Jose Wiley

Open Versus Endovascular Stent Graft Repair of Abdominal Aortic Aneurysms: A Meta-Analysis of Randomized Trials

OBJECTIVESnThis study sought to evaluate the short-, intermediate-, and longer-term outcomes after endovascular versus open repair of abdominal aortic aneurysms (AAA), including both AAA-related and all-cause mortality.nnnBACKGROUNDnEndovascular stent graft placement for AAA has gained broad acceptance as an alternative to open surgical repair due to a lower perioperative morbidity and mortality. The intermediate- and long-term all-cause and aneurysm-related mortality vary among studies. Thus, we sought to perform a meta-analysis of open versus endovascular repair for treating AAA.nnnMETHODSnElectronic databases were queried for identification of prospective, randomized trials of open surgery versus endovascular stent graft repair of AAA. A total of 10 published papers reporting on 6 studies at different follow-up intervals were identified; they involved 2,899 patients with AAA repair procedures, of whom, 1,470 underwent endovascular stent graft AAA exclusion and 1,429 were treated by open AAA repair.nnnRESULTSnAt 30 days, the pooled relative risk of all-cause mortality was lower in the endovascular group (relative risk [RR]: 0.35, 95% confidence interval [CI]: 0.19 to 0.64) than in the open surgery group. At intermediate follow-up, the all-cause mortality had a nonsignificant difference (RR: 0.78, 95% CI: 0.57 to 1.08), the AAA-related mortality was significantly lower (RR: 0.46, 95% CI: 0.28 to 0.74) and reintervention rates were higher (RR: 1.48, 95% CI: 1.06 to 2.08) in the endovascular group than in the open surgery group. At long-term follow-up, there was no significant difference in all-cause mortality (RR: 0.99, 95% CI: 0.85 to 1.15) or AAA-related mortality (RR: 1.58, 95% CI: 0.20 to 12.74), whereas the significant difference in the rate of reinterventions persisted (RR: 2.54, 95% CI: 1.58 to 4.08).nnnCONCLUSIONSnIn patients randomized to open or endovascular AAA repair, all-cause perioperative mortality, as well as AAA-related mortality at short- and intermediate-term follow-up are lower in patients undergoing endovascular stent graft placement. This was associated with greater reintervention in the endovascular group noted at intermediate follow-up. Long-term survival appears to converge between the 2 groups.

Genotype-Dependent Impairment of Hemoglobin Clearance Increases Oxidative and Inflammatory Response in Human Diabetic Atherosclerosis

Objective—Haptoglobin (Hp) protein is responsible for hemoglobin clearance after intra-plaque hemorrhage. Hp gene exists as Hp-1 and Hp-2 alleles and the phenotypes show important molecular heterogeneity. We tested the hypothesis that hemoglobin clearance may be deficient in diabetic atheroma from patients with Hp2-2, triggering increased oxidative, inflammatory, and angiogenic patterns compared with controls. Methods and Results—Forty patients with diabetes mellitus were genotyped and their peripheral plaques compared after atherectomy. Plaque hemorrhage, iron content, hemoglobin-binding protein CD163, and heme-oxygenase-1 were quantified. Oxidative, inflammatory, and angiogenic patterns were evaluated by measuring myeloperoxidase, interleukin-10, macrophages, vascular cell adhesion molecule-1, smooth muscle actin, and plaque neovascularization (CD34/CD31). Plaques with Hp2-2 (n=7) had increased hemorrhage (P<0.005), iron content (P<0.001), and reduced CD163 expression (P<0.002) compared with controls (n=14). Hp2-2 plaques had increased heme-oxygenase-1 protein (P<0.02), myeloperoxidase gene (P<0.05), and protein (P<0.0001). Anti-inflammatory interleukin-10 gene (P<0.04), and protein expressions (P<0.0001) were decreased in Hp2-2. Finally, macrophage (P<0.0001), vascular cell adhesion molecule-1 (P=0.001), smooth muscle actin (P=0.002) scores, and neovessels density (P<0.0001) were increased in Hp2-2. Conclusion—Genotype-dependent impairment of hemoglobin clearance after intra-plaque hemorrhage is associated with increased oxidative, inflammatory, and angiogenic response in human diabetic atherosclerosis.

Expression of angiotensin-converting enzyme 2 and its end product angiotensin 1-7 is increased in diabetic atheroma: implications for inflammation and neovascularization

AIMSnThe angiotensin-converting enzyme 2 (ACE2) and its end product angiotensin 1-7 (Ang1-7) are key counterregulatory proteins to offset the deleterious effects of angiotensin II. ACE2 is decreased in diabetic kidney disease but overexpressed in metabolically active atheroma. We tested the hypothesis that ACE2 is increased in diabetic peripheral atheroma, concomitantly with Ang1-7, angiotensin II receptor 1 (AT1R), proinflammatory cytokines, macrophage infiltration, and plaque neovascularization.nnnMETHODS AND RESULTSnPeripheral atherectomy plaques collected from 12 diabetic (DM) and 12 non-DM patients were immunostained for ACE2, Ang1-7, AT1R, and proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Macrophage infiltration and neovascularization were counted using double-label immunochemistry with CD68/CD3 and CD34, respectively. Quantification was performed blindly by randomly counting positively stained cells in 20 high-power fields using previously validated methods. Tissue content of ACE2, Ang1-7, and AT1R was increased in DM when compared to non-DM (P<.0001). IL-6 and TNF-α were also increased in DM when compared to non-DM (P<.0001), as well as macrophage infiltration score and neovessel counting (P<.0001).nnnCONCLUSIONnExpression of ACE2 and its end product Ang1-7 is increased in DM atheroma, along with overexpression of AT1R, IL6, TNF-α, macrophage infiltration, and neovascularization. These results suggest that the renin-angiotensin system counterregulatory pathway may be preserved in metabolically active atheroma, offering potential targets for future therapies in diabetic atherosclerosis.

