True Abdominal Aortic Aneurysm Research Articles

Abstract P3016: Pathologic Matrix Markers Are Differentially Modulated By VSMC-Specific SGK-1 Activity In Hypertension And Abdominal Aortic Aneurysm

Introduction: The VSMC switch to synthetic phenotype promotes aortic pathology such as hypertension (HTN) and abdominal aortic aneurysm (AAA). Mechanical activation of serum and glucocorticoid inducible kinase-1 (SGK-1) alters the VSMC synthetic profile to promote remodeling. Plasma biomarkers may represent opportunities to assess VSMC function in aortic disease, and we hypothesize that analysis of a panel of plasma pathologic matrix markers (PMM) representing synthetic VSMC phenotype can reflect SGK-1-dependent activity. Methods: HTN was induced in wild-type C57Bl/6 (WT) and smooth muscle cell specific SGK-1 knockout (SMC-SGK-1KO +/- ) mice with AngiotensinII infusion (1.46mg/kg/day, n=4-6). Separate mice underwent AAA induction by peri-adventitial CaCl 2 application (n=4-6). Terminal procedure included collecting systolic blood pressure (SBP), aortic diameter (AoD), and plasma. ELISA for PMMs included Interleukin-6 (IL-6), Matrix Metalloproteinase-9 (MMP-9), Cathepsin S (CtsS), and Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). Impact of the panel was evaluated by a composite T-score. Statistics included T-test and ANOVA. Results: WT+HTN had >30% increased SBP and elevation of IL-6, CtsS, CysC, and TNC (p<0.05). SMC-SGK-1KO +/- +HTN had equally elevated SBP, but no change in PMMs, suggesting that SGK-1 contributed to HTN-induced VSMC synthetic activity. WT+AAA had >65% increased AoD and elevation of all PMMs (p<0.05). Alternatively, SMC-SGK-1KO +/- +AAA had abrogated growth (29.4 + 3.6%, p<0.05 vs WT and WT+AAA) with IL-6, CtsS, CysC, and TNC returning to baseline, suggesting that SGK-1-dependent production of these PMMS was necessary for true AAA growth. Composite T-scores differed between Control, HTN, and AAA in WT mice (0.78 + 0.08 vs 2.91 + 0.29 vs 7.11 + 0.71 respectively, p<0.05). In SMC-SGK-1KO +/- mice, T-score normalized in HTN but remained elevated in AAA (2.19 + 0.21, p<0.05 vs Control and WT+AAA), attributable to the elevations in MMP-9 and OPG, peptides produced by inflammatory infiltrate. Conclusion: A panel of PMMs can be scored to reflect synthetic activity of VSMCs in aortic pathology, as well as response to inhibition, and warrants further investigation for the clinical care of patients with vascular disease.

Signaling through the IL-6-STAT3 Pathway Promotes Proteolytically-Active Macrophage Accumulation Necessary for Development of Small AAA.

Elevated interleukin-6 (IL-6) plasma levels have been associated with abdominal aortic aneurysm (AAA), but whether this cytokine plays a causative role in the degenerative remodeling or represents an effect from the inflammatory cascades initiated by infiltrating leukocytes remained unclear. This project aims to demonstrate that within the aortic wall, signaling from IL-6 through the STAT3 transcription factor is necessary for infiltration of proteolytically-active macrophages and development of small AAA. Following measurement of baseline infrarenal aortic diameter (AoD, digital microscopy), C57Bl/6 and IL-6 knockout (IL-6KO) mice underwent AAA induction by application of peri-adventitial CaCl2 (0.5M) +/- implantation of an osmotic mini-pump delivering IL-6 (4.36µg/kg/day over 21days). At the terminal procedure, AoDs were measured by digital microscopy and aortas harvested for immunoblot (pSTAT3/STAT3), matrix metalloproteinase (MMP) quantification, or flow cytometric analysis of macrophage content. Plasma was collected for cytokine analysis. IL-6 infusion significantly increased the plasma IL-6 levels in C57Bl/6 and IL-6KO animals. The C57Bl/6 + CaCl2 group developed AAA (AoD >50% above baseline) but IL-6KO + CaCl2 did not. In the IL-6KO + IL-6+CaCl2 group, AAA developed to match that of C57Bl/6 + CaCl2 mice. STAT3 activity was significantly increased in animals with advanced stages of dilation (>40% from baseline), compared to those with ectasia (≤25%). Although cytokine profiles did not support T-cells or neutrophils as being active contributors in this stage of aortic remodeling, changes in the profile of elaborated MMPs suggested macrophage activity with a trend toward alternatively activated pathways. Flow cytometry confirmed significantly increased macrophage abundance specifically in animals with upregulated STAT3 activity and advanced aortic dilation. In this murine model of AAA, progressive dilation to development of true AAA was only accomplished when IL-6 signaling upregulated STAT3 activity to effect accumulation of proteolytically-active macrophages. This pathway warrants further investigation to identify potential therapeutic avenues to abrogate growth of small AAA.

