Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: There is increasing awareness that women may have worse outcomes following repair of abdominal aortic aneurysm (AAA). The aim of this study was to analyse the association between sex, age and in-hospital mortality after AAA using hospital episode data collected routinely at the nationwide level. METHODS: Data were extracted from the nationwide statutory Diagnosis Related Group statistics provided by the German Federal Statistical Office. Patients with a diagnosis of intact (non-ruptured) AAA (ICD-10 GM I71.4) and procedure codes (OPS; 2005-2013) for endovascular aneurysm repair (EVAR) (5-38a.1*) or open aneurysm repair (5-384.5, 5-384.7), treated from 2005 to 2013, were included. A multilevel multivariable regression model was applied to adjust for medical risk (using the Elixhauser co-morbidity score), type of procedure, type of admission, and to account for clustering of patients within centres. The primary outcome was in-hospital mortality. RESULTS: Some 84 631 patients were identified, of whom 10 039 (11·9 per cent) were women. Women were significantly older than men at admission (median 74 (i.q.r. 69-80) versus 72 (66-77) years; P < 0·001). EVAR was used less frequently in women (48·1 versus 54·7 per cent; P < 0·001). The in-hospital mortality rate was higher in women, overall (5·0 versus 3·1 per cent; relative risk 1·60, 95 per cent c.i. 1·45 to 1·75), and for EVAR (2·8 versus 1·5 per cent; RR 1·90, 1·60 to 2·30) and open repair (6·8 versus 5·0 per cent; RR 1·36, 1·22 to 1·52). In-hospital mortality increased with age and was highest in patients aged over 80 years. In multivariable regression analysis, female sex (RR 1·20, 1·07 to 1·35) and age per 10-year increase (RR 1·83, 1·73 to 1·95) were independent risk factors for higher in-hospital mortality. CONCLUSION: In Germany, women were older when undergoing AAA repair and were less likely to receive EVAR. Mortality rates were higher in older patients and in women, irrespective of the surgical technique used.

Outcomes of Endovascular Abdominal Aortic Aneurysm Repair in Octogenarians: Meta-analysis and Systematic Review.

OBJECTIVES: This meta-analysis and systematic review aimed to highlight the results of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) to assess safety and effectiveness in patients older than 80 years of age compared with younger patients. METHODS: PRISMA guidelines were used; quality was appraised, and data were extracted and analysed following the Cochrane collaboration. The MEDLINE and Embase databases were searched on December 31, 2016. All studies related to clinical outcomes following EVAR for AAA treatment in octogenarians compared with those in younger patients were included for a meta-analysis and systematic review of short- and midterm outcomes. Data were analysed using a fixed or random effects model by pooling and calculating odds ratios (ORs) or hazard ratios (HRs) and weighted mean differences, to investigate the safety and feasibility of endoluminal treatment in octogenarians. RESULTS: Published literature search identified nine observational studies, comprising 25,723 patients with AAA (5989 octogenarians and 19,734 younger patients). More males (OR 0.621, p=.002) and smokers (OR 0.457, p<.001) were observed in the younger group. Frequent concomitant diseases were associated with advanced age, thus, the procedural duration, blood loss estimation, and length of stay were considerably higher among octogenarians. Although elderly patients have a higher 30 day mortality (2.7% vs. 1.5%, p<.001), endoleak, pulmonary, and renal diseases, no significant difference was found in the technical success of the procedure. As expected, the HR for octogenarians was markedly higher than that of younger patients (HR 1.946, p<.001) for midterm all-cause mortality. However, the re-intervention rate to maximum follow-up period of 5 years was not significantly different (HR 1.148, p=.408) between the groups. CONCLUSION: Compared with younger patients, EVAR in octogenarians is associated with a significantly higher but still acceptable peri-operative and midterm mortality rate. Because of similar midterm re-intervention rates, these findings suggest that EVAR remains an appropriate therapeutic approach in the elderly group if comprehensive pre-operative evaluation and post-operative surveillance are incorporated.

Trends in Patient Safety of Intact Abdominal Aortic Aneurysm Repair: German Registry Data on 36,594 Procedures.