Intravascular ultrasound is an effective tool for predicting histopathology-confirmed evidence of adventitial injury following directional atherectomy for the treatment of peripheral artery disease

To the Editors: Directional atherectomy (DA) has emerged as a viable option for treatment of superficial femoral artery (SFA) occlusive disease. Despite excellent initial success, longterm patency with this therapy has had varying success. This variation in patency may be due to injury to the arterial wall during DA. Recently, we showed that histopathology evidence of deep injury to the adventitial layer of the vessel wall has a substantial negative effect on patency rates at 1 year. Continuing this work, we examined the relationship between intravascular ultrasound (IVUS)–identified external elastic lamina (EEL) disruption against the histopathology of the adventitia retrieved in the DA specimens. Of the 116 patients with TransAtlantic Inter-Society Consensus (TASC) A/B femoropopliteal lesions in our initial cohort, 108 had an IVUS examination after DA. IVUS imaging was performed by advancing the catheter to the most distal aspect of the lesion, and with data collected at 1 frame/s using a motorized pullback device set at 0.1 mm/s, raw sequential radiofrequency IVUS data were captured and transferred to a workstation for analysis. IVUS images were reconstructed utilizing IVUS lab software, and contours defining the internal elastic lamina (IEL) and EEL were identified automatically. A physician manually corrected the lumen and media-adventitial contours for each grayscale image. The IVUS definition of adventitial injury was disruption of the EEL and extension of the atherectomy cut past the EEL. Three board-certified interventional cardiologists independently reviewed all anonymized IVUS films to determine the presence or absence of EEL disruption; they had no knowledge of the histology outcomes. The IEL/EEL border was clearly identified, and the vessel structure at the site of atherectomy was comparatively examined to determine depth of disruption of vessel structures. Unanimous agreement of EEL border disturbance caused by the atherectomy device (Figure 1) was required for a “positive” EEL disruption assessment. Disagreements were classified as a negative for IVUSidentified adventitial injury. Investigator determination was then compared against histopathology findings of the atherectomy specimen as the reference gold standard. 647364 JETXXX10.1177/1526602816647364Journal of Endovascular TherapyKrishnan et al letter2016

Relation of Internal Elastic Lamellar Layer Disruption to Neointimal Cellular Proliferation and Type III Collagen Deposition in Human Peripheral Artery Restenosis

Smooth muscle cell proliferation and extracellular matrix formation are responsible for disease progression in de novo and restenotic atherosclerosis. Internal elastic lamella (IEL) layer maintains the structural integrity of intima, and disruption of IEL may be associated with alterations in neointima, type III collagen deposition, and lesion progression in restenosis. Nineteen restenotic plaques (12 patients) procured during peripheral interventions were compared with 13 control plaques (12 patients) without restenosis. Hematoxylin & Eosin and elastic trichrome stains were used to measure length and percentage of IEL disruption, cellularity, and inflammation score. Type I and III collagens, smooth muscle cell (smc), fibroblast density, and nuclear proliferation (Ki67) percentage were evaluated by immunohistochemistry. IEL disruption percentage (28 ± 3.6 vs 6.1 ± 2.4; p = 0.0006), type III collagen content (0.33 ± 0.06 vs 0.17 ± 0.07; p = 0.0001), smc density (2014 ± 120 vs 923 ± 150; p = 0.0001), fibroblast density (2,282 ± 297 vs 906 ± 138; p = 0.0001), and Ki67 percentage (21.6 ± 2 vs 8.2 ± 0.65; p = 0.0001) were significantly increased in restenotic plaques compared to de novo plaques. Logistic regression analysis identified significant correlation between IEL disruption and neointimal smc density (r = 0.45; p = 0.01) and with type III collagen deposition (r = 0.61; p = 0.02) in restenosis. Increased IEL disruption may trigger cellular proliferation, altering collagen production, and enhancing restenotic neointima. In conclusion, understanding the pathologic and molecular basis of restenosis and meticulous-guided interventions oriented to minimize IEL damage may aid to reduce neointimal proliferation and the occurrence of restenosis.

Intravascular ultrasound guided directional atherectomy versus directional atherectomy guided by angiography for the treatment of femoropopliteal in-stent restenosis

Background: The aim of this study was to compare 1-year outcomes for patients with femoropopliteal in-stent restenosis using directional atherectomy guided by intravascular ultrasound (IVUS) versus directional atherectomy guided by angiography. Methods and results: This was a retrospective analysis for patients with femoropopliteal in-stent restenosis treated with IVUS-guided directional atherectomy versus directional atherectomy guided by angiography from a single center between March 2012 and February 2016. Clinically driven target lesion revascularization was the primary endpoint and was evaluated through medical chart review as well as phone call follow up. Conclusions: Directional atherectomy guided by IVUS reduces clinically driven target lesion revascularization for patients with femoropopliteal in-stent restenosis.

Chronic Venous Insufficiency

Varicose veins are a common manifestation of chronic venous disease and affect approximately 25% of adults in the western hemisphere. The historical standard treatment has been surgery, with high ligation and stripping, combined with phlebectomies. In the past decade, alternative treatments such as endovenous ablation of the great saphenous vein (GSV) with laser, radiofrequency ablation, and ultrasonography-guided foam sclerotherapy have gained popularity. Performed as office-based procedures using tumescent local anesthesia, the new minimally invasive techniques have been shown in numerous studies to obliterate the GSV, eliminate reflux, and improve symptoms safely and effectively.