Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial.

BACKGROUND: The optimal treatment for patients with asymptomatic carotid artery stenosis is under debate. Since best medical treatment (BMT) has improved over time, the benefit of carotid endarterectomy (CEA) or carotid artery stenting (CAS) is unclear. Randomised data comparing the effect of CEA and CAS versus BMT alone are absent. We aimed to directly compare CEA plus BMT with CAS plus BMT and both with BMT only. METHODS: SPACE-2 was a multicentre, randomised, controlled trial at 36 study centres in Austria, Germany, and Switzerland. We enrolled participants aged 50-85 years with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70%, according to European Carotid Surgery Trial criteria. Initially designed as a three-arm trial including one group for BMT alone (with a randomised allocation ratio of 2·9:2·9:1), the SPACE-2 study design was amended (due to slow recruitment) to become two substudies with two arms each comparing CEA plus BMT with BMT alone (SPACE-2a) and CAS plus BMT with BMT alone (SPACE-2b); in each case in a 1:1 randomisation. Participants and clinicians were not masked to allocation. The primary efficacy endpoint was the cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years. The primary safety endpoint was any stroke or death from any cause within 30 days after CEA or CAS. The primary analysis was by intention-to treat, which included all randomly assigned patients in SPACE-2, SPACE-2a, and SPACE-2b, analysed using meta-analysis of individual patient data. We did two-step hierarchical testing to first show superiority of CEA and CAS to BMT alone then to assess non-inferiority of CAS to CEA. Originally, we planned to recruit 3640 patients; however, the study had to be stopped prematurely due to insufficient recruitment. This report presents the primary analysis at 5-year follow-up. This trial is registered with ISRCTN, number ISRCTN78592017. FINDINGS: 513 patients across SPACE-2, SPACE-2a, and SPACE-2b were recruited and surveyed between July 9, 2009, and Dec 12, 2019, of whom 203 (40%) were allocated to CEA plus BMT, 197 (38%) to CAS plus BMT, and 113 (22%) to BMT alone. Median follow-up was 59·9 months (IQR 46·6-60·0). The cumulative incidence of any stroke or death from any cause within 30 days or any ipsilateral ischaemic stroke within 5 years (primary efficacy endpoint) was 2·5% (95% CI 1·0-5·8) with CEA plus BMT, 4·4% (2·2-8·6) with CAS plus BMT, and 3·1% (1·0-9·4) with BMT alone. Cox proportional-hazard testing showed no difference in risk for the primary efficacy endpoint for CEA plus BMT versus BMT alone (hazard ratio [HR] 0·93, 95% CI 0·22-3·91; p=0·93) or for CAS plus BMT versus BMT alone (1·55, 0·41-5·85; p=0·52). Superiority of CEA or CAS to BMT was not shown, therefore non-inferiority testing was not done. In both the CEA group and the CAS group, five strokes and no deaths occurred in the 30-day period after the procedure. During the 5-year follow-up period, three ipsilateral strokes occurred in both the CAS plus BMT and BMT alone group, with none in the CEA plus BMT group. INTERPRETATION: CEA plus BMT or CAS plus BMT were not found to be superior to BMT alone regarding risk of any stroke or death within 30 days or ipsilateral stroke during the 5-year observation period. Because of the small sample size, results should be interpreted with caution. FUNDING: German Federal Ministry of Education and Research (BMBF) and German Research Foundation (DFG).

