Objective: The objective of this study was to assess the durability of multibranched endovascular repair of thoracoabdominal aortic aneurysms (TAAAs) and pararenal aortic aneurysms by examining the rates of late-occurring (beyond 30 days) complications. Methods: There were 146 patients who underwent endovascular TAAA repair using a stent graft, with a total of 538 caudally oriented self-expanding branches. Four patients died in the perioperative period and were excluded, leaving 142 patients (mean age, 73 +/- 8 years; 35 [24.7%] women). Follow-up included clinical examination and computed tomography angiography at 1 month, 6 months, and 12 months and yearly thereafter. Results: Mean aneurysm diameter was 67 +/- 9 mm. Sixty-seven TAAAs (47.2%) were Crawford type I, II, III, or V; 75 (52.8%) were type IV or pararenal. Three patients (2.1%) died > 30 days after operation from perioperative complications. During a mean follow-up of 36 months (+/- 28 months), there were four additional aneurysm-related deaths: one (0.7%) as a result of aneurysm rupture in the presence of untreatable type I endoleak, one (0.7%) after conversion to open repair for stent graft infection, one (0.7%) after occlusion of superior mesenteric artery and celiac branches, and one (0.7%) due to bilateral renal branch occlusion. There was one additional open conversion for stent graft infection (0.7%). Nineteen patients (13.3%) underwent 20 reinterventions for late-occurring complications, including 11 (7.7%) for renal branch occlusion or stenosis, 1 (0.7%) for mesenteric branch stenosis, 4 (2.8%) for graft limb occlusion, 1 (0.7%) for type IB endoleak (distal stent graft migration), and 1 (0.7%) for type III endoleak (fabric erosion); 2 (1.4%) open conversions were performed for stent graft infection. There were no late type IA endoleaks. By Kaplan-Meier analysis, freedom from aneurysm-related death was 91.1% and freedom from aneurysm-related death or reintervention was 76.8% at 5 years. The 5-year overall survival rate of 49.1% reflects the high rate of cardiopulmonary comorbidity. Although renal branch occlusion (23 occlusions of 256 renal branches [8.9%]) was the most common late complication, only five patients required permanent dialysis. Conclusions: Total endovascular repair of TAAAs and pararenal aortic aneurysms using axially oriented cuffs is safe, effective, and durable in the long term.

Background Peripheral artery disease is highly prevalent among patients with end stage renal disease. Non-contrast CT scans of the abdomen and pelvis (CT A/P) are performed for pre-transplant (tx) evaluation in patients at high risk for cardiovascular events. The purpose of this study is to examine the severity and distribution of common iliac artery (CIA) and external iliac artery (EIA) calcifications and the associations with operative complications and clinical outcomes following renal tx. Methods Retrospective analysis of 202 renal tx recipients between 2/2013-11/2014 who underwent pre-operative CT A/P within 3 years of their surgery. All CT scans were assessed using a previously described scoring system (Table 1). Results The mean age was 57.2±11.2 years and 132/202 (65%) were men. 189/202 (94%) had hypertension, 124/202 (61%) had diabetes mellitus (DM), and 77/202 (38%) had coronary artery disease (CAD). There was no significant difference in calcification scores between sides (Table 2). In a regression analysis, previous cerebrovascular accident (CVA) (OR 5.43, p=0.03), CAD (OR 3.56, p<0.001), history of smoking (OR 2.08, p=0.02), DM (OR 2.23, p=0.01), and older age (OR 1.10, p<0.001) were significantly associated with moderate/severe CIA plaque (morphology score ≥ 2). One patient could not undergo tx due to severe, diffuse calcifications. 