Risk Analysis of Aneurysm Sac Enlargement Caused by Type II Endoleak after Endovascular Aortic Repair

Although the preoperative risk factors associated with the occurrence of type II endoleak (ETII) after endovascular aortic repair (EVAR) have gradually become more evident, the preoperative risk factors associated with aneurysm sac enlargement caused by ETII remain unclear. This study aimed to determine the preoperative risk factors associated with aneurysm sac enlargement caused by ETII after EVAR. This retrospective cohort study reviewed 519 EVARs performed for true abdominal aortic aneurysm between January 2006 and December 2018 at our institution. EVARs using commercially available bifurcated devices with no type I or III endoleaks during follow-up and with ≥12 months follow-up were included. A total of 320 patients were enrolled in the study. To identify the preoperative risk factors of sac enlargement after EVAR, Cox regression analysis was used to assess preoperative data. The median follow-up period was 60.8 months. Overall, 135 of 320 patients (42%) had ETII during follow-up, and 47 of 135 patients (35%) developed aneurysm sac enlargement. Multivariate analysis revealed that chronic kidney disease (CKD) stage ≥4 (hazard ratio [HR], 4.65; 95% confidence interval [CI], 2.13-10.15; P=0.001), patent inferior mesenteric artery (IMA) (HR, 17.85; 95% CI, 2.46-129.73; P< 0.001), and number of patent lumbar arteries (LAs) (HR, 1.37; 95% CI, 1.13-1.68; P= 0.002) were risk factors of aneurysm sac enlargement caused by ETII. CKD stage ≥4, patent IMA, and number of patent LAs were independent risk factors for aneurysm sac enlargement after EVAR. In particular, patent IMA had the highest HR and seemed to have the greatest impact on long-term aneurysm sac enlargement. Hence, taking preoperative measures to address a patent IMA appears to be important in reducing the incidence of sac enlargement.

Identification of a Plasma Microrna Signature as Biomarker of Subaneurysmal Aortic Dilation in Patients with High Cardiovascular Risk.

Patients with subaneurysmal aortic dilation (SAD; 25–29 mm diameter) are likely to progress to true abdominal aortic aneurysm (AAA). Despite these patients having a higher risk of all-cause mortality than subjects with aortic size <24 mm, early diagnostic biomarkers are lacking. MicroRNAs (miRs) are well-recognized potential biomarkers due to their differential expression in different tissues and their stability in blood. We have investigated whether a plasma miRs profile could identify the presence of SAD in high cardiovascular risk patients. Using qRT-PCR arrays in plasma samples, we determined miRs differentially expressed between SAD patients and patients with normal aortic diameter. We then selected 12 miRs to be investigated as biomarkers by construction of ROC curves. A total of 82 significantly differentially expressed miRs were found by qPCR array, and 12 were validated by qRT-PCR. ROC curve analyses showed that seven selected miRs (miR-28-3p, miR-29a-3p, miR-93-3p, miR-150-5p, miR-338-3p, miR-339-3p, and miR-378a-3p) could be valuable biomarkers for distinguishing SAD patients. MiR-339-3p showed the best sensitivity and specificity, even after combination with other miRs. Decreased miR-339-3p expression was associated with increased aortic abdominal diameter. MiR-339-3p, alone or in combination with other miRs, could be used for SAD screening in high cardiovascular risk patients, helping to the early diagnosis of asymptomatic AAA.

