Biomedical subjects

Michael S Conte

Publications and source records attributed to Michael S Conte.

At least 19 recordsLinked to original sources

PubMed2006

Elevated C-reactive protein levels are associated with postoperative events in patients undergoing lower extremity vein bypass surgery.

OBJECTIVES: Inflammatory markers such as high-sensitivity C-reactive protein (hsCRP) are associated with an increased risk of cardiovascular events and with the severity of peripheral arterial disease. The effects of inflammation on the development of vein graft disease remain speculative. We hypothesized that high levels of inflammatory markers would identify patients at increased risk for adverse events (graft failure, major cardiovascular events) after lower extremity bypass surgery. METHODS: Patients (n = 91) scheduled to undergo lower extremity bypass using autogenous vein were enrolled into a prospective study at two institutions. Exclusion criteria included the presence of major infection. A baseline plasma sample was obtained on the morning of lower extremity bypass. Biomarkers for inflammation included hsCRP, fibrinogen, and serum amyloid A (SAA). Values between patients with and without critical limb ischemia were compared. Proportions of events among dichotomized populations (upper limit of normal of each laboratory assay) were compared by log-rank test. RESULTS: Of the patients undergoing lower extremity bypass, 69% were men, 53% were diabetic, 81% were smokers, and their mean ankle-brachial index was 0.51 +/- 0.19. The indication for lower extremity bypass was critical limb ischemia in 55%. There were no perioperative deaths and two early graft occlusions. During a mean follow-up of 342 days (range, 36-694 days) there were four deaths, 27 graft-related events, and 10 other cardiovascular events. No relationships were found between events and demographics, comorbidities, baseline ankle-brachial index, or statin use. High-sensitivity CRP (P = .005), fibrinogen (P < .001), and SAA (P = .0001) levels were associated with critical limb ischemia at presentation. Among patients with an elevated hsCRP (>5 mg/L) immediately before surgery, major postoperative vascular events occurred in 60% (21/35), compared with a 32% (18/56) rate in those with a baseline CRP <5 mg/L (P = .004, log-rank test). On multivariable analysis, only elevated hsCRP correlated with adverse graft-related or cardiovascular events (P = .018). CONCLUSIONS: The inflammatory biomarkers of hsCRP, fibrinogen, and SAA correlate with peripheral arterial disease severity at presentation in patients undergoing lower extremity bypass. Patients with elevated hsCRP are at increased risk for postoperative vascular events, most of which are related to the vein graft. These findings suggest a potential relationship between inflammation and outcomes after lower extremity vein bypass surgery.

Arterial Occlusive Diseases↗

PubMed2006

Early biomechanical changes in lower extremity vein grafts--distinct temporal phases of remodeling and wall stiffness.

BACKGROUND: The geometric and biomechanical changes that contribute to vein graft remodeling are not well established. We sought to measure patterns of adaptation in lower extremity vein grafts and assess their correlation with clinical outcomes. METHODS: We conducted a prospective, longitudinal study of patients undergoing infrainguinal reconstruction with autogenous conduit. In addition to standard duplex surveillance, lumen diameter (of a defined index segment of the conduit) and pulse wave velocity (PWV) were assessed by ultrasound imaging at surgery and at 1, 3, and 6 months postoperatively. Graft dimensions and wall stiffness were correlated with clinical outcomes. RESULTS: There were 92 patients and 96 limbs in this study. On average, vein graft lumen diameter increased during the first month of implantation from 0.37 +/- .01 cm to 0.45 +/- 0.02 cm (mean +/- SEM; P = .002), representing a relative change of +21.6% (median +/- 14%; range, -31 to +67%) during this period. Of the entire cohort, 72% of grafts demonstrated appreciable dilation of the index segment during the first month. Index segment lumen diameter did not change appreciably beyond 1 month, with the notable exception of arm vein conduits, which showed continued tendency to dilate. PWV increased during the first 6 months (17.2 +/- 1.2 m/s to 23.2 +/- 2.4 m/s; P = .008), reflecting a nearly 40% increase in conduit stiffness (2.0 +/- .6 Mdynes/cm to 3.3 +/- .8 Mdynes/cm, P = .01). The greatest relative increase (25%) in PWV occurred from months 1 to 3. Loss of primary patency occurred in 24 cases (19 revisions, 5 occlusions), with a mean reintervention time of 7.6 months. Grafts that demonstrated early positive remodeling (lumen dilatation) had a trend of increased primary patency (P = .08, log rank). Among the grafts that failed, a trend was noted toward greater wall stiffness at 1 month, 2.7 vs 1.5 Mdynes (P = .08). CONCLUSION: Vein graft remodeling appears to involve at least two distinct temporal phases. Outward remodeling of the lumen occurs early, and wall stiffness changes occur in a more delayed fashion. Early outward remodeling may be important for successful vein graft adaptation.

