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Objective: As thoracic aortic disease (TAD) is generally asymptomatic, biomarkers are needed to provide insight into early progression. We aimed to examine the association between circulating blood biomarkers and the maximal thoracic aortic diameter (TADmax)., Methods: In this cross-sectional study, consecutive adult patients with a thoracic aortic diameter ≥40 mm and/or genetically proven hereditary TAD (HTAD) visiting our specialised outpatient clinic between 2017 and 2020 were prospectively included. Venous blood sampling and CT angiography and/or transthoracic echocardiography of the aorta were performed. Linear regression analyses were performed and estimates were presented as mean difference in TADmax in mm per doubling of standardised biomarker level., Results: In total, 158 patients were included (median age 61 (50.3-68.8) years, 37.3% female). HTAD diagnosis was confirmed in 36 of 158 (22.7%) patients. TADmax was 43.9±5.2 mm in men vs 41.9±5.1 in women (p=0.030). In unadjusted analysis, significant associations with TADmax were found for interleukin-6 (1.15 (95% CI 0.33 to 1.96), p=0.006), growth differentiation factor-15 (1.01 (95% CI 0.18 to 1.84), p=0.018), microfibrillar-associated protein 4 (MFAP4) (-0.88 (95% CI -1.71 to 0.05), p=0.039) and triiodothyronine (T3) (-2.00 (95%CI -3.01 to 0.99), p<0.001). The association of MFAP4 with TADmax was stronger in women (p for interaction=0.020) and for homocysteine, an inverse association with TADmax was observed when compared with men (p for interaction=0.008). When adjusted for age, sex, hyperlipidaemia and HTAD, total cholesterol (1.10 (95% CI 0.27 to 1.93), p=0.010) and T3 (-1.20 (95% CI -2.14 to 0.25), p=0.014) were significantly associated with TADmax., Conclusions: Circulating biomarkers indicative of inflammation, lipid metabolism and thyroid function might be associated with TAD severity. Possible distinct biomarker patterns for men and women warrant further investigation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Vascular smooth muscle cells are exposed to interstitial flow across aortic walls. Fluid shear stress changes the phenotype of smooth muscle cells to the synthetic type; hence, the fast interstitial flow might be related to aortic diseases. In this study, we propose a novel method to directly measure the interstitial flow velocity from the spatiotemporal changes in the concentration of a fluorescent dye. The lumen of a mouse thoracic aorta was filled with a fluorescent dye and pressurized in ex vivo. The flow of the fluorescent dye from the intimal to the adventitial sides was successfully visualized under a two-photon microscope. The flow velocity was determined by applying a one-dimensional advection-diffusion equation to the kymograph obtained from a series of fluorescent images. The results confirmed a higher interstitial flow velocity in the aortic walls under higher intraluminal pressure. A comparison of the interstitial flow velocity in the radial direction showed faster flow on the more intimal side, where hyperplasia is often found in hypertension. These results indicate that the proposed method can be used to visualize the interstitial flow directly and thus, determine the local interstitial flow velocity., (© 2022. The Author(s).)

Mid-aortic syndrome (MAS) is a rare condition characterized by stenosis of the distal thoracic and/or abdominal aorta. Williams-Beuren syndrome (WBS) is a relatively rare cause of MAS. We report a case of incidentally diagnosed MAS caused by WBS without typical manifestations caused by an atypical small-sized deletion in chromosome 7q11.23, which was initially misdiagnosed as Takayasu arteritis.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable technique for management of noncompressible torso hemorrhage. The major limitation of the current unilobed fully occlusive REBOA catheters is below-the-balloon ischemia-reperfusion complications. We hypothesized that partial aortic occlusion with a novel bilobed partial (p)REBOA-PRO would result in the need for less intraaortic balloon adjustments to maintain a distal goal perfusion pressure as compared with currently available unilobed ER-REBOA., Methods: Anesthetized (40-50 kg) swine randomized to control (no intervention), ER-REBOA, or pREBOA-PRO underwent supraceliac aortic injury. The REBOA groups underwent catheter placement into zone 1 with initial balloon inflation to full occlusion for 10 minutes followed by gradual deflation to achieve and subsequently maintain half of the baseline below-the-balloon mean arterial pressure (MAP). Physiologic data and blood samples were collected at baseline and then hourly. At 4 hours, the animals were euthanized, total blood loss and urine output were recorded, and tissue samples were collected., Results: Baseline physiologic data and basic laboratories were similar between groups. Compared with control, interventions similarly prolonged survival from a median of 18 minutes to over 240 minutes with comparable mortality trends. Blood loss was similar between partial ER-REBOA (41%) and pREBOA-PRO (51%). Partial pREBOA-PRO required a significantly lower number of intraaortic balloon adjustments (10 ER-REBOA vs. 3 pREBOA-PRO, p < 0.05) to maintain the target below-the-balloon MAP. The partial ER-REBOA group developed significantly increased hypercapnia, fibrin clot formation on TEG, liver inflammation, and IL-10 expression compared with pREBOA-PRO., Conclusion: In this highly lethal aortic injury model, use of bilobed pREBOA-PRO for a 4-hour partial aortic occlusion was logistically superior to unilobed ER-REBOA. It required less intraaortic balloon adjustments to maintain target MAP and resulted in less inflammation.