Abdominal aortic aneurysm screening in Sweden

A large body of evidence from four international randomised controlled trials (RCT) on abdominal aortic aneurysm (AAA) screening indicate that ultrasound-based screening in elderly men with a high prevalence (4 %–7 %) reduces AAA-related mortality by 40 % through early AAA detection and increased preventive elective repair and subsequently halves rupture incidence. Coinciding with the planned launch of national AAA screening programs, a dramatic change in AAA epidemiology became evident: a lower AAA prevalence in the targeted population of men and falling mortality rates, most likely related to a drop in rates of smoking, and a paradoxical increase in elective AAA repairs. These changes have called AAA screening in today’s context into question. Sweden was the first country to provide national coverage with an AAA screening program targeting 65-year-old men. The scientifically evaluated screening initiative, started in 2006, reported the lower than expected prevalence (1.7 %) in 65-year-old men early on. Cost-effectiveness seems to be maintained despite the altered epidemiology, as shown in a health-economic study. The current prevalence of AAA among Swedish women is very low, and general population-based screening of women is likely to be futile, although targeted screening among female smokers should be evaluated. Sub-aneurysmal aortas detected at screening are likely to progress to a true AAA within 5 years, indicating a need for continued surveillance in this group. Differences in screening compliance seem to be linked to socio-economic factors. The aim of this topical review is to highlight AAA screening within a Swedish context and point to areas where information is lacking and further research is needed.

A Case of Ruptured Abdominal Aortic Dissection Associated with True Abdominal Aortic Aneurysm

A Case of Ruptured Abdominal Aortic Dissection Associated with True Abdominal Aortic Aneurysm

True abdominal aortic aneurysm in Marfan syndrome

True abdominal aortic aneurysm (AAA) in patients with Marfan syndrome is relatively rare because most aortic aneurysms in this disease are dissecting aneurysms in the thoracic area. Therefore, its clinical characteristics and long-term outcome are still unclear. We examined six patients (3 men, 3 women) with Marfan syndrome who had a true AAA. These patients underwent surgical treatment from 1972 to 2004, and we investigated the clinical and histologic findings. The patients were a median age of 45 years (range, 23-73 years) at the time of operation. The median maximum AAA diameter was 76 mm (range, 30-140 mm). Two AAAs ruptured, one of which had twice undergone stent graft insertion before open repair. There was one anastomotic aneurysm and three aortic dissections with additional repair. Marfan-related cardiac complications, all found perioperatively or postoperatively, comprised three patients with annuloaortic ectasia and four with aortic regurgitation. Three patients died, including one death during the operation. Only slight mural thrombus was seen at nonruptured AAAs, and each surgical specimen of aneurysmal wall demonstrated significant cystic medial necrosis in the tunica media. True AAAs in Marfan syndrome seemed to have several specific features, such as the tendency to occur in relatively young patients, lack of mural thrombus, and susceptibility to dissection and rupture, and the patients have poor life expectancy. Therefore, careful follow-up, keeping these features in mind, is important to treat Marfan syndrome patients with a true AAA.

Surgical treatment of recurrent abdominal aortic aneurysm in a patient with systemic lupus erythematosus

Reports of true abdominal aortic aneurysms (AAAS), especially those due to severe inflammation, in patients with systemic lupus erythematosus (SLE) are very few in number. However, we had the experience of surgically treating a recurrent AAA due to severe inflammation found in a patient with SLE. The recurrence took place after an earlier operation for an infrarenal AAA and involved the left renal artery. In both situations, the previous infrarenal aaa and the recurrence, the aneurysms demonstrated more rapid growth and more irregularities in shape. Etiology of the AAA might be a combination of Takayasu's arteritis and SLE because the two entities appeared to have overlapped. (J Vasc Surg 2000;32:209-12.)

Concurrent comparison of endoluminal versus open repair in the treatment of abdominal aortic aneurysms: Analysis of 303 patients by life table method

