Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

In the United States, over 200,000 new patients are diagnosed with abdominal aortic aneurysm (AAA) each year. Consequently, over 40,000 highly morbid aortic reconstructions are performed each year to prevent aneurysm rupture, a catastrophic event associated with near-certain mortality. No pharmaceutical currently exists to slow aneurysm growth, but a 50% reduction in diameter growth per annum could halve the number of aortic reconstructions required. Therefore, successful use of cell therapy to modulate chronic inflammation hallmark to AAA to slow diameter expansion represents a potentially paradigm-altering treatment

Comorbidities Associated with Large Abdominal Aortic Aneurysms

BACKGROUND: Abdominal aortic aneurysm has become increasingly important owing to demographic changes. Some other diseases, for example, cholecystolithiasis, chronic obstructive pulmonary disease, and hernias, seem to co-occur with abdominal aortic aneurysm. The aim of this retrospective analysis was to identify new comorbidities associated with abdominal aortic aneurysm. METHODS: We compared 100 patients with abdominal aortic aneurysms and 100 control patients. Their preoperative computed tomographic scans were examined by two investigators independently, for the presence of hernias, diverticulosis, and cholecystolithiasis. Medical records were also reviewed. Statistical analysis was performed using univariate analysis and multiple logistic regression analysis. RESULTS: The aneurysm group had a higher frequency of diverticulosis (p = 0.008). There was no significant difference in the occurrence of hernia (p = 0.073) or cholecystolithiasis (p = 1.00). Aneurysm patients had a significantly higher American Society of Anesthesiology score (2.84 vs. 2.63; p = 0.015) and were more likely to have coronary artery disease (p < 0.001), congestive heart failure (p < 0.001), or chronic obstructive pulmonary disease (p < 0.001). Aneurysm patients were more likely to be former (p = 0.034) or current (p = 0.006) smokers and had a significantly higher number of pack years (p < 0.001). Aneurysm patients also had a significantly poorer lung function. In multivariate analysis, the following factors were associated with aneurysms: chronic obstructive pulmonary disease (odds ratio, OR = 12.24; p = 0.002), current smoking (OR = 4.14; p = 0.002), and coronary artery disease (OR = 2.60; p = 0.020). CONCLUSIONS: Our comprehensive analysis identified several comorbidities associated with abdominal aortic aneurysms. These results could help to recognize aneurysms earlier by targeting individuals with these comorbidities for screening

Ascending aortic aneurysm and aortic valve dysfunction in bicuspid aortic valve disease

BACKGROUND: The relationship of aortic valve dysfunction and ascending aortic aneurysm is unclear in adults with bicuspid aortic valve disease. METHODS: We retrospectively studied 134 consecutive out-patients (98 men, 36 women aged 43+/-18years) with bicuspid aortic valve disease. To investigate the relationship of ascending aortic aneurysm and aortic valve dysfunction we exclusively considered severe pathologies that required treatment by surgical or percutaneous intervention. RESULTS: Of 134 patients, 39 had aortic valve dysfunction without concomitant ascending aortic aneurysm which had been treated previously with isolated valve surgery or percutaneous valvuloplasty comprising 25 patients with aortic stenosis (19%) and 14 patients with aortic regurgitation (10%). Conversely, 26 patients had ascending aortic aneurysm which had been treated previously with aortic surgery (19%). Of these, ascending aortic aneurysm was associated with severe aortic stenosis in 13 patients and with severe aortic regurgitation in 7 patients, whereas aneurysm was unrelated to severe aortic valve dysfunction in the remaining 6 patients including 2 without any degree of aortic valve dysfunction. The maximal aortic diameters were similar at the time of aortic surgery irrespective of presence of severe aortic valve dysfunction (P=.527). Other characteristics of patients with ascending aortic aneurysm were also similar irrespective of presence or type of aortic valve dysfunction. CONCLUSION: The majority of patients with bicuspid aortic valve disease exhibit ascending aortic aneurysm in conjunction with severe aortic valve dysfunction. However, in our study 6 of 134 (5%) of persons with bicuspid aortic valve disease developed ascending aortic aneurysm without aortic valve dysfunction

A double nellix and chimney covered stents: challenging treatment of pararenal aortic aneurysm