This case highlights the importance of diagnosing Grade I aortic injuries after trauma. Although the prognosis for minimal aortic injury is typically quite good, the patient in this case suffered the unlikely complication of minimal intimal injury progression with resultant thromboembolism and massive stroke. Due to motion artifact and CT resolution limitations, the initial aortic injury was not detected. Thus, potentially life-saving measures such as serial CT monitoring of injury, blood pressure control, and endovascular repair were unable to be performed. This is a demonstration of the unfortunate complications of minimal aortic injury., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Background: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations., Methods: We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells., Results: Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta., Conclusions: We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions.

Objective: To evaluate the early results of fenestrated endovascular aortic repair (FEVAR) using physician-modified stent grafts (PMSGs) for the treatment of patients with thoracoabdominal pathologies. Methods: Nineteen consecutive patients who underwent FEVAR using PMSGs between April 2012 and September 2017 were retrospectively reviewed. The modality of FEVAR technique was assessed, perioperative clinical data was recorded and the early results were evaluated. Results: Indications were thoracoabdominal aortic pathologies, including juxtarenal abdominal aortic aneurysm (JAAA) ( n =12), chronic thoracoabdominal aortic dissection with aneurysmal dilatation ( n =3), thoracoabdominal aortic aneurysm (TAAA) ( n =1), infrarenal AAA with an accessory renal artery in the segment of the aneurysmal neck ( n =2) and type Ⅰ endoleak after EVAR for AAA( n =1). Nineteen fenestrated stent grafts were deployed , including custom-made Cook Zenith fenestrated stent graft( n =1), home-made Cook Zenith TX2 fenestrated stent graft( n =6), home-made Cook Zenith TFFB fenestrated stent graft( n =9), home-made Cook Zenith Cuff fenestrated stent graft( n =2), home-made Gore C3 fenestrated stent graft( n =1). Mean duration for stent graft modification was 110 (90-140) min. Mean operative time was 268.0 (59.0-334.0) min, and fluoroscopy time was 66.0 (15.0-175.0) min. There were a total of 50 target vessels, of which 45 (95%) were stented. Bare metal stents were used in 28 vessels, and covered stents were used in 17 vessels. Technical success rate was 100%. No intraoperative target vessel loss was observed. Perioperative mortality was 5.3% (1/19). Endoleaks were persisted even after ballooning in five patients. A small type Ⅰ proximal endoleak and type Ⅲ endoleak were found in 2 and 1 patients, respectively. Type Ⅲ endoleak combined with type Ⅱ endoleak were observed in 2 patients. All the endoleaks were accepted and needed watching. In two patients, iliofemoral artery problems were resolved after local endarterectomy and stenting. Two patients presented renal deterioration postoperatively and recovered after the conservative therapy. Median length of stay was 6.6 (2.0-12.0)d. No early reintervention (<30 days) was performed. The mean duration of follow-up was 11.2 (2.0-41.0) months. One patient died 6 months after FEVAR due to advanced renal carcinoma. All target vessels remained patent except for one accessory artery occlusion. Conclusion: FEVAR using PMSGs may be a viable alternative for high-risk patients with thoracoabdominal pathologies.

