Investigating the association between gut microbiome and aortic aneurysm diseases: a bidirectional two-sample Mendelian randomization analysis.

Objective: This study aims to investigate the associations between specific bacterial taxa of the gut microbiome and the development of aortic aneurysm diseases, utilizing Mendelian Randomization (MR) to explore these associations and overcome the confounding factors commonly present in observational studies. Methods: Employing the largest available gut microbiome and aortic aneurysm Genome-Wide Association Study databases, including MiBioGen, Dutch Microbiome Project, FinnGen, UK Biobank, and Michigan Genomics Initiative, this study performs two-sample bidirectional MR analyses. Instrumental variables, linked to microbiome taxa at significant levels, were selected for identifying relationships with abdominal aortic aneurysms (AAA), thoracic aortic aneurysms (TAA), and aortic dissection (AD). Methods like inverse variance weighted, MR-PRESSO, MR-Egger, weighted median, simple mode, and mode-based estimate were used for MR analysis. Heterogeneity was assessed with the Cochran Q test. MR-Egger regression and MR-PRESSO addressed potential unbalanced horizontal pleiotropy. Results: The analysis did not find any evidence of statistically significant associations between the gut microbiome and aortic aneurysm diseases after adjusting for the false discovery rate (FDR). Specifically, while initial results suggested correlations between 19 taxa and AAA, 25 taxa and TAA, and 13 taxa with AD, these suggested associations did not hold statistical significance post-FDR correction. Therefore, the role of individual gut microbial taxa as independent factors in the development and progression of aortic aneurysm diseases remains inconclusive. This finding underscores the necessity for larger sample sizes and more comprehensive studies to further investigate these potential links. Conclusion: The study emphasizes the complex relationship between the gut microbiome and aortic aneurysm diseases. Although no statistically significant associations were found after FDR correction, the findings provide valuable insights and highlight the importance of considering gut microbiota in aortic aneurysm diseases research. Understanding these interactions may eventually contribute to identifying new therapeutic and preventive strategies for aortic aneurysm diseases.

Exploiting the anti-fibrotic effects of statins on thoracic aortic aneurysm progression: results from a meta-analysis and experimental data.

Aims: Thoracic aortic aneurysm (TAA) that progress to acute aortic dissection is often fatal and there is no pharmacological treatment that can reduce TAA progression. We aim to evaluate statins' effects on TAA growth rate and outcomes using a meta-analysis approach. Methods and results: A detailed search related to the effects of statins on TAA was conducted according to PRISMA guidelines. The analyses of statins' effects on TAA growth rate were performed on 4 studies (n = 1850), while the impact on outcomes was evaluated on 3 studies (n = 2,867). Patients under statin treatment showed a reduced TAA growth rate (difference in means = -0.36 cm/year; 95%CI: -0.64, -0.08; p = 0.013) when compared to controls, patients not taking statins. Regarding the outcomes (death, dissection, or rupture of the aorta, and the need for operative repair), statins exhibited a protective effect reducing the number of events (log odds ratio = -0.56; 95%CI: -1.06, -0.05; p = 0.030). In vitro, the anti-fibrotic effect of atorvastatin was tested on vascular smooth muscle cells (VMSC) isolated from patients with TAA. Our results highlighted that, in transforming growth factor beta 1 (TGF-ß1) pro-fibrotic condition, VSMC expressed a significant lower amount of collagen type I alpha 1 chain (COL1A1) when treated with atorvastatin (untreated = +2.66 ± 0.23 fold-change vs. treated = +1.63 ± 0.09 fold-change; p = 0.014). Conclusion: Statins show a protective effect on TAA growth rate and adverse outcomes in patients with TAA, possibly via their anti-fibrotic properties on VSMC. Given the current lack of effective drug treatments for TAA, we believe our findings highlight the need for more in-depth research to explore the potential benefits of statins in this context.

Physician Modified Endograft for Ruptured Dissecting Aortic Arch Aneurysm.