A 77-year-old male patient presented with a symptomatic, 66-mm pararenal aortic aneurysm. The patient was classified as unsuitable for open surgery due to significant comorbidities. Fenestrated or branched endografts were contraindicated due to the poor iliac access (6 mm diameter). A double Nellix with chimney endovascular aneurysm sealing (ChEVAS) technique was selected to exclude the pararenal aortic aneurysm and to preserve renal arteries and the superior mesenteric artery. Technical preplanning considered the ideal proximal landing zone to be close to the origin of the almost occluded celiac trunk and the distal common iliac arteries as the ideal distal landing zone. The total length of the aorta to cover was estimated as >180 mm, requiring 2 aortic EVAS systems, bilaterally overlapped. Technical success was achieved, and the patient was discharged on postoperative day 8 in good general condition. Successful aneurysm exclusion and target vessel patency without endoleak or stent-graft kinking or migration were confirmed at angio-computed tomography at 6 months

Long term outcomes in men screened for abdominal aortic aneurysm : prospective cohort study

PMID: 22563092 [PubMed - indexed for MEDLINE] PMCID: PMC3344734 Free PMC ArticlePeer reviewedPublisher PD

Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms.

OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm. BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed medial degeneration, which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm. METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n = 9), along with control aortas (n = 5). Immunohistochemistry staining was performed using antibodies directed against markers of lymphocytes and macrophages. Real-time polymerase chain reaction analysis was performed to quantify the expression level of the T-cell receptor beta-chain variable region gene. RESULTS: Immunohistochemistry of thoracic aortic aneurysm aortas demonstrated that the media and adventitia from Marfan syndrome, familial thoracic aortic aneurysm, and sporadic cases had increased numbers of T lymphocytes and macrophages when compared with control aortas. The number of T cells and macrophages in the aortic media of the aneurysm correlated inversely with the patient\u27s age at the time of prophylactic surgical repair of the aorta. T-cell receptor profiling indicated a similar clonal nature of the T cells in the aortic wall in a majority of aneurysms, whether the patient had Marfan syndrome, familial thoracic aortic aneurysm, or sporadic disease. CONCLUSION: These results indicate that the infiltration of inflammatory cells contributes to the pathogenesis of thoracic aortic aneurysms. Superantigen-driven stimulation of T lymphocytes in the aortic tissues of patients with thoracic aortic aneurysms may contribute to the initial immune response

Spontaneous sealing of a type Ia endoleak after ovation stent graft implantation in a patient with on-label aortic neck anatomy

We report a case of an early type Ia endoleak after endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm by Ovation Stent Graft implantation and spontaneously resolved without further reintervention. The patient presents a conical aortic neck, but EVAR was performed within the instruction for use proposed by manufactory. At completion angiography, a low-flow type Ia endoleak was present and left untreated. Computed tomographic angiography performed on the third postoperative day showed infolding of the 2 sealing rings. The patient was dismissed without further treatment. At 3-month follow-up, the leak appeared spontaneously sealed with partial expansion of the 2 rings.We report a case of an early type Ia endoleak after endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm by Ovation Stent Graft implantation and spontaneously resolved without further reintervention. The patient presents a conical aortic neck, but EVAR was performed within the instruction for use proposed by manufactory. At completion angiography, a low-flow type Ia endoleak was present and left untreated. Computed tomographic angiography performed on the third postoperative day showed infolding of the 2 sealing rings. The patient was dismissed without further treatment. At 3-month follow-up, the leak appeared spontaneously sealed with partial expansion of the 2 rings

Systematic review and meta-analysis of the growth and rupture rates of small abdominal aortic aneurysms: implications for surveillance intervals and their cost-effectiveness.

