Engineered vascular grafts lend unique insight to pathophysiology of aortic aneurysms.

Yang et al.1 generate tissue engineered blood vessels from hiPSC-derived smooth muscle cells harboring a mutation found in Loeys-Dietz syndrome. In vitro and in vivo data from these vessels provide new insight into the molecular physiology of aortic aneurysms and may create a paradigm for understanding a suite of vascular diseases.

Frozen Elephant Trunk Procedure for Acute Type a Aortic Dissection: Analysis of Distal Aortic Remodeling According to the Society for Vascular Surgery (SVS)/Society of Thoracic Surgeons (STS) Reporting Standard.

BACKGROUND: To investigate impact of frozen elephant trunk (FET) on long-term distal aortic remodeling in acute A aortic dissection (AAD) according to the latest recommended standards from the Society for Vascular Surgery (SVS)/Society of Thoracic Surgeons (STS). METHODS: Clinical data and imaging of patients who underwent FET to treat acute AAD over the last 8 years were retrospectively reviewed. Patients were included if a pre and postoperative computed angio tomographies at least 30 days from surgery was available for comparison. Contrasted postprocessed imaging were analyzed with Aquarius iNtuition (TeraRecon Inc., Foster City, CA, USA) to analyze long-term positive aortic remodeling, false lumen thrombosis, and aortic expansion according to the SVS or STS recommendations. Secondary endpoints were the rate of in-hospital and long-term mortality, spinal cord ischemia (SCI), and aortic-related reinterventions. RESULTS: Out of 75 patients who underwent FET for type A AAD, n = 41 (54.6%) were included. Significant positive aortic remodeling was reported in Ishimaru zone 1-4 but not in visceral or infrarenal aorta (P < 0.001), and the overall rate of false lumen thrombosis was 95.1% (n = 39). Aortic expansion rates were as follows: 4.9% in zones 1-4, 8.3% in zones 5-6, and 15% in zone 7. The rates of in-hospital mortality and long-term mortality were 7.3% (n = 3) and 9.7% (n = 4), respectively. At a median follow-up of 11 months (range 1-141, reintervention rate was 17.1%. CONCLUSIONS: We report positive aortic remodeling of the distal thoracic aorta in patients who underwent FET for acute AAD according to the SVS or STS reporting standards. The positive effect on the distal aorta is limited to the thoracic segments but not in the visceral aorta.

Multicenter CT Image-Based Anatomic Assessment of Patients with Aortoiliac Aneurysm Undergoing Endovascular Repair with Iliac Branch Devices.

BACKGROUND: The Global Iliac Branch Study (NCT05607277) is an international, multicenter, retrospective cohort study of anatomic predictors of adverse iliac events (AIEs) in aortoiliac aneurysms treated with iliac branch devices (IBDs). METHODS: Patients with pre-IBD and post-IBD computed tomography imaging were included. We measured arterial diameters, stenosis, calcification, bifurcation angles, and tortuosity indices using a standardized, validated protocol. A composite of ipsilateral AIE was defined, a priori, as occlusion, type I or III endoleak, device constriction, or clinical event requiring reintervention. Paired t-test compared tortuosity indices and splay angles pretreatment and post-treatment for all IBDs and by device material (stainless steel and nitinol). Two-sample t-test compared anatomical changes from pretreatment to post-treatment by device material. Logistic regression assessed associations between AIE and anatomic measurements. Analysis was performed by IBD. RESULTS: We analyzed 297 patients (286 males, 11 females) with 331 IBDs (227 stainless steel, 104 nitinol). Median clinical follow-up was 3.8 years. Iliac anatomy was significantly straightened with all IBD treatment, though stainless steel IBDs had a greater reduction in total iliac artery tortuosity index and aortic splay angle compared to nitinol IBDs (absolute reduction -0.20 [-0.22 to -0.18] vs. -0.09 [-0.12 to -0.06], P < 0.0001 and -19.6° [-22.4° to -16.9°] vs. -11.2° [-15.3° to -7.0°], P = 0.001, respectively). There were 54 AIEs in 44 IBDs in 42 patients (AIE in 13.3% of IBD systems), requiring 35 reinterventions (median time to event 41 days; median time to reintervention 153 days). There were 18 endoleaks, 29 occlusions, and 5 device constrictions. There were no strong associations between anatomic measurements and AIE overall, though internal iliac diameter was inversely associated with AIE in nitinol devices (nAIE, nitinol = 8). CONCLUSIONS: Purpose-built IBDs effectively treat aortoiliac disease, including that with tortuous anatomy, with a high patency rate (91.5%) and low reintervention rate (9.1%) at 4 years. Anatomic predictors of AIE are limited.