Aged↗

PubMed2006

Results of PREVENT III: a multicenter, randomized trial of edifoligide for the prevention of vein graft failure in lower extremity bypass surgery.

OBJECTIVE: The PREVENT III study was a prospective, randomized, double-blinded, multicenter phase III trial of a novel molecular therapy (edifoligide; E2F decoy) for the prevention of vein graft failure in patients undergoing infrainguinal revascularization for critical limb ischemia (CLI). METHODS: From November 2001 through October 2003, 1404 patients with CLI were randomized to a single intraoperative ex vivo vein graft treatment with edifoligide or placebo. After surgery, patients underwent graft surveillance by duplex ultrasonography and were followed up for index graft and limb end points to 1 year. A blinded Clinical Events Classification committee reviewed all index graft end points. The primary study end point was the time to nontechnical index graft reintervention or major amputation due to index graft failure. Secondary end points included all-cause graft failure, clinically significant graft stenosis (>70% by angiography or severe stenosis by ultrasonography), amputation/reintervention-free survival, and nontechnical primary graft patency. Event rates were based on Kaplan-Meier estimates. Time-to-event end points were compared by using the log-rank test. RESULTS: Demographics, comorbidities, and procedural details reflected a population with CLI and diffuse atherosclerosis. Tissue loss was the presenting symptom in 75% of patients. High-risk conduits were used in 24% of cases, including an alternative vein in 20% (15% spliced vein and 5% non-great saphenous vein) and 6% less than 3 mm in diameter; 14% of the cases were reoperative bypass grafts. Most (65%) grafts were placed to infrapopliteal targets. Perioperative (30-day) mortality occurred in 2.7% of patients. Major morbidity included myocardial infarction in 4.7% and early graft occlusion in 5.2% of patients. Ex vivo treatment with edifoligide was well tolerated. There was no significant difference between the treatment groups in the primary or secondary trial end points, primary graft patency, or limb salvage. A statistically significant improvement was observed in secondary graft patency (estimated Kaplan-Meier rates were 83% edifoligide and 78% placebo; P = .016) within 1 year. The reduction in secondary patency events was manifest within 30 days of surgery (the relative risk for a 30-day event for edifoligide was 0.45; 95% confidence interval, 0.27-0.76; P = .005). For the overall cohort at 1 year, the estimated Kaplan-Meier rate for survival was 84%, that for primary patency was 61%, that for primary assisted patency was 77%, that for secondary patency was 80%, and that for limb salvage was 88%. CONCLUSIONS: In this prospective, randomized, placebo-controlled clinical trial, ex vivo treatment of lower extremity vein grafts with edifoligide did not confer protection from reintervention for graft failure.

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PubMed2006

Prospective multicenter study of quality of life before and after lower extremity vein bypass in 1404 patients with critical limb ischemia.

BACKGROUND: Patients with critical limb ischemia (CLI) have multiple comorbidities and limited life spans. The ability of infrainguinal vein bypass to improve quality of life (QoL) in patients with CLI has therefore been questioned. Prospective preoperative and postoperative QoL data for patients undergoing lower extremity vein bypass for CLI are presented. METHODS: A validated, disease-specific QoL questionnaire (VascuQoL) with activity, symptom, pain, emotional, and social domains and responses scored 1 (lowest QoL) to 7 (best QoL) was administered before surgery and at 3 and 12 months after lower extremity vein bypass for CLI. Changes in QoL at 3 and 12 months after lower extremity vein bypass and multiple predetermined variables potentially influencing QoL after lower extremity vein bypass were analyzed to determine the effect of lower extremity vein bypass on QoL in CLI patients. RESULTS: A total of 1404 patients had lower extremity vein bypass for CLI at 83 centers in the United States and Canada as part of the PREVENT III clinical trial. Surveys were completed in 1296 patients at baseline, 862 patients at 3 months, and 732 patients at 12 months. The global QoL score (mean +/- SD) was 2.8 +/- 1.1 at baseline and was 4.7 +/- 1.4 and 5.1 +/- 1.4 at 3 and 12 months, respectively. Mean changes from baseline at 3 and 12 months were statistically significant (P < .0001). Improved QoL scores extended across all domains. Diabetes and the development of graft-related events were associated with decreased improvement in QoL scores, though the mean relative change from baseline remained positive. CONCLUSIONS: Patients with CLI have a low QoL at baseline that is improved at 3 and 12 months after lower extremity vein bypass. QoL improvements are lower in diabetic patients and those who develop graft-related events. Successful revascularization can be expected to improve QoL in patients with CLI, with benefits that are sustained to at least 1 year.

