Editor's Choice - Carotid Stenosis Treatment: Variation in International Practice Patterns.

OBJECTIVES: The aim was to determine current practice for the treatment of carotid stenosis among 12 countries participating in the International Consortium of Vascular Registries (ICVR). METHODS: Data from the United States Vascular Quality Initiative (VQI) and the Vascunet registry collaboration (including 10 registries in Europe and Australasia) were used. Variation in treatment modality of asymptomatic versus symptomatic patients was analysed between countries and among centres within each country. RESULTS: Among 58,607 procedures, octogenarians represented 18% of all patients, ranging from 8% (Hungary) to 22% (New Zealand and Australia). Women represented 36%, ranging from 29% (Switzerland) to 40% (USA). The proportion of carotid artery stenting (CAS) among asymptomatic patients ranged from 0% (Finland) to 26% (Sweden) and among symptomatic patients from 0% (Denmark) to 19% (USA). Variation among centres within countries for CAS was highest in the United States and Australia (from 0% to 80%). The overall proportion of asymptomatic patients was 48%, but varied from 0% (Denmark) to 73% (Italy). There was also substantial centre level variation within each country in the proportion of asymptomatic patients, most pronounced in Australia (0-72%), Hungary (5-55%), and the United States (0-100%). Countries with fee for service reimbursement had higher rates of treatment in asymptomatic patients than countries with population based reimbursement (OR 5.8, 95% CI 4.4-7.7). CONCLUSIONS: Despite evidence about treatment options for carotid artery disease, the proportion of asymptomatic patients, treatment modality, and the proportion of women and octogenarians vary considerably among and within countries. There was a significant association of treating more asymptomatic patients in countries with fee for service reimbursement. The findings reflect the inconsistency of the existing guidelines and a need for cooperation among guideline committees all over the world.

Results of endovascular superficial femoral endarterectomy.

BACKGROUND: Endovascular superficial femoral artery (SFA) endarterectomy with a ring stripper/cutter and distal stenting has been suggested to have a patency comparable with above-knee bypass surgery. We report our initial experience with this technique. METHODS: Seventeen patients (13 men and 4 women; mean age, 64 years) with SFA occlusion and above-knee popliteal reconstitution underwent attempted remote endarterectomy with a ring cutter system combined with primary stenting of the distal end point. Analysis was performed in a prospective manner with patency rates determined by Kaplan-Meier life-table analysis. RESULTS: The indication for operation was claudication in 8 patients, rest pain in 6, and tissue loss in 3. Initial technical success was achieved in 11 patients (65%). Reasons for technical failure included SFA perforation (4), inability to traverse a calcified/diseased segment (1), and inability to retract/remove the ring cutter (1). Life-table analysis of all patients revealed a primary patency at 1 year of 26% +/- 11%. Primary-assisted patency was 38% +/- 12% at 1 year, with 59% of patients ultimately requiring surgical bypass grafting. In patients in whom initial technical success was achieved, the 1-year primary and primary-assisted patency rates were 40% and 59%, respectively. There were four reocclusions requiring surgical revascularization with below-knee popliteal (2) or tibial (2) bypass grafting, 1 symptomatic restenosis requiring repeat angioplasty, and 1 symptomatic restenosis treated conservatively. CONCLUSION: The results of endovascular SFA endarterectomy were disappointing, with technical success in less than two thirds of patients and a 1-year primary patency of only 26%. Remote SFA endarterectomy appears less effective than above-knee femoropopliteal bypass grafting, and after early failure, patients may require more distal revascularization for limb salvage.

Early results of infragenicular revascularization based solely on duplex arteriography.

