Top 10 candidate aortic disease trials.

Aortic pathologies such as aneurysm, dissection and trauma are relatively common and potentially fatal diseases. Over the past two decades, we have experienced unprecedented technical and medical developments in the field. Despite this, there is a great need, and great opportunities, to further explore the area. In this review, we have identified important areas that need to be further studied and selected priority aortic disease trials. There is a pressing need to update the AAA natural history and the role for endovascular AAA repair as well as to define biomarkers and genetic risk factors as well as influence of gender for development and progression of aortic disease. A key limitation of contemporary treatment strategies of AAA is the lack of therapy directed at small AAA, to prevent AAA expansion and need for surgical repair, as well as to reduce the risk for aortic rupture. Currently, the most promising potential drug candidate to slow AAA growth is metformin, and RCTs to verify or reject this hypothesis are warranted. In addition, the role of endovascular treatment for ascending pathologies and for uncomplicated type B aortic dissection needs to be clarified.

Rapamycin limits the growth of established experimental abdominal aortic aneurysms.

OBJECTIVES: Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease affecting 4-8% of men older than 60 years. No pharmacologic strategies limit disease progression, aneurysm rupture, or aneurysm-related death. We examined the ability of rapamycin to limit the progression of established experimental AAAs. METHODS: AAAs were created in 10-12-week-old male C57BL/6J mice via the porcine pancreatic elastase (PPE) infusion method. Beginning 4 days after PPE infusion, mice were treated with rapamycin (5 mg/kg/day) or an equal volume of vehicle for 10 days. AAA progression was monitored by serial ultrasound examination. Aortae were harvested for histological analyses at sacrifice. RESULTS: Three days after PPE infusion, prior to vehicle or rapamycin treatment, aneurysms were enlarging at an equal rate between groups. In the rapamycin group, treatment reduced aortic enlargement by 38%, and 53% at 3 and 10 days, respectively. On histological analysis, medial elastin and smooth muscle cell populations were relatively preserved in the rapamycin group. Rapamycin treatment also reduced mural macrophage density and neoangiogenesis. CONCLUSION: Rapamycin limits the progression of established experimental aneurysms, increasing the translational potential of mechanistic target of rapamycin-related AAA inhibition strategies.

EVAR deployment in anatomically challenging necks outside the IFU.

OBJECTIVE: Treatment of abdominal aortic aneurysms with high-risk anatomy (neck length <10-15 mm, neck angle >60°) using commercially available devices has become increasingly common with expanding institutional experience. We examined whether placement of approved devices in short angled necks provides acceptable durability at early and intermediate time points. METHODS: A total of 218 patients (197 men, 21 women) at a single academic center underwent endovascular aneurysm repair (EVAR) with a commercially available device between January 2004 and December 2007. Available medical records, pre- and postoperative imaging, and clinical follow-up were retrospectively reviewed. Patients were divided into those with suitable anatomy (instructions for use, IFU) for EVAR and those with high-risk anatomic aneurysm characteristics (non-IFU). RESULTS: IFU (n = 143) patients underwent repair with Excluder (40%), AneuRx (34%), and Zenith (26%) devices, whereas non-IFU (n = 75) were preferentially treated with Zenith (57%) over Excluder (25%) and AneuRx (17%). Demographics and medical comorbidities between the groups were similar. Operative mortality was 1.4% (2.1% IFU, 0% non-IFU) with mean follow-up of 35 months (range 12-72). Non-IFU patients tended to have larger sac diameters (46.7% ≥60 mm) with shorter (30.7% ≤10 mm), conical (49.3%), and more angled (68% >60°) necks (all p < .05 compared with IFU patients). Operative characteristics revealed that the non-IFU patients were more likely to be treated utilizing suprarenal fixation devices, to require placement of proximal cuffs (13.3% vs. 2.1%, p = .003), and needed increased fluoroscopy time (31 vs. 25 minutes, p = .02). Contrast dose was similar between groups (IFU = 118 mL, non-IFU = 119 mL, p = .95). There were no early or late surgical conversions. Rates of migration, endoleak, need for reintervention, sac regression, and freedom from aneurysm-related death were similar between the groups (p > .05). CONCLUSIONS: EVAR may be performed safely in high-risk patients with unfavorable neck anatomy using particular commercially available endografts. In our experience, the preferential use of active suprarenal fixation and aggressive use of proximal cuffs is associated with optimal results in these settings. Mid-term outcomes are comparable with those achieved in patients with suitable anatomy using a similar range of EVAR devices. Careful and mandatory long-term follow-up will be necessary to confirm the benefit of treating these high-risk anatomic patients.