Purpose: Valve mediated hemodynamics have been postulated to contribute to pathology of the ascending aorta (AAo). The objective of this study is to assess the association of aortic valve morphology and hemodynamics with downstream AAo size in subjects with bicuspid aortic valve (BAV) disease., Materials and Methods: Four-dimensional flow MRI at 1.5 or 3 Tesla was used to evaluate the hemodynamics in the proximal AAo of 52 subjects: size-matched controls with tricuspid aortic valves (n = 24, mid ascending aorta [MAA] diameter = 38.0 ± 4.9 mm) and BAV patients with aortic dilatation (n = 14 right and left coronary leaflet fusion [RL]-BAV, MAA diameter = 38.1 ± 5.3 mm; n = 14 right and noncoronary leaflet fusion [RN]-BAV, MAA diameter = 36.5 ± 6.6 mm). A validated semi-automated technique was used to evaluate hemodynamic metrics (flow angle, flow displacement, and jet quadrant) and valve morphology (orifice circularity) for all subjects. Regression analysis of these metrics to AAo diameter was performed., Results: RN-BAV subjects displayed a stronger correlation between hemodynamic metrics in the proximal AAo with diameter in the distal AAo compared with size-matched tricuspid aortic valve (TAV) controls and RL-BAV subjects. The distal AAo diameter was found to be strongly correlated to the upstream flow displacement (R 2 adjusted = 0.75) and flow angle (R 2 adjusted = 0.66) measured at the sino-tubular junction (STJ). Orifice circularity was also strongly correlated (R 2 adjusted = 0.53) to the distal AAo diameter in RN-BAV subjects. For TAV controls and RL-BAV subjects, correlations were weaker (R 2 adjusted < 0.2)., Conclusion: Hemodynamics in the STJ were strongly correlated to the distal AAo diameter for the RN-BAV subjects. Hemodynamic metrics were more strongly correlated to the downstream aortic size when compared with valve morphology metrics., Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:246-254., (© 2017 International Society for Magnetic Resonance in Medicine.)

Aortic size increases with age, but factors related to such dilatation in healthy young adult population have not been studied. We aim to evaluate changes in aortic dimensions and its principal correlates among young adults over a 20-year time period. Reference values for aortic dimensions in young adults by echocardiography are also provided. Healthy Coronary Artery Risk Development in Young Adults (CARDIA) study participants aged 23 to 35 years in 1990-1991 (n=3051) were included after excluding 18 individuals with significant valvular dysfunction. Aortic root diameter (ARD) by M-mode echocardiography at year-5 (43.7% men; age, 30.2 ± 3.6 years) and year-25 CARDIA exams was obtained. Univariable and multivariable analyses were performed to assess associations of ARD with clinical data at years-5 and -25. ARD from year-5 was used to establish reference values of ARD in healthy young adults. ARD at year-25 was greater in men (33.3 ± 3.7 versus 28.7 ± 3.4 mm; P<0.001) and in whites (30.9 ± 4.3 versus 30.5 ± 4.1 mm; P=0.006). On multivariable analysis, ARD at year-25 was positively correlated with male sex, white ethnicity, age, height, weight, 20-year gain in weight, active smoking at baseline, and 20-year increase in diastolic, systolic, and mean arterial pressure. A figure showing the estimated 95th percentile of ARD by age and body surface area stratified by race and sex is provided. This study demonstrates that smoking, blood pressure, and increase in body weight are the main modifiable correlates of aortic root dilation during young adulthood. Our study also provides reference values for ARD in young adults., (© 2015 American Heart Association, Inc.)

Background: Aortic dissection type A is a disease with high mortality. Iatrogenic aortic dissection after interventional procedures is infrequent, and prognostic data are scarce. Our objective was to analyze its incidence, patient profile, and long-term prognosis., Methods and Results: Between 2000 and 2014, we retrospectively analyzed 74 patients with dissection of the ascending aorta. Clinical and procedural data were reviewed, and later, we performed a prospective clinical follow-up by telephone or in the office. The incidence of aortic dissection was 0.06%. Our patients, predominantly male (67.6%), had a mean age of 66.9±10.8 years. With multiple cardiovascular risk factors, the main reason for cardiac catheterization was an acute coronary syndrome (n=54). The complication was detected acutely in all, trying to engage the right coronary artery in 47 and the left main artery in 30 and after other maneuvers in 2, mostly complex therapeutic procedures (78.4%). A coronary artery was involved in 45 patients (60.8%). Thirty-five patients underwent an angioplasty and stent implantation; 3 had cardiac surgery; and 36 were managed conservatively. Two patients died of cardiogenic shock after the dissection. After a median follow-up of 51.2 months (range, 16.4-104.8 months), none of the remaining patients developed complications as a result of the dissection, progression, ischemia, pain, or dissection recurrence., Conclusions: Iatrogenic catheter dissection of the aorta is a rare complication that carries an excellent short- and long-term prognosis with the adoption of a conservative approach. When a coronary artery is involved as an entry point, it usually can be safely sealed with a stent with good long-term outcomes., (© 2015 American Heart Association, Inc.)