BACKGROUND: Endovascular repair of thoracic aortic aneurysms (TAA) in elective settings has demonstrated successful clinical outcomes. However, life-threatening conditions such as rupture are more often managed with open surgical repair due to the high complexity of arch endovascular repair, lack of available off-the-shelf devices, and limited long-term data. CASE SUMMARY: A 49-year-old female with a recent history of prior ascending aortic repair for Type A10 aortic dissection presented with chest pain and dyspnea. Chest computed tomography angiogram (CTA) revealed acute bilateral pulmonary emboli and a 6.2 cm post dissection aneurysm of the posterior aortic arch with the dissection extending to the right iliac artery. She was treated with thrombolysis and subsequently became hemodynamically unstable. Repeat CTA revealed a massive left hemithorax with concern for aortic arch rupture. Given significant cardiorespiratory compromise and recent open repair, she was considered unfit for redo open repair. Thoracic endovascular aortic repair (TEVAR) with a physician-modified endograft (PMEG) was planned. An Alpha Zenith endograft was modified adding an internal branch for the innominate artery and a fenestration for the left common carotid artery. The left subclavian artery was occluded with a microvascular plug and coil embolization up to the level of the vertebral artery. TEVAR PMEG extension to the celiac artery was performed followed by deployment of a Zenith dissection stent to the aortic bifurcation. Completion angiogram demonstrated successful aneurysm exclusion and patency of target vessels. CONCLUSION: Endovascular treatment of ruptured TAA with PMEGs is feasible. This approach may be an alternative for unfit patients for open repair in emergent settings.

Generation of Marfan syndrome-specific induced pluripotent stem cells harboring FBN1 mutations.

Marfan syndrome (MFS) is a hereditary condition caused by mutations in the FBN1 gene. Genetic mutations in the FBN1 locus impact the function of the encoded protein, Fibrillin 1, a structural molecule forming microfibrils found in the connective tissue. MFS patients develop severe cardiovascular complications including thoracic aortic aneurysm and aortic dissection, which predispose them to an enhanced risk of premature death. Here, we generated two induced pluripotent stem cell (iPSC) lines harboring mutations in the FBN1 gene (p.C1942C>A and c.1954 T>C), directly derived from MFS patients. We have shown that both iPSC lines displayed expression of pluripotency markers, normal karyotype and ability of trilineage differentiation, representing a valuable tool for the identification of new therapeutic strategies for intervening in this disease.

Identifying Acute Aortic Syndrome and Thoracic Aortic Aneurysm from Chest Radiography in the Emergency Department Using Convolutional Neural Network Models.

(1) Background: Identifying acute aortic syndrome (AAS) and thoracic aortic aneurysm (TAA) in busy emergency departments (EDs) is crucial due to their life-threatening nature, necessitating timely and accurate diagnosis. (2) Methods: This retrospective case-control study was conducted in the ED of three hospitals. Adult patients visiting the ED between 1 January 2010 and 1 January 2020 with a chief complaint of chest or back pain were enrolled in the study. The collected chest radiography (CXRs) data were divided into training (80%) and testing (20%) datasets. The training dataset was trained by four different convolutional neural network (CNN) models. (3) Results: A total of 1625 patients were enrolled in this study. The InceptionV3 model achieved the highest F1 score of 0.76. (4) Conclusions: Analysis of CXRs using a CNN-based model provides a novel tool for clinicians to interpret ED patients with chest pain and suspected AAS and TAA. The integration of such imaging tools into ED could be considered in the future to enhance the diagnostic workflow for clinically fatal diseases.

Identification of Variants of Uncertain Significance in the Genes Associated with Thoracic Aortic Disease in Russian Patients with Nonsyndromic Sporadic Subtypes of the Disorder.

