Amputation For Critical Limb Ischemia Research Articles

Effects of iloprost in patients with critical limb ischemia: Results of a cohort study from the COPART registry

Iloprost has been proposed as an alternative to amputation in Critical Limb Ischemia (CLI) patients when revascularization was unsuccessful or not possible. Nonetheless, there is limited evidence of its benefit. The main objective was to evaluate the effectiveness of iloprost and the secondary objective was to evaluate its safety. In this cohort study including CLI patients from the COPART registry from 2006/10 to 2021/01, patients exposed to iloprost were matched with up to three unexposed patients according to age, sex, and Propensity Score (PS) for exposure to iloprost. The main outcome combined the occurrence of all-cause death and major amputations; survival was assessed over one-year using Kaplan-Meier estimates and Cox model analyses. Major Adverse Cardiovascular Events (MACE) were chosen as the safety outcome; the association with iloprost was estimated using a logistic regression model. Among 1850 CLI patients, 201 were exposed to iloprost (71.6% men; median age: 72 years vs. 72.1%; 75 years for unexposed). In 134 exposed patients matched to 375 unexposed patients, 14 major amputations and 24 deaths occurred in exposed patients (28.4%) vs. 33 and 46 respectively in the unexposed patients (20.9%). The hazard ratio (HR) was of 1.49 (95% Confidence Interval: 1.01-2.20). The association remained in the subgroup of "no option" patients (HR: 1.74; [1.01-2.20]). Regarding safety, 21/201 (10.7%) exposed patients experienced MACE vs. 146/1649 (9.41%) unexposed patients (unadjusted Odds Ratio [OR]: 1.17 [0.72-1.90]; adjusted OR: 1.23 [0.72-2.11]). The study did not find any benefit of iloprost in CLI patients and even suggested a deleterious effect.

ERICVA Risk Scale simplified as a predictor of amputation in critical limb ischemia.

Demonstrate that simplified ERICVA (Valladolid Critical Limb Ischaemia Risk Scale) is useful in predicting amputation in chronic limb-threatening ischemia (CLI) after one year of revascularization. A retrospective cohort study was performed. We analyzed the medical records of 93 patients over the age of 35 with the diagnosis of CLI who were treated in the Department of Internal Medicine, Orthopedics or in the Cardiovascular Surgery Unit of the Víctor Lazarte Echegaray Hospital and the High Complexity Virgen de La Puerta Hospital during the period 2015-2018. The simplified ERICVA score was determined in patients before surgical and endovascular revascularization. We included 31 patients who scored 2 or more points in the exposed group and 62 patients who scored less than 2 points in the group not exposed to amputation risk. The collected data was analyzed with the statistical program SPSS where the Relative Risk and significance was obtained with Pearson's Chi-square. The multivariate analysis was also carried out in order to obtain the adjusted relative risk. It was identified that the simplified ERICVA score greater than or equal to 2 points was more frequent in those who underwent amputation (90.3%) compared to patients who did not undergo amputation (4.8%), increasing the risk of amputation in those patients with CLI who underwent revascularization (RR: 18.67, P<0.001). It was also possible to identify that within the group of patients that showed a high risk of amputation according to the ERICVA scale, they had a higher risk of major amputation (RR: 9.32, P<0.001) as opposed to the risk of minor amputation (RR: 1, 89, P=0.193). Among the items of the simplified ERICVA scale, the preoperative neutrophil-lymphocyte ratio and hematocrit were significantly higher in the group of amputated patients (P<0.001). In addition, it was possible to identify that the score greater than or equal to 2 was independently associated with the risk of amputation in patients revascularized with CLI (RR: 13.5, P<0.001). In our patient population, the simplified ERICVA scale is useful in predicting major and minor amputation in critical limb ischemia after revascularization. The present data showed that the patients who had a simplified ERICVA score greater than or equal to 2 had a higher risk of major amputation compared to the risk of minor amputation. However, it is important to highlight that the impact on the prediction of minor amputation is greater because in some circumstances major amputation can appear as a complication of CLI.

