Clinical significance of the clopidogrel-proton pump inhibitor interaction after peripheral endovascular intervention for claudication.

OBJECTIVE: Despite numerous studies in the cardiology literature, the clinical impact of proton pump inhibitor (PPI) administration on the antiplatelet effect of clopidogrel remains controversial. The objective of this study is to evaluate the effects of concurrent PPI and clopidogrel administration on outcomes after percutaneous transluminal angioplasty and stenting (PTA&S) of the superficial femoral artery (SFA) for claudication. METHODS: Retrospective review of a prospectively maintained database (2004-2010) identified patients undergoing PTA&S of the SFA for lifestyle-limiting claudication (Rutherford Class III). Statistical analysis included univariate comparison (Wilcoxon, chi-square) of demographics, lesion characteristics, complication rates, and outcome measures. Patency comparisons were made with Cox-PH multivariable models and Kaplan-Meier survival analysis. RESULTS: Totally, 109 limbs were treated in 103 patients. All were prescribed clopidogrel for 1 month; concurrent PPI use (+PPI) was identified after 42 (38.5%) interventions. There were no statistically significant differences in demographics, comorbidity prevalence, lesion length, degree of stenosis, or runoff associated with PPI use. There were no cases of early thrombosis in either group. There were more instances of patency loss (28 [50%] vs 21 [42%]; P = .40) in patients with +PPI, and a trend toward reduced primary patency that did not achieve statistical significance (P = .5). By multivariate analysis only TransAtlantic Inter-Society Consensus (TASC) D lesions were independent predictors of primary (hazards ratio [HR] = 4.366; [95% confidence interval (CI): 1.291-14.764; P = .018) and assisted patency loss (HR = 6.815 [1.181-39.327]; P = .032). CONCLUSIONS: The clinical significance of the clopidogrel-PPI interaction is a controversial topic that has been the subject of numerous studies in the cardiology literature. This is the first report to examine this medication interaction after peripheral intervention. While there is no apparent association between PPI coadministration with clopidogrel in this series, the high prevalence of PPI use among patients prescribed clopidogrel following peripheral intervention warrants ongoing attention to this purported medication interaction.

Choosing the appropriate intervention for symptomatic and asymptomatic carotid disease in the era of multiple therapies: integration of risk profile and technical data.

With rapid evolution of endovascular techniques, carotid artery stenting has emerged as an alternative to carotid endarterectomy. Several investigations have been performed that examine the roles of carotid endarterectomy and carotid artery stenting and some trials have sought to compare the two treatment modalities. There have also been advances in the understanding of optimal medical management of carotid artery stenosis. The obvious question that arises is what is the most appropriate treatment option for patients with symptomatic and asymptomatic carotid artery stenosis? The answer is not straightforward and requires an understanding of differential outcomes in select subgroups. A review of the major studies, including some of the most recent trials, will help to elucidate the optimal therapy.

Endovascular management of type B aortic dissection after attempted central venous catheterization.

A 41-year-old woman, status postmastectomy for breast cancer had an attempted 8-F left subclavian vein chemotherapy port placed in her. She developed severe upper back pain radiating to the left shoulder. A computed tomographic scan and angiography revealed catheter placement in the left subclavian artery and a type B aortic dissection. A thoracic stent-graft was used to treat the aortic dissection. While removing the catheter, a covered stent was deployed to seal the arterial puncture and a balloon-expandable stent was placed over a persistent subclavian dissection. This case illustrates an example of the feasibility of endovascular management to treat serious iatrogenic access complications.

Determining criteria for predicting stenosis with ultrasound duplex after endovascular intervention in infrainguinal lesions.