Nonsyndromic sporadic thoracic aortic aneurysm (nssTAA) is characterized by diverse genetic variants that may vary in different populations. Our aim was to identify clinically relevant variants in genes implicated in hereditary aneurysms in Russian patients with nssTAA. Forty-one patients with nssTAA without dissection were analyzed. Using massive parallel sequencing, we searched for variants in exons of 53 known disease-causing genes. Patients were found to have no (likely) pathogenic variants in the genes of hereditary TAA. Six variants of uncertain significance (VUSs) were identified in four (9.8%) patients. Three VUSs [FBN1 c.7841C>T (p.Ala2614Val), COL3A1 c.2498A>T (p.Lys833Ile), and MYH11 c.4993C>T (p.Arg1665Cys)] are located in genes with "definitive" disease association (ClinGen). The remaining variants are in "potentially diagnostic" genes or genes with experimental evidence of disease association [NOTCH1 c.964G>A (p.Val322Met), COL4A5 c.953C>G (p.Pro318Arg), and PLOD3 c.833G>A (p.Gly278Asp)]. Russian patients with nssTAA without dissection examined in this study have ≥1 VUSs in six known genes of hereditary TAA (FBN1, COL3A1, MYH11, NOTCH1, COL4A5, or PLOD3). Experimental studies expanded genetic testing, and clinical examination of patients and first/second-degree relatives may shift VUSs to the pathogenic (benign) category or to a new class of rare "predisposing" low-penetrance variants causing the pathology if combined with other risk factors.

A comprehensive MRI-based computational model of blood flow in compliant aorta using radial basis function interpolation.

BACKGROUND: Properly understanding the origin and progression of the thoracic aortic aneurysm (TAA) can help prevent its growth and rupture. For a better understanding of this pathogenesis, the aortic blood flow has to be studied and interpreted in great detail. We can obtain detailed aortic blood flow information using magnetic resonance imaging (MRI) based computational fluid dynamics (CFD) with a prescribed motion of the aortic wall. METHODS: We performed two different types of simulations-static (rigid wall) and dynamic (moving wall) for healthy control and a patient with a TAA. For the latter, we have developed a novel morphing approach based on the radial basis function (RBF) interpolation of the segmented 4D-flow MRI geometries at different time instants. Additionally, we have applied reconstructed 4D-flow MRI velocity profiles at the inlet with an automatic registration protocol. RESULTS: The simulated RBF-based movement of the aorta matched well with the original 4D-flow MRI geometries. The wall movement was most dominant in the ascending aorta, accompanied by the highest variation of the blood flow patterns. The resulting data indicated significant differences between the dynamic and static simulations, with a relative difference for the patient of 7.47±14.18% in time-averaged wall shear stress and 15.97±43.32% in the oscillatory shear index (for the whole domain). CONCLUSIONS: In conclusion, the RBF-based morphing approach proved to be numerically accurate and computationally efficient in capturing complex kinematics of the aorta, as validated by 4D-flow MRI. We recommend this approach for future use in MRI-based CFD simulations in broad population studies. Performing these would bring a better understanding of the onset and growth of TAA.

Left subclavian artery bridging stent fracture after in-situ laser fenestration during emergent thoracic endovascular aortic repair.

In-situ laser fenestration (ISLF) has been described as a viable option for urgent thoracic aortic aneurysm cases involving supra-aortic vessels. There are, however, limited data on its durability. Here, we present a case of a 70-year-old man with a symptomatic 13-cm thoracic aortic aneurysm extending proximally to the origin of the left subclavian artery (LSA). Emergent thoracic endovascular aortic repair with chimney stenting of the left common carotid artery and ISLF for the LSA was successfully performed. During the follow-up, a compression of the bridging stent to the LSA progressed to a stent fracture needing realignment. Despite ISLF's reported technical success, this case highlights the risk of bridging stent complications, emphasizing the need for a close follow-up.

Predictors for reintervention and survival during long-term follow-up after TEVAR for descending thoracic aortic aneurysm.