End-stage renal disease patients undergoing angioplasty and bypass for critical limb ischemia have worse outcomes compared to non-ESRD patients: Systematic review and meta-analysis.

End-stage renal disease (ESRD) is associated with increased morbidity and mortality following lower extremity amputation for critical limb ischemia (CLI). Angioplasty and bypass are used in ESRD patients with CLI; however, the treatment of choice remains controversial. We compared the long-term outcomes in patients with CLI undergoing angioplasty or bypass to evaluate the differences between patients with ESRD and those without ESRD. Established databases were searched for observational studies comparing outcomes following bypass or angioplasty for CLI in patients with ESRD to those in non-ESRD patients. End points included survival, limb salvage, amputation-free survival (AFS), and primary and secondary patency at 1-year post-procedure. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effect model. We included 20 studies with a total of 24,851 patients. ESRD patients compared to non-ESRD patients with CLI had significantly lower survival post-angioplasty (OR 0.51, 95% CI 0.36-0.72, p < .001) and post-bypass (OR 0.26, 95% CI 0.15-0.45, p < .001). ESRD patients had lower rates of limb salvage post-bypass (OR 0.33, 95% CI 0.21-0.53, p < .001) and post-angioplasty (OR 0.54, 95% CI 0.41-0.70, p < .001). AFS was significantly lower in ESRD patients compared to non-ESRD patients following angioplasty (OR 0.48, 95% CI 0.32-0.71, p < .001) and bypass (OR 0.28, 95% CI 0.16-0.47, p < .001) despite no significant differences in primary patency. ESRD patients had overall worse secondary patency post-angioplasty and/or bypass (OR 0.54, 95% CI 0.32-0.94, p=.03) compared to non-ESRD patients. A meta-analysis of four studies directly comparing survival in ESRD patients with CLI based on whether they underwent angioplasty or bypass showed no difference (OR 0.93, 95% CI 0.64-1.35, p=.69). ESRD patients have worse survival, limb salvage, and AFS outcomes following angioplasty and bypass for CLI compared to non-ESRD patients. Large randomized controlled trials comparing these two modalities of treatment in this patient population are needed for further clarity.

Calcifying characteristics of peripheral vascular smooth muscle cells of chronic kidney disease patients with critical limb ischemia.

The role of vascular smooth muscle cells (VSMCs) in vascular calcification, which is related to chronic kidney disease (CKD), has been studied in greater detail in the major arteries relative to the peripheral arteries. We compared the calcifying characteristics of peripheral VSMCs relative to non-pathologic major VSMCs in patients with severe peripheral artery disease (PAD). We isolated peripheral VSMCs from the posterior tibial artery of 10 patients with CKD who underwent below-knee amputation for critical limb ischemia (CLI). Using normal human aortic VSMCs as a control group, we cultured the cells in normal and high phosphate media for 10 days, and subsequently tested by immunofluorescence staining. We compared the calcification levels between the two groups using various assays, tests for cell viability, and scanning electron microscopy. As a result, calcification of pathologic peripheral VSMCs increased significantly with time (p = 0.028) and was significantly higher than that in human aortic VSMCs in calcium assays (p = 0.043). Dead cells in the pathologic VSMC group were more distinct in high phosphate media than in human aortic VSMCs. In conclusion, VSMCs from the peripheral artery of patients with severe CKD and CLI who underwent amputation surgery showed marked calcifying characteristics compared to normal human aortic VSMCs.

Preventing Major Amputations in Patients with Critical Limb Ischemia.