BACKGROUND: Studies examining duplex surveillance of lower extremity bypass grafts have defined a role for guiding graft re-intervention. The goal of this study is to determine the utility of duplex scanning to detect angiographic restenosis after endovascular therapy in patients with infrainguinal arterial disease. METHODS: A prospective registry including all patients treated for lower extremity atherosclerotic disease between February 2004 and September 2008 was established. Patients were followed up with duplex ultrasound at 1, 3, 6, 12 months, and then annually. Patients receiving repeat angiograms were identified and angiogram and duplex data were abstracted. Velocity ratios (Vr) were calculated for each lesion by dividing the peak velocity within the lesion by the peak velocity proximal to the lesion. Logarithmic regression and receiver operator characteristic (ROC) curve analyses were used. RESULTS: Repeat angiograms were performed on 345 lesions in 143 patients, and 254 lesions in 103 patients had a corresponding duplex ultrasound. Indications for the initial intervention were claudication (n = 62, 43.4%), rest pain (n = 23, 16.1%), and tissue loss (n = 58, 40.5%). A total of 178 superficial femoral artery (SFA) lesions, 59 popliteal lesions, and 17 tibial lesions were identified by surveillance duplex in 103 patients. In all, 70.5% of the intervened vessels that were studied were nonstented and the remaining 29.5% were stented. A total of 65% of the patients had diabetes. On determining correlations for peak systolic velocity (PSV) as measured by duplex ultrasound with degree of angiographic stenosis, strong correlation coefficients for SFA disease (R² = 0.84) and popliteal disease (R² = 0.88) were found. However, poor correlation was found in patients with tibial disease. When analyzing the lesions on the basis of Vr < 2.0, 11 of 86 (12.8%) had >70% angiographic stenosis. In lesions with ratios from 2 to 2.5, 12 of 13 (92.3%) had >70% angiographic stenosis and in lesions with ratios >2.5, 69 of 75 (92.0%) had >70% angiographic stenosis. ROC curve analysis showed that to detect ≥ 70% stenosis in the SFA, a PSV ≥ 204 cm/sec had a sensitivity of 97.6% and specificity of 94.7%. To detect ≥ 70% stenosis in the overall femoropopliteal region, a PSV ≥ 223 cm/sec had a sensitivity of 94.1% and specificity of 95.2%. CONCLUSIONS: Duplex ultrasound surveillance correlates to the degree of angiographic stenosis on the basis of PSV in the SFA and popliteal region. Correlation in the tibial vessels is poor. Vr > 2.0 appear to correlate to angiographic stenosis of > 70%. ROC analysis shows that PSV can have sufficiently high sensitivity and specificity to predict angiographic stenosis in the femoropopliteal region.

A20 modulates lipid metabolism and energy production to promote liver regeneration.

BACKGROUND: Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. METHODOLOGY AND PRINCIPAL FINDINGS: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.ßgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. CONCLUSION: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation.

Endovascular management of superior mesenteric artery pseudoaneurysm.

A 31-year-old man underwent a Whipple procedure for a pancreatic neuroendocrine tumor, which consists of a pancreaticoduodenectomy and reconstruction to restore intestinal continuity. Six weeks after the operation, he presented with severe mid-epigastric pain radiating to his back. Imaging studies revealed a large pseudoaneurysm arising from the superior mesenteric artery. Selective superior mesenteric angiography confirmed the presence of the pseudoaneurysm. A 6 mm × 2.5 cm stent graft (Viabhan; W.L. Gore, Flagstaff, Ariz) was deployed across the pseudoaneurysm origin with preservation of the mesenteric branches. The patient had immediate resolution of symptoms and follow-up imaging showed patency of the stent graft and exclusion of the pseudoaneurysm.

Lesion types and device characteristics that predict distal embolization during percutaneous lower extremity interventions.

