinary, goal-oriented decision-making that integrates oncologic prognosis, functional status, and patients’ priorities. As cancer survivorship continues to expand, prospective studies, integrated risk stratification tools, and closer alignment between cardio-oncology and structural heart programs are essential to guide evidence-based and equitable care. Full article

(1) Background: Coronary artery disease (CAD) frequently coexists with thoracic aortic disease and may increase the risk of adverse outcomes after thoracic endovascular aortic repair (TEVAR). Whether routine preoperative coronary angiography (CAG) improves outcomes remains unclear. (2) Methods: We retrospectively analyzed 177 patients undergoing elective TEVAR between 2015 and 2025 with a median follow-up of 4.9 years. Two analyses were performed: patients who underwent preoperative CAG versus those who did not, and patients with versus without CAD. Survival was assessed using Kaplan–Meier analysis and overlap-weighted Cox regression. (3) Results: Preoperative CAG was performed in 94 patients (53.1%) and identified newly diagnosed or progressive CAD in 42 (44.7%). Overall, 24 patients (13.6%) underwent coronary revascularization before TEVAR. Patients with CAD were older and had a greater comorbidity burden. Despite these differences, preoperative CAG was not associated with differences in in-hospital mortality (2.1% vs. 6.0%, p = 0.159), major adverse cardiovascular events (11.3% vs. 9.0%, p = 0.754), or long-term survival (log-rank p = 0.10). Patients with CAD showed higher unadjusted long-term mortality than those without CAD (31.7% vs. 17.5%; log-rank p = 0.003). However, after overlap weighting, CAD was no longer significantly associated with mortality (adjusted HR 1.4, 95% CI 0.71–2.8). Among patients with angiographically verified coronary disease, preoperative revascularization before TEVAR was not associated with improved long-term survival (HR 2.20, 95% CI 0.69–6.98). (4) Conclusions: Preoperative CAG detects clinically relevant, often unrecognized CAD in a substantial proportion of TEVAR candidates and enables revascularization before surgery. Despite a higher coronary burden, patients who underwent CAG had outcomes comparable to those who did not, and the crude long-term survival disadvantage of CAD was largely explained by the accompanying systemic atherosclerotic burden. Routine preoperative coronary assessment appears justified in elective TEVAR. Full article

Aortic aneurysms (AAs), both abdominal and thoracic, remain one of the most lethal cardiovascular diseases, with increasing prevalence and incidence, especially in sporadic forms, in our populations, primarily represented by elderly individuals. The high mortality risk is primarily due to delayed management, although their management has shown progress, particularly regarding imaging techniques that facilitate diagnosis and otherwise complex surgical procedures. This is due to the clinical decision-making approach, which, unfortunately, is still based, according to guidelines, on the maximum aortic diameter. The maximum aortic diameter, as repeatedly emphasized, fails to capture the biological and biomechanical complexity of these pathological conditions, which are influenced, among other things, by highly individual factors (genetics, gender, lifestyle, etc.). Thanks to the advent of network medicine and omics sciences, diverse and complex clinical, imaging, and biomarker datasets are available. Artificial intelligence (AI) could process this data to facilitate the complex management of aneurysms and accurately predict risk. AI could prove an excellent tool for aneurysm management, improving risk prediction and radically transforming the way we understand, monitor, and manage aneurysm patients, despite some limitations, as well as improving its therapeutic applications towards personalized strategies. This narrative review provides an overview of these aspects based on current evidence. Full article

The aortic arch remains one of the most complex segments of the thoracic aorta to treat, demanding strategies that safeguard cerebral and spinal perfusion while achieving durable proximal and distal repair. Contemporary management strategies include open hemi/total arch replacement, hybrid approaches such as frozen elephant trunk (FET) or debranching with thoracic endovascular aortic repair (TEVAR), and fully endovascular repair using branched or fenestrated devices. Updated guidelines (American College of Cardiology/American Heart Association [ACC/AHA] 2022; European Society of Cardiology [ESC] 2024) emphasize multidisciplinary, patient-specific decision-making grounded in standardized imaging, genetics, and lifelong surveillance. Procedurally, selective antegrade cerebral perfusion with moderate-to-low hypothermia has replaced routine deep hypothermic circulatory arrest for most open arch operations. Zone-based planning using Ishimaru’s map, complemented by the Modified Arch Landing Areas Nomenclature (MALAN), improves feasibility assessment and risk stratification, while entry-focused schemas like TEM (Type, Entry, Malperfusion) further refine management. Emerging data indicate that open repair remains the durability benchmark in younger populations and those with connective tissue disease, and FET enables single-stage treatment capability with acceptable early outcomes but requires vigilant neurologic protection and reintervention surveillance. An integrated, zone-driven approach guided by center expertise optimizes patient selection for open, hybrid, or endovascular options to maximize safety and durability. Full article

