Temporary Reperfusion of the Aneurysm Sac as a Prevention of Spinal Cord Ischemia After Endovascular Treatment of Thoracoabdominal Aortic Aneurysm: Systematic Review and Meta-analysis.

BACKGROUND: Spinal cord ischemia (SCI) is still a feared complication for patients suffering from thoracoabdominal aortic aneurysm (TAAA) who undergo endovascular treatment. The aims of this work are to review the available literature on different reperfusion methods of the aneurysm sac, and to analyze whether the different reperfusion methods, also in combination with other factors, are effective in reducing SCI risk and if the impact varies with the patient's age. METHODS: PubMed/MEDLINE library was searched for studies published until November 2020 concerning TAAA, endovascular repair, and SCI preventive measures. Systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. Primary outcome consisted of correlation between endovascular repair techniques (type A: single step; type B: staged approach with reperfusion branches; type C: staged sequential approach with positioning of the thoracic component). A logistic-weighted regression for each event (SCI, transient, and permanent) was then performed with type of treatment, age, and interaction between them as input factors. Finally, another logistic-weighted regression was performed to analyze the other relevant factors for which observations are available together with the endovascular technique. RESULTS: Data from 53 studies with a total of 3095 patients were analyzed. Type A, type B, and type C endovascular strategies were adopted in 75%, 13%, and 12% of studied patients, respectively. Data showed that both type B and type C treatments are associated with lower risk of SCI, with a higher reduction of type C with respect to type B, although this positive trend is limited for elder patients. Moreover, a greater aortic diameter, a reduced aneurysm extent, and the absence of cerebrospinal fluid drainage positioning contribute to lower the risk of SCI. Concerning permanent SCI, both type B and type C are effective in reducing percentages for all ages, with type C treatment more beneficial for younger patients and type B for elder ones. CONCLUSION: According to the anatomy and the endovascular repair feasibility criteria, staged endovascular treatment appears to offer relevant advantages over single-step treatment in reducing the risk of SCI, regardless of the reperfusion method adopted.

Artificial Intelligence Application to Screen Abdominal Aortic Aneurysm Using Computed tomography Angiography.

The aim of our study is to validate a totally automated deep learning (DL)-based segmentation pipeline to screen abdominal aortic aneurysms (AAA) in computed tomography angiography (CTA) scans. We retrospectively evaluated 73 thoraco-abdominal CTAs (48 AAA and 25 control CTA) by means of a DL-based segmentation pipeline built on a 2.5D convolutional neural network (CNN) architecture to segment lumen and thrombus of the aorta. The maximum aortic diameter of the abdominal tract was compared using a threshold value (30 mm). Blinded manual measurements from a radiologist were done in order to create a true comparison. The screening pipeline was tested on 48 patients with aneurysm and 25 without aneurysm. The average diameter manually measured was 51.1 ± 14.4 mm for patients with aneurysms and 21.7 ± 3.6 mm for patients without aneurysms. The pipeline correctly classified 47 AAA out of 48 and 24 control patients out of 25 with 97% accuracy, 98% sensitivity, and 96% specificity. The automated pipeline of aneurysm measurements in the abdominal tract reported a median error with regard to the maximum abdominal diameter measurement of 1.3 mm. Our approach allowed for the maximum diameter of 51.2 ± 14.3 mm in patients with aneurysm and 22.0 ± 4.0 mm in patients without an aneurysm. The DL-based screening for AAA is a feasible and accurate method, calling for further validation using a larger pool of diagnostic images towards its clinical use.

Modifications in Aortic Stiffness After Endovascular or Open Aortic Repair: A Systematic Review and Meta-Analysis.