OBJECTIVE: Distal embolization (DE) during percutaneous lower extremity revascularization (LER) may cause severe clinical sequelae. To better define DE, we investigated which lesion types and treatment modalities increase the risk for embolization. METHODS: A prospective registry of LER from 2004 to 2009 was reviewed. All cases with runoff evaluated before and after intervention were included. Angiograms and operative reports were reviewed for evidence of DE. Interventions included percutaneous transluminal angioplasty (PTA), with or without stent placement, and atherectomy with four different devices. Chi-square analysis and Fisher's exact test were used to assess significance. Patency rates were calculated using Kaplan-Meier analysis and compared using log-rank analysis. RESULTS: There were 2137 lesions treated in 1029 patients. The embolization rate was 1.6% (34 events). Jetstream (Pathway, Kirkland, Wash) and DiamondBack 360 (Cardiovascular Systems Inc, St Paul Minn) devices had a combined embolization rate of 22% (8 of 36), 4 of 18 (22%) in each group, which was significantly higher than with PTA alone (5 of 570, 0.9%), PTA and stent (5 of 740, 0.7%), SilverHawk (ev3, Plymouth, Minn) atherectomy (14 of 736, 1.9%), and laser atherectomy (2 of 55, 3.6%; P < .001). There was a significantly higher rate of embolization for in-stent restenosis (6 of 188, 3.2%) and chronic total occlusions (15 of 615, 2.4%) compared with stenotic lesions (13 of 1334, 0.9%; P = .01). The embolization rate was significantly higher in Transatlantic Inter-Society Consensus (TASC) II C and D lesions compared with TASC A and B lesions (P = .018). DE rates were not affected by preoperative runoff status (P = .152). Patency was restored at the completion of the procedure in 32 of 34 cases of DE. The 24-month primary patency, assisted primary patency, and secondary patency in the DE group was 54.0% ± 11.9%, 70.0% ± 10.3%, and 73.2% ± 10.3%, respectively, and was 44.4% ± 1.7%, 61.5% ± 1.7%, and 68.2% ± 1.6%, respectively, when embolization did not occur (P > .05). Limb salvage was 72.6% ± 3.1% in lesions in which no DE occurred vs 83.3% ± 15.2% in lesions in which DE occurred (P = .699). CONCLUSIONS: DE is a rare event that occurs more often with the Jetstream and DiamondBack 360 devices. In-stent and complex native lesions are at higher risk for DE. DE is typically reversible with endovascular techniques and has no effect on patency rates and limb salvage.

O-glycosylation regulates ubiquitination and degradation of the anti-inflammatory protein A20 to accelerate atherosclerosis in diabetic ApoE-null mice.

BACKGROUND: Accelerated atherosclerosis is the leading cause of morbidity and mortality in diabetic patients. Hyperglycemia is a recognized independent risk factor for heightened atherogenesis in diabetes mellitus (DM). However, our understanding of the mechanisms underlying glucose damage to the vasculature remains incomplete. METHODOLOGY/PRINCIPAL FINDINGS: High glucose and hyperglycemia reduced upregulation of the NF-κB inhibitory and atheroprotective protein A20 in human coronary endothelial (EC) and smooth muscle cell (SMC) cultures challenged with Tumor Necrosis Factor alpha (TNF), aortae of diabetic mice following Lipopolysaccharide (LPS) injection used as an inflammatory insult and in failed vein-grafts of diabetic patients. Decreased vascular expression of A20 did not relate to defective transcription, as A20 mRNA levels were similar or even higher in EC/SMC cultured in high glucose, in vessels of diabetic C57BL/6 and FBV/N mice, and in failed vein grafts of diabetic patients, when compared to controls. Rather, decreased A20 expression correlated with post-translational O-Glucosamine-N-Acetylation (O-GlcNAcylation) and ubiquitination of A20, targeting it for proteasomal degradation. Restoring A20 levels by inhibiting O-GlcNAcylation, blocking proteasome activity, or overexpressing A20, blocked upregulation of the receptor for advanced glycation end-products (RAGE) and phosphorylation of PKCßII, two prime atherogenic signals triggered by high glucose in EC/SMC. A20 gene transfer to the aortic arch of diabetic ApoE null mice that develop accelerated atherosclerosis, attenuated vascular expression of RAGE and phospho-PKCßII, significantly reducing atherosclerosis. CONCLUSIONS: High glucose/hyperglycemia regulate vascular A20 expression via O-GlcNAcylation-dependent ubiquitination and proteasomal degradation. This could be key to the pathogenesis of accelerated atherosclerosis in diabetes.

Delayed permanent paraplegia after endovascular repair of abdominal aortic aneurysm.

