Aortic Morphology Research Articles

Dynamic Morphology of Dilated Ascending Aorta and its Implications for Proximal Landing During Thoracic Endovascular Aortic Repair.

To improve the outcomes of thoracic endovascular aortic repair (TEVAR), we investigated the dynamic morphology of dilated and nondilated ascending aortas (AAs) to determine whether an appropriate proximal landing zone for TEVAR exists if the middle AA is dilated. Patients with dilated (diameter 40-50 mm) and nondilated (<40 mm) AAs underwent electrocardiogram-gated computed tomography angiography of the entire AA in the systolic and diastolic phases. For each plane of each AA segment, the maximal and minimal diameters in systole and diastole were recorded. A total of 105 patients were enrolled (54% male; median age: 80 years [IQR 78-85]). A total of 35 patients were included in the dilated AA group (DG), and 70 patients were included in the nondilated AA group (n-DG). The aortic planes of the AA segment at the sinotubular junction (STJ) showed a more oval-shaped morphology compared with the distal planes of the same segment (the differences between the maximum and minimum diameters were 8.9% to 9.4% and 4.8% to 5.6%, respectively). If the mid-ascending aorta was dilated, the aortic segment at the STJ showed a more pronounced reversed-funnel 3D morphology, with a 14% (IQR 11%-19%) difference in diameters between the proximal and distal segmental planes shown in the n-DG and 18% (IQR 16%-22%, p<0.001) in the DG. If the middle AA is dilated, it is considered unsuitable to perform TEVAR using conventional endografts without additional proximal fixation in the aortic segment at the STJ due to its pronounced reversed-funnel segmental morphology. By contrast, the aortic segment at the brachiocephalic trunk seems to be promising for performing TEVAR using an endograft of the appropriate size and conformability. Moreover, endograft sizing using the average aortic diameter instead of the maximal AA diameter in an oval-shaped aortic plane morphology should be considered. If the middle ascending aorta is dilated, it is considered unsuitable to perform TEVAR with a proximal landing in the aortic segment at the sinotubular junction due to its pronounced reversed-funnel segmental morphology and high risk of type Ia endoleak and endograft migration. By contrast, the aortic segment at the brachiocephalic trunk seems to be promising for performing TEVAR due to its moderate funnel morphology using an endograft of appropriate size and conformability.

Inter-ethnic heterogeneity in valvular morphology and aortopathy of a worldwide bicuspid aortic valve cohort referred for TAVR

Abstract Background Bicuspid aortic valve (BAV) represents one of the most common congenital heart disease. BAV stenosis tipycally occurs in younger, low-surgical risk patients compared to tricuspid aortic valves (TAV). With the predicted expansion of trans-catheter aortic valve replacement (TAVR) into lower-risk patients, the proportion of BAV is expected to rise. Although some observational studies have investigated the characteristics of Asian versus European patients with BAV undergoing TAVR, little is known about the inter-ethnic differences within the large and diverse Asian, African, Russian, and Caucasian population. Purpose To evaluate the inter-ethnic differences of aortic valve morphology, annular size and associated aortopathy, in a worldwide population of patients with severe aortic stenosis referred for TAVR. Methods Cardiovascular multislice computed tomography data of patients with severe aortic valve stenosis referred for TAVR worldwide were obtained from the database of the Meril Life Core Lab. Inter-ethnic and epidemiological differences in terms of valvular phenotype, annular size and aortic morphology were evaluated with particular focus on patients with BAV. Results Among 12,712 patients (59% male), n=3,203 subjects (25%) exhibited a BAV morphology. According to the Siever’s BAV classification, type 1 (71%, n=2,284) was the most prevalent BAV morphology and particularly Type 1a was the most common in almost all population, with 26% exhibiting a type 0 BAV, while only 3% of the patients (n= 92) had a type 2 (Table 1). A significantly higher prevalence of severe calcium score (&amp;gt;1000 mm3) was found in patients with BAV compared with patients exhibiting a TAV morphology (51% vs. 32, p&amp;lt;0.01). Additionally, larger ascending aorta (AA) diameter (AA &amp;gt;40 mm) (BAV: 31% vs TAV 7%, p = 0.04), along with a higher prevalence of horizontal aorta (HA) (BAV: 20% vs TAV: 9%, p&amp;lt;0.01) was found in patients with BAV compared with TAV. As for inter-ethnic characteristics, there was a higher prevalence of BAV in Indian and Asian Pacific populations (respectively 43% and 28%), with the African population exhibiting the lowest prevalence (7%, n= 28, p=0.02) (Table 2). In Indian patients a higher prevalence of BAV was found in an earlier age (61-70 years old) compared to Western countries (p=0.05). Finally, smaller annular size (456±98 mm2 vs 584±99 mm2, p&amp;lt;0.01) and lower coronary ostia height (Asia and India: RCA 14.5±3 mm, LCA 14±2.9mm vs Caucasian and Russian: RCA 16±3.2 mm, LCA 16.9±3.3mm; p&amp;lt;0.01) were found in the Asian and Indian population when compared with Russian, African and Caucasian subjects. Conclusions BAV morphology, aortopathy and annular size resulted widely heterogenous according to the ethnicity and geographical origin of patients referred for TAVR worldwide. These features may lead different therapeutical decision making and outcomes following TAVR in patients with BAV.Table 1Table 2

Assessing aortic morphology post aortic valve replacement using unsupervised hierarchical clustering and statistical shape modelling

