Search Engines to Capture Missing Deaths From Institutional Data Warehouse.

INTRODUCTION: Clinical publications use mortality as a hard end point. It is unknown how many patient deaths are under-reported in institutional databases. The objective of this study was to query mortality in our patient cohort from our data warehouse and compare these deaths to those identified in different databases. METHODS: We passed the first/last name and date of birth of 134 patients through online mortality search engines (Find a Grave Index, US Cemetery and Funeral Home Collection, etc.) to assess their ability to capture patient deaths and compared that to deaths recorded from our institutional data warehouse. RESULTS: Our institutional data warehouse found approximately one-third of the total patient mortalities. After the Social Security Death Index, we found that the Find a Grave Index captured the most mortalities missed by the institutional data warehouse. These results highlight the advantages of incorporating readily available search engines into institutional data warehouses for the accurate collection of patient mortalities, particularly those that occur outside of index operative admission. CONCLUSIONS: The incorporation of the mortality search engines significantly augmented the capture of patient deaths. Our approach may be useful for tailored patient outreach and reporting mortalities with institutional data.

Perfusion Assessment in Critical Limb Ischemia: Principles for Understanding and the Development of Evidence and Evaluation of Devices: A Scientific Statement From the American Heart Association.

There are >12 million patients with peripheral artery disease in the United States. The most severe form of peripheral artery disease is critical limb ischemia (CLI). The diagnosis and management of CLI is often challenging. Ethnic differences in comorbidities and presentation of CLI exist. Compared with white patients, black and Hispanic patients have higher prevalence rates of diabetes mellitus and chronic renal disease and are more likely to present with gangrene, whereas white patients are more likely to present with ulcers and rest pain. A thorough evaluation of limb perfusion is important in the diagnosis of CLI because it can not only enable timely diagnosis but also reduce unnecessary invasive procedures in patients with adequate blood flow or among those with other causes for ulcers, including venous, neuropathic, or pressure changes. This scientific statement discusses the current tests and technologies for noninvasive assessment of limb perfusion, including the ankle-brachial index, toe-brachial index, and other perfusion technologies. In addition, limitations of the current technologies along with opportunities for improvement, research, and reducing disparities in health care for patients with CLI are discussed.

Association of Statin Dose With Amputation and Survival in Patients With Peripheral Artery Disease.

BACKGROUND: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. METHODS: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003-2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate-intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score-matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy-only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67; 95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins (P<0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score-matched, sensitivity, and subgroup analyses. CONCLUSIONS: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate-intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.

Poor glycemic control is a strong predictor of postoperative morbidity and mortality in patients undergoing vascular surgery.

OBJECTIVE: Hyperglycemia is a common occurrence in patients undergoing cardiovascular surgery. It has been identified in several surgical cohorts that improved perioperative glycemic control reduced postoperative morbidity and mortality. A significant portion of the population with peripheral arterial disease suffers from the sequelae of diabetes or metabolic syndrome. A paucity of data exists regarding the relationship between perioperative glycemic control and postoperative outcomes in vascular surgery patients. The objective of this study was to better understand this relationship and to determine which negative perioperative outcomes could be abated with improved glycemic control. METHODS: This is a retrospective review of a vascular patient database at a large academic center from 2009 to 2013. Eligible procedures included carotid endarterectomy and stenting, endovascular and open aortic aneurysm repair, and all open bypass revascularization procedures. Data collected included standard demographics, outcome parameters, and glucose levels in the perioperative period. Perioperative hyperglycemia was defined as at least one glucose value >180 mg/dL within 72 hours of surgery. The primary outcome was 30-day mortality, with secondary outcomes of complications, need to return to the operating room, and readmission. RESULTS: Of the total 1051 patients reviewed, 366 (34.8%) were found to have perioperative hyperglycemia. Hyperglycemic patients had a higher 30-day mortality (5.7% vs 0.7%; P < .01) and increased rates of acute renal failure (4.9% vs 0.9%; P < .01), postoperative stroke (3.0% vs 0.7%; P < .01), and surgical site infections (5.7% vs 2.6%; P = .01). In addition, these patients were also more likely to undergo readmission (12.3% vs 7.9%; P = .02) and reoperation (6.3% vs 1.8%; P < .01). Furthermore, multivariable logistic regression demonstrated that perioperative hyperglycemia had a strong association with increased 30-day mortality and multiple negative postoperative outcomes, including myocardial infarction, stroke, renal failure, and wound complications. CONCLUSIONS: This study demonstrates a strong association between perioperative glucose control and 30-day mortality in addition to multiple other postoperative outcomes after vascular surgery.