This review summarizes the risks of lower extremity amputation associated with critical limb ischemia (CLI) and discusses current therapies that can prevent amputation in CLI. CLI remains an under-recognized condition associated with high rates of major amputation and disparities in care. Optimal medical therapy can reduce the risk of major adverse cardiovascular and limb events, but revascularization combined with close wound care remains the cornerstone of amputation prevention. Endovascular revascularization has become more common over time and has been associated with a reduction in amputation rates. Ongoing clinical trials will help inform best practices for revascularization strategies and techniques. Vascular care is inconsistent across the USA, with significant variation in access to care revascularization rates and rates of major amputation. Major amputation can be prevented in patients with CLI when optimal medical therapy, lifestyle modification, and revascularization are provided in a multidisciplinary setting.

Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes

ObjectiveMultiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. MethodsPlasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry. ResultsPlasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, <0.001; 95% CI, <0.001-0.003; P < .001), indole-3-propionic acid (OR, 0.27; 95% CI, 0.019-0.91; P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P < .001) correlated with the ankle-brachial index, a surrogate for overall atherosclerotic disease burden. Fourteen patients experienced a major postoperative cardiac complication within 30 days in the advanced atherosclerosis cohort, which was associated with baseline kynurenine/tryptophan ratio (P = .001) and hippuric acid (P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid (P = .002) and the kynurenine/tryptophan ratio (P < .001) at baseline. Both hippuric acid and the kynurenine/tryptophan ratio were independently associated with a major adverse cardiac event in multivariate analyses that included diabetes mellitus. ConclusionsSpecific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted.

Post-treatment neutrophil-lymphocyte ratio independently predicts amputation in critical limb ischemia without operation

OBJECTIVES:Limited information is available concerning the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients who receive conservative therapy. Accordingly, this study was designed to evaluate the predictive value of the post-treatment neutrophil-lymphocyte ratio in critical limb ischemia patients without surgery.METHOD:From January 2009 to January 2011, critical limb ischemia patients were admitted to a vascular center. The demographic data, patient histories, comorbidities and risk factors were documented, and the differential cell count was determined at admission and seven days later after conservative therapy. The cutoff value of the post-treatment neutrophil-lymphocyte ratio was determined by an ROC curve. Patients were divided into groups A and B according to the cutoff value. Amputation-free survival was compared between groups. Univariate and multivariate analyses were used to identify independent risk factors.RESULT:A total of 172 patients were identified with a mean age 71.98±10.09 years; among them, 122 were male. A value of 3.8 was identified as the cutoff value of the post-treatment neutrophil-lymphocyte ratio. Groups A (post-treatment neutrophil-lymphocyte ratio ≥3.8) and B (post-treatment neutrophil-lymphocyte ratio <3.8) showed a significant difference in amputation-free survival (P<0.001). The 1-year, 2-year and 3-year amputation-free survival rates were 79.6%, 55.6% and 46.3%, respectively, in group A; however, in group B, these values were 89.7%, 79.3% and 75.9%, respectively. The post-treatment neutrophil-lymphocyte ratio was identified as an independent predictive factor for amputation in critical limb ischemia patients (P<0.001).CONCLUSION:The post-treatment neutrophil-lymphocyte ratio is an independent predictive factor for amputation in critical limb ischemia patients. Patients with a post-treatment neutrophil-lymphocyte ratio ≥3.8 are likely to suffer from amputation; amputation-free survival usually occurs in patients with a post-treatment neutrophil-lymphocyte ratio <3.8.

Lower Extremity Revascularization Using Directional Atherectomy: 12-Month Prospective Results of the DEFINITIVE LE Study

