James M. Seeger

Patency of autogenous and polytetrafluoroethylene upper extremity arteriovenous hemodialysis accesses: a systematic review

OBJECTIVE Patency rates for autogenous accesses are presumed to be better than for polytetrafluoroethylene (PTFE) accesses, although the strength of the supporting evidence is limited. We undertook this study to test the hypothesis that patency rates for upper extremity autogenous hemodialysis arteriovenous accesses in adults are superior to those for PTFE counterparts. METHODS A systematic review of relevant literature and meta-analysis of the patency data were performed. Studies were considered acceptable if patency data were reported by either life table or Kaplan-Meier method, including number of patients at risk. RESULTS The thirty-four studies that satisfied the inclusion criteria were composed predominantly of case series or nonrandomized controlled studies; no randomized, controlled studies comparing autogenous and PTFE accesses were included. The primary patency rate for autogenous accesses was 72% (95% confidence interval [CI], 70%-74%) at 6 months and 51% (95% CI, 48%-53%) at 18 months, and the corresponding primary patency rate for PTFE accesses was 58% (95% CI, 56%-61%) and 33% (95% CI, 31%-36%), respectively. The secondary patency rate for autogenous accesses was 86% (95% CI, 84%-88%) at 6 months and 77% (95% CI, 74%-79%) at 18 months, and the corresponding secondary patency rate for PTFE accesses was 76% (95% CI, 73%-79%) and 55% (95% CI, 51%-59%), respectively. CONCLUSIONS The patency rate for autogenous upper extremity arteriovenous hemodialysis accesses in adults is superior to that for PTFE counterparts, although the overall quality of the studies in the meta-analysis was less than ideal. Randomized, controlled studies to further examine the differences in outcome between these two access types are necessary.

Direct Evidence for Cytokine Involvement in Neointimal Hyperplasia

BackgroundTumor necrosis factor-&agr; (TNF-&agr;) and interleukin 1 (IL-1) are proximal inflammatory cytokines that stimulate expression of adhesion molecules and induce synthesis of other proinflammatory cytokines. In addition, TNF-&agr; and IL-1 influence vascular smooth muscle cell migration and proliferation in vitro. In view of the inflammatory nature of neointimal hyperplasia (NIH), we tested the hypothesis that endogenous TNF-&agr; and IL-1 modulate low shear stress–induced NIH. Methods and ResultsMice underwent unilateral common carotid artery (CCA) ligation. Low shear stress in the patent ligated CCA has previously been shown to result in remodeling and NIH. Reverse transcriptase–polymerase chain reaction for TNF-&agr; and IL-1&agr; mRNA demonstrated both TNF-&agr; and IL-1&agr; mRNA in ligated CCAs, whereas normal and sham-operated CCAs had none. Mice lacking functional TNF-&agr; (TNF−/−) developed 14-fold less neointimal area than WT controls (P <0.05). p80 IL-1 type I receptor knockout (IL-1RI−/−) mice tended to develop less (7-fold, P >0.05) neointimal area than WT controls. Furthermore, no IL-1&agr; mRNA expression was detected in CCAs from TNF−/− mice; however, TNF-&agr; mRNA expression was found in the IL-1RI−/− mice. Mice that overexpress membrane-bound TNF-&agr; but produce no soluble TNF-&agr; display an accentuated fibroproliferative response to low shear stress (P <0.05). ConclusionsThese results directly demonstrate that TNF-&agr; and IL-1 modulate NIH induced by low shear stress. NIH can proceed by way of soluble TNF-&agr;–independent mechanisms. Specific anti–TNF-&agr; and anti–IL-1 therapies may lessen NIH.

Laser angioplasty with angioscopic guidance in humans

An experimental study was conducted in 11 patients to evaluate the immediate effects of laser recanalization during peripheral arterial bypass surgery. Angioscopy allowed precise localization and identification of the occlusion. A 1 or 2 mm optical fiber probe was used. Laser energy was regulated using the least amount of energy necessary for recanalization. New vascular channels were made in 10 of the 11 patients. After recanalization the arterial segment was excised for histologic evaluation. Smaller channel diameters were made with the 1 mm probe (1.5 +/- 0.6 mm) than with the 2 mm probe (3 +/- 0.3 mm) (p less than 0.05). Flow through channels (mean pressure 80 mm Hg) made with the 2 mm probe was greater than that through channels made with the 1 mm probe (150 +/- 102 versus 19.7 +/- 10 cc/min) (p less than 0.05). The amount of debris formed was small with both probes. Vascular perforations were less frequent with the 2 mm probe (two of nine arteries) compared with the 1 mm probe (four of four arteries). Successful recanalization with flow rates expected to maintain vascular patency was achieved only with the 2 mm probe. Histologic studies at nonperforated sites demonstrated that the elastica of the artery appeared to be preserved whereas the overlying plaque and underlying media were thermally disrupted. This suggests that the elastic tissue acts as an optical window allowing the argon beam to go through it without causing morphologic damage. Except for fresh thrombus, atheromas including calcific plaque and old organized thrombus were readily vaporized. These results are encouraging for the use of the laser for vascular recanalization in humans.