Disturbed Flow Promotes Arterial Stiffening Through Thrombospondin-1.

BACKGROUND: Arterial stiffness and wall shear stress are powerful determinants of cardiovascular health, and arterial stiffness is associated with increased cardiovascular mortality. Low and oscillatory wall shear stress, termed disturbed flow (d-flow), promotes atherosclerotic arterial remodeling, but the relationship between d-flow and arterial stiffness is not well understood. The objective of this study was to define the role of d-flow on arterial stiffening and discover the relevant signaling pathways by which d-flow stiffens arteries. METHODS: D-flow was induced in the carotid arteries of young and old mice of both sexes. Arterial stiffness was quantified ex vivo with cylindrical biaxial mechanical testing and in vivo from duplex ultrasound and compared with unmanipulated carotid arteries from 80-week-old mice. Gene expression and pathway analysis was performed on endothelial cell-enriched RNA and validated by immunohistochemistry. In vitro testing of signaling pathways was performed under oscillatory and laminar wall shear stress conditions. Human arteries from regions of d-flow and stable flow were tested ex vivo to validate critical results from the animal model. RESULTS: D-flow induced arterial stiffening through collagen deposition after partial carotid ligation, and the degree of stiffening was similar to that of unmanipulated carotid arteries from 80-week-old mice. Intimal gene pathway analyses identified transforming growth factor-ß pathways as having a prominent role in this stiffened arterial response, but this was attributable to thrombospondin-1 (TSP-1) stimulation of profibrotic genes and not changes to transforming growth factor-ß. In vitro and in vivo testing under d-flow conditions identified a possible role for TSP-1 activation of transforming growth factor-ß in the upregulation of these genes. TSP-1 knockout animals had significantly less arterial stiffening in response to d-flow than wild-type carotid arteries. Human arteries exposed to d-flow had similar increases TSP-1 and collagen gene expression as seen in our model. CONCLUSIONS: TSP-1 has a critical role in shear-mediated arterial stiffening that is mediated in part through TSP-1's activation of the profibrotic signaling pathways of transforming growth factor-ß. Molecular targets in this pathway may lead to novel therapies to limit arterial stiffening and the progression of disease in arteries exposed to d-flow.

Reversible secretome and signaling defects in diabetic mesenchymal stem cells from peripheral arterial disease patients.

OBJECTIVE: Regenerative medicine seeks to stall or to reverse the pathologic consequences of chronic diseases. Many people with diabetes have peripheral arterial disease (PAD), which increases their already high risk of major amputation. Cellular therapies are a promising regenerative medicine approach to PAD that can be used to focally inject regenerative cells to endangered tissue beds. Mesenchymal stem cells (MSCs) are known to promote tissue regeneration through stromal support and paracrine stimulation of new blood vessels (angiogenesis). Whereas little is known about human diabetic MSCs (dMSCs), particularly those from patients with PAD, dMSCs have a limited expansion capacity but can be improved with human platelet lysate (PL) supplementation. PL is rich in many growth factors, including epidermal growth factor (EGF), which is known to be important to cell proliferation and survival signaling pathways. We hypothesize that dMSCs have a reversible defect in EGF receptor pathways. The objective of this work was to test this hypothesis using dMSCs from PAD patients. METHODS: The secretome expression of EGF and prominent angiogens was characterized from bone marrow (BM)-derived and adipose tissue-derived (ATD) dMSCs from five patients (six limbs) undergoing major amputation. Western blot was used to characterize the AKT and extracellular signal-regulated protein kinases 1 and 2 expression in dMSCs under standard culture (5% fetal bovine serum plus fibroblast growth factor 2 [FGF2]), 5% human PL, or 5% fetal bovine serum plus EGF. Healthy donor MSCs were control cells. The angiogenic activity of BM- and ATD-dMSCs was tested on human umbilical vein endothelial cells (ECs). Paired t-test, analysis of variance, and Kruskal-Wallis tests were used as appropriate. RESULTS: Both BM- and ATD-dMSCs had typical MSC surface marker expression and similar expansion profiles, and they did not express EGF in their secretome. PL supplementation of dMSCs improved AKT signaling, but they were resistant to FGF2 activation of extracellular signal-regulated protein kinases 1 and 2. EGF supplementation led to similar AKT expression as with PL, but PL had greater phosphorylation of AKT at 30 and 60 minutes. The conditioned media from both BM- and ATD-dMSCs had robust levels of prominent angiogens (vascular endothelial growth factor, monocyte chemoattractant protein 1, hepatocyte growth factor), which stimulated EC proliferation and migration, and the co-culture of dMSCs with ECs led to significantly longer EC sprouts in three-dimensional gel than EC-alone pellets. CONCLUSIONS: PL and EGF supplementation improves AKT expression in dMSCs over that of FGF2, but PL improved pAKT over that of EGF. Thus, PL supplementation strategies may improve AKT signaling, which could be important to MSC survival in cellular therapies. Furthermore, BM- and ATD-dMSCs have similar secretomes and robust in vitro angiogenic activity, which supports pursuing dMSCs from both reservoirs in regenerative medicine strategies.