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Successful implementation of best medical treatment for patients with asymptomatic carotid artery stenosis within a randomized controlled trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) can be treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or best medical treatment (BMT) only. For all treatment options, optimization of vascular risk factors such as arterial hypertension, hyperlipidemia, smoking, obesity, and insufficient physical activity is essential. Data on adherence to BMT and lifestyle modification in patients with ACS are sparse. The subject of this investigation is the implementation and quality of risk factor adjustment in the context of a randomized controlled trial. METHODS: A total of 513 patients in the prematurely terminated, randomized, controlled, multicenter SPACE-2 trial (ISRCTN 78592017) were analyzed within one year after randomization into 3 groups (CEA, CAS, and BMT only) for implementation of prespecified BMT recommendations and lifestyle modifications. Measurement time points were the screening visit and visits after one month (D30), 6 months (M6), and one year (A1). Differences between groups and follow-up visits (FUVs) relative to the screening visit were investigated. FINDINGS: For all FUVs, a significant increase in statin medication (91% at A1; p < 0.0001) was demonstrated to be associated with a significant decrease (p < 0.01) in cholesterol levels (median 167 mg/dl at A1) and LDL cholesterol levels (median 93 mg/dl at A1). The lowest cholesterol levels were achieved by patients in the BMT group. Seventy-eight percent of all patients reached predefined target cholesterol levels (< 200 mg/dl), with significantly better rates in the BMT group (p = 0.036 at D30). Furthermore, a significant decrease in arterial blood pressure at all FUVs (p < 0.05) was associated with a significant increase in antihypertensive medication (96% at A1, p < 0.0001). However, only 28% of patients achieved the predefined treatment goal of a systolic blood pressure of ≤ 130 mmHg. Forty-two of a total of 100 smokers at the screening visit quit smoking within one year, resulting in a significant increase in nonsmokers at all FUVs (p < 0.0001). Recommended HbA1c levels (< 7%) were achieved in 82% without significant changes after one year. Only 7% of obese (BMI > 25) patients achieved sufficient weight reduction after one year without significant changes at all FUVs (median BMI 27 at A1; p = 0.1201). The BMT group showed significantly (p = 0.024) higher rates of adequate physical activity than the intervention groups. Furthermore, after one year, the BMT group showed a comparatively significantly better implementation of risk factor modification (77%; p = 0.027) according to the treating physician. INTERPRETATION: SPACE-2 demonstrated sustained improvement in the noninterventional management of vascular risk factors in patients treated in a clinical trial by general practitioners, internists and neurologists. The best implemented treatment targets were a reduction in cholesterol and HbA1c levels. In this context, a significant increase in statin use was demonstrated. Blood pressure control missed its target but was significantly reduced by intensification of antihypertensive medication. Patients on BMT only had better adjusted lipid parameters and were more physically active. However, all groups failed to achieve sufficient weight reduction. Due to insufficient patient recruitment, the results must be interpreted cautiously. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN78592017, Registered 16 June 2007, https://www.isrctn.com/search?q=78592017 .

Cardiac output and cerebral blood flow during carotid surgery in regional versus general anesthesia: A prospective randomized controlled study.

OBJECTIVE: Carotid endarterectomy (CEA) is a preventive procedure aimed at decreasing the subsequent risk of fatal or disabling stroke in patients with significant carotid stenosis. It is well-known that carotid surgery under ultrasound-guided regional anesthesia (US-RA) causes a significant increase in blood pressure, heart rate and stress hormone levels owing to increased sympathetic activity. However, little is known about the effects on cardiac output (CO), cardiac index (CI), and cerebral blood flow (CBF) under US-RA as compared with general anesthesia (GA). METHODS: Patients scheduled for CEA were randomized prospectively to receive US-RA (n = 37) or GA (n = 41). The primary end point was the change in CI after induction of anesthesia and the change from baseline over time at four different times during the entire procedure in the respective randomized US-RA and GA groups. In addition to systolic blood pressure and heart rate, we also recorded peak systolic velocity, end-diastolic velocity, and minimum diastolic velocity as seen from transcranial Doppler ultrasound examination, as well as regional cerebral oxygenation (rSO2) as seen from near-infrared refracted spectroscopy to evaluate cerebral blood flow. RESULTS: In the US-RA group, the CI increased after induction of anesthesia (3.7 ± 0.8 L/min/m2) and remained constant until the end of the procedure. In the GA group CI was significantly lower (2.4 ± 0.6 L/min/m2; P < .001). After induction of anesthesia, the rSO2 remained constant in the GA group on both the ipsilateral (63 ± 9 rSO2) and the contralateral (65 ± 7 rSO2) sides; in contrast, it significantly increased in the US-RA group (ipsilateral 72 ± 8 rSO2; P < .001; contralateral 72 ± 6 rSO2; P < .001). The transcranial Doppler ultrasound parameters (peak systolic velocity, end-diastolic velocity, and minimum diastolic velocity) did not differ between the US-RA and the GA group. The clinical outcome was similarly favorable for both groups. CONCLUSIONS: CI was maintained near baseline values throughout the procedure during US-RA, whereas a significant decrease in CI values was observed during CEA under GA. Near-infrared refracted spectroscopy values, reflecting blood flow in small vessels, were higher in US-RA patients than in those with GA. These differences did not influence clinical outcome.

