Soluble Glycoprotein VI Predicts Abdominal Aortic Aneurysm Growth Rate and is a Novel Therapeutic Target.

A common feature in patients with abdominal aortic aneurysms (AAA) is the formation of a nonocclusive intraluminal thrombus (ILT) in regions of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understood. Thus, we sought to investigate how platelet activation impacts the pathogenesis of AAA. Using RNA-sequencing, we identify that the platelet-associated transcripts are significantly enriched in the ILT compared to the adjacent aneurysm wall and healthy control aortas. We found that the platelet specific receptor glycoprotein VI (GPVI) is among the top enriched genes in AAA ILT and is increased on the platelet surface of AAA patients. Examination of a specific indicator of platelet activity, soluble GPVI (sGPVI), in two independent AAA patient cohorts is highly predictive of a AAA diagnosis and associates more strongly with aneurysm growth rate when compared to D-dimer in humans. Finally, intervention with the anti-GPVI antibody (JAQ1) in mice with established aneurysms blunted the progression of AAA in two independent mouse models. In conclusion, we show that levels of sGPVI in humans can predict a diagnosis of AAA and AAA growth rate, which may be critical in the identification of high-risk patients. We also identify GPVI as a novel platelet-specific AAA therapeutic target, with minimal risk of adverse bleeding complications, where none currently exist.

Long-term value in open and endovascular repair of chronic mesenteric ischemia.

OBJECTIVE: Guidelines recommend open revascularization (OR) over endovascular revascularization (ER) for the treatment of chronic mesenteric ischemia (CMI) for younger, healthier patients. However, little is known about the long-term costs of these recommendations with respect to patients' overall life expectancy. This study investigated whether 5-year value differs between these treatment modalities. METHODS: Patient data were extracted from the Statewide Planning and Research Cooperative System, the New York statewide all-payor database containing demographics, diagnoses, treatments, and charges. The database was queried for patients with an International Classification of Diseases, ninth revision, code for CMI, with the specific exclusion of acute ischemia cases. A propensity score match was performed using the Charlson Comorbidity Index, age, sex, race, renal status, and pulmonary disease for the final cohort of patients. Multiple linear regression and mixed effects linear regression were used to determine factors associated with 5-year value, calculated as life-years/$100k in charges. Charges were gathered from the index admission and subsequent admissions for acute or CMI, mesenteric angiography, or follow-up reintervention. Kaplan-Meier estimation was performed for survival and reintervention-free survival. RESULTS: From 2000 to 2014, 875 patients underwent intervention for CMI. Of those meeting inclusion criteria, 209 (28.1%) underwent OR and 535 (71.9%) ER. After propensity score matching (n = 209 in each group), the ER group showed higher value at 5 years after the procedure (8.04 ± 11.42 life-years/$100k charges vs 4.89 ± 5.28 life-years/$100k charges; P < .01). More patients underwent reintervention in the ER group (37 patients vs 17 patients; P < .01), with 55 reinterventions in the ER group and 19 in the OR group (P < .01). Multiple linear regression analysis showed that age, congestive heart failure, dysrhythmia, cancer, and days spent in the intensive care unit were negatively associated with value at 5 years, whereas ER was positively associated. Survival was 59.6 ± 3.76% vs 62.3% ± 3.49% at 5 years (P = .91), and reintervention-free survival was 43.7 ± 3.86% vs 58.1 ± 3.53% (P = .04), for ER and OR respectively. CONCLUSIONS: Despite increased reinterventions and lower reintervention-free survival, the value for patients with CMI was higher in those who underwent ER in the largest propensity score-matched cohort to date looking at long-term value. Factors negatively associated with value were OR, age, days in intensive care, congestive heart failure, dysrhythmia, and cancer. In patients with amenable anatomy, ER is validated as the first-choice treatment for CMI based on the superior procedural value.

A national census for the off-label treatment of complex aortic aneurysms.

OBJECTIVE: Despite regulatory challenges, device availability, and rapidly expanding techniques, off-label endovascular repair of complex aortic aneurysms (cAAs) has expanded in the past decade. Given the lack of United States Food and Drug Administration-approved endovascular technology to treat cAAs, we performed a national census to better understand volume and current practice patterns in the United States. METHODS: Targeted sampling identified vascular surgeons with experience in off-label endovascular repair of cAAs. An electronic survey was distributed with institutional review board approval from the University of Rochester to 261 individuals with a response rate of 38% (n = 98). RESULTS: A total of 93 respondents (95%) reported off-label endovascular repair of cAAs. Mean age was 45.7 ± 8.3 years, and 84% were male. Most respondents (59%) were within the first 10 years of practice, and 69% trained at institutions with a high-volume of off-label endovascular procedures for complex aortic aneurysms with or without a physician-sponsored investigational device exemption (PS-IDE). Twelve respondents from 11 institutions reported institutional PS-IDEs for physician-modified endografts (PMEGs), in-situ laser fenestration (ISLF), or parallel grafting technique (PGT), including sites with PS-IDEs for custom-manufactured devices. Eighty-nine unique institutions reported elective off-label endovascular repair with a mean of 20.2 ± 16.5 cases/year and ∼1757 total cases/year nationally. Eighty reported urgent/emergent off-label endovascular repair with a mean of 5.7 ± 5.4 cases/year and ∼499 total cases/year nationally. There was no correlation between high-volume endovascular institutions (>15 cases/year) and institutions with high volumes of open surgical repair for cAAs (>15 cases/year; odds ratio, 0.7; 95% confidence interval, 0.3-1.5; P = .34). Elective techniques included PMEG (70%), ISLF (30%), hybrid PMEG/ISLF (18%), and PGT (14%), with PMEG being the preferred technique for 63% of respondents. Techniques for emergent endovascular treatment of complex aortic disease included PMEG (52%), ISLF (40%), PGT (20%), and hybrid-PMEG/ISLF (14%), with PMEG being the preferred technique for 41% of respondents. Thirty-nine percent of respondents always or frequently offer referrals to institutions with PS-IDEs for custom-manufactured devices. The most common barrier for referral to PS-IDE centers included geographic distance (48%), longitudinal relationship with patient (45%), and costs associated with travel (33%). Only 61% of respondents participate in the Vascular Quality Initiative for complex endovascular aneurysm repair, and only 57% maintain a prospective institutional database. Eighty-six percent reported interest in a national collaborative database for off-label endovascular repair of cAA. CONCLUSIONS: Estimates of off-label endovascular repair of cAAs are likely underrepresented in the literature based on this national census. PMEG was the most common technique for elective and emergent procedures. Under-reported off-label endovascular repair of cAA outcomes data appears to be limited by non-standardized PS-IDE reporting to the United States Food and Drug Administration, and the lack of Vascular Quality Initiative participation and prospective institutional data collection. Most participants are interested in a national collaborative database for endovascular repair of cAAs.

