Frans L. Moll

Management of Abdominal Aortic Aneurysms Clinical Practice Guidelines of the European Society for Vascular Surgery

Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands b Imperial College, London, UK University Hospital Innsbruck, Austria Azienda Ospedaliera di Perugia, Italy Hopital Cardiologique, CHRU de Lille, Lille, France f St Thomas’ Hospital, London, UK g St George’s Vascular Institute, London, UK Yale University School of Medicine, New Haven, Connecticut, USA University of Siena, Siena, Italy University of Poitiers, Poitiers, France

Composition of Carotid Atherosclerotic Plaque Is Associated With Cardiovascular Outcome A Prognostic Study

Background— Identification of patients at risk for primary and secondary manifestations of atherosclerotic disease progression is based mainly on established risk factors. The atherosclerotic plaque composition is thought to be an important determinant of acute cardiovascular events, but no prospective studies have been performed. The objective of the present study was to investigate whether atherosclerotic plaque composition is associated with the occurrence of future vascular events. Methods and Results— Atherosclerotic carotid lesions were collected from patients who underwent carotid endarterectomy and were subjected to histological examination. Patients underwent clinical follow-up yearly, up to 3 years after carotid endarterectomy. The primary outcome was defined as the composite of a vascular event (vascular death, nonfatal stroke, nonfatal myocardial infarction) and vascular intervention. The cumulative event rate at 1-, 2-, and 3-year follow-up was expressed by Kaplan–Meier estimates, and Cox proportional hazards regression analyses were performed to assess the independence of histological characteristics from general cardiovascular risk factors. During a mean follow-up of 2.3 years, 196 of 818 patients (24%) reached the primary outcome. Patients whose excised carotid plaque revealed plaque hemorrhage or marked intraplaque vessel formation demonstrated an increased risk of primary outcome (risk difference=30.6% versus 17.2%; hazard ratio [HR] with [95% confidence interval]=1.7 [1.2 to 2.5]; and risk difference=30.0% versus 23.8%; HR=1.4 [1.1 to 1.9], respectively). Macrophage infiltration (HR=1.1 [0.8 to 1.5]), large lipid core (HR=1.1 [0.7 to 1.6]), calcifications (HR=1.1 [0.8 to 1.5]), collagen (HR=0.9 [0.7 to 1.3]), and smooth muscle cell infiltration (HR=1.3 [0.9 to 1.8]) were not associated with clinical outcome. Local plaque hemorrhage and increased intraplaque vessel formation were independently related to clinical outcome and were independent of clinical risk factors and medication use. Conclusions— The local atherosclerotic plaque composition in patients undergoing carotid endarterectomy is an independent predictor of future cardiovascular events.

Hemodialysis Arteriovenous Fistula Patency Revisited: Results of a Prospective, Multicenter Initiative

BACKGROUND AND OBJECTIVES Vascular access standards are predominantly based on older, single-center reports; however, the hemodialysis population has changed dramatically and primary arteriovenous fistula failure is a huge problem. This prospective, multicenter study used standardized definitions to analyze patency rates and potential risk factors that affect functional patency and late arteriovenous fistula functionality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Eleven centers participated in a guidelines implementation program. All new permanent vascular accesses were included. Patency and functional patency, defined as access survival from creation and from first dialysis use, respectively, were calculated using Kaplan-Meier analysis. Risk factors for primary functional patency loss (intervention-free interval) and secondary failure (abandonment) were determined using regression models. RESULTS A total of 491 arteriovenous fistulas were placed in 395 patients. Six-, 12-, and 18-mo secondary patency and functional patency were 75 +/- 2.0, 70 +/- 2.3, and 67 +/- 2.7% and 90 +/- 1.9, 88 +/- 2.2, and 86 +/- 2.7%, respectively. Primary failure rate was 40%. Thrombosis rate was 0.14 per patient-year. Diabetes and arteriovenous fistula surveillance were significantly associated with primary functional patency loss. Preoperative duplex was inversely related to secondary failure. The secondary failure rate per hospital varied from 0 to 39%. CONCLUSIONS This study showed a marked difference between patency and functional patency, likely to be explained by high primary failure rates. Hemodialysis patients with diabetes can be expected to have reduced primary functional patency rates, but if treated adequately, then arteriovenous fistula functionality can be maintained as long as in patients without diabetes.