Editor's Choice - Risk of Stroke before Revascularisation in Patients with Symptomatic Carotid Stenosis: A Pooled Analysis of Randomised Controlled Trials.

OBJECTIVE: Current guidelines recommending rapid revascularisation of symptomatic carotid stenosis are largely based on data from clinical trials performed at a time when best medical therapy was potentially less effective than today. The risk of stroke and its predictors among patients with symptomatic carotid stenosis awaiting revascularisation in recent randomised controlled trials (RCTs) and in medical arms of earlier RCTs was assessed. METHODS: The pooled data of individual patients with symptomatic carotid stenosis randomised to stenting (CAS) or endarterectomy (CEA) in four recent RCTs, and of patients randomised to medical therapy in three earlier RCTs comparing CEA vs. medical therapy, were compared. The primary outcome event was any stroke occurring between randomisation and treatment by CAS or CEA, or within 120 days after randomisation. RESULTS: A total of 4 754 patients from recent trials and 1 227 from earlier trials were included. In recent trials, patients were randomised a median of 18 (IQR 7, 50) days after the qualifying event (QE). Twenty-three suffered a stroke while waiting for revascularisation (cumulative 120 day risk 1.97%, 95% confidence interval [CI] 0.75 - 3.17). Shorter time from QE until randomisation increased stroke risk after randomisation (χ2 = 6.58, p = .011). Sixty-one patients had a stroke within 120 days of randomisation in the medical arms of earlier trials (cumulative risk 5%, 95% CI 3.8 - 6.2). Stroke risk was lower in recent than earlier trials when adjusted for time between QE and randomisation, age, severity of QE, and degree of carotid stenosis (HR 0.47, 95% CI 0.25 - 0.88, p = .019). CONCLUSION: Patients with symptomatic carotid stenosis enrolled in recent large RCTs had a lower risk of stroke after randomisation than historical controls. The added benefit of carotid revascularisation to modern medical care needs to be revisited in future studies. Until then, adhering to current recommendations for early revascularisation of patients with symptomatic carotid stenosis considered to require invasive treatment is advisable.

Elevated levels of serum PCSK9 in male patients with symptomatic peripheral artery disease: The CAVASIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) affects more than 200 million people worldwide. Increased low-density lipoprotein cholesterol (LDL-C)levels are a risk factor for PAD and the concentrations are influenced by proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 regulates the recycling of the LDL receptors to the cell membrane surface. Only a limited number of mostly small studies investigated the association between serum PCSK9 concentrations and PAD of different definition, which revealed contrasting results. METHODS: Serum PCSK9, lipoprotein(a) [Lp(a)] and other lipoprotein concentrations were measured in male participants of the CAVASIC study, a case-control study of 248 patients with intermittent claudication and 251 age and diabetes-matched controls. RESULTS: PAD patients had significantly higher PCSK9 concentrations when compared to controls (250 ± 77 vs. 222 ± 68 ng/mL, p < 0.001). Logistic regression analysis with adjustment for age revealed that an increase in PCSK9 concentrations of 100 ng/mL was associated with a 1.78-fold higher risk for PAD (95%CI 1.38-2.33, p = 1.43 × 10-5). The association attenuated, but was still significant when adjusting additionally for age, Lp(a)-corrected LDL cholesterol, HDL cholesterol, high-sensitivity-CRP, statin treatment, hypertension, diabetes mellitus and smoking (OR = 1.49, 95%CI 1.03-2.18, p = 0.035). The strongest association was observed when both PCSK9 concentrations were above the median and Lp(a) concentrations were above 30 mg/dL (OR = 3.35, 95%CI 1.49-7.71, p = 0.0038). CONCLUSIONS: Our findings suggest an association of higher PCSK9 concentrations with PAD, which was independent of other lipid parameters and classical cardiovascular risk factors.