Early Financial Outcomes of Physician Modified Endograft Programs Are Dictated by Device Cost.

INTRODUCTION: Physician-modified endografts (PMEGs) have been used for repair of thoracoabdominal aortic aneurysms (TAAAs) for 2 decades with good outcomes but limited financial data. This study compared the financial and clinical outcomes of PMEGs to the Cook Zenith-Fenestrated (ZFEN) graft and open surgical repair (OSR). METHODS: A retrospective review of financial and clinical data was performed for all patients who underwent endovascular or OSR of juxtarenal aortic aneurysms and TAAAs from January 2018 to December 2022 at an academic medical center. Clinical presentation, demographics, operative details, and outcomes were reviewed. Financial data was obtained through the institution's finance department. The primary end point was contribution margin (CM). RESULTS: Thirty patients met inclusion criteria, consisting of twelve PMEG, seven ZFEN, and eleven open repairs. PMEG repairs had a total CM of -$110,000 compared to $18,000 for ZFEN and $290,000 for OSR. Aortic and branch artery implants were major cost-drivers for endovascular procedures. Extent II TAAA repairs were the costliest PMEG procedure, with a total device cost of $59,000 per case. PMEG repairs had 30-d and 1-y mortality rates of 8.3% which was not significantly different from ZFEN (0.0%, P = 0.46; 0.0%, P = 0.46) or OSR (9.1%, P = 0.95; 18%, P = 0.51). Average intensive care unit and hospital stay after PMEG repairs were comparable to ZFEN and shorter than OSR. CONCLUSIONS: Our study suggests that PMEG repairs yield a negative CM. To make these cases financially viable for hospital systems, device costs will need to be reduced or reimbursement rates increased by approximately $8800.

Locoregional Anesthesia's Association With Reduced Intensive Care Unit Stay After Elective Endovascular Aneurysm Repair: Impact of Temporal Changes in Practice Patterns.

BACKGROUND: Elective endovascular aneurysm repair (EVAR) can be performed via local anesthetics and/or regional (epidural or spinal) anesthesia (locoregional [LR]), versus general anesthesia (GA), conferring reduced intensive care unit (ICU) and hospital stays. Current analyses fail to account for temporal changes in vascular practice. Therefore, this study aimed to confirm reductions in ICU and hospital stays among LR patients while accounting for changes in practice patterns. MATERIALS AND METHODS: Using the Society for Vascular Surgery's Vascular Quality Initiative, elective EVARs from August 2003 to June 2021 were grouped into LR or GA. Outcomes included ICU admission and prolonged hospital stay (>2 d). Procedures were stratified into groups of 2 y periods, and outcomes were analyzed within each time period. Univariable and multivariate analyses were used to assess outcomes. RESULTS: LR was associated with reduced ICU admissions (22.3% versus 32.1%, P < 0.001) and prolonged hospital stays (14.3% versus 7.9%, P < 0.001) overall. When stratified by year, LR maintained its association with reduced ICU admissions in 2014-2015 (21.8% versus 34.0%, P < 0.001), 2016-2017 (23.6% versus 31.6%, P < 0.001), 2018-2019 (18.5% versus 30.2%, P < 0.001), and 2020-2021 (15.8% versus 28.8%, P < 0.001), although this was highly facility dependent. LR was associated with fewer prolonged hospital stays in 2014-2015 (15.6% versus 20.4%, P = 0.001) and 2016-2017 (13.3% versus 16.6%, P = 0.006) but not after 2017. CONCLUSIONS: GA and LR have similar rates of prolonged hospital stays after 2017, while LR anesthesia was associated with reduced rates of ICU admissions, although this is facility-dependent, providing a potential avenue for resource preservation in patients suitable for LR.

Locoregional anesthesia is associated with reduced hospital stay and need for intensive care unit care of elective endovascular aneurysm repair patients in the Vascular Quality Initiative.

