John B. Wild

Endovascular Aortic Aneurysm Repair in Patients with Hostile Neck Anatomy

Purpose To report a systematic review and meta-analysis of outcomes following endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy (HNA) vs. those with favorable neck anatomy (FNA). Methods Systematic review and meta-analysis of data on EVAR in patients with HNA and FNA was performed by 2 reviewers in February 2013. An eligible study was required to have at least 50 participants and to incorporate one or more of the HNA criteria of neck length <15 mm, neck diameter >28 mm, and/or angulation >60°. Of the 24 full-length articles ultimately reviewed, 8 were excluded, resulting in 16 articles that were suitable for inclusion in the meta-analysis. The study size ranged from 55 to 5183 participants, with a total of 8920 patients in the FNA group and 3039 patients in the HNA group. Mean follow-up ranged from 9 to 49 months. Results Analysis of the pooled data revealed a significant increase in 30-day mortality (2.4% FNA vs. 3.5% HNA; OR 1.60, 95% CI 1.13 to 2.27; p<0.01), intraoperative adjuncts (8.8% FNA vs. 15.4% HNA; OR 1.88, 95% CI 1.15 to 3.07; p=0.01), and 30-day migration (0.9% FNA vs. 1.6% HNA; OR 2.08, 95% CI 1.20 to 3.62; p=0.009) in patients with HNA. A decrease in primary technical success (97.5% FNA vs. 93.8% HNA; OR 0.41, 95% CI 0.18 to 0.93; p=0.03) was significant when all 3 criteria were used to define HNA. For outcomes at >30 days, the increase in secondary interventions (OR 1.29, 95% CI 1.00 to 1.66; p=0.05) approached significance, but aneurysm-related mortality, all-cause mortality, migration, and aortic rupture did not achieve statistical significance. There was no difference in rates of sac expansion. Analysis of endoleak rates revealed a significant increase in 30-day type I endoleaks (OR 2.92,95% CI 1.61 to 5.30; p<0.001) and late type I endoleaks (OR 1.71,95% CI 1.31 to 2.23; p<0.0001) in patients with HNA. Conclusion These results suggest that performing EVAR in patients with HNA increases the technical difficulty and results in poorer short-term outcomes. The higher rates of early and late type I endoleaks, along with secondary interventions, suggest that increased monitoring should be performed in this category of patient to ensure rapid treatment.

Differential microRNA expression profiles in peripheral arterial disease.

Background—Peripheral arterial disease (PAD) is a clinical condition caused by an atherosclerotic process affecting the arteries of the limbs. Despite major improvements in surgical endovascular techniques, PAD is still associated with high mortality and morbidity. Recently, microRNAs (miRNAs), a class of short noncoding RNA controlling gene expression, have emerged as major regulators of multiple biological processes. Methods and Results—A whole-miRNA transcriptome profiling was performed in peripheral blood from an initial sample set of patients and controls. A 12-miRNA PAD-specific signature, which includes let 7e, miR-15b, -16, -20b, -25, -26b, -27b, -28-5p, -126, -195, -335, and -363, was further investigated and validated in 2 additional sample sets. Each of these 12 miRNAs exhibited good diagnostic value as evidenced by receiver operating characteristic curve analyses. Pathway enrichment analysis using predicted and validated targets identified several signaling pathways relevant to vascular disorders. Several of these pathways, including cell adhesion molecules, were confirmed by quantifying the expression level of several candidate genes regulating the initial stages of the inflammatory atherosclerotic process. The expression level of 7 of these candidate genes exhibits striking inverse correlation with that of several, if not all, of the miRNAs of the PAD-specific miRNA signature. Conclusions—These results demonstrate the potential of miRNAs for the diagnosis of PAD and provide further insight into the molecular mechanisms leading to the development of PAD, with the potential for future therapeutic targets.

A variant in LDLR is associated with abdominal aortic aneurysm

Background—Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance. Methods and Results—A genome-wide association study was conducted using 1830 cases from the United Kingdom, New Zealand, and Australia with infrarenal aorta diameter ≥30 mm or ruptured AAA and 5435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1×10−4 were carried through to in silico replication in 1292 AAA cases and 30 503 controls. One single-nucleotide polymorphism associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1063 controls from the United Kingdom, 507 AAA cases and 199 controls from Denmark, and 885 AAA cases and 1000 controls from New Zealand). Low-density lipoprotein receptor (LDLR) rs6511720 A was significantly associated overall and in 3 of 5 individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio, 0.76; 95% confidence interval, 0.70–0.83; P=2.08×10−10). Conclusions—LDLR rs6511720 is associated with AAA. This finding is consistent with established effects of this variant on coronary artery disease. Shared causal pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

A multicentre observational study of the outcomes of screening detected sub-aneurysmal aortic dilatation.

