Two-year evaluation of fenestrated and parallel branch endografts for the treatment of juxtarenal, suprarenal, and thoracoabdominal aneurysms at a single institution.

OBJECTIVE: Despite numerous recent pivotal and small-scale trials, real-world endovascular management of juxtarenal aneurysms (JRA), suprarenal aneurysms (SRA), and thoracoabdominal aortic aneurysms (TAAA) remains challenging without consensus best practices. This study evaluated the mortality, graft patency, renal function, complication, and reintervention rates for fenestrated and parallel endografts in complex aortic aneurysms repairs. METHODS: This retrospective review of consecutive included patients with JRA, SRA, or TAAA who underwent complex endovascular repair from August 2014 to March 2017 at one high-volume institution. Treatment modality was a single surgeon decision based on patients anatomy and the urgency of the repair. Patient demographics, hospital course, and follow-up visits inclusive of imaging were analyzed. Ruptured aneurysms were excluded. Survival rates and outcomes were determined using the Kaplan-Meier method with log-rank tests. RESULTS: Seventy complex endovascular aortic repairs were performed; 38 patients with TAAA were treated with snorkel/sandwich parallel endografts (21 celiac, 28 superior mesenteric arteries, 58 renal arteries) and 32 patients with JRA/SRA were treated by fenestrated endovascular aneurysm repair (FEVAR) with 94 total fenestrations (2 celiac, 30 SMA, 62 renal). The mean patient age was 74.8 ± 10.0 years. Sixty percent were male, and the mean aortic aneurysm diameter was 6.0 ± 1.4 cm. Perioperative mortality was 3.1% (1/32) for FEVAR compared with 2.6% (1/38) for parallel endografts (P = .9). All-cause reintervention rates were 15.6% in FEVAR (5/32) vs 23.6% with parallel endografts (9/38; P = .4). Branch reintervention rates per each branch endograft were 4.3% for FEVAR (4/94; 2 renal stent occlusions, 1 colonic ischemia without technical issue found on reintervention, 1 perinephric hematoma) vs 3.7% for parallel endografts (4/107; 2 renal and 1 celiac stent thromboses, and 1 renal stent kink; P = .41). The endograft branch thrombosis rate was 2.1% in FEVAR (2/94) vs 2.7% in parallel endografts (3/109; P = .77). Reinterventions owing to endoleaks were performed in five patients (2 type I, 2 type III, and 1 gutter endoleak; 13.1%) with parallel grafts vs no endoleak reinterventions in FEVAR. The overall survival and freedom from aneurysm-related mortality at 24 months was 78% and 96.9% in FEVAR vs 73% and 93.4% for parallel endografts (P = .8 and P = .6). The median follow-up was 12 months (range, 1-32 months). CONCLUSIONS: Parallel and fenestrated endografts have acceptable and comparable mortality and patency rates in endovascular treatment of JRA, SRA, and TAAA. This study reaffirms that parallel endografts are a safe and viable alternative to fenestrated devices for complex aortic aneurysmal disease despite often treating more urgent patients and more complicated anatomy unable to be treated with FEVAR.

Post-General Anesthesia Ultrasound-Guided Venous Mapping Increases Autogenous Access Placement Rates.