OBJECTIVE: It has been shown local or regional anesthetic techniques are a feasible alternative to general anesthesia for endovascular aortic aneurysm repair (EVAR). However, studies to date have shown controversial findings with respect to the benefit of locoregional anesthesia (LR) in the elective setting. The objective of this study is to compare postoperative outcomes between LR and general anesthesia (GA) in the setting of elective EVAR, using a large, multicenter database. METHODS: Using the Society for Vascular Surgery Vascular Quality Initiative database, we retrospectively analyzed all patients who underwent elective EVAR from August 2003 to June 2021. Patients were grouped by anesthetic type based on the level of consciousness afforded by the anesthetic: local or regional anesthesia (LR) vs GA. Primary outcomes were total postoperative hospital length-of-stay (LOS) and intensive care unit (ICU) LOS. Propensity score matching was used for risk adjustment and to analyze the primary outcomes with confirmatory analysis using logistic or linear regression, as appropriate, in single and multilevel models. Secondary outcomes were 30-day mortality, 1-year mortality, postoperative outcomes, operative time, fluoroscopy time, and reoperation rate. These were analyzed following propensity score matching as well as using logistic regression and Cox proportional hazard regression in single and multilevel models, as appropriate. RESULTS: A total of 50,809 patients underwent elective EVAR from 2003 to 2021. Of these, 4302 repairs used LR (8.5%) and 46,507 (91.5%) were performed under GA. After employing propensity score matching, two groups of 3027 patients were produced. These showed no significant difference in 30-day mortality (odds ratio, 1.22; P = .53), 1-year mortality (hazard ratio, 1.06; P = .62), or any postoperative outcomes. LR was found to be significantly associated with shorter hospital stays (≤2 days) (12.5% vs 14.8%; P = .01), decreased ICU utilization (19.3% vs 30.6%; P < .001), decreased operative time (110.8 vs 117.3 minutes; P < .001), decreased fluoroscopy time (21.0 vs 22.7 minutes; P < .001), and a slight reduction in reoperation rate (1.2% vs 1.9%; P = .02), which all remained significant following single-level and multilevel multivariate analyses accounting for hospital and physician random effects. CONCLUSIONS: These data suggest that LR anesthesia is safe and may offer advantages in reducing resource utilization for patients undergoing elective EVAR, primarily based on associations with reduced ICU care and reduced hospital stay. Given these findings, LR may prove an advantageous technique in appropriately selected patient populations.

Impact of calcified plaque volume on technical and 3-year outcomes after transcarotid artery revascularization.

OBJECTIVE: We sought to quantify the percent calcification within carotid artery plaques and assess its impact on percent residual stenosis and rate of restenosis in patients undergoing transcarotid artery revascularization for symptomatic and asymptomatic carotid artery stenosis. METHODS: A retrospective review of prospectively collected institutional Vascular Quality Initiative data was performed to identify all patients undergoing transcarotid artery revascularization from December 2015 to June 2021 (n = 210). Patient and lesion characteristics were extracted. Using a semiautomated workflow, preoperative computed tomography head and neck angiograms were analyzed to determine the calcified plaque volume in distal common carotid artery and internal carotid artery plaques. Intraoperative digital subtraction angiograms were reviewed to calculate the percent residual stenosis post-intervention according to North American Symptomatic Carotid Endarterectomy Trial criteria. Peak systolic velocity and end-diastolic velocity were extracted from outpatient carotid duplex ultrasound examinations. Univariate logistic regression was performed to analyze the relationship of calcium volume percent and Vascular Quality Initiative lesion calcification to percent residual stenosis in completion angiograms. Kaplan-Meier analysis examined the relationship between calcium volume percent and in-stent stenosis over 36 months. RESULTS: One hundred ninety-seven carotid arteries were preliminarily examined. Predilation was performed in 87.4% of cases with a mean balloon diameter of 5.1 ± 0.7 mm and a mean stent diameter was 8.8 ± 1.1 mm. The mean calcium volume percent was 11.9 ± 12.4% and the mean percent residual stenosis was 16.1 ± 15.6%. Univariate logistic regression demonstrated a statistically significant difference between calcium volume percent and percent residual stenosis (odds ratio [OR], 1.324; 95% confidence interval [CI], 1.005-1.746; P = .046). Stratified by quartile, only the top 25% of calcified plaques (>18.7% calcification) demonstrated a statistically significant association with higher percent residual stenosis (OR, 2.532; 95% CI, 1.049-6.115; P =.039). There was no statistical significance with lesion calcification (OR, 1.298; 95% C,: 0.980-1.718; P = .069). A Kaplan-Meier analysis demonstrated a statistically significant increase in the rate of in-stent stenosis during a 36-month follow-up for lesions containing >8.2% calcium volume (P = .0069). CONCLUSIONS: A calcium volume percent of >18.7% was associated with a higher percent residual stenosis, and a calcium volume percent of >8.2% was associated with higher in-stent stenosis at 36 months. There was one clinically diagnosed stroke during the follow-up period, demonstrating the overall safety of the procedure.

Use of Glycoprotein IIb-IIIa Inhibitors in Patients Undergoing Carotid Artery Stenting in the Vascular Quality Initiative.