ObjectivesThe aim of this study was to assess the safety and effectiveness of directional atherectomy (DA) for endovascular treatment of peripheral arterial disease (PAD) in infrainguinal arteries in patients with claudication or critical limb ischemia. BackgroundTo date, no prospective, multicenter, independently-adjudicated study has evaluated the effectiveness and durability of DA in the treatment of PAD. Previous DA studies have not been prospectively powered to evaluate any differences in outcomes in patients with and without diabetes. MethodsDEFINITIVE LE (Determination of EFfectiveness of the SilverHawk® PerIpheral Plaque ExcisioN System (SIlverHawk Device) for the Treatment of Infrainguinal VEssels / Lower Extremities) prospectively enrolled subjects at 47 multinational centers with an infrainguinal lesion length up to 20 cm. Primary endpoints were defined as primary patency at 12 months for claudicants and freedom from major unplanned amputation for critical limb ischemia (CLI) subjects. A pre-specified statistical hypothesis evaluated noninferiority of primary patency in diabetic versus nondiabetic claudicants. Independent angiographic and sonographic core laboratories assessed outcomes, and events were adjudicated by a clinical events committee. ResultsA total of 800 subjects were enrolled. The 12-month primary patency was 78% (95% confidence interval: 74.0% to 80.6%) in claudicants, with a 77% rate in the diabetic subgroup versus 78% in the nondiabetic subgroup (noninferior, p < 0.001). The rate of freedom from major unplanned amputation of the target limb at 12 months in CLI subjects was 95% (95% confidence interval: 90.7% to 97.4%). Periprocedural adverse events included embolization (3.8%), perforation (5.3%), and abrupt closure (2.0%). The bail-out stent rate was 3.2%. ConclusionsThe DEFINITIVE LE study demonstrated that DA is a safe and effective treatment modality at 12 months for a diverse patient population with either claudication or CLI. Furthermore, DA was shown to be noninferior for treating PAD in patients with diabetes compared with those without diabetes. (Study of SilverHawk/TurboHawk in Lower Extremity Vessels [DEFINITIVE LE]; NCT00883246).

Global Remodeling of the Vascular Stem Cell Niche in Bone Marrow of Diabetic Patients

Rationale: The impact of diabetes mellitus on bone marrow (BM) structure is incompletely understood. Objective: Investigate the effect of type-2 diabetes mellitus (T2DM) on BM microvascular and hematopoietic cell composition in patients without vascular complications. Methods and Results: Bone samples were obtained from T2DM patients and nondiabetic controls (C) during hip replacement surgery and from T2DM patients undergoing amputation for critical limb ischemia. BM composition was assessed by histomorphometry, immunostaining, and flow cytometry. Expressional studies were performed on CD34 pos immunosorted BM progenitor cells (PCs). Diabetes mellitus causes a reduction of hematopoietic tissue, fat deposition, and microvascular rarefaction, especially when associated with critical limb ischemia. Immunohistochemistry documented increased apoptosis and reduced abundance of CD34 pos -PCs in diabetic groups. Likewise, flow cytometry showed scarcity of BM PCs in T2DM and T2DM+critical limb ischemia compared with C, but similar levels of mature hematopoietic cells. Activation of apoptosis in CD34 pos -PCs was associated with upregulation and nuclear localization of the proapoptotic factor FOXO3a and induction of FOXO3a targets, p21 and p27 kip1 . Moreover, microRNA-155, which regulates cell survival through inhibition of FOXO3a, was downregulated in diabetic CD34 pos -PCs and inversely correlated with FOXO3a levels. The effect of diabetes mellitus on anatomic and molecular end points was confirmed when considering background covariates. Furthermore, exposure of healthy CD34 pos -PCs to high glucose reproduced the transcriptional changes induced by diabetes mellitus, with this effect being reversed by forced expression of microRNA-155. Conclusions: We provide new anatomic and molecular evidence for the damaging effect of diabetes mellitus on human BM, comprising microvascular rarefaction and shortage of PCs attributable to activation of proapoptotic pathway.

