Systematic Long-term Follow Up After Endovascular Abdominal Aortic Aneurysm Repair With the Zenith Stent Graft.

OBJECTIVE/BACKGROUND: Although endovascular aneurysm repair (EVAR) has been widely adopted, long-term data remain limited. This study analyses the long-term outcome (16 years) after EVAR with the Zenith stent graft in a single academic centre. METHODS: From 2000 to 2010, 282 patients with an abdominal aortic aneurysm (AAA) were treated electively and monitored annually. Primary outcomes were overall and AAA rupture free survival; the secondary outcomes were complication and re-intervention free survival. Kaplan-Meier analysis was used to examine survival. RESULTS: The median patient age was 76 years (range 49-92 years) and mean aneurysm diameter 61 mm (range 40-110 mm). Patients were followed for a median of 76 months (range 0-201 months). Overall survival was 93% (SE 0.02), 61% (SE 0.08), 25% (SE 0.16), and 9% (0.19) at 1, 2, 5, 10, and 16 years, respectively. Ten (3.5%) AAA ruptures occurred, and the cumulative AAA rupture free survival was 100%, 98% (SE 0.01), 96% (SE0.02), and 79% (SE 0.12) at 1, 5, 10, and 16 years, respectively. The mean annual AAA rupture rate was 0.5%. Freedom from any stent graft related complications was 68% (SE 0.03), 58% (SE 0.09), 54% (SE 0.17), and 52% (SE 0.21), respectively; freedom from graft related re-interventions was 95% (SE 0.01), 80% (SE 0.08), 73% (SE 0.11), 70% (SE 0.16), at 1, 5, 10, and 16 years, respectively. Five (1.8%) late conversions were required during follow up. The variables that significantly and independently correlated with ruptured AAA were pre-operative aneurysm size and primary type II endoleak. The latter was the only independent significant factor to increase the risk of re-intervention. CONCLUSION: The number of graft related complications is high after EVAR, and new complications keep appearing years after the initial procedure. Even though fatal AAA rupture after EVAR is rare, it cannot be totally avoided despite systematic follow up.

Survival of Patients and Treatment-Related Outcome After Intra-Arterial Thrombolysis for Acute Lower Limb Ischemia.

BACKGROUND: The aim of this study is to evaluate the long-term survival and treatment-related outcome in patients treated with intra-arterial thrombolysis for acute lower limb ischemia. METHODS: The study was based on a prospective vascular database with retrospectively obtained supplementary information from the patients' files. Additionally, data on the patients' date and cause of death were obtained from Statistics Finland. A total of 155 patients with symptoms or signs of category I-IIa acute lower limb ischemia and angiographic evidence of native artery or bypass graft thromboembolic events were treated with intra-arterial catheter-directed thrombolysis (CDT). Patients with severe ischemic stages at admission or those with contraindications for thrombolysis (n = 185) were treated with conventional surgical modalities and excluded from further analysis. RESULTS: The mean age of the patients at admission was 73 years (95% confidence interval 70.1-74.6). For descriptive purposes, age quartiles were used (≤64, 65-74, 75-82.5, ≥83). The mean follow-up time was 126.3 months. The primary patency rates of native arteries/bypass grafts were 59.8%/31.7%, 35.4%/17.1%, and 18.7%/15.2% at 1, 5, and 10 years, respectively (P = 0.01). Correspondingly, the respective secondary patency rates were 65.2%/55.6%, 46.7%/39.8%, and 22.8%/30.5% (P = 0.88). A total of 190 additional procedures on 122 patients were required to preserve the patency after hospital discharge. At 1 year the cumulative survival was 78%, at 5 years 56%, and at 10 years 29%. The most common cause of death was cardiovascular (68.5%), predominantly presented by an acute coronary syndrome, while 9.6% died of cancer, 6.8% of pulmonary diseases, 8.2% of cerebrovascular causes, and 19.2% owing to trauma and other reasons. Atrial fibrillation (hazards ratio [HR] 2.31) and age over 83 years (HR 5.23 per age category) were significantly and independently associated with poorer cumulative post-procedural survival. Bypass graft thrombosis was associated with an increase in major amputations after CDT (HR 14.77). However, the presence of synthetic bypass grafts had a protective influence on limb salvage (HR 0.086). A total of 39 (25.2%) major amputations were performed during the follow-up period. Age over 75 years was the only significant and independent factor to negatively impact on amputation-free survival (HR 2.01), which was 24% at 10 years. CONCLUSIONS: The long-term patency after CDT is unfavorable, and additional procedures are needed to preserve adequate distal perfusion. Approximately 30% of the patients are alive at 10 years after the initial CDT. Increasing age and atrial fibrillation have a negative effect on the patients' survival.