BACKGROUND: Antiplatelet therapies with thromboxane inhibitors and adenosine 5'-diphosphate antagonists have been widely used following carotid artery stenting (CAS). However, these therapies may not apply to patients who are intolerant or present acutely. Glycoprotein IIb/IIIa inhibitors (GPI) are a proposed alternative therapy in these patients; however, their use has been limited due to concerns of increased risk for intracranial bleeding. Thus, this study aims to assess the safety profile of GPI in patients undergoing CAS. METHODS: All patients undergoing CAS in the Society of Vascular Surgery - Vascular Quality Initiative database from 2012 to 2021 was included and grouped into GPI versus non-GPI therapy (control). The primary outcome was in-hospital stroke or death, and secondary outcomes included in-hospital stroke/transient ischemic attack (TIA), death, myocardial infarction, and intracranial hemorrhage (ICH)/seizure. Patients were stratified by surgical approach (Transcarotid artery revascularization using flow reversal (TCAR) and transfemoral carotid artery stenting), and stepwise backward logistic regression analysis was conducted to evaluate major primary and secondary outcomes. RESULTS: A total of 50,628 patients underwent carotid revascularization. Of these, 4.4% of the patients received GPI. Mean age was similar between control versus GPI (71.35(9.67) vs. 71.36(10.20) years). Compared to the control group, patients who receive GPI are less likely to be on optimal medical therapy, including aspirin (83.0% vs. 88.1%), P2Y12 inhibitor (73.0% vs. 82.7%), and statin (82.3% vs. 86.0%) (All P < 0.05). In addition, patients in the GPI group were more likely to undergo TCAR for carotid revascularization (52.2% vs. 48.4%) for emergent/urgent (29.4% vs. 16.8%) and symptomatic indications (55.5% vs. 49.7%) (All P < 0.001). After stratifying by surgical approach, if patients underwent TFCAS and received a GPI, they were at increased odds of developing stroke/death (1.77(1.25-2.51)), death (odds ratio (OR) (95% CI): 1.67(1.07-2.61)), stroke/TIA (OR (95% confidence interval (CI)): 1.65(1.09-2.51)), and ICH/seizure (OR (95% CI): 2.13(1.23-3.68)) (All P < 0.05). No difference was seen in outcomes between the 2 groups if undergoing TCAR. CONCLUSIONS: Patients who receive GPI were more likely to be symptomatic at presentation and less likely to be medically optimized before their carotid revascularization. Transfemoral access in patients receiving GPI was associated with increased odds of morbidity and mortality. However, this was not observed if undergoing TCAR. TCAR can be considered for its overall favorable results in high-risk patients who are not medically optimized.

Gender Differences in Aortic Anatomic Severity Grade and Long-Term Survival Following Elective Abdominal Aortic Aneurysm Repair at a Single Tertiary Center.

BACKGROUND: Anatomic severity grade (ASG) score is utilized to assess preoperative abdominal aortic aneurysms (AAA) and provide a quantitative data on its anatomic complexity. The aim of this study is to determine the anatomical differences and long-term survival between male and female patients undergoing elective AAA repair. METHODS: All patients undergoing intact AAA repair from 2007 to 2014 were included. ASG scores were calculated based on preoperative anatomical characteristics including aortic neck, aneurysm, and iliac artery. Standard univariate analysis was used to evaluate patient and anatomical characteristics. Kaplan-Meier survival curves were used to evaluate long-term survival at 1 and 5 years. RESULTS: A total of 379 patients were identified, of which, majority of them were males (80%). Females were on average 3 years older (mean [SD]: 74.32 [8.63] vs. 71.92 [8.64] years) and were more likely to undergo open repair (29.7% vs. 17.5%) (both P < 0.05). Both groups had similar comorbidities. The mean long-term follow-up (S.D.) was 6.21 (3.81) years. No significant difference was seen between males versus females in long-term survival at both 1 year (86.3% vs. 92.8, P = 0.06) and 5 year (68.5% vs. 72.7%, P = 0.38). In regard to the anatomical characteristics, females had shorter aortic neck length (mean in mm [S.D.]: 17.67 [1.41] vs. 27.20 [15.76]), increased tortuosity index [mean (S.D.): 1.11 (0.07) vs. 1.09 (0.07)]) and higher calcification [mean % (S.D.): 17.12 (21.17) vs. 10.59 (16.82)] (All P < 0.05). In contrast, males had larger aortic neck (mean in mm (S.D.): 23.81 (4.17) vs. 22.41 (4.16)] and iliac artery [mean in mm (S.D.): 7.70 (1.91) vs. 6.28 (1.67)] diameter (both P < 0.05). The mean total ASG score was significantly higher among females versus males [mean (S.D.): 17.23 (4.01) vs. 15.67 (3.96), P = 0.003]. After stratifying by ASG score ≥15, females had significantly lower survival at 1 year compared to males (82.6% vs. 92.1%, P = 0.04). However, this difference disappeared at 5 years. CONCLUSIONS: The data demonstrate that females present at an older age with more complex AAA anatomy than males. Based on anatomical complexities, females were more likely to undergo open repair, with a corresponding increase in 1-year mortality, but not at 5 year. The data suggest that care processes for optimization of aortic surgery in females are needed to improve 1-year survival.

Survival, Reintervention, and Value of Open and Endovascular Repair for Chronic Mesenteric Ischemia.