Factors predicting resource utilization and survival after major amputation

Major amputation is associated with increased short-term healthcare resource utilization (RU), early mortality, and socioeconomic status (SES) disparities. Our objective is to study patient-specific and SES-related predictors of long-term RU and survival after amputation. This retrospective analysis identified 364 adult patients who underwent index major amputation for critical limb ischemia from January 1995 through December 2000 at two tertiary centers with outcomes through December 2010. Age, gender, SES (race, income, insurance, and marital status), comorbidities (congestive heart failure [CHF], diabetes, diabetes with complications, and renal failure [RF]), subsequent procedures, cumulative length of stay (cLOS), and mortality were analyzed. Bivariate and multivariate Poisson regression for subsequent procedures and cLOS and Cox proportional hazard modeling for all-cause mortality were undertaken. During a mean follow-up of 3.25 years, amputation patients had mean cLOS of 71.2 days per person-year (median, 17.6), 19.5 readmissions per person-year (median, 2.1), 0.57 amputation-related procedures (median, 0), and 0.31 cardiovascular procedures (median, 0). Below-knee amputation as the index procedure was performed in 70% of patients, and 25% had additional amputation procedures. Of readmissions at ≤ 30 days, 52% were amputation-related. Overall mortality during follow-up was 86.9%; 37 patients (10.2%) died within 30 days. Among patients surviving >30 days, multivariate Poisson regression demonstrated that younger age (incidence rate ratio [IRR], 0.98), public insurance (IRR, 1.63), CHF (IRR, 1.60), and RF (IRR, 2.12) were associated with increased cLOS. Diabetes with complications (IRR, 1.90) and RF (IRR, 2.47) affected subsequent amputation procedures. CHF (IRR, 1.83) and RF (IRR, 3.67) were associated with a greater number of cardiovascular procedures. Cox proportional hazard modeling indicated older age (hazard ratio [HR], 1.04), CHF (HR, 2.26), and RF (HR, 2.60) were risk factors for decreased survival. Factors associated with SES were not significantly related to the outcomes. This study found that RU is high for amputees, and increased RU persists beyond the perioperative period. Results were similar across SES indices, suggesting higher SES may not be protective against poor outcomes when limb salvage is no longer attainable. These findings support the hypothesis that SES disparities may be more modifiable during earlier stages of care for critical limb ischemia.

Abstract 14: Intensity of Vascular Care for PAD: More Spending, But Not Fewer Amputations.

Introduction: While significant disparities exist in the care of patients with severe PAD, the relationship between the intensity of vascular care, spending, and limb salvage remains unclear. Methods: We studied the vascular care provided to 20,058 Medicare patients in the year prior to amputation for critical limb ischemia, using the 306 hospital referral regions (HRRs) as defined in the Dartmouth Atlas of Healthcare. We examined associations between the intensity of vascular care (defined as the number of revascularization procedures or vascular-related admissions in the year prior to amputation), price-adjusted Medicare spending, and population-based amputation rates. Results: Overall, 54% of patients did not undergo any revascularization in the year prior to amputation. Of the 46% who underwent open or endovascular revascularization, 18% had one procedure, and 28% had more than one revascularization procedure. Among patients who underwent revascularization, the mean regional cost of vascular care in the year prior to amputation was $14,155, such as in Gainesville FL (Figure, Panel A). However, in HRRs where at least 25 patients underwent amputation, spending on vascular care in the year prior to amputation varied from $9,475 (Bismarck, North Dakota) to $26,787 (St. Paul, Minnesota). The intensity of vascular care, as measured by procedures and hospitalizations, was well correlated with spending (r=0.36), but higher spending was not associated with lower population-based amputation rates (r=0.07) (Figure, Panel B). Conclusion: While Medicare spending is directly related to the intensity of vascular care, there is little evidence to suggest that higher spending is associated with lower population-based rates of amputation. Future health policy is needed to better direct Medicare spending for patients at risk for amputation.

Perioperative and Rehabilitation Outcome after Lower-Limb Amputation for Critical Ischemia

The Trans-Antlantic Intersociety Consensus (TASC) II Working Group estimated that the incidence of major amputations (amputations above the ankle) varies from 12 to 50 per 100.000 population per year and that the annual rate of primary amputation in critical limb ischemia is 25% despite aggressive revascularization programs [1]. Indications for amputation include: a) complications of diabetes (70%), b) infection without diabetes (15%), c) ischemia without infection (10%), d) trauma and miscellaneous (5%) [2]. Aging of the population and increase of diabetes and obesity are the main reasons to support that future trends in these areas will have a great effect on health care systems.

