Faculty Bibliography

OBJECTIVE: Matrix metalloproteinase (MMP) activity is essential for remodeling of ischemic tissue. The murine hindlimb ischemia model exhibits tissue remodeling including revascularization in part due to angiogenesis. MMP-2 and -9 are type IV collagenases necessary for basement membrane degradation as a part of extracellular matrix remodeling and angiogenesis. Polymorphonuclear leukocytes (PMNs) contain MMP-9, and in the presence of membrane type 1 (MT1)-MMP, are able to activate proMMP-2 in vitro. Activation of MMP-2 and -9 may be essential in ischemic limbs both for tissue remodeling and revascularization via angiogenesis. We hypothesized that MMP-2 and -9 would be activated following acute hindlimb ischemia (HI), and this activation would be temporally related to PMN infiltration. DESIGN OF STUDY: HI was achieved by unilateral femoral artery ligation in 20 FVB/N mice. Five mice underwent sham operation without hindlimb ischemia. Gastrocnemius muscle was harvested from both hindlimbs at 1, 3, 14, and 30 days following ligation and assayed for MMP-2, -9 (gelatin zymography), and MT1-MMP (Western blotting). MMP-2 and -9 expression and activation were analyzed by gelatin zymography and quantified by densitometry with NIH Image Analysis software. Neutrophils per high power field were counted. The results were expressed as a ratio of ischemic to nonischemic limbs and compared at each time point using ANOVA. RESULTS: Zymographic analysis revealed a 212% increase in active MMP-2 3 days postligation (P <.05). Active MMP-9 reached its maximum level (800% over baseline) on postoperative day 3 and continued to be elevated on day 14 (737% over baseline) (P <.05). The increase in active MMP-2 and -9 levels paralleled PMN infiltration that also peaked 3 days postligation (1184% over baseline) (P <.05). PMN count, MMP-2, and -9 all returned to baseline levels by postoperative Day 30. MT1-MMP was present in tissue samples from all time points as confirmed by Western blot. CONCLUSIONS: Limb ischemia causes an early activation of MMP-2 and -9 in temporal relation to PMN infiltration. HI may prime PMNs, leading to their sequestration in ischemic tissue. Primed PMNs, along with constitutively expressed MT1-MMP, may activate MMPs-2 and -9 and enable tissue remodeling essential for limb revascularization and angiogenesis

Proponents of carotid angioplasty and stenting (CAS) believe that this technique would be preferred over carotid endarterectomy (CEA) for the high-risk patient. Presumably this would include patients over 80 years of age. However, a recent large series of patients undergoing CAS revealed a 16% incidence of nonfatal strokes and deaths for patients over the age of 80; these results were significantly worse than those for younger patients undergoing CAS. The objective of this study was to reassess results of CEA in patients over 80, and to compare surgical results with the published results of CAS in this patient group. A review was conducted of a prospectively maintained database of all carotid surgery performed at our institution. Primary CEA that took place from 1997 through 1999 were included for analysis (n = 698). Our institutional results were compared with representative results from a recently published large series of CAS. Our analysis showed that CEA can be performed safely in the octogenarian, and results are equivalent to those of younger patients. CEA appears to have significantly better results in the octogenarian than CAS. The reasons for the poor outcomes of CAS in the octogenarian are unclear. The results of CAS in the older patient population are worrisome, and this 'less invasive' technique may prove to be an inferior alternative in this patient group

