Relevance of BEST-CLI trial endpoints in a tertiary care limb preservation program.

OBJECTIVE: Major adverse limb event-free survival (MALE-FS) differed significantly by initial revascularization approach in the BEST-CLI randomized trial. The BEST-CLI trial represented a highly selected subgroup of patients seen in clinical practice; thus, we examined the endpoint of MALE-FS in an all-comers tertiary care practice setting. METHODS: This is a single-center retrospective study of consecutive, unique patients who underwent technically successful infrainguinal revascularization for chronic limb-threatening ischemia (2011-2021). MALE was major amputation (transtibial or above) or major reintervention (new bypass, open bypass revision, thrombectomy, or thrombolysis). RESULTS: Among 469 subjects, the mean age was 70 years, and 34% were female. Characteristics included diabetes (68%), end-stage renal disease (ESRD) (16%), Wound, Ischemia, and foot Infection (WIfI) stage 4 (44%), Global Limb Anatomic Staging System (GLASS) stage 3 (62%), and high pedal artery calcium score (pMAC) (22%). Index revascularization was autogenous vein bypass (AVB) (30%), non-autogenous bypass (NAB) (13%), or endovascular (ENDO) (57%). The composite endpoint of MALE or death occurred in 237 patients (51%) at a median time of 189 days from index revascularization. In an adjusted Cox model, factors independently associated with MALE or death included younger age, ESRD, WIfI stage 4, higher GLASS stage, and moderate-severe pMAC, whereas AVB was associated with improved MALE-FS. Freedom from MALE-FS, MALE, and major amputation at 30 days were 90%, 92%, and 95%; and at 1 year were 63%, 70%, and 83%, respectively. MALE occurred in 144 patients (31%) and was associated with ESRD, WIfI stage, GLASS stage, pMAC score, and index revascularization approach. AVB had superior durability, with adjusted 2-year freedom from MALE of 72%, compared with 66% for ENDO and 51% for NAB. Within the AVB group, spliced vein conduit had higher MALE compared with single-segment vein (hazard ratio, 1.8; 95% confidence interval, 0.9-3.7; P = .008 after inverse propensity weighting), but there was no statistically significant difference in major amputation. Of the 144 patients with any MALE, the first MALE was major reintervention in 47% and major amputation in 53%. Major amputation as first MALE was associated with non-AVB index approach. Indications for major reintervention were symptomatic stenosis/occlusion (54%), lack of clinical improvement (28%), asymptomatic graft stenosis (16%), and iatrogenic events (3%). Conversion to bypass occurred after 6% of ENDO cases, two-thirds of which involved distal bypass targets at the ankle or foot. CONCLUSIONS: In this consecutive, all-comers cohort, disease complexity was associated with procedural selection and MALE-FS. AVB independently provided the greatest MALE-FS and freedom from MALE and major amputation. Compared with the BEST-CLI randomized trial, MALE after ENDO in this series was more frequently major amputation, with relatively few conversions to open bypass.

Renal Embolization-Induced Uremic Swine Model for Assessment of Next-Generation Implantable Hemodialyzers.

Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m2 and 140-165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.

Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.

The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes.

Characterization of human islet function in a convection-driven intravascular bioartificial pancreas.

Clinical islet transplantation for treatment of type 1 diabetes (T1D) is limited by the shortage of pancreas donors and need for lifelong immunosuppressive therapy. A convection-driven intravascular bioartificial pancreas (iBAP) based on highly permeable, yet immunologically protective, silicon nanopore membranes (SNM) holds promise to sustain islet function without the need for immunosuppressants. Here, we investigate short-term functionality of encapsulated human islets in an iBAP prototype. Using the finite element method (FEM), we calculated predicted oxygen profiles within islet scaffolds at normalized perifusion rates of 14-200 nl/min/IEQ. The modeling showed the need for minimum in vitro and in vivo islet perifusion rates of 28 and 100 nl/min/IEQ, respectively to support metabolic insulin production requirements in the iBAP. In vitro glucose-stimulated insulin secretion (GSIS) profiles revealed a first-phase response time of <15 min and comparable insulin production rates to standard perifusion systems (~10 pg/min/IEQ) for perifusion rates of 100-200 nl/min/IEQ. An intravenous glucose tolerance test (IVGTT), performed at a perifusion rate of 100-170 nl/min/IEQ in a non-diabetic pig, demonstrated a clinically relevant C-peptide production rate (1.0-2.8 pg/min/IEQ) with a response time of <5 min.

Patients with abdominal aortic aneurysms have reduced levels of microRNA 122-5p in circulating exosomes.