OBJECTIVE: Increased aortic stiffness (AoS) has been recognised as a risk factor in the development of cardiovascular disease. The aim of this systematic review and meta-analysis was to assess the impact of aortic repair on AoS. DATA SOURCES: PubMed, Scopus, and Web of Science were searched systematically for relevant studies evaluating the consequences of endovascular and open aortic repair on AoS. REVIEW METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement was followed to perform the research process. Papers containing data on AoS before and after both thoracic (TEVAR) and abdominal (EVAR) endovascular repair, as well as open surgical repair (OSR), were included for detailed evaluation. A fixed effects model was used to perform analysis. The Newcastle-Ottawa Scale was calculated for each included study. RESULTS: The first article cluster comprised 367 papers. After removal of duplicates and the adoption of inclusion/exclusion criteria, 14 articles remained, 13 of which were selected for meta-analysis. Ten studies analysed EVAR and three analysed TEVAR. Five of the selected papers were case control studies, with OSR adopted in four of these as the EVAR comparator. Several graft types were used in the endovascular group. AoS increased after TEVAR and EVAR, in terms of pulse wave velocity (PWV), even though several spatial levels and measurement modalities were adopted. No differences were described after OSR, although no pooled data could be analysed. CONCLUSION: EVAR and TEVAR both demonstrated a significant increase in AoS measurement (PWV). Although the heterogeneity and the low number of available studies limit the strength of the results, this review highlights the potential deleterious endograft role in the cardiovascular system although further studies are needed to achieve robust evidence. Further studies are needed to improve the mutual interaction between aorta and endograft, minimising their impact on the native aortic wall properties.

Prediction model of isolated iliac and abdominal aneurysms.

OBJECTIVES: We analyse the cardiovascular risk factors in patients undergoing screening for Isolated Iliac Aneurysm (IIA) and Abdominal Aortic Aneurysm (AAA) and propose a logistic regression model to indicate patients at risk of IIA and/or AAA. METHODS: A screening programme was carried out to identify the presence of aneurysm based on Duplex scan examination. Cardiovascular risk factors information was collected from each subject. A descriptive analysis for the incidence of IIA and AAA stratified by age and sex was carried out to evaluate factors incidence. A logistic regression model was developed to predict the probability of developing an aneurysm based on the observed risk factor levels. A threshold probability of aneurysm risk for a datum patient was also identified to effectively direct screening protocols to patients most at risk. RESULTS: A cohort of 10 842 patients was evaluated: 1.52% affected by IIA, 2.69% by AAA and 3.90% by at least one. Risk factors analysis showed that: IIA was correlated with cardiological status, diabetes, cardiovascular disease family history, and dyslipidaemia; AAA was correlated with cardiological status, body mass index, hypertension, and dyslipidaemia; diabetes and dyslipidaemia were the most relevant factors with at least one aneurysm. The prediction tool based on the logistic regression and the threshold probability predict the presence of IIA and AAA in 69.7% and 83.8% of cases, under k-fold cross-validation. CONCLUSIONS: The proposed regression model can represent a valid aid to predict IIA and AAA presence and to select patients to be screened.

Drag Forces after Thoracic Endovascular Aortic Repair. General Review of the Literature.

BACKGROUND: Despite the great evolution of endograft devices for thoracic endovascular aortic repair (TEVAR), threatening related complication such as graft migration and endoleaks still occur during follow up. The Drag Forces (DF), that is the displacement forces that play a role in graft migration and endoleaks caused by the blood flow against the thoracic graft, can be studied by means of Computational Fluid Dynamics (CFD). METHOD: A general review of papers found in current literature was performed. CFD studies available on the topic of thoracic aortic diseases and DF were analyzed. All anatomic, hemodynamics or graft related factors which could have an impact on DF were reported. RESULTS: Different factors deeply influence DF magnitude in the different site of the Ishimaru's zones classification: angulation, tortuosity and length of the landing zone, graft diameter, length and deployment position, blood pressure, pulse waveform, blood viscosity and patient heart rate have been related to the magnitude of DF. Moreover, also the three-dimensional orientation of DF is emerging as a fundamental issue from CFD studies. DF can be divided in sideways and upward components. The former, even of higher magnitude in zone 0, maintain always an orthogonal orientation and does not change in any type of aortic arch; the latter result strictly related to the anatomic complexity of the aortic arch with values up to four times higher in zone 3. CONCLUSION: Different DF magnitude and orientation could explain how TEVAR have higher rate of migration and endoleaks when we face with more complex aortic anatomies. All these aspects should be foreseen during the planning of TEVAR procedure. In this field, collaboration between physicians and engineers is crucial, as both parts have a primary role in understanding and describing hidden aspects involved in TEVAR procedures.

