G. Matthew Longo

Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms

Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic aneurysm (AAA) tissue, but their precise role and potential interaction remain unclear. Experimental induction of aortic aneurysms in mice genetically deficient in these peptidases could provide new insight into AAA pathogenesis. Mice deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their corresponding wild-type background mice (WT) underwent AAA induction by abluminal application of calcium chloride (CaCl(2)). No aneurysm formation was observed at 10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the corresponding WT mice showed an average 74% and 52% increase in aortic diameter, respectively. Reinfusion of competent macrophages from the corresponding WT strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and mesenchymal cell MMP-2 are both required and work in concert to produce AAA.

Cerebral Protection Devices Reduce Periprocedural Strokes during Carotid Angioplasty and Stenting: A Systematic Review of the Current Literature:

Purpose: To compare through a systematic review of published literature the stroke outcomes in protected and unprotected carotid artery stenting (CAS). Methods: PubMed and Cochrane electronic databases were queried to identify peer-reviewed publications from 1995 to 2007 meeting our pre-defined criteria for inclusion (English language, human only, at least 20 patients reported) and exclusion (procedures performed for the treatment of total occlusion, dissection, or aneurysmal disease; urgently performed procedures; use of covered stents; access other than transfemoral). Information was collected on a standardized data abstraction form for pooled analysis of total strokes within 30 days of procedure in all patients and in symptomatic and asymptomatic subgroups. A random effects meta-analysis of studies with concurrently reported data on protected and unprotected CAS was performed. Results: Initial database query resulted in 2485 articles, of which 134 were included in the final analyses (12,263 protected CAS patients and 11,198 unprotected CAS patients). Twenty-four studies included data on both protected and unprotected CAS. Using pooled analysis of all 134 reports, the relative risk (RR) for stroke was 0.62 (95% CI 0.54 to 0.72) in favor of protected CAS. Subgroup analysis revealed a significant benefit for protected CAS in both symptomatic (RR 0.67; 95% CI 0.52 to 0.56) and asymptomatic (RR 0.61; 95% CI 0.41 to 0.90) patients (p<0.05). Meta-analysis of the 24 studies reporting data on both protected and unprotected stenting demonstrated a relative risk of 0.59 (95% CI 0.47 to 0.73) for stroke, again favoring protected CAS (p<0.001). Conclusion: Our systematic review indicated that the use of cerebral protection devices decreased the risk of perioperative stroke with CAS. A well designed randomized trial can further confirm our findings and possibly indicate the device with the best outcomes.

Claudication distances and the Walking Impairment Questionnaire best describe the ambulatory limitations in patients with symptomatic peripheral arterial disease

BACKGROUND Claudication secondary to peripheral arterial disease leads to reduced mobility, limited physical functioning, and poor health outcomes. Disease severity can be assessed with quantitative clinical methods and qualitative self-perceived measures of quality of life. Limited data exist to document the degree to which quantitative and qualitative measures correlate. The current study provides data on the relationship between quantitative and qualitative measures of symptomatic peripheral arterial disease. METHOD This descriptive case series was set in an academic vascular surgery unit and biomechanics laboratory. The subjects were symptomatic patients with peripheral arterial disease patients presenting with claudication. The quantitative evaluation outcome measures included measurement of ankle-brachial index, initial claudication distance, absolute claudication distance, and self-selected treadmill pace. Qualitative measurements included the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study Short Form-36 (SF-36) Health Survey. Spearman rank correlations were performed to determine the relationship between each quantitative and qualitative measure and also between the WIQ and SF-36. RESULTS Included were 48 patients (age, 62 +/- 9.6 years; weight, 83.0 +/- 15.4 kg) with claudication (ABI, 0.50 +/- 0.20). Of the four WIQ subscales, the ankle-brachial index correlated with distance (r = 0.29) and speed (r = 0.32); and initial claudication distance and absolute claudication distance correlated with pain (r = 0.40 and 0.43, respectively), distance (r = 0.35 and 0.41, respectively), and speed (r = 0.39 and 0.39 respectively). Of the eight SF-36 subscales, no correlation was found for the ankle-brachial index, initial claudication distance correlated with Bodily Pain (r = 0.46) and Social Functioning (r = 0.30), and absolute claudication time correlated with Physical Function (r = 0.31) and Energy (r = 0.30). The results of both questionnaires showed reduced functional status in claudicating patients. CONCLUSIONS Initial and absolute claudication distances and WIQ pain, speed, and distance subscales are the measures that correlated the best with the ambulatory limitation of patients with symptomatic peripheral arterial disease. These results suggest the WIQ is the most specific questionnaire for documenting the qualitative deficits of the patient with claudication while providing strong relationships with the quantitative measures of arterial disease. Future studies of claudication patients should include both quantitative and qualitative assessments to adequately assess disease severity and functional status in peripheral arterial disease patients.