Bacterial signatures in thrombus aspirates of patients with lower limb arterial and venous thrombosis.

OBJECTIVE: Increasing data supports the role of bacterial inflammation in adverse events of cardiovascular and cerebrovascular diseases. In our previous research, DNA of bacterial species found in coronary artery thrombus aspirates and ruptured cerebral aneurysms were mostly of endodontic and periodontal origin, where Streptococcus mitis group DNA was the most common. We hypothesized that the genomes of S mitis group could be identified in thrombus aspirates of patients with lower limb arterial and deep venous thrombosis. METHODS: Thrombus aspirates and control blood samples taken from 42 patients with acute or acute-on-chronic lower limb ischemia (Rutherford I-IIb) owing to arterial or graft thrombosis (n = 31) or lower limb deep venous thrombosis (n = 11) were examined using a quantitative real-time polymerase chain reaction to detect all possible bacterial DNA and DNA of S mitis group in particular. The samples were considered positive, if the amount of bacterial DNA in the thrombus aspirates was 2-fold or greater in comparison with control blood samples. RESULTS: In the positive samples the mean difference for the total bacterial DNA was 12.1-fold (median, 7.1), whereas the differences for S mitis group DNA were a mean of 29.1 and a median of 5.2-fold. Of the arterial thrombus aspirates, 57.9% were positive for bacterial DNA, whereas bacterial genomes were found in 75% of bypass graft thrombosis with 77.8% of the prosthetic grafts being positive. Of the deep vein thrombus aspirates, 45.5% contained bacterial genomes. Most (80%) of bacterial DNA-positive cases contained DNA from the S mitis group. Previous arterial interventions were significantly associated with the occurrence of S mitis group DNA (P = .049, Fisher's exact test). CONCLUSIONS: This is the first study to report the presence of bacterial DNA, predominantly of S mitis group origin, in the thrombus aspirates of surgical patients with lower limb arterial and deep venous thrombosis, suggesting their possible role in the pathogenesis of thrombotic events. Additional studies will, however, be needed to reach a final conclusion.

Preoperative white matter lesions are independent predictors of long-term survival after internal carotid endarterectomy.