A totally calcified ascending aorta prevents aortic crossclamping and aortotomy during aortic valve replacement, and replacement of the ascending aorta is a valid option in these cases. We describe a simple technique for calcified ascending aorta replacement using the Cavitron Ultrasonic Surgical Aspirator. This can be used in aortic endarterectomy for removal of the calcified plaque in the anastomotic part., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Aortic 3-dimensional blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy., Methods and Results: Four-dimensional flow MRI measured in vivo 3-dimensional blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.4 mm; n=15 RN-BAV, 39.6±7.2 mm); aorta size controls with tricuspid aortic valves (n=30, 41.0±4.4 mm); healthy volunteers (n=15, 24.9±3.0 mm). Aortopathy type (0-3), systolic flow angle, flow displacement, and regional wall shear stress were determined for all subjects. Eccentric outflow jet patterns in BAV patients resulted in elevated regional wall shear stress (P<0.0125) at the right-anterior walls for RL-BAV and right-posterior walls for RN-BAV in comparison with aorta size controls. Dilatation of the aortic root only (type 1) or involving the entire AAo and arch (type 3) was found in the majority of RN-BAV patients (87%) but was mostly absent for RL-BAV patients (87% type 2). Differences in aortopathy type between RL-BAV and RN-BAV patients were associated with altered flow displacement in the proximal and mid AAo for type 1 (42%-81% decrease versus type 2) and distal AAo for type 3 (33%-39% increase versus type 2)., Conclusions: The presence and type of BAV fusion was associated with changes in regional wall shear stress distribution, systolic flow eccentricity, and expression of BAV aortopathy. Hemodynamic markers suggest a physiological mechanism by which the valve morphology phenotype can influence phenotypes of BAV aortopathy.

Background: Disturbed calcium-phosphorus metabolism is associated with increased kidney angiotensin-converting enzyme (ACE) in experimental chronic renal insufficiency (CRI). However, information about the effects of phosphate binding and loading on vascular ACE is lacking., Methods: Fifteen weeks after 5/6 nephrectomy (NX), rats were placed on a phosphate-binding (NX+Ca, 3.0% Ca), phosphate-loading (NX+Pi, 1.5% Pi), or control diet for 12 weeks (NX and sham)., Results: Aortic ACE, blood pressure, plasma phosphate, and parathyroid hormone were increased in the NX and NX+Pi groups, but were reduced with phosphate binding. Endothelium-mediated relaxations of isolated mesenteric conduit artery rings to acetylcholine were impaired in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. Experiments with nitric oxide (NO) synthase inhibition in vitro suggested that the NO-mediated component of acetylcholine response was lower in the NX and NX+Pi groups, but did not differ from sham in NX+Ca rats. In all NX groups, aortic endothelial NO synthase (eNOS) was reduced, while plasma and urine concentrations of NO metabolites were increased. Aortic nitrated proteins and calcification were increased in the NX and NX+Pi groups when compared with the NX+Ca and sham groups., Conclusion: Hypertension in the NX model of CRI was associated with reduced vasorelaxation, decreased eNOS, and increased ACE and nitrated proteins in the aorta. Phosphate binding with calcium carbonate enhanced vasorelaxation via endogenous NO and suppressed elevation of ACE and nitrated proteins, suggesting reduced vascular oxidative stress. Our findings support the view that correction of the calcium-phosphorus balance prevents CRI-induced vascular pathophysiology.