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PubMed2006

Resource utilization in the treatment of critical limb ischemia: The effect of tissue loss, comorbidities, and graft-related events.

OBJECTIVE: Resource utilization (RU) in the care of patients with critical limb ischemia (CLI) is not well quantified. We present a cohort study to quantify in-hospital RU and analyze the role of tissue loss (TL), comorbidities, and vascular graft-related events (GREs) in patients undergoing peripheral bypass for CLI. METHODS: A retrospective analysis of 1404 patients enrolled in a multicenter clinical trial (PREVENT III) of vein bypass grafting for CLI was performed with analysis of RU during the 1-year follow-up period. Univariate and multivariable linear regressions were performed to determine RU predictors and outcomes. RESULTS: Compared with patients with rest pain, patients presenting with TL as the indication for bypass surgery had a longer index length of stay (mean, 9.8 vs 6.2 days), more rehospitalizations (mean, 1.6 vs 1.2), and a longer cumulative length of stay (mean, 27.7 vs 17.3 days; P < .0001 for all comparisons). Rehospitalizations over the ensuing year were for additional procedures (37.5%), wound infection (14.6%), graft failure (10.7%), and other cardiovascular (10%) and noncardiovascular (26%) reasons. Early GRE (stenosis > or =70%, thrombosis, revision, or major amputation within 30 days) occurred in 162 (11.5%) patients, resulting in a longer index length of stay (mean, 11.8 vs 8.6 days; P = .0002) and cumulative length of stay (mean, 25.9 vs 24.6 days; P = .0043), but no difference in the number of rehospitalizations (mean, 1.6 vs 1.5 days; P = .3272). During the 1-year follow-up, 554 (39.5%) patients had GREs, and this resulted in more rehospitalizations (mean, 2.1 vs 1.1; P < .0001) and a longer cumulative length of stay (mean, 28.2 vs 21.9 days; P < .0001) compared with patients without GRE. Multivariable analysis demonstrated the highly positive association of TL (hazard ratio [HR], 1.75) and early GRE (HR, 1.77) with the index length of stay, whereas comorbidities-namely, dialysis dependency (HR, 1.31), nonsmoking status (HR, 1.29), hypertension (HR, 1.26), and increasing age (HR, 1.01)-also had strong effects. The effect of TL and GRE on later RU (number of rehospitalizations and cumulative length of stay) was present but less pronounced than patient comorbidities (namely, dialysis). CONCLUSIONS: The stage of disease at presentation (TL vs rest pain) and the patency of the bypass graft (freedom from GRE) are critical determinants of RU over the first year after limb-salvage surgery. These effects predominate early (index length of stay) and persist through 1 year. Patient-specific factors, particularly dialysis-dependent renal failure, are also critical comorbidities affecting RU in these patients.

Aged↗

PubMed2006

Survivin regulation of vascular injury.

Survivin is a protein member of the inhibitor of apoptosis family that has attracted attention for its dual essential roles in the regulation of cell division and the control of apoptosis. Although extensively characterized as a tumor gene and exploited for new opportunities in cancer diagnostics and therapeutics, fresh experimental evidence has uncovered a critical role of survivin in vascular cell responses in vivo. Dynamically embedded in broad signaling pathways controlling smooth muscle cell adaptation, survivin not only controls vascular wall homeostasis but also acts as a critical upstream regulator of gene expression and second mediators.

Animals↗

PubMed2005

Regulation of vein graft hyperplasia by survivin, an inhibitor of apoptosis protein.

OBJECTIVE: Survivin (SVV) is an inhibitor of apoptosis protein (IAP) that is upregulated in cancer and has recently been implicated in vascular injury. We sought to investigate the role of SVV in vein graft hyperplasia. METHODS AND RESULTS: Adenoviral constructs expressing a dominant-negative (AdT34A) and wild-type (AdWT) SVV were used. Proliferation and apoptosis were assayed on endothelial cells (ECs) and smooth muscle cells (SMCs) from human saphenous vein. A rabbit carotid interposition vein graft model (N=31) was used, with adventitial gene transfer of SVV constructs. In vitro, overexpression of SVV was associated with protection from cytokine-induced apoptosis in ECs and SMCs; conversely, AdT34A directly induced apoptosis in these cells. SMC proliferation was increased by AdWT infection, whereas AdT34A reduced proliferation; both effects were serum-dependent. Expression of platelet-derived growth factor (PDGF) in SMCs was regulated by functional SVV expression in analogous fashion. In vivo, proliferation and apoptosis (7 days), as well as wall thickness (30 days), were modified by adenoviral-mediated SVV expression. Adventitial angiogenesis was regulated by the SVV-expressing constructs in a fashion parallel to wall thickness changes. CONCLUSIONS: SVV is a critical regulator of multiple processes, including proliferation, apoptosis, and angiogenesis, that determine the remodeling response of vein grafts following arterialization.