BACKGROUND: Cerebral white matter lesions (WMLs) predict long-term survival of conservatively treated acute stroke patients with etiology other than carotid stenosis. In carotid endarterectomy patients, WMLs are associated with severe carotid stenosis and unstable plaques, with the risk of perioperative complications and with increased 30-day perioperative risk of death. However, no data exist on their effect on postoperative long-term survival, a factor important when considering the net benefit from carotid endarterectomy. Whether this effect is independent of classical risk factors and indications for surgery is not known either. We hypothesized that WMLs could be evaluated from preoperative routine computed tomography (CT) scans and are predictors of postoperative survival, independent of classical cardiovascular risk factors, indication category and degree of carotid stenosis. METHODS: A total of 353 of 481 (73.4%) consecutive patients subjected to carotid endarterectomy due to different indications, i.e. asymptomatic stenosis (n = 28, 7.9%), amaurosis fugax (n = 52, 14.7%), transient ischemic attack (n = 135, 38.2%) or ischemic stroke (n = 138, 39.1%), from prospective vascular registries during the years 2001-2010 with digital preoperative CT scans, were included in the study. WMLs were rated by a radiologist (Wahlund criteria) in a blinded fashion. Internal carotid artery (ICA) stenoses were angiographically graded (<50, 50-69, 70-99 and 100%). Odds ratios (ORs) and hazard ratios (HRs) are reported (ORs and HRs ≤1 indicate a beneficial effect). The median follow-up time was 67 months (interquartile range 45.5, range 0-129 months). Spearman's rho was used to estimate intraobserver agreement. Binary logistic regression was performed to analyze the association of risk factors with WMLs. Cox regression proportional hazards analysis was used to study the effect of different factors on survival. RESULTS: WML severity could be assessed with a substantial intraobserver agreement (Spearman's rho 0.843, p < 0.0001). Only age (OR 1.10, 95% CI 1.06-1.15; p < 0.0001 per year), degree of ipsilateral ICA stenosis (OR 2.22, 95% CI 1.08-4.55; p < 0.05 per stenosis grade) and indication category (OR 1.63, 95% CI 1.19-2.24; p < 0.01 per category) remained independently associated with WMLs. Age (HR 1.04, 95% CI 1.01-1.08; p < 0.05 per year), diabetes (HR 1.59, 95% CI 1.01-2.49; p < 0.05), peripheral arterial disease (HR 2.47, 95% CI 1.46-4.15; p < 0.01), degree of ipsilateral ICA stenosis (HR 2.56, 95% CI 1.12-5.87; p < 0.05 per stenosis grade) and WMLs (HR 3.83, 95% CI 1.17-12.5; p < 0.05) remained independently associated with increased long-term mortality. CONCLUSIONS: WMLs in a preoperative CT scan provide a substantially reliable estimate of postoperative long-term survival of carotid endarterectomy patients independent of currently used criteria, i.e. cardiovascular risk factors, indication category and degree of ipsilateral ICA stenosis.

Independent factors predicting early lower limb intra-arterial thrombolysis failure.

BACKGROUND: Risk factors for early catheter-directed intra-arterial thrombolysis failure in acute lower limb ischemia remain unclear. METHODS: One hundred forty-nine limbs with acute artery or bypass graft thrombosis underwent catheter-directed thrombolysis (maximum of 48 hours). A retrospective data analysis was carried out to assess possible risk factors for early, 30-day treatment failure. RESULTS: Seventy-nine men (53%) and 70 women (47%) with a median age of 70 (range 32-93) years were treated. Treatment outcomes were determined as success (N = 115, 77%) or failure (N = 34, 23%). The failure criteria comprised rapid progression of ischemia (N = 4, 2.7%) and major bleeding complications (N = 2, 1.3%), both requiring thrombolysis termination and surgery. Inability to reopen native arteries/grafts (N = 10, 6.7%), run-off vessels (N = 10, 6.7%), in-hospital death (N = 4, 2.7%), the need for major amputation (N = 13, 8.7%), and reocclusions (N = 5, 3.4%) within the 30-day follow-up period were also considered as failures. Multivariate analysis of the risk factors' impact on the success of thrombolysis revealed such independent parameters as hypercholesterolemia (OR 0.16, 95% CI 0.06-0.42, P < 0.0001), previous bypass grafting of the ipsilateral limb (OR 0.18, 95% CI 0.06-0.53, P = 0.002), and duration of ischemia prior to the initiation of thrombolysis (OR 0.95, 95% CI 0.91-0.99, P = 0.009, per day). CONCLUSION: According to our results, factors independently predicting early failure include hypercholesterolemia, previous bypass grafting, and a delay in treatment initiation. Moreover, catheter-directed intra-arterial thrombolysis can be considered safe and effective in the treatment of acute lower limb ischemia.

[Should we start AAA screening in Finland?]. / Onko vatsa-aortan aneurysman seulontaan aihetta suomessa?

Abdominal aortic aneurysms (AAA) are usually asymptomatic before rupture. Through ultrasound screening AAA can be found before rupture. In Europe England and Sweden have started one-time ultrasound screening for men at age 65. Many studies around Europe have shown that screening is cost-effective. In a recent Finnish study one-time screening for men at age 65 would be a more effective option than the current practice where no screening is offered. Screening for abdominal aortic aneurysm among 65-year-old women would entail less additional costs but fewer life years gained than screening for men. Starting the screening would require additional resources in the Finnish health care system as compared to the current policy.

Challenging treatment of multiple late complications after endovascular aneurysm repair.