High hemoglobin A1c associated with increased adverse limb events in peripheral arterial disease patients undergoing revascularization.

OBJECTIVE: Diabetes and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has not been studied. We examined the effects of poor glycemic control (high hemoglobin A1c level) on the risk of amputation and modified major adverse limb events (mMALEs) after lower extremity revascularization. METHODS: Patients undergoing PAD revascularization who had hemoglobin A1c (HbA1c) levels available within 6 months were identified in the Veterans Affairs database of 2003 to 2014 (N = 26,799). The diagnosis of preoperative diabetes mellitus (PreopDM) was defined using diabetes diagnosis codes and evidence of treatment. Amputation and mMALE risk was compared for HbA1c levels using Kaplan-Meier analysis. Cox proportional hazards models were created to assess the effect of high HbA1c levels on amputation and mMALE (adjusted for age, gender, race, socioeconomic status, comorbidities, cholesterol levels, creatinine concentration, suprainguinal or infrainguinal procedure, open or endovascular procedure, severity of PAD, year of cohort entry, and medications) for all patients and stratified by PreopDM. RESULTS: High HbA1c levels were present in 33.2% of the cohort, whereas 59.9% had PreopDM. Amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had mMALE. Kaplan-Meier curves showed the worst outcomes in patient with PreopDM and high HbA1c levels. In the Cox model, incremental HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8% were associated with 26% (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.39), 53% (HR, 1.53; 95% CI, 1.37-1.7), and 105% (HR, 2.05; 95% CI, 1.87-2.26) higher risk of amputation, respectively. Similarly, the risk of mMALE also increased by 5% (HR, 1.05; 95% CI, 0.99-1.11), 21% (HR, 1.21; 95% CI, 1.13-1.29), and 33% (HR, 1.33, 95% CI, 1.25-1.42) with worsening HbA1c levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8%, respectively (vs HbA1c ≤6.0%). In stratified analysis by established PreopDM, the relative risk of amputation or mMALE was much higher with poor glycemic control (HbA1c >7.0%) in patients without PreopDM. CONCLUSIONS: PAD patients with worse perioperative glycemic control have a significantly higher risk of amputation and mMALE. Incremental increases in HbA1c levels are associated with higher hazards of adverse limb outcomes independent of PreopDM status. Poor glycemic control (HbA1c >7.0%) in patients without a PreopDM diagnosis carries twice the relative risk of amputation and mMALE than in those with good glycemic control. These results suggest that screening of diabetic status and better management of glycemic control could be a target for improvement of perioperative and long-term outcomes in PAD patients.

An endovascular model of ischemic myopathy from peripheral arterial disease.