BACKGROUND: There are limited analyses of survival and postoperative outcomes in chronic mesenteric ischemia (CMI) using data from large cohorts. Current guidelines recommend open repair (OR) for younger, healthier patients when long-term benefits outweigh increased perioperative risks or for poor endovascular repair (ER) candidates. This study investigates whether long-term survival, reintervention, and value differ between these treatment modalities. METHODS: A retrospective cohort analysis was performed on data extracted from the Statewide Planning and Research Cooperative System, the New York statewide all-payer database containing demographics, diagnoses, treatments, and charges. Patients were selected for CMI and subsequent ER or OR using International Classification of Diseases, Ninth Revision codes. Patients with peripheral arterial disease were excluded to account for ambiguity in the International Classification of Diseases, Ninth Revision procedure code for angioplasty of noncoronary vessels, which includes angioplasty of upper and lower extremity vessels. Kaplan-Meier analysis was used to compare 1-year and 5-year survival and reintervention between treatment modalities using a propensity-matched cohort. Cox proportional hazards testing was performed to find factors associated with 1-year and 5-year survival and reintervention. Analysis of procedural value was performed using linear regression. RESULTS: From 2000 to 2014, 744 patients met inclusion criteria. Of these, 209 (28.1%) underwent OR and 535 (71.9%) ER. No difference between propensity-matched groups was found in 1-year (P = 0.46) or 5-year (P = 0.91) survival. Congestive heart failure (hazard ratio [HR]: 2.8, 95% confidence interval [CI]: 1.7-4.4; P < 0.01), cancer (HR: 2.8, 95% CI: 1.3-5.8; P < 0.01), and dysrhythmia (HR: 1.8, 95% CI: 1.1-2.8; P = 0.02) correlated with 1-year mortality. Cancer (HR: 2.9, 95% CI: 1.6-5.5; P < 0.01), congestive heart failure (HR: 2.2, 95% CI: 1.5-3.2; P < 0.01), chronic pulmonary disease (HR: 1.4, 95% CI: 1.0-2.0; P = 0.04), and age (HR: 1.03, 95% CI: 1.01-1.05; P < 0.01) correlated with 5-year mortality. Treatment modality was not associated with reintervention at 1 year on Kaplan-Meier analysis (P = 0.29). However, ER showed increased instances of reintervention at 5 years (P < 0.01). Additionally, ER was associated with an increased 5-year value (0.7 ± 0.9 vs. 0.5 ± 0.5 life years/charges at index admission [$10k], P < 0.01; b coefficient: 0.2, 95% CI: 0.1-0.4, P < 0.01). CONCLUSIONS: This is the largest retrospective propensity-matched single-study cohort to analyze long-term survival outcomes after intervention for CMI. Long-term mortality was independent of treatment modality and rather was associated with patient comorbidities. Therefore, treatment selection should depend on anatomic considerations and long-term value. ER should be considered over OR in patients with amenable anatomy based on the superior procedural value.

Long-term anticoagulation is associated with type II endoleaks and failure of sac regression after endovascular aneurysm repair.

OBJECTIVE: Within the context of endovascular aneurysm repair (EVAR), the role of anticoagulation therapy on endoleak development and subsequent reintervention is unclear with conflicting data in the literature. The hypothesis of this study is that long-term anticoagulation is associated with persistent type II endoleaks and failure of sac regression in patients undergoing endoluminal repair of intact infrarenal aortic aneurysm. METHODS: Retrospective cohort abstracted from the Vascular Quality Initiative index hospitalization and long-term follow-up datasets for EVAR (2003-2017) were included in the analysis. Patients not taking aspirin preoperatively and postoperatively were excluded. Patients taking anticoagulation and aspirin concomitantly (treatment) after the index procedure were compared against patients taking aspirin alone (control). Anticoagulation included warfarin and novel oral anticoagulants, including factor Xa inhibitors and direct thrombin inhibitors. One-to-one greedy matching using propensity scores was implemented to match patients. The primary end points were failure of aneurysm sac regression, sac expansion, risk of endoleak, and reintervention rate for endoleak at follow-up. Sac regression was defined as a decrease of at least 5 mm and sac expansion was defined as an increase of at least 5 mm. RESULTS: There were 9004 patients who received ASA alone and 332 patients who received ASA and anticoagulation. Propensity scores were used to create 301 matching pairs to account for differences in baseline characteristics and comorbidities, including but not limited to age, sex, smoking, coronary artery disease, heart failure, and chronic kidney disease between the treatment and control groups. After adjusting for covariables anticoagulation use was independently associated with a significantly decreased abdominal aortic aneurysm sac regression (41.59% vs 58.41%; P = .001), but no statistically significant difference in sac expansion with long-term anticoagulation use (9.7% vs 4.9%; P = .056). There was increased risk of type II endoleaks (11.96% vs 6.31%; P = .023; relative risk, 1.89; 95% confidence interval, 1.11-3.23; P = .016), but no significant differences in type I, III, or indeterminate endoleaks. There was no statistical difference in 2-year reintervention rates (4.32% vs 2.66%; hazard ratio, 1.43; 95% confidence interval, 0.55-3.77; P = .461). There were no differences in any primary outcome between warfarin and novel oral anticoagulants. CONCLUSIONS: These data demonstrate that long-term aspirin plus anticoagulation use is associated with a lack of aortic sac reduction and persistent type II endoleak, but not an increased risk for subsequent reintervention. Because prior studies have demonstrated that sac regression is a correlate of survival, these findings associating regression failure suggest a potential therapeutic failure for patients undergoing EVAR who also require long-term anticoagulation therapy. Although not a contraindication, long-term anticoagulation should be considered when counseling patients with a surgical indication aortic aneurysm.