Snorkel/chimney and fenestrated endografts for complex abdominal aortic aneurysms.

Complex endovascular aneurysm repair (EVAR) involves extension of the proximal aortic seal zone with preservation of branch vessel patency, thereby expanding the applicability of endografting from the infrarenal to the suprarenal aorta. Snorkel/chimney (Sn-EVAR) and fenestrated EVAR (f-EVAR) serve as the two most commonly utilized advanced endovascular techniques to combat hostile proximal neck anatomy. The purpose of this article is to describe the principles and evolution of these advanced endovascular strategies, technical considerations, and results of sn- and f-EVAR in the management of challenging neck anatomy in abdominal aortic aneurysm disease.

Matrix metalloproteinase inhibition limits arterial enlargements in a rodent arteriovenous fistula model.

BACKGROUND: We administered a specific, nonselective matrix metalloproteinase (MMP) inhibitor (RS-113,456) to examine the effect of MMP inhibition on flow-mediated arterial enlargement in a rodent arteriovenous fistula (AVF) model. METHODS: Four groups of male Sprague-Dawley rats were created: sham (sham operated; n = 10), control (2.0 mm left common femoral AVF alone; n = 16), vehicle (AVF plus 0.5 mL vehicle orally twice a day; n = 20), and treatment (AVF plus 25 mg/kg RS-113,456 in 0.5 mL vehicle orally twice a day; n = 16). Heart rate, mean arterial pressure, and body weight were recorded on postoperative days 0, 7, 14, and 21. On day 21, AVF patency was confirmed, the infrarenal aorta and common iliac arteries were exposed, blood flow velocity and external diameter were measured, and wall shear stress (WSS) was calculated. Analysis was performed by paired, two-tailed Student t test, one-way analysis of variance, and the Bonferroni/Dunn procedure for post hoc testing. RESULTS: Heat rate, mean arterial pressure, and weight did not vary at any time between groups. Aortic and left iliac diameter was larger in the AVF groups than in sham groups (P < .001), and control and vehicle groups were larger than treatment groups (P < .0001). Changes in aortic and left iliac flow were also significant (AVF was more than sham and control, and vehicle was more than treatment). No difference in aortic and left iliac artery velocity and WSS or right iliac diameter, velocity, flow, or WSS was observed between groups. CONCLUSIONS: MMP inhibition diminishes flow-mediated arterial enlargement in the rat AVF model.

Limb salvage vs amputation for critical ischemia. The role of vascular surgery.

Since 1980, 498 patients with 627 critically ischemic legs (rest pain, gangrene, ischemic ulcer, and ankle-brachial pressure index less than 0.40) were treated with revascularization regardless of operative risk or anticipated operative difficulty. Primary amputation was performed only when no graftable distal vessels were present (14 primary amputations [2.8%]) or in neurologically impaired, hopelessly nonambulatory patients. The mortality for revascularization was 2.3%, and the median hospital stay was 11 days. During follow-up, 41 limbs (7%) required amputation, 31 after failure of revascularization and 10 despite patent revascularizations. Renal failure had an adverse influence on limb salvage (67%) because of a significantly increased requirement for amputation despite patent revascularizations. We conclude aggressive limb revascularization in patients with critical lower-extremity ischemia results in low operative morbidity and mortality and excellent long-term limb salvage. Patients with critical leg ischemia and renal failure are at higher risk for limb loss than patients without renal failure.

Duplex surveillance of abdominal aortic stent grafts.

Aortic stent grafting is gaining acceptance rapidly as a durable and effective alternative to open surgery for abdominal aortic aneurysms (AAA). Unlike follow-up after open surgical procedures, postplacement surveillance protocols are necessary to ensure long-term freedom from device failure or aneurysm rupture. Surveillance protocols incorporating duplex scanning are effective and may reduce overall postplacement expenses. Specific device or patient anatomic features may be prone to failure, and familiarity with each approved device is a prerequisite to the performance of effective device surveillance studies. Mechanisms of failure of aneurysm exclusion after device placement, or "endoleak," have been described and categorized. Endoleak significance is directly related to location, duration, and influence on AAA diameter. Endoleak type also determines when and whether additional interventions are indicated. Future progress in endovascular AAA exclusion will depend in large part on the reliability and utility of cost-effective postprocedure surveillance protocols incorporating duplex ultrasound imaging.

In vivo flow-independent T2 measurements of superior mesenteric vein blood in diagnosis of chronic mesenteric ischemia: a preliminary evaluation.

