Aneurysm severity is suppressed by deletion of CCN4

Patients with abdominal aortic aneurysms are frequently treated with high-risk surgery. A pharmaceutical treatment to reverse aneurysm progression could prevent the need for surgery and save both lives and healthcare resources. Since CCN4 regulates cell migration, proliferation and apoptosis, processes involved in aneurysm progression, it is a potential regulator of aneurysm progression. We investigated the role of CCN4 in a mouse aneurysm model, using apolipoprotein-E knockout (ApoE−/−) mice fed high fat diet and infused with Angiotensin II (AngII). Blood pressure was similarly elevated in CCN4−/−ApoE−/− mice and CCN4+/+ApoE−/− mice (controls) in response to AngII infusion. Deletion of CCN4 significantly reduced the number of ruptured aortae, both thoracic and abdominal aortic area, and aneurysm grade score, compared to controls. Additionally, the frequency of vessel wall remodelling and the number of elastic lamina breaks was significantly suppressed in CCN4−/−ApoE−/− mice compared to controls. Immunohistochemistry revealed a significantly lower proportion of macrophages, while the proportion of smooth muscle cells was not affected by the deletion of CCN4. There was also a reduction in both proliferation and apoptosis in CCN4−/−ApoE−/− mice compared to controls. In vitro studies showed that CCN4 significantly increased monocyte adhesion beyond that seen with TNFα and stimulated macrophage migration by more than threefold. In summary, absence of CCN4 reduced aneurysm severity and improved aortic integrity, which may be the result of reduced macrophage infiltration and cell apoptosis. Inhibition of CCN4 could offer a potential therapeutic approach for the treatment of aneurysms.

Diameter change in completely remodelled proximal descending aorta after acute type I dissection repair: implications for estimating the pre-dissection size

OBJECTIVES Pre-dissection diameter of the proximal descending thoracic aorta (p-DTA), if available, would be the reference for determining the size of the stent graft or elephant trunk. Acute type B dissection is known to increase p-DTA diameter by 23% (Rylski factor). This study aimed to investigate the accuracy of estimating post-remodelling diameter of the p-DTA based on the Rylski factor and other post-dissection morphological parameters in acute type I dissection, based on the assumption that the post-remodelling diameter is similar to the pre-dissection diameter. METHODS In 60 patients with acute type I dissection showing complete remodelling of the p-DTA false lumen after surgical repair, preoperative and post-remodelling computed tomography scans were reviewed. Parameters, including maximal true lumen diameter (TLDmax) and aortic area-derived diameter divided by the Rylski factor (AoDRylski), were measured at the p-DTA. RESULTS After complete remodelling, p-DTA diameter decreased by 4.1 mm (P < 0.001). The equivalent to the Rylski factor was 15%. Both TLDmax and AoDRylski frequently showed ≥2 mm discrepancy from post-remodelling aortic diameter (36.7% and 48.3%, respectively, P = 0.30). When 2 parameters coincided within 2 mm, two-third of their estimations were accurate. AoDRylski was more accurate than TLDmax in patients with a large extent of circumferential dissection, and vice versa with less circumferential dissection (P = 0.027). CONCLUSIONS Prediction of post-remodelling aortic diameter relying on a single morphologic parameter carries a substantial risk of overestimation and underestimation. Evaluation based on the extent of circumferential dissection together with the 2 parameters may provide a more reliable estimation.

Aortic Arch Anatomy Pattern in Patients Treated Using Double Homemade Fenestrated Stent-Grafts for Total Endovascular Aortic Arch Repair