PURPOSE: Recent reports have both advocated and questioned the utility of duplex arteriography (DA) as the sole preoperative imaging modality for planning infragenicular revascularization. This study compares the outcome of patients with critical limb ischemia who underwent infragenicular vein grafts on the basis of DA alone versus conventional preoperative contrast arteriography (CA). METHODS: The study group is composed of 23 consecutive patients who underwent infragenicular vein bypass grafting solely on the basis of preoperative DA from 1998 to 1999. They were compared with 50 consecutive patients who underwent infragenicular vein bypass grafting after CA from 1996 to 1998. Peak systolic velocity and end-diastolic velocity of potential target arteries were recorded during DA studies. In situ saphenous vein grafts were used preferentially, and technical adequacy of all grafts was assessed with completion duplex or arteriography. RESULTS: DA and CA groups were comparable on the basis of age and risk factors. In one limb (4%), the target artery selected by DA was abandoned because of dense calcification. No other revision in target or inflow artery was required on the basis of intraoperative completion studies. At 1 year, primary graft patency (78% vs 70%, P =.72) and limb salvage (70% vs 81%, P =.21) were comparable between the two groups. In the DA group, mean preoperative target artery peak systolic velocity in patent versus failed grafts was 49 +/- 18 cm/s versus 31 +/- 9 cm/s (P =.04), whereas mean end-diastolic velocity was 22 +/- 7 cm/s versus 14 +/- 8 cm/s (P =.08). CONCLUSION: Infragenicular revascularization directed by DA alone provides early graft patency and limb salvage rates comparable to similar procedures that are based on CA. Preoperative DA target artery velocities may predict outcome and improve target selection. These initial results justify further clinical testing of DA as the primary imaging modality for planning infragenicular vein grafts.

Results of an aortic endograft trial: impact of device failure beyond 12 months.

PURPOSE: Analysis endpoints of patient survival and aortic rupture at a reporting interval of 12 months are regularly used to compare endograft aortic aneurysm (EAG) repair to conventional open surgical (COS) repair. This study reports a multicenter EAG repair versus COS repair parallel cohort trial at 12 months and additional observations of specific device failure types and their impact on an aortic endograft design beyond that follow-up period. METHODS: From August 1997 to September 1998, 240 patients who were treated with bifurcation EAG repairs and 28 patients who were treated with straight EAG repairs were compared with 98 patients who were treated with COS repair for elective infrarenal aortic aneurysm repair. Allocation to treatment was based on aneurysm anatomy. All cohorts underwent infrarenal procedures. Data from concurrent, nonrandomized patient accrual from 17 United States institutions were prospectively gathered and independently adjudicated for safety and efficacy. An independent core laboratory evaluated all imaging data. RESULTS: There were 308 men and 58 women (mean age, 72 years; range, 42-94 years) treated for infrarenal aortic aneurysm (mean diameter, 55 mm; range, 40-115 mm). Mean preoperative aneurysm diameters were clinically similar (EAG repair, 54 mm vs COS repair, 57 mm). The two cohorts were not significantly different in terms of gender (P = .30) or age (P = .32). EAG repair technical success (aneurysm exclusion, graft patency, patient survival) at 30 days was 89.2%. Five patients required immediate conversion to COS repair, four caused by access complications and one caused by operator-induced EAG repair malposition. The 30-day mortality rate was 1.5% for EAG repair and 3.1% for COS repair (P = .59). The 12-month survival rate was 94.3% for EAG repair and 95.9% for COS repair. The intermediate-term cumulative survival rate at 24 months was 84.9% for EAG repair and 80.3% for COS repair (P = .48). EAG repair device failure occurred from fabric erosion in six patients, with two deaths from ruptured aneurysm at 18 and 28 months after endografting and four device failures resolved by secondary procedures. Five endograft limb dislocations were all resolved by secondary endovascular procedures. Major or minor endograft migration required secondary procedures in five patients, including conversion in two patients. CONCLUSION: The clinical outcome at 12 months demonstrated effective aneurysm treatment and comparable safety between EAG repair and COS repair by conventional endpoints. Ongoing follow-up beyond 12 months revealed device-related adverse events that required endograft design changes. Diligent surveillance of outcomes beyond 12 months is necessary to adequately evaluate EAG repair devices.

Pedal branch artery bypass: a viable limb salvage option.