OBJECTIVE/BACKGROUND: The study aim was to determine whether patient safety for non-ruptured abdominal aortic aneurysm (nrAAA) repair has changed between 1999 and 2010 in a large German cohort. METHODS: The data source was the prospective quality assurance registry of the German Vascular Society from 1999 to 2010. Patient characteristics, surgical techniques (open aortic repair [OAR], endovascular aortic repair [EVAR]), procedural time and outcomes, including the length of hospital stay (LOS), were analysed using the Cochran-Armitage test for binary parameters and Spearman's correlation coefficient for quantitative parameters. RESULTS: A total of 36,594 operations (23,037 OAR, 13,557 EVAR) for infrarenal nrAAA in 201 hospitals in Germany were investigated. Patients' mean age increased from 69.6 to 72.0 years (p < .001). The rate of patients with American Society of Anesthesiologists scores of 3 or 4 increased (p < .001). Use of EVAR increased (1999: 16.7%; 2010: 62.7%; p < .001), and since 2009, EVAR has been more frequently used than OAR. The overall in hospital mortality decreased from 3.1% in 1999 to 2.3% in 2010 (p < .001). There were no temporal trends for mortality rates for EVAR (p = .233) or OAR (p = .281) when considered separately. Cardiac (1999: 8.1%; 2010: 5.1%; p < .001) and pulmonary (1999: 7.8%; 2010: 4.8%; p < .001) complications decreased. The rate of post-operative renal failure increased (1999: 3.6%; 2010 4.1%; p = .017), without increasing the rate of patients needing dialysis (1999: 1.7%; 2010: 1.7%; p = .171). The median LOS decreased from 17 days in 1999 to 10 days in 2010 (p < .001). CONCLUSION: This study shows significantly improved post-procedural in hospital outcomes and decreased use of resources for nrAAA repair. This trend can probably be attributed to the implementation of EVAR as a standard technique, but some trends could also possibly be explained by a change in the remuneration system. The main limitation of the registry is the lack of internal and external validation. However, in hospital patient safety for AAA repair seems to have improved significantly in the participating hospitals.

Association of Matrix Metalloproteinase Levels with Collagen Degradation in the Context of Abdominal Aortic Aneurysm.

OBJECTIVE/BACKGROUND: Matrix metalloproteinases (MMPs) have already been identified as key players in the pathogenesis of abdominal aortic aneurysm (AAA). However, the current data remain inconclusive. In this study, the expression of MMPs at mRNA and protein levels were investigated in relation to the degradation of collagen I and collagen III. METHODS: Tissue samples were obtained from 40 patients with AAA undergoing open aortic repair, and from five healthy controls during kidney transplantation. Expression of MMPs 1, 2, 3, 7, 8, 9, and 12, and tissue inhibitor of metalloproteinase (TIMP)1, and TIMP2 were measured at the mRNA level using quantitative reverse transcription polymerase chain reaction. At the protein level, MMPs, collagen I, and collagen III, and their degradation products carboxy-terminal collagen cross-links (CTX)-I and CTX-III, were quantified via enzyme linked immunosorbent assay. In addition, immunohistochemistry and gelatine zymography were performed. RESULTS: In AAA, significantly enhanced mRNA expression was observed for MMPs 3, 9, and 12 compared with controls (p ≤ .001). MMPs 3, 9, and 12 correlated significantly with macrophages (p = .007, p = .018, and p = .015, respectively), and synthetic smooth muscle cells with MMPs 1, 2, and 9 (p = .020, p = .018, and p = .027, respectively). At the protein level, MMPs 8, 9, and 12 were significantly elevated in AAA (p = .006, p = .0004, and p < .001, respectively). No significant correlation between mRNA and protein was observed for any MMP. AAA contained significantly reduced intact collagen I (twofold; p = .002), whereas collagen III was increased (4.6 fold; p < .001). Regarding degraded collagen I and III relative to intact collagens, observations were inverse (1.4 fold increase for CTX-1 [p < .001]; fivefold decrease for CTX-III [p = .004]). MMPs 8, 9, and 12 correlated with collagen I (p = .019, p < .001, and p = 0.003, respectively), collagen III (p = .015, p < .001, and p < .001, respectively), and degraded collagen I (p = .012, p = .049, and p = .001, respectively). CONCLUSION: No significant relationship was found between mRNA and protein and MMP levels. MMPs 9 and 12 were overexpressed in AAA at the mRNA and protein level, and MMP-8 at the protein level. MMP-2 was detected in synthetic SMCs. Collagen I and III showed inverse behaviour in AAA. In particular, MMPs 8, 9, and 12 appear to be associated with collagen I, collagen III, and their degradation products.