7 patients required arterial reconstruction during renal tx, all of whom had tx to the right EIA. Patients with moderate/severe right EIA plaque were more likely to require arterial reconstruction compared to those with none/mild plaque (4/34 [11.7%] v. 3/130 [2.3%]; p=0.03). There were 58 cases of delayed graft function (DGF), 51 of which occurred in transplants to the right EIA. In these cases, DGF was significantly associated with moderate/severe right EIA plaque (OR 2.82, p=0.009). Post-operative cardiac events occurred in 17/201 (8.5%) patients. In a multivariable logistic regression model, history of CAD (OR 3.79, p=0.03), congestive heart failure (OR 5.54, p=0.009), and severe CIA plaque (morphology score=3) (OR 4.98, p=0.04) were significantly associated with post-operative cardiac complications. 21 patients died during a mean follow-up of 1153 ± 1784 days. In a multivariable model, DM (p=0.05) and previous CVA (p=0.02) were significantly associated with increased risk of death. Conclusions Local calcified plaque of the recipient iliac artery is associated with increased operative complexity and higher rates of DGF. Plaque burden in the CIA is associated with both patient demographic factors and post-operative cardiac events, and is likely indicative of a greater severity of systemic atherosclerotic disease. Routine pre-tx CT scans in high risk patients may guide operative strategy and facilitate perioperative management to improve clinical outcomes. Table. No title available. Table. No title available. Research reported in this publication was supported in part by an NIAID T32 training grant from the National Institutes of Health under an award to the University of California, San Francisco (T32AI125222). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Peripheral artery disease is a growing health care burden, with rising costs related to use of lower extremity revascularization (LER). We sought to examine recent trends in procedure volumes by level of disease, provider specialty, and encounter setting. The Medicare claims database was queried for 2012 and 2016 LER Current Procedural Terminology codes, and data were extracted for allowed charges, allowed claims, billing provider, and procedure place of service. We examined trends in procedure by level of arterial disease treated. In 2012, there were 246,513 Current Procedural Terminology codes for LER billed to Medicare (14% open, 86% endovascular). In 2016, this number was 279,029 (10% open, 90% endovascular), a 13% increase in overall utilization. In 2012, there were 99,823 outpatient and 28,903 office-based endovascular procedures. By 2016, there were 104,083 outpatient and 71,873 office-based procedures. The breakdown of endovascular procedures in 2012 was 36% angioplasty, 43% stenting, and 21% atherectomy. Of these, 9%, 11%, and 26%, respectively, were performed in an office-based setting. Comparatively in 2016, endovascular interventions were composed of 35% angioplasty, 36% stenting, and 29% atherectomy, of which 16%, 23%, and 51%, respectively, were performed in an office-based setting (P < .001). There was no significant change in iliac interventions during the time period; however, differences were pronounced at the infrainguinal level. Total femoropopliteal interventions were 101,071 (47%) in 2012 and 118,540 (47%) in 2016, with atherectomy increasing from 25,038 (25%) in 2012 to 37,453 (32%) in 2016 (Fig). Total tibial endovascular interventions increased strikingly from 56,378 (23%) in 2012 to 79,333 (32%) in 2016, a relative volume increase of 41%. This was driven largely by increased use of tibial atherectomy, 19,008 (34%) in 2012 vs 34,438 (43%) in 2016 (P < .001). Notably, office-based procedures accounted for the bulk of the increase in atherectomy in 2016 (Fig). In keeping with the trend, atherectomy performed on an “additional tibial vessel” increased from 3707 in 2012 to 6494 in 2016. These trends were consistent across all provider specialties. Despite a lack of comparative evidence to support its use, the volume of office-based atherectomy procedures in the Medicare population continues to grow dramatically, particularly at the tibial level. These secular trends were similar across provider specialties and have significant cost implications.