Abstract Introduction There are different surgical procedures used to treat aortic valve disease such as aortic valve replacement (AVR), the Ozaki procedure, the Ross procedure, and the valve-sparing procedure. There may be postoperative side effects associated with aortic morphology. Computational analyses that assess morphology are thus necessary in such scenario. Statistical shape modelling is used to assess three-dimensional morphology, discover unique shape features, create mean shapes, and create shape modes that display morphological variability. Hierarchical cluster analysis is a machine learning method used to classify a population into subgroups. Both of these statistical methods were applied to aortic valve replacement patients to evaluate morphological variability after aortic valve replacement (AVR) surgery. Purpose The purpose of this study is to assess the aortic morphology of AVR patients, identify morphological differences between different surgical procedures, identify subgroups postoperatively using statistical shape modelling and hierarchical cluster analysis, and assessing possible correlations between the resultant clusters and function i.e. ejection fraction. Methods Computed tomography and cardiac magnetic resonance images were used to reconstruct aortas into 3D models using segmentation and 3D reconstruction software. For each patient, two models were created (i.e. ascending aorta only and aorta including the arch and the descending aorta). N=35 patients were included in the study. Statistical shape analysis was run to create templates and shape modes. Statistical environment and language software was used to run hierarchical cluster analysis. Results Overall, the hierarchical cluster analysis did not classify the aortas based on type of surgery, but most patients in the Ross group demonstrated morphological differences from the other surgical groups and many of the aortas belonging to the Ross group were clustered together in both clustering analyses. No significant differences between clusters were seen (p=0.47 for ascending, p=0.19 for whole aorta). No correlation was found between clusters and ejection fraction (p=0.75, r2&amp;lt;0.01), possibly indicating that post-AVR aortic morphology in this sample does not reflect overt functional changes. Conclusion Both statistical shape modelling and hierarchical cluster analyses were successful in assessing morphological variability and identifying subgroups in this population. This framework could therefore be extended to larger samples to inform on surgical decision-making allowing surgeons to choose the appropriate surgery for the patient or design prosthetic valves that are more customised to the patient’s anatomy.Cluster-Ejection Fraction Correlation

Lipoprotein(a) induces spontaneous aortic dissection via increasing monocyte mediated vascular smooth muscle cell phenotype transformation in human Lp(a) transgenic mice

Abstract Background Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent risk factor of atherosclerotic cardiovascular disease and aortic valve stenosis. Recent studies have reported that high levels of Lp(a) are strongly associated with aortic dissection (AD), independent of other cardiovascular risk factors. However, orthologues of Lp(a) are only found in humans, Old World monkeys, apes, and hedgehogs. The lack of a proper animal model has hindered elucidation of the true pathophysiological mechanisms of Lp(a). Here, we conducted the first humanized Lp(a) transgenic mice experiment to verify the pathological mechanism of Lp(a) in aortic dissection. Methods We conducted ApoE knock out and human ApoA transgenic mice via CRISPR-Cas9 and then crossed with human ApoB transgenic mice to achieve high levels of human-like Lp(a) particles in plasma. Plasma was assayed by ELISA for the concentrations of each lipoprotein. Echocardiography was performed to detect aortic morphology in vivo. Single cell transcriptome analysis was performed on the dissection lesion. Cell interaction was examined in macrophage from Lp(a) transgenic mice and vascular smooth muscle cell (VSMC) coculture system. Result Our results indicate that the concentration of ApoA and ApoB in plasma were increased in transgenic mice fed a chow diet. Low density lipoprotein (LDL) levels were increased and shows that LDL is the major cholesterol carrier in these mice. We were surprised to find that the dissection of the ascending aortic arch could be seen by echocardiography in transgenic mice as early as 2 months, and transgenic mice showed significant increase in aortic enlargement, dissection, and rupture in both the thoracic and abdominal aortic regions, resulting in a survival rate of only 58% after 12 months. Single cell transcriptome analysis revealed that Lp(a) transgene induced the inflammatory response, dedifferentiation and pathological VSMC phenotypical switch, and matrix metalloproteinase expression in macrophages. Monocytes isolated from transgenic mice with elevated Lp(a) remain in a long-lasting primed state, as evidenced by an increased capacity to transmigrate and produce proinflammatory cytokines on stimulation. Monocytes isolated from wild type mice cultured in media with high level Lp(a) for 24h also showed the ability to facilitated cocultured VSMC phenotype transformation, which was reversed by E06, a monoclonal antibody blocking the oxidized phospholipids in Lp(a). Conclusion These findings demonstrate that Lp(a) induces spontaneous aortic dissection via increasing monocyte trafficking to the arterial wall, mediating proinflammatory responses and VSMC phenotype transformation through its OxPL content. The study presents a rodent model of spontaneous aortic dissection and provide a novel mechanism by which Lp(a) mediates aortic dissection.Graphical abstract

Effects of pedicle subtraction osteotomy on aortic morphology and hemodynamics in ankylosing spondylitis with kyphosis: a finite element analysis study