OBJECTIVE: There are currently no specific biomarkers to identify patients with abdominal aortic aneurysms (AAAs). Circulating exosomes contain microRNAs (miRNA) that are potential biomarkers for the presence of disease. This study aimed to characterize the exosomal miRNA expression profile of patients with AAAs in order to identify novel biomarkers of disease. METHODS: Patients undergoing duplex ultrasound (US) or computed tomography (CT) for screening or surveillance of an AAA were screened to participate in the study. Cases with AAA were defined as having a max aortic diameter >3 cm. Circulating plasma exosomes were isolated using Cushioned-Density Gradient Ultracentrifugation and total RNA was extracted. Next Generation Sequencing was performed on the Illumina HiSeq4000 SE50. Differential miRNA expression analysis was performed using DESeq2 software with a Benjamini-Hochberg correction. MicroRNA expression profiles were validated by Quantitative Real-Time PCR. RESULTS: A total of 109 patients were screened to participate in the study. Eleven patients with AAA and 15 non-aneurysmal controls met study criteria and were enrolled. Ultrasound measured aortic diameter was significantly larger in the AAA group (mean maximum diameter 4.3 vs 2.0 cm, P = 6.45x10-6). More AAA patients had coronary artery disease (5/11 vs 1/15, P = 0.05) as compared to controls, but the groups did not differ significantly in the rates of peripheral arterial disease and chronic obstructive pulmonary disease. A total of 40 miRNAs were differentially expressed (P<0.05). Of these, 18 miRNAs were downregulated and 22 were upregulated in the AAA group compared to controls. After false discovery rate (FDR) adjustment, only miR-122-5p was expressed at significantly different levels in the AAA group compared to controls (fold change = 5.03 controls vs AAA; raw P = 1.8x10-5; FDR P = 0.02). CONCLUSION: Plasma exosomes from AAA patients have significantly reduced levels of miRNA-122-5p compared to controls. This is a novel exosome-associated miRNA that warrants further investigation to determine its use as a diagnostic biomarker and potential implications in AAA pathogenesis.

Presenting limb severity is associated with long-term outcomes after infrainguinal revascularization for chronic limb-threatening ischemia.

OBJECTIVE: The SVS Wound, Ischemia, foot Infection (WIfI) limb staging system was established to estimate risk of major amputation in chronic limb-threatening ischemia (CLTI) and better stratify outcomes comparisons. There is little data on treatment outcomes beyond 1 year based on presenting WIfI stage. METHODS: This is a single-institution retrospective study of 413 patients who underwent infrainguinal revascularization for CLTI (2011-2021) with data available for WIfI staging. Patient characteristics and outcomes were gathered from the electronic medical record. Data were analyzed based on presenting WIfI stage and initial treatment received at our center. RESULTS: Presenting WIfI stages were 1 to 2 (23%), 3 (27%), and 4 (50%). Index revascularization approach was endoluminal (59%), autogenous vein bypass (29%), or non-autogenous bypass (13%). Operative mortality within 30 days was 2.9% and was not associated with WIfI stage or revascularization approach. Median limb follow-up time was 502 days (interquartile range [IQR], 112-1256 days), and median survival follow-up time was 932 days (IQR, 343-1770 days). Major amputation or death occurred in 19% and 46% of patients at median times of 119 days (IQR, 28-314 days) and 739 days (IQR, 204-1475 days), respectively. WIfI stage was independently associated with major amputation (P = .001), as was initial revascularization approach (P = .01). In a Cox proportional hazards model, factors independently associated with major amputation were male sex (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.04-2.0; P = .03), diabetes (HR, 1.8; 95% CI, 1.3-2.5; P = .001), WIfI stage 4 (HR, 2.3; 95% CI, 1.5-3.5; P < .001), and non-autogenous bypass (HR, 2.9; 95% CI, 2.1-4.2; P < .001). In a Cox proportional hazards model for mortality, independently associated factors were age (HR, 1.04; 95% CI, 1.02-1.05; P < .001), end-stage renal disease (HR, 2.8; 95% CI, 1.9-4.0; P < .001), congestive heart failure (HR, 1.9; 95% CI, 1.4-2.5; P < .001), chronic obstructive pulmonary disease (HR, 1.5; 95% CI, 1.1-2.1; P = .02), and WIfI stage 4 (HR, 1.6; 95% CI, 1.04-2.2; P = .03). Among those presenting with WIfI stage 4 limbs, Kaplan-Meier estimated rates of freedom from major amputation or death at 2 years were 71% ± 3.7% and 68% ± 3.5%, respectively. In an inverse propensity weighted Cox proportional hazards model, non-white race (HR, 1.5; 95% CI, 1.01-2.2; P = .047), diabetes (HR, 2.0; 95% CI, 1.2-3.3; P = .008), Global Anatomic Staging System infrapopliteal grade (HR, 1.2; 95% CI, 1.05-1.3; P = .005), non-autogenous bypass (HR, 3.2; 95% CI, 1.9-5.3; P < .001), and endoluminal revascularization (HR, 2.6; 95% CI, 1.6-4.3; P < .001) were independently associated with major amputation in the WIfI stage 4 subgroup. CONCLUSIONS: Presenting WIfI stage is strongly associated with long-term risks of major amputation and death following infrainguinal revascularization for CLTI and should be used to stratify outcomes comparisons. Effective revascularization is critical in WIfI stage 4 disease, and autogenous vein bypass provides durable long-term limb preservation.