Over the last two decades, imaging of the aorta has undergone a clinically relevant change. As part of the change non-invasive imaging techniques have replaced invasive intra-arterial digital subtraction angiography as the former imaging gold standard for aortic diseases. Computed tomography (CT) and magnetic resonance imaging (MRI) constitute the backbone of pre- and postoperative aortic imaging because they allow for imaging of the entire aorta and its branches. The first part of this review article describes the imaging principles of CT and MRI with regard to aortic disease, shows how both technologies can be applied in every day clinical practice, offering exciting perspectives. Recent CT scanner generations deliver excellent image quality with a high spatial and temporal resolution. Technical developments have resulted in CT scan performed within a few seconds for the entire aorta. Therefore, CT angiography (CTA) is the imaging technology of choice for evaluating acute aortic syndromes, for diagnosis of most aortic pathologies, preoperative planning and postoperative follow-up after endovascular aortic repair. However, radiation dose and the risk of contrast induced nephropathy are major downsides of CTA. Optimisation of scan protocols and contrast media administration can help to reduce the required radiation dose and contrast media. MR angiography (MRA) is an excellent alternative to CTA for both diagnosis of aortic pathologies and postoperative follow-up. The lack of radiation is particularly beneficial for younger patients. A potential side effect of gadolinium contrast agents is nephrogenic systemic fibrosis (NSF). In patients with high risk of NSF unenhanced MRA can be performed with both ECG- and breath-gating techniques. Additionally, MRI provides the possibility to visualise and measure both dynamic and flow information.

Background: Use of an aortic partial clamp for proximal anastomosis during off-pump coronary artery bypass is known to increase the risk of fatal complications. The purpose of this study was to assess the management of the ascending aorta evaluated with epiaortic ultrasonography during off-pump coronary artery bypass., Methods: Intraoperative ultrasonography of the ascending aorta with a 10-MHz probe was performed consecutively in 155 patients undergoing off-pump coronary artery bypass between August 1999 and July 2001. The findings from ultrasonography, surgical modifications, and operative results were analyzed., Results: In 54 patients (34.8%), epiaortic ultrasonography showed atherosclerotic findings in the anterior side of the ascending aorta (group A). The remaining 101 patients had either normal findings or atherosclerotic findings in only the posterior side (group NA). A proximal anastomosis to the aorta was preoperatively planned in 117 patients (group A, 42; group NA, 75). In group A, a graft modification without clamping was implemented in 29 patients (24.8% of 117 patients), whereas the clamp site was modified to a different segment in 13 patients (11.1% of 117 patients). In all 75 patients in group NA, partial clamping was used in the standard fashion. There were no cerebral infarctions or operative deaths related to partial clamping. However, aortic dissection occurred in 1 patient in group NA., Conclusions: In 35% of patients undergoing off-pump coronary artery bypass, epiaortic ultrasonography identified atherosclerotic findings in the anterior wall of the ascending aorta. This study suggests that revascularization without aortic manipulation during off-pump coronary artery bypass is indicated in as many as 25% of patients.

Dense calcification of the ascending aorta predisposes to aortic injury and distal embolization when the aorta is cross-clamped or partially clamped in the performance of cardiac operations. We occluded the ascending aorta with a Foley balloon catheter in 2 patients undergoing aortocoronary bypass grafting. The technique used is described in this report.

To evaluate the use of microvascular prosthetic grafts, the infrarenal aorta in 33 male Sprague-Dawley rats was replaced by an interposition graft of PTFE (polytetrafluoroethylene, Gore-Tex). Three groups of experimental animals were studied: Group A consisted of rats with 7-mm-long grafts, group B consisted of rats with 20-mm-long grafts, and group C consisted of rats with 20-mm-long grafts and ligatures of one patent after varying observation periods (6-92 days, median value 28 days, mean value 49 days). In group B all grafts but one (13/14) were patent (0-201 days, median value 198 days, mean value 118 days). In group C two grafts occluded immediately postoperatively, whereas the remaining six were patent (0-24 days, median and mean values 9 days). Twelve of 13 grafts observed for 3 months or more remained patent. There were no signs of infection. Angiography did not reveal any stenosis in the anastomoses of patent grafts. Light microscopy demonstrated a good adaptation between the grafts and the aorta in all animals. In the short grafts observed for 3 months and in the long grafts observed for 6 months, the luminal surfaces were completely covered by endothelial-like cells. In the occluded graft in group B, a stenosis was demonstrated in one of the anastomoses. This was not found in any other specimen. The results of this study document the possibility of using PTFE grafts of 1 mm diameter in experimental microvascular position.