Louis L. Nguyen

Disparity in outcomes of surgical revascularization for limb salvage: Race and gender are synergistic determinants of vein graft failure and limb loss

Background— Vein bypass surgery is an effective therapy for atherosclerotic occlusive disease in the coronary and peripheral circulations; however, long-term results are limited by progressive attrition of graft patency. Failure of vein bypass grafts in patients with critical limb ischemia results in morbidity, limb loss, and additional resource use. Although technical factors are known to be critical to the success of surgical revascularization, patient-specific risk factors are not well defined. In particular, the relationship of race/ethnicity and gender to the outcomes of peripheral bypass surgery has been controversial. Methods and Results— We analyzed the Project of Ex Vivo Vein Graft Engineering via Transfection III (PREVENT III) randomized trial database, which included 1404 lower extremity vein graft operations performed exclusively for critical limb ischemia at 83 North American centers. Trial design included intensive ultrasound surveillance of the bypass graft and clinical follow-up to 1 year. Multivariable modeling (Cox proportional hazards and propensity score) was used to examine the relationships of demographic variables to clinical end points, including perioperative (30-day) events and 1-year outcomes (vein graft patency, limb salvage, and patient survival). Final propensity score models adjusted for 16 covariates (including type of institution, technical factors, selected comorbidities, and adjunctive medications) to examine the associations between race, gender, and outcomes. Among the 249 black patients enrolled in PREVENT III, 118 were women and 131 were men. Black men were at increased risk for early graft failure (hazard ratio [HR], 2.832 for 30-day failure; 95% confidence interval [CI], 1.393 to 5.759; P=0.0004), even when the analysis was restricted to exclude high-risk venous conduits. Black patients experienced reduced secondary patency (HR, 1.49; 95% CI, 1.08 to 2.06; P=0.016) and limb salvage (HR, 2.02; 95% CI, 1.27 to 3.20; P=0.003) at 1 year. Propensity score models demonstrate that black women were the most disadvantaged, with an increased risk for loss of graft patency (HR, 2.02 for secondary patency; 95% CI, 1.27 to 3.20; P=0.003) and major amputation (HR, 2.38; 95% CI, 1.18 to 4.83; P=0.016) at 1 year. Perioperative mortality and 1-year mortality were similar across race/gender groups. Conclusions— Black race and female gender are risk factors for adverse outcomes after vein bypass surgery for limb salvage. Graft failure and limb loss are more common events in black patients, with black women being a particularly high-risk group. These data suggest the possibility of an altered biological response to vein grafting in this population; however, further studies are needed to determine the mechanisms underlying these observed disparities in outcome.

Cellular interactions in vascular growth and differentiation.

In nature, mammalian cells do not exist in isolation, but rather are involved in interactions with other cells and matrix. In this review, several aspects of cellular interactions that are important in vascular growth and development will be highlighted. The cardiovascular system is the earliest to develop in the embryo. A number of growth factors and their receptors mediate the complex stages of migration, assembly, organization, and stabilization of developing vessels. In the adult organism, normal angiogenesis is restricted primarily to tissue growth (such as muscle and fat), the wound healing process and the female reproductive system. However, pathological angiogenesis, such as with tumor growth, diabetic retinopathy, and arthritis, is of great concern. The identification and/or development of exogenous and endogenous angiogenesis inhibitors has added to the understanding of these pathological processes. In addition to cellular interactions via ligands and receptors, cells also interact directly through physical contacts. These interactions facilitate anchorage, communication, and permeability. Since vessels serve as non-leaky conduits for blood flow as well as interfaces for molecular diffusion, the physical interactions between the cells that make up vessels must be specific for the function at hand. Permeability is a specialized function of vessels and is mediated by intracellular mechanisms and intercellular interactions. Cells also interact with the surrounding extracellular matrix. Integrin-matrix interaction is a two-way exchange critical for angiogenesis. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases play major roles in embryonic remodeling, adult injury, and pathological conditions. Several experimental model systems have been useful in our understanding of cellular interactions. These in vitro models incorporate heterotypic cell-cell interactions and/or allow cell-matrix interactions to occur.