Osteotomy can correct kyphosis, restore the spinal sequence, and restore the healthy appearance of a patient. However, the aorta is stretched during pedicle subtraction osteotomy (PSO), and some surgeons are concerned about aortic injury. We used finite element analysis to construct an aortic model to simulate hemodynamic changes during osteotomy. 16 patients with ankylosing spondylitis kyphosis who had undergone a two-level osteotomy at the L1 and L3 levels was included in this study. Aortic computed tomography angiography (CTA) was performed, and a 3D image model was constructed. The length, transverse diameter, and curvature of the aorta were used to evaluate morphological changes. Finite element analysis was used to analyze the changes in aortic fluid dynamics. Blood pressure, wall shear stress, and blood flow velocity were compared pre- and postoperatively. The overall length of the aorta before surgery was 424.3 ± 42.9 mm, and the overall length of the aorta after surgery was 436.2 ± 54.8 mm. The aortic curvature decreased from 0.27 ± 0.13 to 0.17 ± 0.09. The mean transverse diameter of the aorta did not change (19.3 ± 6.6 vs. 19.2 ± 7.4 mm, P > 0.05). The blood flow velocity (2.8 ± 1.1 vs. 1.5 ± 0.8 m/s, P < 0.05), blood pressure (6.6 ± 1.7 vs. 4.3 ± 1.2 Kpa, P < 0.05), and wall shear stress (47.6 ± 17.3 vs. 22.3 ± 8.6, P < 0.05) at the T10-L4 level decreased postoperatively. Changes in LL were significantly correlated with changes in ld, dc, blood flow velocity, blood pressure and wall shear stress (ld : r = 0.713, P < 0.001; dc: r = 0.626,P = 0.010; blood flow velocity: r= − 0.541, P = 0.041; blood pressure: r = − 0.601, P = 0.016; wall shear stress: r= − 0.594, P = 0.027). The aorta was stretched, and its curvature decreased. The mean transverse diameter of the aorta did not change. Blood flow velocity, blood pressure, and wall shear stress decreased after surgery. Our study provides hemodynamic support for the possible cardiovascular benefits of osteotomes.

ASSOCIATIONS BETWEEN AORTIC DIAMETER AND ANTHROPOMETRIC MEASURES IN MEN: A CT STUDY

Cardiovascular diseases are a leading cause of death globally, with Ukraine experiencing a mortality rate of 64.3% in 2019, predominantly affecting men. Aortic aneurysms, assessed by aorta diameter, are significant among these diseases. While computed tomography (CT) is the gold standard for diagnosing aortic syndromes, there's a lack of comprehensive data on aortic morphometrics in Ukraine, particularly in men. This research aims to bridge this gap by analyzing CT-derived data on the ascending aorta in Ukrainian men. Aim. To enhance diagnostic accuracy and guide treatment strategies, including surgical interventions, by understanding the correlation between aortic morphology, age, and anthropometric variables in this high-risk demographic. Materials and methods. The study used DICOM images from computed tomography angiography of the aorta with contrast enhancement and ECG synchronization. Methods included anthropometric assessments, CT imaging, and statistical analysis. The study involved 62 male subjects without heart or ascending aorta pathology. Data included age, body length, and weight, which were used to calculate BMI and BSA. Diameter measurements of the aorta were taken at specific levels: the aortic ring, aortic sinus, sinotubular junction, maximum diameter of the ascending aorta, mid-section of the ascending aorta, and just before the brachiocephalic trunk departure. Statistical analyses employed the Student's t-test and Pearson's correlation analysis, with a significance level of p&lt;0.05. Results. The study encompassed 62 male subjects without cardiovascular pathology, with an average age of 52.56±13.52 years, average body length of 1.76±0.07 m, average body weight of 84.74±14.14 kg, average BMI of 27.54± 4.74 kg/m², and BSA of 2.03±0.18 m². A moderate positive correlation between age and aortic diameter was observed, ranging from +0.35 for the average diameter of the aorta at the aortic ring level to +0.57 for the maximum diameter of the aorta (p&lt;0.05). However, no significant correlations were found between aortic diameters and body height in men (p&gt;0.05). Notably, a moderate positive correlation was observed between body weight and aortic diameter at the sinotubular junction level (r=+0.61, p&lt;0.001) and the aortic sinus level (r=+0.34, p= 0.027). Furthermore, an increase in aortic diameter at the sinotubular junction level was significantly correlated with an increase in BMI (r=+0.59, p&lt;0.001) and BSA (r=+0.57, p&lt;0.001). Additionally, body surface area demonstrated a significant positive correlation with an aortic diameter at the aortic sinus level, exhibiting a moderate positive correlation (r=+0.35, р=0.023). Men with a BMI of 25 kg/m² or higher (n=45) showed significantly larger aortic diameters at almost all levels (excluding the aortic ring diameter) compared to those with lower BMIs (р&lt;0.05). Conclusions. CT-morphometric indicators of the diameter of the aorta in men normally increase with age. Body weight is directly correlated with the diameter of the aorta at the level of the sinotubular junction and aortic sinuses. In men with excess body weight and obesity, larger values of the diameters of the aorta were established at all studied levels, except for the level of the sinotubular junction.

Impact of peripheral venoarterial extracorporeal membrane oxygenation support for heart failure on systemic hemodynamics and aortic blood flow

Peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an advanced temporary life support system for patients with refractory cardiogenic shock or severe cardiopulmonary failure. However, the reperfusion of oxygenated blood into the arterial system via a peripheral artery will induce substantial hemodynamic changes that might contribute to the development of complications. In this study, we developed two types of computational models to quantify the hemodynamic changes induced by the peripheral VA-ECMO support for systolic heart failure (HF) of various severities. One was a lumped-parameter model used for exploring the optimal workload of extracorporeal membrane oxygenation (ECMO) for a specific severity of HF, whereas the other one was a geometrical multiscale model capable of simulating the detailed flow field in the aorta while accounting for the hemodynamic coupling of VA-ECMO with the cardiovascular system. Numerical results revealed that the retrograde transmission of ECMO-supplied blood flow toward the heart not only considerably inhibited cardiac output but also induced marked flow disturbance and regionally high or oscillatory wall shear stress (WSS) in the aorta that may increase the risk of thrombosis and vascular dysfunction. The major characteristics of flow disturbance and spatial distribution of abnormal WSS were codetermined by the cardiac function and workload of ECMO while less influenced by the morphology of aorta. These findings emphasized the importance of tuning the workload of ECMO based on patient-specific cardiac function to balance the amount of blood oxygenation support by ECMO against the risk of complications associated with hemodynamic abnormalities.