Pedal arterial calcification score is associated with hemodynamic change and major amputation after infrainguinal revascularization for chronic limb-threatening ischemia.

OBJECTIVE: Pedal medial arterial calcification (pMAC) is associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). We hypothesize that this association would be related to unresolved distal ischemia. We investigated relationships across pMAC score, hemodynamic change, and major amputation after infrainguinal revascularization for CLTI. METHODS: This is a single-institution, retrospective study of 306 patients who underwent technically successful infrainguinal revascularization for CLTI (2011-2020) and had foot x-rays for blinded pMAC scoring (0-5). A total of 136 (44%) patients had toe pressure measurements performed within 90 days before and 60 days after revascularization. Ischemia grade (0-3) was assigned using the Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) system. RESULTS: The revascularization approach was open bypass in 118 (38%) and endovascular in 188 (62%) patients. pMAC scores were trichotomized (0-1 [125; 41%], 2-4 [116; 38%], 5 [65; 21%]). Post-revascularization WIfI ischemia grade was improved in 78 of 136 (57%) and unchanged/worsened in 58 of 136 (43%). A lower pMAC score was associated with hemodynamic improvement (P = .004). Failure to improve the ischemia grade was associated with major amputation (P = .0002). In the endovascular subgroup, WIfI ischemia grade was improved in 43 of 90 (48%) with available measurements, and 37 of 188 (20%) underwent major amputation. In a multivariate logistic model, pMAC 5 was the only factor independently associated with unimproved ischemia grade after endovascular treatment (odds ratio: 4.0 [1.1-16.6], P = .04). In a Cox proportional hazards model, factors independently associated with major amputation after endoluminal revascularization were WIfI stage 4 (hazard ratio [HR]: 2.7 [1.3-5.7], P = .007) and pMAC score (pMAC: 2-4: HR: 10.6 [1.4-80.7], P = .02; pMAC: 5: HR: 15.5 [2.0-119], P = .008). In the bypass subgroup, WIfI ischemia grade was improved in 35 of 46 (76%) with available measurements but was not associated with pMAC score (P = .88) or any other baseline patient or limb characteristics. A total of 19 of 118 (16%) patients underwent major amputation. In a Cox proportional hazards model including bypass conduit, WIfI stage, and pMAC score, the only factor independently associated with major amputation after bypass was use of nonautologous conduit (HR: 5.6 [1.8-17.6], P = .003). CONCLUSIONS: The pMAC score is independently associated with persistent distal ischemia and major amputation after technically successful revascularization for CLTI. These data suggest that pMAC may be a marker for hemodynamic response to revascularization and risk of limb loss, and it may have a stronger influence on the outcome of endoluminal interventions.

Limb-based patency as a measure of effective revascularization for chronic limb-threatening ischemia.

OBJECTIVE: In 2019, the Global Vascular Guidelines on chronic limb-threatening ischemia (CLTI) introduced the concept of limb-based patency (LBP) defined as maintained patency of a target artery pathway after intervention. The purpose of this study was to investigate the relationship between LBP and major adverse limb events (MALE) after infrainguinal revascularization for CLTI. METHODS: Consecutive patients undergoing revascularization for CLTI between 2016 and 2019 at a single tertiary institution with a dedicated limb preservation team were included. Subjects with aortoiliac disease, prior infrainguinal stents, or existing bypass grafts were excluded. Demographics, Global Limb Anatomic Staging System scores, Wound, Ischemia, foot Infection (WIfI) stages, revascularization details, and limb-specific outcomes were reviewed. LBP was defined by the absence of reintervention, occlusion, critical stenosis (>70%), or hemodynamic compromise with ongoing symptoms of CLTI. MALE included thrombectomy or thrombolysis, new bypass, open surgical graft revision and/or major amputation. RESULTS: We analyzed 184 unique limbs in 163 patients. This cohort was composed of 66.9% male patients with a mean age of 72 years. Baseline characteristics included diabetes (66%), tissue loss (91%), and advanced WIfI stages (30% stage 3, 51% stage 4). Global Limb Anatomic Staging System stage 3 anatomic patterns were common (n = 119 [65%]). Sixty limbs were treated with open bypass (65% involving tibial targets) and 124 underwent endovascular intervention (70% including infrapopliteal targets). The 12-month freedom from MALE and loss of LBP were 74.0% ± 3.7% and 48.6% ± 4.2%, respectively. Diabetes (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.13-5.83; P = .025) and loss of LBP (HR, 4.12; 95% CI, 1.96-8.64; P < .001) were independent predictors of MALE in a Cox proportional hazard model. Loss of LBP was the sole independent predictor of major limb amputation after revascularization (HR, 4.97; 95% CI, 1.89-13.09; P = .001). Loss of LBP impacted both intermediate-risk limbs (HR, 2.85; 95% CI, 1.02-7.97; P = .047 in WIfI stages 1-3) and high-risk limbs (HR, 3.99; 95% CI, 1.32-12.11; P = .014 in WIfI stage 4). However, the loss of LBP had the greatest impact on patients presenting with WIfI stage 4 disease (31% vs 8% major limb amputation at 12 months in limbs without vs with maintained LBP). CONCLUSIONS: The anatomic durability of revascularization, as measured by LBP, is a key determinant of treatment outcomes in CLTI regardless of the initial mode of intervention undertaken. Loss of LBP is most detrimental in patients presenting with advanced limb threat (WIfI stage 4).