Clinical results of carotid artery stenting compared with carotid endarterectomy

OBJECTIVES Carotid artery stenting (CAS) is an alternative to carotid endarterectomy (CEA) for treating carotid artery stenosis. We conducted a systematic review and meta-analysis of the clinical trials to date comparing these two procedures to determine their relative safety and efficacy. METHODS Searches of the Cochrane Controlled Trials Register, MEDLINE, and EMBASE identified two cohort studies and eight randomized, controlled trials (RCTs) comparing CEA and CAS. Meta-analysis was performed for the primary outcome of 30-day stroke or death, using an intention-to-treat analysis. Between-trial heterogeneity was assessed using the chi2 test, and fixed-effects models were used to pool estimates in the absence of heterogeneity. Meta-regression was conducted to investigate potential effect differences by patient, intervention, and trial characteristics. To evaluate the effect of study design and inclusion criteria, sensitivity and subgroup analyses were performed. RESULTS Ten trials encompassing 3580 patients were analyzed. Patients who underwent CAS had a higher risk of 30-day stroke/death relative to patients who underwent CEA (risk ratio [RR], 1.30; 95% CI, 1.01-1.67). Meta-analysis and meta-regression demonstrated no between-trial heterogeneity. Sensitivity analysis of only RCTs showed similar higher risk for stroke/death (RR, 1.38; 95% CI, 1.06-1.79) in CAS patients. Subgroup analysis of trials enrolling only symptomatic patients showed higher risk of 30-day stroke/death (RR, 1.63; 95% CI, 1.18-2.25), but trials enrolling both symptomatic and asymptomatic patients showed no significant differences (RR, 0.89; 95% CI, 0.59-1.35). CONCLUSIONS Meta-analysis of trials to date shows CAS is associated with higher 30-day risk of stroke/death compared with CEA. Thus, for the patient at average surgical risk, the role of CAS is unproven, especially for symptomatic patients. And for the patient at high surgical risk, the role of any intervention is uncertain in the setting of competing comorbidities. The results of ongoing clinical trials in this area will likely provide additional evidence to support treatment choices for carotid artery stenosis.

Predictive factors of 30-day unplanned readmission after lower extremity bypass

BACKGROUND Thirty-day unplanned readmission after lower extremity bypass represents a large cost burden and is a logical target for cost-containment strategies. We undertook this study to evaluate factors associated with unplanned readmission after lower extremity bypass. METHODS This is a retrospective analysis from a prospective institutional registry. All lower extremity bypasses for occlusive disease from January 1995 to July 2011 were included. The primary end point was 30-day unplanned readmission. Secondary end points included graft patency and limb salvage. RESULTS Of 1543 lower extremity bypasses performed, 84.5% were for critical limb ischemia and 15.5% were patients with intermittent claudication. Twenty-seven patients (1.7%) died in-house and were excluded from further analysis. Of 1516 lower extremity bypasses analyzed, 42 (2.8%) were in patients with a planned readmission within 30 days, and 349 (23.0%), in patients with an unplanned readmission. Most unplanned readmissions were wound related (62.9%). By multivariable analysis, preoperative predictive factors for unplanned readmission were dialysis dependence (odds ratio [OR], 1.73; P = .004), tissue loss indication (OR, 1.62; P = .0004), and history of congestive heart failure (OR, 1.43; P = .03). Postoperative predictors included distal inflow source (OR, 1.38; P = .016), in-hospital wound infection (OR, 8.30; P < .0001), in-hospital graft failure (OR, 3.20; P < .0001), and myocardial infarction (OR, 1.96; P < .04). Neither index length of stay nor discharge disposition independently predicted unplanned readmission. Unplanned readmission was associated with loss of assisted primary patency (hazard ratio, 1.39; 95% confidence interval, 1.08-1.80; P = .01) and long-term limb loss (hazard ratio, 1.68; 95% confidence interval, 1.23-2.29; P = .001). CONCLUSIONS Thirty-day unplanned readmission is a frequent occurrence after lower extremity bypass (23.0%). Stratifying patients by risk factors associated with unplanned readmission is essential for quality improvement and equitable resource allocation when disease-specific bundling strategies are being derived.

Under-representation of Women and Ethnic Minorities in Vascular Surgery Randomized Controlled Trials

OBJECTIVES Gender and ethnicity are factors affecting the incidence and severity of vascular disease as well as subsequent treatment outcomes. Although well studied in other fields, balanced enrollment of patients with relevant demographic characteristics in vascular surgery randomized controlled trials (RCTs) is not well known. This study describes the reporting of gender and ethnicity data in vascular surgery RCTs and analyzes whether these studies adequately represent our diverse patient population. METHODS We conducted a retrospective review of United States-based RCTs from 1983 through 2007 for three broadly defined vascular procedures: aortic aneurysm repair (AAR), carotid revascularization (CR), and lower extremity revascularization (LER). Included studies were examined for gender and ethnicity data, study parameters, funding source, and geographic region. The Nationwide Inpatient Sample (NIS) database was analyzed to obtain group-specific procedure frequency as an estimate of procedure frequency in the general population. RESULTS We reviewed 77 studies, and 52 met our inclusion criteria. Only 85% reported gender, and 21% reported ethnicity. Reporting of ethnicity was strongly associated with larger (>280 participants), multicenter, government-funded trials (P < .001 for all). Women are disproportionately under-represented in RCTs for all procedure categories (AAR, 9.0% vs 21.5%; CR, 30.0% vs 42.9%; LER, 22.4% vs 41.3%). Minorities are under-represented in AAR studies (6.0% vs 10.7%) and CR studies (6.9% vs 9.5%) but are over-represented in LER studies (26.0% vs 21.8%, P < .001 for all). CONCLUSIONS Minority ethnicity and female gender are under-reported and under-represented in vascular surgery RCTs, particularly in small, non-government-funded and single-center trials. The generalizability of some trial results may not be applicable to these populations. Greater effort to enroll a balanced study population in RCTs may yield more broadly applicable results.