Purpose: The aim of this study was to compare the outcome of consecutive patients with abdominal aortic aneurysm (AAA) treated concurrently by open operation and endoluminal intervention by the same surgeons during a defined interval. Methods: Between May 1992 and May 1996, 362 consecutive patients with AAA underwent repair. Fifty-three patients who underwent open operations for ruptured AAA plus two patients who underwent endoluminal repair of false AAA and four patients who underwent secondary endoluminal repair of AAA were excluded, leaving 303 patients who underwent elective repair of true AAA in the study. The elective operations were conventional open repair (OR) in 195 patients (151 men, 44 women; mean age, 69 years) and endoluminal repair (ER) in 108 patients (100 men, 8 women; mean age, 70 years). The decision to perform ER was based on comorbidities that precluded open repair (n = 48) and patient choice (n = 60). Graft configuration in the open repair group was tubular (n = 180) and bifurcated (n = 15), and in the ER group tubular (n = 48), aortoiliac/femoral (n = 25), and bifurcated (n = 35). All procedures were performed in the operating department, and radiographic guidance was used in the ER group. Follow-up was by interview, examination, and telephone. In addition, contrast-enhanced computed tomography was performed within the first 10 days after operation, 6 months and 12 months after operation, and then annually thereafter in the ER group. Outcome measures were successful exclusion of the aneurysm sac from the general circulation and survival. Data were analyzed by the life table method. Other outcome measures were length of hospital stay, length of intensive care unit stay, and operative blood loss. Results: No significant difference was found between the perioperative mortality rate for OR (11 deaths [5.6%] in 195 patients) and ER (six deaths [5.6%] in 108 patients). Three of the six deaths in the latter group occurred in patients with successful ER, and three occurred in 18 patients with failed ER who were converted to OR. Similarly, no significant difference was seen in the survival rate between the endoluminal and open repair groups when analyzed by the log-rank test ( p = 0.14). The rate of graft failure, however, was significantly higher in the ER group than in the OR group (Fisher's exact test, p < 0.001). Success in the ER group was defined as continuing graft function without endoleak or conversion to open repair. Kaplan-Meier curve for graft failure times for the endoluminal group revealed a 3-year graft success probability of 70%. Conclusions: This study suggests that ER is safe, sharing the same perioperative mortality risk as OR despite 44% of the ER group being rejected as unfit for OR. Conventional open repair is the most reliable method of successfully managing AAA. The endoluminal method, however, results in shorter length of hospital stay, shorter length of intensive care unit stay, and less blood loss than the open method. Patients who opt for the endoluminal method of repair should be made aware that the minimally invasive technique carries the disadvantage of a higher failure rate. (J Vasc Surg 1998;27:213-21.)

Abdominal aortic aneurysms: experience with the Ivancev-Malmö endovascular system for aortomonoiliac stent-grafts.

To describe a component-based aortomonoiliac stent-graft system and the first clinical results achieved with this device in endovascular abdominal aortic aneurysm (AAA) repair. From November 1993 to October 1996, 45 patients aged 60 to 86 years underwent endoluminal exclusion of true AAAs (median diameter 60 mm) involving the common iliac arteries (median diameter 16 mm right and 15 mm left) using unilimb stent-grafts deployed with the Iancev-Malmö system. Six immediate conversions occurred in the beginning of the series due to endografts that were too short. Complications, including 2 inadvertent renal artery occlusions, 7 kinked grafts, 6 iliac artery dissections, and 3 perioccluder leaks, were prominent features in the first 15 patients. Five patients died in the postoperative period, four of whom were nonsurgical candidates. There were five significant stent-graft migrations: one 3 weeks after surgery due to mechanical injury of the proximal stent and four after 1 year owing to continuous dilation of a wide proximal neck, stent-graft placement in a conical, thrombus-lined proximal neck, and two instances of proximal extension separation from the main graft. Translumbar aneurysm perfusion required embolization in 3 patients. Despite early complications associated with a learning curve, exclusion of large AAAs using unilimb stent-grafts is feasible. Strict inclusion criteria are necessary in order to improve mortality among nonsurgical candidates and minimize the risk for late migration.

Abdominal Aortic Aneurysms: Experience With the Ivancev-Malmö Endovascular System for Aortomonoiliac Stent-Grafts