Geometrical Evaluation of Aortic Sac Remodeling During Two-Step Thoracoabdominal Aortic Aneurysm Endovascular Repair.

BACKGROUND: The present study evaluates aneurysmal sac remodeling and the loss of the intercostal arteries after the first step of staged treatment of thoracoabdominal aortic aneurysms (TAAAs). The purpose of this approach is to keep the aneurysmal sac temporarily perfused to induce progressive thrombosis of the aneurysm while simultaneously allowing the spinal cord to establish adequate perfusion thereby promoting the development of collateral circulation. METHODS: All patients with type II or type III TAAAs, having undergone 2-step endovascular treatment with at least a 2-branch endoprosthesis at our institution between April 2017 and May 2019, were retrospectively evaluated. Thirty-day mortality and spinal cord ischemia was assessed. The mean number of the intercostal and lumbar arteries, coverage length between the left subclavian artery and the stent graft proximal landing zone, total volume of the aneurysmal sac, lumen volume, and thrombosis volume were measured by preoperative and first-step postoperative computed tomography angiography. Patients were also grouped based on the chosen endoprosthesis (group A: double-branch aneurysmal sac reperfusion; group B: single-branch aneurysmal sac reperfusion). RESULTS: Eleven patients (mean age: 76.5 years; range: 61-86) were considered. No 30-day mortality was observed after the first-step procedure, and 1 patient died after second-step treatment. No permanent paraplegia was observed after either the first or second endovascular steps. The lumen volume significantly decreased (27%; P < 0.001) after first-step endovascular treatment although there was a significant increase in aneurysm thrombosis (34% to 54%). The mean number of the intercostal arteries decreased from 19.7 to 9.3 (P < 0.001) after first-step endovascular treatment. Volume variations and percentage of intercostal loss did not significantly differ between the 2 groups. CONCLUSIONS: Although aneurysm volume continued to increase after first-step treatment, two-step endovascular treatment is a feasible alternative to reduce the risk of severe ischemia in patients with extended TAAAs.

Endovascular Treatment of an Internal Iliac Artery Aneurysm in a Patient with Previous Aortic Surgery Using a Novel Covered Stent Graft.

BACKGROUND: We report endovascular treatment of a patient with an isolated Internal Iliac Artery (IIA) aneurysm who was treated by positioning a novel covered stent that could adapt to different proximal and distal diameters. CASE REPORT: A 68-year-old man who had already had several previous aortic surgeries underwent endovascular treatment for a 41 mm isolated right IIA aneurysm. Two Viabahn VBX (W. L. Gore & Associates, Flagstaff, AZ) covered stents (7 × 79 mm and 8Lx59 mm) were placed from a 6 mm gluteal artery to an 11 mm Dacron hypogastric artery via contralateral femoral surgical access. No complications occurred. One-month follow-up computed tomography angiography (CTA) scan showed the complete exclusion of the aneurysmal sac with spontaneous endoleak resolution and patency of the covered stents. Geometric analysis of the postoperative CTA highlighted VBX conformability to the native vessel. Maximum stented vessel diameter ranged between 9 and 13 mm, and circularity was maintained along the whole stent length, even in zones of higher centerline curvature. CONCLUSIONS: The Viabahn VBX covered stent could be used to treat aneurysms of the IIA.

Brassica rapa hairy root based expression system leads to the production of highly homogenous and reproducible profiles of recombinant human alpha-L-iduronidase.

The Brassica rapa hairy root based expression platform, a turnip hairy root based expression system, is able to produce human complex glycoproteins such as the alpha-L-iduronidase (IDUA) with an activity similar to the one produced by Chinese Hamster Ovary (CHO) cells. In this article, a particular attention has been paid to the N- and O-glycosylation that characterize the alpha-L-iduronidase produced using this hairy root based system. This analysis showed that the recombinant protein is characterized by highly homogeneous post translational profiles enabling a strong batch to batch reproducibility. Indeed, on each of the 6 N-glycosylation sites of the IDUA, a single N-glycan composed of a core Man3 GlcNAc2 carrying one beta(1,2)-xylose and one alpha(1,3)-fucose epitope (M3XFGN2) was identified, highlighting the high homogeneity of the production system. Hydroxylation of proline residues and arabinosylation were identified during O-glycosylation analysis, still with a remarkable reproducibility. This platform is thus positioned as an effective and consistent expression system for the production of human complex therapeutic proteins.