PURPOSE: We reviewed our experience with pedal branch artery (PBA) bypass to confirm the role of these target arteries for limb salvage and to identify patient and technical factors that may be associated with graft patency and limb salvage. METHODS: In this retrospective study we analyzed 24 vein grafts to PBAs performed from 1988 to 1998 for limb salvage in 23 patients who had no suitable tibial, peroneal, or dorsal pedal target arteries. These PBA grafts were compared with 133 perimalleolar posterior tibial, defined at or below the ankle, or dorsalis pedis bypass grafts performed contemporaneously; the Kaplan-Meier life table was used in the analysis of graft patency and limb salvage. Life table analyses and logistic regression analysis of prognostic patient variables were also performed. RESULTS: The PBA bypass represented 3% of infrainguinal revascularizations for chronic critical limb ischemia at our institution over the study period. Patients who received PBA bypasses were more likely to be male (92% vs. 69%, P =.02) with lower incidences of overt coronary artery disease (33% vs. 50%, P =.12) and stroke (0% vs 15%, P =.04), and a higher incidence of end-stage renal disease (21% vs 8%, P =.06) than those undergoing perimalleolar bypass. Seventeen percent of PBA bypasses were performed with the anterior lateral malleolar artery, a vessel not previously described as a common bypass target. Two-year primary patency and limb salvage for PBA versus perimalleolar bypass was 70% versus 80% (P =.16) and 78% versus 91% (P = .28), respectively. Patency and limb salvage rates were no different in bypasses with above-knee or below-knee inflow arteries. CONCLUSION: An autogenous vein bypass to the PBA, though rarely required, provides acceptable primary patency and limb salvage when compared with perimalleolar tibial artery bypass when no suitable, more proximal target arteries are available. The PBA bypass should be considered before major amputation is undertaken.

Predicting outcome of angioplasty and selective stenting of multisegment iliac artery occlusive disease.

BACKGROUND: Patients who require angioplasty and stenting of multiple iliac arterial segments often require reintervention to maintain long-term patency. Morphologic predictors and causes of failure are unknown. The purpose of the current study was to define arteriographic predictors of angioplasty and selective stent failure in the treatment of multisegment iliac occlusive disease. METHODS: All iliac segments (two common and two external) of 75 patients who underwent angioplasty and selective stent placement for multisegment iliac occlusive disease (>/= two segments) were scored through use of a modification of the Society of Cardiovascular and Interventional Radiology classification for iliac angioplasty (0 = no lesion; 4 = most severe). Total iliac score was calculated by summing scores from each segment. A separate external iliac score was calculated by adding only the external iliac scores. Arteriograms were reviewed initially and at the time of lesion recurrence and stratified by lesion location and previous intervention. RESULTS: The area of previous endovascular intervention was the site of recurrence in 75% of patients. New lesions, presumably a result of progressive atherosclerosis, occurred in 15% of patients, and lesions occurred in both new and previously treated iliac segments in 10% of patients. Only the external iliac score was an independent predictor of failed endovascular therapy despite reintervention. For patients with an external iliac score of 2 or less, the endovascular primary-assisted patency rates at 6, 12, and 24 months were 96%, 92%, and 89%, respectively. This was improved in comparison with the 90%, 63%, and 45% patency rates observed in patients with an external iliac score of 3 or more (P =.001). Patients with an external iliac score of 3 or more had a significantly lower incidence of hemodynamic and clinical improvement after intervention and a threefold higher need for surgical inflow procedures than patients with an external iliac score of 2 or less. CONCLUSIONS: Lesion formation after treatment of multisegment iliac occlusive disease typically occurs in areas of prior intervention. The extent of external iliac disease can be used to stratify patients with multisegment iliac occlusive disease who will likely respond to endovascular treatment with a durable result. Patients with extensive external iliac disease (score >/= 3) have poor results after angioplasty and selective stenting as applied in this study, even with endovascular reintervention. They are ideal subjects for prospective comparative studies of competing initial therapies, including stenting, endografting, and aortobifemoral bypass grafting.

The durability of endovascular treatment of multisegment iliac occlusive disease.