BACKGROUND: Several studies have reported short- and intermediate-term outcomes after TEVAR for descending thoracic aortic aneurysm (DTAA), however, reports on long-term (10 years) outcomes are sparse. Therefore, the aim of this study was to analyze predictors impacting long-term outcome following thoracic endovascular aortic repair (TEVAR) for DTAA. MATERIALS AND METHODS: Databases from four academic institutions were reviewed and consecutive cases of TEVAR for DTAA between 1999 and 2021 were included in this retrospective multicenter study (Case series). Ethical approval from Institutional review board was obtained and patient demographics, treatment data as well as follow-up information were retrieved and analyzed. RESULTS: 305 patients (mean age 72±10 years) treated with TEVAR for degenerative DTAA with mean aortic diameter of 64mm were identified. Altogether 445 endografts were implanted via femoral access (93%) with a technical success of 94%. Operative mortality, stroke rate and rate of spinal cord ischemia were 6% (5% for intact, 12% for ruptured DTAA), 4% and 3%, respectively. Kaplan-Meier estimates for overall survival rates were 76%, 59% and 34% at 1, 5 and 10 years and freedom from reintervention rates were 84%, 73% and 58% at 1, 5 and 10 years, respectively. In multivariate analysis, ASA grade 3-5 and non-elective case were identified as predictors for death, wheres as fusiform DTAA, proximal landing zone 2 and hypertension but not device generation were predictive for reintervention. CONCLUSION: This is to date the largest study reporting long-term (10 years) outcome on TEVAR for DTAA. We found acceptable rates for long-term survival and freedom-from reintervention that were independent of endovascular device generation.

Longitudinal Outcomes of Thoracic Endovascular Aortic Repair for Ruptured Thoracic Aortic Aneurysms.

OBJECTIVES: Limited data exist on long-term mortality and reintervention rates of emergent thoracic endovascular aortic repair (TEVAR) for ruptured thoracic aortic aneurysm (rTAA). This study aimed to characterize the long-term outcomes of emergent TEVAR for rTAA. METHODS: This study reviewed all TEVARs for emergent rTAA and elective intact thoracic aortic aneurysms (iTAA) from August 2005 to March 2022 at a large academic medical center. Outcomes, including overall survival and reinterventions, were considered over eight years. RESULTS: Of 321 patients, 65 received TEVAR for rTAA (34 hemodynamically stable) and 256 for iTAA. Respective mean (SD) ages were 74.4 (11.9) and 74.7 (9.1) years. Median follow-up was 5.1 years. rTAA patients had lower 30-day survival (69.2% vs 96.9%, P < .001) and higher rates of stroke, pneumonia, and prolonged ventilation (all P ≤ .01). Survival was significantly worse for rTAA at 1 year (46% vs 86%), 5 years (27% vs 48%), and 8 years (20% vs 32%; all P < .001). For patients surviving at least 90 days, the long-term survival difference narrowed to statistical insignificance. Ruptured aneurysms required more reinterventions within 30 days, but comparable long-term reintervention rates. Indications for reintervention were similar, with type I endoleak as the leading cause. Long-term survival for hemodynamically stable rTAA patients did not differ significantly from iTAA patients (49% vs 48% at 5 years). CONCLUSIONS: Short-to-medium-term outcomes are worse for ruptured aneurysms. However, long-term survival of hemodynamically stable rTAA patients and rTAA patients who survive the first 90 days are comparable to iTAA patients.

Repair of thoracic aortic aneurysm with bilateral aberrant subclavian artery.

We present a rare anatomical configuration of a 19-year-old woman, characterized by descending thoracic aortic aneurysm with right aberrant subclavian arteries with a Kommerell's diverticulum in a left aortic arch. The complexity of this vascular anomaly was accompanied by an anomalous origin of left subclavian artery. The patient underwent a single-stage open surgical repair via left thoracotomy under deep hypothermic circulatory arrest. The bilateral aberrant subclavian arteries were separately reconstructed in situ using hand-sewn branched grafts.

ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Contributions of Germline and Somatic Mosaic Genetics to Thoracic Aortic Aneurysms in Nonsyndromic Individuals.