BACKGROUND: To report a case of multiple additional procedures after successful endovascular treatment of abdominal aortic aneurysm. METHODS: An endovascular abdominal aortic aneurysm repair with a bifurcated aortic Vanguard endograft successfully performed in 1999 resulted in multiple complications, including endoleaks and a row separation, treated endovascularly. Subsequently, tuberculosis sepsis and prosthesis infection resulted in long-term antibiotic treatment. Additional graft leaks, aneurysm sack growth, and sack ruptures were also treated endovascularly because the patient consistently denied open repair. Endovascular procedures, however, did not solve the problem, turning to be increasingly challenging. The patient finally approved open graft removal and aortobifemoral reconstruction that were successfully performed 11 years after the initial endograft implantation. RESULTS: The patient has recovered from surgery well and is asymptomatic. No evidence of bacterial colonization was found according to the specimen taken during the laparotomy. CONCLUSION: Vanguard and other first-generation aortic endografts are associated with high incidence of complications and reinterventions. Open surgery is a method of choice in similar cases.

[Vascular malformations associated with Marfan syndrome, Ehlers-Danlos syndrome and neurofibromatosis 1 and their surgical treatment]. / Marfanin oireyhtymään, Ehlers-Danlosin oireyhtymään ja neurofibromatoosi 1: een liittyvät verisuonimuutokset ja niiden kirurginen hoito.

The Marfan syndrome, vascular type Ehlers-Danlos syndrome and neurofibromatosis 1 are associated with vascural complications that may be fatal. Therefore, referral to treatment should be properly timed, followed by therapy taking special features of the disease into consideration. When treating a vascular malformation related to an inherited disorder, it is important to collaborate with clinical geneticists in order to obtain genetic counseling and DNA diagnostics as well as to elucidate the status of close relatives.

[Subclavian steal syndrome]. / Subclavian steal -oireyhtymä.

Subclavian steal syndrome is a circulatory disorder usually caused by atherosclerosis and accompanied by ischemic symptoms of the vertebrobasilar region and the hand. In many cases, significant vascular lesions are found also in other arteries. In more than 80% of cases the blood vessel lesion is on the left, and a significant stenosis or occlusion causes an inter-arm pressure gradient of > 20 mmHg, resulting in retrograde blood flow of the ipsilateral vertebral artery. In local stenosis, conservative treatment can be combined with an intravascular procedure, and in occlusions or other arterial lesions requiring operative treatment, with bypass surgery.

Activation of indoleamine 2,3-dioxygenase-induced tryptophan degradation in advanced atherosclerotic plaques: Tampere vascular study.

OBJECTIVE: We aimed to characterize the expression of indoleamine 2,3-dioxygenase (IDO) or IDO-induced tryptophan degradation-dependent pathways, which may lead to suppression of T cells and possible protection against atherosclerosis. METHODS AND RESULTS: Expression of IDO and IDO-related pathway components was analyzed in advanced human atherosclerotic plaques (n = 24) and in non-atherosclerotic arteries (n = 6). Up-regulation of IDO and genes related to the IDO pathway was found to be pronounced in atherosclerotic plaques. Immunohistochemistry demonstrated IDO protein in the atheromatous core and co-distribution with monocyte-macrophages (CD68-positive cells). In gene-set enrichment analysis, the IDO pathway revealed a significant (false discovery rate (FDR) = 0.07) regulatory T cell, fork-head box protein 3 (FoxP3)-initiated CD28-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-inducible T cell co-stimulator (ICOS)-driven pathway leading to activation of IDO expression in antigen-presenting cells (APCs). Expression of these IDO pathway genes varied between 2.1- and 16.8-fold as compared to control tissues (P < 0.05 for all). CONCLUSIONS: IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis offering new viable therapeutic targets for the development of antiatherogenic immunosuppressive therapies.

[What is known about the effectiveness of vascular surgery?]. / Mitä tiedetään verisuonikirurgian vaikuttavuudesta.

According to nationally consistent guidelines for nonurgent care, the aim is to make decisions of treatment and prioritizing on systematically clear grounds both within the public and the private sector. In vascular surgery, vertical prioritizing has been carried out and attempts have been made to extensively assess the effectiveness of therapy. We aim to provide a review of the current state of vascular surgery and the resulting health benefit by using the available rough effectiveness indicators, as a register for national quality assurance is lacking.

ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries--Tampere vascular study.

BACKGROUND AND AIMS: The expression of disintegrin and metalloprotease ADAM-9, ADAM-15, and ADAM-17 has been associated with cell-cell, cell-platelet, and cell-matrix interactions and inflammation. They are possibly implicated in the pathophysiology of atherosclerosis. METHODS AND RESULTS: Whole-genome expression array and quantitative real-time polymerase chain reaction (PCR) analysis confirmed that ADAM-9, ADAM-15, and ADAM-17 are upregulated in advanced human atherosclerotic lesions in samples from carotid, aortic, and femoral territories compared to samples from internal thoracic artery (ITA) free of atherosclerotic plaques. Western analysis indicated that the majority of these ADAMs were in the catalytically active form. ADAM-9, ADAM-15, and ADAM-17-expressing cells were shown to co-localize with CD68-positive cells of monocytic origin in the atherosclerotic plaques using immunohistochemistry and double-staining immunofluorescence analysis. Co-localization was demonstrated in all vascular territories. In the carotid territory, cells expressing the ADAMs co-distributed also with smooth muscle cells and, in femoral territory, with CD31-positive endothelial cells, indicating that the ADAM expression pattern depends on vascular bed territory. CONCLUSIONS: Present findings provide strong evidence for the involvement of catalytically active ADAM-9, ADAM-15, and ADAM-17 in advanced atherosclerosis, most notably associated with cells of monocytic origin.

Risk-scoring method for prediction of 30-day postoperative outcome after infrainguinal surgical revascularization for critical lower-limb ischemia: a Finnvasc registry study.

BACKGROUND: The aim of the present study was to develop a risk-scoring method for prediction of immediate postoperative outcome after infrainguinal surgical revascularization for critical limb ischemia. METHODS: The Finnvasc registry included data on 3,925 infrainguinal surgical revascularization procedures. This database was randomly divided into a derivation and a validation data set of similar sizes. RESULTS: In the overall series, 30-day postoperative mortality and major amputation rates were 3.1% and 6.3%, respectively. The 30-day postoperative mortality and/or limb-loss rate was 9.2%. Diabetes, coronary artery disease, foot gangrene, and urgent operation were independent predictors of 30-day postoperative mortality and/or major lower-limb amputation. A risk score was developed by assigning 1 point each to the latter risk factors. In the derivation data set, the 30-day postoperative mortality/amputation rates in patients with scores of 0, 1, 2, 3, and 4 were 7.7%, 6.4%, 11.1%, 20.4%, and 27.3%, respectively, (P < 0.0001); mortality rates were 1.3%, 2.3%, 4.1%, 7.7%, and 12.1%, respectively, (P < 0.0001); and major amputation rates were 6.4%, 4.3%, 7.1%, 12.7%, and 18.2%, respectively, (P < 0.0001). In the validation data set, the 30-day postoperative mortality/amputation rates in patients with scores of 0, 1, 2, 3, and 4 were 4.8%, 7.5%, 10.1%, 15.9%, and 22.2%, respectively, (P < 0.0001); mortality rates were 0.7%, 2.3%, 4.2%, 5.5%, and 14.8%, respectively, (P < 0.0001); and major amputation rates were 4.6%, 5.3%, 6.4%, 11.0%, and 14.0%, respectively (P = 0.011). CONCLUSIONS: This simple risk-scoring method can be useful to stratify the immediate postoperative outcome of patients undergoing infrainguinal surgical revascularization for critical lower-limb ischemia.

Nonoperative approach to endotension.