OBJECTIVE: Total occlusion of the contralateral internal carotid artery has often been considered to be a predictor of poor outcome after carotid endarterectomy (CEA) of ipsilateral carotid stenosis. Data from both the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Atherosclerosis Study have suggested this to be true. However, each of these trials had relatively few patients with contralateral occlusion in the surgical arms of the studies. Recently, advocates of carotid angioplasty and stenting have suggested that this technique may be preferable in patients with a contralateral occlusion because of the perceived poor outcome with surgery. The purpose of this study was to review a large series of CEAs performed in patients with contralateral occlusion to see whether results differed from patients with patent contralateral arteries and to determine whether the presence of preoperative symptoms was an important factor in outcome in these cases. PATIENTS AND METHODS: A review was conducted of a prospectively compiled database of all primary CEAs performed at our institution from 1985 to 1999. Surgery was performed on 2420 patients, of whom 338 (14.0%) had contralateral total occlusion. RESULTS: Patients with contralateral total occlusion were more likely to be symptomatic (65.7% versus 60.1%; P =.1), male (70.9% versus 58%; P <.001), and hypertensive (63.9% versus 58.4%; P =.07) with a positive smoking history (42.6% versus 31.4%; P <.001) than patients with patent contralateral carotid artery. No significant difference was seen in the rates of perioperative neurologic events between patients with contralateral occlusion (3.0%) and those without (2.1%; P =.34). Among the total of 913 asymptomatic patients, of whom 115 had contralateral occlusion, no difference was seen in the rate of perioperative neurologic events (1.8% for contralateral occlusion cases; 1.9% for cases without contralateral occlusion). Among the total of 1507 symptomatic patients, of whom 223 had contralateral occlusion, no significant difference was seen in the rate of perioperative neurologic events (3.7% for contralateral occlusion cases; 2.2% for cases without contralateral occlusion; P =.2). CONCLUSION: The presence of contralateral occlusion does not appear to increase the perioperative risk of CEA. Although the risk of CEA in symptomatic patients with contralateral occlusion may be slightly increased, this must be weighed against the risk with medical treatment alone. CEA can be performed safely in patients with contralateral occlusion, which should not necessarily be considered a high-risk condition for surgery in favor of angioplasty and stenting

Since the Food and Drug Administrations' approval of endovascular devices for abdominal aortic aneurysm (AAA) repair, clinicians have been relaxing the strict inclusion criteria present during the clinical trials. Although the long-term natural history of endoleaks remains unclear, attachment site leaks (type I) are believed to represent an ongoing risk for future rupture. We reviewed our experience with endovascular AAA repair to elucidate factors that predispose toward the development of endoleaks and found that larger AAAs are significantly more likely to have a short proximal neck and severe proximal angulation. These factors likely contribute to the significantly increased rate of type I endoleaks that occurred after endovascular repair of large AAAs. Small AAAs (<5) had the lowest rate of endoleaks overall (8.3%) and of type I endoleaks in particular (0%). We conclude that AAA size and morphology can be used to predict which aneurysms will experience attachment site endoleaks in their course; AAAs from 4.5 to 5 cm in diameter may be particularly well suited for endovascular repair in this regard

BACKGROUND: Since the FDA approval of endovascular devices for abdominal aortic aneurysm (AAA) repair, clinicians have been relaxing the strict inclusion criteria of the clinical trials. We have reviewed our experience during and after the clinical trials to examine changes in patient selection, technical aspects of the procedure, and outcome. METHODS: A review of a prospectively compiled database of all endovascular AAA repairs performed at our institution was performed. RESULTS: Endovascular AAA repair was attempted in 130 patients: 46 (35.4%) as a part of clinical trials (Group I), and 84 (64.6%) since the FDA approval of the devices (Group II). Significant differences in patient selection included: a higher proportion of short (<15 mm) proximal necks in Group II (28.6 vs 0.0%, p<0.001), and a higher proportion of iliac occlusive disease in Group II (48.8 vs 15.4%, p=0.001). Additional trends suggested that Group II AAA's were more complex, including increased proximal neck angulation, increased proximal calcification, increased presence of proximal thrombus, and increased iliac tortuosity. Significant differences in technical aspects of the procedure included increased usage of iliac angioplasty (46.4 vs 13.3%, p<0.001), iliac stenting (31 vs 8.9%, p<0.01), and conduit access to the external iliac artery (10.7 vs 0%, p=0.03) in Group II. Analysis of outcome revealed a decreased incidence of the following in Group II cases: conversions to open repair (2.4 vs 10.9%), lower extremity ischemia (3.6 vs 13.0%), and graft limb occlusion (2.4 vs 8.7%). Other major perioperative complications did not differ significantly between the 2 groups. However, although the overall rate of any endoleak noted in the postoperative course was decreased in Group II cases (26.2 vs 32.6%), the incidence of proximal or distal attachment site leaks has increased (11.9 vs 4.3%, p=0.14). Although this comparison did not reach statistical significance, the magnitude of the increase is concerning. CONCLUSIONS: Although we have been able to offer endovascular AAA repair to a larger number of patients since FDA approval, endovascular management of increasingly complex proximal necks and increased iliac artery disease appears to have increased the incidence of attachment site endoleaks. Although many of these leaks have been successfully managed with adjunctive endovascular procedures, their increasing incidence is worrisome and suggests that we may need to re-evaluate current inclusion criteria for using this technology. Although difficult access issues have been handled with adjunctive procedures, the presence of a short, angulated proximal neck may be difficult to overcome, and may not be well suited for endovascular repair with the currently available devices