BACKGROUND: Thoracic aortic aneurysm (TAA) is associated with significant morbidity and mortality. Although individuals with family histories of TAA often undergo clinical molecular genetic testing, adults with nonsyndromic TAA are not typically evaluated for genetic causes. We sought to understand the genetic contribution of both germline and somatic mosaic variants in a cohort of adult individuals with nonsyndromic TAA at a single center. METHODS AND RESULTS: One hundred eighty-one consecutive patients <60 years who presented with nonsyndromic TAA at the Massachusetts General Hospital underwent deep (>500×) targeted sequencing across 114 candidate genes associated with TAA and its related functional pathways. Samples from 354 age- and sex-matched individuals without TAA were also sequenced, with a 2:1 matching. We found significant enrichments for germline (odds ratio [OR], 2.44, P=4.6×10-6 [95% CI, 1.67-3.58]) and also somatic mosaic variants (OR, 4.71, P=0.026 [95% CI, 1.20-18.43]) between individuals with and without TAA. Likely genetic causes were present in 24% with nonsyndromic TAA, of which 21% arose from germline variants and 3% from somatic mosaic alleles. The 3 most frequently mutated genes in our cohort were FLNA (encoding Filamin A), NOTCH3 (encoding Notch receptor 3), and FBN1 (encoding Fibrillin-1). There was increased frequency of both missense and loss of function variants in TAA individuals. CONCLUSIONS: Likely contributory dominant acting genetic variants were found in almost one quarter of nonsyndromic adults with TAA. Our findings suggest a more extensive genetic architecture to TAA than expected and that genetic testing may improve the care and clinical management of adults with nonsyndromic TAA.

Somatic Variants Acquired Later in Life Associated with Thoracic Aortic Aneurysms: JAK2 V617F.

The JAK2 V617F somatic variant is a well-known driver of myeloproliferative neoplasms (MPN) associated with an increased risk for athero-thrombotic cardiovascular disease. Recent studies have demonstrated its role in the development of thoracic aortic aneurysm (TAA). However, limited clinical information and level of JAK2 V617F burden have been provided for a comprehensive evaluation of potential confounders. A retrospective genotype-first study was conducted to identify carriers of the JAK2 V617F variant from an internal exome sequencing database in Yale DNA Diagnostics Lab. Additionally, the overall incidence of somatic variants in the JAK2 gene across various tissue types in the healthy population was carried out based on reanalysis of SomaMutDB and data from the UK Biobank (UKBB) cohort to compare our dataset to the population prevalence of the variant. In our database of 12,439 exomes, 594 (4.8%) were found to have a thoracic aortic aneurysm (TAA), and 12 (0.049%) were found to have a JAK2 V617F variant. Among the 12 JAK2 V617F variant carriers, five had a TAA (42%), among whom four had an ascending TAA and one had a descending TAA, with a variant allele fraction ranging from 11.2% to 20%. Among these five patients, 60% were female, and average age at diagnosis was 70 (49-79). The mean ascending aneurysm size was 5.05 cm (range 4.6-5.5 cm), and four patients had undergone surgical aortic replacement or repair. UKBB data revealed a positive correlation between the JAK2 V617F somatic variant and aortic valve disease (effect size 0.0086, p = 0.85) and TAA (effect size = 0.004, p = 0.92), although not statistically significant. An unexpectedly high prevalence of TAA in our dataset (5/594, 0.84%) is greater than the prevalence reported before for the general population, supporting its association with TAA. JAK2 V617F may contribute a meaningful proportion of otherwise unexplained aneurysm patients. Additionally, it may imply a potential JAK2-specific disease mechanism in the developmental of TAA, which suggests a possible target of therapy that warrants further investigation.

Coding and Non-Coding Transcriptomic Landscape of Aortic Complications in Marfan Syndrome.

Marfan syndrome (MFS) is a rare congenital disorder of the connective tissue, leading to thoracic aortic aneurysms (TAA) and dissection, among other complications. Currently, the most efficient strategy to prevent life-threatening dissection is preventive surgery. Periodic imaging applying complex techniques is required to monitor TAA progression and to guide the timing of surgical intervention. Thus, there is an acute demand for non-invasive biomarkers for diagnosis and prognosis, as well as for innovative therapeutic targets of MFS. Unraveling the intricate pathomolecular mechanisms underlying the syndrome is vital to address these needs. High-throughput platforms are particularly well-suited for this purpose, as they enable the integration of different datasets, such as transcriptomic and epigenetic profiles. In this narrative review, we summarize relevant studies investigating changes in both the coding and non-coding transcriptome and epigenome in MFS-induced TAA. The collective findings highlight the implicated pathways, such as TGF-ß signaling, extracellular matrix structure, inflammation, and mitochondrial dysfunction. Potential candidates as biomarkers, such as miR-200c, as well as therapeutic targets emerged, like Tfam, associated with mitochondrial respiration, or miR-632, stimulating endothelial-to-mesenchymal transition. While these discoveries are promising, rigorous and extensive validation in large patient cohorts is indispensable to confirm their clinical relevance and therapeutic potential.