The effect of aortic morphology on perioperative rupture of abdominal aortic aneurysm-a retrospective cohort study.

The high mortality from ruptured abdominal aortic aneurysm (AAA) is well-documented. However, the perioperative rupture risk is often underestimated. Aortic morphology is a key unresolved factor influencing this risk. This study aims to assess the impact of aortic morphology on the risk of perioperative rupture of AAAs. A multicenter retrospective cohort study was conducted among patients undergoing perioperative endovascular aneurysm repair (EVAR) for AAAs between September 2017 and October 2021. All measurements were obtained using dedicated hospital reconstruction software. The primary endpoints were mortality and AAAs rupture. Univariate and multivariate logistic regression were used to analyze the association of risk factors with rupture. Piecewise linear regression was used to analyze the threshold effect of proximal neck angulation on rupture of AAAs. The clinical correlation between proximal aneurysm neck angulation and rupture was retrospectively studied after adjusting for potential confounders. A total of 160 patients were included. The incidence of AAAs rupture in patients with severe proximal aneurysm neck angulation was significantly higher than in patients without proximal aneurysm neck angulation (15.9% vs. 7.8%, P=0.001). After adjusting for gender, max aneurysm diameter and symptom, severe proximal aneurysm neck angulation was independently associated with AAAs rupture [odds ratio (OR) =8.159, 95% confidence interval (CI): 2.202-30.236; P=0.001]. After adjusting for gender, proximal aneurysm neck angulation and symptom, max aneurysm diameter was independently associated with AAAs rupture (OR =1.093, 95% CI: 1.046-1.143; P<0.001). The female seemed to have severe proximal neck angulation. When the angulation was greater than 41°, the risk of rupture increased linearly. EVAR remains the preferred surgical approach for managing AAAs, guided by morphological and anatomical considerations. We have established a significant correlation between the extent of proximal neck angulation and the risk of perioperative rupture in aneurysms. Proximal neck angulation differs significantly between genders, with females exhibiting greater angulation than males. Clinicians should meticulously assess proximal neck angulation in patients undergoing EVAR and consider early intervention for those with severe angulation to mitigate the risk of rupture.

Interplay of atherosclerosis and medial degeneration in human ascending aorta

The previous understanding has been that atherosclerosis tends to increase distally from the ascending aorta, but recent studies and practical experience have indicated that atherosclerosis occurs in the ascending aorta more than previously thought. Medial degeneration is linked to aortic aneurysms, dissection and dilatation and has been related to increased mortality. There is a lack of data on the coexistence of atherosclerosis and medial degeneration in the ascending aorta and its outcome to clinical morbidity and mortality. Earlier studies have shown coexisting atherosclerosis and medial degeneration as significant risk indicators for coronary and cerebrovascular events. We aimed to analyze aortic specimens classified according to the consensus documents of the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology particularly the comparison of variable morphological features with the atherosclerotic grade to gain more data about the coexistence of atherosclerosis and medial degeneration. We evaluated 217 specimens of human ascending aorta resected at Tampere University Heart Hospital because of aortic aneurysm, dissection or dilatation. None of the samples contained normal aortic morphology; atherosclerosis was found in a total of 75.8% of the samples and medial degeneration in all the samples. The present study is mostly in agreement with earlier research regarding the prevalence of different histological findings, even though a higher prevalence of atherosclerosis was found compared with most studies. There was no statistically significant association between atherosclerosis and medial degeneration, but a higher atherosclerotic grade was significantly associated with the presence of smooth muscle cell nuclei loss, smooth muscle cell disorganisation, elastic fibre thinning and medial fibrosis. Our study reinforces the perception that atherosclerotic lesions significantly occur in the ascending aorta and coexist with individual components of the medial degeneration.

Exploring aortic morphology and determining variable-distance insertion lengths for fluoroscopy-free resuscitative endovascular balloon occlusion of the aorta (REBOA)

Background (Rationale/Purpose/Objective)Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to temporary control non-compressible truncal hemorrhage (NCTH) as bridge to definitive surgical treatment. The dependence on radiography for safe balloon positioning is one factor that limits the extended use of REBOA in civilian and military pre-hospital settings. We aimed to determine standardized sex and age-based variable-distance catheter insertion lengths for accurate REBOA placement without initial fluoroscopic confirmation.MethodsContrast enhanced CT-scans from a representative sample of a Dutch non-trauma population were retrospectively analyzed. Intravascular distances were measured from the bilateral common femoral artery access points (FAAP) to the middle of the aortic occlusion zones and accompanying boundaries. Means and 95% confidence intervals for the distances from the FAAPs to the boundaries and mid-zone III were calculated for all (combined) sex and age-based subgroups. Optimal insertion lengths and potentially safe regions were determined for these groups. Bootstrap analysis was performed in combination with a 40-mm long balloon introduction simulation to determine error-rates and REBOA placement accuracy for the general population.ResultsIn total, 1354 non-trauma patients (694 females) were included. Vascular distances increased with age and were longer in males. The iliofemoral trajectory was 7 mm longer on the right side. The optimal zone I catheter insertion length would be 430 mm. Optimal zone III catheter insertion lengths showed up to 30 mm difference, ranging between 234 and 264 mm. Statistically significant and potentially clinically relevant differences were observed between the anatomical distances and necessary introduction depths for each subgroup.ConclusionThis is the first study to compare aortic morphology and intravascular distances between combined sex and age-based subgroups. As zone III length was consistent, length variability and elongation seem to mainly originate in the iliofemoral trajectory and zone II. The optimal zone I catheter insertion length would be 430 mm. Optimal zone III catheter insertion ranged between 234 and 264 mm. These standardized variable-distance insertion lengths could facilitate safer fluoroscopy-free REBOA in austere, pre-hospital settings.