Matrix Metalloproteinase 2 Is Associated With Stable and Matrix Metalloproteinases 8 and 9 With Vulnerable Carotid Atherosclerotic Lesions: A Study in Human Endarterectomy Specimen Pointing to a Role for Different Extracellular Matrix Metalloproteinase Inducer Glycosylation Forms

Background and Purpose— We studied matrix metalloproteinases (MMP) 2, 8, and 9 and extracellular matrix metalloproteinase inducer (EMMPRIN) levels in relation to carotid atherosclerotic plaque characteristics. Methods— Carotid atherosclerotic plaques (n=150) were stained and analyzed for the presence of collagen, smooth muscle cell (SMC), and macrophages. Adjacent segments were used to isolate total protein to assess MMP-2 and MMP-9 activities and gelatin breakdown, MMP-8 activity, and EMMPRIN levels. Results— Macrophage-rich lesions revealed higher MMP-8 and MMP-9 activities, whereas SMC-rich lesions showed higher MMP-2 activity. The levels of less glycosylated EMMPRIN-45kD were higher in SMC-rich lesions and lower in macrophage-rich plaques. EMMPRIN-45kD was associated with MMP-2 levels, whereas EMMPRIN-58kD was related to MMP-9 levels. Conclusions— MMP-2, MMP-8, and MMP-9 activities differed among carotid plaque phenotypes. Different EMMPRIN glycosylation forms are associated with either MMP-2 or MMP-9 activity, which suggests that EMMPRIN glycosylation may play a role in MMP regulation and plaque destabilization.

The significance of microemboli detection by means of transcranial Doppler ultrasonography monitoring in carotid endarterectomy

PURPOSE Carotid endarterectomy (CEA) performed with continuous transcranial Doppler monitoring provides a unique opportunity to determine the number of cerebral microemboli and to relate their occurrence to the surgical technique. The purpose of this study was to assess in CEA the impact of cerebral microembolism on clinical outcome and brain architecture. We also evaluated the influence of the audible transcranial Doppler signal on the surgeon and his or her technique. METHODS In a prospective series of 301 patients, CEA was monitored with electroencephalography and transcranial Doppler ultrasonography of the ipsilateral middle cerebral artery. Preoperative and intraoperative risk factors were entered in a logistic regression analysis program to assess their correlation with cerebral outcome. To evaluate the impact of cerebral microembolism on brain architecture, we compared preoperative and postoperative computed tomography scans or magnetic resonance images of the brain in two subgroups of 58 and 40 patients, respectively. RESULTS Seven (2.3%) patients had intraoperative transient ischemic symptoms, three (1%) had intraoperative strokes, 1 (0.3%) had transient ischemic symptoms after operation, and 10 (3.3%) had postoperative strokes. Four (1.3%) patients died. Microemboli (> 10) noticed during dissection were related to both intraoperative (p < 0.002) and postoperative (p < 0.02) cerebral complications. Microemboli that occurred during shunting were also related to intraoperative complications (p < 0.007). Microembolism never resulted in new morphologic changes on postoperative computed tomography scans. On the contrary, the phenomenon of more than 10 microemboli during dissection was significantly (p < 0.005) related to new hyperintense lesions on postoperative T2-weighted magnetic resonance images. CONCLUSIONS During CEA the presence of microembolism (> 10 microemboli) during dissection shows a statistically significant relationship with perioperative cerebral complications and with new ischemic lesions on magnetic resonance images of the brain. Moreover, microembolism during shunting is also related to intraoperative complications. Surgeons can be guided by the audio Doppler and emboli signals by changing their technique. This change may result in a decrease of microembolism and consequently in a decline of the intraoperative stroke rate.