OBJECTIVE:Prior reports have suggested unfavorable outcomes after endovascular aortic aneurysm repair (EVAR) performed outside of the recommended instructions for use (IFU) guidelines. We report our long-term EVAR experience in a large multicenter registry with regard to adherence to IFU guidelines.METHODS:Between 2000 and 2010, 489 of 1736 patients who underwent EVAR had preoperative anatomic measurements obtained from the M2S, Inc, imaging database (West Lebanon, NH). We examined outcomes in these patients with regard to whether they had met the device-specific IFU criteria. Primary outcomes were all-cause mortality and aneurysm-related mortality. Secondary outcomes were endoleak status, adverse events, reintervention, and aneurysm sac size change.RESULTS:The median follow-up for the 489 patients was 3.1 years (interquartile range, 1.6-5.0 years); 58.1% (n = 284) had EVAR performed within IFU guidelines (IFU-adherent group), and 41.9% (n = 205) had EVAR performed outside of IFU guidelines (IFU-nonadherent group). Preoperative anatomic data showed that 62.4% of the IFU-nonadherent group had short neck length, 10.2% had greater angulation than recommended, 7.3% did not meet neck diameter criteria, and 20% had multiple anatomic issues. A small portion (n = 49; 10%) of the 489 patients were lost to follow-up because of leaving membership enrollment (n = 28), moving outside the region (n = 10), or discontinuing image surveillance (n = 11). There was no significant difference in any of the primary or secondary outcomes between the IFU-adherent and IFU-nonadherent groups. Aneurysm sac size change at any time point during follow-up also did not differ significantly between the two groups. A Cox proportional hazard model showed that IFU nonadherence was not predictive of all-cause mortality (hazard ratio, 1.0; P = .91). Similarly, IFU nonadherence was not identified as a risk factor for aneurysm-related mortality or adverse events in stepwise Cox proportional hazards models.CONCLUSIONS:In our cohort of EVAR patients with detailed preoperative anatomic information and long-term follow-up, overall mortality and aneurysm-related mortality were unaffected by IFU adherence. In addition, rates of endoleak and reintervention after initial EVAR were similar, suggesting that lack of IFU-based anatomic suitability was not a driver of outcomes.

Objective: There is considerable controversy about the significance and appropriate treatment of type II endoleaks (T2Ls) after endovascular aneurysm repair (EVAR). We report our long-term experience with T2L management in a large multicenter registry.Methods: Between 2000 and 2010, 1736 patients underwent EVAR, and we recorded the incidence of T2L. Primary outcomes were mortality and aneurysm-related mortality (ARM). Secondary outcomes were change in aneurysm sac size, major adverse events, and reintervention.Results: During the follow-up (median of 32.2 months; interquartile range, 14.2-52.8 months), T2L was identified in 474 patients (27.3%). There were no late abdominal aortic aneurysm ruptures attributable to a T2L. Overall mortality (P = .47) and ARM (P = .26) did not differ between patients with and without T2L. Sac growth (median, 5 mm; interquartile range, 2-10 mm) was seen in 213 (44.9%) of the patients with T2L. Of these patients with a T2L and sac growth, 36 (16.9%) had an additional type of endoleak. Of all patients with T2L, 111 (23.4%) received reinterventions, including 39 patients who underwent multiple procedures; 74% of the reinterventions were performed in patients with sac growth. Reinterventions included lumbar embolization in 66 patients (59.5%), placement of additional stents in 48 (43.2%), open surgical revision in 14 (12.6%), and direct sac injection in 22 (19.8%). The reintervention was successful in 35 patients (31.5%). After patients with other types of endoleak were excluded, no difference in overall all-cause mortality (P = .57) or ARM (P = .09) was observed between patients with T2L-associated sac growth who underwent reintervention and those in whom T2L was left untreated.Conclusions: In our multicenter EVAR registry, overall all-cause mortality and ARM were unaffected by the presence of a T2L. Moreover, patients who were simply observed for T2L-associated sac growth had aneurysm-related outcomes similar to those in patients who underwent reintervention. Our future work will investigate the most cost-effective ways to select patients for intervention besides sac growth alone.

Background: Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1 alpha-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease.Methods: This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels were also available. Levels were considered deficient at < 20 ng/mL. Multivariable analysis was used to determine the association between vitamin D and mortality and vascular access outcomes.Results: The mean age was 66.7 years, 96.8% were male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among the vitamin D-deficient and nondeficient groups. During a median follow-up of 2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be younger (P = .01) and to have higher total cholesterol (P = .001) and lower albumin (P = .017) and calcium (P = .007) levels. Despite their younger age, mortality was significantly higher (P = .026) and vascular access failure was increased (P = .008) in the vitamin D-deficient group. Multivariate logistic regression analysis found vitamin Ddeficiency (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR, 3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI, 1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009), and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent predictors of vascular access failure in a Cox proportional hazard model.Conclusions: Vitamin D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient in vitamin D have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population.