Applicability of the Vascular Quality Initiative mortality prediction model for infrainguinal revascularization in a tertiary limb preservation center population.

OBJECTIVE: Patients undergoing revascularization for chronic limb-threatening ischemia (CLTI) are at elevated risk for both mortality and limb loss. To facilitate therapeutic decision-making, a mortality prediction model derived from the Vascular Quality Initiative (VQI) database has stratified patients into low, medium, and high risk, defined by 30-day mortality estimates of ≤3%, 3%-5%, or >5% and 2-year mortality estimates of ≤30%, 30%-50%, or ≥50%, respectively. The purpose of this study was to compare expected mortality risk derived from this model with observed outcomes in a tertiary center. METHODS: Consecutive patients treated at a single center between 2016 and 2019 were analyzed. Baseline demographics, approach, and mortality events were reviewed. Observed mortality was obtained using life-table methods and compared using a log-rank test with the expected mortality risk that was calculated using the VQI model. RESULTS: This study cohort consisted of 195 revascularization procedures in 169 unique patients stratified into 128 (66%) low-, 50 (26%) medium-, and 17 (8%) high-risk cases based on the VQI model. Ninety percent of revascularizations were performed for tissue loss. Compared with the VQI population, comorbidities were prevalent and included unstable angina or myocardial infarction within 6 months (6% vs 2.4% in VQI; P < .001), congestive heart failure (30% vs 23%; P < .001), and dialysis dependence (14% vs 0.9%; P < .001). Patients were also older (31% vs 21% ≥80 years old; P < .001) and more likely to be frail (45% vs 64% independent; P < .001). High-risk patients were more prevalent in the endovascular group (11% of 132 endovascular interventions vs 3% of 63 bypasses; P = .056). Thirty-day observed mortality exceeded expected VQI prediction model mortality in all groups, although was not statistically significant. The VQI model adequately stratified the studied population into risk groups (P < .001). Low-risk patients with CLTI (65% of the overall cohort) experienced 2-year mortality of 18.9%. However, observed mortality rates for medium- and high-risk VQI strata were similar. After a median follow-up of 28 months, medium-risk patients incurred a significantly higher mortality than predicted (53.5% ± 2.1% vs 36.8% ± 1.1%; P = .016). CONCLUSIONS: The VQI mortality prediction model discriminates mortality risk after limb revascularization in CLTI, accurately identifying a majority subgroup of patients who are suitable for either open or endovascular intervention. However, it may underestimate mortality in a tertiary referral population with high comorbidity burden and was not well calibrated for the medium-risk group. It may be more appropriate to dichotomize patients with CLTI who are candidates for limb salvage into an average-risk and high-risk group.

Pedal arterial calcification score is associated with the risk of major amputation in chronic limb-threatening ischemia.

OBJECTIVE: The medial arterial calcification (MAC) score is a simple metric that describes the burden of inframalleolar calcification using a plain foot radiograph. We hypothesized that a higher MAC score would be independently associated with the risk of major amputation in patients with chronic limb-threatening ischemia (CLTI). METHODS: We performed a single-institution, retrospective study of 250 patients who had undergone infrainguinal revascularization for CLTI from January 2011 to July 2019 and had foot radiographs available for MAC score calculation. A single blinded reviewer assigned MAC scores of 0 to 5 using two-view minimum plain foot radiographs, with 1 point each for calcification of >2 cm in the dorsalis pedis, plantar, and metatarsal arteries and >1 cm in the hallux and non-hallux digital arteries. RESULTS: The MAC score was 0 in 36%, 1 in 5.2%, 2 in 8.4%, 3 in 14%, 4 in 14%, and 5 in 21%. The MAC score was trichotomized to facilitate analysis and clinical utility (mild, MAC score 0-1; moderate, MAC score 2-4; and severe, MAC score 5). The variables independently associated with a higher MAC score were male sex, diabetes, end-stage renal disease, and the global limb anatomic staging system pedal score. The MAC score was not associated with the Society for Vascular Surgery WIfI (wound, ischemia, foot infection) grade or overall WIfI stage (P = .58). The median follow-up was 759 days (interquartile range, 264-1541 days). A higher MAC score was significantly associated with the risk of major amputation (P < .0001). In a Cox proportional hazards multiple regression model for major amputation that included the trichotomized MAC score, diabetes, end-stage renal disease, and WIfI stage (1-3 vs 4). The MAC score (MAC score 5: hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.9-13.1; P = .001; MAC score 2-4: HR, 3.4; 95% CI, 1.3-8.8; P = .01) and WIfI stage (WIfI stage 4: HR, 2.1; 95% CI, 1.1-3.9; P = .03) were significantly associated with the risk of major amputation. In the subsets of patients with the most advanced WIfI stage of 3 to 4 (191 of 250; 76%) and patients with diabetes (185 of 250; 74%), the MAC score further stratified the risk of major amputation on univariate and multivariate analyses. CONCLUSIONS: The MAC score is a simple, practical tool and a strong independent predictor of major amputation in patients with CLTI. It provides novel clinical data that are currently unmeasured using any validated CLTI staging system. The MAC score is a promising standardized measure of inframalleolar disease burden that can be used in conjunction with the WIfI staging system to help improve outcomes stratification and determine the optimal treatment strategies for patients with CLTI.