BACKGROUND: This study investigates the impact of introducing a post-general anesthesia ultrasound (PAUS) mapping on the type of vascular access chosen for hemodialysis in patients without previous accesses. METHODS: Two hundred three of 297 consecutive patients met inclusion criteria and were reviewed. Within-subjects analysis was performed on patients with both an outpatient ultrasound-guided vein mapping and a PAUS using sign tests and Wilcoxon signed rank tests. Furthermore, a between-subjects analysis added patients with only the outpatient vein mapping; demographic and comorbidity data were analyzed using t-tests and chi-squared tests. An ordinal logit regression was run for the type of access placed, while a bivariate logit regression was used to compare rates of autogenous access maturation. RESULTS: One hundred sixty-five (81%) patients received both a standard outpatient vein mapping and a PAUS. At the outpatient vein mapping, 130 (79%) patients had suitable veins for an autogenous access, whereas 35 (21%) patients did not have suitable veins for an autogenous access and were planned for a prosthetic access. During PAUS, all 165 (100%) patients were found to have suitable veins for autogenous access formation (P < 0.001). When comparing specific autogenous access configurations, Wilcoxon signed rank testing showed significantly more preferable access configurations in the PAUS group than the outpatient mapping (P < 0.001); outpatient mapping resulted in 81 (47%) radiocephalic accesses, 10 (6%) radiobasilic accesses, 20 (12%) brachiocephalic accesses, 19 (12%) brachiobasilic accesses, and 35 (21%) prosthetic accesses planned, in contrast to 149 (90%) radiocephalic accesses, 3 (2%) radiobasilic accesses, 10 (6%) brachiocephalic accesses, 3 (2%) brachiobasilic accesses, and 0 prosthetic accesses when the same patients were analyzed using PAUS. With the analysis expanded to include the 38 (19%) patients with only the outpatient vein mapping (without-PAUS), the Wilcoxon-Mann-Whitney test showed no significant differences between the groups in terms of outpatient vein mapping plans (P = 0.10); however, when comparing the PAUS plans to the outpatient vein mapping plans, there was again a significantly increased proportion of preferred access types in the PAUS group compared with the outpatient group (P < 0.001). In the ordinal logit multivariate analysis, the only significant variable was the postanesthesia ultrasound, which positively correlated with more favorable access configurations (coefficient = 2.61, P < 0.001). The bivariate logit regression for autogenous access maturation rates found no significant difference between the without-PAUS group and the PAUS group (P = 0.13). CONCLUSIONS: Introducing a postanesthesia ultrasound mapping to guide vein-finding significantly increases the quality and quantity of suitable veins found, subsequently leading to increased proportions preferred access placement (autogenous versus prosthetic and forearm versus upper extremity).

The Transradial Approach for Lower Extremity Vascular Intervention.

Simultaneous technological advancements in both imaging as well as devices have resulted in an expansion of endovascular options for vascular access. In particular, radial access has traditionally been more favored for coronary interventions; its use in the aortoiliac and lower extremity vasculature has been constrained by the length of devices and the size of sheaths required. However, with increasing catheter shaft lengths, in addition to new thin-walled sheaths allowing for downsizing, the ability to perform transradial interventions on infrainguinal and infrageniculate vessels has been more readily facilitated. In this review, we analyze the potential for transradial therapies in the treatment of peripheral arterial disease (PAD).

Endothelial cAMP deactivates ischemia-reperfusion-induced microvascular hyperpermeability via Rap1-mediated mechanisms.

Approaches to reduce excessive edema due to the microvascular hyperpermeability that occurs during ischemia-reperfusion (I/R) are needed to prevent muscle compartment syndrome. We tested the hypothesis that cAMP-activated mechanisms actively restore barrier integrity in postischemic striated muscle. We found, using I/R in intact muscles and hypoxia-reoxygenation (H/R, an I/R mimic) in human microvascular endothelial cells (HMVECs), that hyperpermeability can be deactivated by increasing cAMP levels through application of forskolin. This effect was seen whether or not the hyperpermeability was accompanied by increased mRNA expression of VEGF, which occurred only after 4 h of ischemia. We found that cAMP increases in HMVECs after H/R, suggesting that cAMP-mediated restoration of barrier function is a physiological mechanism. We explored the mechanisms underlying this effect of cAMP. We found that exchange protein activated by cAMP 1 (Epac1), a downstream effector of cAMP that stimulates Rap1 to enhance cell adhesion, was activated only at or after reoxygenation. Thus, when Rap1 was depleted by small interfering RNA, H/R-induced hyperpermeability persisted even when forskolin was applied. We demonstrate that 1) VEGF mRNA expression is not involved in hyperpermeability after brief ischemia, 2) elevation of cAMP concentration at reperfusion deactivates hyperpermeability, and 3) cAMP activates the Epac1-Rap1 pathway to restore normal microvascular permeability. Our data support the novel concepts that 1) different hyperpermeability mechanisms operate after brief and prolonged ischemia and 2) cAMP concentration elevation during reperfusion contributes to deactivation of I/R-induced hyperpermeability through the Epac-Rap1 pathway. Endothelial cAMP management at reperfusion may be therapeutic in I/R injury.NEW & NOTEWORTHY Here, we demonstrate that 1) stimulation of cAMP production deactivates ischemia-reperfusion-induced hyperpermeability in muscle and endothelial cells; 2) VEGF mRNA expression is not enhanced by brief ischemia, suggesting that VEGF mechanisms do not activate immediate postischemic hyperpermeability; and 3) deactivation mechanisms operate via cAMP-exchange protein activated by cAMP 1-Rap1 to restore integrity of the endothelial barrier.