Spinal cord ischemia is a rare complication after abdominal aortic surgery and has been attributed to surgical devascularization of the spinal cord, atheroembolization of the cord circulation, or hypoperfusion of cord structures secondary to hypotension or cord edema. We present a diabetic, hypertensive 75-year-old male with endstage renal disease who presented with a 5.5 cm asymptomatic infrarenal abdominal aortic aneurysm, and concomitant 3.5 cm right common iliac artery aneurysm. After undergoing successful endovascular repair with an aorto-uni-iliac device, unilateral hypogastric artery embolization, and femoral-femoral bypass, he was discharged to a rehabilitation facility neurologically intact with a stage 2 decubitus ulcer. He returned on postoperative day 21 with a large stage 4 septic decubitus ulcer, fever, leukocytosis, hypotension, and paraplegia. We hypothesize that the compromised blood flow from the initial reconstruction, combined with the delayed hypotension imposed by sepsis, resulted in spinal cord infarction. He was eventually discharged to a nursing facility with no improvement in his neurologic status. We report the first case of significantly delayed permanent paraplegia after endovascular abdominal aortic aneurysmorrhaphy.

MARCKS silencing differentially affects human vascular smooth muscle and endothelial cell phenotypes to inhibit neointimal hyperplasia in saphenous vein.

Intimal hyperplasia (IH) limits the patency of all cardiovascular vein bypass grafts. We previously found the myristoylated alanine-rich C kinase substrate (MARCKS), a key protein kinase C (PKC) substrate, to be up-regulated in canine models of IH. Here, we further characterize the role of MARCKS in IH and examine the phenotypic consequences of MARCKS silencing by small interfering RNA (siRNA) transfection in human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) in vitro and use a rapid 10-min nonviral siRNA transfection technique to determine the effects of MARCKS silencing in human saphenous vein cultured ex vivo. We demonstrate MARCKS silencing attenuates VSMC migration and arrests VSMC proliferation in part through the up-regulation of the cyclin-dependent kinase inhibitor p27(kip1). Conversely, MARCKS silencing had little or no effect on EC migration or proliferation. These phenotypic changes culminated in reduced neointimal formation in cultured human saphenous vein. These data identify MARCKS as a pathogenic contributor to IH and indicate therapeutic MARCKS silencing could selectively suppress the "atherogenic," proliferative phenotype of VSMCs without collateral harm to the endothelium. This approach could be readily translated to the clinic to silence MARCKS in vein bypass grafts prior to implantation.

Use and abuse of atherectomy: where should it be used?

Surgical bypass has long been considered the "gold standard" for treatment of peripheral arterial disease. Endovascular therapy with percutaneous transluminal angioplasty and adjunctive stenting has recently become a primary treatment of lower extremity peripheral arterial disease. However, there has been concern regarding the long-term patency of percutaneous interventions and the increased need for reintervention. An alternative to standard percutaneous transluminal angioplasty and stent is the excision of the obstructing arterial plaque using atherectomy devices. There are several different types of atherectomy devices including directional atherectomy devices, such as the SilverHawk Atherectomy (EV3, Minneapolis, MN) device, orbital atherectomy devices, such as the CSI DiamondBack 360 (CSI, Minneapolis, MN) rotational atherectomy device, such as the Pathway Jetstream (Pathway Medical Technologies, Inc., Kirkland, WA), the Rotablator device (Boston Scientific, Natick, MA), and laser atherectomy devices, including the Spectranetics Excimer Laser (Spectranetics, Colorado Springs, CO). All of these devices will be reviewed. Multiple series, including our experience with atherectomy devices, will be discussed. Overall, atherectomy devices have an important emerging role for complex lesions, especially those extending into tibial vessels. Atherectomy devices have the distinct advantage of removing the obstructing atherosclerotic or intimal hyperplastic lesions without the disadvantage of a foreign body such as a stent in the artery. If reintervention is required after atherectomy, this can be generally accomplished at the same site with low risk of complications or discomfort to the patient. Finally, atherectomy also does not preclude use of bypass for the treatment of peripheral arterial disease nor, in most cases, change the anastomotic sites if surgical bypass is required, in contrast to stenting.

Low ejection fraction predicts shortened survival in patients undergoing infrainguinal arterial reconstruction.