An efficient procedure for the blood flow computer simulation of patient-specific aortic dissections.

In this work we present a novel methodology for the numerical simulation of patient-specific aortic dissections. Our proposal, which targets the seamless virtual prototyping of customized scenarios, combines an innovative two-step segmentation procedure with a CutFEM technique capable of dealing with thin-walled bodies such as the intimal flap. First, we generate the fluid mesh from the outer aortic wall disregarding the intimal flap, similarly to what would be done in a healthy aorta. Second, we create a surface mesh from the approximate midline of the intimal flap. This approach allows us to decouple the segmentation of the fluid volume from that of the intimal flap, thereby bypassing the need to create a volumetric mesh around a thin-walled body, an operation widely known to be complex and error-prone. Once the two meshes are obtained, the original configuration of the dissection into true and false lumen is recovered by embedding the surface mesh into the volumetric one and calculating a level set function that implicitly represents the intimal flap in terms of the volumetric mesh entities. We then leverage the capabilities of unfitted mesh methods, specifically relying on a CutFEM technique tailored for thin-walled bodies, to impose the wall boundary conditions over the embedded intimal flap. We tested the method by simulating the flow in four patient-specific aortic dissections, all involving intricate geometrical patterns. In all cases, the preprocess is greatly simplified with no impact on the computational times. Additionally, the obtained results are consistent with clinical evidence and previous research.

The influence of sex on left ventricular remodeling in patients with aortic dissection.

AIMS: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection. METHODS: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60 days before or after the diagnosis of aortic dissection from three Brazilian centers. RESULTS: Men and women had similar clinical characteristics, except for higher age (59.4 ±â€Š13.4 vs. 55.9 ±â€Š11.6 years; P  = 0.013) and use of antihypertensive classes (1.4 ±â€Š1.3 vs. 1.1 ±â€Š1.2; P  = 0.024) and diuretics (32 vs. 19%; P  = 0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P  = 0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P  = 0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence interval = 0.42, 0.20-0.87; P  = 0.019) and were more likely to have LVH (odds ratio, 95% confidence interval = 1.91, 1.11-3.27; P  = 0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence interval = 1.16, 0.77-1.75; P  = 0.49). CONCLUSION: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women.

Two surgical strategies (early carotid reperfusion vs. Central aortic repair-first) of acute type a aortic dissection complicated with cerebral malperfusion syndrome: a meta-analysis and systematic review.

OBJECTIVE: Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes. METHODS: The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated. RESULTS: A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h. CONCLUSION: This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications. TRIAL REGISTRATION: The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023.

Comparison of Various Functional Assessment Tools to Identify Older Patients Undergoing Aortic Aneurysm Repair at Risk for Postoperative Complications.

BACKGROUND: To estimate whether the benefits of aortic aneurysm repair will outweigh the risks, determining individual risks is essential. This single-center prospective cohort study aimed to compare the association of functional tools with postoperative complications in older patients undergoing aortic aneurysm repair. METHODS: Ninety-eight patients (≥65 years) who underwent aortic aneurysm repair were included. Four functional tools were administered: the Montreal Cognitive Assessment (MoCA); the 4-Meter Walk Test (4-MWT); handgrip strength; and the Groningen Frailty Indicator (GFI). Primary outcome was the association between all tests and 30-day postoperative complications. RESULTS: After adjusting for confounders, the odds ratio for MoCA was 1.39 (95% confidence interval [CI] 0.450; 3.157; P = 0.723), for 4-MWT 0.63 (95% CI 0.242; 1.650; P = 0.348), for GFI 1.82 (95% CI 0.783; 4.323, P = 0.162), and for weak handgrip strength 4.78 (95% CI 1.338; 17.096, P = 0.016). CONCLUSIONS: Weak handgrip strength is significantly associated with the development of postoperative complications after aortic aneurysm repair. This study strengthens the idea that implementing a quick screening tool for risk assessment at the outpatient clinic, such as handgrip strength, identifies patients who may benefit from preoperative enhancement with help from, for example, Comprehensive Geriatric Assessment, eventually leading to better outcomes for this patient group.

Fracture mechanics modeling of aortic dissection.