To describe a component-based aortomonoiliac stent-graft system and the first clinical results achieved with this device in endovascular abdominal aortic aneurysm (AAA) repair. From November 1993 to October 1996, 45 patients aged 60 to 86 years underwent endoluminal exclusion of true AAAs (median diameter 60 mm) involving the common iliac arteries (median diameter 16 mm right and 15 mm left) using unilimb stent-grafts deployed with the Iancev-Malmö system. Six immediate conversions occurred in the beginning of the series due to endografts that were too short. Complications, including 2 inadvertent renal artery occlusions, 7 kinked grafts, 6 iliac artery dissections, and 3 perioccluder leaks, were prominent features in the first 15 patients. Five patients died in the postoperative period, four of whom were nonsurgical candidates. There were five significant stent-graft migrations: one 3 weeks after surgery due to mechanical injury of the proximal stent and four after 1 year owing to continuous dilation of a wide proximal neck, stent-graft placement in a conical, thrombus-lined proximal neck, and two instances of proximal extension separation from the main graft. Translumbar aneurysm perfusion required embolization in 3 patients. Despite early complications associated with a learning curve, exclusion of large AAAs using unilimb stent-grafts is feasible. Strict inclusion criteria are necessary in order to improve mortality among nonsurgical candidates and minimize the risk for late migration.

Aortic Anastomotic Pseudoaneurysms

Correlation of imaging and anatomic findings in seven men with abdominal aortic graft prostheses (four "end-to-end" anastomoses and three "end-to-side" anastomoses) was done to compare the value of different imaging modalities in detecting postoperative complications, especially aortic anastomotic pseudoaneurysms (AAPs). In all cases, angiographic and CT studies were carried out. In six patients ultrasound and MR examinations were also performed. Anatomic verification was obtained by surgery in six patients and autopsy in one case. Five patients had an AAP (four at surgery and one at autopsy), one had a true abdominal aortic aneurysm above the anastomosis, and one a nondetectable abnormality of the aortic suture line. Digital subtraction angiography diagnosed one of five AAPs, missed the true aneurysm in the sixth patient, and was normal in the patient without any aneurysm. Computed tomography correctly diagnosed the five AAPs and the true aneurysm and was normal in the last patient. Ultrasound correctly diagnosed the AAPs in three of four patients, incorrectly diagnosed an AAP in the patient who had the true aneurysm, and was normal in the patient without any aneurysm. Magnetic resonance diagnosed four of four AAPs and the true aneurysm and was normal in the last patient. Computed tomography seems to be the best imaging modality with which to diagnose and evaluate an aortic AAP in patients with aortoiliofemoral graft prosthesis.

Rupture of an Internal Iliac Artery Aneurysm into the Rectum: Fatal Consequence of an Ilioenteric Fistula —A Case Report

Fistulization of a true aneurysm or pseudoaneurysm of major arteries into the gastrointestinal tract has been reported in the literature since 1943. More common is the fistulization of a true abdominal aortic aneurysm and pseu doaneurysm at an anastomotic site, proximally at the aortic level or distally at the site of iliac arteries, after a vascular reconstructive procedure. Rupture of an isolated aneurysm of the common iliac arteries is less fre quent, and rupture of an internal iliac artery aneurysm into the gastrointestinal tract is rare. In searching the literature, the authors did not find documentation of any previous report of rupture of an internal iliac artery aneurysm into the rectum. They report a case of an acute rupture of a left internal iliac artery aneurysm into the rectum with a fatal outcome.

Atherosclerotic abdominal aortic aneurysms: Comparative data of different types based on the degree of inflammatory reaction

Two-hundred two patients who consecutively underwent histological examination of the aneurysm wall with the full thickness at the time of repair procedure of infrarenal true abdominal aortic aneurysm were retrieved from the files of the Department of Pathology at the National Cardiovascular Center in the 13-year period from September 1977 to August 1990. Inflammatory aneurysms were present in 15 patients (7.4%);14 men, 1 woman. The other 187 patients with ordinary atherosclerotic aneurysms were classified into four groups according to the thickness of adventitia and periadventitia, and clinical and pathological variables were compared between these groups and patients with inflammatory aneurysms. Patients with inflammatory aneurysms were significantly more likely to be younger and demonstrate weight loss, ureteric obstruction, absence of abdominal bruit, more accelerated erythrocyte sedimentation rate, and more thickening of adventitial and periadventitial tissue. The microscopic features of ordinary atherosclerotic aneurysms that had remarkable thickening of adventitia and periadventitia showed no sharp distinction from those of inflammatory aneurysms. Our study suggests that atherosclerosis plays a major role in the aneurysmal dilatation of the aorta and in the periaortic inflammatory process, and that inflammatory aneurysms are located at one end of the spectrum of atherosclerotic abdominal aortic aneurysms.