Purpose: To analyze the structural variation of the aortic arch and the supra-aortic arteries and establish an average spatial configuration that would be a pattern for a “universal double fenestration” design for physician-modified endovascular grafts (PMEGs) used in total thoracic endovascular aortic repair (TEVAR). Materials and Methods: Aortic arch morphology was retrospectively analyzed by reviewing the preoperative thoracic computed tomography angiography scans in 33 consecutive patients (mean age 68 years; 27 men) treated between January 2017 and March 2019 using double-fenestrated PMEGs for zone 0 TEVAR. Image analysis was completed according to a standardized technique on a vascular workstation with center lumen line reconstruction for all measurements. Variations in branching pattern of the aortic arch were classified into 8 types. Results: The arch trunk configuration was type I in 26 patients (79%), type II in 5 (15%), type III in 1, and type IV in 1. Mean aortic diameters at the level of mid ascending aorta, innominate artery (IA), left common carotid artery (LCCA), and left subclavian artery (LSA) were 35.7±3.7, 34.2±4.5, 33.3±6.7, and 33.7±4.7 mm, respectively. Mean diameters of the trunk were 12.2±1.7, 7.5±1.4, and 8.0±0.8 mm, respectively. Mean longitudinal center to center lengths were 15.9±2.5 mm between the LSA and LCCA and 12.1±3.0 mm between the LCCA and IA. Mean clock positions using the LSA as reference were 12:50 for the IA and 12:05 for the LCCA. In 32 patients (97%) all the supra-aortic branch vessels fit perfectly inside two delimited areas defined by a proximal common square area of 30×30 mm for the IA and LCCA and a second distal 8-mm-diameter circle for the LSA. Conclusion: Variations of the aortic arch anatomy are numerous and common. A general morphological pattern is described that delimits the aortic area where these variations occur. This information can be utilized for the design of an off-the-shelf double-fenestrated stent-graft for zone 0 TEVAR.

Successful Repair of Coarctation of the Aorta and Obstructive Total Anomalous Pulmonary Veins Connection in a One-Day-Old Newborn

A clinical case of successful repair of a combination of total anomalous pulmonary venous connection (TAPVC) with collector stenosis in one-day-old newborn. Only one case of successful correction of such a pathology is reported previously. The operation was performed with cardiopulmonary bypass and temporary antegrade brain perfusion. The narrowed aortic area was resected, the integrity of the aortic arch was restored using an extended anastomosis, and TAPVC correction was performed using a “sutureless technique”. The postoperative period was uneventful. The newborn was discharged from hospital on the 12th day.

Abstract P135: Aortic Areas at Multiple Locations are Independent Correlates of Multiple Subclinical Cardiovascular Disease Measures

To handle the force from high blood pressure, arteries throughout the vasculature undergo outward remodeling, which can be assessed through measurement of arterial dimension. While the proximal aortic size is indicative of aneurysm risk, other regions of the aorta, such as the descending or abdominal aorta, may be more reflective of general aortic remodeling. However, there have been no studies using multiple measures of aortic size and their association with established subclinical cardiovascular disease (CVD) markers. Therefore, we aimed to measure aortic area at three locations along its length: the ascending thoracic aorta (ASC), the descending thoracic aorta (DSC), and the abdominal aorta (ABD) and to test for associations with subclinical CVD measured via carotid ultrasound, arterial calcification, and brachial ankle pulse-wave velocity (PWV). Preliminary analyses were conducted on data from 279 African ancestry men from Tobago (mean age 64 years, range 53-89 years). Aortic areas (cm 2 ) were measured from computed tomography (CT) scans of the chest (ASC and DSC; measured on the same transverse plane at the location of the pulmonary artery) and the abdomen (ABD; measured at the midpoint of L3). The mean of 3 contiguous CT slices was used for each aortic area measure. Each area was individually tested for association with age, body size, blood pressures, and lifestyle factors (including smoking, physical activity, and alcohol), and significant covariates were included in the fully adjusted models. All aortic areas were correlated with each other (r=0.40-0.66, all P<0.0001). Greater age and weight were predictive of greater aortic area at all three locations (P<0.0001 for all). ASC and DSC were also associated with higher blood pressures (P<0.01, for all). No aortic measure was significantly associated with lifestyle factors. After full adjustment, ASC, DSC, and ABD areas were associated with carotid interadventitial diameter (r=0.34, 0.22, 0.20, respectively; all P<0.001). ASC was also positively associated with carotid intima-media thickness (P<0.01). While ABD was associated with abdominal aortic calcification (P<0.001), no area was associated with coronary artery calcification. Lastly, both ABD and DSC were correlated with greater PWV (r=0.24 and 0.16, P<0.005 for both), with DSC being significantly associated with PWV independent of ABD. This is the first study to test the association of aortic size measured at multiple points with established measures of subclinical CVD. While ASC and DSC were associated with age, blood pressures, and carotid outward remodeling, ABD was more strongly correlated with aging-related vascular changes. Additionally, DSC, which can be measured from clinical chest CTs, may be a novel indicator of arterial stiffness independent of age and blood pressures. Longitudinal studies are needed to determine the predictive value of aortic area measurement.