OBJECTIVE: The necessity of operative treatment of endotension after endovascular grafting of abdominal aortic aneurysms (endovascular aneurysm repair; EVAR) is under debate. The proposed causes of endotension and related treatment protocols are controversial. We report the outcome of a nonoperative approach to five patients with endotension after EVAR. METHODS: From February 1997 to August 2004, 160 patients who underwent EVAR of an infrarenal abdominal aortic aneurysm were evaluated for the incidence of endotension. According to the endovascular protocol, plain radiographs, spiral computed tomography, and angiography were performed before and after surgery for follow-up. To detect endotension, spiral computed tomography was performed by using a delayed imaging technique after the infusion of contrast medium. Endotension was defined as an aneurysm sac enlargement after EVAR without evidence of endoleak. Aneurysm sac rupture was defined as discontinuity of the calcific rim of the aneurysmal sac and the presence of intra-aneurysmal fluid outside the sac. RESULTS: We found five (3.1%) patients with endotension. Three of these experienced aneurysmal sac rupture. Only one of the three was underwent operation on experiencing sudden intestinal occlusion due to intra-abdominal adhesions. This patient had no intra-abdominal or retroperitoneal bleeding or hematoma but died after intensive care as a result of non-aneurysm-related problems. Four patients with endotension are still being closely followed up according to our surveillance protocol, and they are doing clinically well. After rupture, clear shrinking of the aneurysm sac was seen in two patients. CONCLUSIONS: Endotension after EVAR may cause subsequent aneurysm rupture. Endotension is evidently not associated with endoleak I to III provided that the endovascular graft is maintained in appropriate position and that free endovascular flow is observed. We propose to consider a nonoperative approach in the clinically asymptomatic patient with aneurysm enlargement after EVAR if endoleak is excluded by well-performed imaging techniques.

Does diabetes protect the femoral artery against atherosclerosis?

AIM: To compare the extent of angiographically detected stenoses in different segments of the lower leg arteries in diabetics and nondiabetics. METHODS: The study group consisted of 60 nondiabetic and 38 diabetic patients with lower extremity disease and no previous vascular interventions. Arterial lesions were analysed by digital subtraction angiography (DSA). The patients were evaluated by walking distance and ankle-brachial index (ABI) and the reason for hospitalization was recorded. RESULTS: Statistically significantly fewer stenoses were found in the superficial femoral artery in diabetics than in nondiabetics. Although a tendency to more diffuse changes in crural arteries was found, no statistically significant difference were found in other segments of the lower leg arteries apart from the femoral arteries. CONCLUSIONS: Judging from the present results there are fewer angiographically detectable stenoses in the superficial arteries in diabetics than nondiabetics.

Biodegradable self-expanding poly-L/D-lactic acid vascular stent: a pilot study in canine and porcine iliac arteries.

PURPOSE: To report results of an in vivo pilot study to evaluate the biocompatibility and delivery system of a new biodegradable vascular stent and validate the study design. METHODS: Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) and a medical stainless steel stent (Wallstent) were implanted in the common iliac arteries of 2 postpuberal female pigs and 3 laboratory-bred beagle dogs. Specimens were harvested after 45 days in the dogs and 32 days in the pigs for histomorphometry of the stented iliac artery segments. Preliminary measurements were made to assess the reliability of the quantitative histomorphometric measurements before final measurements. RESULTS: Histomorphometry analyses showed that mean luminal diameter and area were decreased in the PLA stent group (1.97+/-0.48 mm and 14+/-6.4 mm2, respectively) compared to the control stent group (4.28+/-0.83 mm and 61+/-19 mm2, respectively). The intimal thickness was higher in the PLA stent group (0.65+/-0.07 mm) than in the control group (0.44+/-0.21 mm). The mean injury score was 0.19+/-0.12 in the PLA stent group and 0.78+/-0.39 in the controls. In the PLA stent group, the mean inflammation score was 1.46+/-0.78 compared to 0.58+/-0.40 in the control group. There were no differences observed between the animal models. CONCLUSIONS: The PLA stent showed increased neointimal formation and reduced patency during early follow-up. Mechanical properties of the new biodegradable vascular stents are still inadequate, and the stent and the delivery device require modifications. The study methods were assessed as reliable and reproducible.

Diabetes as an independent risk factor for early postoperative complications in critical limb ischemia.