OBJECTIVE:The purpose of this study was to present the experience with aneurysm rupture after deployment of Guidant/EVT (Guidant) endografts and review previously reported cases with other devices. METHODS:Records from Guidant/EVT clinical trials and postmarket approval databases from February 1993 to August 2000 were analyzed to identify patients with rupture and to extract pertinent data. Previously reported cases were obtained with a Medline search. RESULTS:Seven ruptures were found with Guidant/EVT devices. Five of these occurred among the 686 patients in US Food and Drug Administration protocols (group I) who were followed for a mean of 41.8 +/- 21.9 months and limited to the subgroup of 93 first generation tube endografts. Two ruptures occurred in group II (3260 patients after market approval with limited follow-up), specifically in the subgroup of 166 patients who underwent treatment with second generation tube grafts. No ruptures were found in patients with bifurcation or unilateral iliac implants followed for a mean of 37.5 months. All ruptures were caused by distal aortic type I endoleaks on the basis of attachment system fractures (first generation devices only), aortic neck dilatations, persistent primary endoleaks, migration, overlooked imaging abnormalities, refused reintervention, and poor patient selection. The mortality rate was 57% (4/7) overall and was 50% for surgical repair (3/6). A literature search identified 40 additional ruptures related to other devices, for a total of 47. All 44 that were documented with adequate data were caused by endoleaks (26 type I, 2 type II, 11 type III, and 5 source not reported). Other contributing factors were graft module separation and graft wall deterioration. The overall mortality rate for the combined series was 50%, with an operative mortality rate of 41%. CONCLUSION/CONCLUSIONS:Postendograft AAA rupture is infrequent, although the true incidence rate is unclear because of inadequate follow-up of individual device designs. Tube endografts should be limited to the rare patient with ideal anatomy, no other alternatives, and at high risk for standard open repair. Prevention of aneurysm rupture requires long-term surveillance with attention to subtle imaging abnormalities and the establishment of reliable follow-up protocols for specific devices. The outcome of postendograft aneurysm rupture is similar to that of rupture without prior endograft therapy.

The natural history and clinical significance of type II or branch vessel endoleaks following endovascular aortic aneurysm (AAA) repair remain unclear. Some investigators have suggested that these endoleaks have a benign course and outcome and that they can be safely observed. The purpose of this study was to document the natural history and outcome of all type II endoleaks that have occurred following endovascular AAA repair at our institution. A review of a prospectively compiled database of all endovascular AAA repairs performed at our institution was performed. From this review, we determined that type II endoleaks appear to have a relatively benign course, with a reasonable chance of spontaneously sealing within a 2-year period. No cases of rupture or aneurysm enlargement were documented in patients with open type II leaks. However, almost one-third of the patients did not manifest a type II leak until after their initial CT scan. The implications of such a 'delayed' leak are unclear. Careful follow-up remains mandatory in patients with type II endoleaks to better define outcome