A morphological indicator for aortic dissection: fitting circle of the thoracic aorta

BackgroundThis study aims to identify a morphological indicator of aortic dissection (AD) based on the geometrical characteristics of the thoracic aorta.MethodsWe evaluated computed tomographic angiograms of 63 samples with AD (22 with type A AD, 41 with type B AD) and 71 healthy samples. Via centerline extraction and spatial transformation, the spatial entanglement of the aorta was minimized, and the expanded 2D aortic morphology was obtained. The 2D morphology of the thoracic aorta was fit to a circle. The applicability of the fitting circle method for identifying aortic dissection was verified by multivariable logistic regression analysis.ResultsVia the 3D coordinate transformation algorithm, the optimal aortic view was obtained. On this view, the geometrical characteristics of the thoracic aortas of the healthy controls were similar to a portion of a circle (sum of residuals: 3502.45 ± 2566.71, variance: 86.23 ± 56.60), while that of AD samples had poorer similarity to the circle (sum of residuals: 5404.78 ± 3891.69, variance: 129.90 ± 90.09). This difference was significant (p < 0.001). A logistic regression model showed that increased deformation of the thoracic aorta was a significant indicator of aortic dissection (odds ratio: 1.35, p = 0.034).ConclusionsThe morphology of the healthy thoracic aorta could be fit to a circle, while that of the dissected aorta had poorer similarity to the circle. The statistics of the circle are an effective indicator of aortic deformation in AD.Trial registrationThis study is registered in the Chinese Clinical Trial Registry (ChiCTR2000029219).

Machine Learning and Statistical Shape Modelling Methodologies to Assess Vascular Morphology before and after Aortic Valve Replacement.

Introduction: Statistical shape modelling (SSM) is used to analyse morphology, discover qualitatively and quantitatively unique shape features within a population, and generate mean shapes and shape modes that show morphological variability. Hierarchical agglomerative clustering is a machine learning analysis used to identify subgroups within a given population in relation to shape features. We tested the application of both methods in the clinically relevant scenario of patients undergoing aortic valve repair (AVR). Every year, around 5000 patients undergo surgical AVR in the UK. Aims: Evaluate aortic morphology and identify subgroups amongst patients who had undergone AVR, including Ozaki, Ross, and valve-sparing procedures using SSM and unsupervised hierarchical clustering analysis. This methodological framework can evaluate both pre- and post-surgical variability across subgroups undergoing different surgeries. Methods: Pre- (n = 47) and post- (n = 35) operative three-dimensional (3D) aortic models were reconstructed from computed tomography (CT) and cardiac magnetic resonance (CMR) images. Computational analyses for SSM and hierarchical clustering were run separately for the two subgroups, assessing (a) ascending aorta only and (b) the whole aorta. This allows for exploring possible variations in morphological classification related to the input shape. Results: Most patients in the Ross procedure subgroup exhibited differences in aortic morphology from other subgroups, including an elongated ascending and wide aortic arch pre-operatively, and an elongated ascending aorta with a slightly enlarged sinus post-operatively. In hierarchical clustering, the Ross aortas also appeared to cluster together compared to the other surgical procedures, both pre-operatively and post-operatively. There were significant differences between clusters in terms of clustering distance in the pre-operative analyses (p = 0.003 for ascending aortas, p = 0.016 for whole aortas). There were no significant differences between the clusters in post-operative analyses (p = 0.47 for ascending, p = 0.19 for whole aorta). Conclusions: We demonstrated the feasibility of evaluating aortic morphology before and after different aortic valve surgeries using SSM and hierarchical clustering. This framework could be used to further explore shape features associated with surgical decision-making pre-operatively and, importantly, to identify subgroups whose morphology is associated with poorer clinical outcomes post-operatively. Statistical shape modelling (SSM) and unsupervised hierarchical clustering are two statistical methods that can be used to assess morphology, show morphological variations, with the latter being able to identify subgroups within a population. These methods have been applied to the population of aortic valve replacement (AVR) patients since there are different surgical procedures (traditional AVR, Ozaki, Ross, and valve-sparing). The aim is to evaluate aortic morphology and identify subgroups within this population before and after surgery. Computed tomography and cardiac magnetic resonance images were reconstructed into 3D models of the ascending aorta and whole aorta, which were then input into SSM and hierarchical clustering. The results show that the Ross aortic morphology is quite different from the other aortas. The clustering did not classify the aortas based on the surgical procedures; however, most of the Ross group did cluster together, indicating low variability within this surgical group.