Adenoviridae↗

PubMed2005

Survivin expression is up-regulated in vascular injury and identifies a distinct cellular phenotype.

OBJECTIVES: The healing response to vascular injury is characterized by neointimal thickening. Proliferation and phenotypic transformation of vascular smooth muscle cells (SMCs) have been implicated in this process. We sought to investigate the role of survivin, a dual regulator of cell proliferation and apoptosis, in lesion formation after diverse forms of vascular injury. METHODS: Rabbits underwent either carotid interposition vein grafting (n = 17) or bilateral femoral balloon injury (BI; n = 29); some in the BI group were placed on a high-cholesterol diet. A subset of BI arteries were treated with local adenoviral gene delivery of a survivin dominant negative-mutant (AdT34A) versus vector or saline controls. Survivin expression in vessels was analyzed by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry (IHC), which also included markers of SMC differentiation. Specimens of human tissue including failed lower extremity bypass grafts and carotid plaque were also examined. RESULTS: RT-PCR and IHC demonstrated increased survivin expression in all experimental models, colocalizing at early times with proliferating and alpha-actin-expressing cells but was largely absent in mature, contractile SMCs. Delivery of AdT34A after BI attenuated neointimal hyperplasia. CONCLUSION: These studies provide strong evidence supporting a role for survivin in the cellular response to vascular injury. CLINICAL RELEVANCE: The regulation of cell proliferation, death, and phenotype after vascular interventions remains incompletely understood. We investigated the role of the inhibitor of apoptosis protein survivin in diverse models of vascular injury. The results suggest that survivin is an important modulator of the generalized vascular injury response and may represent a relevant target for therapies targeting intimal hyperplasia.

Angioplasty, Balloon↗

PubMed2005

Risk factors, medical therapies and perioperative events in limb salvage surgery: observations from the PREVENT III multicenter trial.

OBJECTIVES: Patients who require infrainguinal revascularization for critical limb ischemia (CLI) are at elevated risk for cardiovascular events. The PREVENT III study was a prospective, randomized, multicenter, phase 3 trial of edifoligide for the prevention of vein graft failure in patients with CLI. We examined the baseline characteristics, perioperative medical therapies, and 30-day incidence of major cardiovascular events in the PREVENT III cohort. METHODS: Demographics, medical and surgical history, mode of presentation for the index limb, procedural details, and concomitant medications were reviewed for all patients enrolled in PREVENT III (N = 1,404). Major adverse cardiovascular events, including death, myocardial infarction, or cerebrovascular event (stroke or transient ischemic attack) were tabulated. Univariate and multivariate analyses were performed to discern factors that were associated with the utilization of medical therapies and with perioperative events. RESULTS: Demographics and comorbidities reflected a population with diffuse, advanced atherosclerosis. Perioperative mortality was 2.7%, and major morbidity included myocardial infarction in 4.7% and stroke/transient ischemic attack in 1.4%. Among this population of CLI patients, 33% were not on antiplatelet therapy at study entry, and 24% were not receiving antithrombotics of any type. In addition, 54% of patients were not receiving lipid-lowering therapy, and 52% were not prescribed beta-blocker medications at study entry. On multivariate analysis, race was a significant determinant of antithrombotic utilization, with African-American patients less frequently treated both at baseline and discharge (adjusted odd ratios, 0.5 and 0.6, P < .0001). Antithrombotic and beta-blocker drug usage increased in the overall cohort from baseline (76% and 48%) to discharge (88% and 60%; P < .0001). Patients treated in a university hospital setting were more likely to be prescribed antiplatelet, lipid-lowering, and beta-blocker medications. Advanced age (>75 years), coronary artery disease (prior myocardial infarction or revascularization), and dialysis-dependent renal failure were associated with an increased 30-day risk of death, myocardial infarction, or stroke. Protective effects of beta-blocker and lipid-lowering medications were noted in these defined subgroups. CONCLUSIONS: A significant percentage of the population that undergoes surgical revascularization for CLI is not prescribed therapies of proven benefit in reducing cardiovascular events. Utilization of antithrombotics and beta-blockers increases during hospitalization for limb salvage surgery but that of lipid-lowering therapy does not. African-American patients appear to be at greater risk for undertreatment with antithrombotics, and the data suggest that patients undergoing leg bypass surgery in a university hospital setting receive more comprehensive medical treatment of atherosclerosis. Treatment guidelines for medical therapy are needed to standardize care and improve outcomes for patients with CLI.