RATIONALE AND OBJECTIVES: The authors attempted to determine whether the T2 relaxation time of superior mesenteric vein (SMV) blood would decrease in patients with chronic mesenteric ischemia after a meal. MATERIALS AND METHODS: Thirty-two patients without chronic mesenteric ischemia and eight patients with symptomatic chronic mesenteric ischemia underwent magnetic resonance (MR) imaging. All examinations were performed with a 1.5-T unit, a modified Carr-Purcell-Meiboom-Gill sequence, final section-selective pulse of 180 degrees, and spiral readout gradients. Measurements of SMV blood T2 were obtained after at least 6 hours of fasting and 15 and 35 minutes after ingestion of 240 mL of a liquid nutritional supplement. Maximal change of the SMV blood T2 was expressed as a percentage of the fasting T2 in all patients. RESULTS: In control patients, SMV blood T2 increased postprandially by 9.4% +/- 1.3 (95% confidence level; range, 6.8%-11.9%) (data range, -7.3% to 25.6%) compared with fasting T2. In symptomatic patients, SMV blood T2 decreased postprandially by 15.8% +/- 2.2 (95% confidence level; range, -20.1% to -10.7%) (data range, -7.9% to -25.3%). The difference between the two groups was statistically significant (P < .0001 by Student unpaired t test). CONCLUSION: Measurement of SMV blood T2 is a promising test for chronic mesenteric ischemia diagnosis. Therefore, conversion of T2 measurements to estimate oxygen saturation may not be necessary for all cases of this clinical indication.

In vivo magnetic resonance evaluation of blood oxygen saturation in the superior mesenteric vein as a measure of the degree of acute flow reduction in the superior mesenteric artery: findings in a canine model.

RATIONALE AND OBJECTIVES: The authors tested the hypothesis that changes in oxygen saturation (%HbO2) in the superior mesenteric vein (SMV), as measured with in vivo magnetic resonance (MR) oximetry, correlate with the degree of acute superior mesenteric artery (SMA) flow reduction. METHODS: Ten mongrel dogs were studied. A catheter was inserted into the SMV, and a perivascular ultrasonic flow probe and an adjustable mechanical occluder were placed around the SMA. MR oximetry was carried out at the resting state and after the SMA was constricted to predetermined levels (0%-75% of initial flow). In seven dogs, SMV blood samples were obtained immediately before and after each MR measurement; %HbO2 was measured simultaneously by using an oximeter. With linear regression analysis, the SMV %HbO2 measurements obtained at MR imaging were compared with those obtained at oximetry. With a logistic model, MR imaging changes in SMV %HbO2 were compared with the degree of SMA flow reduction. RESULTS: SMV %HbO2 measurements obtained with MR imaging correlated well with those obtained with oximetry (r = .97). Changes in SMV %HbO2 measured at MR imaging also correlated well with the degree of SMA flow reduction, as determined with a logistic model (P = .01). CONCLUSION: Noninvasive in vivo MR measurements of SMV %HbO2 can be used to determine the degree of acute SMA flow reduction with a high degree of accuracy in a canine model.

Viability and biodistribution of 68Ga MPO-labelled human platelets.

The viability and biodistribution of 68Ga-mercaptopyridine-N-oxide (MPO)-labelled autologous platelets was studied in 10 patients. The average platelet labelling yield was 36 +/- 12% and injected activity was 2.0 +/- 0.9 mCi 68Ga. The % activity in platelets per ml whole blood was 64 +/- 20% at 15 min-1.0 h postinjection and 76 +/- 14% at 2-4h. The average recovery of platelets (% injected platelets circulating in peripheral blood) was 31 +/- 21% at 15 min-1 h and 39 +/- 20% at 2-4 h. The positron emission tomographic (PET) images showed high circulating vascular background. Two patients had technically inadequate scans, and six were false negative due to high blood background. One patient with a massive pulmonary embolus occurring 24 h prior to scanning had marked uptake of 68Ga platelets in a large clot in the superior branch of the right main pulmonary artery. A second patient, with 68Ga platelets circulating during angioplasty of a left posterior tibial artery stenosis, had intense uptake in the lesion shown on the PET scan obtained 4 h following the procedure. These results indicate good viability of 68Ga-MPO-labelled autologous human platelets, but poor visualization of clots by PET imaging, due to the high blood background at early times.

Subclavian vein thrombosis: outcome analysis based on etiology and modality of treatment.