The relation between aortic morphology and transcatheter aortic heart valve thrombosis: Particle tracing and platelet activation in larger aortic roots with and without neo-sinus

Transcatheter aortic heart valve thrombosis (THVT) affects long-term valve durability, transvalvular pressure gradient and leaflet mobility. In this study, we conduct high-fidelity fluid–structure interaction simulations to perform Lagrangian particle tracing in a generic model with larger aortic diameters (THVT model) with and without neo-sinus which is compared to a model of unaffected TAVI patients (control model). Platelet activation indices are computed for each particle to assess the risk of thrombus formation induced by high shear stresses followed by flow stagnation. Particle tracing indicates that fewer particles contribute to sinus washout of the THVT model with and without neo-sinus compared to the control model (−34.9%/−34.1%). Stagnating particles in the native sinus of the THVT model show higher platelet activation indices than for the control model (+39.6% without neo-sinus, +45.3% with neo-sinus). Highest activation indices are present for particles stagnating in the neo-sinus of the larger aorta representing THVT patients (+80.2% compared to control).This fluid–structure interaction (FSI) study suggests that larger aortas lead to less efficient sinus washout in combination with higher risk of platelet activation among stagnating particles, especially within the neo-sinus. This could explain (a) a higher occurrence of thrombus formation in transcatheter valves compared to surgical valves without neo-sinus and (b) the neo-sinus as the prevalent region for thrombi in TAV. Pre-procedural identification of larger aortic roots could contribute to better risk assessment of patients and improved selection of a patient-specific anti-coagulation therapy.

Mechanism of astragaloside Ⅳ modulation of Nrf2/HO-1/GPX4 pathway to inhibit ferroptosis and ameliorate atherosclerosis in ApoE~(-/-) mice

The intervention effect of astragaloside Ⅳ(AS-Ⅳ) on atherosclerosis in apolipoprotein E gene knockout(ApoE)~(-/-) mice was observed based on the nuclear factor erythroid-2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) signaling pathway to explore the potential mechanism of AS-Ⅳ in improving ferroptosis in atherosclerotic mice. This study established an atherosclerosis mouse model by feeding them a high-fat diet. After modeling for 8 weeks, ApoE~(-/-) mice were randomly divided into the model group, AS-Ⅳ group, AS-Ⅳ+Nrf2 inhibitor(ML385) group, and ferrostatin-1(Fer-1) group. Additionally, a blank control group was also established. Corresponding drugs were administered via intraperitoneal injection, with the control group receiving an equivalent amount of normal saline injection as the model group. After the experiment, serum biochemical levels were measured using an automatic blood lipid analyzer, hematoxylin-eosin(HE) staining was used to observe morphological changes in aortic sinus tissues, colorimetric methods were used to detect levels of ferrous ion(Fe~(2+)), malondialdehyde(MDA), glutathione(GSH), and superoxide dismutase(SOD) in mouse serum, immunofluorescence was used to observe the expressions of ferritin heavy chain 1(FTH1) and ferritin light chain(FTL) proteins in the aortic sinus of mice, Western blot was used to detect the protein levels of Nrf2, HO-1, and GPX4 in mouse aortic tissues, and transmission electron microscopy was used to observe ultrastructural changes in aortic tissues. RESULTS:: showed that compared to the control group, the model group of mice had significantly increased calcification and plaque deposition areas in the aortic sinus, increased mitochondrial membrane density, decreased or disappeared mitochondrial cristae, elevated levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), Fe~(2+), and MDA, decreased levels of high-density lipoprotein cholesterol(HDL-C), SOD, and GSH, and significant inhibition of Nrf2, HO-1, GPX4 proteins, as well as iron storage proteins FTH1 and FTL expressions in the aorta. Compared to the model group, AS-Ⅳ treatment resulted in decreased serum TC, TG, LDL-C, Fe~(2+), and MDA levels, increased HDL-C, SOD, and GSH levels, increased expressions of Nrf2, HO-1, and GPX4 proteins, and iron storage proteins FTH1 and FTL, and significant improvement in aortic tissue morphology. Compared to the AS-Ⅳ group, the Nrf2 inhibitor ML385 could reverse the therapeutic effect of AS-Ⅳ on atherosclerosis mice. These findings suggest that AS-Ⅳ can inhibit ferroptosis and improve atherosclerosis in ApoE~(-/-) mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Vascular endothelial effects of dibutyl phthalate: In vitro and in vivo evidence

Dibutyl phthalate (DBP) is widely used in many consumer and personal care products. Here, we report vascular endothelial response to DBP in three different exposure scenarios: after short-term exposure (24 h) of human endothelial cells (ECs) EA.hy926 to 10−6, 10−5, and 10−4 M DBP, long-term exposure (12 weeks) of EA.hy926 cells to 10−9, 10−8, and 10−7 M DBP, and exposure of rats (28 and 90 days) to 100, 500, and 5000 mg DBP/kg food. We examined different vascular functions such as migration of ECs, adhesion of ECs to the extracellular matrix, tube formation, the morphology of rat aorta, as well as several signaling pathways involved in controlling endothelial function. Short-term in vitro exposure to DBP increased migration of ECs through G protein-coupled estrogen receptor, extracellular signal-regulated kinase 1/2, and nitric oxide (NO) signaling and decreased adhesion to gelatin. Long-term in vitro exposure to DBP transiently increased EC migration and had a bidirectional effect on EC adhesion to gelatin and tube formation. These effects were accompanied by a sustained increase in NO production and endothelial NO synthase (eNOS) and Akt activity. In vivo, exposure to DBP for 90 days decreased the aortic wall-to-lumen ratio and increased eNOS and Akt phosphorylation in ECs of rat aorta. This comparative investigation has shown that exposure to DBP may affect vascular function by altering EC migration, adhesion to gelatin, and tube formation after short- and long-term in vitro exposure and by decreasing the aortic wall-to-lumen ratio in vivo. The eNOS-NO and Akt signaling could be important in mediating the effects of DBP in long-term exposure scenarios.