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

OBJECTIVE 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). METHODS 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. RESULTS 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. CONCLUSIONS 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.

Suprarenal aortic cross-clamp position: A reappraisal of its effects on outcomes for open abdominal aortic aneurysm repair

OBJECTIVES With the increasing use of endovascular aneurysm repair, a greater proportion of open aneurysm repairs in the future are expected to be more complex and require suprarenal cross-clamping. We sought to evaluate the effects of suprarenal (SR) vs infrarenal (IR) aortic cross-clamp position in abdominal aortic aneurysm (AAA) repair in an updated single center series. METHODS All elective open AAA repairs performed at our institution between 1990 and 2006 were entered into a prospective database and reviewed retrospectively. Our main stratification variable was SR vs IR. The SR group was further subdivided into those requiring an adjunctive renal revascularization procedure (SR+RRP; n = 54) and those who did not (SR-RRP; n = 117). Univariate and multivariate models were used to analyze the effect of baseline variables and operative variables on our primary endpoint 30-day mortality as well as secondary endpoints such as major adverse events, postoperative decline in renal function (defined as doubling of baseline creatinine to level >2 mg/dL, or new-onset dialysis) and long-term survival. A propensity score model was developed to control for confounding variables associated with the use of an SR cross-clamp. RESULTS A total of 1020 patients underwent elective AAA repair, of which 849 (83.2%) were IR and 171 (16.8%) were SR. Diabetes (14.6% vs 9.1%, P = .027), hypertension (70.2% vs 61.4%, P = .03), and chronic renal failure (14.0% vs 4.7%, P = .001) were more prevalent in the SR group, and mean aneurysm size was larger (6.0 cm vs 5.6 cm, P = .001). Estimated blood loss was higher (1919 mL vs 1257 mL, P = .001) in the SR group, as was mean length of stay (12.6 days vs 10.7 days, P = .047). Perioperative (30-day) mortality rate was 1.8% for the SR group and 1.2% for the IR group (P = .44). Postoperative decline in renal function was 17.0% in SR vs 9.5% in IR (P = .003), however, new-onset dialysis was rare (0.6% SR, 0.8% IR, P = NS). The combination of SR+RRP was associated with an increased risk for postoperative decline in renal function (14.8% SR+RRP, 4.3% SR-RRP, P = .016). Preoperative renal failure was strongly associated with postoperative renal decline (odds ratio [OR] 8.15, 2.92-22.8, P < .0001). Propensity score analysis demonstrated that the use of an SR cross-clamp was associated with an increased risk for postoperative renal decline (OR 2.66, 1.28-5.50, P = .009). Major adverse events were more prevalent in the SR group compared to the IR group (17.0% vs 9.5%, P = .003). Five-year survival was 69.1% + 1.9% for the IR group and 67.7% + 4.3% for the SR group (P = 0.38) by life table analysis. CONCLUSION Suprarenal cross-clamping is associated with low mortality and significant but acceptable morbidity, including postoperative decline in renal function. The results from this series may serve as relevant background data when evaluating emerging branched and fenestrated endograft technologies.