PURPOSE: The effectiveness of endovascular treatment of multisegment iliac occlusive disease (involving two or more common and/or external iliac arteries) was determined. METHODS: All patients who underwent angioplasty or stenting of at least two separate iliac artery segments were identified. Demographic data were recorded. Technical success, hemodynamic success, and aortoiliac primary and primary-assisted patency were analyzed by using the Society for Vascular Surgery and International Society for Cardiovascular Surgery (SVS/ISCVS) criteria. Multivariate, life table analysis was used as a means of determining outcome predictors. RESULTS: Eighty-seven patients underwent 207 iliac artery angioplasties and 115 iliac artery stents, which were performed in 210 iliac segments for disabling claudication in 60% of cases, for rest pain in 17% of cases, and for tissue loss in 23% of cases. Two iliac segments were treated in 64% of patients, three segments were treated in 28% of patients, and four segments were treated in 8% of patients. The complication rate was 11%. Initial hemodynamic success was achieved in 72% of cases. Clinical improvement occurred in 88% of patients. Subsequent endovascular reintervention was required in 29% of patients, whereas surgical inflow procedures were required in 14% of patients to maintain aortoiliac patency. The mean time from the primary intervention to the first reintervention was 10 +/- 3 months. At 6, 12, and 36 months after intervention, the primary patency rates of the aortoiliac segment were 76%, 61%, and 43%, respectively, and the primary assisted patency rates were 95%, 87%, and 72%, respectively. Only the presence of an external iliac artery stenosis adversely affected both primary and assisted-primary patency. At 6, 12, and 36 months, the aortoiliac primary patency rates in patients without the presence of an external iliac artery stenosis were 88%, 78%, and 69%, respectively, compared with 68%, 47%, and 18%, respectively, in patients with external iliac artery lesions (P <. 0001). CONCLUSION: Endovascular therapy for multisegment aortoiliac occlusive disease has acceptable patency rates; however, reintervention is often needed. The presence of external iliac artery disease is a significant predictor of poor outcome.

Cost-effectiveness of surgery for small abdominal aortic aneurysms on the basis of data from the United Kingdom small aneurysm trial.

PURPOSE: Although the United Kingdom small aneurysm trial reported no survival benefit for early operation in patients with small (4. 0-5.5 cm) abdominal aortic aneurysms (AAAs), the trial lacked statistical power to detect small but potentially meaningful gains in life expectancy, particularly for specific subgroups. We used decision analysis to better characterize the potential benefits and cost-effectiveness of early surgery. METHODS: We used a Markov model to assess the marginal cost-effectiveness (incremental cost per quality-adjusted life year [QALY] saved) of early surgery relative to surveillance for small AAAs, using data from the UK Trial. Subgroup analyses were performed by patient age and AAA diameter. Sensitivity analysis was used to evaluate the effect of elective operative mortality on cost-effectiveness. RESULTS: In our baseline analysis, early operations provided a small survival advantage (0.14 QALYs) at a small incremental cost of $1510. Thus, despite a small survival benefit, early surgery appeared cost-effective ($10, 800/QALY). The small cost differential resulted from the large proportion of patients who underwent surveillance, who eventually underwent AAA repair, and therefore incurred the cost of the surgical procedures. The survival advantage and cost-effectiveness of early operation increased with lower operative mortality, younger age, and larger AAA diameter. CONCLUSION: Despite the negative conclusions of the UK trial, early surgery may be cost-effective for patients with small AAAs, particularly younger patients (<72 years of age) with larger AAAs (> or = 4.5 cm). Because the gains in life expectancy are relatively small, however, clinical decision making should be strongly guided by patient preferences.

A specific inhibitor of apoptosis decreases tissue injury after intestinal ischemia-reperfusion in mice.