Background: Immune dysregulation and clinical immunosuppression are biologically plausible contributors to thoracic aortic wall vulnerability through endothelial injury, protease-mediated extracellular matrix remodeling, vascular smooth muscle cell dysfunction, and impaired vascular repair. Yet, the clinical relevance of immunomodulated states to thoracic aortic aneurysm (TAA) incidence or growth and acute aortic syndromes remains undefined. Methods: This comprehensive review synthesizes clinical and translation evidence linking immunomodulated states in solid organ transplantation, autoimmune disease (predominantly systemic lupus erythematosus), HIV, and oncologic therapies to thoracic aortic dilation, aneurysmal progression, and acute aortic events. Principal Findings: Across transplant, autoimmune, and HIV cohorts, recurring themes include chronic immune dysregulation, endothelial dysfunction, proteolytic matrix remodeling, and impaired vascular repair capacity, although thoracic segment-specific longitudinal growth data remain limited and are often embedded within analyses of multiple vascular beds. In oncologic cohorts, aggregate analyses generally do not demonstrate uniform acceleration of aneurysm growth with malignancy or chemotherapy exposure, although agent-level models suggest that regimen-specific effects may be obscured in pooled estimates. Two studies most directly addressed our question in thoracic-relevant contexts reported (1) very low mean annual ascending aortic aneurysm growth (0.18 ± 0.64 mm/year) with no detectable association with chemotherapy or radiotherapy and (2) prior immunosuppressive/cytostatic chemotherapy exposure to be common in a proximal TAA surgical cohort (39.3%) without a clear difference in thoracic phenotype at presentation or postoperative outcomes. In HIV cohorts, available evidence supports modest but reproducible proximal aortic remodeling and a clinically meaningful aneurysm burden across vascular beds, yet definitive thoracic segment-specific natural history data remain limited. Conclusions: The available literature supports clinical vigilance and exposure-aware surveillance, while suggesting that thoracic aortic risk is unlikely to be uniform across immunosuppressive and cytotoxic therapies. Standardized, segment-specific longitudinal imaging with granular agent-level exposure characterization (dose, duration, sequencing, and combination regimens), consistent definitions of baseline diameter and growth, careful adjustment for key confounders, and prospective ascertainment of dissection/rupture and operative endpoints are needed to translate immunobiology into actionable risk stratification and long-term management strategies. Full article

Heritable thoracic aortic diseases (HTAD) are inherited conditions that increase the risk of thoracic aortic aneurysms, dissections, and premature aortic rupture. Advances in human genetics and experimental models have transformed our understanding of these disorders from a phenotype-based classification system to a mechanism-based view involving extracellular matrix (ECM) architecture, transforming growth factor-β (TGFβ) signaling, and vascular smooth muscle cell contractility. Marfan syndrome, Loeys–Dietz syndrome, and nonsyndromic HTAD demonstrate how genetic mutations can disrupt the components that stabilize the aortic wall. These pathogenic mechanisms influence matrix organization, intracellular signaling, and the contractile machinery within the mechanically stressed proximal aorta. In this review, we summarize current mechanistic insights into the major forms of HTAD and discuss how new molecular and cellular concepts could influence surveillance, genetic counseling, and genotype-guided therapeutic strategies. Full article

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. Full article

Objectives: Several measurement techniques have been proposed to address the non-circular geometry of the aortic root. The Laplace diameter metric incorporates the cloverleaf anatomy of the aortic root and is derived via measurement of sinus-to-commissure lengths with subsequent doubling of the largest radius from the center. This study compares the conventional sinus-to-sinus with the novel Laplace method for sizing the aortic root and quantifying its implication on surgical decision-making. Methods: Patients undergoing surveillance at a high-volume aortic center were categorized by aortic root morphology as nondilated, non-syndromic dilated, bicuspid aortic valve and Marfan syndrome. Aortic root diameters by sinus-to-sinus and Laplace diameter methods were measured on computed tomography, compared using paired t-tests, and correlated using Spearman rank coefficients. Results: Of the 1297 patients assessed, 530 were included in the final analysis (nondilated n = 113, non-syndromic dilated n = 347, bicuspid aortic valve n = 50, Marfan syndrome n = 17). Aortic root diameters were significantly larger by Laplace than sinus-to-sinus diameter across all groups (sinus-to-sinus: 1.9 ± 5.5 mm; Laplace: 44.9 ± 7.0 mm; 95% confidence interval 2.72–3.34; p < 0.0001). Although Laplace and sinus-to-sinus diameter were correlated (Spearman r = 0.6789, 95% CI 0.6–0.7; p < 0.0001), the relationship was non-linear (R² = 0.492). Laplace diameter increased the proportion of patients meeting surgical thresholds (2022 AHA/ACC guidelines) versus sinus-to-sinus: nondilated 0% vs. 1.77%, non-syndromic dilated 4.9% vs. 25.1%, bicuspid aortic valve 10.0% vs. 26.0%, and Marfan syndrome 23.5% vs. 52.9%. Conclusions: On average, Laplace diameter exceeded sinus-to-sinus diameter by 3 mm and would extend surgical eligibility to an additional 21% of patients under current guidelines. Full article