OBJECTIVE: The purpose of this study was to evaluate the significance of diabetes mellitus as a risk factor for postoperative major morbidity and mortality after surgery for critical lower limb ischemia (CLI). SUBJECTS: A national vascular registry (Finnvasc)-based survey included 5709 operations for CLI from 1991 through 1999. Of these operations, 2508 (44%) were performed on diabetics. Tissue loss was the indication for surgery in 77% of diabetics and in 52% of nondiabetics. The proportion of femorodistal bypasses was 43% in diabetics and 24% in nondiabetics, whereas the proportion of reconstructions for aortofemoral arterial occlusive disease was 16% in diabetics and 34% in nondiabetics. RESULTS: Thirty-day mortality was 4.5% in diabetics and 3.4% in nondiabetics ( P = .05). The rate for early below-knee amputation was 6.5% in diabetics and 3.3% in nondiabetics ( P < .001). Independent factors for postoperative death were aortofemoral reconstruction (odds ratio [OR], 4.0), preoperative cardiac risk factor (OR, 3.1), primary surgery (OR, 2.0), renal insufficiency (OR, 1.9), urgent surgery (OR, 1.7), and age (OR, 1.3). Diabetes was an independent risk factor for postoperative below-knee amputation (OR, 1.7), cardiac complications (OR, 1.5), and superficial wound infection (OR, 1.3). There was an inverse association between diabetes and acute graft occlusion (OR, 0.8). Independent risk factors for early postoperative mortality in diabetes were aortofemoral reconstruction (OR, 2.5), urgent surgery (OR, 2.0), male gender (OR, 2.0), renal insufficiency (OR, 1.9), cardiac risk factor (OR, 1.7), and age (OR, 1.4). In nondiabetics independent risk factors for early postoperative mortality were aortofemoral reconstruction (OR, 4.5), cardiac risk factor (OR, 3.6), primary surgery (OR, 2.6), and extra-anatomic bypass (OR, 2.3). CONCLUSIONS: Diabetes was not an independent risk factor for early postoperative mortality in CLI as there was an increased morbidity in diabetics associated with old age, male gender, known coronary artery disease, and renal insufficiency, as well as urgent surgery. As diabetics have increased proclivity for these factors, special attention needs to be paid to their preoperative assessments.

Requirements for quantitative analysis of intimal reaction in arteries treated with intraluminal stents.

PURPOSE: To assess the reliability of quantitative histomorphometry measurements for the intimal reaction that occurs after intraluminal stenting in an animal model. METHODS: Two self-expanding intravascular stents, a biodegradable poly-D/L-lactic acid (PLA) stent and a stainless steel Wallstent, were implanted in the common iliac arteries of a beagle dog. After 45 days, the histomorphometry of the stented iliac artery segments was quantitatively measured. The relative standard error (RSE) of the estimate was calculated, and the reliability of measurements for maximal (LDmax) and minimal (LDmin) luminal diameters and internal (IELT) and external (EELT) elastic lamina thicknesses was assessed. RESULTS: The PLA stent required more measurements of variables from a single slide to ensure reliable (RSE<10%) results (1 for LDmax, 1 for LDmin, 8 for IELT, and 4 for EELT) compared to the Wallstent (1 for LDmax, 1 for LDmin, 2 for IELT, and 2 for EELT 2). The measured results were reliable for both stent materials when variables were measured from 2 slides of each segment (proximal/central/distal) of the stent. CONCLUSIONS: We conclude that these preliminary measurements to estimate the reliability of quantitative histomorphometry measurements should be made and reported before final results are given.

Postthrombotic syndrome after isolated calf deep venous thrombosis: the role of popliteal reflux.