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses.

BACKGROUND: Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. METHODS: SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). RESULTS: The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n = 203); CAS vs. BMT (n = 197), and BMT alone (n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. CONCLUSIONS: Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration.

Measurements After Image Post-processing Are More Precise in the Morphometric Assessment of Thoracic Aortic Aneurysms: An Intermodal and Intra-observer Evaluation.

OBJECTIVES: Precise pre-procedural anatomical analysis of aneurysmal anatomy is essential for successful thoracic endovascular aortic repair (TEVAR). Since surgeons and radiologists have to perform multiple measurements in the same patient, high intra-observer reliability of any imaging method is mandatory. Commercially available three dimensional (3D) post-processing techniques are expected to be superior to conventional two dimensional multiplanar reconstructions (MPRs) derived from computed tomography angiograms (CTAs). However, few data exist to support this view. This study aims to evaluate the intermodal and intra-observer differences using 3D software (3surgery) in descending thoracic aortic aneurysms (dTAAs). METHODS: Pre-operative CTAs (performed between 2004 and 2010) of 30 dTAAs (mean maximum diameter 61.4 ± 13 mm) were assessed by three independent investigators with different experience in the measurement of aortic pathologies. Intra-observer reliability and intermodal differences (3D vs. 2D) were investigated using pre-specified measurement points (distances of total length, maximum diameter, proximal and distal landing zones). Statistical analyses were performed using the Bland-Altman method and a mixed regression model. RESULTS: Intermodal comparison showed that 2D measurements significantly underestimate the measured distances (maximum diameter 3.7 mm [95% CI -5.3 to -2.1] and landing zone maximum 1.4 mm [95% CI -2.0 to -0.2] shorter with 2D, p < .05). In almost all 3D measurements, all investigators showed lower variability comparing the intra-observer differences, most notably in the measuring point total length (reduction of the SD up to 7.9 mm). CONCLUSIONS: These data show that both techniques led to significant measurement disparity. This occurs especially at the point of indication (maximum diameter) and the total length of the aneurysm (important for correct stent graft selection). But overall the variability is reduced with the 3D technique, which also tends to measure greater distances. The use of post-processing software therefore leads to more precise device selection for TEVAR in TAA.

[Indications and results of endovascular therapy of critical limb ischemia]. / Indikationen und Ergebnisse der endovaskulären Therapie der kritischen Extremitätenischämie.

BACKGROUND: Critical limb ischemia (CLI) is the most severe form of peripheral artery occlusive disease and is characterized by high amputation, morbidity and mortality rates. Therefore, revascularization is the essential step in therapy for retention of the affected limb. OBJECTIVES: Although for a long time bypass surgery represented the gold standard in the treatment of CLI, in recent years there has been a disproportionate increase of endovascular treatment despite the lack of level-data. In this review the indications and results of endovascular therapy of CLI are presented on the basis of published data. METHODS: A literature search was carried out to identify publications that compared the results of endovascular and surgical therapy as well as observational studies about different endovascular techniques. RESULTS: The BASIL study provided the highest quality data comparing endovascular and surgical treatment of CLI. The long-term data of the BASIL trial showed that apart from patients with a suitable vein and a life expectancy of more than 2 years, first line endovascular therapy is equivalent to surgical treatment. The equivalence could also be demonstrated in a meta-analysis comparing operative and endovascular treatment of CLI. CONCLUSION: The CLI is a disease with high mortality and morbidity risks. Due to the comparable amputation-free survival times with lower complication rates in the published data, in most patients an endovascular first strategy in experienced centers can be justified.