PURPOSE: Apoptosis is a stereotypical pathway of cell death that is orchestrated by a family of cysteine endoproteases called caspases. This study examined the effect of apoptosis inhibition with a specific caspase inhibitor on murine intestinal viability after ischemia-reperfusion (IR). METHODS: C57Bl6 X SV129 mice underwent segmental small bowel ischemia by vascular isolation of 10 cm of terminal ileum. In separate experiments, the ischemic time was varied from 30 to 130 minutes with a reperfusion interval of 6 hours. The degree of small bowel injury was quantified from 1 to 5 (increasing severity) by standardized, blinded histologic grading. The degree of apoptosis was assessed with a specific assay (terminal deoxyamcleotydil transferase-mediated deoxyuridine triphosphate nick end labeling [TUNEL]) and quantified by calculating the apoptotic index (apoptotic cells/10 high-power fields). To evaluate for activation of interleukin-1beta converting enzyme we measured tissue mature interleukin-1beta levels using a specific enzyme-linked immunosorbent assay. To evaluate the effect of apoptosis inhibition on intestinal viability after IR, mice received 3.0 mg of the caspase inhibitor ZVAD (N-benzyloxycarbonyl Val-Ala-Asp-Ome-fluoromethylketone) subcutaneously before and after IR in five divided doses (n = 11), the same dose of ZFA (N-benzyloxycarbonyl Phe-Ala fluoromethylketone), a structurally similar molecule with no anticaspase activity (n = 9), or sham operation (n = 6). RESULTS: A linear relationship existed between ischemic interval and histologic grade (r = 0.69, P <.006). Increasing the ischemic interval from 0 to 50 minutes was associated with a fivefold increase in apoptotic index (P =.05). Ischemic bowel was measured to have an average of 57.3 +/- 7.8 pg/mL whereas normal bowel had an average of 1.8 +/- 0.5 pg/mL of mature interleukin-1beta present. Mice tolerated multiple injections of ZVAD and ZFA without signs of toxicity. Animals treated with ZVAD (apoptosis inhibitor) had little injury after 50 minutes of ischemia and 6 hours of reperfusion (injury grade 1.8) compared with sham controls (injury grade 1.2, P =.7) and had significantly less injury than mice treated with ZFA (placebo) (injury grade 3.0, P <.006). CONCLUSIONS: Increasing ischemic interval in a segmental small bowel murine IR model is associated with increased histologic injury and augmented apoptosis as evidenced by increased TUNEL staining and interleukin-1beta converting enzyme activation. Inhibition of apoptosis with a specific caspase inhibitor significantly diminishes the degree of small bowel injury.

A caspase inhibitor decreases oxidized low-density lipoprotein-induced apoptosis in bovine endothelial cells.

BACKGROUND: Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Oxidized low density lipoprotein (oxLDL) is a putative cause of atherogenesis. We examined the effect of oxLDL on endothelial cell (EC) apoptosis and the ability of a caspase antagonist to inhibit oxLDL-induced EC injury. METHODS: Bovine ECs were plated at a concentration of 5.0 x 10(5) cells/ml and exposed to LDL oxidized by ultraviolet radiation at a concentration of 100 microgram oxLDL/ml for 20 h. Some ECs were pretreated with an irreversible caspase inhibitor (ZVAD). Samples were analyzed histologically. Apoptosis was measured using the Annexin V assay (flow cytometry) which detects phosphatidylserine on plasma membranes and confirmed by TUNEL assay (flow cytometry). Statistical assessments were performed using ANOVA. RESULTS: ECs treated with LDL were morphologically similar to untreated cells. Cells treated with oxLDL demonstrated cytoplasmic shrinkage, plasma membrane blebbing, chromatin condensation, and loss of adhesion. These effects were diminished after pretreatment with the caspase inhibitor ZVAD. The Annexin V assay showed: (a) cells exposed to LDL had a 12 +/- 1% apoptosis rate, (b) exposure to oxLDL induced apoptosis in 30 +/- 0.3% of the cells, and (c) pretreatment with the caspase inhibitor ZVAD decreased the oxLDL-induced apoptosis to 16 +/- 1% (P < 0.05). This decrease in apoptosis was also reflected by an increase in the percentage of alive cells from 34 +/- 7% after oxLDL exposure to 55 +/- 6% after apoptosis inhibition with ZVAD. TUNEL assay demonstrated a 2.5-fold reduction in mean fluorescence intensity between cells treated with oxLDL alone and those treated with ZVAD, suggesting a significant decrease in apoptosis in the latter group. CONCLUSIONS: We conclude that treatment of bovine ECs with oxLDL induces apoptosis which can be significantly reduced by a specific caspase inhibitor.