S-nitrosylation regulates VE-cadherin phosphorylation and internalization in microvascular permeability.

The adherens junction complex, composed mainly of vascular endothelial (VE)-cadherin, ß-catenin, p120, and γ-catenin, is the main element of the endothelial barrier in postcapillary venules.S-nitrosylation of ß-catenin and p120 is an important step in proinflammatory agents-induced hyperpermeability. We investigated in vitro and in vivo whether or not VE-cadherin isS-nitrosylated using platelet-activating factor (PAF) as agonist. We report that PAF-stimulates S-nitrosylation of VE-cadherin, which disrupts its association with ß-catenin. In addition, based on inhibition of nitric oxide production, our results strongly suggest that S-nitrosylation is required for VE-cadherin phosphorylation on tyrosine and for its internalization. Our results unveil an important mechanism to regulate phosphorylation of junctional proteins in association with S-nitrosylation.

Inhibition of endothelial to mesenchymal transition in a large animal preclinical arterio-venous fistula model leads to improved remodeling and reduced stenosis.

AIMS: Vein grafts are used for many indications, including bypass graft surgery and arterio-venous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia and adverse remodeling. Recently, endothelial to mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts. We aimed to evaluate the clinical potential of inhibiting EndMT, and developed the first dedicated preclinical model to study the efficacy of local EndMT inhibition immediately prior to AVF creation. METHODS AND RESULTS: We first undertook pilot studies to optimize the creation of a femoral AVF in pigs and verify that EndMT contributes to neointimal formation. We then developed a method to achieve local in vivo SMAD3 knockdown by dwelling a lentiviral construct containing SMAD3 shRNA in the femoral vein prior to AVF creation. Next, in Phase 1, 6 pigs were randomized to SMAD3 knockdown or control lentivirus to evaluate the effectiveness of SMAD3 knockdown and EndMT inhibition 8 days after AVF creation. In Phase 2, 16 pigs were randomized to SMAD3 knockdown or control lentivirus and were evaluated to assess longer-term effects on AVF diameter, patency and related measures at 30 days after AVF creation.In Phase 1, compared to controls, SMAD3 knockdown achieved a 75% reduction in the proportion of CD31+ endothelial cells co-expressing SMAD3 (p<0.001), and also a significant reduction in the extent of EndMT (p<0.05). In Phase 2, compared to controls, SMAD3 knockdown was associated with an increase in the minimum diameter of the venous limb of the AVF (1.56±1.66 versus 4.26±1.71mm, p<0.01) and a reduced degree of stenosis (p<0.01). Consistent with this, neointimal thickness was reduced in the SMAD3 knockdown group (0.88±0.51 versus 0.45±0.19mm, p<0.05). Furthermore, endothelial integrity (the proportion of luminal cells expressing endothelial markers) was improved in the SMAD3 knockdown group (p<0.05). CONCLUSIONS: EndMT inhibition in a preclinical AVF model by local SMAD3 knockdown using gene therapy led to reduced neointimal hyperplasia, increased endothelialization and a reduction in the degree of AVF stenosis. This provides important proof-of-concept to pursue this approach as a clinical strategy to improve the patency of AVFs and other vein grafts.

Spontaneous recanalization of a total occlusion of an infrarenal abdominal aorta after left axillary-bifemoral bypass.

Acute aortic occlusion is an infrequent clinical event with high morbidity and mortality. Management is determined by the cause of the occlusion, with thromboembolectomy used for embolic events and bypass for thrombotic events. After bypass, recanalization of a total aortic occlusion has been sparsely reported. We present a case of a total occlusion of an infrarenal abdominal aorta that was managed surgically with a left axillary-bifemoral bypass. Imaging performed 6 months postoperatively revealed a spontaneously recanalized aorta and occluded bypass graft.

Regulation of glia number in Drosophila by Rap/Fzr, an activator of the anaphase-promoting complex, and Loco, an RGS protein.