Therapeutic options for subclavian vein thrombosis (SVT) include anticoagulation, thrombolysis, endovascular repair, and direct surgical intervention. The most effective method of treatment remains undetermined. We reviewed our institutional experience over 7 years with SVT patients to compare the results of treatment based on etiology of thrombosis. Nineteen patients suffered SVT secondary to malignancy, catheter placement, radiation, or hypercoagulability. Thirteen were Paget-Schroetter (PSS), or primary effort-related SVT. Patients with dialysis access procedures were excluded. Thrombolysis was initiated in 31/32 patients. Success was defined as complete obliteration of clot. Adjunctive treatment to relieve external compression or improve lumenal contour was performed on 16/32 patients (eight PSS, eight secondary SVT). Success of adjunctive treatment was defined as return to baseline activity without symptoms. Objective follow up (venography or duplex scanning) was included when available. Adjunctive treatment included balloon angioplasty (6), stent placement (5), first rib resection and scalenectomy (4), and vein reconstruction (4). Initial treatment success with thrombolysis was achieved in 26/31 patients (84%). Angioplasty failed in three PSS and three secondary SVT patients. Stent placement was successful in 2/5 patients (both secondary SVT). Surgery was performed only on PSS patients: first rib resection and scalenectomy succeeded 4/4 times, vein reconstruction 2/4. Twenty-eight patients were given long-term therapy with oral anticoagulation with good long-term results. Seven patients experienced complications, including one death. Results of SVT therapy including thrombolysis and oral anticoagulation are very good. Angioplasty and stent placement in secondary SVT patients appears to add little long term benefit. Surgery may improve outcome in selected PSS patients, although the additional benefit could not be determined by the design of this study. Evaluation and treatment limited only to PSS excludes the majority of SVT patients.

Use of outpatient preoperative evaluation to decrease length of stay for vascular surgery.

UNLABELLED: Interventions that decrease perioperative length of stay can result in considerable cost-savings. This study assesses the impact of same-day admission using outpatient preoperative evaluation on the lengths of stay and hospital costs for patients who underwent carotid end-arterectomy (CEA) or lower extremity revascularization (LER). Patient characteristics and length of stay were compared for two 1-yr periods before and after outpatient preoperative evaluation had been implemented. There were no significant differences before and after the initiation of outpatient preoperative evaluation in the CEA and LER groups in mean age and ASA physical status distributions. The average preoperative length of stay decreased significantly from 7.0 to 1.9 days in the CEA group and from 9.0 to 2.8 days in the LER group. This reduction in the length of stay was associated with a cost-savings of $900 per patient and did not have an adverse effect on patient outcome. We conclude that outpatient preoperative evaluation clinics reduce the cost and length of stay in vascular surgery patients. IMPLICATIONS: We found that outpatient preoperative evaluation and same-day admission were associated with a decrease of 4.5 days in the preoperative length of stay for carotid endarterectomy and lower-extremity revascularization. This was not accompanied by increased mortality and led to hospital cost-savings of approximately $900 per patient.

Is completion arteriography mandatory after reversed-vein bypass grafting?

Many surgeons advocate uniform performance of operative completion arteriography after leg bypass surgery to ensure technical success and to optimize short- and intermediate-term graft patency. To determine the impact of this practice on the outcome of reversed-vein bypass surgery and associated patient charges, we reviewed our series of consecutive nonemergent leg bypass procedures. Ninety-three infrainguinal bypass procedures were performed in 80 patients (76 men and 4 women) from September 1991 to August 1994. The patients' average age was 67 years (range, 30 to 92 years). Follow-up (mean, 113.1 months; range, 1 to 36 months) was available on 91 grafts (97%). Indications for surgery included limb salvage in 75 cases, claudication in 12 cases, and popliteal aneurysm exclusion in 6 cases. All patients survived surgery. Primary graft patency rates as determined by life-table analysis were 87%, 81%, 78%, and 78% at 6 months and at 1, 2, and 3 years, respectively. Limb-salvage rates were 95%, 91%, 87% and 87% at the same intervals. Bypass procedures were divided into two groups. The 25 grafts in group 1 were evaluated with inspection, continuous-wave Doppler insonation, and routine completion arteriography. The 68 grafts in group 2 were evaluated by inspection and insonation alone. Fourteen grafts occluded after surgery (average, 5 months; range, 1 to 12 months), five in group 1 and nine in group 2. The likelihood of graft occlusion was similar in both groups (p = 0.42). The optimal method of confirming technical adequacy after bypass surgery in the clinically satisfactory graft remains uncertain. Charges for completion arteriography at our institution average $700, including 15 minutes of additional operative time. In our experience, these charges do not appear to be justified by improved short- or intermediate-term graft patency rates in reversed-vein grafts when completion arteriography is performed.

Spontaneous late carotid-cutaneous fistula following radical neck dissection: a case report.