Carotid Stenting Done Exclusively by Vascular Surgeons: First 175 Cases

Background:Percutaneous CAS may well replace CEA as standard of care. CAS has been performed largely by interventional cardiologists; however, with recent Food and Drug Administration approval, vascular surgeons are now hurriedly attempting to obtain the requisite endovascular skills. Reported are our 30-day and midterm outcomes of CAS. Methods:Retrospective review of 175 cervical carotid stenoses treated with elective CAS from April 2001 to February 2005. All procedures were performed under local anesthesia via percutaneous femoral access in an operating room angiosuite. Mechanical cerebral protection was used in 90% of cases. Data analysis includes demographics, procedural records, and duplex exams over a mean follow-up of 21 months. Results:Mean age is 70 years (74% men and 26% women). Preprocedural neurologic symptoms were present in 32%. Intraoperative complications included 2 seizures (1.1%) and 4 asystolic arrests (2.3%), all managed medically without sequelae. Over the 30-day follow-up there were no deaths, no myocardial infarctions (MIs), 2 major strokes (1.1%), 2 minor strokes (1.1%), 3 transient ischemic attacks (TIAs) (1.7%), and 1 major access-site complication (0.6%). At late follow-up, 3 cases (1.7%) of restenosis occurred; all were treated with repeat angioplasty and remain patent. One (0.6%) asymptomatic occlusion was detected at 6-month follow-up. There have been no late carotid-related complications or deaths. Conclusions:Vascular surgeons possessing advanced catheter-based skills can safely perform CAS and achieve perioperative results comparable to CEA. Such skills are crucial to those surgeons intent on the future management of carotid occlusive disease.

Abnormal joint powers before and after the onset of claudication symptoms.

OBJECTIVE Claudication is the most common manifestation of peripheral arterial disease, producing significant ambulatory compromise. Our study evaluated patients with bilateral lower limb claudication and characterized their gait abnormality based on advanced biomechanical analysis using joint torques and powers. METHODS Twenty patients with bilateral claudication (10 with isolated aortoiliac disease and 10 with combined aortoiliac and femoropopliteal disease) and 16 matched controls ambulated on a walkway while 3-dimensional biomechanical data were collected. Patients walked before and after onset of claudication pain. Joint torques and powers at early, mid, and late stance for the hip, knee, and ankle joints were calculated for claudicating patients before and after the onset of claudication pain and were compared to controls. RESULTS Claudicating patients exhibited significantly reduced hip and knee power at early stance (weight-acceptance phase) due to decreased torques produced by the hip and knee extensors. In mid stance (single-limb support phase), patients had significantly reduced knee and hip power due to the decreased torques produced by the knee extensors and the hip flexors. In late stance (propulsion phase), reduced propulsion was noted with significant reduction in ankle plantar flexor torques and power. These differences were present before and after the onset of pain, with certain parameters worsening in association with pain. CONCLUSIONS The gait of claudication is characterized by failure of specific and identifiable muscle groups needed to perform normal walking (weight acceptance, single-limb support, and propulsion). Parameters of gait are abnormal with the first steps taken, in the absence of pain, and certain of these parameters worsen after the onset of claudication pain.

Three-dimensional bending, torsion and axial compression of the femoropopliteal artery during limb flexion

High failure rates of femoropopliteal artery reconstruction are commonly attributed to complex 3D arterial deformations that occur with limb movement. The purpose of this study was to develop a method for accurate assessment of these deformations. Custom-made stainless-steel markers were deployed into 5 in situ cadaveric femoropopliteal arteries using fluoroscopy. Thin-section CT images were acquired with each limb in the straight and acutely bent states. Image segmentation and 3D reconstruction allowed comparison of the relative locations of each intra-arterial marker position for determination of the arterys bending, torsion and axial compression. After imaging, each artery was excised for histological analysis using Verhoeff-Van Gieson staining. Femoropopliteal arteries deformed non-uniformly with highly localized deformations in the proximal superficial femoral artery, and between the adductor hiatus and distal popliteal artery. The largest bending (11±3-6±1 mm radius of curvature), twisting (28±9-77±27°/cm) and axial compression (19±10-30±8%) were registered at the adductor hiatus and the below knee popliteal artery. These deformations were 3.7, 19 and 2.5 fold more severe than values currently reported in the literature. Histology demonstrated a distinct sub-adventitial layer of longitudinally oriented elastin fibers with intimal thickening in the segments with the largest deformations. This endovascular intra-arterial marker technique can quantify the non-uniform 3D deformations of the femoropopliteal artery during knee flexion without disturbing surrounding structures. We demonstrate that 3D arterial bending, torsion and compression in the flexed lower limb are highly localized and are substantially more severe than previously reported.

Preoperative frailty Risk Analysis Index to stratify patients undergoing carotid endarterectomy.