Aortic dissection, a critical cardiovascular condition with life-threatening implications, is distinguished by the development of a tear and its propagation within the aortic wall. A thorough understanding of the initiation and progression of these tears, or cracks, is essential for accurate diagnosis and effective treatment. This paper undertakes a fracture mechanics approach to delve into the mechanics of tear propagation in aortic dissection. Our objective is to elucidate the impact of geometric and material parameters, providing valuable insights into the determinants of this pivotal cardiovascular event. Through our investigation, we have gained an understanding of how various parameters influence the energy release rate for tear propagation in both longitudinal and circumferential directions, aligning our findings with clinical data.

Long-term outcome of multilayer flow modulator in aortic aneurysms.

BACKGROUND: This retrospective study investigated the efficacy of endovascular treatment with multilayer flow modulators (MFMs) for treating aortic aneurysms in high-risk patients unsuitable for conventional treatments. PATIENTS AND METHODS: Conducted from 2011 to 2019 at a single center, this retrospective observational study included 17 patients who underwent endovascular treatment with MFMs. These patients were selected based on their unsuitability for traditional surgical or endovascular procedures. The study involved meticulous pre-procedural planning, precise implantation of MFMs, and follow-up using CT angiography. The primary focus was on volumetric and flow volume changes in aneurysms, along with traditional diameter measurements. Moreover, the technical success and post-procedural complications were also registered. RESULTS: The technical success rate was 100%, and 30-day procedural complication rate was 17.6%. Post-treatment assessments revealed that 11 out of 17 patients showed a decrease in flow volume within the aneurysm sac, indicative of a favorable hemodynamic response. The median decrease in flow volume was 12 ml, with a median relative decrease of 8%. However, there was no consistent reduction in aneurysm size; most aneurysms demonstrated a median increase in volume for 46 ml and median increase in diameter for 18 mm. CONCLUSIONS: While MFMs offer a potential alternative for high-risk aortic aneurysm patients, their effectiveness in preventing aneurysm expansion is limited. The results suggest that MFMs can provide a stable hemodynamic environment but do not reliably reduce aneurysm size. This underscores the need for ongoing vigilance and long-term monitoring in patients treated with this technology.

Patient-Specific Haemodynamic Analysis of Virtual Grafting Strategies in Type-B Aortic Dissection: Impact of Compliance Mismatch.

INTRODUCTION: Compliance mismatch between the aortic wall and Dacron Grafts is a clinical problem concerning aortic haemodynamics and morphological degeneration. The aortic stiffness introduced by grafts can lead to an increased left ventricular (LV) afterload. This study quantifies the impact of compliance mismatch by virtually testing different Type-B aortic dissection (TBAD) surgical grafting strategies in patient-specific, compliant computational fluid dynamics (CFD) simulations. MATERIALS AND METHODS: A post-operative case of TBAD was segmented from computed tomography angiography data. Three virtual surgeries were generated using different grafts; two additional cases with compliant grafts were assessed. Compliant CFD simulations were performed using a patient-specific inlet flow rate and three-element Windkessel outlet boundary conditions informed by 2D-Flow MRI data. The wall compliance was calibrated using Cine-MRI images. Pressure, wall shear stress (WSS) indices and energy loss (EL) were computed. RESULTS: Increased aortic stiffness and longer grafts increased aortic pressure and EL. Implementing a compliant graft matching the aortic compliance of the patient reduced the pulse pressure by 11% and EL by 4%. The endothelial cell activation potential (ECAP) differed the most within the aneurysm, where the maximum percentage difference between the reference case and the mid (MDA) and complete (CDA) descending aorta replacements increased by 16% and 20%, respectively. CONCLUSION: This study suggests that by minimising graft length and matching its compliance to the native aorta whilst aligning with surgical requirements, the risk of LV hypertrophy may be reduced. This provides evidence that compliance-matching grafts may enhance patient outcomes.

A Monte Carlo Sensitivity Analysis for a Dimensionally Reduced-Order Model of the Aortic Dissection.