Toward endovascular treatment of type A aortic dissection with smaller landing zones and more patient eligibility.

OBJECTIVE: Type A or ascending aortic dissection is an acute life-threatening condition with high morbidity and mortality. Open surgery remains the standard of care. The development of minimally invasive endografts for type A aortic dissection (TAAD) will require a detailed understanding of the dissection and aortic root anatomy to determine patient eligibility and optimal device specifications. METHODS: Computed tomography images of TAAD cases at our institution from 2012 to 2019 were identified, and three-dimensional reconstructions were performed using OsiriX, version 10.0 (Pixmeo SARL, Bernex, Switzerland). We analyzed key anatomic structures, including centerline length measurements, ascending aorta and aortic root dimensions, and the location and extent of dissection in relationship to the coronary ostia. RESULTS: A total of 53 patients were identified (mean ± standard deviation age, 60.4 ± 17.1 years; 36 men and 17 women), 46 of whom had undergone surgery for TAAD. Four patients had died within 30 days of surgery. In 47 patients (88.7%), the entry tear was distal to the highest coronary ostium. These cases were retrospectively considered for endovascular intervention using a nonbranched, single endograft stent. The proximal landing zone (LZ) was defined as the distance from the highest coronary ostium to the entry tear. Of the 53 patients, 35 (66.0%) had a proximal LZ length of ≥2.0 cm, 38 (71.7%) had a proximal LZ length of ≥1.5 cm, and 42 (79.2%) had a proximal LZ length of ≥1.0 cm. The median proximal and distal LZ diameters of the sinotubular junction (STJ) and distal ascending aorta regions were 3.29 cm (interquartile range [IQR], 2.73-4.10 cm) and 3.49 cm (IQR, 3.09-3.87 cm, respectively), with a median length from the STJ to the innominate takeoff of 8.08 cm (IQR, 6.96-9.40 cm). The median ascending aorta radius of curvature was 6.48 cm (IQR, 5.27-8.00 cm). Of the 53 patients, 25 (47.2%) could be treated with a straight tube graft with a ≤20% diameter mismatch between the proximal and distal LZs. CONCLUSIONS: Almost 80% of the patients with TAAD had had a proximal LZ of ≥1.0 cm. Of these patients, 47.2% had anatomy amenable for endovascular therapy with a nontapered straight tube graft using commercially available devices. To increase patient eligibility for TAAD endovascular intervention, enhanced precision deployment with an adequate seal in shorter LZs will be required. Our results can serve as a guide for endovascular device specifications designed to treat this devastating condition.

Contemporary Experience with Paravisceral Aortic Aneurysm (PVAAA) Repair in a Tertiary Center.

OBJECTIVES: To describe contemporary outcomes from a single center capable of both complex open and endovascular aortic repair for paravisceral aortic aneurysms (PVAAA). METHODS: Data on all patients receiving open or endovascular (endo) treatment for aortic aneurysms with proximal extent at or above the renal arteries and distal to the inferior pulmonary ligament (IPL) were reviewed. Coarsened exact matching (CEM) on age, aneurysm type, gender, coronary artery disease (CAD), previous aortic surgery and symptomatic status created balanced cohorts for outcomes comparisons. RESULTS: Between October, 2006 and February, 2018, 194 patients were treated for juxtarenal (40%), pararenal (21%), paravisceral (6%) and Type 4 thoracoabdominal (34%) aortic aneurysms with open (81, 42%) or endo (113, 58%) at a single tertiary center. Endo repairs included renal coverage with a bifurcated graft (2%), unilateral (13%) or bilateral (4%) renal snorkels, Z-fen (15%), multi-branched graft (IDE protocol; 62%) and unique complex configurations (4%). On multivariable analysis, patients selected for open surgery were more likely to be symptomatic, whereas older patients, female patients and those with Type 4 TAAA extent were more often selected for endovascular treatment. Matching based on the significant independent covariates reduced the open and endovascular groups by one-third. Survival at 30 days was 97% for endo and 94% for open repair, 98% for both subgroups when excluding symptomatic cases, and was not different between the matched groups (98% vs 89%; P=0.23). Hospital and ICU stays were longer in open patients (8 vs. 10 days, 2 vs. 4, both P≤0.001). Post-op CVA, MI, lower extremity ischemia, surgical site infections and reoperation were not different between matched groups (all p>0.05), while pulmonary and intestinal complications, as well as grade 1/2 renal dysfunction by RIFLE criteria, were more common after open repair (all P<0.05). Spinal cord ischemia was significantly more frequent in the unmatched Endo group (11% vs. 1%, P=0.02), but this difference was not significant after matching. Composite major aortic complications was no different between treatment groups (unmatched P=0.91, matched P=0.87). Endo treatment resulted in patients more frequently discharged to home (84% vs. 66%, P=0.02). Reintervention after 30 days occurred more frequently in the endo group (P=0.002). Estimated survivals at 1 and 5 years for endo and open are 96% vs. 81% and 69% vs. 81% respectively (Log-rank P=0.57). CONCLUSIONS: Contemporary repair of PVAAA demonstrates safe outcomes with durable survival benefit when patients are well-selected for open or complex endovascular repair. We believe these data have implications for off-label device use in the treatment of PVAAA, and that open repair remains an essential option for younger, good risk patients in experienced centers.