CXCR4: A Potential Marker for Inflammatory Activity in Abdominal Aortic Aneurysm Wall.

OBJECTIVES: The aim of the study was to evaluate the potential role of chemokine receptor CXCR4 and its ligand CXCL12 in the pathogenesis of abdominal aortic aneurysm (AAA). METHODS: AAA tissue specimens were obtained from the anterior or lateral aneurysm sac of patients (n = 32, 26 males, 6 females; 66.8 ± 11.2 years, diameter 64.4 ± 17.0 mm), who underwent elective open surgical repair. Twelve non-aneurysmal aortic specimens from transplant donors served as controls. Expression analysis of CXCR4 and CXCL12 at mRNA and protein level was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Immunohistochemical staining of corresponding histological sections for CD3 (T-cells), CD20 (B-cells), and CD68 (macrophages) was performed to determine the cellular localization of CXCR4 and CXCL12. Data were analyzed with SPSS 20.0 using Mann-Whitney U test and Spearman's rank correlation coefficient. RESULTS: Gene expression of CXCR4 and CXCL12 was 9.6 and 4.6 fold higher in AAA than in non-aneurysmal aorta (p = .0004 and p < .0001, respectively). Likewise, the protein level of CXCR4 was increased 3.2 fold in AAA wall compared with non-aneurysmal aortic tissue (p < .0001), although CXCL12 could not be detected. Immunohistochemical analysis revealed that CXCR4 was expressed in B and T lymphocytes and macrophages, and CXCL12 was observed only in plasma cells. CONCLUSIONS: This study confirmed the over expression of CXCR4 in human AAA tissue. CXCR4 was detected both at the mRNA and the protein level and by immunohistochemistry, especially in inflammatory cells. In contrast, CXCL12 expression was observed only at the mRNA level, with the exception of plasma cells. The exact role of CXCR4/CXCL12 in AAA has to be further elucidated.

Interaction of biomechanics with extracellular matrix components in abdominal aortic aneurysm wall.

OBJECTIVE: Little is known about the interactions between extracellular matrix (ECM) proteins and locally acting mechanical conditions and material macroscopic properties in abdominal aortic aneurysm (AAA). In this study, ECM components were investigated with correlation to corresponding biomechanical properties and loads in aneurysmal arterial wall tissue. METHODS: Fifty-four tissue samples from 31 AAA patients (30♂; max. diameter Dmax 5.98 ± 1.42 cm) were excised from the aneurysm sac. Samples were divided for corresponding immunohistological and mechanical analysis. Collagen I and III, total collagen, elastin, and proteoglycans were quantified by computational image analysis of histological staining. Pre-surgical CT data were used for 3D segmentation of the AAA and calculation of mechanical conditions by advanced finite element analysis. AAA wall stiffness and strength were assessed by repeated cyclical, sinusoidal and destructive tensile testing. RESULTS: Amounts of collagen I, III, and total collagen were increased with higher local wall stress (p = .002, .017, .030, respectively) and strain (p = .002, .012, .020, respectively). AAA wall failure tension exhibited a positive correlation with collagen I, total collagen, and proteoglycans (p = .037, .038, .022, respectively). α-Stiffness correlated with collagen I, III, and total collagen (p = .011, .038, and .008), while ß-stiffness correlated only with proteoglycans (p = .028). In contrast, increased thrombus thickness was associated with decreased collagen I, III, and total collagen (p = .003, .020, .015, respectively), and AAA diameter was negatively associated with elastin (p = .006). CONCLUSIONS: The present results indicate that in AAA, increased locally acting biomechanical conditions (stress and strain) involve increased synthesis of collagen and proteoglycans with increased failure tension. These findings confirm the presence of adaptive biological processes to maintain the mechanical stability of AAA wall.

Endovascular repair of acute uncomplicated aortic type B dissection promotes aortic remodelling: 1 year results of the ADSORB trial.