Electrocardiogram (ECG)-gated contrast-enhanced computed tomography angiography (CTA) is the reference method for follow-up of ascending aortic aneurysms but delivers substantially higher radiation doses than ECG-gated non-contrast CT (NCCT). NCCT can be acquired at a lower dose while enabling measurements of the aortic outer diameter. This study aimed to quantify the radiation dose of both techniques and determine whether a significant difference exists in ascending thoracic aorta diameter measurements between NCCT and CTA. Eighty patients who underwent ECG-gated cardiac CT for suspected coronary artery disease were retrospectively analyzed. Three observers measured the ascending aortic diameter at the level of the pulmonary artery in a plane perpendicular to the aorta on both NCCT and CTA images. Inter-rater reliability was assessed using intraclass correlation coefficients, and paired samples t-tests were used to evaluate measurement differences. Dose-length products (DLP) were collected. Median DLP values were 16.1 mGy·cm (interquartile range 11.8–25.1) for NCCT and 190.3 mGy·cm (interquartile range 120.5–298.9) for CTA. NCCT measurements were consistently larger than CTA measurements, with mean differences of 2.1 ± 0.8 mm, 2.6 ± 0.96 mm, and 2.9 ± 1.09 mm for the senior radiologist, junior radiologist, and resident, respectively (all p < 0.001). Inter-observer agreement was excellent (ICC = 0.99, p < 0.001). NCCT delivered an 11.8-fold lower radiation dose than CTA. NCCT may replace CTA for ascending aortic diameter follow-up if measurements are adjusted by approximately 2–3 mm relative to CTA-derived inner-diameter thresholds. Full article

Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency characterized by important sex-related differences in presentation, management, and outcomes. Although women account for a smaller proportion of cases, they typically present at older ages and more frequently exhibit atypical symptoms, hemodynamic instability, and complications such as pericardial effusion or tamponade, contributing to diagnostic delays and higher pre-hospital mortality. Beyond clinical factors, biological differences may influence disease expression in women. Menopause-associated vascular aging, hormonal modulation of extracellular matrix remodeling, and pregnancy-related hemodynamic and connective tissue changes may alter aortic wall integrity and susceptibility to dissection. Notably, women often experience dissection at smaller absolute aortic diameters, highlighting the potential importance of body-size indexing in risk stratification and surgical thresholds. In type A AAD, women are less likely to undergo extensive surgical repair in some cohorts, and although contemporary in-hospital mortality differences are narrowing, long-term survival disparities may persist. In type B AAD, women are more frequently managed conservatively, while outcomes following thoracic endovascular aortic repair appear broadly comparable between sexes. Pregnancy and the postpartum period represent particularly vulnerable windows, especially among patients with underlying heritable aortopathies. Greater awareness of sex-specific biological and clinical characteristics, incorporation of indexed aortic dimensions, and improved multidisciplinary management strategies are essential to optimize outcomes for women with acute aortic dissection. Full article

Zone 2 thoracic endovascular aortic repair (TEVAR) frequently requires left subclavian artery (LSA) preservation to maintain vertebrobasilar and upper-extremity perfusion while obtaining a durable proximal seal. Dedicated single-branch endografts were developed to standardize this step and to facilitate a reproducible fully endovascular strategy. Two main device concepts currently shape this field: integrated unibody branch platforms, represented by Castor and the second-generation Cratos, and modular retrograde-branch systems, represented by the Gore TAG Thoracic Branch Endoprosthesis (TBE). The Castor/Cratos evidence base is broader and older, and is mainly centered on type B aortic dissection, with prospective multicenter and real-world data showing favorable branch patency and aortic remodeling. By contrast, TBE evidence is expanding rapidly and is supported by prospective midterm data in arch aneurysms as well as by increasingly large post-commercial series and comparative analyses across zones 0–2. Beyond outcomes, the two platforms differ substantially in branch directionality, potential contribution to proximal fixation, modularity, branch diameter range, proximal landing requirements, access profile, and regulatory/off-the-shelf availability, all of which have direct consequences for anatomical suitability in dissection, aneurysm disease, and trauma. This narrative review synthesizes current evidence and proposes an anatomy-first, pathology-aware framework for selecting between Castor/Cratos and TBE in totally endovascular zone 2 TEVAR with LSA revascularization. Full article