PURPOSE: Aortic dissection is associated with a high mortality rate. Although computational approaches have shed light on many aspects of the disease, a sensitivity analysis is required to determine the significance of different factors. Because of its complex geometry and high computational expense, the three-dimensional (3D) fluid-structure interaction (FSI) simulation is not a suitable approach for sensitivity analysis. METHODS: We performed a Monte Carlo simulation (MCS) to investigate the sensitivity of hemodynamic quantities to the lumped parameters of our zero-dimensional (0D) model with numerically calculated lumped parameters. We performed local and global analyses on the effect of the model parameters on important hemodynamic quantities. RESULTS: The MCS showed that a larger lumped resistance value for the false lumen and the tears result in a higher retrograde flow rate in the false lumen (the coefficient of variation, c v , i = 0.0183 , the sensitivity S X i σ = 0.54 , Spearman's coefficient, ρ s = 0.464 ). For the intraluminal pressure, our results show a significant role in the resistance and inertance of the true lumen (the coefficient of variation, c v , i = 0.0640 , the sensitivity S X i σ = 0.85 , and Spearman's coefficient, ρ s = 0.855 for the inertance of the true lumen). CONCLUSION: This study highlights the necessity of comparing the results of the local and global sensitivity analyses to understand the significance of multiple lumped parameters. Because of the efficiency of the method, our approach is potentially useful to investigate and analyze medical planning.

Therapeutic window for obtaining favorable remodeling after thoracic endovascular aortic repair of type B aortic dissection.

OBJECTIVE: The purpose of the present study was to determine the most appropriate timing for thoracic endovascular aortic repair (TEVAR) of type B aortic dissection (TBAD) in terms of remodeling of the aorta. METHODS: A total of 41 patients who had undergone TEVAR for the treatment of aortic dissection were included in the present study. The patients were divided into two groups: those who had undergone TEVAR in the acute or subacute phase (group A) and those who had undergone TEVAR in the chronic phase (group B). The indications for TEVAR as the treatment of TBAD were the presence of aortic rupture or malperfusion of the aortic branches, a maximum aortic diameter of ≥40 mm on the initial diagnostic computed tomography scan, and/or expansion of the aorta of ≥5 mm within 3 months for acute and subacute TBAD. The indication was a maximum aortic diameter of ≥50 mm or expansion of the aorta of ≥5 mm within 1 year for chronic TBAD. The diameters of the aorta, true lumen, and false lumen were measured at the level of the most dilated part of the descending aorta (level M) and at the diaphragm (level D) on the computed tomography scan obtained before TEVAR and at the 2-year follow-up examination. RESULTS: The median interval between TEVAR and the onset of TBAD was 0.2 month (interquartile range, 0.03-0.7 month) in group A (n = 21) and 32 months (interquartile range, 4.7-35.2 months) in group B (n = 20). Except for the aortic diameter at level D in group B, favorable remodeling was obtained at both levels in both groups. The diameter change ratio of the aorta at level D was significantly greater in group A than in group B (P = .02). Receiver operating characteristic curve analysis of the interval for a significant decrease in the aortic diameter at level D yielded 4.2 months as the optimal threshold for performing TEVAR (area under the curve, 0.859; 95% confidence interval, 0.7-1.0). CONCLUSIONS: TEVAR for TBAD will result in favorable outcomes, irrespective of the timing of the procedure. However, it might be more effective to perform TEVAR within 4.2 months of the onset of TBAD, provided that the TEVAR procedure can be performed safely.

P-Selectin Glycoprotein Ligand-1 Deficiency Protects Against Aortic Aneurysm Formation Induced by DOCA Plus Salt.

PURPOSE: P-selectin glycoprotein ligand-1 (PSGL-1) acts as a crucial regulator for the inflammatory cells infiltration by mediating the adhesion of leukocytes. However, the role of PSGL-1 in aortic aneurysm remains elusive. Here, we investigated the role of PSGL-1 in aortic aneurysm (AA) development. METHODS: We first detected PSGL-1 expression in samples from aortic aneurysm patients and mouse AA models via western blotting, immunofluorescence, and flow cytometry, and then we used global PSGL-1 knockout mice and their wild type controls to establish an aortic aneurysm model induced by deoxycorticosterone acetate (DOCA) plus high salt (HS). The incidence, fatality rates, and the pathological changes of aortic aneurysm were analyzed in each group. The inflammation, adhesion molecules expression, and PSGL-1 mediated leukocyte-endothelial adhesion and their underlying mechanisms were explored further. RESULTS: Increased PSGL-1 levels were observed in human and mouse aortic aneurysm, and on leukocytes of mice treated with DOCA+HS. PSGL-1 deficiency reduced the incidence and severity of aortic aneurysm significantly, as well as decreased elastin fragmentation, collagen accumulation, and smooth muscle cells degeneration. Mechanistically, the protective effect of PSGL-1 inhibition was mediated by the reduced adhesion molecules, and the subsequently reduced leukocyte-endothelial adhesion through the NF-κB pathway, which finally led to reduced inflammatory cells infiltration and decreased inflammatory factors expression. CONCLUSION: PSGL-1 deficiency is protective against inflammatory cells migration and recruitment in the condition of AA through attenuation of leukocyte-endothelial adhesion. Inhibition of PSGL-1 may be a potential therapeutic target for the prevention and treatment of human AA.