BACKGROUND: With the advent of endovascular therapy for lower extremity ischemia it is important to better determine what factors may affect the outcome. The goal of the present study was to evaluate whether ejection fraction (EF) is predictive of outcome in infrainguinal arterial reconstruction. METHODS: We retrospectively reviewed 736 patients undergoing 897 infrainguinal arterial reconstructions from July 1999 to February 2002. Patients were divided into two groups: group I contained 54 patients with an EF<35% and group II had 216 patients with an EF > or =35%. The outcome evaluated was major adverse clinical events (MACEs), defined as postoperative myocardial infarction (MI), arrhythmia, congestive heart failure (CHF), and perioperative mortality. RESULTS: Major adverse clinical events occurred in 20.3% of patients (11/54) in group I and 10.6% patients (23/216) in group II (p = 0.068). Group I had a trend toward a greater incidence of MACEs compared to group II. Two-year survival for group I was 61.7%, whereas survival for group II was 78.4% (p = 0.0085). CONCLUSIONS: Low EF predicts a significantly shortened 2-year survival after infrainguinal arterial reconstruction and a trend toward increased perioperative complications. This is another factor to be considered in choosing open versus endovascular options.

A novel function for cadherin 11/osteoblast-cadherin in vascular smooth muscle cells: modulation of cell migration and proliferation.

OBJECTIVE: Intimal hyperplasia is a common cause of vein graft failure in cardiovascular surgery. The molecular basis for intimal hyperplasia remains poorly defined. We have previously identified, by gene chip analysis of vein grafts, increased messenger (mRNA) for the adhesion molecule cadherin 11/osteoblast-cadherin (CDH11). The function of CDH11 in vascular cells is unknown. The aim of the present study is to confirm CDH11 expression in vein grafts and characterize its role in vascular remodeling. METHODS: Cephalic vein interposition grafts were implanted in a canine model and harvested at predetermined time points. CDH11 protein expression was determined by immunohistochemistry. Early passage human coronary artery smooth muscle cells (SMCs) were used for in vitro studies. Real-time polymerase chain reaction was used to assess cellular CDH11 mRNA levels. CDH11 signaling was inhibited by either transfection with silencing RNA targeting CDH11 or with a blocking antibody to CDH11. Cellular migration was evaluated and cellular proliferation was assessed. RESULTS: Expression of CDH11 was increased in medial SMCs of vein grafts recovered at 7, 14, and 30 days after surgery compared with control veins from the same animals. In vitro CDH11 mRNA was up-regulated 1.8 +/- 0.2-fold (P = .003) in SMCs after treatment with tumor necrosis factor-alpha. Cellular migration was attenuated by inhibition of CDH11 both with a blocking antibody (0.67 +/- 0.09; P = .063) and gene knockdown mediated by small interfering RNA (0.67 +/- 0.14; P = .036). SMC proliferation decreased by 3.1-fold (P = .006) in the presence of CDH11-blocking antibody. Knockdown of CDH11 mediated by small interfering RNA resulted in a 1.3-fold (P = .018) decrease in proliferation. CONCLUSIONS: CDH11 is up-regulated in SMC in vivo and in vitro as part of the response to injury. Inhibition of CDH11 decreases SMC migration and proliferation, two pathogenic effectors of intimal hyperplasia.

A20, a modulator of smooth muscle cell proliferation and apoptosis, prevents and induces regression of neointimal hyperplasia.

A20 is a NF-kappaB-dependent gene that has dual anti-inflammatory and antiapoptotic functions in endothelial cells (EC). The function of A20 in smooth muscle cells (SMC) is unknown. We demonstrate that A20 is induced in SMC in response to inflammatory stimuli and serves an anti-inflammatory function via blockade of NF-kappaB and NF-kappaB-dependent proteins ICAM-1 and MCP-1. A20 inhibits SMC proliferation via increased expression of cyclin-dependent kinase inhibitors p21waf1 and p27kip1. Surprisingly, A20 sensitizes SMC to cytokine- and Fas-mediated apoptosis through a novel NO-dependent mechanism. In vivo, adenoviral delivery of A20 to medial rat carotid artery SMC after balloon angioplasty prevents neointimal hyperplasia by blocking SMC proliferation and accelerating re-endothelialization, without causing apoptosis. However, expression of A20 in established neointimal lesions leads to their regression through increased apoptosis. This is the first demonstration that A20 exerts two levels of control of vascular remodeling and healing. A20 prevents neointimal hyperplasia through combined anti-inflammatory and antiproliferative functions in medial SMC. If SMC evade this first barrier and neointima is formed, A20 has a therapeutic potential by uniquely sensitizing neointimal SMC to apoptosis. A20-based therapies hold promise for the prevention and treatment of neointimal disease.