In Vivo Morphological Changes of the Femoropopliteal Arteries due to Knee Flexion After Endovascular Treatment of Popliteal Aneurysm.

Purpose: To evaluate morphological changes of the femoropopliteal (FP) arteries due to limb flexion in patients undergoing endovascular treatment of popliteal artery aneurysms (PAAs). Materials and Methods: Seven male patients (mean age 68 years) underwent endovascular treatment of PAA with a Viabahn stent-graft between January 2013 and December 2017. During follow-up, one contrast-enhanced computed tomography angiography (CTA) scan of the lower limbs was acquired for each recruited patient. A standardized CTA protocol for acquisitions in both straight-leg and bent-leg positions was used to visualize changes in artery shape due to limb flexion. Three-dimensional reconstruction of the FP segment was performed to compute mean diameter and eccentricity of the vascular lumen and to measure length, tortuosity, and curvature of the vessel centerline in 3 arterial zones: (A) between the origin of the superficial femoral artery and the proximal end of the stent-graft, (B) within the stent-graft, and (C) from the distal end of the stent-graft to the origin of the anterior tibial artery. Results: After limb flexion, all zones of the FP segment foreshortened: 6% in zone A (p=0.001), 4% in zone B (p=0.001), and 8% in zone C (p=0.07), which was the shortest (mean 4.5±3.6 cm compared with 23.8±5.7 cm in zone A and 23.6±7.4 cm in zone B). Tortuosity increased in zone A (mean 0.03 to 0.05, p=0.03), in zone B (0.06 to 0.15, p=0.005), and in zone C (0.027 to 0.031, p=0.1). Mean curvature increased 15% (p=0.05) in zone A, 27% (p=0.005) in zone B, and 95% (p=0.06) in zone C. In all zones, the mean artery diameter and eccentricity were not significantly affected by limb flexion. Conclusion: Limb flexion induces vessel foreshortening and increases mean curvature and tortuosity of the FP segment both within and outside the area of the stent-graft.

Twelve-year Follow-up Post-Thoracic Endovascular Repair in Type B Aortic Dissection Shown by Three-dimensional Printing.

BACKGROUND: Thoracic endovascular repair (TEVAR) is currently considered the therapy of choice for complicated type B acute aortic dissection (TBAAD). Although several papers have reported good outcomes at short- and medium-term follow-up, some questions still remain regarding the long-term durability and re-intervention rate during follow-up. METHODS: We describe a case of a patient originally treated with TEVAR for TBAAD complicated by impending aortic rupture. RESULTS: Endovascular repair successfully excluded the flow through the primary entry tear but during the 12-year follow-up period the patient experienced several complications and re-interventions. Various full-size three-dimensional (3D) models of the patient-specific vasculature were printed to better explain the different interventional interventions over the 12 years of follow-up and as a hands-on tool for medical education. CONCLUSIONS: The present case report, involving long-term follow-up, provides an example of the effectiveness and the safety of TEVAR for the treatment of complicated TBAAD shown at short and medium-term follow-up. However, the long-term complications that were observed in this patient during follow-up support the importance of lifelong CTA surveillance. Furthermore, this study confirms the capability of 3D printing technology as a powerful tool to support communication with patients and residents' education through the physical analysis of the real cases.

Midterm outcomes and evolution of gutter area after endovascular aneurysm repair with the chimney graft procedure.