Investigations into the Potential of Using Open Source CFD to Analyze the Differences in Hemodynamic Parameters for Aortic Dissections (Healthy versus Stanford Type A and B).

BACKGROUND: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters. METHODS: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated. RESULTS: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow. CONCLUSIONS: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.

Application of the Type, Entry Site, and Malperfusion Classification in Treatment of Aortic Dissection.

BACKGROUND: Our goal is to investigate a new practical dissection classification system, including type of dissection, location of the tear of the primary entry, and malperfusion. METHODS: The outcome of 151 patients with aortic dissection between January 2019 and May 2020 retrospectively were analyzed. All cases were classified with the Stanford dissection classification (A and B) by adding type non-A non-B. They were then further classified by the new classification system, including location of the primary Entry (E) and Malperfusion (M). All cases were followed up for six months. RESULTS: The distribution of 151 patients was 53.0%, 27.8%, and 19.2%, respectively, in type A, B, and non-A non-B. The in-hospital mortality rate was 8.8%, 2.4%, and 3.4% in type A, B, and non-A non-B (P < 0.05) and postoperative neurological complications occurred in 33.8%, 7.1%, and 13.8% in type A, B, and non-A non-B (P < 0.05). Total arch replacement was performed in 53.8%, 4.8%, and 13.8% in type A, B, and non-A non-B. The in-hospital mortality rate was 12.0%, 10.4%, and 8.5% in type E1, E2 and E3, while it was 20.0%, 10.4%, and 8.5% in type M1, M2 and M3 (P < 0.05). CONCLUSIONS: The new practical dissection classification system is useful as a supplement to the Stanford dissection classification by regarding the extent of the disease process, aiding in decision-making about the operative indication and plan, and helping in anticipating prognosis.

Inflammasomes in the Pathophysiology of Aortic Disease.

Aortic diseases comprise aneurysms, dissections, and several other pathologies. In general, aging is associated with a slow but progressive dilation of the aorta, along with increased stiffness and pulse pressure. The progression of aortic disease is characterized by subclinical development or acute presentation. Recent evidence suggests that inflammation participates causally in different clinical manifestations of aortic diseases. As of yet, diagnostic imaging and surveillance is mainly based on ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Little medical therapy is available so far to prevent or treat the majority of aortic diseases. Endovascular therapy by the introduction of covered stentgrafts provides the main treatment option, although open surgery and implantation of synthetic grafts remain necessary in many situations. Because of the risks associated with surgery, there is a need for identification of pharmaceutical targets interfering with the pathophysiology of aortic remodeling. The participation of innate immunity and inflammasome activation in different cell types is common in aortic diseases. This review will thus focus on inflammasome activities in vascular cells of different chronic and acute aortic diseases and discuss their role in development and progression. We will also identify research gaps and suggest promising therapeutic targets, which may be used for future medical interventions.

Aorta smooth muscle-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease.

Background: Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. Insufficiency of NOTCH1 expression is highly related to BAV-TAA, but the underlying mechanism remains to be clarified. Methods: A comparative proteomics analysis was used to explore the biological differences between non-diseased and BAV-TAA aortic tissues. A microfluidics-based aorta smooth muscle-on-a-chip model was constructed to evaluate the effect of NOTCH1 deficiency on contractile phenotype and mitochondrial dynamics of human aortic smooth muscle cells (HAoSMCs). Results: Protein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) partially rescued the disorders of mitochondrial dynamics in HAoSMCs derived from BAV-TAA patients. Conclusions: The aorta smooth muscle-on-a-chip model simulates the human pathophysiological parameters of aorta biomechanics and provides a platform for molecular mechanism studies of aortic disease and related drug screening. This aorta smooth muscle-on-a-chip model and human tissue proteomic analysis revealed that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA. Funding: National Key R and D Program of China, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai Science and Technology Commission, and Shanghai Municipal Education Commission.

