En los últimos años el stenting carotídeo ha emergido como una potencial alternativa a la endarterectomía carotídea en téminos de seguridad y eficacia. El estudio SAPPHIRE probó que en los pacientes de alto riesgo con estenosis carotídea grave, el stenting carotídeo realizado con protección cerebral mediante filtro distal no es inferior a la endarterectomía. Aunque los sistemas de protección cerebral que utilizan los filtros distales reducen las complicaciones tromboembólicas durante el stenting carotídeo, la protección parece ser insuficiente. Por el contrario, cuando la protección cerebral implica la oclusión de la arteria carótida común y la creación de un flujo reverso en la arteria carótida interna se consigue una importante ventaja: la protección cerebral se realiza antes de atravesar la lesión, uno de los pasos más embolígenos durante el stenting carotídeo. En nuestra experiencia, el flujo reverso a través de un acceso transcervical es un método simple y seguro que elimina los inconvenientes de la instrumentación del arco aórtico y el hecho de atravesar la lesión sin protección. Es además más barato que los métodos que requieren un filtro distal y los resultados a corto y medio plazo son comparables a los reportados para la endarterectomía. Se ha sugerido que los pacientes de edad avanzada podrian constituir un subgrupo de alto riesgo para el stenting carotídeo. Distintas experiencias individuales y particularmente los resultados del estudio CREST, parecen confirmar esta idea. Tradicionalmente y fuera de experiencias individuales de endarterectomía carotídea en octogenarios, este subgrupo de pacientes fueron excluidos de los estudios multicéntricos que compararaban la endarterectomía con el mejor tratamiento médico, por lo que la incidencia de complicaciones de la endarterectomía en estos pacientes no es bien conocida haciendo más dificil establecer la mejor opción de tratamiento en esta población. La hipótesis que podría explicar la mayor tasa de complicaciones con el stenting carotídeo por vía transfemoral en pacientes añosos es la mayor dificultad técnica debido a la mayor complejidad del arco aórtico y a la tortuosidad de los troncos supraórticos en este grupo de edad. El stent carotídeo trancervical con flujo reverso evita ambos pasos: permite el despliegue del stent en la lesión estenótica sin instrumentación del arco aórtico. Los resultados de nuestro estudio confirman que la revascularización carotídea mediante stenting carotídeo transcervical con inversión de flujo para la protección cerebral es tan seguro como la endarterectomía en pacientes octogenarios, en contraste con las consideraciones de la mayoría de los autores que no recomiendan stenting carotídeo en este subgrupo de pacientes. Además, en la actualidad, los resultados del meta-análisis y revisiones sistemáticas ponen de manifieso altas tasas de ictus y muerte en pacientes de edad avanzada (mayores de 70 años) sometidos a stenting carotídeo por vía transfemoral y sugieren que el stent carotídeo se debe evitar en esta población. En esta tesis doctoral se ha podido demostrar que en pacientes octogenarios el stent carotídeo realizado con abordaje transcervical y flujo reverso es tan seguro como la endarterectomía carotídea a corto plazo. El acceso transcervical evita las limitaciones anatómicas antes mencionados y la inversión del flujo reduce el número de microembolias que ocurren durante el procedimiento. Hemos podido además confirmar los mismos resultados en pacientes mayores de 70 años. Creemos que lo que se debe evitar en esta población es la instrumentación del arco aórtico y de los troncos supraórtcicos, no el stenting carotídeo y por tanto el uso de la vía transcervical y la creación del flujo reverso es una técnica segura y eficaz en este grupo de pacientes. / In the last few years transfemoral carotid artey stenting has emerged as a potential alternative to endarterectomy in terms of both safety and efficacy. The SAPPHIRE trial proved that among high risk patients with severe carotid artery stenosis and coexisting conditions, carotid artey stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy: Cerebral filtering devices reduce thromboembolic complications durins carotid artey stenting , however the degree of protection appears to be incomplete. Systems for cerebral protection that involve proximal common carotid artery occlusion and establishment of flow reversal in the internal carotid artery offer an important advantage: cerebral protection is established before crossing the lesion, which is one of the most emboligenic maneuvers in carotid stenting. The use of a transfemoral route to establish flow reversal presents