OBJECTIVE: The objective of this study was to describe our experience with endovascular aneurysm repair (EVAR) with the use of chimney grafts for branch vessel preservation. METHODS: Patients treated with a chimney graft procedure between October 2009 and May 2015 were included for analysis. Patients who were not considered eligible for open surgical repair or for conventional, branched, or fenestrated endovascular repair were selected. A standardized operating procedure with left brachial or axillary artery cutdown access for the chimney grafts and bilateral femoral artery cutdown access for the aortic main device was used. Outcomes were noted according to the Society for Vascular Surgery reporting standards. In addition, evolution of gutter area over time was determined. Estimated rates of survival, freedom from aneurysm growth, and clinical success at 24 months of follow-up were calculated. RESULTS: Thirty-three patients (mean age, 77.6 ± 6.8 years; 87.9% male) with a mean preoperative maximum aneurysm diameter of 71.7 ± 13.5 mm were included. A total of 54 of an intended 54 chimney grafts were deployed. Primary technical success and 30-day secondary clinical success rates were 87.9% and 84.8%, respectively. The early mortality rate was 6.1% (n = 2). The early type IA endoleak rate was 6.1% (n = 2), and the chimney graft occlusion rate was 6.1% (n = 2). Median follow-up duration was 26 months (interquartile range, 14.8-37.3 months). The estimated 2-year actuarial survival rate was 78.1% (standard error, ±7.4%). Late complications included type IA endoleak (n = 1), chimney graft occlusion (n = 2), type II endoleak with aneurysm growth (n = 4), and distal stent graft limb kinking and occlusion (n = 1). Late reinterventions included coil or glue embolization (n = 3), distal limb extension (n = 2), open endoleak ligation (n = 2), Palmaz stent placement (n = 1), repeated EVAR (n = 1), and femorofemoral bypass graft (n = 1). At 2 years, the estimated secondary clinical success and freedom from aneurysm growth rates were 80.5% (±7.2%) and 84.4% (±7.2%). Gutter size showed a small but significant decrease over time at the level of the proximal markers and at 10 mm distal from the markers. CONCLUSIONS: Midterm results show that a standardized procedure for EVAR using chimney grafts for branch vessel preservation is an acceptable option for high-risk patients with large, complex aneurysms who are unfit for open repair and who have been excluded from fenestrated EVAR. Gutter size decreases over time, but the rate of branch vessel loss and reinterventions demonstrate that this approach should remain reserved for those who are at truly prohibitive risk for open or fenestrated stent graft repair.

Comparative Analysis of Porcine and Human Thoracic Aortic Stiffness.

OBJECTIVES: To compare porcine and human thoracic aortic stiffness using the available literature. METHODS: The available literature was searched for studies reporting data on porcine or human thoracic aortic mechanical behaviour. A four fibre constitutive model was used to transform the data from included studies. Thus, equi-biaxial stress stretch curves were generated to calculate circumferential and longitudinal aortic stiffness. Analysis was performed separately for the ascending and descending thoracic aorta. Data on human aortic stiffness were divided by age <60 or ≥60 years. Porcine and human aortic stiffness were compared. RESULTS: Eleven studies were included, six reported on young porcine aortas, four on human aortas of various ages, and one reported on both. In the ascending aorta, circumferential and longitudinal stiffness were 0.42±0.08 MPa and 0.37±0.06 MPa for porcine aortas (4-9 months) versus 0.55±0.15 MPa and 0.45±0.08 MPa for humans <60 years, and 1.02±0.59 MPa and 1.03±0.54 MPa for humans ≥60 years. In the descending aorta, circumferential and longitudinal stiffness were 0.46±0.03 MPa and 0.44±0.01 MPa for porcine aortas (4-10 months) versus 1.04±0.70 MPa and 1.24±0.76 MPa for humans <60 years, and 3.15±3.31 MPa and 1.17±0.31 MPa for humans ≥60 years. CONCLUSIONS: The stiffness of young porcine aortic tissue shows good correspondence with human tissue aged <60 years, especially in the ascending aorta. Young porcine aortic tissue is less stiff than human aortic tissue aged ≥60 years.

The Modified Arch Landing Areas Nomenclature (MALAN) Improves Prediction of Stent Graft Displacement Forces: Proof of Concept by Computational Fluid Dynamics Modelling.