To function properly, the heart must remain a one-way system, pumping out oxygenated blood into the aorta ­ the largest artery in the body ­ so it can be distributed across the organism. The aortic valve, which sits at the entrance of the aorta, is a key component of this system. Its three flaps (or 'cusps') are pushed open when the blood exits the heart, and they shut tightly so it does not flow back in the incorrect direction. Nearly 1.4% of people around the world are born with 'bicuspid' aortic valves that only have two flaps. These valves may harden or become leaky, forcing the heart to work harder. This defect is also associated with bulges on the aorta which progressively weaken the artery, sometimes causing it to rupture. Open-heart surgery is currently the only way to treat these bulges (or 'aneurysms'), as no drug exists that could slow down disease progression. This is partly because the biological processes involved in the aneurysms worsening and bursting open is unclear. Recent studies have highlighted that many individuals with bicuspid aortic valves also have lower levels of a protein known as NOTCH1, which plays a key signalling role for cells. Problems in the mitochondria ­ the structures that power up a cell ­ are also observed. However, it is not known how these findings are connected or linked with the aneurysms developing. To answer this question, Abudupataer et al. analyzed the proteins present in diseased and healthy aortic muscle cells, confirming a lower production of NOTCH1 and impaired mitochondria in diseased tissues. They also created an 'aorta-on-a-chip' model where aortic muscle cells were grown in the laboratory under conditions resembling those found in the body ­ including the rhythmic strain that the aorta is under because of the heart beating. Abudupataer et al. then reduced NOTCH1 levels in healthy samples, which made the muscle tissue less able to contract and reduced the activity of the mitochondria. Applying drugs that tweak mitochondrial activity helped tissues from patients with bicuspid aortic valves to work better. These compounds could potentially benefit individuals with deficient aortic valves, but experiments in animals and clinical trials would be needed first to confirm the results and assess safety. The aorta-on-a-chip model developed by Abudupataer et al. also provides a platform to screen for drugs and examine the molecular mechanisms at play in aortic diseases.

Ruptured sinus of valsalva aneurysm presenting as syncope and hypotension: a case report.

BACKGROUND: Unruptured sinus of valsalva aneurysm (SOVA) are typically asymptomatic, and hence can be easily ignored. Ruptured sinus of valsalva aneurysm (RSOVA) usually protrude into the right atrium or ventricular. However, in this case, the RSOVA protruded into the space between the right atrium and the visceral pericardium leading to compression of the right proximal coronary artery. Very few such cases have been reported till date. CASE PRESENTATION: We describe a case of ruptured right SOVA in a 61-year-old man with syncope and persistent hypotension. At the beginning, considered the markedly elevated troponin, acute myocardial infarction was considered. However, emergency coronary angiography unexpectedly revealed a large external mass compressed right coronary artery (RCA) resulting in severe proximal stenosis. Then, aorta computed tomography angiography (CTA) and urgent surgery confirmed that the ruptured right SOVA led to external compression of the right proximal coronary artery. Finally, ruptured right SOVA repair and RCA reconstruction were successfully performed, and the patient was discharged with no residual symptoms. CONCLUSIONS: It is very important to be vigilant about the existence of SOVA. RSOVA should be suspected in a patient presenting with acute hemodynamic compromise, and echocardiography should be immediately performed. Moreover, it is very important to achieve dynamic monitoring by using cardiac color ultrasound. Definitive diagnosis often requires cardiac catheterization, and an aortogram should be performed unless endocarditis is suspected.

Efficacy and Safety of Jotec E-Ventus BX Stent Graft for Iliac Branch Device Procedure: A Retrospective Clinical Study.

BACKGROUND: The endovascular aneurysm repair (EVAR) is a successful treatment for aorto-iliac aneurysms. The success of EVAR is enhanced by the use of devices that maintain the patency of targeted arteries namely the iliac branch device (IBD) With this study we aimed to evaluate the association between the use of Jotec E-ventus during EVAR with IBD and prognosis in patients with aorto-iliac aneurysms. METHODS: This is a retrospective, multicentric study enrolling patients referred to our Vascular Surgery Units from January 2015 to January 2020. All patients underwent EVAR with IBD using Jotec E-ventus as bridging stent. Primary endpoint was the development of types I and III endoleaks. Secondary endpoint was the onset of device occlusion with loss of vascular patency. RESULTS: We studied 32 patients (mean age 71.7±4.5y). Of these, 25 patients were treated with standard EVAR procedure whereas 7 were treated with isolated IBD due to extension of disease involving iliac bifurcation. Median follow-up lasted 15[IQR11-27] months. During follow-up, incidence rates for endoleaks and occlusion were 3.98(95%CI 0.48-14.41) and 1.99(95%CI 0.05-11.12) per 100 pts/year. CONCLUSIONS: Jotec E-ventus during EVAR is associated with a low rate of severe complications in a small cohort of patients with aorto-iliac aneurysms.