OBJECTIVES Currently most abdominal aortic aneurysm screening programmes discharge patients with aortic diameter of less than 30 mm. However, sub-aneurysmal aortic dilatation (25 mm-29 mm) does not represent a normal aortic diameter. This observational study aimed to determine the outcomes of patients with screening detected sub aneurysmal aortic dilatation. DESIGN AND METHODS Individual patient data was obtained from 8 screening programmes that had performed long term follow up of patients with sub aneurysmal aortic dilatation. Outcome measures recorded were the progression to true aneurysmal dilatation (aortic diameter 30 mm or greater), progression to size threshold for surgical intervention (55 mm) and aneurysm rupture. RESULTS Aortic measurements for 1696 men and women (median age 66 years at initial scan) with sub-aneurysmal aortae were obtained, median period of follow up was 4.0 years (range 0.1-19.0 years). Following Kaplan Meier and life table analysis 67.7% of patients with 5 complete years of surveillance reached an aortic diameter of 30 mm or greater however 0.9% had an aortic diameter of 54 mm. A total of 26.2% of patients with 10 complete years of follow up had an AAA of greater that 54 mm. CONCLUSION Patients with sub-aneurysmal aortic dilatation are likely to progress and develop an AAA, although few will rupture or require surgical intervention.

Identification of microRNAs associated with abdominal aortic aneurysms and peripheral arterial disease

MicroRNAs are crucial in the regulation of cardiovascular disease and represent potential therapeutic targets to decrease abdominal aortic aneurysm (AAA) expansion. The aim of this study was to identify circulating microRNAs associated with AAA.

Low Density Lipoprotein Receptor Related Protein 1 and Abdominal Aortic Aneurysms

OBJECTIVES A recent GWAS demonstrated an association between low density lipoprotein receptor related protein 1 (LRP1) and abdominal aortic aneurysm (AAA). This review aims to identify how LRP1 may be involved in the pathogenesis of abdominal aortic aneurysm. DESIGN AND MATERIALS A systematic review of the English language literature was undertaken in order to determine whether LRP1 and associated pathways were plausible candidates for contributing to the development and/or progression of AAA. METHODS AND RESULTS A comprehensive literature search of MEDLINE (since 1948), Embase (since 1980) and Health and Psychological Instruments (since 1985) was conducted in January 2012 identified 50 relevant articles. These studies demonstrate that LRP1 has a diverse range of biological functions and is a plausible candidate for playing a central role in aneurysmogenesis. Importantly, LRP1 downregulates MMP (matrix metalloproteinase) activity in vascular smooth muscle cells and regulates other key pathways involved in extracellular matrix remodelling and vascular smooth muscle migration and proliferation. Crucially animal studies have shown that LRP1 depletion leads to progressive destruction of the vascular architecture and aneurysm formation. CONCLUSIONS Published evidence suggests that LRP1 may play a key role in the development of AAA.

Outcomes Following Limb Crossing in Endovascular Aneurysm Repairs.

Background: Crossing the limbs of the stent during endovascular aneurysm repair (EVAR) is often used to aid cannulation of the contralateral limb. This study assessed outcomes following the use of this technique. Methods: Retrospective review of crossed (n = 43) and uncrossed (n = 269) EVARs was performed at a tertiary vascular center over 5 years. Primary end points were graft limb occlusion (GLO), endoleak, and sac expansion rates. Indications for limb crossing were also assessed. Results: Two-year GLO (P = .34) and type 1 endoleak (P = .413) rates were similar between groups. Patients undergoing crossed EVAR experienced more type 2 endoleaks (P = .002) at 24 months but no increase in sac expansion rates was observed (P = .275). Thirty-day (P = .57) and late (P = .268) mortalities were similar between groups. The main indication for limb crossing was distal aortic angulation (48.8%). Conclusions: Crossed EVAR does not increase the risk of GLOs or clinically significant endoleaks. Further studies are needed to determine the effect on type 2 endoleak rates.