A20 protects mice from lethal radical hepatectomy by promoting hepatocyte proliferation via a p21waf1-dependent mechanism.

The liver has a remarkable regenerative capacity, allowing recovery following injury. Regeneration after injury is contingent on maintenance of healthy residual liver mass, otherwise fulminant hepatic failure (FHF) may arise. Understanding the protective mechanisms safeguarding hepatocytes and promoting their proliferation is critical for devising therapeutic strategies for FHF. We demonstrate that A20 is part of the physiological response of hepatocytes to injury. In particular, A20 is significantly upregulated in the liver following partial hepatectomy. A20 protects hepatocytes from apoptosis and ongoing inflammation by inhibiting NF-kappaB. Hepatic expression of A20 in BALB/c mice dramatically improves survival following extended and radical lethal hepatectomy. A20 expression in the liver limits hepatocellular damage hence maintains bilirubin clearance and the liver synthetic function. In addition, A20 confers a proliferative advantage to hepatocytes via decreased expression of the cyclin-dependent kinase inhibitor p21(waf1). In conclusion, A20 provides a proliferative advantage to hepatocytes. By combining anti-inflammatory, antiapoptotic and pro-proliferative functions, A20-based therapies could be beneficial in prevention and treatment of FHF.

Preoperative cardiac evaluation does not improve or predict perioperative or late survival in asymptomatic diabetic patients undergoing elective infrainguinal arterial reconstruction.

OBJECTIVE: Patients undergoing infrainguinal arterial reconstruction frequently have increased cardiac risk factors. Diabetic patients are often asymptomatic despite advanced cardiac disease. This study investigates whether preoperative cardiac testing improves the outcome in diabetic patients at risk for cardiac disease. METHODS: We retrospectively reviewed all patients undergoing lower-extremity arterial reconstructions in a 32-month period from July 1999 to February 2002. Of the 433 patients identified undergoing 539 procedures, 295 had diabetes mellitus and considered in this study. The patients were stratified into two groups according to the present American College of Cardiology, American Heart Association (ACC/AHA) algorithm. We identified 140 patients with two or more of ACC (Eagle) criteria who met the inclusion criteria for a preoperative cardiac evaluation. These patients were separated into two groups: those undergoing a cardiac work-up (WU) according to the ACC/AHA algorithm and those not undergoing the recommended work-up (NWU). Outcomes included perioperative mortality, postoperative myocardial infarction, congestive heart failure, arrhythmia, and length of hospitalization. Significance of association was assessed by the Fisher exact test. Length of hospitalization was compared using the Kruskal-Wallis rank sum test. Survival data was analyzed with the Kaplan-Meier method. RESULTS: One hundred forty patients met the criteria for moderate risk. There were 61 patients in the NWU group and 79 in the WU group. Ten patients in the WU group underwent preoperative coronary revascularization (6 had percutaneous transluminal coronary angioplasty, 4 underwent coronary artery bypass grafting). There was no difference between perioperative mortality (WU, 1%; NWU, 2%; P = 1.00) or in postoperative cardiac morbidity, including myocardial infarction, congestive heart failure, and arrhythmia requiring treatment (WU, 5%; NWU, 6%; P = .71). There were no perioperative deaths and one episode of congestive heart failure in the group that had preoperative coronary revascularization. Median length of hospitalization was 10 days in the WU group and 8 days in the NWU group ( P = .11). Patient survival at 12 months for the NWU, WU, and revascularized groups was 85.3%, 78.5%, and 80.0%, respectively; 36-month survival was 73.6%, 62.9%, and 80.0%, respectively. The three survival curves did not differ significantly ( P = .209). CONCLUSIONS: Preoperative cardiac evaluation, as defined by the ACC/AHA algorithm, does not predict or improve postoperative morbidity, mortality, or 36-month survival in asymptomatic, diabetic patients undergoing elective lower-extremity arterial reconstruction. These data do not support the current ACC/AHA recommendations as a standard of care for diabetic patients with an intermediate clinical predictor who undergo peripheral arterial reconstruction, a high-risk surgical procedure.