the drawbacks related to femoral access. In our experience, flow reversal using a transcervical access route is a simple, safe method that eliminates the drawbacks of aortic arch instrumentation and crossing the target lesion without protection. In addition, it is less expensive than methods requiring a filter device, and the short- and long-term outcomes are comparable to the reported results for carotid vascularization by endarterectomy. It has been suggested that patients of advanced age may constitute a high-risk subgroup for carotid artery angioplasty and stenting .Various individual experiences, and particularly the preliminary results of the lead-in phase of the CREST study, seem to confirm this idea. Moreover, apart from individual experiences with carotid endarterectomy in octogenarians, this age group was historically excluded from multicenter trials comparing endarterectomy and the best medical therapy. Thus, the precise incidence of complications associated with carotid endarterectomy is not known, making even more difficult to establish the best treatment option in this population. The hypothesis that may explain the higher rate of complications with the use of transfemoral carotid artey stenting in elderly patients is the greater technical difficulty of the treatment due to frequent anatomical complexity of the aortic arch and tortuosity of the supraaortic trunks in this age group. Transcervical carotid stenting with flow reversal is a technique that allows stent deployment over the stenotic lesion without aortic arch instrumentation. The results of our study confirm that carotid revascularization by transcervical carotid artey stenting with flow reversal for cerebral protection is as safe as carotid endarterectomy in octogenarian patients in contrast to the considerations of most authors who do not recommend carotid artey stenting in this patient subgroup. Currently, the results of meta-analyses and systematic reviews have pointed to elevated rates of stroke/death in older patients ( over 70 years) undergoing transfemoral carotid artery angioplasty and stenting , and strongly suggest that carotid stenting should be avoided in this population. The hypotheses are the same as those discussed above. This thesis has been demonstrated that carotid stenting octogenarians performed with transcervical approach and reverse flow is as safe as carotid endarterectomy in the short term. Transcervical access anatomical avoids the limitations mentioned above and the reversal of the flow reduces the number of microemboli which occur during the procedure. We could also confirm the same results in patients over 70 years. We believe that what should be avoided in this population is the implementation of the aortic arch and supraórtcicos trunks, not carotid stenting and therefore the use of the transcervical and the creation of flow reversal is a safe and effective in this group patients.

Made available in DSpace on 2016-03-22T17:26:32Z (GMT). No. of bitstreams: 1 MESTRADO FERNANDA.pdf: 502799 bytes, checksum: ac66c75ef6d7608e98e8cb58e8b514d8 (MD5) Previous issue date: 2010-12-09 / OBJECTIVES: Assess the carotid intima-media thickness (IMT) in a sample of male adolescents in a southern Brazil city, and investigate the association of this measure with biological and demographics variables. METHODS: Cross-sectional study in a random sample of 239 eighteen years old male adolescents, in the Pelotas city military recruitment, in the south of Brazil, held in July 2010. The presence of cardiovascular risk factors was investigated by a questionnaire and physical examination (weight, height, blood pressure and waist circumference). The study was performed in B-mode ultrasound of both common carotid arteries, with IMT measurement in the posterior wall, at a distance of 1.0 to 2.0 cm of the carotid bifurcation. We obtained five measurements of each common carotid and the mean of both sides corresponded to the carotid IMT of each participant. RESULTS: The mean carotid IMT was 0.4969 (± 0.0466) mm and atheromatous plaque were not identified in any adolescent. In the multivariate analysis, BMI (p=0.005) and waist circumference (p<0.001) were positively associated with carotid IMT. CONCLUSION: The association of BMI and waist circumference with the carotid IMT during adolescence shows the importance of adiposity as a cardiovascular risk factor / OBJECTIVES: Assess the carotid intima-media thickness (IMT) in a sample of male adolescents in a southern Brazil city, and investigate the association of this measure with biological and demographics variables. METHODS: Cross-sectional study in a random sample of 239 eighteen years old male adolescents, in the Pelotas city military recruitment, in the south of Brazil, held in July 2010. The presence of cardiovascular risk factors was investigated by a questionnaire and physical examination (weight, height, blood pressure and waist circumference). The study was performed in B-mode ultrasound of both common carotid arteries, with IMT measurement in the posterior wall, at a distance of 1.0 to 2.0 cm of the carotid bifurcation. We obtained five measurements of each common carotid and the mean of both sides corresponded to the carotid IMT of each participant. RESULTS: The mean carotid IMT was 0.4969 (± 0.0466) mm and atheromatous plaque were not identified in any adolescent. In the multivariate analysis, BMI (p=0.005) and waist circumference (p<0.001) were positively associated with carotid IMT. CONCLUSION: The association of BMI and waist circumference with the carotid IMT during adolescence shows the importance of adiposity as a cardiovascular risk factor

O acidente vascular cerebral (AVC) e a primeira causa de obito no Brasil e a principal de incapacidade no mundo. A doenca aterosclerotica carotidea esta associada a cerca de 15% dos AVC. A endarterectomia cirurgica e o tratamento padrao-­ouro para as estenoses carotideas sintomaticas. A angioplastia carotidea com stent via endovascular (ACS) e uma alternativa terapeutica a endarterectomia. O desenvolvimento de dispositivos de protecao embolica levou a reducao das taxas de complicacao durante a ACS. A tecnica de protecao mais utilizada na pratica clinica e a protecao distal com filtro. As estrategias de protecao proximal, por bloqueio ou reversao do fluxo carotideo, tem revelado resultados promissores em relacao a protecao distal com filtro durante a ACS. Assim, o objetivo do estudo foi comparar a reversao de fluxo e o filtro de protecao durante a ACS. Os objetivos primarios foram a incidencia, o numero e o tamanho das lesoes cerebrais isquemicas por ressonancia magnetica pela sequencia diffusion-­weighted-­imaging (DWI) apos a ACS. Os objetivos secundarios foram as complicacoes cardiacas e eventos cerebrovasculares (CCEC), ataque isquemico transitorio (AIT) e as lesoes cerebrais isquemicas definitivas na imagem por ressonancia magnetica pela sequencia fluid-­attenuated inversion recovery (FLAIR) no seguimento de tres meses. As lesoes isquemicas foram obtidas por ressonancia magnetica (RM) de campo 3 Tesla. Os pacientes foram avaliados quanto aos desfechos neurologicos atraves das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS). Quarenta pacientes foram incluidos randomicamente no estudo. Comparado a reversao de fluxo (n=21) o filtro de protecao (n=19) resultou em uma reducao significativa na incidencia (15,8% vs. 47,6%, p=0,03), no numero (0,73 vs. 2,6, p=0,05) e no tamanho (0,81 vs. 2,23 mm, p=0,05) das novas lesoes cerebrais isquemicas. Dois pacientes, um de cada grupo, apresentaram AIT no seguimento de tres meses. Nao foram observadas CCEC na internacao ou no seguimento de tres meses. Neste estudo, o filtro de protecao mais eficaz que a reversao de fluxo na protecao cerebral durante a angioplastia carotidea com stent por acesso femoral. / Objectives: Carotid artery stenting (CAS) has become an alternative treatment for patients presenting symptomatic carotid artery stenosis. The improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices. The trial aim is to compare flow-­reversal versus filter protection during CAS through femoral access. Methods: Patients were randomly enrolled in CAS using flow-­reversal or filter protection. The primary endpoints were the incidence, number and size of new ischemic brain lesions after CAS. The secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE), transient ischemic attack (TIA) and definitive ischemic brain lesions on fluid-­attenuated inversion recovery magnetic resonance image (FLAIR-­MRI) at a three-­month follow-­up. Ischemic brain lesions were assessed by a 3T-­MRI. Neurological outcomes were evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Results: Forty consecutive patients were randomly assigned. Compared to flow-­reversal (n=21), filter protection (n=19) resulted in a significant reduction in the incidence (15.8% vs. 47.6%, p=0.03), number (0.73 vs. 2.6, p=0.05) and size (0.81 vs. 2.23 mm, p=0.05) of new ischemic brain lesions. Two patients, one from each group, presented TIA at the three-­month follow-­up. There were no MACCE in the hospital or at the three-­month follow-­up. Conclusions: In this small sample size trial, filter protection was more effective than flow-­reversal in reducing ischemic brain lesions during CAS through femoral approach.

Orientador: Luis Gustavo Modelli de Andrade / Resumo: Introdução: Os inibidores do alvo de rapamicina em mamíferos (mTORI) podem conferir vantagens cardioprotetoras. Em modelos animais, o mTORI pode prevenir a aterogênese pela regulação da homeostase do colesterol e pela redução da resposta inflamatória. Além disso, a administração de mTORI pode levar à redução da massa ventricular esquerda. O objetivo deste estudo é comparar a espessura médio intimal da carotída (cIMT) e a massa ventricular esquerda indexada (LVMi) entre o grupo de tacrolimus associado a micofenolato (grupo micofenolato) e tacrolimo associado a sirolimo (grupo sirolimo) em baixas doses. A cIMT é considerada um marcador substituto da aterosclerose. Métodos: Nós avaliamos a cIMT e a LVMi no início e aos 6 e 12 meses após o transplante renal. Foram randomizados prospectivamente todos os receptores de transplante renal com mais de 60 anos para um dos dois grupos: tacrolimus / sirolimus (n = 21) ou tacrolimus / micofenolato (n = 23). A cIMT foi avaliada por ultrassonografia na parede da artéria carótida comum e o LVMi pelo ecocardiograma. Resultados: Os níveis de colesterol total e de lipoproteína de alta densidade (HDL) foram maiores no grupo do sirolimus aos 6 e 12 meses. O cIMT diminuiu com o tempo aos 6 e 12 meses no grupo do sirolimus (p = 0,012); esta diminuição continuou a ser significativa em um modelo ajustado para idade, sexo, presença de diabetes, uso de estatina e tabagismo. Houve redução ao longo do tempo na massa ventricular esquerda indexada, mas não ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Mammalian target of rapamycin inhibitors (mTORI) may confer cardioprotective advantages. In animal models, the mTORI may prevent atherogenesis by the regulation of homeostasis of cholesterol and by a reduced inflammatory response. In addition, the administration of mTORI may lead to reduction of left ventricular mass. The aim of this study is to compare the carotid intima-media thickness (cIMT) and left ventricular mass index (LVMi) between de novo tacrolimus/mycophenolate and tacrolimus/sirolimus at low doses. The cIMT is considered a surrogate marker of atherosclerosis. Methods: We evaluated cIMT and LVMi at baseline and at 6 and 12 months after kidney transplantation. We prospectively randomly assigned kidney transplant recipients older than 60 years of age to one of two groups: tacrolimus/sirolimus (n=21) or tacrolimus/mycophenolate (n=23). The cIMT was evaluated by using ultrasound in the common carotid artery wall in both sides ant the LVMi by echocardiogram. Results: The total and high-density lipoprotein cholesterol levels were higher in the sirolimus group at 6 and 12 months. The cIMT decreased over time at 6 and 12 months in the sirolimus group (p = 0.012); this decrease continued to be significant in a model adjusted for age, sex, presence of diabetes, statin use and smoking. There was a reduction over time in LVMi, but there were no differences between groups suggesting absence of sirolimus class effect. Conclusions: The use of sirolimus plus tacrolimu... (Complete abstract click electronic access below) / Mestre

O acidente vascular cerebral (AVC) e a primeira causa de obito no Brasil e a principal de incapacidade no mundo. A doenca aterosclerotica carotidea esta associada a cerca de 15% dos AVC. A endarterectomia cirurgica e o tratamento padrao-­ouro para as estenoses carotideas sintomaticas. A angioplastia carotidea com stent via endovascular (ACS) e uma alternativa terapeutica a endarterectomia. O desenvolvimento de dispositivos de protecao embolica levou a reducao das taxas de complicacao durante a ACS. A tecnica de protecao mais utilizada na pratica clinica e a protecao distal com filtro. As estrategias de protecao proximal, por bloqueio ou reversao do fluxo carotideo, tem revelado resultados promissores em relacao a protecao distal com filtro durante a ACS. Assim, o objetivo do estudo foi comparar a reversao de fluxo e o filtro de protecao durante a ACS. Os objetivos primarios foram a incidencia, o numero e o tamanho das lesoes cerebrais isquemicas por ressonancia magnetica pela sequencia diffusion-­weighted-­imaging (DWI) apos a ACS. Os objetivos secundarios foram as complicacoes cardiacas e eventos cerebrovasculares (CCEC), ataque isquemico transitorio (AIT) e as lesoes cerebrais isquemicas definitivas na imagem por ressonancia magnetica pela sequencia fluid-­attenuated inversion recovery (FLAIR) no seguimento de tres meses. As lesoes isquemicas foram obtidas por ressonancia magnetica (RM) de campo 3 Tesla. Os pacientes foram avaliados quanto aos desfechos neurologicos atraves das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS). Quarenta pacientes foram incluidos randomicamente no estudo. Comparado a reversao de fluxo (n=21) o filtro de protecao (n=19) resultou em uma reducao significativa na incidencia (15,8% vs. 47,6%, p=0,03), no numero (0,73 vs. 2,6, p=0,05) e no tamanho (0,81 vs. 2,23 mm, p=0,05) das novas lesoes cerebrais isquemicas. Dois pacientes, um de cada grupo, apresentaram AIT no seguimento de tres meses. Nao foram observadas CCEC na internacao ou no seguimento de tres meses. Neste estudo, o filtro de protecao mais eficaz que a reversao de fluxo na protecao cerebral durante a angioplastia carotidea com stent por acesso femoral. / Objectives: Carotid artery stenting (CAS) has become an alternative treatment for patients presenting symptomatic carotid artery stenosis. The improvement in clinical outcomes with CAS has been associated with the development of embolic protection devices. The trial aim is to compare flow-­reversal versus filter protection during CAS through femoral access. Methods: Patients were randomly enrolled in CAS using flow-­reversal or filter protection. The primary endpoints were the incidence, number and size of new ischemic brain lesions after CAS. The secondary endpoints included major adverse cardiac and cerebrovascular events (MACCE), transient ischemic attack (TIA) and definitive ischemic brain lesions on fluid-­attenuated inversion recovery magnetic resonance image (FLAIR-­MRI) at a three-­month follow-­up. Ischemic brain lesions were assessed by a 3T-­MRI. Neurological outcomes were evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Results: Forty consecutive patients were randomly assigned. Compared to flow-­reversal (n=21), filter protection (n=19) resulted in a significant reduction in the incidence (15.8% vs. 47.6%, p=0.03), number (0.73 vs. 2.6, p=0.05) and size (0.81 vs. 2.23 mm, p=0.05) of new ischemic brain lesions. Two patients, one from each group, presented TIA at the three-­month follow-­up. There were no MACCE in the hospital or at the three-­month follow-­up. Conclusions: In this small sample size trial, filter protection was more effective than flow-­reversal in reducing ischemic brain lesions during CAS through femoral approach.