Apelin protects against abdominal aortic aneurysm and the therapeutic role of neutral endopeptidase resistant apelin analogs.

Abdominal aortic aneurysm (AAA) remains the second most frequent vascular disease with high mortality but has no approved medical therapy. We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to enhance APLN action as a therapeutic intervention for this disease. Loss of APLN potentiated angiotensin II (Ang II)-induced AAA formation, aortic rupture, and reduced survival. Formation of AAA was driven by increased smooth muscle cell (SMC) apoptosis and oxidative stress in Apln-/y aorta and in APLN-deficient cultured murine and human aortic SMCs. Ang II-induced myogenic response and hypertension were greater in Apln-/y mice, however, an equivalent hypertension induced by phenylephrine, an α-adrenergic agonist, did not cause AAA or rupture in Apln-/y mice. We further identified Ang converting enzyme 2 (ACE2), the major negative regulator of the renin-Ang system (RAS), as an important target of APLN action in the vasculature. Using a combination of genetic, pharmacological, and modeling approaches, we identified neutral endopeptidase (NEP) that is up-regulated in human AAA tissue as a major enzyme that metabolizes and inactivates APLN-17 peptide. We designed and synthesized a potent APLN-17 analog, APLN-NMeLeu9-A2, that is resistant to NEP cleavage. This stable APLN analog ameliorated Ang II-mediated adverse aortic remodeling and AAA formation in an established model of AAA, high-fat diet (HFD) in Ldlr-/- mice. Our findings define a critical role of APLN in AAA formation through induction of ACE2 and protection of vascular SMCs, whereas stable APLN analogs provide an effective therapy for vascular diseases.

Effect of obesity on radiation exposure, quality of life scores, and outcomes of fenestrated-branched endovascular aortic repair of pararenal and thoracoabdominal aortic aneurysms.

BACKGROUND: The aim of the present study was to assess the effect of obesity on procedural metrics, radiation exposure, quality of life (QOL), and clinical outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms. METHODS: We reviewed the clinical data from 334 patients (236 men; mean age, 75 ± 8 years) enrolled in a prospective nonrandomized study to evaluate FB-EVAR from 2013 to 2019. The patients were classified using the body mass index (BMI) as obese (BMI ≥30 kg/m2) or nonobese (BMI <30 kg/m2). QOL questionnaires (short-form 36-item questionnaire) and imaging studies were obtained preoperatively and at 2 months and 6 months postoperatively, and annually thereafter. The procedures were performed using two different fixed imaging systems. The end points included procedural metrics (ie, total operative time, fluoroscopic time, contrast volume), radiation exposure, technical success, 30-day mortality, and major adverse events, QOL changes, freedom from target vessel instability, freedom from reintervention, and patient survival. RESULTS: The aneurysm extent was a pararenal aortic aneurysm in 117 patients (35%) and a thoracoabdominal aortic aneurysm in 217 patients (65%). Both groups had similar demographics, cardiovascular risk factors, and aneurysm extent, except for a greater incidence of hyperlipidemia and diabetes among the obese patients (P < .05). No significant differences were found in the procedural metrics or intraprocedural complications between the groups, except that the obese patients had greater radiation exposure than the nonobese patients (mean, 2.5 vs 1.6 Gy; P < .001), with the highest radiation exposure in those obese patients who had undergone the procedure using system 1 (fusion alone) instead of system 2 (fusion and digital zoom; mean, 4.1 vs 1.5 Gy; P < .001). Three patients had died within 30 days (0.8%), with no difference in mortality or major adverse events between the groups. The mental QOL scores had improved in the obese group at 2 and 12 months compared with the nonobese patients, with persistently higher scores up to 3 years. At 3 years, the obese and nonobese patients had a similar incidence of freedom from target vessel instability (74% ± 6% vs 80% ± 3%; P = .99, log-rank test), freedom from reintervention (66% ± 6% vs 73% ± 4%; P = .77, log-rank test), and patient survival (83% ± 5% vs 75% ± 4%; P = .16, log-rank test). CONCLUSIONS: FB-EVAR was performed with high technical success and low mortality and morbidity, with no significant differences between the obese and nonobese patients. The procedural metrics and outcomes were similar, with the exception of greater radiation exposure among obese patients, especially for the procedures performed using system 1 with fusion alone compared with system 2 (fusion and digital zoom). Obese patients had higher QOL mental scores at 2 and 12 months, with a similar reintervention rate, target vessel outcomes, and survival compared with nonobese patients.

Hypoxia and Ischemia Promote a Maladaptive Platelet Phenotype.

OBJECTIVE: Reduced blood flow and tissue oxygen tension conditions result from thrombotic and vascular diseases such as myocardial infarction, stroke, and peripheral vascular disease. It is largely assumed that while platelet activation is increased by an acute vascular event, chronic vascular inflammation, and ischemia, the platelet activation pathways and responses are not themselves changed by the disease process. We, therefore, sought to determine whether the platelet phenotype is altered by hypoxic and ischemic conditions. APPROACH AND RESULTS: In a cohort of patients with metabolic and peripheral artery disease, platelet activity was enhanced, and inhibition with oral antiplatelet agents was impaired compared with platelets from control subjects, suggesting a difference in platelet phenotype caused by the disease. Isolated murine and human platelets exposed to reduced oxygen (hypoxia chamber, 5% O2) had increased expression of some proteins that augment platelet activation compared with platelets in normoxic conditions (21% O2). Using a murine model of critical limb ischemia, platelet activity was increased even 2 weeks postsurgery compared with sham surgery mice. This effect was partly inhibited in platelet-specific ERK5 (extracellular regulated protein kinase 5) knockout mice. CONCLUSIONS: These findings suggest that ischemic disease changes the platelet phenotype and alters platelet agonist responses because of changes in the expression of signal transduction pathway proteins. Platelet phenotype and function should, therefore, be better characterized in ischemic and hypoxic diseases to understand the benefits and limitations of antiplatelet therapy.

Aspirin use is associated with decreased radiologically-determined thrombus sac volume in abdominal aortic aneurysms.

Introduction Formation and renewal of intramural thrombus is associated with inflammation, and contributes to the complexity of aneurysm repair. Current cardiovascular pharmacotherapy includes several inflammatory modulators such as aspirin, statins, clopidogrel, and angiotensin-converting enzyme inhibitors. The purpose of our study was to investigate the effect of these inflammatory modulators on radiographically-determined thrombus sac volume. Methods Pre-operative computed tomography scans were reviewed in patients who underwent elective infrarenal aortic aneurysm repair. Thrombus sac volume was obtained using a Hounsfield unit restricted region growth algorithm. Co-morbid conditions such as diabetes mellitus and post-operative complications were evaluated compared to thrombus sac volume. Receiver-operator characteristic curves were generated for thrombus sac volume and patients on the various cardiovascular pharmacotherapies. Results A total of 266 patients (mean age = 72.6 ± 0.6 years; mean thrombus sac volume = 58.7 (34.4-89.0) cm3) were identified. Acetylsalicylic acid use was associated with a decreased thrombus sac volume ≤50 cm3 (AUC = 0.616, p = 0.013) whereas statins ( p = 0.26), angiotensin-converting enzyme inhibitors ( p = 0.46), and clopidogrel ( p = 0.62) had no correlation to thrombus sac volume. Diabetes mellitus was not associated with thrombus sac volume ( p = 0.31). Conclusion Acetylsalicylic acid use is associated with decreased thrombus sac volume in a patient population undergoing elective abdominal aortic aneurysms repair. The effect of acetylsalicylic acid over other anti-inflammatory and anti-platelet agents is possibly attributable to its distinct mechanism of cyclooxygenase-1 inhibition. Diabetes mellitus, a known correlate of aneurysm incidence, is not associated with thrombus burden. The potential to alter aneurysm thrombus volume, thereby affecting aneurysm morphology, may yield a more favorable aneurysmal repair.

Outcomes for critical limb ischemia are driven by lower extremity revascularization volume, not distance to hospital.

OBJECTIVE: The objective of this study was to identify relationships among geographic access to care, vascular procedure volume, limb preservation, and survival in patients diagnosed with critical limb ischemia (CLI). METHODS: Using New York State administrative data from 2000 to 2013, we identified a patient's first presentation with CLI defined by International Classification of Diseases, Ninth Revision diagnosis and procedure codes. Distance from the patient's home to the index hospital was calculated using the centroids of the respective ZIP codes. A multivariable logistic regression model was employed to estimate the impact of distance, major lower extremity amputation (LEA) volume, and lower extremity revascularization (LER) volume on major amputation and 30-day mortality. Volumes and distances were analyzed in quintiles. The farthest distance quintile and the highest procedure volume quintiles were used as references for generating odds ratios (ORs). RESULTS: There were 49,576 patients identified with an initial presentation of CLI. The median age was 73 years, 35,829 (73.2%) had Medicare as a primary insurer, 11,395 (23.0%) had a major amputation, and 4249 (8.6%) died within 30 days of admission. Patients in the closest distance quintile were more likely to undergo amputation (OR, 1.53 [1.39-1.68]; P < .0001). Patients who visited hospitals in the lowest LER volume quintile with at least one procedure per year faced higher 30-day mortality rates (OR, 2.05 [1.67-2.50]; P < .0001) and greater odds of amputation (OR, 9.94 [8.5-11.63]; P < .0001). Patients who visited hospitals in the lowest LEA volume quintile had lower odds of 30-day mortality (OR, 0.66 [0.50-0.87]; P = .0033) and lower odds of amputation (OR, 0.180 [0.142-0.227]; P < .0001). CONCLUSIONS: Rates of major amputation are inversely associated with distance from the index hospital, whereas rates of both major amputation and mortality are inversely associated with LER volume. Rates of major amputation and mortality are directly associated with LEA volume. We believe that unless it is otherwise contraindicated, these data support consideration for selective referral of CLI patients to high-volume centers for LER regardless of distance. Within the context of value-based health care delivery, policy supporting regionalization of CLI care into centers of excellence may improve outcomes for these patients.

A model to demonstrate that endotension is a nonvisualized type I endoleak.

OBJECTIVE: Unexplained aneurysm growth despite multimodality imaging after endovascular aneurysm repair is often attributed to endotension. We tested a hypothesis that endotension may be from a type Ia endoleak pressurizing the aneurysm sac, without net forward flow, not visualized on standard angiographic imaging. METHODS: A patient-specific aortic aneurysm phantom was constructed of polyvinyl alcohol using three-dimensional molding techniques. A bifurcated stent graft was implanted, and the phantom was connected to a hemodynamic simulator for testing. Type Ia endoleaks were created using 7F catheters. Three scenarios were studied: complete exclusion (no endoleak), inflow with no sac outflow, and inflow with sac outflow. Imaging with digital subtraction angiography was performed at 48 kVp at 5 frames/s, followed by delayed imaging at 1 frame/min for 30 minutes. RESULTS: With no endoleak, the systemic pressure averaged 113 mm Hg and aneurysm sac pressure averaged 101 mm Hg. With an endoleak present without outflow, the systemic pressure averaged 116 mm Hg, the aneurysm sac pressure averaged 120 mm Hg, and endoleak flow was bidirectional with no net forward flow. With endoleak present with aneurysm sac outflow, the systemic pressure averaged 119 mm Hg, aneurysm sac pressure averaged 105.5 mm Hg, and net endoleak flow into the aneurysm sac was 21 mL/min across the endoleak channel. With digital subtraction imaging, the endoleak with no outflow was noted after >9 minutes of delayed imaging. CONCLUSIONS: In our model, the creation of a type Ia endoleak in the absence of sac outflow resulted in a mean pressure higher than the systemic mean pressure with zero net flow into the aneurysm sac. Consequently, the endoleak could only be visualized with markedly delayed imaging and not with standard contrast digital subtraction angiography like that used in clinical practice. Our findings suggest that endotension may in fact be the result of undetected endoleaks secondary to the limitations of present iodinated contrast imaging modalities.

In vitro hemodynamic model of the arm arteriovenous circulation to study hemodynamics of native arteriovenous fistula and the distal revascularization and interval ligation procedure.

BACKGROUND: Experimental modeling of arteriovenous hemodialysis fistula (AVF) hemodynamics is challenging. Mathematical modeling struggles to accurately represent the capillary bed and venous circulation. In vivo animal models are expensive and labor intensive. We hypothesized that an in vitro, physiologic model of the extremity arteriovenous circulation with provisions for AVF and distal revascularization and interval ligation (DRIL) configurations could be created as a platform for hemodynamic modeling and testing. METHODS: An anatomic, upper extremity arteriovenous model was constructed of tubing focusing on the circulation from the subclavian artery to subclavian vein. Tubing material, length, diameter, and wall thickness were selected to match vessel compliance and morphology. All branch points were constructed at physiologic angles. The venous system and capillary bed were modeled using tubing and one-way valves and compliance chambers. A glycerin/water solution was created to match blood viscosity. The system was connected to a heart simulator. Pressure waveforms and flows were recorded at multiple sites along the model for the native circulation, brachiocephalic AVF configuration, and the AVF with DR without and with IL (DR no IL and DRIL). RESULTS: A preset mean cardiac output of 4.2 L/min from the heart simulator yielded a subclavian artery pressure of 125/55 mm Hg and a brachial artery pressure of 121/54 mm Hg with physiologic arterial waveforms. Mean capillary bed perfusion pressure was 41 mm Hg, and mean venous pressure in the distal brachial vein was 17 mm Hg with physiologic waveforms. AVF configuration resulted in a 15% decrease in distal pressure and a 65% decrease in distal flow to the hand. DR no IL had no change in distal pressure with a 27% increase in distal flow. DRIL resulted in a 3% increase in distal pressure and a 15% increase in distal flow to the hand above that of DR no IL. Flow through the DR bypass decreased from 329 mL/min to 55 mL/min with the addition of IL. Flow through the AVF for both DR no IL and DRIL was preserved. CONCLUSIONS: Through the construction and validation of an in vitro, pulsatile arteriovenous model, the intricate hemodynamics of AVF and treatments for ischemic steal can be studied. DR with or without IL improved distal blood flow in addition to preserving AVF flow. IL decreased the blood flow through the DR bypass itself. The findings of the AVF as a pressure sink and the relative role of IL with DR bypass has allowed this model to provide hemodynamic insight difficult or impossible to obtain in animal or human models. Further study of these phenomena with this model should allow for more effective AVF placement and maturation while personalizing treatment for associated ischemic steal. CLINICAL RELEVANCE: The complications of arteriovenous fistula (AVF)-associated steal with its concurrent surgical treatments have been clinically described but have relatively little published, concrete hemodynamic data. A further understanding of the underlying hemodynamics is necessary to prevent the occurrence of steal and improve treatment when it occurs. Specific objectives are to study the blood flow through an AVF with varying anatomic and physiologic parameters, determine what factors contribute to the development of arterial steal distal to an AVF, and create optimal interventions to treat arterial steal from an AVF when it occurs. The long-term goal is creation of AVF tailored to patient-specific parameters, resulting in higher rates of functional fistulas with decreases in fistula-related complications. The ability to study fluid dynamics using a unique, in vitro, upper extremity pulsatile arteriovenous circulation simulator creates the ideal platform for this work.

Percutaneous endovascular stenting to treat left ventricular assist device outflow graft stenosis.

A 72-year-old woman presented with acute symptoms of congestive heart failure exacerbation and cardiogenic shock secondary to flow alarms in her HeartMate II left ventricular assist device (LVAD) placed in 2013. Her rapid deterioration required venoarterial extracorporeal membrane oxygenation placement with subsequent cardiac catheterization. A computed tomography scan corroborated 90% stenosis of the LVAD outflow graft with mural thrombus causing cardiogenic shock. A multidisciplinary team proceeded with endovascular treatment of the LVAD outflow obstruction via realignment with percutaneous angioplasty and placement of covered stent grafts. After in-hospital recovery, she was discharged to a rehabilitation facility.