Warfarin improves the outcome of infrainguinal vein bypass grafting at high risk for failure

OBJECTIVE Patients with marginal venous conduit, poor arterial runoff, and prior failed bypass grafts are at high risk for infrainguinal graft occlusion and limb loss. We sought to evaluate the effects of anticoagulation therapy after autogenous vein infrainguinal revascularization on duration of patency, limb salvage rates, and complication rates in this subset of patients. METHODS This randomized prospective trial was performed in a university tertiary care hospital and in a Veterans Affairs Hospital. Fifty-six patients who were at high risk for graft failure were randomized to receive aspirin (24 patients, 27 bypass grafts) or aspirin and warfarin (WAR; 32 patients, 37 bypass grafts). All patients received 325 mg of aspirin each day, and the patients who were randomized to warfarin underwent anticoagulation therapy with heparin immediately after surgery and then were started on warfarin therapy to maintain an international normalized ratio between 2 and 3. Perioperative blood transfusions and complications were compared with the Student t test or with the chi2 test. Graft patency rates, limb salvage rates, and survival rates were compared with the Kaplan-Meier method and the log-rank test. RESULTS Sixty-one of the 64 bypass grafts were performed for rest pain or tissue loss, and 3 were performed for short-distance claudication. There were no differences between the groups in ages, indications, bypass graft types, risk classifications (ie, conduit, runoff, or graft failure), or comorbid conditions (except diabetes mellitus). The cumulative 5-year survival rate was similar between the groups. The incidence rate of postoperative hematoma (32% vs 3.7%; P = .004) was greater in the WAR group, but no differences were seen between the WAR group and the aspirin group in the number of packed red blood cells transfused, in the incidence rate of overall nonhemorrhagic wound complications, or in the overall complication rate (62% vs 52%). The immediate postoperative primary graft patency rates (97.3% vs 85.2%) and limb salvage rates (100% vs 88.9%) were higher in the WAR group as compared with the aspirin group. Furthermore, the cumulative 3-year primary, primary assisted, and secondary patency rates were significantly greater in the WAR group versus the aspirin group (74% vs 51%, P = .04; 77% vs 56%, P = .05; 81% vs 56%, P = .02) and cumulative limb salvage rates were higher in the WAR group (81% vs 31%, P = .01). CONCLUSIONS Perioperative anticoagulation therapy with heparin increases the incidence rate of wound hematomas, but long-term anticoagulation therapy with warfarin improves the patency rate of autogenous vein infrainguinal bypass grafts and the limb salvage rate for patients at high risk for graft failure.

Risk factors for perioperative stroke during thoracic endovascular aortic repairs (TEVAR).

PURPOSE To determine the clinical and anatomical risk factors for cerebrovascular accidents (CVA) in patients undergoing thoracic endovascular aortic repair (TEVAR). METHODS Between September 2000 and December 2006, 196 patients (135 men; mean age 68.6+/-13.5 years, range 17-92) underwent TEVAR for a variety of aortic pathologies. The majority (156, 79.6%) were treated with the TAG stent-graft. Demographics, pathologies, intraoperative procedure-related measures, device usage, and postoperative outcomes were assessed. CVA was defined as a new focal or global neurological (motor or sensory) deficit lasting >48 hours associated with acute intracranial abnormalities on computed tomography or magnetic resonance brain imaging. Spinal cord ischemia was excluded. In a subset of patients with planned left subclavian artery (LSA) coverage and an incomplete circle of Willis or a dominant left vertebral artery, prophylactic carotid-subclavian bypasses were performed. RESULTS Nine (4.6%) patients suffered a CVA. Factors not predictive of a CVA on univariate analysis included aortic pathology, urgency of repair, ASA classification, type of anesthesia, blood loss, procedure time, and device used. Proximal extent of repair (with or without extra-anatomical revascularization) was significantly associated with a higher incidence of strokes (zones 0-2 versus 3-4, p=0.025). Five (55.6%) patients with a CVA had documented intraoperative hypotension (systolic blood pressure<80 mmHg). Additionally, while 2 patients had hemispheric infarcts, 5 had acute posterior circulation infarcts involving the cerebellum and brainstem; a single patient had both anterior and posterior circulation infarcts. Seven of the CVA patients had proximal coverage of the thoracic aorta in zones 0-2; of these, 6 had posterior circulation infarcts. Selective LSA revascularization based on preoperative cerebrovascular imaging resulted in lower rates of CVA (6.4% to 2.3%, p=0.30) and posterior circulation infarcts (5.5% to 1.2%, p=0.13). CONCLUSION Proximal extent of repair may serve as a surrogate marker for greater severity of degenerative disease of the aortic arch. Avoidance of intraoperative hypotension and preservation of antegrade vertebral perfusion may be important in prevention of posterior circulation strokes.