Ultrasound-Guided Fibrin Glue Injection for Treatment of Iatrogenic Femoral Pseudoaneurysms.

INTRODUCTION: Arterial pseudoaneurysms (PSAs) are the most common access site complication following transarterial catheter intervention. Ultrasound-guided injection of thrombogenic substances into perfused arterial PSAs followed by compression therapy is a well-established and less invasive treatment option than surgical repair. Different agents are available to induce thrombosis including thrombin and a fibrin-based tissue glue, which is used as first-line treatment at our institution. This paper deals with our experience using ultrasound-guided fibrin glue injection (UGFI). MATERIALS AND METHODS: Retrospective data analysis: all patients (55) treated for iatrogenic femoral PSA following digital subtraction angiography of the lower extremities between January 1, 2010, and December 31, 2018, were included. Data on epidemiology, PSA location and size, vascular risk factors, fibrin glue injection (fibrin glue volume), primary success rate of UFGI, and complications related to the treatment were analyzed. RESULTS: A total of 55 consecutive femoral iatrogenic PSAs were treated during the defined period and 32 (58.2%) of the patients were female. Imaging was performed using ultrasound in all cases. The most common PSA location (80.0%) was the common femoral artery, mean PSA size (± SD) was 2.7 ± 1.2 cm, and neck length was 1.6 ± 1.0 cm. The dose (mean ± SD) of fibrin glue was 2.6 mL (± 1.0; maximum: 6 mL). Primary UGFI success rate was 87.3% and conversion rate to open surgery was 12.7%. Two (4%) patients required embolectomy for peripheral embolization after UGFI. CONCLUSION: Early results achieved with UGFI for treatment of iatrogenic femoral PSA are promising. In our cohort, UGFI was a safe and effective first-line alternative to traditional open surgery, which then was unnecessary in the vast majority of PSA cases. Further prospective studies for comparison of ultrasound-guided techniques should be encouraged.

68Ga-DOTATOC PET/CT in the localization of head and neck paraganglioma compared with 18F-DOPA PET/CT and 123I-MIBG SPECT/CT.

PURPOSE: 18F-Fluoro-L-dihydroxyphenylalanine (18F-DOPA) PET offers high sensitivity and specificity in the imaging of non-malignant head and neck paraganglioma (HNPGL) but lower sensitivity in metastatic disease of these neuroendocrine tumours (NET). In contrast to the radiotracer 18F-DOPA, both 123I-meta-iodo-benzylguanidine (123I-MIBG) and 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTA-TOC) offer valuable clinical information on norepinephrine and somatostatin (SST) receptor status for planning 131I-MIBG and radionuclide peptide therapy (PRRT), respectively. Therefore, we compared 68Ga-DOTA-TOC and 18F-DOPA PET/CT with 123I-MIBG planar and SPECT/CT imaging, for the detection of HNPGL. Combined cross-sectional imaging was the reference standard. METHODS: A total of 3 men and 7 women (age range 22 to 73 years) with anatomical and/or histologically proven HNPGL were included in this study. Of these patients, 3 patients had metastatic HNPGL. Comparative evaluation included morphological imaging with CT and functional imaging with 68Ga-DOTA-TOC and 18F-DOPA PET, including 123I-MIBG imaging. The imaging results were analysed on a per-patient and per-lesion basis. RESULTS: On a per-patient analysis, the detection rate of both 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT was 100%, that of planar 123I-MIBG imaging 10.0% and that of SPECT/CT 20.0%. On a per-lesion basis and in reference to diagnostic CT, the sensitivity of 68Ga-DOTA-TOC PET/CT was 100% (McNemar, P < 0.5), that of 18F-DOPA PET/CT was 66.7% (McNemar, P < 0.01), that of planar 123I-MIBG imaging was 3.7% (McNemar, P < 0.0001), and that of SPECT/CT was 7.4% (McNemar, P < 0.0001) in HNPGL. Overall, 68Ga-DOTA-TOC PET identified 29 lesions and anatomical imaging identified 27 lesions. 18F-DOPA PET identified 18 lesions, whereas planar 123I-MIBG imaging identified 1 lesion and SPECT/CT 2 lesions. CONCLUSION: 68Ga-DOTA-TOC PET/CT is superior for imaging, non-malignant and metastatic HNPGL compared to 18F-DOPA PET/CT and planar 123I-MIBG imaging, including SPECT/CT, particularly in bone lesions. Combined functional/anatomical imaging (68Ga-DOTA-TOC PET/CT) enables excellent delineation of tumour extent in these rare tumour entities. Compared to 123I-MIBG scintigraphy, 68Ga-DOTA-TOC PET appears far more useful for planning radionuclide therapy in patients with surgically inoperable tumours or metastatic disease.