OBJECTIVE: To assess whether the Modified Arch Landing Areas Nomenclature (MALAN), which merges Ishimaru's map with the Aortic Arch Classification, predicts the magnitude of displacement forces and their orientation in proximal landing zones for TEVAR. METHODS: Computational fluid dynamic (CFD) modelling was employed to prove the hypothesis. Healthy aorta CT angiography scans were selected based on aortic arch geometry to reflect Types I to III arches equally (each n = 5). CFDs were used to compute pulsatile displacement forces along the Ishimaru's landing zones in each aorta including their three dimensional orientation along the upward component and sideways component. Values were normalised to the corresponding aortic wall area to calculate equivalent surface traction (EST). RESULTS: In Types I and II arches, EST did not change across proximal landing zones (p = .297 and p = .054, respectively), whereas in Type III, EST increased towards more distal landing zones (p = .019). Comparison of EST between adjacent zones, however, showed that EST was greater in 3/II than in 2/II (p = .016), and in 3/III than in 2/III (p = .016). Notably, these differences were related to the upward component, that was four times greater in 3/II compared with 2/II (p < .001), and five times greater in 3/III compared with 2/III (p < .001). CONCLUSION: CFD modelling suggests that MALAN improves discrimination of expected displacement forces in proximal landing zones for TEVAR, which might influence clinical outcomes. The clinical relevance of the finding, however, remains to be validated in a dedicated post-operative outcome analysis of patients treated by TEVAR of the arch.

Midterm Follow-up Geometrical Analysis of Thoracoabdominal Aortic Aneurysms Treated with Multilayer Flow Modulator.

BACKGROUND: Aim of our study is the analysis of clinical results and aneurysmal sac evolution after multilayer flow modulator (MFM) placement, in patients with thoracoabdominal aortic aneurysms (TAAs). METHODS: All patients with asymptomatic TAA treated at our institution between 2012 and 2014 with MFM were retrospectively analyzed. Thirty-day evaluated outcomes were mortality and complications. Follow-up evaluated outcomes were mortality, aneurysm collateral branches patency, and reintervention. A geometrical analysis of 2-year follow-up computed tomography scans was carried out to evaluate the total aneurysm volume, the percentage of aneurysm growth, and the evolution of maximum aneurysm diameter. RESULTS: Seven patients (mean age: 71.8 years, range: 63-85 years) were considered in the study. Mean preoperative aneurysm diameter was 6.8 cm (range 6-8.3 cm). No 30-day mortality or complications were observed. Mean follow-up was 29.4 months. During follow-up, 3 deaths (42.8%) were observed, not related to MFM complications. Reintervention rate was 42.8%, occurred in all cases after 2-year follow-up; in 2 cases, the reintervention was necessary due to an excessive increase of the aneurysmal sac. During the follow-up, a mean growth rate of 6 mm/year (4 patients) for the diameter of the aneurysm external wall and a total aneurysm volume increase from 2.45 × 105 mm3 to 3.50 × 105 mm3 (4 patients) was evaluated. CONCLUSIONS: Our results have shown no mortality related to aneurysm rupture during the follow-up and high rate of reinterventions after MFM placement. Further geometrical analyses, based on the proposed approach, regarding a larger group of patients with long-term follow-up are required to draw indications about the MFM use.

Aortic Expansion Induces Lumen Narrowing in Anomalous Coronary Arteries: A Parametric Structural Finite Element Analysis.

Anomalous aortic origin of coronary arteries (AAOCA) is a congenital disease that can lead to cardiac ischemia during intense physical activity. Although AAOCA is responsible for sudden cardiac death (SCD) among young athletes and soldiers, the mechanisms underlying the coronary occlusion during physical effort still have to be clarified. The present study investigates the correlation between geometric features of the anomaly and coronary lumen narrowing under aortic root dilatations. Idealized parametric computer-aided designed (CAD) models of the aortic root with anomalous and normal coronaries are created and static finite element (FE) simulations of increasing aortic root expansions are carried out. Different coronary take-off angles and intramural penetrations are investigated to assess their role on coronary lumen narrowing. Results show that increasing aortic and coronary pressures lead to lumen expansion in normal coronaries, particularly in the proximal tract, while the expansion of the anomalous coronaries is impaired especially at the ostium. Concerning the geometric features of the anomaly, acute take-off angles cause elongated coronary ostia, with an eccentricity increasing with aortic expansion; the impact of the coronary intramural penetration on the lumen narrowing is limited. The present study provides a proof of concept of the biomechanical reasons underlying the lumen narrowing in AAOCA during aortic expansion, promoting the role of computational simulations as a tool to assess the mechanisms of this pathology.