OBJECTIVE Rapid and objective preoperative assessment of patients undergoing carotid endarterectomy (CEA) remains problematic. Preoperative variables correlate with increased morbidity and mortality, yet no easily implemented tool exists to stratify patients. We determined the relationship between our fully implemented frailty-based bedside Risk Analysis Index (RAI) and complications after CEA. METHODS Patients undergoing CEA in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2011 were included. Variables of frailty RAI were matched to preoperative NSQIP variables, and outcomes including stroke, mortality, myocardial infarction (MI), and length of stay were analyzed. We further analyzed patients who were symptomatic and asymptomatic before CEA. RESULTS With use of the NSQIP database, 44,832 patients undergoing CEA were analyzed (17,696 [39.5%] symptomatic; 27,136 [60.5%] asymptomatic). Increasing frailty RAI score correlated with increasing stroke, death, and MI (P < .0001) as well as with length of stay. RAI demonstrated increasing risk of stroke and death on the basis of risk stratification (low risk [0-10], 2.1%; high risk [>10], 5.0%). Among patients undergoing CEA, 88% scored low (<10) on the RAI. In symptomatic patients, the risk of stroke and death for patients with a score of ≤10 is 2.9%, whereas if the RAI score is 11 to 15, it is 5.0%; 16 to 20, 6.9%; and >21, 8.6%. In asymptomatic patients, the risk of stroke and death for patients with a score of ≤10 is 1.6%, whereas if the RAI score is 11 to 15, it is 2.9%; 16 to 20, 5.2%; and >21, 6.2%. CONCLUSIONS Frailty is a predictor of increased stroke, mortality, MI, and length of stay after CEA. An easily implemented RAI holds the potential to identify a limited subset of patients who are at higher risk for postoperative complications and may not benefit from CEA.

Transcervical Carotid Stenting with Flow Reversal for Neuroprotection: Technique, Results, Advantages, and Limitations

Carotid angioplasty and stenting are progressively earning a role as a less invasive alternative in the treatment of carotid occlusive disease. The most common approach for carotid artery stenting involves transfemoral access and use of a filter or balloon device for neuroprotection. This approach has limitations related to both the site of access and the method of neuroprotection. Specifically, an aortoiliac segment with advanced occlusive or aneurysmal disease or an anatomically unfavorable or atheromatous arch and arch branches can significantly limit the safety of the retrograde transfemoral pathway to the carotid bifurcation. Additionally, data provided by the use of transcranial Doppler monitoring and diffusion-weighted magnetic resonance imaging in patients undergoing filter- or balloon-protected carotid artery stenting demonstrate that currently available devices are associated with a considerable incidence of cerebral embolization. To address these limitations, we, along with others, have employed a direct transcervical approach for carotid artery stenting that incorporates the principle of flow reversal for neuroprotection. The technique bypasses all of the anatomic limitations of transfemoral access and simplifies the application of flow reversal, which is one of the safest neuroprotection techniques. The purpose of this review is to describe our method of transcervical carotid artery stenting, review the accumulating outcomes data, and discuss the clinical advantages of and indications for this increasingly popular technique.

Carotid endarterectomy is superior to carotid angioplasty and stenting for perioperative and long-term results

Objective: Carotid angioplasty and stenting (CAS) has challenged carotid endarterectomy (CEA) as the therapy of choice for carotid disease. This meta-analysis aims at summarizing the most current body of evidence. Methods: All prospective, controlled clinical trials comparing CEA versus CAS were included. The outcome measures of interest were relative risk (RR) of 30-day stroke, 30-day stroke/death, long-term risk of stroke, and risk of restenosis. Results: The RR of 30-day stroke for CAS was 1.6 times that of CEA (RR 1.6; 95%CI 1.2-2.0, P = .001). The 30-day RR of stroke/death was 1.5 times higher for CAS (RR 1.5; 95%CI 1.1-2.1, P = .008). There was a higher risk of long-term stroke (RR 1.2; 95%CI 1.0-1.5, P = .043). The risk of restenosis was twice for CAS (RR 1.8; 95%CI 1.1-3.1, P = .04). Conclusion: The 30-day RR of stroke, stroke/death, long-term risk of stroke, and risk of restenosis are consistently higher for carotid artery stenting (CAS).

One patent intracranial collateral predicts tolerance of flow reversal during carotid angioplasty and stenting.

Internal carotid artery (ICA) flow reversal is an effective means of cerebral protection during carotid stenting. Its main limitation is that in the absence of adequate collateral flow it may not be tolerated by the patient. The purpose of this study was to determine if preoperative identification of intracranial collaterals with computerized tomographic (CTA) or magnetic resonance (MRA) angiography can predict adequate collateral flow and neurological tolerance of ICA flow reversal for embolic protection. This was a study of patients undergoing transcervical carotid angioplasty and stenting. Neuroprotection was established by ICA flow reversal. All patients underwent preoperative cervical and cerebral noninvasive angiography with CTA or MRA and had at least one patent intracranial collateral. Mean carotid artery back pressure was measured. Neurological changes during carotid clamping and flow reversal were continuously monitored with electroencephalography (EEG). Thirty-seven patients with at least one patent intracranial collateral on brain imaging with CTA or MRA were included. Mean carotid artery back pressure was 58 mm Hg. All procedures were technically successful. No EEG changes were present with common carotid artery occlusion and ICA flow reversal. One patent intracranial collateral provides sufficient cerebral perfusion to perform carotid occlusion and flow reversal with absence of EEG changes. Continued progress in noninvasive imaging modalities is becoming increasingly helpful in our understanding of cerebral physiology and selection of patients for invasive carotid procedures.