Long-term Resource Utilization and Survival After Major Amputation for Critical Limb Ischemia

direct and indirect hospital costs of the initial and subsequent reinterventions was applied to a prospectively collected vascular database. Analysis was done via Student t test and log-ranked Kaplan-Meier analysis. Results: The mean length in the ER group was 18.5 cm. A prosthetic conduit was used in 51% of SR group. Patency at 1 year was similar in both groups and superior for SR thereafter. The rate of all reinterventions was 28 of 85 (33%) in ER and 40 of 98 (41%) in SR. The average hospital costs for the SR group were significantly greater than costs for the ER group ($18,506 $,877 vs $11,740 $709, P .005); however, this difference was not significant when comparing amortized costs per day of patency at 1 year ($82 $21 vs $136 103), 2 years ($55 $28 vs $152 134), 3 years ($56 $44 vs $16 3), or 4 years ($8 $1 vs $10 $2) in patients with claudication or chronic limb ischemia. Conclusions: The amortized cost/day model is valuable for evaluating resource utilization, enabling us to examine the cost efficacy of the procedure, patency, and reinterventions. Our findings indicate that although initially endovascular therapy for femoropopliteal occlusive disease is associated with significant savings, long term the amortized cost per day is comparable in selected patients undergoing ER or SR.

Results of open vascular surgical therapy in chronic peripheral arterial disease

Surgery in chronic peripheral arterial disease (PAD) can alleviate symptoms in claudicants and may impede amputation in critical limb ischemia. The current data on different surgical strategies and techniques from the aortoiliac region to the pedal arteries as well as amputation as last resort are described and discussed. Treatment of PAD depends on the condition of the patient and his comorbidities. The question of optimal therapy for each patient cannot always be answered in the operating theatre or the angio-suite.

Predictors of wound complications following major amputation for critical limb ischemia

For patients with end-stage critical limb ischemia (CLI) who have already suffered over an extended period of time, a major amputation that is free of wound complications remains paramount. Utilizing data from the American College of Surgeons, National Surgical Quality Improvement Program (ACS-NSQIP), the objective of this report was to determine critical factors leading to wound complications following major amputation. ACS-NSQIP was used to identify patients ≥ 50 years, with CLI, and having an ipsilateral below-(BKA) or above-knee amputation (AKA). The primary outcome was wound occurrence (WO) defined by affirmative findings of superficial infection, deep infection, and/or wound disruption. The secondary outcome was 30-day mortality. Following univariate analyses, a multiple logistic regression was performed to identify predictive factors. Between January 1, 2005 and December 31, 2008, 4250 patients fulfilled inclusion criteria (2309 BKAs and 1941 AKAs). WOs were 10.4% for BKAs and 7.2% for AKAs. For BKAs, increasing elevation in international normalized ratio (INR) predicted more WOs (P = .008, odds ratio [OR] 1.5 for every integral increase in INR) as did age 50 to 59 compared with older patients (P = .002, OR 1.9). For AKAs, being a current smoker predicted more WOs (P = .0008, OR 1.8) as did an increasing body mass index (BMI) (P = .02, OR 1.3 for every 10 kg/m(2) increase in BMI). Mortality was 7.6% for BKAs and 12% for AKAs. Complete functional dependence was most predictive of mortality following AKA (P < .0001, OR 2.5). Medical comorbidities such as history of myocardial infarcation (MI) (OR 1.8), congestive heart failure (CHF, OR 1.6), and chronic obstructive pulmonary disease (COPD, OR 1.6) predicted mortality following BKA, while dialysis use (OR 2.4), CHF (OR 2.3), and COPD (OR 2.1) predicted mortality following AKA. Wound occurrences and mortality rates after major amputation for CLI continue to be a prevalent problem. Normalization of the INR prior to BKA should decrease WOs. Heightened awareness in higher risk patients with improved preventive measures, earlier disease recognition, better treatments, and increased education remain critical to improving outcomes in an already stressed patient cohort.