Prior studies have suggested that young patients may be more prone to recurrent disease after carotid endarterectomy (CEA). The goal of this study was to review a series of CEAs performed on younger patients (< or = 55 years) and to determine if these patients are more likely to develop recurrent stenosis. A review was conducted of CEAs performed from 1985 through 1994. Analysis was performed on a study group of 94 young patients who underwent 109 CEAs during this time. A control group of 222 patients older than 55 years who underwent 256 CEAs during the years 1991 through 1993 was selected for comparison. During a mean of nearly 4 years of follow-up, younger patients were significantly more likely to experience a late failure of CEA, including total occlusion of the operated artery, or recurrent stenosis requiring redo surgery. Careful patient evaluation is important in choosing younger patients who require CEA. Implications of these data include mandating careful noninvasive follow-up examinations for younger patients undergoing CEA

OBJECTIVES: Although the results of the Asymptomatic Carotid Atherosclerosis Study clearly demonstrated the benefit of surgical over medical management of severe carotid artery stenosis, the results for women in particular were less certain. This was to some extent because of the higher perioperative complication rate observed in the 281 women (3.6% vs 1.7% in men). The objective of this study was to review a large experience with carotid endarterectomy in female patients and to determine whether the perioperative results differed from those of male patients. METHODS: A review was conducted of a prospectively compiled database on all carotid endarterectomies performed between 1982 and 1997. Operations performed in 991 female patients were compared with those performed in 1485 male patients. RESULTS: Female patients had a significantly lower incidence of diabetes, coronary artery disease, and contralateral carotid artery occlusion than did male patients. Female patients had a significantly higher incidence of hypertension. There were no significant differences in the age, smoking history, anesthetic route, shunt use, or clamp tolerance between the two groups. Of 991 female patients, 659 (66.5%) had preoperative symptoms, whereas 332 (33.5%) cases were performed for asymptomatic stenosis. Among 1485 male patients, 1041 (70.1%) had symptoms, and 444 (29.9%) were symptom free before surgery. There were no significant differences noted in the perioperative stroke rates between men and women overall (2.3% vs 2.4%, P =.92), or when divided into symptomatic (2.5% vs 3.0%, P =.52) and asymptomatic (2.0% vs 1.2%, P =.55) cases. CONCLUSIONS: Carotid endarterectomy can be performed with equally low perioperative stroke rates in men and women in both symptomatic and asymptomatic cases. In this series, symptom-free female patients had the lowest overall stroke rate. The concerns of the Asymptomatic Carotid Atherosclerosis Study regarding the benefit of carotid endarterectomy in female patients should therefore not prevent clinicians from recommending and performing carotid endarterectomy in appropriately selected symptom-free female patients

In order to maximize the efficacy of carotid endarterectomy (CEA), the rate of perioperative stroke must be kept to a minimum. A recent analysis of carotid surgery at our institution found that most perioperative strokes were due to technical errors resulting in thrombosis or embolization. From 1992 through 1997 we have performed nearly 1200 additional CEAs; the purpose of this study was to examine recent trends in the causes of perioperative stroke, with specific attention to differences in symptomatic and asymptomatic patients. The records of 1041 patients undergoing 1165 CEAs were reviewed from a prospectively compiled database. Analysis of these data showed that a history of preoperative stroke appears to increase the risk of perioperative stroke after CEA. Surgical factors associated with perioperative stroke include an inability to tolerate clamping, use of an intraarterial shunt, and having surgery performed under general anesthesia; these factors are clearly interrelated and only the use of intraarterial shunting remains a risk factor by multivariate analysis. Over half of all perioperative strokes (54%) appear to be caused by intraoperative or postoperative thrombosis and embolization. The patient requiring use of intraarterial shunting and/or with a preoperative stroke most likely has a significant watershed area of brain at increased risk of infarction. However, technical errors are still the most common cause of perioperative stroke in these high-risk patients. Such high-risk patients may manifest clinical stroke from small emboli that may be tolerated by asymptomatic clamp-tolerant patients. Technical precision and appropriate cerebral protection are particularly critical for successful outcomes in high-risk patients