The authors present an unusual case of a spontaneous carotid-cutaneous fistula occurring as a late complication 4 years after radical neck dissection and postoperative radiation therapy for tonsillar squamous cell carcinoma in a 50-year-old patient. The etiologic factors predisposing patients to carotid artery rupture following radical neck dissection and a surgical option for carotid artery reconstruction instead of ligation are discussed.

Limb salvage surgery in spinal cord injury patients.

Advances in the care and rehabilitation of patients with spinal cord injuries (SCI) have resulted in extended survival following injury. Increasingly, we are faced with difficult chronic lower extremity ischemic complications in SCI patients. Recognizing limitations associated with amputation in these nonambulatory patients, we report the preliminary results of a program of selective limb salvage via arterial reconstructive surgery. Retrospective chart review was performed on the records of the Veterans Affairs Palo Alto Health Care System SCI unit. Since 1989, 15 revascularization procedures were identified in 10 SCI patients. All patients suffered from ischemic ulceration and/or gangrene. Procedures performed included femorotibial bypass (8), aortofemoral bypass (4), femoro-femoral bypass (2), and axillobifemoral bypass (AXF) (1). All patients were men. The mean age was 56 (range 43-73). Follow-up was available on 10 procedures performed in seven patients since 1992. Mean follow-up was 17 months. One patient died 3 months following distal bypass. The AXF occluded within 1 month. One distal bypass occluded in the immediate postoperative period and could not be salvaged. All other grafts remain patent, and all wounds have healed following successful bypass. One patient developed pressure ulceration following AXF grafting due to postoperative upper extremity limitations. No other complications were encountered. Standard arterial reconstructive procedures can be performed safely and successfully in SCI patients, despite diminished limb blood flow due to inactivity, and atrophic arteries, muscle, and fascia. Axillobifemoral bypass grafting may not be suitable in SCI due to requirements for upper extremity-based mobility. Confirmation of benefit of limb salvage versus amputation awaits comparison between patients eligible for either procedure.

Diminished postprandial hyperemia in patients with aortic and mesenteric arterial occlusive disease. Quantification by magnetic resonance flow imaging.

BACKGROUND: Superior mesenteric blood flow in the fasting and postprandial state in humans can be measured accurately by cine phase-contrast (CPC) magnetic resonance (MR) imaging. Postprandial flow changes associated with mesenteric arterial occlusive disease (MAOD) are unknown. METHODS AND RESULTS: We used CPC MR imaging to measure fasting and postprandial blood flow in the superior mesenteric artery (SMA) and vein (SMV) in 22 patients (mean age, 69 years) with aortic occlusive disease and MAOD and compared the results with similar measurements in 8 younger, asymptomatic volunteers (mean age, 34 years). All 22 patients had stenosis or occlusion of the splanchnic or pelvic arteries demonstrated by contrast aortography; 19 were asymptomatic and 3 had symptoms of chronic mesenteric ischemia. Mean fasting blood flow was higher in patients (4.5 mL.kg-1.min-1) than in volunteers (2.3 mL.kg-1.min-1; P < .01). However, postprandial hyperemia (mean percentage change in SMV blood flow) was less in the asymptomatic (70%; P < .001) and symptomatic patients (29%; P < .01) than in the volunteers. Postprandial SMV flow was similar to SMA flow in the patients but was significantly greater than SMA flow in the volunteers (P < .005). CONCLUSIONS: Postprandial mesenteric hyperemia is reduced in older patients with MAOD. The role of aging alone has not been determined. Fasting and postprandial flow changes in these patients may predict the onset of chronic mesenteric ischemia.

Open saphenectomy complications following lower extremity revascularization.

A review of saphenectomy site complications following lower extremity revascularization was conducted. Leg incisions used for 133 consecutive infrainguinal bypass procedures were categorized by location. Patient and procedural risk factors were analyzed for risk of wound complications. Procedure, limb and patient outcome were reported via life table analysis. Incisional wound complications followed 32/133 procedures (24%), including 15 groin, eight saphenectomy, five distal and four vein/distal incisions. There were five grade I and three grade II saphenectomy complications. Only weight (body mass index) predicted the likelihood of wound complication (P < 0.05). The 6-month primary patency rate was 79% (mean follow-up 22 months). Four-year assisted primary patency, limb salvage and survival rates were 75, 87 and 57%, respectively. Most bypass-related wound complications (24/32, 75%) involve arterial access incisions. Incisional complications are related to body mass index. Only 6% of GS vein bypass procedures develop saphenectomy site complications. Limiting saphenectomy size may not significantly reduce incisional morbidity following bypass grafting.