Aged↗

PubMed2005

Comparative analysis of autogenous infrainguinal bypass grafts in African Americans and Caucasians: the association of race with graft function and limb salvage.

OBJECTIVE: African Americans (AAs) are at risk for developing diabetes mellitus and atherosclerosis. Whether race influences the results of infrainguinal arterial reconstruction is unclear. The purpose of this study was to compare the results of autogenous infrainguinal bypasses in AAs and Caucasians to determine the association of race with graft function and limb salvage. METHODS: This was a retrospective, comparative cohort study of AA and Caucasian patients who had undergone autogenous infrainguinal bypass surgery. Only single-limb bypasses in each patient cohort were considered in this analysis. In patients who had undergone bilateral lower limb bypasses, the first limb bypass was chosen as the index bypass procedure. RESULTS: From January 1985 to December 2003, 1459 autogenous infrainguinal bypasses were performed in 1459 patients for lower limb ischemia. Within this group, 89 AA patients/vein grafts formed the study cohort. The control group comprised 1370 Caucasian patients/vein grafts. Compared with the Caucasian cohort, AA patients were significantly younger (median age, 65 vs 70 years, respectively; P = .001) and predominantly female (57% vs 41%, respectively; P = .002). AA patients also had a higher prevalence of diabetes mellitus, hypertension, cerebrovascular disease, congestive heart failure, and dialysis-dependent renal failure. More AA than Caucasian patients presented with gangrene (34% vs 16%, respectively; P = .001), and more underwent bypass surgery for limb salvage indications (91% vs 81%, respectively; P = .01). The venous conduit used was predominantly the greater saphenous vein (AA, 83%; Caucasian, 85%), and the site of distal anastomosis was at the tibial/pedal level in 67% of AA and 61% of Caucasian patients. Overall morbidity (AA, 28%; Caucasian, 23%) and 30-day mortality (AA, 3%; Caucasian, 3%) were similar. Thirty-day graft failure was significantly greater in AAs than Caucasians (12% vs 5%, respectively; P = .003). The overall 5-year primary graft patency (+/-SE) was significantly worse in AA patients (AA, 52% +/- 6%; Caucasian, 67% +/- 2%; P = .009). The 5-year limb salvage rate (+/-SE) was also significantly worse in AA patients (AA, 81% +/- 5%; Caucasian, 90% +/- 1%; P = .04). With the Cox proportional hazard model, significant risk factors associated with primary graft failure were AA race, age younger than 65 years, female sex, secondary reconstructions, tibial bypasses, and critical limb ischemia. Significant risk factors associated with limb loss were age younger than 65 years, female sex, absence of coronary disease, presence of critical limb ischemia, and secondary reconstructions. CONCLUSIONS: Autogenous infrainguinal bypass surgery in AAs is associated with poorer primary graft patency and limb salvage rates compared with those of Caucasians. This may partially account for the higher rate of limb loss in AA patients with peripheral arterial occlusive disease.

Black or African American↗

PubMed2005

Lower-extremity arterial disease.

Peripheral arterial disease is a common disorder in the aging United States population that is both underdiagnosed and undertreated. In this review, we outline the general approaches to the diagnosis and management of lower-extremity arterial diseases. A broad array of current treatment options, including medical, catheter-based, and open surgical interventions are available for patients with symptomatic peripheral arterial disease. A patient-oriented approach based on anatomic and physiologic principles for the treatment of peripheral arterial disease is presented. Embolic and aneurysmal diseases of the lower-extremity arteries are also briefly reviewed. All surgeons should be aware of these common conditions and their applicable management strategies.

Aneurysm↗

PubMed2004

Early adaptation of human lower extremity vein grafts: wall stiffness changes accompany geometric remodeling.

OBJECTIVE: To quantitatively describe the temporal changes in elastic properties and wall dimensions in lower-extremity vein grafts after implantation. DESIGN OF STUDY: This is a prospective study of patients (N = 38) undergoing lower extremity bypass grafts (N = 41) with autologous veins. Pulse wave velocity (PWV), luminal diameter, and wall thickness measurements were obtained by duplex ultrasound scan intraoperatively and at 1, 3, and 6 months postoperatively for assessment of graft dimensions and wall stiffness. RESULTS: Lower extremity vein grafts showed an increase in PWV (from 16 +/- 1 to 21 +/- 3 cm/s; mean +/- SEM; P =.08), reflecting an increase in wall stiffness (from 1.2 +/- 0.2 to 2.5 +/- 0.7 x 10(6) dynes/cm; P =.02) and wall thickness (from 0.47 +/- 0.03 to 0.61 +/- 0.004 mm; P =.04) over the first 6 months after implantation. Changes in lumen diameter were positively correlated with changes in external graft diameter (P <.01) and negatively correlated with initial lumen diameter (P <.01) but not with changes in the wall thickness. CONCLUSIONS: These results suggest complex remodeling of vein grafts during the first several months after implantation, with increased wall thickness occurring independent of variable changes in lumen diameter. Simultaneously, a marked increase in wall stiffness over this interval suggests a likely role for collagen deposition.