The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm

Background Decision‐making related to the care of patients with an abdominal aortic aneurysm (AAA) is complex. Aneurysms present with varying risks of rupture, and patient‐specific factors influence anticipated life expectancy, operative risk, and need to intervene. Careful attention to the choice of operative strategy along with optimal treatment of medical comorbidities is critical to achieving excellent outcomes. Moreover, appropriate postoperative surveillance is necessary to minimize subsequent aneurysm‐related death or morbidity. Methods The committee made specific practice recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system. Three systematic reviews were conducted to support this guideline. Two focused on evaluating the best modalities and optimal frequency for surveillance after endovascular aneurysm repair (EVAR). A third focused on identifying the best available evidence on the diagnosis and management of AAA. Specific areas of focus included (1) general approach to the patient, (2) treatment of the patient with an AAA, (3) anesthetic considerations and perioperative management, (4) postoperative and long‐term management, and (5) cost and economic considerations. Results Along with providing guidance regarding the management of patients throughout the continuum of care, we have revised a number of prior recommendations and addressed a number of new areas of significance. New guidelines are provided for the surveillance of patients with an AAA, including recommended surveillance imaging at 12‐month intervals for patients with an AAA of 4.0 to 4.9 cm in diameter. We recommend endovascular repair as the preferred method of treatment for ruptured aneurysms. Incorporating knowledge gained through the Vascular Quality Initiative and other regional quality collaboratives, we suggest that the Vascular Quality Initiative mortality risk score be used for mutual decision‐making with patients considering aneurysm repair. We also suggest that elective EVAR be limited to hospitals with a documented mortality and conversion rate to open surgical repair of 2% or less and that perform at least 10 EVAR cases each year. We also suggest that elective open aneurysm repair be limited to hospitals with a documented mortality of 5% or less and that perform at least 10 open aortic operations of any type each year. To encourage the development of effective systems of care that would lead to improved outcomes for those patients undergoing emergent repair, we suggest a door‐to‐intervention time of <90 minutes, based on a framework of 30‐30‐30 minutes, for the management of the patient with a ruptured aneurysm. We recommend treatment of type I and III endoleaks as well as of type II endoleaks with aneurysm expansion but recommend continued surveillance of type II endoleaks not associated with aneurysm expansion. Whereas antibiotic prophylaxis is recommended for patients with an aortic prosthesis before any dental procedure involving the manipulation of the gingival or periapical region of teeth or perforation of the oral mucosa, antibiotic prophylaxis is not recommended before respiratory tract procedures, gastrointestinal or genitourinary procedures, and dermatologic or musculoskeletal procedures unless the potential for infection exists or the patient is immunocompromised. Increased utilization of color duplex ultrasound is suggested for postoperative surveillance after EVAR in the absence of endoleak or aneurysm expansion. Conclusions Important new recommendations are provided for the care of patients with an AAA, including suggestions to improve mutual decision‐making between the treating physician and the patients and their families as well as a number of new strategies to enhance perioperative outcomes for patients undergoing elective and emergent repair. Areas of uncertainty are highlighted that would benefit from further investigation in addition to existing limitations in diagnostic tests, pharmacologic agents, intraoperative tools, and devices.

Inferior outcomes of autogenous infrainguinal bypass in Hispanics: an analysis of ethnicity, graft function, and limb salvage.

INTRODUCTION Recent evidence suggests disparities exist among racial groups with peripheral arterial disease (PAD). Hispanics (HI) are the fastest growing demographic in the United States, but little outcome data is available for this population. Therefore, we undertook this study to compare the results of autogenous infrainguinal bypass grafting in HI to Caucasians (CA) and African Americans (AA). METHODS This was a comparative cohort study of prospectively collected registry data of infrainguinal bypass performed at a tertiary center. Patient demographics and comorbidities, operative indications, bypass graft characteristics, and postoperative courses were analyzed. Cumulative patency rates, limb salvage, mortality, and factors associated with these outcomes were determined using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS From January 1, 1985, through December 31, 2007, 1646 consecutive patients (1408 CA, 57 HI, and 181 AA) underwent 1646 autogenous infrainguinal reconstructions. HI and AA were younger and more often diabetic than CA but HI had less chronic renal insufficiency (CRI) and dialysis-dependence than AA. AA, but not HI, more commonly underwent bypass for critical limb ischemia (CLI) in comparison to CA (AA 90% vs CA 80%, P < .0001; HI 86%). HI and AA bypass grafts had inflow and outflow distal to that in CA. Perioperative mortality (2.3%) and morbidity were similar between groups. Five-year primary patency (+/- standard error [SE]) was significantly lower in HI compared to CA and similar to that in AA (HI 54% +/- 7% vs CA 69% +/- 1%, P = .02; AA 58% +/- 4%). Cox proportional hazard modeling showed high-risk conduit, age <65, CLI, female gender, and AA race were risk factors for failure of primary patency. Secondary patency of HI grafts, unlike AA, was not different than that in CA. Five-year limb salvage (+/- SE) was significantly lower in HI compared to CA and similar to that in AA (HI 80% +/- 6% vs CA 91% +/- 1%, P = .004; AA 83% +/- 3%). Hispanic ethnicity, CLI, high-risk conduit, age <65, CRI, female gender, and diabetes were significant predictors of limb loss. CONCLUSION Autogenous infrainguinal bypass surgery in HI is associated with primary patency and limb salvage inferior to that of CA and similar to that of AA, despite HI rates of CLI equivalent to CA and HI comorbidities less severe than AA. HI ethnicity was an independent predictor of limb loss. Our data provides evidence of outcome disparities in HI treated aggressively for their PAD. Further investigation with regard to biologic and social factors is required to delineate the reasons for these inferior outcomes in HI patients.

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.