Impact of microembolism and hemodynamic changes in the brain during carotid endarterectomy.

Background and Purpose Monitoring of carotid endarterectomy with electroencephalography and transcranial Doppler ultrasonography provides instantaneous information about hemodynamic changes and embolic signals. However, a relation between these findings and intraoperative infarcts has not yet been demonstrated. Methods In this study we compared preoperative and postoperative computed tomographic scans (58 patients) or magnetic resonance imaging (40 patients) of the brain, assessed by two independent observers, to detect intraoperative infarcts, and we related any such new lesions to the findings of intraoperative monitoring. Results In the computed tomography series one intraoperative infarct occurred, with corresponding clinical deficits. In the magnetic resonance group four patients developed new lesions that occurred intraoperatively, all of which were clinically silent. There was a significant relation between the number of embolic signals during the surgical dissection of the carotid artery and the occurrence of intraoperative infarcts (P<.005). Three of the four infarcts were of the lacunar type; the fourth patient had a border-zone infarct, associated not only with many embolic signals but also with low flow during cross-clamping. There were no demonstrable ultrasound side effects on brain tissue. Conclusions Embolic signals detected by transcranial Doppler monitoring in the dissection phase of carotid endarterectomy show a significant relation to new ischemic lesions and therefore are potentially harmful. The phenomenon should alert the vascular surgeon.

High Neutrophil Numbers in Human Carotid Atherosclerotic Plaques Are Associated With Characteristics of Rupture-Prone Lesions

Objective—To score the number of plaque neutrophils and relate the score to plaque morphology and inflammatory status. Methods and Results—Neutrophils are inflammatory cells with tissue destruction capabilities that have been found at the site of an atherosclerotic plaque rupture or erosion. Poor evidence exists for neutrophil infiltration in human carotid atherosclerotic plaques, and its association with plaque morphology has not yet been described. A set of 355 human carotid plaques was stained for the neutrophil marker CD66b. High neutrophil numbers were found in plaques with a large lipid core, high macrophage numbers, and low collagen amount and smooth muscle cell numbers. High neutrophil numbers were associated with high interleukin 8 (P<0.001) and matrix metalloproteases 8 (P=0.005) and 9 (P<0.001) plaque levels. High microvessel density within plaques was correlated with high neutrophil numbers (P=0.01). In addition, low numbers of neutrophils were associated with female sex and use of &bgr;-blockers. Conclusion—For the first time to our knowledge, these results show that neutrophil numbers are strongly associated with the histopathologic features of rupture-prone atherosclerotic lesions and suggest a role for neutrophils in plaque destabilization.

Aneurysm Rupture after EVAR: Can the Ultimate Failure be Predicted?

OBJECTIVES To provide insight into the causes and timing of AAA rupture after EVAR. DESIGN Original data regarding AAA ruptures following EVAR were collected from MEDLINE and EMBASE databases. Data were extracted systematically and patient and procedural characteristics were analyzed. RESULTS 270 patients with AAA ruptures after EVAR were identified. Causes of rupture included endoleaks (in 160: type IA 57, type IB 31, type II 23, type III 26, type IV 0, endotension 9, unspecified 14), graft migration 41, graft disconnection 11 and infection 6. Most of the described AAA ruptures occurred within 2-3 years after EVAR. Mean initial AAA diameter was relatively large (65 mm). No abnormalities were present in 41 patients during follow-up before rupture. Structural graft failure was described in 96 and a fatal course in 119 patients. CONCLUSIONS Focus of surveillance on the first 2-3 years after EVAR may possibly reduce the AAA rupture rate, especially in patients with increased risk of early rupture (relatively large initial AAA diameter or presence of endoleak or graft migration). Better stent-graft durability and longevity is required to further reduce the AAA rupture risk after EVAR. Complete prevention will however remain challenging since AAA rupture may occur even if no predisposing abnormalities are present.