OBJECTIVES: Uncomplicated acute type B aortic dissection (AD) treated conservatively has a 10% 30-day mortality and up to 25% need intervention within 4 years. In complicated AD, stent grafts have been encouraging. The aim of the present prospective randomised trial was to compare best medical treatment (BMT) with BMT and Gore TAG stent graft in patients with uncomplicated AD. The primary endpoint was a combination of incomplete/no false lumen thrombosis, aortic dilatation, or aortic rupture at 1 year. METHODS: The AD history had to be less than 14 days, and exclusion criteria were rupture, impending rupture, malperfusion. Of the 61 patients randomised, 80% were DeBakey type IIIB. RESULTS: Thirty-one patients were randomised to the BMT group and 30 to the BMT+TAG group. Mean age was 63 years for both groups. The left subclavian artery was completely covered in 47% and in part in 17% of the cases. During the first 30 days, no deaths occurred in either group, but there were three crossovers from the BMT to the BMT+TAG group, all due to progression of disease within 1 week. There were two withdrawals from the BMT+TAG group. At the 1-year follow up there had been another two failures in the BMT group: one malperfusion and one aneurysm formation (p = .056 for all). One death occurred in the BMT+TAG group. For the overall endpoint BMT+TAG was significantly different from BMT only (p < .001). Incomplete false lumen thrombosis, was found in 13 (43%) of the TAG+BMT group and 30 (97%) of the BMT group (p < .001). The false lumen reduced in size in the BMT+TAG group (p < .001) whereas in the BMT group it increased. The true lumen increased in the BMT+TAG (p < .001) whereas in the BMT group it remained unchanged. The overall transverse diameter was the same at the beginning and after 1 year in the BMT group (42.1 mm), but in the BMT+TAG it decreased (38.8 mm; p = .062). CONCLUSIONS: Uncomplicated AD can be safely treated with the Gore TAG device. Remodelling with thrombosis of the false lumen and reduction of its diameter is induced by the stent graft, but long term results are needed.

[Treatment of asymptomatic carotid artery stenosis: improvement of evidence with new SPACE-2 design necessary]. / Therapie asymptomatischer Karotisstenosen: Notwendige Klärung der Evidenz mit neuem SPACE-2-Design.

Asymptomatic carotid artery stenosis may be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS) or with best medical treatment (BMT) only. Definitive and evidence-based treatment recommendations for one of these options are currently not possible. Studies showing an advantage of CEA over BMT alone do not meet current standards from a pharmacological point of view. On the other hand, more recent data point to a further stroke risk reduction using BMT according to current standards. Studies on carotid artery stenting as a third alternative treatment are partially insufficient, especially when comparing CAS with BMT. Initiated in 2009, the randomized, controlled, multicenter SPACE-2 trial is intended to answer the question about the best treatment option of asymptomatic carotid artery stenosis; however, to increase recruitment rates as a condition for the successful completion of this important study, the trial design had to be modified.

C-type natriuretic peptide and its receptors in atherosclerotic plaques of the carotid artery of clinically asymptomatic patients.

OBJECTIVES: C-type natriuretic peptide (CNP) has anti-inflammatory, anti-proliferative and anti-migratory properties. No data exist on the presence of CNP in human atherosclerotic plaques of the carotid artery. Therefore, this study aimed to analyse qualitatively the distribution pattern and characteristics of CNP and its receptors in both, early and advanced human carotid plaques, as well as in stable and unstable lesions. In addition, the aim of this study was to evaluate CNP and its receptors as possible biomarkers to predict plaque stability in advanced lesions. METHODS: Advanced carotid artery plaques of 40 asymptomatic patients (20 histologically stable and 20 histologically unstable) and early arteriosclerotic lesions of three patients were analysed. RESULTS: Serum level of CNP was similar in patients with stable and unstable plaques (196 ± 19 pg ml(-1) vs. 198 ± 25 pg ml(-1), p = 0.948). Expression level of natriuretic peptide receptor 3 (NPR3) was significantly higher in unstable plaques compared to stable plaques (5.6 ± 1.8% vs. 1.7 ± 0.5%, p = 0.045). Expression levels of CNP and NPR2 were higher in unstable plaques but the differences were not statistically significant. The distribution pattern of CNP, NPR2 and NPR3 varied qualitatively between early and advanced carotid plaques. No relevant histological differences were observed with respect to plaque stability. CONCLUSIONS: This study shows the presence of CNP and its receptors in atherosclerotic plaques of human carotid artery, with increased expression of NPR3 in histologically unstable plaques. In this study, serum CNP was not associated with histological plaque stability. In future, larger studies are required to further evaluate whether proteins of the CNP axis would be useful as biomarkers.