Technical Aspects and Outcome of Multi-Staged and Single-Staged Thoracoabdominal Fenestrated Endovascular Aortic Repair.

In some cases of endovascular thoracoabdominal or juxtarenal aortic aneurysm repair, a thoracic endograft in combination with a fenestrated renovisceral device may be needed in order to create a sufficient proximal landing zone. This study aimed to evaluate the technical aspects and postoperative morbidity of a single- or 2-stage approach. Eighty-seven consecutive patients undergoing thoracic endovascular aortic repair (TEVAR) in combination with elective fenestrated repair (fenestrated endovascular aortic repair [FEVAR]; fenestrated Anaconda device) from 2015 to 2022 were included in this retrospective bicentric study. Underlying pathologies, aortic morphology, technical details, and postoperative morbidity were recorded. Single-staged ("1S," n=61) and 2-staged ("2S," n=26) interventions were compared. Indications were thoracoabdominal aneurysms (TAAAs) (Crawford I-IV) (n=56, 64%) and juxtarenal aneurysms (n=31, 36%). In 2S, the proportion of TAAA was higher than in 1S (2S: 77%, 1S: 59%; p=0.001). In 2S, the covered length of the descending aorta was longer (1S: 128±60 mm, 2S: 202±64 mm; p=0.003). Temporary aneurysm sack perfusion (TASP) was established in 11 (18%) of 1S and 1 (4%) of 2S patients (p=0.079), as well as cerebrospinal fluid (CSF) drainage catheter in 48 (79%) of 1S and 19 (73%) of 2S. The rate of spinal cord ischemia (SCI) and the severity of SCI were not different in both groups, with a total of 3 cases of persisting paraplegia. The rate of access complications was higher in 2S (n=6, 23%) than in 1S (n=4, 7%; p=0.027). Postoperative 30 day morbidity did not significantly differ in both groups and neither did 30 day mortality (4.6% in 1S vs 3.8% in 2S; p=0.083). The combination of TEVAR and FEVAR using a fenestrated endograft is feasible and safe. Aortic morphology does not change significantly after endovascular repair. A single-staged strategy is feasible with excellent results, especially in Crawford IV, Crawford V, or juxtarenal aneurysms. Two-staged repair is recommended in cases with long aortic coverage and a higher American Society of Anesthesiologists (ASA) class. Follow-up data are needed to evaluate the long-term stability of the TEVAR/FEVAR interconnection. Our study has revealed the safety and efficacy of the combination of TEVAR and FEVAR in the treatment of TAAAs and juxtarenal aneurysms with compromised supravisceral landing zones. A single-staged concept is not necessary in all cases. Staged procedures may reduce postoperative morbidity in cases with long aortic coverage and higher ASA class.

Influence of Aortic Arch Morphology on Renal Perfusion in Patients with Coarctation of the Aorta: An Exploratory Study.

Objectives: The configuration of the aortic arch, particularly a Gothic arch shape, in individuals with corrected coarctation of the aorta (CoA) has been associated with a decreased systolic wave amplitude across the arch, which could potentially impair renal perfusion and elevate the risk of arterial hypertension. This study aims to explore the relationship between the morphological characteristics of the aortic arch and their impact on renal perfusion in patients with CoA. Methods: Seventy-one subjects with corrected CoA underwent continuous 24 h ambulatory blood pressure monitoring, computed tomography to assess the aortic arch, and renal perfusion scanning. Subjects were stratified into three groups based on the height-to-width (H/W) ratio of their aortic arch: Group 1 with a H/W ratio of <0.65, Group 2 with a H/W ratio between 0.65 and 0.85, and Group 3 with a H/W ratio of >0.85. Results: Groups 1 and 2 (53,78% and 62.63%) presented with a higher hypertension prevalence of elevated blood pressure than Group 3 (38.89%). Notable variations were observed among the subjects in the time to peak perfusion (Tmax) in the left kidney across the groups. Group 1 showed a median Tmax at 0.27, Group 2 at 0.13, and Group 3 at -0.38 (p-value = 0.079). The differences in Tmax for the right kidney followed a similar trend but were not statistically significant (Group 1 at 0.61, Group 2 at 0.22, and Group 3 at 0.11; p-value = 0.229). Conclusions: This study suggests that variations in the aortic arch morphology might not significantly influence renal perfusion in CoA patients. This indicates the potential adaptability of the renal blood flow, which appears to compensate for reduced perfusion, thus minimizing adverse effects on the kidney function. This adaptability suggests an inherent physiological resilience, emphasizing the need for further targeted research to understand the specific interactions and impacts on treatment strategies for CoA.