Impact of Thoracic Endovascular Aortic Repair on Pulsatile Circumferential and Longitudinal Strain in Patients With Aneurysm.

PURPOSE: To quantify both pulsatile longitudinal and circumferential aortic strains before and after thoracic endovascular aortic repair (TEVAR), potentially clarifying TEVAR-related complications. METHODS: This retrospective study assessed the impact of TEVAR on pulsatile aortic strains through custom developed software and cardiac-gated computed tomography imaging of 8 thoracic aneurysm patients (mean age 71.0±8.2 years; 6 men) performed before TEVAR and during follow-up (median 0.1 months, interquartile range 0.1-5.8). Lengths of the ascending aorta, the aortic arch, and the descending aorta were measured. Diameters and areas were computed at the sinotubular junction, brachiocephalic trunk, left subclavian artery, and the celiac trunk. Pulsatile longitudinal and circumferential strains were quantified as systolic increments of length and circumference divided by the corresponding diastolic values. RESULTS: Average pulsatile longitudinal strain ranged from 1.4% to 7.1%, was highest in the arch (p<0.001), and increased after TEVAR by 77% in the arch (7.1%±2.5% vs 12.5%±5.1%, p=0.04) and by 69% in the ascending aorta (5.6±2.3% vs 9.4±4.4%, p=0.06). Average pulsatile circumferential strain ranged from 3.6% to 5.0% before TEVAR and did not differ significantly throughout the thoracic aorta; there was a nonsignificant increase after TEVAR at the unstented sinotubular junction (5.0%±1.4% vs 6.3%±1.0%, p=0.18), with a significant increase at the celiac trunk (3.6%±1.8% vs 6.2%±1.8%, p=0.02). Pulsatile circumferential strains within stented segments were deemed unreliable due to image artifacts. CONCLUSION: TEVAR was associated with an increase of pulsatile longitudinal strains (in the arch) and circumferential strains (at the celiac trunk) in unstented aortic segments. These observations suggest increased pulsatile wall stress after TEVAR in segments adjacent to the device, which may contribute to the understanding of stent-graft-related complications such as retrograde dissection, aneurysm formation, and rupture.

Stent-Graft Deployment Increases Aortic Stiffness in an Ex Vivo Porcine Model.

BACKGROUND: Aortic stiffness is an independent predictor of cardiovascular mortality. In this study, the effect of thoracic endovascular aortic repair (TEVAR) on aortic stiffness is investigated by measuring aortic pulse wave velocity (PWV) in an ex vivo porcine model. METHODS: Fifteen fresh porcine thoracic aortas were connected to a benchtop pulsatile system. Intraluminal pressures were recorded in the ascending aorta and at the celiac trunk using a needle connected to a pressure sensor. The distance between the needles was divided by the time difference between the base of the pressure peaks to calculate aortic PWV at baseline and after stent-graft deployment and distal stent-graft extension. RESULTS: Mean aortic PWV was 5.0 m/s at baseline. PWV increased by 4% after proximal stent-graft deployment (P = 0.09) and by 18% after stent-graft extension (P < 0.001). Pulse pressure in the nonstented ascending aorta increased by 11.0 ± 1.2 mm Hg after proximal stent-graft deployment (P < 0.001) and by 17.3 ± 1.5 mm Hg after stent-graft extension (P < 0.001). The increases in PWV and pulse pressure showed a positive linear correlation with the percentage of stent-graft coverage (P < 0.001 and P < 0.001). CONCLUSIONS: In this experimental setup, aortic stiffness increased after stent-graft deployment, dependent on the percentage of the aorta that was covered by stent graft. These results show that TEVAR leads to significant changes in aortic hemodynamics, which merits evaluation in the clinical setting.

13C NMR and LC-MS Profiling of Stilbenes from Elicited Grapevine Hairy Root Cultures.