Socioeconomic and hospital-related predictors of amputation for critical limb ischemia

Disparities in limb salvage procedures may be driven by socioeconomic status (SES) and access to high-volume hospitals. We sought to identify SES factors associated with major amputation in the setting of critical limb ischemia (CLI). The 2003-2007 Nationwide Inpatient Sample was queried for discharges containing lower extremity revascularization (LER) or major amputation and chronic CLI (N = 958,120). The Elixhauser method was used to adjust for comorbidities. Significant predictors in bivariate logistic regression were entered into a multivariate logistic regression for the dependent variable of amputation vs LER. Overall, 24.2% of CLI patients underwent amputation. Significant differences were seen between both groups in bivariate and multivariate analysis of SES factors, including race, income, and insurance status. Lower-income patients were more likely to be treated at low-LER-volume institutions (odds ratio [OR], 1.74; P < .001). Patients at higher-LER-volume centers (OR, 15.16; P <.001) admitted electively (OR, 2.19; P < .001) and evaluated with diagnostic imaging (OR, 10.63; P < .001) were more likely to receive LER. After controlling for comorbidities, minority patients, those with lower SES, and patients with Medicaid were more likely receive amputation for CLI in low-volume hospitals. Addressing SES and hospital factors may reduce amputation rates for CLI.

Randomized Controlled Trial of Dual Antiplatelet Therapy in Patients Undergoing Surgery for Critical Limb Ischemia

Patients with critical limb ischemia have a perioperative cardiovascular morbidity comparable to patients with acute coronary syndromes. We hypothesized that perioperative dual antiplatelet therapy would improve biomarkers of atherothrombosis without causing unacceptable bleeding in patients undergoing surgery for critical limb ischemia. In a double-blind randomized controlled trial, 108 patients undergoing infrainguinal revascularization or amputation for critical limb ischemia were maintained on aspirin (75 mg daily) and randomized to clopidogrel (600 mg prior to surgery, and 75 mg daily for 3 days; n = 50) or matched placebo (n = 58). Platelet activation and myocardial injury were assessed by flow cytometry and plasma troponin concentrations, respectively. Clopidogrel reduced platelet-monocyte aggregation before surgery (38%-30%; P = 0.007). This was sustained in the postoperative period (P = 0.0019). There were 18 troponin-positive events (8 [16.0%] clopidogrel vs. 10 [17.2%] placebo; relative risk [RR]: 0.93, 95% confidence interval [CI]: 0.39-2.17; P = 0.86). Half of troponin-positive events occurred preoperatively with clopidogrel causing a greater decline in troponin concentrations (P < 0.001). There was no increase in major life-threatening bleeding (7 [14%] vs. 6 [10%]; RR: 1.4, 95% CI: 0.49-3.76; P = 0.56) or minor bleeding (17 [34%] vs. 12 [21%]; RR 1.64, 95% CI: 0.87-3.1; P = 0.12), although blood transfusions were increased (28% vs. 12.6%, RR: 2.3, 95% CI: 1.0-5.29; P = 0.037). In patients with critical limb ischemia, perioperative dual antiplatelet therapy reduces biomarkers of atherothrombosis without causing unacceptable bleeding. Large-scale randomized controlled trials are needed to establish whether dual antiplatelet therapy improves clinical outcome in high-risk patients undergoing vascular surgery.