Objective: Understanding the molecular mechanisms of vascular remodeling is critical to improving outcomes following revascularization procedures. While extensive animal data exists, correlative data on the mechanisms and kinetics of vascular healing in humans are lacking. Creation of brachio-basilic arteriovenous fistulas (AVF), often completed in 2 stages, offers an opportunity to examine the same vessel at 2 distinct time points. We hypothesized that immune and developmental related pathways are involved in AVF maturation. Methods: Human basilic vein samples were obtained at the time of AVF creation as baseline. Second samples were taken at basilic vein transposition after exposure to arterial hemodynamic forces. These paired samples were analyzed for differential gene expression using whole genome microarray. Structural staining and confirmatory qPCR were performed in selected genes. Results: Paired vein samples were collected from 3 patients. All subjects had successful AVF maturation. An average of 3 months transpired between collection of the first and second samples. Overall, 700 genes were significantly down-regulated and 732 genes were significantly up-regulated. Gene ontogeny analysis revealed no difference in the genes regulating developmental re-activation pathways or angiogenesis. However, inflammatory and fibrosis genes were still significantly up-regulated 3 months following AVF creation (p <<.05). Structural stains confirmed an increase in lumen and total vessel area and deposition of elastin and collagen with significant intimal hyperplasia between baseline and 3 month samples. Additionally, qPCR showed a 9.7 fold increase in IL-6 and a 10.4 fold increase in e-selectin at 3 months. Conclusions: Inflammatory and fibrosis gene pathways remain activated in mature fistulas despite stabilization of geometric remodeling. Further study is warranted to characterize these pathways and determine their significance in AVF patency.

Objective: Rupture after abdominal endovascular aortic aneurysm repair (EVAR) is a function of graft maintenance of the seal and fixation. We describe our 10-year experience with rupture after EVAR.Methods: From 2000 to 2010, 1736 patients with abdominal aortic aneurysm (AAA) from 17 medical centers underwent EVAR in a large, regional integrated health care system. Preoperative demographic and clinical data of interest were collected and stored in our registry. We retrospectively identified patients with postoperative rupture, characterized as "early" and "delayed" rupture (<= 30 days and >30 days after the initial EVAR, respectively), and identified predictors associated with delayed rupture.Results: The overall follow-up rate was 92%, and the median follow-up was 2.7 years (interquartile range, 1.2-4.4 years) in these 1736 EVAR patients. We identified 20 patients with ruptures; 70% were male, the mean age was 79 years, and mean AAA size at the initial EVAR was 6.3 cm. Six patients underwent initial EVAR for rupture (n = 2) or symptomatic presentation (n = 4). Of the 20 post-EVAR ruptures, 25% (five of 20) were early, all occurring within 2 days after the initial EVAR. Of these five patients, four had intraoperative adverse events leading directly to rupture, with one type I and one type III endoleak. Of the five early ruptures, four patients underwent endovascular repair and one received repair with open surgery, resulting in two perioperative deaths. Among the remaining 15 patients, the median time from initial EVAR to rupture was 31.1 months (interquartile range, 13.8-57.3 months). Most of these delayed ruptures (10 of 15) were preceded by AAA sac increases, including three patients with known endoleaks who underwent reintervention. At the time of delayed rupture, nine of 15 patients had new endoleaks. Among all 20 patients, six patients did not undergo repair (all delayed patients) and died, nine underwent repeated EVAR, and five had open repair. For patients who underwent repair for delayed rupture, mortality at 30 days and 1 year were 44.4% and 66.7%, respectively. Multivariable Cox regression analysis identified age 80 to 89 (hazard ratio, 3.3; 95% confidence interval, 1.1-9.4; P = . 03), and symptomatic or ruptured initial indication for EVAR (hazard ratio, 7.4; 95% confidence interval, 2.2-24.8; P < .01) as significant predictors of delayed rupture.Conclusions: Rupture after EVAR is a rare but devastating event, and mortality after repair exceeds 60% at 1 year. Most delayed cases showed late AAA expansion, thereby implicating late loss of seal and increased endoleaks as the cause of rupture in these patients and mandating vigilant surveillance.