Comparison of Ellipsys Percutaneous and Proximal Forearm Gracz-Type Surgical Arteriovenous Fistulas.

RATIONALE & OBJECTIVE: Percutaneous arteriovenous fistulas (AVF) are created by establishing a proximal forearm anastomosis and offer a safe and reliable vascular access. This study compares the Ellipsys percutaneous AVF with a proximal forearm Gracz-type surgical AVF, chosen for comparison as it is constructed at the same anatomical site. STUDY DESIGN: Retrospective study of prospectively collected clinical data. SETTING & PARTICIPANTS: All vascular access procedures conducted during a 34-month period were reviewed. The study groups comprised 89 percutaneous AVFs and 69 surgical AVFs. EXPOSURE: Percutaneous or surgical AVF placement. OUTCOME: AVF patency, function, and complications. ANALYTICAL APPROACH: Patency rates for each AVF group were evaluated by competing risk survival analysis using a cumulative incidence function. Association of primary, primary assisted, and secondary patency with the AVF groups was examined by Cox proportional hazard models. RESULTS: Technical success was 100% for both groups. Average procedure times were 14 minutes for percutaneous AVFs and 74 minutes for surgical AVFs (P < 0.001). Proximal radial artery (PRA) was used in all percutaneous AVF cases. Inflow for surgical AVFs included radial (30%), ulnar (12%), and brachial (58%) arteries. Outflow veins for both groups were the cephalic and/or basilic veins. Access flow volumes, times to maturation, and overall numbers of interventions per patient-year were not significantly different. Cumulative incidence of primary patency failure at 12 months was lower for surgical AVF (47% vs 64%, P = 0.1), but secondary patency failure was not different between groups (20% vs 12%, P = 0.3). PRA surgical AVFs had similar primary patency (65% vs 64%, P = 0.8) but higher secondary patency failure rates than percutaneous AVFs at 12 months (34% vs 12%, P = 0.04). LIMITATIONS: Retrospective study with a relatively short follow-up period, and not all patients required hemodialysis at the end of study. CONCLUSIONS: Both percutaneous and surgical AVFs demonstrated high rates of technical success and secondary patency. Percutaneous AVFs required shorter procedure times. The rate of intervention was similar. When a distal radial artery AVF is not feasible, percutaneous AVF might offer an appropriate procedure for creating a safe and functional access, maintaining further proximal forearm surgical AVF creation options.

The Global Limb Anatomic Staging System is associated with outcomes of infrainguinal revascularization in chronic limb threatening ischemia.

OBJECTIVE: The Global Limb Anatomic Staging System (GLASS) has been proposed to facilitate clinical decision-making regarding revascularization for chronic limb threatening ischemia (CLTI). The purpose of the present study was to define its relationship to the treatment outcomes in CLTI. METHODS: Consecutive patients who had undergone peripheral angiography for rest pain or tissue loss from January 2017 to July 2019 at a tertiary referral center with a dedicated limb preservation program were reviewed. Subjects with significant aortoiliac disease, previous infrainguinal stenting or functioning bypass grafts, or GLASS stage 0 were excluded. The GLASS score was assigned from the preintervention angiography findings, and the treating surgeon determined the primary infrapopliteal target artery pathway for the limb at risk. The demographic data, procedural details, and clinical outcomes were analyzed. RESULTS: The study cohort included 167 patients and 194 limbs, of which 175 of 194 limbs (90%) had presented with tissue loss and 149 of 182 limbs (83%) with WIfI (Wound, Ischemia and foot Infection) stage 3 or 4. The GLASS stage was GLASS 1 in 14%, GLASS 2 in 18%, and GLASS 3 in 68%. GLASS 3 anatomy was present in 85% of 52 limbs treated by bypass and 55% of 108 limbs treated by endovascular intervention (EVI; P < .001). Revascularization was not performed in 34 limbs, most of which were GLASS 3 (85%). Immediate technical failure for EVI (ie, failure to establish target artery pathway) occurred exclusively in the setting of GLASS 3 anatomy (n = 13; 22%). After a median follow-up of 10 months, limb-based patency after EVI was significantly lower in GLASS 3 than in GLASS 1 or 2 limbs (42% vs 59%; P = .018). GLASS 3 was associated with reduced major adverse limb events-free survival in both the EVI group (P = .002) and the overall revascularized cohort (P = .001). GLASS 3 was also associated with significantly reduced overall survival, amputation-free survival, and reintervention-free survival. In a Cox proportional hazards model, GLASS 3 (hazard ratio, 2.35; 95% confidence interval, 1.30-4.24; P = .005) and WIfI wound grade 3 (hazard ratio, 2.64; 95% confidence interval, 1.26-5.53; P = .010) were independent predictors of reduced major adverse limb events-free survival after revascularization. CONCLUSIONS: GLASS stage 3 was strongly associated with major adverse clinical outcomes after revascularization in patients with CLTI.