Aged↗

PubMed2004

Thoracovisceral segment aneurysm repair after previous infrarenal abdominal aortic aneurysm surgery.

OBJECTIVE: Repair of thoracovisceral aortic aneurysms (TVAA) after previous open repair of an infrarenal abdominal aortic aneurysm (AAA) poses significant challenges. We sought to better characterize such recurrent aneurysms and to evaluate their operative outcome. METHODS: We reviewed the records and radiographs of 49 patients who underwent repair of TVAAs between 1988 and 2002 after previous repair of an AAA. Visceral artery reconstructions were completed with combinations of beveled anastomoses, inclusion patches, and side arm grafts. In 14 patients visceral endarterectomy was required to treat associated occlusive disease. Sixteen patients had cerebrospinal fluid drainage, and 10 patients had distal perfusion during cross-clamping. RESULTS: Patient mean age was 72 years, and 80% were men. Fifty-one percent of patients had symptomatic disease, and average TVAA diameter was 6.2 cm. Mean time between AAA and TVAA repair was 77 months. Twenty-six percent of aneurysms were restricted to the lower visceral aortic segment, 35% extended to the diaphragm, another 35% extended to the distal or middle thoracic aorta, and 4% involved the entire remaining visceral and thoracic aorta. The 30-day operative mortality rate was 4.1% in patients with nonruptured aneurysms and 50% in patients with ruptured aneurysms, for an overall mortality rate of 8.2%. Fifteen patients (30.6%) had major morbidity, including paresis in two patients and dialysis-dependent renal failure in five patients. At late follow-up, three patients required further aortic operations to treat additional aneurysms, and four patients had fatal aortic ruptures. Two-year and 5-year cumulative survival rates were 61% (+/-7.5%) and 37% (+/-7.8%), respectively. At univariate analysis, operative blood loss was the sole significant predictor of major morbidity (P <.023), and rupture (P <.030, P <.0001) and aneurysm extent (P <.0007, P <.0001) correlated with both operative death and long-term survival. Only aneurysm extent (P <.010, relative risk 37.3) remained a significant predictor of long-term survival at multivariate analysis. CONCLUSION: Elective repair of TVAAs after previous AAA repair can be performed with an acceptable level of operative mortality, though with considerable operative morbidity. Limited long-term survival mandates careful patient selection, and the high mortality associated with ruptured TVAA underscores the need for post-AAA surveillance.

Aged↗

PubMed2004

Statin therapy is associated with improved patency of autogenous infrainguinal bypass grafts.

OBJECTIVE: HMG-CoA reductase inhibitors (statins) broadly reduce cardiovascular events, effects that are only partly related to cholesterol lowering. Recent studies suggest important anti-inflammatory and antiproliferative properties of these drugs. The purpose of this study was to determine the influence of statin therapy on graft patency after autogenous infrainguinal arterial reconstructions. METHODS: A retrospective analysis of consecutive patients (1999-2001) who underwent primary autogenous infrainguinal reconstructions with a single segment of greater saphenous vein was performed. Patients were categorized according to concurrent use of a statin. Graft lesions (identified by duplex surveillance) and interventions were tabulated. Comparisons between groups were made by using the Fisher exact test for categorical variables and the Student t test for continuous variables. Patency, limb salvage, and survival were compared by log rank test. A stepwise Cox proportional hazards analysis was then employed to ascertain the relative importance of factors influencing graft patency. RESULTS: A total of 172 patients underwent 189 primary autogenous infrainguinal arterial reconstructions (94 statin, 95 control) during the study period. The groups were well matched for age, indication, and atherosclerotic risk factors. Procedures were performed primarily for limb salvage (92%), with 65% to an infrapopliteal target. Perioperative mortality (2.6%) and major morbidity (3.2%) were not different between groups. There was no difference in primary patency (74% +/- 5% vs 69% +/- 6%; P =.25), limb salvage (92% +/- 3% vs 90% +/- 4%; P =.37), or survival (69% +/- 5% vs 63% +/- 5%; P =.20) at 2 years. However, patients on statins had higher primary-revised (94% +/- 2% vs 83% +/- 5%; P <.02) and secondary (97% +/- 2% vs 87% +/- 4%; P <.02) graft patency rates at 2 years. Of all factors studied by univariate analysis, only statin use was associated with improved secondary patency (P =.03) at 2 years. This was confirmed by multivariate analysis. The risk of graft failure was 3.2-fold higher (95% confidence interval, 1.04-10.04) for the control group. Perioperative cholesterol levels (available in 47% of patients) were not statistically different between groups. CONCLUSIONS: Statin therapy is associated with improved graft patency after infrainguinal bypass grafting with saphenous vein.