From Biomechanical Properties to Morphological Variations: Exploring the Interplay between Aortic Valve Cuspidity and Ascending Aortic Aneurysm.

Background: This research explores the biomechanical and structural characteristics of ascending thoracic aortic aneurysms (ATAAs), focusing on the differences between bicuspid aortic valve aneurysms (BAV-As) and tricuspid aortic valve aneurysms (TAV-As) with non-dilated aortas to identify specific traits of ATAAs. Methods: Clinical characteristics, laboratory indices, and imaging data from 26 adult patients operated on for aneurysms (BAV-A: n = 12; TAV-A: n = 14) and 13 controls were analyzed. Biomechanical parameters (maximal aortic diameter, strain, and stress) and structural analyses (collagen fiber organization, density, fragmentation, adipocyte deposits, and immune cell infiltration) were assessed. Results: Significant differences in biomechanical parameters were observed. Median maximal strain was 40.0% (control), 63.4% (BAV-A), and 45.3% (TAV-A); median maximal stress was 0.59 MPa (control), 0.78 MPa (BAV-A), and 0.48 MPa (TAV-A). BAV-A showed higher tangential modulus and smaller diameter, with substantial collagen fragmentation (p < 0.001 vs. TAV and controls). TAV-A exhibited increased collagen density (p = 0.025), thickening between media and adventitia layers, and disorganized fibers (p = 0.036). BAV-A patients had elevated adipocyte deposits and immune cell infiltration. Conclusions: This study highlights distinct pathological profiles associated with different valve anatomies. BAV-A is characterized by smaller diameters, higher biomechanical stress, and significant collagen deterioration, underscoring the necessity for tailored clinical strategies for effective management of thoracic aortic aneurysm.

Validating a Curvature-Based Marker of Cervical Carotid Tortuosity for Risk Assessment in Heritable Aortopathies.

BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies. METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). Logistic regression was performed to assess the likelihood of clinical end point according to baseline carotid tortuosity. Total absolute curvature at baseline was 11.13±5.76 and was relatively unchanged at 8 to 10 years (fold change: 0.026±0.298, P=1.00), whereas tortuosity index at baseline was 0.262±0.131, with greater variability at 8 to 10 years (fold change: 0.302±0.656, P=0.818). Baseline total absolute curvature correlated with aortic root diameter (r=0.456, P=0.004) and was independently associated with aortic events during the 4-year follow-up (adjusted odds ratio [OR], 2.64 [95% CI, 1.02-6.85]). Baseline tortuosity index correlated with age (r=0.532, P<0.001) and was not associated with events (adjusted OR, 1.88 [95% CI, 0.79-4.51]). Finally, baseline total absolute curvature had good discrimination of 4-year outcomes (area under the curve=0.724, P=0.014), which may be prognostic or predictive. CONCLUSIONS: Here we introduce cervical carotid tortuosity as a promising quantitative biomarker with validated, standardized characteristics. Specifically, we recommend the adoption of a curvature-based measure, total absolute curvature, for early detection or monitoring of disease progression in Loeys-Dietz syndrome.

Temporal evolution of ascending aortic aneurysm wall stress predicts all-cause mortality.