#2215 Early molecular and cellular features of aortic remodeling in a mild CKD-MBD model with low bone turnover

Abstract Background and Aims Vascular calcification associated with a maladaptive bone response is common in CKD and is a major cause of mortality (up to 60% depending on CKD stage). Alterations in several intracellular signaling pathways have been reported during the cellular phenotype transition and vascular calcification, however the initial phases of vascular remodeling in early CKD-MBD remain poorly understood. The aim of this study was to investigate the early molecular and cellular features of aortic remodeling prior to calcification in a model of mild CKD-MBD with low bone turnover. Method We induced CKD-MBD by 3/4 nephrectomy (Nx, n = 8) in adult male spontaneously hypertensive rats (SHR) with normal phosphate (Pi) intake (0.6%). Controls were sham-operated Wistar rats (n = 8) and SHR (n = 8). Chronic kidney injury and Pi exchange parameters, serum levels of calciprotein particles (CPPs), intact PTH, intact FGF23, dickkopf-1 and sclerostin, static bone histomorphometry, aortic morphology (H&amp;E, Masson's trichrome, calcein, von Kossa stain), CD31, aSMA, nestin, Col1a1, PDGFR-beta, PiT1, LGR4 and intracellular signaling molecules—phospho-ERK1/2, active (non-phospho) beta-catenin, Hes1, Gli1 were analyzed by IHC with quantitative morphometry and IF after 4 months. Confocal microscopy was performed at the Centre for Collective Use of the Pavlov Institute of Physiology, Russian Academy of Sciences (Zeiss LSM 710). Results The study found that Nx rats with chronic kidney injury comparable to human CKD S2 exhibited lower bone turnover (Fig. 1). The Nx group had higher serum levels of Pi and CPPs vs. control group, but there were no differences in Pi-regulatory factors (Figs 1, 2b). Additionally, the Nx group showed aorta remodeling, which was characterized by an increase in intima thickness, cellularity, and collagen accumulation in the medial layer (Figs 1, 2a). The histological parameters of intimal remodeling and perivascular fibrosis were found to be directly correlated with serum levels of Pi and CPPs. In Nx, there was a decrease in medial αSMA expression accompanied by an increase in phospho-ERK1/2, PiT1, nestin, Gli1, beta-catenin, dickkopf-1, and an decrease in Hes1 immunomorphological staining (Figs 1, 2a, c). αSMA-negative cells demonstrated the expression of osteogenesis-related molecules, such as phospho-ERK1/2 (Fig. 2a, c), and occasionally, RunX2 (Fig. 2a). Phospho-ERK1/2 and PiT1 were found to co-localize in Nx (Fig. 2c). Intimal remodeling was observed, characterized by increased beta-catenin and nestin expression (Fig. 2c). Conclusion In mild CKD-MBD with low bone turnover, early intimal and medial aortic remodeling was associated with higher serum Pi and CPPs levels, and upregulation of PiT1, ERK1/2. In addition, other signals likely related to osteogenesis (RunX2, LGR4) and regulation of vascular progenitor cells (Nestin, Wnt, Notch, Hedgehog) may be implicated.

Surgical Management of Norwood Procedure for Atypical Aortic Arch.

Background: Postoperative restenosis of the aortic arch after the Norwood procedure is still an important complication that significantly affects surgical outcomes. The rarity of the Norwood procedure for atypical aortic morphology means appropriate arch reconstruction methods and postoperative complications are still unknown. This study aimed to assess the rate of arch reintervention and clinical outcomes after the Norwood procedure for atypical aortic arch. Methods: This retrospective single-center study was conducted between 2001 and 2022. Sixteen patients were identified, eight with a right aortic arch, five with transposition of the great arteries, one with a right aortic arch and transposition of the great arteries, and two with a large tortuous patent ductus arteriosus connected to the opposite side of the descending aorta. We selected and performed four different surgical techniques depending on each aortic arch morphology. Results: Except for one case, autologous tissue-only arch reconstruction was possible. There was one operative death and four late deaths. Overall, no patients required any surgical or catheter-based reintervention for the aortic arch. On the other hand, left pulmonary artery stenosis due to a narrow subaortic space was found in two patients. Conclusions: The Norwood procedure for atypical aortic arch was performed with good results by choosing the appropriate technique for each morphology. On the other hand, pulmonary artery stenosis is likely to occur especially in the transposition of the great arteries group. Therefore, careful surgical method selection or further improvement of the technique that allows retroaortic space should be considered.

Morphology of the native ascending aorta after the Norwood procedure for aortic atresia: impact on survival and right ventricular dysfunction.

Our goal was to evaluate the impact of variable morphology of the native ascending aorta after the Norwood I procedure in patients with hypoplastic left heart syndrome/aortic atresia on long-term survival and systemic right ventricular dysfunction. Of 151 survivors of the Norwood procedure for hypoplastic left heart syndrome/aortic atresia at our institution between January 2001 and December 2020, we included patients with available and measurable aortograms prior to stage II palliation. The diameter of the native ascending aorta, the length of the native ascending aorta and the angle between the native ascending aorta and the proximal pulmonary artery were measured. We investigated the impact of these morphologic parameters on mortality and on right ventricular dysfunction (defined as at least moderate). Angiograms were available for 78 patients. The median diameter of the native ascending aorta was 3.2 mm (2.6-3.7), the median length of the native ascending aorta was 15.4 mm (13.3-17.9) and the median angle between the native ascending aorta and the proximal pulmonary artery was 44° (35°-51°). During the median follow-up of 6.5 years, 8 (10%) patients died and systemic right ventricular dysfunction occurred in 19 patients (24%). No significant association between aortic morphology and mortality could be detected. Right ventricular function was negatively affected by a larger angle between the native ascending aorta and the proximal pulmonary artery [odds ratio 1.07 (1.01-1.14), P = 0.02]. In survivors of the Norwood procedure for hypoplastic left heart syndrome/aortic atresia with available angiograms, no significant association between native aortic morphology and mortality could be demonstrated after stage II palliation, within the scope of this limited study. A larger anastomosis angle between the native ascending aorta and the proximal pulmonary artery emerged as a risk factor for right ventricular dysfunction.