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PubMed2004

Matrix metalloproteinase-specific inhibition of Ca2+ entry mechanisms of vascular contraction.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common disease with as yet unclear cause. Increased matrix metalloproteinase (MMP) levels in the plasma and aorta are a consistent finding in AAA. Although the role of MMPs in AAA has largely been attributed to degradation of the extracellular matrix proteins, the effects of MMPs on the mechanisms of aortic contraction are unclear. The purpose of this study was to test the hypothesis that MMPs promote aortic dilation by inhibiting the Ca2+ mobilization mechanisms of smooth muscle contraction. METHODS: Isometric contraction and 45Ca2+ influx were measured in aortic strips isolated from male Sprague-Dawley rats treated or not treated with MMP-2 and MMP-9. RESULTS: In normal Krebs solution (2.5 mmol/L Ca2+ ) phenylephrine (10-5 mol/L) caused contraction of the aortic strips, which was significantly inhibited (P < .05) by MMP-2 (maximum, 48.9% +/- 5.0%) and to a greater extent by MMP-9 (maximum, 69.8% +/- 6.2%). The MMP-induced inhibition of phenylephrine contraction depended on concentration and time. The inhibitory effects of MMPs on phenylephrine contraction were reversible. In Ca2+ -free (2 mmol/L ethylene glycol bis[beta-aminoethyl ether]-N,N,N',N'-tetraacetic acid) Krebs solution phenylephrine caused a small contraction that was not inhibited by MMP-2 or MMP-9, which suggests that MMPs do not inhibit Ca2+ release from the intracellular stores. Membrane depolarization with 96 mmol/L of potassium chloride, which stimulates Ca2+ entry from the extracellular space, caused a time-dependent and reversible contraction, which was inhibited by MMP-2 and MMP-9. Histologic studies of MMP-treated tissues stained with hematoxylin-eosin or Verhoeff stain for elastin confirmed the absence of degradation of the extracellular matrix. MMP-2 and MMP-9 also caused significant inhibition of 45Ca2+ influx induced by phenylephrine and potassium chloride. CONCLUSIONS: These data suggest that MMP-2 and MMP-9 promote aortic dilation by inhibiting the Ca2+ entry mechanism of vascular smooth muscle contraction. CLINICAL RELEVANCE: Abdominal aortic aneurysm (AAA) is a slow and progressive disease. The late stages of AAA are characterized by degenerative changes in the extracellular matrix and smooth muscle components of the aortic wall. The present study describes novel inhibitory effects of matrix metalloproteinase (MMP) on the Ca2+ entry mechanisms of aortic smooth muscle contraction, even in the absence of extracellular matrix degradation. The MMP-induced inhibition of aortic contraction may further explain the role of increased MMP activity particularly during the early development of AAA. Chronic exposure to MMPs may lead to protracted inhibition of aortic contraction, progressive aortic dilation, and aneurysm formation. MMP-9 is a more potent inhibitor of aortic contraction than MMP-2, consistent with a more dominant role in AAA. Restoration and preservation of smooth muscle contractile function by specific inhibitors of MMPs may represent a new strategy in preventing the progression of small AAA.

Animals↗

PubMed2004

Infrainguinal vein bypass graft revision: factors affecting long-term outcome.