Differential clinical presentation of Adamantiades-Behçet's disease in non-endemic and endemic areas: retrospective data from a Middle-European cohort study.

OBJECTIVES: To assess demographical and clinical data in a Middle-European cohort of patients with Adamantiades-Behçet's disease (ABD), together with the use of medication in adherence to international guidelines. METHODS: In a retrospective cohort study, in- and outpatients of an Austrian secondary and tertiary university hospital center were analyzed independent from the medical discipline involved. After ethics approval, screening for ABD-patients in the clinical information system resulted in 1821 documents from 1997 to 2016. Patients fulfilling the International Criteria for Behçet's Disease were included, and ABD symptoms and signs together with medical interventions for immunosuppression, anticoagulation and pain management were identified by individual chart reviews and evaluated for conformity with international recommendations. RESULTS: A total of 76 ABD patients were identified with 39.1% Austrian and 37.0% Turkish origin. Genital aphthae and skin manifestations were more frequent, neurological, gastrointestinal and vascular manifestations less frequent in ABD patients of Turkish origin living in Austria compared to those living in Turkey (each P < 0.05). The male-to-female ratio averaged 0.86 (0.39 in patients with Austrian and 1.43 with Turkish backgrounds), and was 3.3 in patients with venous manifestations. Out of 174 medical interventions, 55.2% fully matched the European League Against Rheumatism recommendations of 2008, and 93.7% were considered at least as equal to the recommendations. Indications for tumor necrosis factor inhibition were in line with the 2007 Sfikakis recommendations. CONCLUSIONS: In this Middle-European ABD cohort clinical presentations between patients of Austrian and Turkish origin do not strongly vary, whereas Turkish patients from the non-endemic Innsbruck cohort present differently compared to patients living in Turkey. The role of such cohort analyses will increase, from the epidemiological as well as the management perspective.

Influence of stent design and use of protection devices on outcome of carotid artery stenting: a pooled analysis of individual patient data.

BACKGROUND AND PURPOSE: Carotid artery stenting is an alternative to endarterectomy for the treatment of symptomatic carotid stenosis but was associated with a higher risk of procedural stroke or death in randomized controlled trials (RCTs). Technical aspects of treatment may partly explain these results. The purpose of this analysis was to investigate the influence of technical aspects such as stent design or the use of protection devices, as well as clinical variables, on procedural risk. METHODS: We pooled data of 1557 individual patients receiving stent treatment in three large RCTs comparing stenting versus endarterectomy for symptomatic carotid stenosis. The primary outcome event was any procedural stroke or death occurring within 30 days after stenting. RESULTS: Procedural stroke or death occurred significantly more often with the use of open-cell stents (61/595 patients, 10.3%) than with closed-cell stents (58/962 patients, 6.0%; RR 1.76; 95% CI 1.23 to 2.52; P=0.002). Procedural stroke or death occurred in 76/950 patients (8.0%) treated with protection devices (predominantly distal filters) and in 43/607 (7.1%) treated without protection devices (RR 1.10; 95% CI 0.71 to 1.70; P=0.67). Clinical variables predicting the primary outcome event were age, severity of the qualifying event, history of prior stroke, and level of disability at baseline. The effect of stent design remained similar after adjustment for these variables. CONCLUSIONS: In symptomatic carotid stenosis, the use of stents with a closed-cell design is independently associated with a lower risk of procedural stroke or death compared with open-cell stents. Filter-type protection devices do not appear to reduce procedural risk.

Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. METHODS: We investigated the association between timing of treatment (0-7 days and >7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists' Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. RESULTS: Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). CONCLUSIONS: In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; Unique identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

The fate of patients with intermittent claudication in the 21st century revisited - results from the CAVASIC Study.

Patients with intermittent claudication carry a high risk for cardiovascular complications. The TransAtlantic Inter-Society Consensus (TASC) Group estimated a five-year overall mortality of 30% for these patients, the majority dying from cardiovascular causes. We investigated whether this evaluation is still applicable in nowadays patients. We therefore prospectively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality, vascular morbidity and mortality and local PAD outcomes. Overall mortality reached 16.1% (n = 41). Most patients died from cancer (n = 20). Half of patients (n = 22; 8.6%) died within the first five years. Incident cardiovascular events were observed among 70 patients (27.5%), 54 (21.2%) during the first five years. Vascular mortality was low with 5.1% (n = 13) for the entire and 3.1% for the first five years of follow-up. Prevalent coronary artery disease did not increase the risk to die from all or vascular causes. PAD symptoms remained stable or improved in the majority of patients (67%). In summary, compared to TASC, the proportion of cardiovascular events did not markedly decrease over the last two decades. Vascular mortality, however, was low among our population. This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer.

Compared to 123I-MIBG SPECT/CT, 18F-DOPA PET/CT provides accurate tumor extent in patients with extra-adrenal paraganglioma.

AIM: The aim of this study was to compare the accuracy of 123I-MIBG SPECT/CT with that of 18F-DOPA PET/CT for staging extra-adrenal paragangliomas (PGLs) using both functional and anatomical images (i.e., combined cross-sectional imaging) as the reference standards. METHODS: Three men and seven women (age range 26-73 years) with anatomical and/or histologically proven disease were included in this study. Three patients had either metastatic head-and-neck paragangliomas (HNPGLs) or multifocal PGL, and seven patients had nonmetastatic disease. Comparative evaluation included morphological imaging with CT, functional imaging with 18F-DOPA PET, and 123I-MIBG imaging including SPECT/CT. Imaging results were analyzed on a per-patient and per-lesion basis. RESULTS: On a per-patient basis, 18F-DOPA PET's detection rate for both nonmetastatic and metastatic/multifocal disease was 100%, whereas that of planar 123I-MIBG imaging alone was 10.0% and that of 123I-MIBG SPECT/CT was 20.0%. Overall, on a per-lesion basis, 18F-DOPA PET showed a sensitivity of 69.2% (McNemar p < 0.001) compared with anatomical imaging. Sensitivity of planar 123I-MIBG scintigraphy was 5.6%, and that of SPECT/CT was 11.1% (McNemar p < 0.0001). Overall, 18F-DOPA PET identified 18 lesions, and anatomical imaging identified 26 lesions; planar 123IMIBG imaging identified only 1 lesion, and SPECT/CT, 2 lesions. CONCLUSION: 18F-DOPA PET is more sensitive than is 123I-MIBG imaging, including SPECT/CT, for staging HNPGL. Combined functional and anatomical imaging (PET/CT) is indicated to exclude metastatic disease in extra-adrenal PGL.

Open surgical retrieval of an embolized PFO occluder system.

Device migration after intervention for persistent foramen ovale occlusion is a rare complication. In case of failure of endovascular device retrieval, open surgical removal is indicated, safe, and reliable.

Functional Assessment and Evaluation of Outcome After Endovascular Therapy With Coverage of the Left Subclavian Artery in Case of Blunt Thoracic Aortic Injury.