A Review and Proposed Classification System for the No-Option Patient With Chronic Limb-Threatening Ischemia.

A growing, but poorly defined subset of patients with chronic limb-threatening ischemia (CLTI) have "no option" for revascularization. One notable subgroup includes patients with severe ischemia and advanced pedal artery occlusive disease, termed "desert foot," who are at high risk for major amputation due to a lack of conventional revascularization options. Although new therapies are being developed for no-option patients with desert foot anatomy, this subgroup and the broader group of no-option patients are not well defined, limiting the ability to evaluate outcomes. Based on a systematic review, a classification of the no-option CLTI patient was constructed for use in clinical practice and studies. Several no-option conditions were identified, including type I-severe and pedal occlusive disease (desert foot anatomy) for which there is no accepted method of repair; type II-lack of suitable venous conduit for bypass in the setting of an acceptable target for bypass; type III-extensive tissue loss with exposure of vital structures that renders salvage impossible; type IV-advanced medical comorbidities for which available revascularization options would pose a prohibitive risk; and type V-presence of a nonfunctional limb. While type I and type II patients may have no option for revascularization, type III and type V patients have wounds, infection, comorbidities, or functional status that may leave them with few options for revascularization. As treatment strategies continue to evolve and novel methods of revascularization are developed, the ability to identify no-option patients in a standardized fashion will aid in treatment selection and assessment of outcomes.

Impact of the coronavirus disease 2019 pandemic on an academic vascular practice and a multidisciplinary limb preservation program.

With the aggressive resource conservation necessary to face the coronavirus disease 2019 pandemic, vascular surgeons have faced unique challenges in managing the health of their high-risk patients. An early analysis of patient outcomes after pandemic-related practice changes suggested that patients with chronic limb threatening ischemia have been presenting with more severe foot infections and are more likely to require major limb amputation compared with 6 months previously. As our society and health care system adapt to the new changes required in the post-coronavirus disease 2019 era, it is critical that we pay special attention to the most vulnerable subsets of patients with vascular disease, particularly those with chronic limb threatening ischemia and limited access to care.

Natural history of acute pediatric iliofemoral artery thrombosis treated with anticoagulation.

OBJECTIVE: Acute iliofemoral artery thrombosis (IFAT) can occur in critically ill neonates and infants who require indwelling arterial cannulas for monitoring or as a consequence of cardiac catheterization. Guidelines suggest treatment with anticoagulation, but evidence supporting the optimal duration of therapy and the role of surveillance ultrasound is limited. The objectives of this study were to characterize the kinetics of thrombus resolution and to define an appropriate duration of anticoagulation and interval for surveillance ultrasound. METHODS: This was a single-center retrospective cohort study of pediatric patients with acute IFAT from 2011 to 2019. Medical records and vascular laboratory studies were reviewed. Patients with one or more surveillance ultrasound examinations were included. Thrombus resolution was defined as multiphasic flow throughout the index limb without evidence of echogenic intraluminal material by ultrasound. Time to resolution of thrombus was assessed using Kaplan-Meier analysis. RESULTS: Fifty-four limbs in 50 patients were identified with acute IFAT. The median age was 9.9 weeks (interquartile range, 3.1-21.7 weeks), with a median weight of 4.2 kg (interquartile range, 3.3-5.5 kg). The majority of limbs (65%) with acute IFAT presented with a diminished pedal Doppler signal, commonly after cardiac catheterization (55%). Forty-eight (89%) limbs had complete arterial occlusion on index ultrasound, and flow could not be detected below the ankle in 48%. The median number of ultrasound examinations per limb was three (range, two to seven), and 61% of limbs had a surveillance ultrasound within 7 days of diagnosis. At 14 and 30 days, 33% and 64% of patients, respectively, treated with anticoagulation had an estimated complete resolution of thrombus. Nine (17%) patients did not receive anticoagulation, and only two of these patients experienced IFAT resolution. At the time of diagnosis, one patient underwent open thrombectomy because of a contraindication to anticoagulation, and one patient was treated with thrombolysis. There were no instances of tissue loss or amputation CONCLUSIONS: Management of IFAT with anticoagulation resulted in successful short-term outcomes. Based on the observed rate of resolution, management should start with anticoagulation, followed by surveillance ultrasound at 2-week intervals. With treatment by anticoagulation, resolution can be expected to occur in one-third of patients every 2 weeks.