OBJECTIVES: Diameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality. METHODS: Male veterans with <5.5 cm ascending aortic aneurysms and computed tomography at baseline and 3- to 5-year follow-up underwent three-dimensional aneurysm model construction. Peak circumferential and longitudinal wall stresses at systole were calculated using finite element analysis. Temporal trends were assessed by mixed-effects modelling. Changes in aortic wall stresses, diameter and length over time were evaluated as predictors of subsequent 3-year all-cause mortality by Cox proportional hazards modelling. RESULTS: Sixty-two male veterans were included in the study. Yearly changes in geometric and biomechanical measures were 0.12 mm/year (95% confidence interval, 0.04-0.20) for aortic diameter, 0.41 mm/year (0.12-0.71) for aortic length, 1.19 kPa/year -5.94 to 8.33) for peak circumferential stress, and 0.48 kPa/year (-3.89 to 4.84) for peak longitudinal stress. Yearly change in peak circumferential stress was significantly associated with hazard of death-hazard ratio for peak circumferential stress growth per 10 kPa/year, 1.27 (95% CI, 1.02-1.60; P = 0.037); hazard ratio for peak circumferential stress growth ≥ 32 kPa/year, 8.47 (95% CI, 2.42-30; P < 0.001). CONCLUSIONS: In this population of nonsurgical aneurysm patients, large temporal changes in peak circumferential stress, but not aortic diameter or length, was associated with all-cause mortality. Biomechanical stress and stress changes over time may be beneficial as additional risk factors for elective surgery in small aneurysms.

The rise of endovascular repair for abdominal, thoracoabdominal, and thoracic aortic aneurysms.

BACKGROUND: Given changes in intervention guidelines and the growing popularity of endovascular treatment for aortic aneurysms, we examined the trends in admissions and repairs of abdominal aortic aneurysms (AAAs), thoracoabdominal aortic aneurysms (TAAAs), and thoracic aortic aneurysms (TAAs). METHODS: We identified all patients admitted with ruptured aortic aneurysms and intact aortic aneurysms repaired in the Nationwide Inpatient Sample between 2004 and 2019. We then examined the use of open, endovascular, and complex endovascular repair (OAR, EVAR, and cEVAR) for each aortic aneurysm location (AAA, TAAA, and TAA), alongside their resulting in-hospital mortality, over time. cEVAR included branched, fenestrated, and physician-modified endografts. RESULTS: 715,570 patients were identified with AAA (87% intact repairs and 13% rupture admissions). Both intact AAA repairs and ruptured AAA admissions decreased significantly between 2004 and 2019 (intact 41,060-34,215, P < .01; ruptured 7175-4625, P = .02). Of all AAA repairs performed in a given year, the use of EVAR increased (2004-2019: intact 45%-66%, P < .01; ruptured 10%-55%, P < .01) as well as cEVAR (2010-2019: intact 0%-23%, P < .01; ruptured 0%-14%, P < .01). Mortality after EVAR of intact AAAs decreased significantly by 29% (2004-2019, 0.73%-0.52%, P < .01), whereas mortality after OAR increased significantly by 16% (2004-2019, 4.4%-5.1%, P < .01). In the study, 27,443 patients were identified with TAAA (80% intact and 20% ruptured). In the same period, intact TAAA repairs trended upward (2004-2019, 1435-1640, P = .055), and cEVAR became the most common approach (2004-2019, 3.8%-72%, P = .055). A total of 141,651 patients were identified with ascending, arch, or descending TAAs (90% intact and 10% ruptured). Intact TAA repairs increased significantly (2004-2019, 4380-10,855, P < .01). From 2017 to 2019, the mortality after OAR of descending TAAs increased and mortality after thoracic endovascular aneurysm repair decreased (2017-2019, OAR 1.6%-3.1%; thoracic endovascular aneurysm repair 5.2%-3.8%). CONCLUSIONS: Both intact AAA repairs and ruptured AAA admissions significantly decreased between 2004 and 2019. The use of endovascular techniques for the repair of all aortic aneurysm locations, both intact and ruptured, increased over the past two decades. Most recently in 2019, 89% of intact AAA repairs, infrarenal through suprarenal, were endovascular (EVAR or cEVAR, respectively). cEVAR alone increased to 23% of intact AAA repairs in 2019, from 0% a decade earlier. In this period of innovation, with many new options to repair aortic aneurysms while maintaining arterial branches, endovascular repair is now used for the majority of all intact aortic aneurysm repairs. Long-term data are needed to evaluate the durability of these procedures.