Resveratrol and related oligostilbenes are defense molecules produced by grapevine in response to stresses including various elicitors or signal molecules. Together with their prominent role in planta, these compounds have been the center of much attention in recent decades due to their pharmacological properties. The cost-effective production of resveratrol derivatives such as viniferins or more structurally complex stilbene oligomers remains a challenging task. In this study, the chemical diversity of stilbenes produced by Vitis vinifera Pinot Noir hairy roots was investigated after elicitation for 4 days with a mixture of methyl jasmonate (100 µM) and cyclodextrins (50 mM). Two crude extracts obtained from the culture medium and from the hairy roots were fractionated by centrifugal partition chromatography. The fractions were chemically investigated by two complementary identification approaches involving a 13C NMR-based dereplication method and liquid chromatography coupled to mass spectrometry (LC-MS). In total, groups of 21 and 18 molecules, including flavonoids and stilbenes, were detected in the culture medium and root extracts, respectively. These included resveratrol monomers, dimers, trimers, and a tetramer, thus highlighting the ability of elicited hairy root culture systems to synthesize a wide diversity of secondary metabolites of pharmaceutical significance. The main compounds were unambiguously identified as trans-resveratrol, ε-viniferin, trans-piceatannol, pallidol, scirpusin A, eriodictyol, naringenin, vitisin B, and maackin.

Activities at Thoracic Aortic Research Center, IRCCS Policlinico San Donato.

The Thoracic Aortic Research Center (TARC) of the IRCCS Policlinico San Donato (PSD) aims to promote research on thoracic aortic diseases, to disclose the scientific knowledge and clinical experience and to develop new scientific paths within the Hospital and the aortic community, in collaboration with other national and international centres. Thoracic Aortic Research Center collaborates with many centres in both Europe (e.g. University of Utrecht, the Netherlands) and the USA (e.g. University of Michigan). This has led to multiple highly regarded publications in respected cardiovascular journals and has led to several PhD programmes resulting in doctorate degrees. Within Italy, in association with the Bioengineering School of the University of Pavia, TARC has founded the "BETA-lab" (Biomechanics for Endovascular Treatment of the Aorta laboratory), where MDs, Bioengineers, and PhD fellows conduct experimental studies using in vitro/ex vivo models of the physiologic aorta and aortic diseases. Furthermore, a database (iCardiocloud) where the medical imaging of cardiovascular patients from the PSD is structured, for in silico analysis utilizing computational fluid dynamics, and in vitro studies using also 3D printed aortic models. With the role of principal investigator or co-investigator, TARC at PSD has been participating in other several projects, including the International Registry of Acute Aortic Dissection, the International Aortic Arch Surgery Study Group, the European Registry of Endovascular Aortic Repair Complications, the ADSORB and ASSIST trials, and the GREAT registry. International collaborations have included also studies on predictors of aortic growth after dissection with the Yale University and University of Virginia, and on aortic biomarkers with the University of Tokyo.

Enhanced Stilbene Production and Excretion in Vitis vinifera cv Pinot Noir Hairy Root Cultures.

Stilbenes are defense molecules produced by grapevine in response to stresses including various elicitors and signal molecules. Together with their prominent role in planta, stilbenes have been the center of much attention in recent decades due to their pharmaceutical properties. With the aim of setting up a cost-effective and high purity production of resveratrol derivatives, hairy root lines were established from Vitis vinifera cv Pinot Noir 40024 to study the organ-specific production of various stilbenes. Biomass increase and stilbene production by roots were monitored during flask experiments. Although there was a constitutive production of stilbenes in roots, an induction of stilbene synthesis by methyl jasmonate (MeJA) after 18 days of growth led to further accumulation of ε-viniferin, δ-viniferin, resveratrol and piceid. The use of 100 µM MeJA after 18 days of culture in the presence of methyl-ß-cyclodextrins (MCDs) improved production levels, which reached 1034µg/g fresh weight (FW) in roots and 165 mg/L in the extracellular medium, corresponding to five-and 570-foldincrease in comparison to control. Whereas a low level of stilbene excretion was measured in controls, addition of MeJA induced excretion of up to 37% of total stilbenes. The use of MCDs increased the excretion phenomenon even more, reaching up to 98%. Our results demonstrate the ability of grapevine hairy roots to produce various stilbenes. This production was significantly improved in response to elicitation by methyl jasmonate and/or MCDs. This supports the interest of using hairy roots as a potentially valuable system for producing resveratrol derivatives.