Antegrade common femoral artery closure device use is associated with decreased complications.

OBJECTIVE: Antegrade femoral artery access is often used for ipsilateral infrainguinal peripheral vascular intervention. However, the use of closure devices (CD) for antegrade access (AA) is still considered outside the instructions for use for most devices. We hypothesized that CD use for antegrade femoral access would not be associated with an increased odds of access site complications. METHODS: The Vascular Quality Initiative was queried from 2010 to 2019 for infrainguinal peripheral vascular interventions performed via femoral AA. Patients who had a cutdown or multiple access sites were excluded. Cases were then stratified into whether a CD was used or not. Hierarchical multivariable logistic regressions controlling for hospital-level variation were used to examine the independent association between CD use and access site complications. A sensitivity analysis using coarsened exact matching was performed using factors different between treatment groups to reduce imbalance between the groups. RESULTS: Overall, 11,562 cases were identified and 5693 (49.2%) used a CD. Patients treated with a CD were less likely to be white (74.1% vs 75.2%), have coronary artery disease (29.7% vs 33.4%), use aspirin (68.7% vs 72.4%), and have heparin reversal with protamine (15.5% vs 25.6%; all P < .05). CD patients were more likely to be obese (31.6% vs 27.0%), have an elective operation (82.6% vs 80.1%), ultrasound-guided access (75.5% vs 60.6%), and a larger access sheath (6.0 ± 1.0 F vs 5.5 ± 1.0 F; P < .05 for all). CD cases were less likely to develop any access site hematoma (2.55% vs 3.53%; P < .01) or a hematoma requiring reintervention (0.63% vs 1.26%; P < .01) and had no difference in access site stenosis or occlusion (0.30% vs 0.22%; P = .47) compared with no CD. On multivariable analysis, CD cases had significantly decreased odds of developing any access site hematoma (odds ratio, 0.75; 95% confidence interval, 0.59-0.95) and a hematoma requiring intervention (odds ratio, 0.56; 95% confidence interval, 0.38-0.81). A sensitivity analysis after coarsened exact matching confirmed these findings. CONCLUSIONS: In this nationally representative sample, CD use for AA was associated with a lower odds of hematoma in selected patients. Extending the instructions for use indications for CDs to include femoral AA may decrease the incidence of access site complications, patient exposure to reintervention, and costs to the health care system.

Functional outcomes of arteriovenous fistulas recruited with regional anesthesia.

OBJECTIVE: Regional anesthesia (RA)-induced vasodilation increases the proportion of patients with vein anatomy suitable for arteriovenous fistula (AVF) creation. The functional outcomes of AVFs created with veins initially small for size on preoperative duplex ultrasound mapping (≤2.4 mm) that are recruited under RA have not been clearly defined. We aimed to evaluate freedom from revision or thrombosis, time to first cannulation, and reintervention rates of AVFs created with veins recruited after induction of RA. METHODS: A prospectively maintained quality improvement database from a single institution was queried for patients who had dialysis access created under RA. We compared AVFs created according to the original surgical plan (preoperative minimum vein diameter >2.5 mm) with AVFs recruited with RA (preoperative minimum vein diameter ≤2.4 mm). End points included freedom from revision or thrombosis, time to first cannulation, and reintervention rates. RESULTS: Between May 2014 and April 2018, there were 208 dialysis access cases performed under RA. Excluding grafts, revisions, patients with previous ipsilateral AVFs, and those without preoperative ultrasound vein mapping, 135 patients were included in our analysis. Induction of RA with intraoperative duplex ultrasound allowed a change in surgical plan in 55 of 135 (42%) patients (recruited with RA), including 31 patients originally scheduled for an arteriovenous graft (mean preoperative distal upper arm cephalic vein diameter of 1.8 mm [standard deviation, 0.2 mm]) who were converted to an AVF (12 brachiobasilic, 11 brachiocephalic, and 8 radiocephalic). The remaining patients in the group of AVFs recruited with RA included 13 scheduled for brachiobasilic configurations who were converted to brachiocephalic or radiocephalic AVFs and 11 scheduled for brachiocephalic AVFs who were converted to radiocephalic AVFs. Comparing AVFs created according to the original surgical plan vs AVFs recruited with RA, there were no differences in reintervention rates (48% vs 49%; P = .90) or functional outcomes at 6 months (60% vs 65% used on hemodialysis [P = .58] and 7% vs 2% primary failure [P = .19]). CONCLUSIONS: In this series, RA increased the proportion of patients who underwent AVF creation without compromising functional outcomes. Routine use of RA in access surgery could have significant implications in meeting national guidelines for autogenous access in the prevalent hemodialysis population.