OBJECTIVE: Peripheral arterial disease (PAD) is a significant age-related medical condition with limited pharmacologic options. Severe PAD, termed critical limb ischemia, can lead to amputation. Skeletal muscle is the end organ most affected by PAD, leading to ischemic myopathy and debility of the patient. Currently, there are not any therapeutics to treat ischemic myopathy, and proposed biologic agents have not been optimized owing to a lack of preclinical models of PAD. Because a large animal model of ischemic myopathy may be useful in defining the optimal dosing and delivery regimens, the objective was to create and to characterize a swine model of ischemic myopathy that mimics patients with severe PAD. METHODS: Yorkshire swine (N = 8) underwent acute right hindlimb ischemia by endovascular occlusion of the external iliac artery. The effect of ischemia on limb function, perfusion, and degree of ischemic myopathy was quantified by weekly gait analysis, arteriography, hindlimb blood pressures, femoral artery duplex ultrasound scans, and histologic examination. Animals were terminated at 5 (n = 5) and 6 (n = 3) weeks postoperatively. Ossabaw swine (N = 8) fed a high-fat diet were used as a model of metabolic syndrome for comparison of arteriogenic recovery and validation of ischemic myopathy. RESULTS: There was persistent ischemia in the right hindlimb, and occlusion pressures were significantly depressed compared with the untreated left hindlimb out to 6 weeks (systolic blood pressure, 31 ± 21 vs 83 ± 15 mm Hg, respectively; P = .0007). The blood pressure reduction resulted in a significant increase of ischemic myopathy in the gastrocnemius muscle in the treated limb. Gait analysis revealed a functional deficit of the right hindlimb immediately after occlusion that improved rapidly during the first 2 weeks. Peak systolic velocity values in the right common femoral artery were severely diminished throughout the entire study (P < .001), and the hemodynamic environment after occlusion was characterized by low and oscillatory wall shear stress. Finally, the internal iliac artery on the side of the ischemic limb underwent significant arteriogenic remodeling (1.8× baseline) in the Yorkshire but not in the Ossabaw swine model. CONCLUSIONS: This model uses endovascular technology to produce the first durable large animal model of ischemic myopathy. Acutely (first 2 weeks), this model is associated with impaired gait but no tissue loss. Chronically (2-6 weeks), this model delivers persistent ischemia, resulting in ischemic myopathy similar to that seen in PAD patients. This model may be of use for testing novel therapeutics including biologic therapies for promoting neovascularization and arteriogenesis.

A Novel Approach to Assess the In Situ Versus Ex Vivo Mechanical Behaviors of the Coronary Artery.

Ex vivo mechanical testing has provided tremendous insight toward prediction of the in vivo mechanical behavior and local mechanical environment of the arterial wall; however, the role of perivascular support on the local mechanical behavior of arteries is not well understood. Here, we present a novel approach for quantifying the impact of the perivascular support on arterial mechanics using intravascular ultrasound (IVUS) on cadaveric porcine hearts. We performed pressure-diameter tests (n = 5) on the left anterior descending coronary arteries (LADCAs) in situ while embedded in their native perivascular environment using IVUS imaging and after removal of the perivascular support of the artery. We then performed standard cylindrical biaxial testing on these vessels ex vivo and compared the results. Removal of the perivascular support resulted in an upward shift of the pressure-diameter curve. Ex vivo testing, however, showed significantly lower circumferential compliance compared to the in situ configuration. On a second set of arteries, local axial stretch ratios were quantified (n = 5) along the length of the arteries. The average in situ axial stretch ratio was 1.28 ± 0.16; however, local axial stretch ratios showed significant variability, ranging from 1.01 to 1.70. Taken together, the data suggest that both the perivascular loading and the axial tethering have an important role in arterial mechanics. Combining nondestructive testing using IVUS with traditional ex vivo cylindrical biaxial testing yields a more comprehensive assessment of the mechanical behavior of arteries.

Women undergoing aortic surgery are at higher risk for unplanned readmissions compared with men especially when discharged home.