Differences in patterns of peripheral arterial occlusive disease and eligibility for endovascular treatment.

BACKGROUND: To analyze differences in morphological changes in the vascular tree among patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). In addition, suitability for endovascular treatment was evaluated. PATIENTS AND METHODS: Our study included 690 lower extremities with IC or CLI in 500 consecutive patients who were assessed by magnetic resonance angiography (MRA) according to the TASC II classification and in terms of the below the knee run-off status. Multivariable logistic regressions models adjusted for cardiovascular risk factors were used to evaluate differences in arteriosclerotic lesion patterns and eligibility for endovascular treatment. RESULTS: Multivariable analysis showed that compared with IC extremities, CLI extremities have significantly more severe arteriosclerotic lesions at the aortoiliac (p < 0.001), femoropopliteal (p < 0.001), and crural levels (p < 0.001), with a greater risk of multilevel disease (odds ratio [OR], 1.71; 95 % confidence interval [CI] 1.10 - 2.66; p = 0.018). More than 80 % of extremities with IC and more than 50 % of extremities with CLI appeared to be eligible for endovascular treatment in an isolated evaluation of the aortoiliac and femoropopliteal axis. For combined evaluation of the aortoiliac and femoropopliteal axis, the proportion of endovascular suitability (TASC A+B lesions) decreased to 65 % (IC) and 41 % (CLI). For TASC A+B+C lesions, the proportions were 79 % (IC) and 41 % (CLI). CONCLUSIONS: Lower extremities with IC and CLI significantly differ in terms of arteriosclerotic lesion morphology and patterns of lesion localization. The majority of IC and CLI extremities appear to be eligible for endovascular treatment. Because of further improvement in endovascular equipment, even more patients will be eligible for treatment.

WITHDRAWN: Rationale and Design of a Randomised Controlled Trial Comparing Stent-Protected Angioplasty with Bypass Surgery for Intermittent Claudication: The ABC Study.

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Final results of the prospective European trial of the Endurant stent graft for endovascular abdominal aortic aneurysm repair.

OBJECTIVES: The Endurant Stent Graft System (Medtronic Vascular, Santa Rosa, CA) is specifically designed to treat patients with abdominal aortic aneurysm, including those with difficult anatomies. This is the 1-year report of a prospective, non-randomised, open-label trial at 10 European centres. METHODS: Between November 2007 and August 2008, 80 patients were enrolled for elective endovascular aneurysm repair (EVAR) with the Endurant; 71 with moderate (≤ 60°) and nine with high (60-75°) infrarenal aortic neck angulation. Safety and stent-graft performance were assessed throughout a 1-year follow-up period. RESULTS: The device was successfully delivered and deployed in all cases. All-cause mortality was 5% (4/80), with one possibly device-related death. Serious adverse events were comparable between the high and moderate angulation groups. There were no device migrations, stent fractures, aortic ruptures or conversions to open repair. Maximal aneurysm diameter decreased >5 mm in 42.7% of cases. A total of 28 endoleaks were observed (26 type II, two undetermined). Three secondary endovascular procedures were performed for outflow vessel stenosis, graft limb occlusion and iliac extension, resulting in a secondary patency rate of 100%. No re-interventions were required in the high angulation group. CONCLUSIONS: The Endurant Stent Graft was successfully delivered and deployed in all cases and performed safely and effectively in all patients, including those with unfavourable proximal neck anatomy.

Chapter II: Diagnostic methods.

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.

Chapter III: Management of cardiovascular risk factors and medical therapy.

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations.