What is the clinical utility of a 6-month computed tomography in the follow-up of endovascular aneurysm repair patients?

OBJECTIVE: A drawback of endovascular aneurysm repair (EVAR) is the need for ongoing surveillance. Follow-up schedules including 1-, 6-, and 12-month computed tomography (CT) established by regulatory trials have been carried into clinical practice without critical assessment. The utility of a 6-month CT, with its associated radiation exposure and contrast toxicity, obtained after a normal result at 1-month CT has not been established. METHODS: All EVAR patients from 1996 to 2004 at one institution with complete local 1-year follow-up were reviewed for clinically significant CT findings at 1, 6, and 12 months. Before 2000, all patients underwent 1-, 6-, and 12-month CT. In 2000, a policy of omitting the 6-month CT in patients who had a normal result on the 1-month scan was adopted. RESULTS: During the study period, 573 patients underwent EVAR, and 376 patients who had complete local 1-year follow-up were included in this review. All had a 1-month CT scan and the result was abnormal in 40 (10.6%): five had type 1 leaks (1.3%), 34 had type 2 leaks (9.0%), and one had a type 3 leak (0.3%); all were followed with 6-month CT. The 1-month CT scan result was normal for 336 (89.4%) patients. Of these, group I (130 patients, 67 treated after 2000) underwent routine 6-month CT, with only two abnormalities noted (1.5%); both were type 2 endoleaks not associated with sac growth. No 6-month CT in this group demonstrated findings warranting intervention. The 6-month CT was omitted in group II (206 patients, all treated after 2000), and follow-up was only at 1 year. In this group, no patient's management would have been altered by findings on a 6-month CT. No patient in either group experienced aneurysm sac growth by 1 year. Clinical complications occurred in three group I patients (2.3%): seroma, limb occlusion, and main body thrombosis. Only one group II patient (0.5%) experienced a complication

Treatment of asymptomatic carotid disease with stenting: pro.

The assumptions upon which the decisions to treat asymptomatic patients are founded on landmark studies, such as the Asymptomatic Carotid Atherosclerotic Study (ACAS), the Veterans Affairs Cooperative Study (VA), and the Asymptomatic Carotid Surgical Trial (ACST). In total, these trials randomized more than 5,000 patients to surgical vs. medical therapy. These trials were based on 60% stenosis and basically "no-risk" entry criteria. The carotid stent trials and registries, however, were based on 80% stenosis and all high-risk entry criteria. With a wide range of operator experience, and patient enrollment based on surgical risk criteria, Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events II (CAPTURE) II, Emboshield and Xact Post Approval Carotid Stent Trial (EXACT), and the Carotid Artery Revascularization Using the Boston Scientific EPI FilterWire EX/EZ and the EndoTex NexStent (CABERNET) trials were able to meet the American Heart Association guidelines of 3% procedural events in the asymptomatic subset. Carotid stenting is presently in the first and second generation of devices, and as the technology improves, procedural event rates should also improve. An understanding of the plaque composition and presence or absence of plaque vulnerability will separate those patients best suited for stenting versus endarterectomy. Asymptomatic patients cannot be grouped, but rather require individualization. Those patients with anatomical risks, preocclusive stenosis, and an incomplete Circle of Willis with a poorly collateralized hemisphere, are best managed with stenting versus endarterectomy or best medical management. Those patients, however, with

Isolated iliac artery aneurysms: a contemporary comparison of endovascular and open repair.

OBJECTIVE: Iliac artery aneurysms are rare but associated with significant morbidity and mortality when ruptured. This study compares recent open and endovascular repairs of iliac aneurysms at a single institution. METHODS: Patients were identified and charts reviewed using ICD-9 and CPT codes for iliac artery aneurysm and open or endovascular repair performed between January 2000 and January 2006. Baseline characteristics, procedure-related variables, and follow-up data were retrospectively reviewed. RESULTS: A total of 71 patients were treated with isolated iliac artery aneurysms. There were 19 open and 52 endovascular repairs. Seven presented with acute ruptures and were treated by open (4) or endovascular (3) repair. Preoperative comorbidities were similar between the two groups. Major perioperative (30 day) complications included three deaths in the open group from cardiovascular complications, all after ruptured aneurysm repair, and one death in the endovascular group (after rupture; one additional perioperative death occurred after 30 days due to colonic infarction) (P = NS). Postoperative complications were less frequent in the endovascular group, although this did not reach statistical significance. The mortality was 50% in the open group and 33% in the endovascular group for patients presenting with a ruptured aneurysm (P = NS). Transfusion requirement was significantly higher in the open group (47%) than in the endovascular group (6%) (P = .03). The mean follow-up was 20 +/- 5 months in the open group and 17 +/- 2 months in the endovascular group (P = NS). Long-term complications included two limb thromboses following repair with a bifurcated stent graft that were treated with thrombolysis plus stenting or a fem-fem bypass. Three endoleaks were identified on postop CT scans, all of which were successfully managed with endovascular techniques. There were no postoperative ruptures or aneurysm-related death. The mean postoperative length of stay was 5.2 +/- 2.3 days (open) and 1.3 +/- 1.0 days (endovascular) (P = .04). CONCLUSIONS: This is the first large, case control study comparing open vs endovascular repair of isolated iliac artery aneurysms. Endovascular repair of iliac artery aneurysms is safe and results in decreased length of stay, lower requirement for perioperative blood transfusion, and similar intermediate term outcomes as open repair.

A randomized trial of carotid artery stenting with and without cerebral protection.

BACKGROUND: The use of a distal filter cerebral protection device with carotid artery stenting is commonplace. There is little evidence, however, that filters are effective in preventing embolic lesions. This study examined the incidence of embolic phenomenon during carotid artery stenting with and without filter use. METHODS: This was a prospective, randomized, single-center study of carotid artery stenting with or without a distal cerebral protection filter. A 1:1 scheme was used to randomize 36 carotid artery stenting procedures in 35 patients. Diffusion-weighted magnetic resonance imaging (DW MRI) 24 hours after stenting was used to assess the occurrence of new embolic lesions. Blinded observers calculated lesion number and volume. RESULTS: The mean age was 78.6 +/- 7.0 in the cerebral protection group compared with 74.1 +/- 8.7 in the no cerebral protection group (P = .92). Despite similar average age, the percentage of octogenarians was higher in the cerebral protection group (61.1% vs 22.2%; P = .04). Two procedures in the cerebral protection group were not successful. One was completed without protection because of inability to track the filter, and the second was aborted because of severe tortuosity with a later carotid endarterectomy. New MRI lesions were noted in 72% of the cerebral protection group compared with 44% in the no cerebral protection group (P = .09). The average number of lesions in these patients was 6.1 and 6.2, respectively, with mean DW MRI lesion size of 16.63 mm(3) vs 15.61 mm(3) (P = .79 and .49, respectively). Four strokes occurred (11%), two in each group, in patients aged 75, 80, 82, and 84 years. The only major stroke occurred in the no cerebral protection group. CONCLUSIONS: The use of filters during carotid artery stenting provided no demonstrable reduction of microemboli, as expected. Routine use of cerebral protection filters should undergo a more critical assessment before mandatory universal adoption.

Use of AngioJet mechanical thrombectomy for acute peripheral ischemia associated with stent fracture.

Stent fracture has been an uncommonly described etiology in the development of acute peripheral ischemia. We describe the utilization of a rheolytic thrombectomy catheter with thrombolytics for the rapid treatment of superficial femoral artery thrombosis after recanalization and subsequent stent fracture. The implications of stent fracture and the therapeutic maneuvers associated with their treatment in peripheral applications are discussed.

Thoracic endovascular aortic repair for traumatic aortic transection.

BACKGROUND: Traumatic transection of the thoracic aorta is a highly morbid injury. Treatment may be delayed while attention focuses on concomitant injuries. Thoracic endovascular aortic repair (TEVAR) is effective but remains controversial in these often-young patients. We reviewed our experience in acute and subacute treatment of these injuries with TEVAR. METHODS: A retrospective analysis of five men and five women who underwent TEVAR for aortic transection from 1999 to 2007 was conducted. Procedures were performed with standard endovascular techniques. Follow-up included computed tomography at 1 month and yearly thereafter. RESULTS: Mean age was 44 years (range, 20 to 84 years). Motor vehicle accidents accounted for 7 injuries, a snowmobile accident for 1, skydiving for 1, and balloon angioplasty of a coarctation for 1. Average diameter of the proximal landing zone was 25 mm (range, 23 to 29 mm). Mean external iliac size was 10 mm (range, 7 to 15 mm), and no conduits were required. Immediate technical success was 90%, with no 30-day mortality. Seven patients underwent repair acutely (< or =24 hours) and three patients subacutely (range, 4 days to 2 months) for pseudoaneurysm. Four patients had procedures for concomitant injuries before their transection was repaired (3 laparotomies and a fixation for open fracture). One endoleak was noted, which resolved by the 1-month follow-up. The lone device-related complication was an endograft collapse at 5 months managed by repeat endografting, which was complicated by aortoesophageal fistula requiring esophagectomy and open reconstruction. No iliac injuries occurred. At 20-months of mean follow-up (range, 2 to 70 months), all patients are alive and well. CONCLUSIONS: TEVAR for traumatic aortic transection is feasible, with good initial success. Repair can be delayed in selected cases. Continued surveillance is necessary to ensure good long-term outcomes in these young patients. Care must be taken when performing TEVAR for this off-label indication because these devices are designed for the larger aortic diameters of aneurysm patients.

Contemporary results of open repair of ruptured descending thoracic and thoracoabdominal aortic aneurysms.

OBJECTIVE: The purpose of this study was to evaluate the results of open repair for ruptured descending thoracic and thoracoabdominal aortic aneurysm (RDTAA). METHODS: A retrospective review identified 41 consecutive cases of open surgical repair in 40 patients presenting with nontraumatic, atherosclerotic RDTAA from 1996 to 2006. Patients with traumatic injuries or complicated dissections were excluded. Patient characteristics and preoperative, intraoperative, and postoperative variables were collected from the medical record. Univariate and logistic regression were used to identify factors contributing to mortality and morbidity in these patients. RESULTS: The operative mortality rate was 26.8% (11/41). All but two deaths occurred within 24 hours of operation; seven were intraoperative. Overall actuarial survival rates at 1 and 2 years were 53.7% and 47.1%, respectively. For those who survived to hospital discharge, the respective numbers were 73.3% and 64.4%. Intraoperative hypotension and blood transfusion requirements were independent predictors of perioperative death. Octogenarians had a mortality rate equivalent to that of the younger population (25% vs 27.6%; not significant). There was a strong trend toward an improved outcome in the latter part (2003-2006) compared with the first part (1995-2002; 13.6% vs 42.1%, respectively; P = .075). CONCLUSIONS: Direct open repair for RDTAA can be achieved with acceptable mortality and morbidity rates even in elderly patients. Improved outcome can be expected with increased volume and experience. This series should help establish a reference against which the results of endovascular endeavors and hybrid procedures could be compared.

Nitric oxide-induced inhibition of smooth muscle cell proliferation involves S-nitrosation and inactivation of RhoA.

Nitric oxide (NO) acts as a vasoregulatory molecule that inhibits vascular smooth muscle cell (SMC) proliferation. Studies have illustrated that NO inhibits SMC proliferation via the extracellular signal-regulated kinase (ERK) pathway, leading to increased protein levels of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). The ERK pathway can be pro- or antiproliferative, and it has been demonstrated that the activation status of the small GTPase RhoA determines the proliferative fate of ERK signaling, whereby inactivation of RhoA influences ERK signaling to increase p21(Waf1/Cip1) and inhibit proliferation. The purpose of these investigations was to examine the effect of NO on RhoA activation/S-nitrosation and to test the hypothesis that inhibition of SMC proliferation by NO is dependent on inactivation of RhoA. NO decreases activation of RhoA, as demonstrated by RhoA GTP-binding assays, affinity precipitation, and phalloidin staining of the actin cytoskeleton. Additionally, these effects are independent of cGMP. NO decreases SMC proliferation, and gene transfer of constitutively active RhoA (RhoA(63L)) diminished the antiproliferative effects of NO, as determined by thymidine incorporation. Western blots of p21(Waf1/Cip1) correlated with changes in proliferation. S-nitrosation of recombinant RhoA protein and immunoprecipitated RhoA was demonstrated by Western blotting for nitrosocysteine and by measurement of NO release. Furthermore, NO decreases GTP loading of recombinant RhoA protein. These findings indicate that inactivation of RhoA plays a role in NO-mediated SMC antiproliferation and that S-nitrosation is associated with decreased GTP binding of RhoA. Nitrosation of RhoA and other proteins likely contributes to cGMP-independent effects of NO.

Inhaled carbon monoxide inhibits intimal hyperplasia and provides added benefit with nitric oxide.

OBJECTIVE: Carbon monoxide (CO) and nitric oxide (NO) have both been shown to possess vasoprotective properties. NO has successfully inhibited intimal hyperplasia in both small-animal and large-animal experimental models, whereas CO has only been studied in rodents. Evidence suggests that these two molecules may exert their vascular effects through common as well as unique signaling pathways. The purpose of this study was to determine the effect of a low concentration of inhaled CO on intimal hyperplasia in a large-animal model and if CO and NO treatment could exert a synergistic effect to inhibit this process. METHODS: Balloon angioplasty was performed in a porcine model. Animals received inhaled CO (250 ppm) delivered preoperatively for 60 minutes or preoperatively and intraoperatively. Blood was collected for carboxyhemoglobin (COHgb) measurements at the start of the operation and every 30 minutes during the operation. Heart rate, respiratory rate, and oxygen saturation were monitored throughout. To study the effect of combined CO and NO treatment, another group of pigs received inducible NO synthase (iNOS) gene transfer in one iliac artery and control gene transfer (AdlacZ) in the contralateral iliac artery, with or without preoperative and intraoperative inhaled CO. Adenoviral infection was performed immediately after balloon injury. All animals were euthanized at 3 weeks, and iliac arteries were collected for histologic and morphometric analysis. RESULTS: One hour of pretreatment with CO was associated with modest and transient elevations in COHgb levels, resulting in a 25.6% reduction in neointimal area and a 10% reduction in intimal area/medial area ratio (I/M) 3 weeks after injury (NS). In contrast, preoperative followed by intraoperative CO administration increased COHgb in a sustained fashion and inhibited neointima formation by 51.7% and I/M by 31% (P < .001). There was no evidence of toxicity associated with this administration of CO. The treatment of injured iliac arteries with the control adenoviral vector AdlacZ did not further increase the inhibitory effect of CO on intimal hyperplasia. The combination of inhaled CO and iNOS gene transfer resulted in greater protection, however, with a 64% reduction in neointimal area and a 48% reduction in I/M (P < .001). CONCLUSIONS: CO is an effective means of reducing intimal hyperplasia in large animals after vascular injury when delivered during the operative procedure. No toxicity was associated with the increase in COHgb. The combination of CO and NO provided additional protection against the vascular injury response, with a greater reduction in neointima formation. These data suggest that these agents may prove to be clinically beneficial in prolonging vascular patency after interventions.

Biliverdin protects against polymicrobial sepsis by modulating inflammatory mediators.

Highly inducible heme oxygenase (HO)-1 is protective against acute and chronic inflammation. HO-1 generates carbon monoxide (CO), ferrous iron, and biliverdin. The aim of this study was to investigate the protective effects of biliverdin against sepsis-induced inflammation and intestinal dysmotility. Cecal ligation and puncture (CLP) was performed on Sprague-Dawley rats under isoflurane anesthesia with and without intraperitoneal biliverdin injections, which were done before, at the time of CLP, and after CLP. In vivo gastrointestinal transit was carried out with fluorescein-labeled dextran. Jejunal circular muscle contractility was quantified in vitro using organ bath-generated bethanechol dose-response curves. Neutrophilic infiltration into the muscularis externa was quantified. The jejunal muscularis was studied for cytokine mRNA expressions [interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, inducible nitric oxide synthase, cyclooxygenase-2, biliverdin, IL-10, and HO-1] using real-time RT-PCR. Biliverdin treatment prevented the sepsis-induced suppression of gastrointestinal muscle contractility in vivo and in vitro and significantly decreased neutrophilic infiltration into the jejunal muscularis. Inflammatory mRNA expressions for small bowel IL-6 and MCP-1 were significantly reduced after biliverdin treatment in CLP-induced septic animals compared with untreated septic animals. The anti-inflammatory mediator expression of small bowel IL-10 was significantly augmented after CLP at 3 h compared with untreated septic animals. These findings demonstrate that biliverdin attenuates sepsis-induced morbidity to the intestine by selectively modulating the inflammatory cascade and its subsequent sequelae on intestinal muscularis function.

Inhibition of geranylgeranyltransferase I decreases generation of vascular reactive oxygen species and increases vascular nitric oxide production.

BACKGROUND: Vascular injury with endothelial dysfunction results in an imbalance between the production of vasoprotective molecules such as nitric oxide (NO) and deleterious reactive oxygen species (ROS). The purpose of this work was to test the hypothesis that inhibition of geranylgeranyltransferase I (GG Tase I) reduces vascular injury by increasing vascular NO production while decreasing ROS generation. METHODS AND RESULTS: GGTI-298 decreased the formation of intimal hyperplasia at 14 days following balloon injury. GGTI-298 (10 microm) inhibited activation of RhoA and Rac1 as well as inhibited SMC proliferation. GGTI increased SMC-inducible NO synthase (iNOS) levels and NO production in vitro. Additionally, the activation of NAD(P)H oxidase subunits was decreased by GGTI in vitro. This correlated with a decrease in TNF-alpha- or angiotensin-II-induced ROS production assayed by DCF fluorescence. In vivo, GGTI treatment increased endothelial NOS (eNOS) expression in uninjured arteries and iNOS expression in balloon-injured arteries. Furthermore, GGTI treatment attenuated balloon-injury-induced superoxide generation assayed by MCLA luminescence. CONCLUSIONS: GGTI decreases the production of ROS and increases the production of NO both in vitro and in vivo. These effects may be mediated via the inhibition of activation of the small GTPases Rac1 and RhoA. Pharmacological inhibition of GGTase I may prove to be a useful clinical adjunct in the treatment of cardiovascular diseases.

Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome.

Type 2 diabetes mellitus (DM) and the metabolic syndrome, both characterized by insulin resistance, are associated with an accelerated form of atherosclerotic vascular disease and poor outcomes following vascular interventions. These vascular effects are thought to stem from a heightened inflammatory environment and reduced bioavailability of nitric oxide (NO). To better understand this process, we characterized the vascular injury response in the obese Zucker rat by examining the expression of adhesion molecules, the recruitment of inflammatory cells, and the development of intimal hyperplasia. We also evaluated the ability of exogenous NO to inhibit the sequela of vascular injury in the metabolic syndrome. Obese and lean Zucker rats underwent carotid artery balloon injury. ICAM-1 and P-selectin expression were increased following injury in the obese animals compared with the lean rats. The obese rats also responded with increased macrophage infiltration of the vascular wall as well as increased neointima formation compared with their lean counterparts (intima/media = 0.91 vs. 0.52, P = 0.001). After adenovirus-mediated inducible NO synthase (iNOS) gene transfer, ICAM-1, P-selectin, inflammatory cell influx, and oxidized low-density lipoprotein (LDL) receptor expression were all markedly reduced versus injury alone. iNOS gene transfer also significantly inhibited proliferative activity (54% and 73%; P < 0.05) and neointima formation (53% and 67%; P < 0.05) in lean and obese animals, respectively. The vascular injury response in the face of obesity and the metabolic syndrome is associated with increased adhesion molecule expression, inflammatory cell infiltration, oxidized LDL receptor expression, and proliferation. iNOS gene transfer is able to effectively inhibit this heightened injury response and reduce neointima formation in this proinflammatory environment.

iNOS gene transfer for graft disease.

Vascular bypass surgery involves the use of a vascular conduit to circumvent a site of vascular compromise. Vascular graft failure continues to plague both the patients receiving and the surgeons performing these interventions. Demand for the development of a therapy to reduce intimal hyperplasia--the most common cause of bypass graft failure--is significant and has been the goal of many biotechnology groups. The development of gene therapy as a feasible clinical intervention has allowed for novel methods of inhibiting intimal hyperplasia to be conceived. This review describes the evolution of gene transfer of the inducible nitric oxide synthase (iNOS) gene, one of the most successful preclinical interventions to date for vascular disease.

Nitric oxide and arterial disease.

Nitric oxide (NO) is a molecule that has gained recognition as a crucial modulator of vascular disease. NO has a number of intracellular effects that lead to vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis, and platelet adhesion. Its role in vascular disease has been intensively investigated and further elucidated over the past two decades. It is important in the pathogenesis of many cardiovascular diseases, including atherosclerosis, intimal hyperplasia, and aneurysmal disease. In addition, NO has been used as a therapeutic tool to treat diseases that range from recurrent stenosis to inhibiting thrombotic events. Many commonly used medications have their therapeutic actions through the production of NO. This review highlights the vascular biologic characteristics of NO, its role in the pathogenesis of cardiovascular disease processes, and its potential therapeutic applications.

The emerging role of gene therapy in the treatment of cardiovascular diseases.

Cardiovascular disease is the number one source of morbidity and mortality in the United States. Therapies directed at a variety of cardiovascular diseases have blossomed over the last several decades. The advent of gene therapy, first as an intriguing tool, and subsequently with the early successes of gene trials involving the treatment of SCID, led to the development of gene therapy as a potentially exciting and viable therapy in cardiovascular diseases. A variety of novel vector technologies and delivery systems have been developed to more efficiently deliver the gene product to the desired organ or tissue bed. Early clinical trials focused on stimulating angiogenesis. Subsequently, a number of other aspects of cardiovascular disease have been identified as potential targets for gene therapy, including the prevention of restenosis, the prevention and treatment of thrombosis, and the prevention of transplant vasculopathy. With over forty clinical human trials either completed or currently enrolling, cardiovascular gene therapy has proven to be safe and initial results suggest its efficacy.

Safety of inhaled nitric oxide after lung transplantation.

BACKGROUND: The present study tests the hypothesis that therapy with inhaled nitric oxide (iNO) at the time of lung transplantation in patients undergoing bilateral angle lung transplantation: (i) is safe; and (ii) does not increase either the duration of mechanical ventilation or the incidence of acute graft dysfunction. METHODS: We conducted a prospective, non-randomized trial of iNO at 20 parts per million. The treatment group was comprised of 14 patients (10 females, 4 males) undergoing lung transplantation to address severe end-stage lung disease and pulmonary hypertension (mean pulmonary artery pressure > 30 mmHg). Clinical and histologic parameters were compared with 22 historical control subjects who were matched with the study population for age, diagnosis and disease severity (17 females, 5 males) and had undergone lung transplantation in the preceding 2-year time period. No significant differences were noted between the 2 study groups at baseline. RESULTS: No toxic effect of iNO treatment was evident. Although the incidence of acute graft dysfunction was the same in both groups, the occurrence of acute graft rejection in the initial 4 weeks after transplant was less frequent in the iNO group than in the control group (7% vs 32%, p = 0.05). Fifty percent of the treatment group, as compared with 22% of the control group, were discharged from the hospital within 2 weeks of the procedure (p = 0.05). CONCLUSIONS: Early initiation of iNO in lung transplant patients with pulmonary hypertension is safe and may decrease the incidence of acute graft rejection. We speculate that iNO may exert an immunomodulatory effect.