The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair.

ObjectivesPlasma proinflammatory, anti-inflammatory cytokine, and soluble tumor necrosis factor (TNF) receptor concentrations were examined in hospitalized patients after abdominal and thoracoabdominal aortic aneurysm (TAAA) repair, with and without left atrial femoral bypass. Changes in plasma cytokine concentrations were related to the duration of visceral ischemia and the frequency rate of postoperative, single, or multiple system organ dysfunction (MSOD). DesignProspective, observational study. SettingTwo academic referral centers in the United States and The Netherlands. PatientsWe included 16 patients undergoing TAAA repair without left atrial femoral bypass, 12 patients undergoing TAAA repair with left atrial femoral bypass, and nine patients undergoing infrarenal aortic aneurysm repair. Measurements and Main ResultsTimed, arterial blood sampling for proinflammatory and anti-inflammatory cytokine and soluble TNF receptor concentrations (p55 and p75), and prospective assessment of postoperative single and MSOD. Plasma appearance of TNF-&agr;, interleukin (IL)-6, IL-8, and IL-10 peaked 1 to 4 hrs after TAAA repair, and concentrations were significantly elevated compared with infrarenal abdominal aortic aneurysm repair (p < .05). Left atrial femoral bypass significantly reduced the duration of visceral ischemia (p < .05) and the systemic TNF-&agr;, p75, and IL-10 responses (p < .05). Plasma TNF-&agr; concentrations >150 pg/mL were more common in patients with extended visceral ischemia times (>40 mins). Additionally, patients with early peak TNF-&agr; concentrations >150 pg/mL and IL-6 levels >1,000 pg/mL developed MSOD more frequently than patients without these elevated plasma cytokine levels (both p < .05). ConclusionsThoracoabdominal aortic aneurysm repair results in the increased plasma appearance of TNF-&agr;, IL-6, IL-8, IL-10, and shed TNF receptors. The frequency and magnitude of postoperative organ dysfunction after TAAA repair is associated with an increased concentration of the cytokines, TNF-&agr;, and IL-6 and the increased plasma levels of these cytokines appear to require extended visceral ischemia times.

Improved endothelial cell seeding with cultured cells and fibronectin-coated grafts

A possible approach to the low seeding efficiency of endothelial cells into prosthetic grafts is to increase the number of cells to be seeded in cell culture and improve seeding efficiency by graft precoating with fibronectin. The effect of cell culture on cell adhesion is unknown, however, and fibronectin also binds fibrin, which may increase the thrombogenicity of the graft luminal surface. To investigate these questions, freshly harvested canine jugular vein endothelial cells from six animals and similar cells harvested from six primary and eight secondary cell cultures were labeled with 111Indium and seeded into 5 cm, 4 mm PTFE grafts coated with fibronectin, using similar uncoated PTFE grafts as controls. Platelet accumulation and distribution on six similar coated and uncoated grafts placed in canine carotid, external jugular arterial venous shunts for 2 hr were also determined using autogenous 111Indium-labeled platelets. Significant differences between group means were determined using the paired Students t test. Results reveal that seeding efficiency is significantly better in all groups of coated grafts compared to uncoated grafts (P less than 0.01). Cells derived from cell culture also had significantly higher seeding efficiencies than freshly harvested cells when seeded into coated grafts (P less than 0.05) and tended to have higher seeding efficiencies than harvested cells when seeded into uncoated grafts (P = 0.53). Fibronectin coating increased mean platelet accumulation on the entire graft luminal surface, but not to a statistically significant degree (P greater than 0.1). Whether this increased seeding efficiency will improve graft endothelialization remains to be investigated.

Operative mortality rates after elective infrarenal aortic reconstructions.