Should endovascular surgery lower the threshold for repair of abdominal aortic aneurysms?

PURPOSE: Because endovascular repair of abdominal aortic aneurysms (AAAs) is less invasive, some investigators have suggested that this increasingly popular technique should broaden the indications for elective AAA repair. The purpose of this study was to calculate quality-adjusted life expectancy rates after endovascular and open AAA repair and to estimate the optimal diameter for elective AAA repair in hypothetical cohorts of patients at average risk and at high risk. METHODS: A Markov decision analysis model was used in this study. Assumptions were made on the basis of published reports and included the following: (1) the annual rupture rate is a continuous function of the AAA diameter (0% for <4 cm, 1% for 4.5 cm, 11% for 5.5 cm, and 26% for 6.5 cm); (2) the operative mortality rate is 1% for endovascular repair (excluding the risk of conversion to open repair) and 3.5% for open repair at age 70 years; and (3) immediate endovascular-to-open conversion risk is 5%, and late conversion rate is 1% per year. The main outcome measure in this study was the benefit of AAA repair in quality-adjusted life years (QALYs). The optimal threshold size (the AAA diameter at which elective repair maximizes benefit) was measured in centimeters. RESULTS: The benefit of endovascular repair is consistently greater than that of open repair, but the additional benefit is small-0.1 to 0.4 QALYs. For men in average health with gradually enlarging AAAs with initial diameters of 4 cm, endovascular surgery reduces the optimal threshold diameter by very little: from 4.6 to 4.6 cm (no change) at age 60 years, from 4.8 to 4.7 cm at age 70 years, and from 5.1 to 4.9 cm at age 80 years. For older men in poor health, endovascular surgery reduces the optimal threshold diameter substantially (8.1 to 5.7 cm at age 80 years), but the benefit of repair in this population is small (0.2 QALYs). CONCLUSION: For most patients, the indications for AAA repair are changed very little by the introduction of endovascular surgery. Only for older patients in poor health does endovascular surgery substantially lower the optimal threshold diameter for elective AAA repair.

Fate of the contralateral leg after infrainguinal bypass.

PURPOSE: To identify variables predictive of the need for future vascular intervention in a leg contralateral to one currently undergoing infrainguinal bypass. METHODS: We reviewed the records of 450 consecutively treated patients undergoing infrainguinal bypass for occlusive disease to examine the outcome of a previously untreated contralateral leg. Patients with coexistent contralateral limb-threatening ischemia at the time of initial ipsilateral operation were excluded, as were patients with bilateral disease who underwent a staged contralateral procedure within 3 months of the ipsilateral operation. This yielded a study cohort of 383 patients with no anticipated intervention in the contralateral leg who were followed for a mean value of 38 months. Patient survival and subsequent intervention in the contralateral leg were examined with life-table and regression analysis. RESULTS: Mean age of the patients was 68 years; 60% were men; 54% had diabetes; and 50% had coronary artery disease. The initial ipsilateral operation was performed for limb threat in 90% of instances. Twenty percent of patients subsequently needed intervention in the contralateral leg (infrainguinal bypass 83%, primary major amputation 17%). According to life-table analysis, 30% of patients needed intervention at 5 years, and the overall survival rate was 51% at 5 years. Multivariate analysis indicated that the need for future contralateral intervention was independently predicted with the following four risk factors: diabetes (relative risk [RR] 2.4x), coronary artery disease (RR 1.8x), lower initial ankle-brachial index (RR 2.1x with ankle-brachial index less than 0.7), and younger age (RR 2.2x if age less than 70 years). Regression models predicted the need for contralateral intervention for only 8% of patients at 5 years when none of these risk factors was present but for 67% when all risk factors were present. CONCLUSION: The fate of the contralateral leg after infrainguinal bypass is affected by diabetes, coronary artery disease, contralateral ankle-brachial index, and age at initial ipsilateral bypass. The effect of these risk factors is additive in prediction of the likelihood of future intervention. Knowledge of these factors may help identify instances in which the contralateral greater saphenous vein will be important for future limb salvage and also determine which patients need more careful follow-up care.