Takayasu's Arteritis from the Patients' Perspectives: Measuring the Pulse to the Patient-Reported Outcomes.

BACKGROUND: Patients with Takayasu's arteritis (TA) experience important changes in lifestyle, quality of life, and functional status due to ischemic symptoms or treatment toxicity. PURPOSE: To describe the clinical characteristics and the patient-reported outcomes (PROs), such as quality of life, disability, fatigue, and perception/impact of the disease in Mexican patients with TA. METHODS: Cross-sectional study including patients with established diagnosis of TA recruited at a tertiary care center. Demographics, comorbidities, clinical characteristics, laboratory, imaging, and treatment were retrieved. Disease activity (the Indian Takayasu Clinical Activity Score (ITAS) 2010), damage (Vasculitis Damage Index (VDI)), quality of life (Short Form 36 (SF-36)), disability (Health Assessment Questionnaire Disability Index (HAQ-DI)), fatigue (Multidimensional Fatigue Inventory-20), and patient's disease perceptions were assessed. RESULTS: Fifteen women were included, with a median age of 41 years (interquartile range (IQR) 30-45) and disease duration of 108 months (IQR 55-197). Median ITAS 2010 and VDI scores were 0 (IQR 0-2) and 3 points (IQR 2-6), respectively. Mean SF-36 score was 71.38 ± 13.39, with mean physical and mental component summaries of 66.52 ± 13.37 and 76.24 ± 14.89, respectively. HAQ-DI mean score was 0.48 ± 0.62, being grip the most affected domain. Among fatigue subscales, the higher scores were present in the physical fatigue (16.3 ± 5.8). Correlations between the HAQ-DI and the VDI score (r = 0.64, P = 0.03); between the general fatigue, score, and disease duration (r = -0.71, P = 0.01); and between the SF-36 total score and the HAQ-DI (r = -0.87, P = 0.0004) were found. CONCLUSIONS: It is important to identify disease-specific outcomes of interest to the patients to develop tools that assess them with a holistic approach.

Increased modifiable cardiovascular risk factors in patients with Takayasu arteritis: a multicenter cross-sectional study

Abstract Background: Modifiable cardiovascular risk factors (MCRFs), such as those related to aerobic capacity, muscle strength, physical activity, and body composition, have been poorly studied in Takayasu arteritis (TAK). Therefore, the aim of the study was to investigate MCRFs and their relationships with disease status and comorbidities among patients with TAK. Methods: A multicenter cross-sectional study was conducted between 2019 and 2020, in which 20 adult women with TAK were compared with 16 healthy controls matched by gender, age, and body mass index. The following parameters were analyzed: aerobic capacity by cardiopulmonary test; muscle function by timed-stands test, timed up-and-go test, and handgrip test; muscle strength by one-repetition maximum test and handgrip test; body composition by densitometry; physical activity and metabolic equivalent by IPAQ, quality of life by HAQ and SF-36; disease activity by ITAS2010 and NIH score; and presence of comorbidities. Results: Patients with TAK had a mean age of 41.5 (38.0-46.3) years, disease duration of 16.0 (9.5-20.0) years, and a mean BMI of 27.7±4.5 kg/m2. Three out of the 20 patients with TAK had active disease. Regarding comorbidities, 16 patients had systemic arterial hypertension, 11 had dyslipidemia, and two had type 2 diabetes mellitus, while the control group had no comorbidities. TAK had a significant reduction in aerobic capacity (absolute and relative VO2 peak), muscle strength in the lower limbs, increased visceral adipose tissue, waist-to-hip ratio, reduced walking capacity, decreased weekly metabolic equivalent, and quality of life (P< 0.05) as compared to controls. However, there were no correlations between these MCRFs parameters and disease activity. Conclusions: TAK show impairment in MCRFs; therefore, strategies able to improve MCRF should be considered in this disease.(AU)

Effectiveness of Tocilizumab in juvenile patients with refractory Takayasu arteritis: Two case reports.

RATIONALE: Takayasu arteritis (TA) is a systemic large-vessel vasculitis which can be accompanied by the symptoms associated with vascular stenosis. PATIENT CONCERNS: We describe 2 female juveniles with TA who presented with progressive intermittent claudication. DIAGNOSIS: Contrast-enhanced computed tomography (CT) revealed the stenosis of femoral arteries and increased levels of C-reactive protein (CRP), and serum amyloid A (SAA) were noted in both patients. According to European league against rheumatism consensus criteria for the diagnosis of TA was confirmed in both patients. INTERVENTIONS: Both patients had shown resistance to glucocorticoids and treated with tocilizumab (TCZ) (subcutaneous injections, 162 mg/week). OUTCOMES: These treatments improved claudication symptoms. Follow-up imaging by enhanced CT revealed restoration of advanced stenosis of the femoral arteries in both patients. They achieved normalization of levels of the acute-phase reactants CRP and SAA. Serum levels of interleukin-6 were increased transiently after TCZ injection, but declined to within normal ranges at 12 weeks. LESSONS: Juvenile patients with TA presenting with advanced stenosis of the femoral arteries are not rare. The clinical courses of our patients suggested the beneficial effects of TCZ against the progressive vascular stenosis observed in refractory TA.

Staged Combined Endovascular and Open Surgical Approach in a Patient with Takayasu's Arteritis.

Takayasu's arteritis (TA) is a systemic large vessel vasculitis that affects the aorta and its branches. Most patients with TA respond to medical therapy with a minority of patients requiring surgical intervention. In our report, we describe the case of a 59-year-old Caucasian female with TA who underwent revascularization due to cerebrovascular symptoms refractory to medical therapy. She initially presented with amaurosis fugax and developed episodes of syncope and slurred speech during corticosteroid tapering. Vascular studies showed right common carotid artery (RCCA), left internal carotid artery (LICA), and left subclavian artery (LSA) occlusion with the right vertebral artery (RVA) ostium stenosis, and retrograde flow through the left vertebral artery (LVA). The sole source of cerebral perfusion flowed through her stenosed RVA, so it was decided to first stent the RVA to restore adequate posterior cerebral circulation before creating a right subclavian artery to RCCA bypass to restore anterior circulation. This case represents the successful management of TA utilizing a two-staged combined endovascular and surgical approach.

Midaortic Syndrome due to Takayasu Arteritis in a Child with Acute Decompensated Cardiac Failure Managed by an Emergency Axillo-External Iliac Artery Bypass: A Follow-Up Case Report of Long-Term Outcomes.

Midaortic syndrome (MAS) is characterized by a diffuse narrowing of the distal thoracic or abdominal aorta and is concomitant with various etiologies. The common symptoms of MAS include severe hypertension or arterial insufficiency distal to the stenosis. This includes lower extremity claudication and heart failure due to afterload mismatch. We present the case of an 8-year-old girl who developed acute decompensated cardiac, respiratory, and renal failures because of the occlusion of the descending aorta secondary to Takayasu arteritis (TA). Although thoracoabdominal-aortic bypass is usually performed for patients with MAS, the procedure was considered too invasive, given the patient's condition. Therefore, we performed an emergency axillo-external iliac artery bypass for revascularization. Subsequently, organ failure improved and she was discharged. At postoperative 10 years, an asymptomatic pseudoaneurysm was detected at the distal anastomosis, for which revision surgery was performed. Overall, the long-term prognosis was satisfactory, suggesting that this procedure is less invasive and effective for treatment of MAS due to TA, in emergencies.

Poor obstetric outcomes in Indian women with Takayasu arteritis

Abstract Introduction: Takayasu's arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. Methods: Women aged more than 18 years with Takayasu's arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI. TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. Results: Of the 64 women interviewed, aged 29 (24-38) years and disease duration 5 (4-10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18-30) years. Type 5 disease was the most common ( n = 32, 59.3%), and an equal number of patients had Ishikawa's class I and II disease ( n = 26, 40.6%). Median ITAS ( n = 44) was 13 (7-16), DEI. Tak 12.5 (9-16.75) and TADS 8 (6.5-10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8-8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2-3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong's score greater than or equal to 4 predicted lower birth weight ( p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak ( r = 0.78) and TADS ( r = 0.58). Conclusion: Women with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong's scoring can be useful to predict birth weight.(AU)

[Revascularization of supra-aortic trunks in Takayasu's arteritis]. / Revascularisation des troncs supra-aortiques au cours de la maladie de Takayasu.

INTRODUCTION: Takayasu's disease is an inflammatory arteritis mainly affecting the aorta, its main divisional branches and pulmonary arteries. The arterial damage during Takayasu's disease is essentially occlusive and preferentially affects supra-aortic trunks. Indications for revascularization of supra-aortic trunks are clear but results are rarely reported. The purpose of this study was to evaluate the results of supra-aortic trunk revascularization in Takayasu's arteritis. PATIENTS AND METHODS: We report a retrospective study conducted between 2012 and 2018 about patients with Takayasu's arteritis who underwent revascularization of supra-aortic trunks. RESULTS: Our series consisted of six patients. All patients were female. The average age was 29 (range 18-48) years. The operative indication was cerebrovascular ischemic symptoms in five patients and intermittent claudication of the upper limb in one. We performed aorto-bi-carotid bypass in four patients, a subclavian artery angioplasty in one and a vertebral artery angioplasty in one. At 1 month, operative mortality was zero and morbidity was marked by hemorrhagic stroke in one patient operated by conventional surgery. The average follow-up was 4 years (1.8). During the follow-up, one patient was reoperated after 18 months for an anastomotic false aneurysm in the ascending aorta. We noted a favorable outcome with total resolution of the symptomatology for the other patients and Doppler ultrasound confirmed patency during follow-up. CONCLUSION: Surgical revascularization of supra-aortic trunks in Takayasu's arteritis can be associated with a risk of stroke and a risk of anastomotic pseudoaneurysms. Endovascular revascularization appears to be less invasive but its long-term results are rarely reported.

Takayasu arteritis with multiple coronary involvement and early graft relapse.

Coronary artery disease (CAD) due to Takayasu arteritis (TA) is rare. This article reports a case of severe involvement of multiple coronary arteries in a young woman. She was treated with coronary artery bypass grafting and had an early venous graft stenosis despite immunosuppressants. She became asymptomatic one year after a drug-eluting stent placement. This report shows the complexity of the diagnostic and therapeutic approach to TA with complex CAD.

Aggressive progression of Takayasu's arteritis in infancy: a case report.

Takayasu's arteritis (TA) affects the aorta and its branches. Immunosuppressants are the usual course of therapy, while surgery has been used in acute cases. There is only scant information on TA in infancy, and the nonspecific symptoms in the initial stage of the disease make the diagnosis difficult and delayed, thus increasing the mortality rate. We describe a case of aggressive progression of TA in an infant. This child was the youngest to be affected with the disease as reported in the literature. A 3.5-month-old boy presented with cyanosis of both legs, tachycardia and antithrombin III deficiency. Computed tomography angiography (CTA) revealed thrombosis of distal aorta and both iliac arteries. Thrombectomy was performed at the level of both common femoral arteries. In addition, thigh amputation of the left leg had to be performed. TA was diagnosed postmortem with thrombosis of the distal aorta, its branches and upper mesenteric artery which was not occluded on previous CTA, glomerulonephritis and pulmonary parenchymal granulomatous infiltrations.

Nailfold videocapillaroscopy changes in Takayasu arteritis and their association with disease activity and subclavian artery involvement.

INTRODUCTION: Takayasu arteritis (TA) is a large vessel vasculitis characterized by the involvement of the aorta and its branches. In the present study, the nailfold videocapillaroscopy (NVC) findings of the TA patients were evaluated and compared to healthy individuals. Additionally, the association of NVC abnormalities with disease activity and subclavian artery involvement was also investigated. METHOD: In the present study, NVC changes of 15 TA patients and 15 age- and sex-matched healthy controls were compared. The frequency of hypertension, dyslipidemia, and smoking status was not different between the case and control group. Capillary density, avascular area, tortuosity, micro-hemorrhages, and ramification were investigated. Among capillaries' diameters; capillary length and width, arterial and venous limbs diameters were also compared between two groups. RESULTS: The capillary length and venous limb diameter were lower in TA patients compared to control cases (P-value: 0.026 and 0.049, respectively). Moreover, TA patients have more tortuous capillaries (P-value: 0.035). Among TA patients; capillary length, width, arterial and venous limbs diameter was lower in hands with subclavian involvement (P-value: 0.014, 0.034, 0.009 and 0.022, respectively). Furthermore, the arterial and venous limbs diameter were lower in TA patients with active disease compared to patients with inactive disease (P-value: 0.018 and 0.049, respectively). CONCLUSION: In the present study, we have shown that the hands with subclavian artery involvement have short, thin and tortuous capillaries which could be secondary to hypoperfusion. To the best of our knowledge, this is the first report describing NVC changes in TA.

Simultaneous Multi-Supra-Aortic Artery Bypass Successfully Implemented in 17 Patients with Type I Takayasu Arteritis.

OBJECTIVE: Type I Takayasu arteritis is common in Chinese patients and usually leads to cerebral ischaemia. There are limited data regarding simultaneous multi-supra-aortic artery (SMSAA) bypass in patients with type I Takayasu arteritis. The present study shares experience of using this method. METHODS: Seventeen patients with Takayasu arteritis who received SMSAA bypass from June 2012 to March 2016 were included in this analysis. Demographic features and basic information were recorded. Follow up results, including major complications, patency rates, and survival rates, were also obtained. The EQ-5D questionnaire was also administered to evaluate the quality of life of patients. RESULTS: Among these 17 patients, there were 77 supra-aortic arteries affected by TA and 37 arteries were reconstructed, 10 with great saphenous vein and 27 with artificial blood vessels. All the operations were technical successes and the mean operation time was 396.6 ± 93.4 min. The patients were followed for a mean of 25.2 ± 12.3 months. Two graft restenoses were found, and both were successfully recanalised by balloon dilatation. One patient suffered a minor stroke but was free from obvious sequelae. No major complications, recurrent symptoms, or deaths occurred during the follow up period. The EQ-5D questionnaire scores were significantly improved after the operation compared with the pre-operative scores (87.14 ± 8.25 vs. 58.93 ± 14.4, p < .01), and all the patients enjoyed a satisfactory quality of life. CONCLUSION: SMSAA bypass in type I Takayasu arteritis can be effectively and safely performed with rigorous peri-operative management. Maintaining the patency of the bypass graft relieves the symptoms of cerebral ischaemia and helps sustain patients' quality of life.

[Pulmonary cavities with Takayasu arteritis: report of 3 cases and literature review].

Objective: To analyze the clinical features of 3 cases of Takayasu arteritis(TA) with pulmonary cavities on chest computed tomography(CT). Methods: The clinical data of 3 TA patients with cavities on the chest CT who were admitted into Beijing Chaoyang Hospital were retrospectively analyzed. A literature search was performed with "Takayasu arteritis" and "pulmonary" as the key words in China Knowledge Resource Intergrated Database (CNKI) and Pubmed Database for publications from Jan 1, 2000 to Dec. 31,2017. The relevant literatures were reviewed. Results: Among the 3 patients, 2 were males and 1 was female, aging 49, 28 and 28 years, respectively. They presented with cough, fever and chest pain, and chest CT showed cavities, single or multiple, either with thick or thin wall, or wedge-shaped consolidation, residual stripes after being absorbed, and one case had pulmonary biopsy results which showed hemorrhagic infarction. They were all misdiagnosed before as pneumonia, pulmonary tuberculosis, pulmonary thromboembolism. After being treated by combination therapy of glucocorticoids and immunosuppressive agents, the disease improved significantly. A total of 777 cases with TA involving pulmonary arteries were reported, from which 13 cases with involvement of pulmonary parenchyma were described. Therefore total 16 cases including the 3 cases in this article were included for analysis. Twelve cases showed patchy or wedge-shaped ground-glass opacity and consolidation, and peripheral lung stripes remained after being absorbed. Two cases showed pleural effusion, and 4 cases showed cavities, 3 cases were misdiagnosed as pulmonary tuberculosis, 7 as pulmonary infection, and 5 as pulmonary thromboembolism. Conclusions: TA with pulmonary arteries involved is susceptible to be misdiagnosed and missed, and therefore, in patients with cough, hemoptysis, chest pain and cavities in pulmonary parenchyma, TA should be suspected. Early diagnosis and appropriate treatment can lead to a better prognosis.

Takayasu arteritis: an update

Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual disease activity. Since there are no specific diagnostic laboratory tests, biomarkers, or autoantibodies, many patients experience considerable delay in diagnosis. Remembering the possibility of TAK together with the use of acute phase responses and appropriate imaging studies may be helpful for early diagnosis. Since there may be discrepancies between systemic and vascular wall inflammation, using only acute phase responses is not reliable in assessing current disease activity. Therefore, physical examination and new imaging findings should also be used to assess current disease activity. Despite its limitations, the Indian Takayasu Clinical Activity Score (ITAS2010) may also be helpful for this purpose. The rationale of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive agents. In cases of refractory disease activity, leflunomide and biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases with persistent lesions that cannot be reversed with medical treatment, endovascular interventions including balloon angioplasty, stent and stent graft replacement, or surgery may be tried. However, such procedures should be performed after suppression of inflammation, i.e. during inactive disease. Prognosis of TAK is probably getting better with lower mortality rates reported in recent years, probably due to the use of more effective medical treatments as well as the use of endovascular interventions when necessary and available.

NMR-Based Serum Metabolomics of Patients with Takayasu Arteritis: Relationship with Disease Activity.

Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis. Assessment of disease activity is a challenge, and there is an unmet need for relevant biomarker(s). In our previous study, NMR based serum metabolomics had revealed distinctive metabolic signatures in TA patients compared with age/sex matched healthy controls and systemic lupus erythematosus (SLE). In this study we investigate whether the metabolites correlate with disease activity. Patients with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled, and disease activity was assessed using Indian Takayasu Clinical Activity Score using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. Sera were analyzed using 800 MHz NMR spectrometer to identify metabolites [based on partial least squares discriminant analysis (PLS-DA) VIP (variable importance in projection) score > 1.0 and permutation test, p-value <0.01]. 45 active and 53 inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37 years], female to male ratio 3.5:1 and 4.9:1, and median duration of illness 5 [(IQR) 2-9 years] and 3 [(IQR) 1-6 years], respectively, were enrolled. The key metabolites with highest discriminatory potential in active TA (ITAS-A ≥ 4) were glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the curve 0.775 and 0.769 ( p-value <0.001). On follow up assessment, metabolic spectra started to differ with change in disease activity. This large cohort of patients revealed metabolic profiles discriminating between clinically active and inactive TA patients. It suggests glutamate and NAG have strong potential as biomarkers for disease activity in TA and may serve as a guide to therapy. We are now working to further validate these results in longitudinal studies.

Concomitant Hybrid Arch Vessel Reconstruction and Intracranial Clot Retrieval in Takayasu's Arteritis Presenting with Acute Cerebral Ischemia: A Case Report.

BACKGROUND: Type 1 Takayasu's arteritis (TA) predominantly affects the supra-aortic branches. Occlusive disease can cause catastrophic complications such as stroke and death. Open and endovascular techniques of revascularization are described for extracranial disease. There is currently no default choice of surgical intervention. Furthermore, the management of distal intracranial complications has not been described. METHODS: A 25-year-old woman with known TA on immunosuppression was presented with acute left middle cerebral artery (MCA) stroke. Computed tomography angiogram and formal cerebral digital subtraction angiography demonstrated critical stenoses or occlusion of all arch vessels except for the left subclavian artery (SCA), which was also stenosed at the origin. The left vertebral artery was the sole inflow to the brain. Furthermore, there was acute embolus in M1 of MCA and A1 of the anterior cerebral artery (ACA). Surgical access was achieved by bilateral common carotid artery (CCA) and left SCA exposures. Extracranial revascularization was performed using a hybrid technique: (i) left SCA covered stent; (ii) left SCA to right CCA bypass; (iii) left CCA thrombectomy; (iv) left CCA covered stent; and (v) left CCA interposition bypass. This was immediately followed by clot retrieval in the MCA and ACA territory for intracranial revascularization. RESULTS: There were no major postoperative complications and the patient made an excellent neurologic recovery. CONCLUSIONS: Hybrid vascular reconstruction for extracranial disease with concomitant clot retrieval for intracranial disease is a novel approach to achieving emergency revascularization in active TA.

Non-glucocorticoid drugs for the treatment of Takayasu's arteritis: A systematic review and meta-analysis.

BACKGROUND: Takayasu's Arteritis (TAK) affects mostly young women and causes significant morbidity. Most patients are refractory to glucocorticoids (GC) or relapse when GC doses are reduced. The objective of this study is to summarize the literature pertaining to the effectiveness of non-GC drugs for the treatment of TAK. METHODS: MEDLINE and Embase were searched for English-language studies of TAK patients with a sample size >5. Studies were included if the effectiveness of non-GC drugs for the treatment of TAK was reported. Random effects meta-analyses of various effect measures were performed. RESULTS: Of the 915 studies identified by the search, 14 of small molecule immunosuppressants (IS) and 25 of biologic therapies were included. Studies had a high risk of bias. Pooled remission rates were similar for both categories of non-GC drugs: 58% (95% CI: 40-74%) and 64% (95% CI: 56-72%), respectively. The relapse rate was 54% (95% CI: 39-68%) for IS therapies and 31% (95% CI: 22-41%) for biologics. Both significantly decreased GC doses and acute phase reactants. Observational studies suggested that anti-TNF agents were more effective than IS at maintaining remission. Randomized-controlled trials (RCTs) of biologics were of small sample size: abatacept was not effective and the trial of tocilizumab was underpowered to detect a difference in time to relapse versus placebo. Serious adverse events were uncommon. CONCLUSIONS: Non-GC agents were moderately effective in inducing remission in TAK, but relapse rates were high. Larger, better designed studies are required to determine the optimal treatment regimen for TAK.

[Staged surgical treatment of a woman with nonspecific aortoarteritis and bilateral occlusion of carotid arteries]. / Poétapnoe khirurgicheskoe lechenie bol'noi nespetsificheskim aortoarteriitom s dvukhstoronnei okkliuziei sonnykh arterii.

Nonspecific aortoarteritis (NAA) is an autoimmune disease characterized by the development of an inflammatory process in large arteries such as the aorta and its branches and pulmonary arteries. Operative interventions for lesions of the aortic arch branches may be divided into extra- and transthoracic. Involvement of all branches of the aortic arch requires transthoracic interventions to be performed. According to the findings of various authors, bicarotid bypass grafting is accompanied by a high incidence rate of complications and lethal outcomes. The most serious complication is haemorrhagic stroke developing in 40% of patients. That is why commencing from 1991 the practice of simultaneous restoration of the two carotid basins was discontinued. A clinical case report presented herein demonstrates the authors' therapeutic policy in patients with NAA and multiple involvement of brachiocephalic arteries and first of all with bicarotid occlusion.