BACKGROUND: Patients suffering blunt thoracic aortic injury (BTAI) can be treated by use of thoracic endovascular aortic repair (TEVAR). In this setting, the coverage of the left subclavian artery (LSA) is frequently necessary. Nevertheless, the functionality of the upper left extremity after TEVAR had been rarely analyzed. Thus, this study intends to underline the safety of TEVAR as well as to determine the functionality of the left arm after coverage of the LSA. METHODS: All patients suffering from BTAI treated by endovascular means in 3 centers (Aachen [Germany], Maastricht [Netherlands], and Innsbruck [Austria]) between 1996 and 2009 were retrospectively analyzed. The safety of the procedure had been assessed by the morbidity and mortality rate. The mid-term functional status of the upper left extremity was evaluated by using the DASH score (disabilities of the arm shoulder and hand). RESULTS: Forty-six patients (40 male, 6 female), mean age 39.4 ± 16.9 years suffered from BTAI caused by traffic accident (n = 31 [67.39%]), by skiing injury (n = 8 [17.39%]), and by fall (n = 7 [15.21%]). All patients underwent TEVAR, the technical success rate was 100%; 1 carotid-carotid subclavian bypass implantation was necessary. LSA coverage was performed in 76% (35/46) of the cases. Total complication rate was 17.3% (8/46); the endoleak rate was 8.6% (4/46) (2 × Ib, 1 × IIa, 1 × IV). Further complications were bypass and endograft occlusion. The postoperative mortality rate was 6% (3/46), the DASH score was completed in 65% (30/46). The study population reached a mean value of 17 ± 20, which is comparable to a nonharmed reference group (10.10 ± 14.68). A significant correlation between the DASH score and patients age could be demonstrated (2-sided P value: 0.0213). CONCLUSIONS: Endovascular therapy of BTAI revealed a good primary success rate. An adequate mid-term functional status of the upper left extremity could be assessed in comparison to a nonharmed reference group.

Ultrasound-guided regional anesthesia for carotid endarterectomy induces early hemodynamic and stress hormone changes.

OBJECTIVE: Locoregional anesthesia is an effective method for evaluating cerebral function during carotid endarterectomy (CEA). Landmark-guided regional anesthesia (RA) is currently used for CEA and can provoke substantial perioperative hypertension. Ultrasound-guided RA (US-RA) is a new method for performing RA in CEA; however, the effect on sympathetic activity and blood pressure is uncertain. This study assessed early sympathetic activity during CEA in US-RA compared with general anesthesia (GA). METHODS: Patients were prospectively randomized to receive US-RA (n = 32) or GA (n = 28) for CEA. The primary end point was the change in systolic arterial blood pressure after induction of anesthesia (just before starting surgery) comparing US-RA with GA. We also recorded heart rate and analyzed concentrations of plasma blood hormones, including cortisol, metanephrine, and normetanephrine at five different times. Creatinine kinase, troponin I, and N-terminal pro-B-type natriuretic peptide were analyzed to detect potential changes in cardiac biomarkers during the procedure. RESULTS: Systolic arterial blood pressure (mean ± standard deviation) increased significantly in US-RA patients compared with GA patients even before surgery was initiated (180 ± 26 mm Hg vs 109 ± 24 mm Hg; P < .001), then remained elevated during the entire surgery and returned to baseline values 1 hour after admission to the postoperative anesthesia care unit. Heart rate (US-RA: 78 ± 16 beats/min, GA: 52 ± 12 beats/min; P < .001) and cortisol levels (US-RA: 155 ± 97 µg/L, GA: 99 ± 43 µg/L; P = .006) were also significantly higher in the US-RA group after induction of anesthesia. Other values did not differ. CONCLUSIONS: The US-RA technique for CEA induces temporary intraoperative hypertension and an increase in stress hormone levels. Nevertheless, US-RA is a feasible, effective, and safe form of locoregional for CEA that enables targeted placement of low volumes of local anesthesia under direct visualization.

Serum concentrations of L-arginine and L-homoarginine in male patients with intermittent claudication: a cross-sectional and prospective investigation in the CAVASIC Study.

BACKGROUND: High serum concentrations of l-arginine and l-homoarginine increase nitric oxide (NO) availability and thereby improve endothelial function. Information about the association of these markers with peripheral arterial disease (PAD) and related outcomes is sparse. METHODS: l-arginine, its metabolites and l-homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls. After the baseline investigation PAD patients were prospectively followed (median 7 years). The association of these markers with symptomatic PAD at baseline, incident cardiovascular events and all-cause mortality was assessed. RESULTS: At baseline each increase of ln-l-homoarginine and l-arginine by one standard deviation was associated with symptomatic PAD: OR=0.75, 95%CI 0.59-0.96, P=0.02 and OR=1.36, 95%CI 1.07-1.73, P=0.01, respectively (both models adjusted for ln-CRP, GFR, HDL cholesterol, and current smoking). Only l-arginine remained significant after additional adjustment for ln-NT-proBNP and hs-cTnT: OR=1.49, P=0.002. In the Cox regression analysis elevated ln-l-homoarginine significantly reduced the risk to die (n=38) even independent from ln-NT-proBNP and hs-cTnT: HR=0.59, 95%CI 0.41-0.84, P=0.004. l-arginine was significantly predicting incident cardiovascular events (n=65): HR=1.68, 95%CI 1.35-2.10, P < 0.001. CONCLUSIONS: This study in male patients with intermittent claudication and age- and diabetes-matched controls showed an association of l-homoarginine and l-arginine with PAD. During follow-up, l-arginine was associated with incident cardiovascular events probably due to its primary role in NO metabolism and impact on endothelial integrity. l-homoarginine was related to all-cause mortality implying a broader role in metabolic processes besides endothelial function.

(68)Ga-DOTATOC PET/CT provides accurate tumour extent in patients with extraadrenal paraganglioma compared to (123)I-MIBG SPECT/CT.

PURPOSE: The aim of this study was to compare the accuracy of (123)I-MIBG SPECT/CT with that of (68)Ga-DOTATOC PET/CT for staging extraadrenal paragangliomas (PGL) using both functional and anatomical images (i.e. combined cross-sectional imaging) as the reference standards. METHODS: The study included three men and seven women (age range 26 to 73 years) with anatomical and/or histologically proven disease. Three patients had either metastatic head and neck PGL (HNPGL) or multifocal extraadrenal PGL, and seven patients had nonmetastatic extraadrenal disease. Comparative evaluation included morphological imaging with CT, functional imaging with (68)Ga-DOTATOC PET, and (123)I-MIBG imaging. The imaging results were analysed on a per-patient and on a per-lesion basis. RESULTS: On a per-patient basis, the detection rate of (68)Ga-DOTATOC PET was 100 %, whereas that of planar (123)I-MIBG imaging was 10.0 % and with SPECT/CT 20.0 % for both nonmetastatic and metastatic/multifocal extraadrenal PGL. On a per-lesion basis, the overall sensitivity of (68)Ga-DOTATOC PET was 100 % (McNemar p < 0.5), that of planar (123)I-MIBG imaging was 3.4 % (McNemar p < 0.001) and that of SPECT/CT was 6.9 % (McNemar p < 0.001). Both (68)Ga-DOTATOC PET and anatomical imaging identified 27 lesions. Planar (123)I-MIBG imaging identified only one lesion, and SPECT/CT two lesions. Two additional lesions were detected by (68)Ga-DOTATOC PET but not by either (123)I-MIBG or CT imaging. CONCLUSION: Our analysis in this patient cohort indicated that (68)Ga-DOTATOC PET/CT is superior to (123)I-MIBG SPECT/CT, particularly in head and neck and bone lesions, and provides valuable information for staging extraadrenal PGL, particularly in patients with surgically inoperable tumours or multifocal/malignant disease.

Subclavian artery rupture in a young man during excessive weight lifting.

We report a 19-year-old man with rupture of the right subclavian artery after an excessive exercise of weight lifting. Imaging showed a hematothorax and hematomediastinum, a pseudoaneurysm with a maximum diameter of 4 cm, and a dissection of the right vertebral artery. As an emergency procedure an interposition graft was performed for reconstruction of the right subclavian artery. The patient's postoperative course was uneventful, and he was symptom free except for regressive hoarseness due to a paresis of the right recurrent laryngeal nerve.