PURPOSE This study was designed to test the hypothesis that cardiac complications (myocardial infarction, congestive heart failure, fatal arrhythmias) are no longer the leading cause of death after elective aortic reconstructions. METHODS The medical records of all elective infrarenal aortic reconstructions performed between January 1982 and June 1994 were retrospectively reviewed. All perioperative deaths were analyzed to determine the cause of death and were compared with a subset of 266 survivors to identify any associated preoperative or intraoperative factors. RESULTS Seven hundred twenty-two aortic reconstructions were performed for aneurysmal or occlusive disease, and there were 44 deaths (overall mortality rate of 6.1%). The mortality rate after aortic reconstruction alone was 4.9% and increased with the addition of renal (8.9%, p = 0.16) or lower extremity vascular procedures (15.8%, p = 0.01). Multisystem organ failure (MSOF) was the cause of death in 56.8%, of the patients (3.5% overall mortality rate) followed by cardiac events in 25% (1.5% overall mortality rate). Visceral organ dysfunction was the most common cause of MSOF leading to death in 14 patients (56.0%), and postoperative pneumonia was responsible for the fatal MSOF in nine patients (36.0%). Patient age, history of myocardial infarction/congestive heart failure, ejection fraction less than 50%, duration of operative time, and performance of additional procedures were associated with increased operative mortality rates by multivariate analysis. CONCLUSIONS MSOF, predominantly from visceral organ dysfunction, was the leading cause of death after elective infrarenal aortic reconstruction. The risk of MSOF and operative death increases with the complexity of the procedure and the number of comorbid conditions.

Improved in vivo endothelialization of prosthetic grafts by surface modification with fibronectin

Endothelial cell growth in vitro is enhanced by coating with fibronectin the surface on which cells grow. Similar coating of prosthetic arterial grafts may promote in vivo graft endothelialization if graft patency is not adversely affected. In each of 15 dogs, two fibronectin-coated polytetrafluoroethylene grafts and two grafts that were not coated were implanted. One graft in each pair was seeded with autologous endothelial cells, so that four different grafts were studied in each animal: a coated, seeded graft; a coated graft that was not seeded; a seeded graft that was not coated; a graft that was neither coated nor seeded. At 2, 4, and 8 weeks, grafts from five animals were examined for patency, surface endothelialization, and indium 111 platelet reactivity. After seeding, surface coverage by endothelium of coated grafts was more complete and more rapid than in uncoated grafts (64% +/- 23% vs 31% +/- 13% at 4 weeks, p less than 0.05). Without seeding, coated grafts also appeared to have increased endothelial cell ingrowth compared with plain grafts (48.8% +/- 15.1% vs 37.6% +/- 1.5% at 8 weeks). Early (2-week) platelet reactivity of coated grafts was increased (p = 0.06), but patency was not adversely affected. Thus fibronectin coating of prosthetic grafts promotes surface endothelialization in vivo without altering graft patency.

Potential predictors of outcome in patients with tissue loss who undergo infrainguinal vein bypass grafting

PURPOSE Aggressive attempts at limb salvage in patients with ischemic tissue loss are justified by favorable initial results in most patients. The identification of patients whose conditions will not benefit from attempted revascularization remains difficult. METHODS This study was designed as a retrospective review of prospectively collected clinical data. The subjects were 210 consecutive patients who underwent infrainguinal vein bypass grafting for ischemic tissue loss in the setting of an academic medical center. Bypass grafting was to the popliteal artery in 56 patients, to the infrapopliteal arteries in 131 patients, and to the pedal arteries in 23 patients. The follow-up examination was complete in 209 of 210 patients. One hundred twenty-five patients underwent blinded review of duplex scan venous mapping and arteriography to determine simplified vein and run-off scores. The outcome measures were the influence of risk factors, venous conduit, and runoff on mortality, limb loss, and graft failure at the 6-month follow-up examination. RESULTS One hundred seventy patients (81%) were alive and had limb salvage. Nineteen patients (9.1%) died, with need for a simultaneous inflow procedure and end-stage renal disease being most commonly associated with mortality. Thirty-three patients (15.8%) had undergone amputation: 18 after graft failure, and 15 for progressive tissue loss despite a patent graft. Amputation was significantly more common in patients with diabetes (P =.05) and with poor runoff scores (poor runoff, 44.4% vs good runoff, 7.4%; P <.01). Amputation despite a patent graft also correlated with runoff (poor runoff, 41.7% vs good runoff, 4.3%; P <.01). Twenty-five patients had graft failure without amputation, so that only 145 patients (69.4%) were alive, had limb salvage, and had a patent graft. Run-off score was the strongest predictor of outcome, with 70% of patients with poor run-off scores having death, amputation, or graft failure. CONCLUSION Aggressive use of infrainguinal vein bypass grafting in patients with ischemic tissue loss results in a high rate of initial limb salvage but significant morbidity and mortality. Arteriographically determined runoff scores appear to potentially identify patients at high risk for a poor initial outcome and may provide a method of selecting patients for primary amputation.