PVSS12. Socioeconomic and Hospital-Related Predictors of Amputation for Critical Limb Ischemia

Disparities in limb salvage procedures may be driven by socioeconomic status (SES) and access to high volume hospitals. We sought to identify SES factors associated with major amputation in the setting of critical limb ischemia (CLI). The 2007 Nationwide Inpatient Sample was queried for discharges containing lower extremity revascularization (LER), major amputation, and chronic CLI (N = 152, 736). The Elixhauser method was used to adjust for comorbidities. Significant predictors in bivariate logistic regression were entered into a multivariate logistic regression for the dependent variable of amputation vs LER. Overall, 18.1% of CLI patients underwent amputation. Significant differences were seen between both groups in bivariate and multivariate analysis of SES factors, including race, income, and insurance status (Table 1). Lower income patients were more likely to be treated at low LER volume institutions (OR 1.44, p = 0.017). Patients at higher LER volume centers (OR 2.11, p < 0.001), admitted electively (OR 1.96, p < 0.001) and evaluated with diagnostic imaging (OR 4.30, p < 0.001) were more likely to receive LER.Table 1Multivariate regression for amputationOdds Ratio for Amputation95% Confidence IntervalMale gender1.22 (p < 0.001)1.13, 1.32Black vs White race2.33 (p < 0.001)2.02, 2.69Hispanic vs White race1.37 (p < 0.001)1.16, 1.62Median income <\$39, 0001.25 (p = 0.005)1.08, 1.45 \$39, 000-47, 9991.11 (p = 0.159)0.96, 1.28 \$48, 000-62, 9991.03 (p = 0.682)0.88, 1.21 >\$63, 000refPrivate payer vs Medicare0.83 (p = 0.002)0.74, 0.94Medicaid vs Medicare1.24 (p = 0.015)1.04, 1.48 Open table in a new tab After controlling for comorbidities, minority patients, those with lower SES, and patients with Medicaid were more likely receive amputation for CLI in low volume hospitals. Addressing SES and hospital factors may reduce amputation rates for CLI.

Disparities in vascular surgery: Is it biology or environment?

Disparities in health care are well documented for several racial, ethnic, and gender groups. In peripheral arterial disease, differences in prevalence, treatment selection, treatment outcomes, and resulting quality of life have negative effects on some minority groups and women. It may be easy to document disparities, but it is harder to understand their underlying causes. Are there biologic differences between members of racial and ethnic groups that influence disease presentation and outcomes? Or is the socioeconomic environment that surrounds them the true driver of observed differences? This article reviews the evidence for racial and gender disparities in vascular surgery and presents some potential mechanisms that may explain the disparities.

Do Differences in Hospital and Surgeon Quality Explain Racial Disparities in Lower-Extremity Vascular Amputations?

To understand whether racial disparities in surgery for lower-extremity arterial disease are minimized by high-quality providers, or instead, differential treatment of otherwise similar patients pervades all settings. Black patients are substantially more likely than whites to undergo amputation rather than revascularization for lower-extremity arterial disease. Because their care is disproportionately concentrated among a small share of providers, some have attributed such disparities to the quality and capacity of these sites. We evaluated all 86,865 white or black fee-for-service Medicare beneficiaries 65 and older who underwent major lower-extremity vascular procedures. Using generalized linear mixed models with random effects, we computed risk-adjusted odds of amputation by race overall, and after serial substratification by salient patient and provider characteristics. Blacks were far more likely to undergo amputation (45% vs. 20%). Their procedures were performed more often by nonspecialists (41% vs. 27%; P < 0.001), in low-volume hospitals (40% vs. 32%; P < 0.001), with high amputation rates (53% vs. 29%; P < 0.001). Controlling for differences in comorbidity, disease severity, and surgeon and hospital performance, blacks' odds of amputation remained 1.7 times greater (95% confidence interval: 1.6-1.9). Even among highest-performing providers-vascular specialists in high-volume, urban teaching hospitals with angioplasty facilities-racial gaps persisted (risk-adjusted amputation rates: 7% for blacks vs. 4% for whites, P < 0.001; odds ratio: 1.8, 95% confidence interval: 1.5-2.1). Black patients with critical limb ischemia face significantly higher risk of major amputation, even when treated by providers with highest likelihoods of revascularization. Increased referral to high-performing providers might increase limb-preservation, but cannot eliminate disparities until equitable treatment can be ensured in all settings.