OBJECTIVES: We sought to determine the long-term results of revision procedures performed for repair of stenotic lesions in infrainguinal vein bypass grafts. METHODS: A retrospective review of 188 vein grafts, from a total series of 1260 bypasses, undergoing revision of stenotic lesions between January 1, 1987, and December 31, 2002, at Brigham & Women's Hospital was undertaken. Lesions were identified by recurrence of symptoms, change in examination findings, or with routine duplex ultrasound graft surveillance. Demographic and medical risk factors, and surgical variables were analyzed with respect to patency outcomes after the initial graft revision, with descriptive statistics, logistic regression, and life table analysis. Primary and secondary patency rates were determined from the time of graft revision. RESULTS: Patients included 108 men (57%) and 80 women (42%) who underwent revision at a mean age of 67.8 years. One hundred thirty grafts required only a single revision, whereas 58 required subsequent additional revisions. Revision procedures included 99 vein patches (52.7%), 23 jump grafts (12.2%), 23 interposition grafts (12.2%), 8 transpositions to new outflow vessels (4.3%), and 35 balloon angioplasty procedures (18.6%). During a mean follow-up of 1535 days, 5-year primary patency rate was 49.3% +/- 4.5% (SE) and 5-year secondary patency rate was 80.3% +/- 3.6%. There was no difference in patency rate for different revision procedures, type of vein graft, indication for the original procedure, or for patients with diabetes mellitus or renal disease. The overall limb salvage rate was 83.2% +/- 3.5% 5 years after graft revision. With COX proportional hazard analysis of time to failure of the revision procedure, the outflow level of the original bypass and the time of revision proved to be an important predictor of durability of the graft revision. Revision of popliteal bypass grafts resulted in a 60% 5-year primary patency rate, whereas revision of tibial grafts resulted in a 42% 5-year primary patency rate (P = .004; hazard ratio [HR], 2.06). Five-year secondary patency rates were 90% and 76%, respectively (P = .009; HR = 3.43). The timing of the graft revision proved an additional predictor. Grafts revised within 6 months of the index operation had lower primary patency than those with later revisions (42.9% vs 80.7%, respectively; HR = 1.754; P = .0152). CONCLUSIONS: Vein graft revisions offer durable patency and limb salvage rates after repair of stenotic infrainguinal bypass grafts. Vigilant ongoing surveillance is essential, because 30.9% of revised grafts will develop additional lesions that will require repair. Tibial level bypass grafts that require early repeat intervention to treat graft stenosis are at particular risk for development of subsequent lesions.

Aged↗

PubMed2004

Carotid endarterectomy: who is the high-risk patient?

The role of carotid endarterectomy in the prevention of stroke was validated by two randomized clinical trials, the North American Symptomatic Carotid Endarterectomy (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS). However, these trials excluded patients at high risk for perioperative stroke and other morbidity, raising concerns for the applicability of the trial results to the general population. Some have also suggested these "high-risk" patients are better suited for carotid artery stenting with the belief that stenting has lower morbidity and mortality. In this article, we review many of the commonly accepted high-risk factors for carotid endarterectomy (CEA) and examine their outcomes. High-risk patients are more common than generally believed and their outcomes may be the same with carotid endarterectomy as it is with carotid stenting. Truly "high-risk" patients with shortened life expectancy are best served with no intervention.

Age Factors↗

PubMed2003

The impact of patient age and aortic size on the results of aortobifemoral bypass grafting.

OBJECTIVES: On the basis of the widespread belief that aortobifemoral bypass (ABF) represents the optimal mode of revascularization for patients with diffuse aortoiliac disease, vascular surgeons are often aggressive about its application in young adults. We undertook this retrospective evaluation of ABFs performed from 1980 to 1999 to determine whether the results justify this approach. Patients of less than 50 years of age (n = 45) were compared with those aged 50 to 59 years (n = 93) and those aged more than 60 years (n = 146). RESULTS: Younger patients were more likely to undergo operation for claudication than were older patients (72% versus 59% and 55%; P <.04). Younger patients were significantly more likely to be smokers (87%) but less likely to have diabetes, hypertension, or cerebrovascular disease. Bypasses were constructed in an end-to-end fashion in 71.1% of patients of less than 50 years versus 68.8% and 71.2% of older patients (P = not significant). The mean diameter of aortic grafts was significantly smaller in younger patients (14.6 mm) than in older patients (15.6 mm and 15.5 mm; P <.01). The need for a subsequent infrainguinal reconstruction was highest in the youngest patients (24% versus 17% and 7%; P <.01). Surgical mortality rates were low in all groups (0%, 1%, and 2.0% for increasing age groups; P = not significant). Five-year primary and secondary patency rates increased significantly with each increase in age interval: 5-year primary patency rate: less than 50 years, 66% +/- 8%; 50 to 59 years, 87% +/- 5%; more than 60 years, 96% +/-2% (P <.05 for all comparisons). Five-year secondary patency rates were: less than 50 years, 79% +/- 7%; 50 to 59 years, 91% +/- 4%; more than 60 years, 98% +/- 2% (P <.05 for all comparisons). Five-year survival rate was comparable in all three groups: less than 50 years, 93% +/- 5%; 50 to 59 years, 92% +/- 4%; more than 60 years, 87% +/- 4% (P = not significant). CONCLUSION: Increased virulence of aortic disease, smaller aortic size, and more progressive infrainguinal disease may all negatively impact the results of ABF in younger patients. Although 5-year results are acceptable, increased caution is warranted in the routine application of ABF in young patients without limb-threatening ischemia.

Adult↗