OBJECTIVE: Women undergoing vascular surgery have higher morbidity and mortality. Our study explores gender-based differences in patient-centered outcomes such as readmission, length of stay (LOS), and discharge destination (home vs nonhome facility) in aortic aneurysm surgery. METHODS: Patients were identified from the American College of Surgeons National Surgical Quality Improvement Project database (2011-2013) undergoing abdominal, thoracic, and thoracoabdominal aortic aneurysms (N = 17,763), who were discharged and survived their index hospitalization. The primary outcome was unplanned readmission, and secondary outcomes were discharge to a nonhome facility, LOS, and reasons for unplanned readmission. Univariate, multivariate, and stratified analyses based on gender and discharge destination were used. RESULTS: Overall, 1541 patients (8.7%) experienced an unplanned readmission, with a significantly higher risk in women vs men (10.8% vs 8%; P < .001) overall (Procedure subtypes: abdominal aortic aneurysm [10.1% vs 7.7%; P < .001], thoracic aortic aneurysm [14.1% vs 13.5%; P = .8], and thoracoabdominal aortic aneurysm [14.8% vs 10%; P = .051]). The higher odds of readmission in women compared with men persisted in multivariate analysis after controlling for covariates (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05-1.4). Similarly, the rate of discharge to a nonhome facility was nearly double in women compared with men (20.6% vs 10.7%; P < .001), but discharge to a nonhome facility was not a significant predictor of unplanned readmission. Upon stratification by discharge destination, the higher odds of readmissions in women compared with men occurred in patients who were discharged home (OR, 1.2; 95% CI, 1.02-1.4) but not in those who were discharged to a nonhome facility (OR, 1.06; 95% CI, 0.8-1.4). Significant differences in LOS were seen in patients who were discharged home. No gender differences were found in reasons for readmission with the three most common reasons being thromboembolic events, wound infections, and pneumonia. CONCLUSIONS: Gender disparity exists in the risk of unplanned readmission among aortic aneurysm surgery patients. Women who were discharged home have a higher likelihood of unplanned readmission despite longer LOS than men. These data suggest that further study into the discharge planning processes, social factors, and use of rehabilitation services is needed for women undergoing aortic procedures to decrease readmissions.

Gender and frailty predict poor outcomes in infrainguinal vascular surgery.

BACKGROUND: Women have poorer outcomes after vascular surgery as compared to men as shown by studies recently. Frailty is also an independent risk factor for postoperative morbidity and mortality. This study examines the interplay of gender and frailty on outcomes after infrainguinal vascular procedures. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent infrainguinal vascular procedures from 2005-2012. Frailty was measured using a modified frailty index (mFI; derived from the Canadian Study of Health and Aging). Univariate and multivariate analysis were performed to investigate the association of preoperative frailty and gender, on postoperative outcomes. RESULTS: Of 24,645 patients (92% open, 8% endovascular), there were 533 deaths (2.2%) and 6198 (25.1%) major complications within 30 d postoperatively. Women were more frail (mean mFI = 0.269) than men (mean mFI = 0.259; P < 0.001). Women and frail patients (mFI>0.25) were more likely to have a major morbidity (P < 0.001) or mortality (P < 0.001) with the highest risk in frail women. On multivariate logistic regression analysis, female gender and increasing mFI were independently significantly associated with mortality (P < 0.05) as well as major complications. The interaction of gender and frailty in multivariate analysis showed the highest adjusted 30-d mortality and morbidity in frail females at 2.8% and 30.1%, respectively and that was significantly higher (P < 0.001) than nonfrail males, nonfrail females and frail males. CONCLUSIONS: Female gender and frailty are both associated with increased risk of complications and death following infrainguinal vascular procedures with the highest risk in frail females. Further studies are needed to explore the mechanisms of interaction of gender and frailty and its effect on long-term outcomes for peripheral vascular disease.

Preoperative Frailty Increases Risk of Nonhome Discharge after Elective Vascular Surgery in Home-Dwelling Patients.

BACKGROUND: Patient-centered quality outcomes such as disposition after surgery are increasingly being scrutinized. Preoperative factors predictive of nonhome discharge (DC) may identify at-risk patients for targeted interventions. This study examines the association among preoperative risk factors, frailty, and nonhome DC after elective vascular surgery procedures in patients living at home. METHODS: The 2011-2012 National Surgical Quality Improvement Project database was queried to identify all home-dwelling patients who underwent elective vascular procedures (endovascular and open aortic aneurysm repair, suprainguinal and infrainguinal bypasses, peripheral endovascular interventions, carotid endarterectomy, and stent). Preoperative frailty was measured using the modified frailty index (mFI; derived from Canadian Study of Health and Aging). Univariate and multivariate logistic regression analysis was performed to examine the association of frailty and nonhome DC. RESULTS: Of 15,843 home-dwelling patients, 1,177 patients (7.4%) did not return home postoperatively. Frailty (mFI > 0.25) conferred a significantly increased 2-fold risk of nonhome DC disposition for each procedure type. Frailty, female gender, open procedures, increasing age, end-stage renal disease, and occurrence of any postoperative complication were associated with increased risk of nonhome DC. On multivariate logistic regression analysis, frailty increased the odds of nonhome DC by 60% (odds ratio 1.6, 95% confidence interval 1.4-1.8) after adjusting for other covariates. In the presence of complications, the risk of nonhome DC was 27.5% in frail versus 16.5% in nonfrail patients (P < 0.001). In the absence of complications, although absolute risk was lower, frail patients were nearly twice as likely to not return home (frail 5.5% vs. nonfrail 2.75%, P < 0.001). CONCLUSIONS: Frail home-dwelling patients undergoing elective vascular procedures are at high risk of not returning home after surgery. Preoperative frailty assessment appears to hold potential for counseling regarding postsurgery disposition and DC planning.

The Readmission Event after Vascular Surgery: Causes and Costs.

BACKGROUND: The study evaluates the readmission diagnoses after vascular surgical interventions and the associated hospital costs. METHODS: Patients readmitted after undergoing carotid artery stenting (CAS), carotid endarterectomy (CEA), infrarenal endovascular abdominal aortic aneurysm repair (EVAR), open abdominal aortic aneurysm repair (OAAA), suprainguinal revascularization (SUPRA), or infrainguinal revascularization (INFRA) between January 1, 2008 and October 20, 2013 at a single academic institution were retrospectively identified. Demographic, preoperative, and postoperative event variables were obtained by chart review. The diagnoses and the costs of the readmission event were obtained by chart review and from hospital financial data. Readmission indications were grouped as unrelated or planned readmissions, procedure-specific complications, wound complications, cardiac causes, and other. Univariate analyses of categorical variables were performed with χ2 or Fisher exact test where appropriate. Continuous variables were analyzed using the Wilcoxon rank-sum test. RESULTS: A total of 1,170 patient records were identified. Thirty-day readmission occurred in 112 patients (9.6%). The readmission rate was significantly different between groups: 4.5% in CAS (n = 8/177), 8.5% in CEA (21/246), 5.8% in EVAR (18/312), 11.4% in OAAA (4/35), 15.6% in INFRA (33/212), 13.5% in SUPRA (24/178), and 40% in combined SUPRA and INFRA (4/10) (P < 0.0001). Readmissions were unrelated or planned in 19.6% of patients. Wound complications were the most common readmission diagnoses (36.6%, 41/112).There was a difference in the distribution of readmission indications among procedure groups, with wound complications being predominant in INFRA and SUPRA groups (60.6% and 58.3%, respectively), and cardiac events predominantly in EVAR patients (42%) (P < 0.001). In univariable analysis of predictors of readmission, significant preoperative factors were chronic obstructive pulmonary disease, renal insufficiency, and lower hematocrit. Significant postoperative predictors included any postoperative complication, number of complications, increased length of stay, wound complications, postoperative infections, blood transfusion, and reoperation. The median hospital cost for readmission for wound complications was 29,723 USD (interquartile range 23,841-36,878), and for cardiac complications was 39,784 USD (26,305-46,918). The median cost of readmission for bypass graft occlusion was 33,366 USD (20,530-43,170). The median length of stay also differed depending on the readmission diagnosis and was highest for bypass graft occlusion (8.5 days). CONCLUSIONS: Readmissions after vascular procedures are associated with high cost and hospital bed utilization. Wound complications continue to be the dominant readmission etiology. The characterization of these costs and risk factors in this study can allow for resource allocation to minimize preventable related readmissions. A significant proportion of readmissions after vascular interventions are planned or unrelated, which should be taken into consideration in metric benchmarking and performance comparisons.

Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease.

Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg · kg(-1) · day(-1) bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.

Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome.

Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine (n = 18) by unilateral external iliac artery deployment of a full cross-sectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post-CLI day 14, pigs were randomized to placebo (n = 9) or SR-nitrite (80 mg, n = 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease.

Frailty increases the risk of 30-day mortality, morbidity, and failure to rescue after elective abdominal aortic aneurysm repair independent of age and comorbidities.

BACKGROUND: Frailty, defined as a biologic syndrome of decreased reserve and resistance to stressors, has been linked to adverse outcomes after surgery. We evaluated the effect of frailty on 30-day mortality, morbidity, and failure to rescue (FTR) in patients undergoing elective abdominal aortic aneurysm (AAA) repair. METHODS: Patients undergoing elective endovascular AAA repair (EVAR) or open AAA repair (OAR) were identified in the National Surgical Quality Improvement Program database for the years 2005 to 2012. Frailty was assessed using the modified frailty index (mFI) derived from the Canadian Study of Health and Aging (CSHA). The primary outcome was 30-day mortality, and secondary outcomes included 30-day morbidity and FTR. The effect of frailty on outcomes was assessed by multivariate regression analysis, adjusted for age, American Society of Anesthesiology (ASA) class, and significant comorbidities. RESULTS: Of 23,207 patients, 339 (1.5% overall; 1.0% EVAR and 3.0% OAR) died ≤30 days of repair. One or more complications occurred in 2567 patients (11.2% overall; 7.8% EVAR and 22.1% OAR). Odds ratios (ORs) for mortality adjusted for age, ASA class, and other comorbidities in the group with the highest frailty score were 1.9 (95% confidence interval [CI], 1.2-3.0) after EVAR and 2.3 (95% CI, 1.4-3.7) after OAR. Similarly, compared with the least frail, the most frail patients were significantly more likely to experience severe (Clavien-Dindo class IV) complications after EVAR (OR, 1.7; 95% CI, 1.3-2.1) and OAR (OR, 1.8; 95%, CI, 1.5-2.1). There was also a higher FTR rate among frail patients, with 1.7-fold higher risk odds of mortality (95% CI, 1.2-2.5) in the highest tertile of frailty compared with the lowest when postoperative complications occurred. CONCLUSIONS: Higher mFI, independent of other risk factors, is associated with higher mortality and morbidity in patients undergoing elective EVAR and OAR. The mortality in frail patients is further driven by FTR from postoperative complications. Preoperative recognition of frailty may serve as a useful adjunct for risk assessment.

Carotid artery stenting has increased risk of external carotid artery occlusion compared with carotid endarterectomy.

OBJECTIVE: The external carotid artery (ECA) can be an important source of cerebral blood flow in cases of high-grade internal carotid artery stenosis or occlusion. However, the treatment of the ECA is fundamentally different between carotid endarterectomy (CEA) and carotid artery stenting (CAS). CEA is routinely associated with endarterectomy of the ECA, whereas CAS excludes the ECA from direct flow. We hypothesize that these differences make ECA occlusion more common after CAS. Further, the impact of CAS on blood flow into the ECA is interesting because the flow from the stent into the ECA is altered in a way that may promote local inflammation and may influence in-stent restenosis (ISR). Thus, our objective was to use our institutional database to identify whether CAS increased the rate of ECA occlusion and, if it did, whether ECA occlusion was associated with ISR. METHODS: Patients undergoing CAS or CEA from February 2007 to February 2012 were identified from our institutional carotid therapy database. Preoperative and postoperative images of patients who followed up in our institution were included in the analysis of ECA occlusion and rates of ISR. RESULTS: There were 210 (67%) CAS patients and 207 (60%) CEA patients included in this analysis. Despite CAS patients being younger (68 vs 70 years), having shorter follow-up (12.5 vs 56.2 months), and being more likely to take clopidogrel (97% vs 35%), they had an increased rate of ECA occlusion (3.8%) compared with CEA patients (0.4%). CAS patients who went on to ECA occlusion had an increased incidence of prior neck irradiation (50% vs 15%; P = .03), but we did not identify an association of ECA occlusion with ISR >50%. CONCLUSIONS: Whereas prior publications have identified increased rates of external carotid stenosis, this is the first demonstration of increased ECA occlusion after CAS. However, ECA occlusion is uncommon (∼4%) and did not have an association with ISR >50%. Future work modeling ECA flow patterns before and after CAS will be used to further test this interaction.

Late mortality in females after endovascular aneurysm repair.

BACKGROUND: Abdominal aortic aneurysm (AAA) rupture is an adverse arterial remodeling event with high mortality risk. Because females have increased rupture risk with smaller AAAs (<5.5 cm), many recommend elective repair before the AAA reaches 5.5 cm. Elective repair improves survival for large AAAs, but long-term benefits of endovascular aneurysm repair (EVAR) for small AAAs in females remain less understood. The objective of this study was to identify if differences in late mortality exist between females undergoing elective EVAR at our institution for small and/or slow-growing AAAs compared with those who meet standard criteria. METHODS: We retrospectively analyzed all patients that underwent EVAR for infrarenal AAA from June, 2009-June, 2013. We excluded patients that were male, treated emergently or for iliac artery aneurysm, and that received renal and/or mesenteric artery stenting. Patients did not meet anatomic criteria if preoperative AAA diameter was <5.5 cm or enlarged <0.5 cm over 6 mo. Late mortality was assessed from the social security death index. RESULTS: Thirty-six of 162 elective EVAR patients (22.2%) were female (mean follow-up, 37.2 mo). Twenty patients (55.6%) met AAA size and/or growth criteria, whereas 16 (44.4%) did not meet criteria. Despite comparable demographics, comorbidities, and complications, patients that did not meet criteria had higher late mortality (37.5% versus 5%; P = 0.03) with a trend toward increased reoperation rate (25% versus. 5%; P = 0.48). Meeting size and/or growth criteria decreased odds of late death (odds ratio, 0.09; 95% confidence intervals, 0.01-0.83). CONCLUSIONS: There is increased late mortality in females receiving elective EVAR at our institution for small and/or slow-growing AAAs. This late mortality may limit the benefits of EVAR for this population.

Carotid duplex criteria for patients with contralateral occlusion.

BACKGROUND: Contralateral occlusion (CLO) occurs in approximately 8% of patients undergoing intervention for carotid artery stenosis. Patients with CLO have increased stroke risk compared with patients without CLO, but standard carotid duplex ultrasonography (CDUS) criteria are not a reliable manner to screen or follow patients with CLO. Because appropriate duplex criteria for these patients are not well understood, this article defines CDUS parameters that accurately predict carotid artery stenosis at our institution. METHODS: Sixty-five patients with ipsilateral carotid stenosis and CLO were identified from our institutional database. Fifteen of sixty-five patients had arteriography, computed tomography angiography, or magnetic resonance angiography within 6 mo of CDUS. We determined accuracy of our laboratory's criteria for determining stenosis category compared with three-dimensional imaging. Receiver operating characteristic curves were used to determine optimal peak systolic velocity (PSV), end diastolic velocity (EDV), and systolic ratio (SR) cutoff values for diagnosing ≥50% stenosis in this pilot cohort. Finally, the revised criteria were prospectively applied to a validation cohort (n = 8) from the same institution. RESULTS: Categorization of stenosis by standard PSV, EDV, and SR criteria saw similar accuracy trends in both pilot (46.7, 53.3, and 66.7%) and validation (25, 25, and 62.5%) cohorts. Receiver operating characteristic curve analysis in the pilot cohort identified optimized PSV, EDV, and SR cutoffs (≥250, ≥90, and ≥2.3 cm/s, respectively) for diagnosing ≥50% stenosis. In the pilot cohort, new PSV criteria increased specificity (60%-100%) with minimal decreased sensitivity (90%-80%), whereas new EDV criteria increased specificity (40%-71.4%) and maintained 100% sensitivity. New SR criteria failed to improve sensitivity or specificity above 80%. Similar trends for the new CDUS velocity criteria were observed in the validation cohort. CONCLUSIONS: Increasingly stringent ultrasound parameters can provide reliable criteria for determining ≥50% carotid stenosis in patients with CLO. Further prospective validation that includes more patients with high-grade ipsilateral stenosis will help identify the role of SR in segregating high-grade versus moderate stenosis in CLO patients.