BACKGROUND: Small abdominal aortic aneurysms (AAAs; 3.0-5.4 cm in diameter) are usually asymptomatic and managed by regular ultrasound surveillance until they grow to a diameter threshold (commonly 5.5 cm) at which surgical intervention is considered. The choice of appropriate surveillance intervals is governed by the growth and rupture rates of small AAAs, as well as their relative cost-effectiveness. OBJECTIVES: The aim of this series of studies was to inform the evidence base for small AAA surveillance strategies. This was achieved by literature review, collation and analysis of individual patient data, a focus group and health economic modelling. DATA SOURCES: We undertook systematic literature reviews of growth rates and rupture rates of small AAAs. The databases MEDLINE, EMBASE on OvidSP, Cochrane Central Register of Controlled Trials 2009 Issue 4, ClinicalTrials.gov, and controlled-trials.com were searched from inception up until the end of 2009. We also obtained individual data on 15,475 patients from 18 surveillance studies. REVIEW METHODS: Systematic reviews of publications identified 15 studies providing small AAA growth rates, and 14 studies with small AAA rupture rates, up to December 2009 (later updated to September 2012). We developed statistical methods to analyse individual surveillance data, including the effects of patient characteristics, to inform the choice of surveillance intervals and provide inputs for health economic modelling. We updated an existing health economic model of AAA screening to address the cost-effectiveness of different surveillance intervals. RESULTS: In the literature reviews, the mean growth rate was 2.3 mm/year and the reported rupture rates varied between 0 and 1.6 ruptures per 100 person-years. Growth rates increased markedly with aneurysm diameter, but insufficient detail was available to guide surveillance intervals. Based on individual surveillance data, for each 0.5-cm increase in AAA diameter, growth rates increased by about 0.5 mm/year and rupture rates doubled. To control the risk of exceeding 5.5 cm to below 10% in men, on average a 7-year surveillance interval is sufficient for a 3.0-cm aneurysm, whereas an 8-month interval is necessary for a 5.0-cm aneurysm. To control the risk of rupture to below 1%, the corresponding estimated surveillance intervals are 9 years and 17 months. Average growth rates were higher in smokers (by 0.35 mm/year) and lower in patients with diabetes (by 0.51 mm/year). Rupture rates were almost fourfold higher in women than men, doubled in current smokers and increased with higher blood pressure. Increasing the surveillance interval from 1 to 2 years for the smallest aneurysms (3.0-4.4 cm) decreased costs and led to a positive net benefit. For the larger aneurysms (4.5-5.4 cm), increasing surveillance intervals from 3 to 6 months led to equivalent cost-effectiveness. LIMITATIONS: There were no clear reasons why the growth rates varied substantially between studies. Uniform diagnostic criteria for rupture were not available. The long-term cost-effectiveness results may be susceptible to the modelling assumptions made. CONCLUSIONS: Surveillance intervals of several years are clinically acceptable for men with AAAs in the range 3.0-4.0 cm. Intervals of around 1 year are suitable for 4.0-4.9-cm AAAs, whereas intervals of 6 months would be acceptable for 5.0-5.4-cm AAAs. These intervals are longer than those currently employed in the UK AAA screening programmes. Lengthening surveillance intervals for the smallest aneurysms was also shown to be cost-effective. Future work should focus on optimising surveillance intervals for women, studying whether or not the threshold for surgery should depend on patient characteristics, evaluating the usefulness of surveillance for those with aortic diameters of 2.5-2.9 cm, and developing interventions that may reduce the growth or rupture rates of small AAAs. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Fenestrated Endovascular Aneurysm Repair versus Snorkel Endovascular Aneurysm Repair: Competing yet Complementary Strategies.

Juxtarenal/pararenal aortic aneurysms and type IV thoracoabdominal aneurysms pose particular technical challenges for endovascular repair as they involve the visceral segment in addition to insufficient infrarenal neck for the use of standard endovascular aneurysm repair (EVAR) devices. To overcome these challenges, complex EVAR techniques have been developed to extend the proximal landing zone cephalad with maintaining perfusion to vital aortic branches, thereby broadening the applicability of endografting from the infrarenal to the suprarenal aorta. Complex EVAR can be divided into two broad categories: fenestrated endovascular aneurysm repair (FEVAR) and snorkel EVAR. FEVAR is a valid procedure with the standardized procedure, although it remains as a relatively complex procedure with a learning curve. Given time constraints for the custom fenestrated graft, snorkel EVAR may be an alternative for complex repairs in symptomatic or ruptured patients for whom custom-made endografts may not be immediately available. This article discusses these two most commonly used complex EVAR strategies

Nellix endovascular aortic sealing endoprosthesis late explantation for concomitant type I endoleak and stent frames proximal caudal migration

Endovascular aneurysm sealing (EVAS) using the Nellix™ System was introduced in clinical practice with the aim of reducing the incidence of complications such as migration, endoleaks, and reinterventions after conventional endovascular aneurysm repair (EVAR). Although, initial efficacy data on this device have been encouraging, EVAS has also demonstrated to undergo adverse events. Herein, we report a case of Nellix graft explant due to endobags shrinkage after air bubble reabsorption leading to proximal type I A endoleak and stent migration. The focus of this article is on the importance of a more assiduous surveillance of this new device, in particular in those cases with air into the endobags immediately after the procedure; this surveillance should be aimed to timely identify complications which can otherwise lead to consequences that require open conversion