Glia mediate a vast array of cellular processes and are critical for nervous system development and function. Despite their immense importance in neurobiology, glia remain understudied and the molecular mechanisms that direct their differentiation are poorly understood. Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase complex well characterized for its role in cell cycle progression. In this study, we have uncovered a novel cellular role for Rap/Fzr. Loss of rap/fzr function leads to a marked increase in the number of glia in the nervous system of third instar larvae. Conversely, ectopic expression of UAS-rap/fzr, driven by repo-GAL4, results in the drastic reduction of glia. Data from clonal analyses using the MARCM technique show that Rap/Fzr regulates the differentiation of surface glia in the developing larval nervous system. Our genetic and biochemical data further indicate that Rap/Fzr regulates glial differentiation through its interaction with Loco, a regulator of G-protein signaling (RGS) protein and a known effector of glia specification. We propose that Rap/Fzr targets Loco for ubiquitination, thereby regulating glial differentiation in the developing nervous system.

Transradial renal salvage after complex endovascular aneurysm repair complicated by left renal artery thrombosis.

Transradial access has been used for percutaneous coronary interventions with success; however, there is limited literature on its use for visceral stenting in the setting of complex endovascular aneurysm repair. We present a case of transradial left renal salvage after renal artery thrombosis in the setting of complex endovascular aneurysm repair.

Minimally Invasive Aortobiilliofemoral Endarterectomy for Aortoiliac Occlusive Disease Is a Compelling Alternative to Bypass.

INTRODUCTION:: Aortobifemoral bypass is a time-honored, durable surgery allowing restoration of lower extremity blood. However, the potential for significant complications exists, impacting mortality, morbidity, and quality of life. Minimally invasive aortobiiliofemoral endarterectomy offers an alternative to prosthetic bypass and its associated complications. Here, we present a case series using remote endarterectomy for aortoiliac occlusive disease. METHODS:: Nine patients with aortoiliac occlusive disease were treated at a single institution, by a single surgeon, with direct and remote endarterectomy combination. Standard femoral access approach was used. A limited longitudinal distal aorta arteriotomy into the right common iliac artery to the hypogastric bifurcation was made. Then, an open thromboendarterectomy was performed. Circumferential common femoral endarterectomies were performed bilaterally and the plaque transected, allowing manually controlled Vollmar ring passage proximally to the iliac bifurcation on the right and the aortic bifurcation on the left. Aortoiliac arteriotomy was closed, followed by the femoral arteriotomies. Morbidity, secondary interventions, recurrent stenosis (adjacent segment velocity ratios ≥2), ankle-brachial index (ABI), and patency rates were tracked postoperatively for 6 years. Kaplan-Meier life-table analysis was used to determine patency rates per the criteria of SVS and ISCS. RESULTS:: The average age was 59.1 years (54-87 years), and 88% were male. Comorbidities included hypertension (75%), former/current smokers (100%), and prior PAD surgical intervention (38%). Revascularization of 100% was achieved, with average ABI improving from 0.42 preoperatively to 0.92 postoperatively (0.91 at 8-month follow-up). Six-year patency rate was 100% without reintervention. Incidence of myocardial infarction, stroke, death, amputation, intestinal ischemia, sexual dysfunction, and aneurysmal degeneration was zero after 6 years of follow-up. CONCLUSION:: Minimally invasive aortobiiliofemoral endarterectomy is a viable alternative to aortobifemoral bypass for the treatment of aortoiliac occlusive disease, allowing reestablishment of normal anatomic anatomy while avoiding the use of prosthetic material. Patency rates in this series was 100% at 6 years, with minimal postoperative complications or morbidity.

Abdominal Aortic Aneurysm With Renal Arteries Originating Above the Superior Mesenteric Artery.

A 63-year-old female presented to clinic following an incidental finding of an abdominal aortic aneurysm (AAA). Preoperative imaging was consistent with an infrarenal AAA over 5-cm in diameter with both renal arteries originating above the superior mesenteric artery (SMA). The patient subsequently underwent an endovascular aneurysm repair (EVAR) using the AFX stent-graft (Endologix, Inc, Irvine, Calif). Notably, the proximal stent-graft piece was unsheathed with the image intensifier in a lateral position to ensure deployment below the SMA. Postoperative course was unremarkable and the patient is currently recovering well.