Meta-analysis of open versus endovascular repair for ruptured descending thoracic aortic aneurysm

INTRODUCTION Ruptured descending thoracic aortic aneurysm (rDTAA) is associated with high mortality rates. Data supporting endovascular thoracic aortic aneurysm repair (TEVAR) to reduce mortality compared with open repair are limited to small series. We investigated published reports for contemporary outcomes of open and endovascular repair of rDTAA. METHODS We systematically reviewed all studies describing the outcomes of rDTAA treated with open repair or TEVAR since 1995 using MEDLINE, Cochrane Library CENTRAL, and Excerpta Medica Database (EMBASE) databases. Case reports or studies published before 1995 were excluded. All articles were critically appraised for relevance, validity, and availability of data regarding treatment outcomes. All data were systematically pooled, and meta-analyses were performed to investigate 30-day mortality, myocardial infarction, stroke, and paraplegia rates after both types of repair. RESULTS Original data of 224 patients (70% male) with rDTAA were identified: 143 (64%) were treated with TEVAR and 81 (36%) with open repair. Mean age was 70 +/- 5.6 years. The 30-day mortality was 19% for patients treated with TEVAR for rDTAA compared 33% for patients treated with open repair, which was significant (odds ratio [OR], 2.15, P = .016). The 30-day occurrence rates of myocardial infarction (11.1% vs 3.5%; OR, 3.70, P < .05), stroke (10.2% vs 4.1%; OR, 2.67; P = .117), and paraplegia (5.5% vs 3.1%; OR, 1.83; P = .405) were increased after open repair vs TEVAR, but this failed to reach statistical significance for stroke and paraplegia. Five additional patients in the TEVAR group died of aneurysm-related causes after 30 days, during a median follow-up of 17 +/- 10 months. Follow-up data after open repair were insufficient. The estimated aneurysm-related survival at 3 years after TEVAR was 70.6%. CONCLUSION Endovascular repair of rDTAA is associated with a significantly lower 30-day mortality rate compared with open surgical repair. TEVAR was associated with a considerable number of aneurysm-related deaths during follow-up.

Growth predictors and prognosis of small abdominal aortic aneurysms

OBJECTIVE Evidence regarding the influence of cardiovascular risk factors, comorbidities, and patient characteristics on the growth of small abdominal aortic aneurysms (AAA) is limited. We assessed, in an observational cohort study, rupture rates, risks of mortality, and the effects of cardiovascular risk factors and patient demographics on growth rates of small AAAs. METHODS Between September 1996 and January 2005, 5057 patients with manifest arterial vascular disease or cardiovascular risk factors were included in the Second Manifestation of ARTerial disease (SMART) study. Measurements of the abdominal aortic diameter were performed in all patients. All patients with an initial AAA diameter between 30 and 55 mm were selected for this study. All AAA measurements during follow-up until August 2007 were collected. Multivariate regression analysis was performed to calculate the effects of demographic patient characteristics, initial AAA diameter, and cardiovascular risk factors on AAA growth. RESULTS Included were 230 patients, with a mean age of 66 years and 90% were male. Seven AAA ruptures (six fatal) occurred in 755 patient years of follow-up (rupture rate 0.9% per patient-year). In 147 patients, AAA measurements were performed for a period of more than 6 months. The median follow-up time was 3.3 years (mean 4.0, range 0.5 to 11.1 years, standard deviation (SD) 2.5). Mean AAA diameter was 38.8 mm (SD 6.8) and mean expansion rate 2.5 mm/y. Patients using lipid-lowering drugs had a 1.2 mm/y (95% confidence interval [CI] -2.34 to -0.060 mm/y) lower AAA growth rate compared to nonusers of these drugs. Initial AAA diameter was associated with a 0.09 mm/y (95% CI 0.01 to 0.18 mm/y) higher growth rate per millimetre increase of the diameter. No other factors, including blood lipid values, were independently associated with AAA growth. CONCLUSIONS Lipid-lowering drug treatment and initial AAA diameter appear to be independently associated with lower AAA growth rates. The risk of rupture of these small abdominal aortic aneurysms was low, which pleads for watchful waiting.