OBJECTIVE: The purpose of this study was to evaluate the long-term clinical and hemodynamic outcomes after isolated first-time calf deep venous thrombosis (cDVT). METHODS: This retrospective clinical study was set in an academic referral center. From 1990 to 1994, 617 patients were seen with acute DVT. This number included 82 patients with phlebographically confirmed cDVT. Of those patients, 50 attended the clinical assessment 6 to 10 years (mean, 8.4 years) after the acute event. All patients with cDVT underwent treatment with anticoagulant therapy (96% heparin and warfarin, 4% only warfarin). The duration of the heparin treatment was 4.0 to 8.0 days (mean, 6.4 days), and warfarin was given for 2.0 to 7.5 months (mean, 3.4 months). Compression stockings were used regularly (mean, 9.2 months; range, 0.25 to 64 months) in 30% of the patients after acute cDVT. The initial ipsilateral phlebograms were reevaluated to confirm the diagnosis of cDVT without popliteal involvement. The clinical assessment included evaluation of both legs according to CEAP clinical classification C0-6. Bilateral color-flow duplex scan imaging was performed to assess reflux in deep popliteal segments. Photoplethysmographic measurement of venous refilling time was conducted in both legs to observe deep reflux. RESULTS: The mean age was 57 years (range, 30 to 76 years) at the time of the clinical assessment. Cause of acute cDVT was idiopathy in 52%, coagulopathy in 2%, trauma in 10%, immobilization in 22%, and postoperative in 14% of the cases. During the follow-up period, seven recurrent DVTs (14%) were seen. In the clinical assessment, 17 legs (34%) with previous cDVT had skin changes (CEAP C4-6). No active ulcers were found. Contralaterally, the frequency of C4-6 was 10% (n = 5; P <.05). After exclusion of recurrent DVTs, the distribution of the clinical classification still remained the same. Deep popliteal reflux was detected in 20 legs (40%) with previous cDVT. Contralaterally, popliteal reflux was seen in nine cases (18%; P <.05). Plethysmography showed deep reflux in 16 legs (33%) with cDVT and in nine cases (18%) contralaterally (P >.05). A significant association was found between deep popliteal reflux and skin changes (P <.05). CONCLUSION: In the long-term follow-up, cDVT may lead to significant postthrombotic disease. Reflux in the primarily uninvolved popliteal vein is frequent and may be associated with more severe disease.

Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial.

OBJECTIVE: The objective of this study was to evaluate the safety and tolerance of increasing single and repeated (n = 2) doses of intramuscular naked plasmid DNA encoding for fibroblast growth factor (FGF) type 1 (NV1FGF) administered to patients with unreconstructible end-stage peripheral arterial occlusive disease (PAD). The secondary objectives were to determine the biologic activity of NV1FGF on hemodynamic and clinical parameters associated with improved perfusion. METHODS: Fifty-one patients with unreconstructible peripheral arterial occlusive disease with rest pain or tissue necrosis underwent treatment with intramuscular NV1FGF. Increasing single (500, 1000, 2000, 4000, 8000, and 16,000 microg) and repeated (2 x 500, 2 x 1000, 2 x 2000, 2 x 4000, and 2 x 8000 microg) doses of NV1FGF were injected into the ischemic thigh and calf. Arteriography was performed before treatment and was repeated 12 weeks after treatment. Side effects and serious adverse events were monitored. Measurements of plasma and urine levels were performed to evaluate NV1FGF plasmid distribution. Serum FGF-1 was measured as an analysis of gene expression at the protein level. Transcutaneous oxygen pressure, ankle brachial index, toe brachial index, pain assessment with visual analog scale, and ulcer healing also were assessed. The safety results are presented for 51 patients, and the clinical outcomes are presented for the first 15 patients (500 to 4000 microg) who completed the 6-month follow-up study. RESULTS: NV1FGF was well tolerated. Sixty-six serious adverse events were reported; however, none were considered to be related to NV1FGF. Four patients had adverse events that were possibly or probably related to the study treatment: injection site pain, pain, peripheral edema, myasthenia, and paresthesia. No laboratory adverse events were related to the study treatment. Two deaths remote from the treatment were considered not related. Biodistribution of plasmid was limited and transient in plasma and absent in urine. No increase in the FGF-1 serum level was detected. A significant reduction in pain (P <.001) and aggregate ulcer size (P <.01) was associated with an increased transcutaneous oxygen pressure (P <.01) as compared with baseline pretreatment values. A significant increase in ankle brachial index (P <.01) was seen. CONCLUSION: NV1FGF is well tolerated and potentially could be effective for the treatment of patients with end-stage limb ischemia. Biologic parameters indicate improved perfusion after NV1FGF administration. Dose response is not yet evident. The safety of NV1FGF and the magnitude of improvement observed in this study encourage further investigation with a placebo-controlled, double-blind clinical trial.