Prior reports have suggested unfavorable outcomes after endovascular aneurysm repair (EVAR) performed outside of the recommended instructions for use (IFU). We report our long-term EVAR experience with regard to IFU in a large multicenter registry. Between 2000 and 2010, 1736 patients underwent EVAR, with 92% follow-up. Baseline anatomic measurements obtained from the M2S Inc imaging database were compared with device-specific IFU. Primary outcomes were mortality and aneurysm-related mortality (ARM). Secondary outcomes were endoleak status, adverse events, and reintervention. During the median follow-up of 2.7 years, 489 patients (28.2%) had preoperative anatomic data available. Overall, 58% had EVAR performed within and 42% outside of IFU guidelines. Of the outside-IFU patients, 62.4% had short neck length, 10.2% had greater angulation, 7.3% did not meet neck diameter criteria, and 20% had multiple anatomic issues. There was no difference in any of the primary or secondary outcomes between the two groups (Table). The percentage change in aneurysm sac size over time appeared similar (−12.1% vs −14.1% at 5 years), with no significant difference in sac increase at any time point during follow-up. Cox proportional hazard models showed that IFU nonadherence was not predictive of overall mortality (hazard ratio [HR], 1.06; P = .80), ARM (HR, 0.17; P = .07). or adverse events (HR, 0.84; P = .61). In our cohort of EVAR patients with detailed preoperative anatomic information and long-term follow-up, overall mortality and ARM were unaffected by IFU adherence, despite a higher proportion of women and larger aneurysms in the nonadherent group. In addition, rates of late endoleak and reintervention were similar, suggesting that operator experience and patient selection influence outcomes despite lack of IFU-based anatomic suitability.TableSelect demographics and outcomes by instructions for use (IFU) statusVariableIFU adherent (n = 284)IFU nonadherent (n = 205)PFemale, %6.714.6<.01Baseline AAA size, mm56.659.7<.01Overall mortality, %21.121.5.93ARM, %2.81.0.20Type I/III leak, %3.54.4.62Adverse events, %8.811.2.38Reintervention, %13.417.6.20AAA, Abdominal aortic aneurysm; ARM, aneurysm-related mortality. Open table in a new tab

Introduction: Balloon angioplasty of peripheral arteries induces a substantial inflammatory response and has a high rate of restenosis. Our hypothesis was that peri-adventitial injection of the antiproliferative, immunosuppressant drug rapamycin would reduce luminal stenosis in a porcine femoral artery model of balloon angioplasty injury. Methods: 16 male crossbred swine had a balloon angioplasty overstretch injury of the femoral artery followed by peri-adventitial injection of saline or 500μg of nanoparticle albumin-bound (nab) rapamycin with an intraluminal microinfusion catheter. Qualitative and quantitative assessments of the femoral arteries, including histomorphometric measurements, were performed on H&E, Masson’s trichrome or immunohistochemistry stained sections. Blood and tissue rapamycin concentration were assessed by liquid chromatography and mass spectrometry at 1h, 3d, 8d and 28d. Results: There was 100% procedural success with periadventitial injection. At 28 days, femoral arteries treated with nab-rapamycin had a 42% reduction in luminal stenosis, 19.5 ± 3.3% vs 11.4 ± 0.84%, p=0.01 t-test (figure). Nab-rapamycin also significantly reduced medial fibrosis by qualitative analysis, p<0.0001 t-test, and media cell proliferation by Ki-67 staining, p=0.02 t-test. There were significantly fewer adventitial leukocytes at 3 days, p=0.03 t-test, but no difference at 28 days. One hour after injection, the perivascular concentration of nab-rapamycin was 1500-times higher than serum and rapamycin persisted in the tissue for at least 8 days. Rapamycin was not detectable in serum or tissue at 28 days. There was no difference in endothelial coverage or regeneration by Factor VII and H&E staining at 3, 8 or 28 days. Conclusions: A single periadventitial dose of nab-rapamycin significantly reduced luminal stenosis in a porcine model of femoral artery balloon angioplasty injury. The observed reduction in early adventitial infiltration by leukocytes and decrease in medial cell proliferation and fibrosis at 28 days suggests a mechanism by which nab-rapamycin may have an effect. Adventitial injection with an intraluminal microinfusion catheter is safe and efficient and represents an alternative to stent- or balloon-based local drug delivery.