Introduction. Atherosclerotic plaque rupture may occur without warning leading to severe clinical events such as heart attack and stroke. The mechanisms causing plaque rupture are not well understood. It is hypothesized that mechanical forces may play an important role in the plaque rupture process and that image-based computational mechanical analysis may provide useful information for more accurate plaque vulnerability assessment. The objectives of this dissertation are: a) develop in vivo magnetic resonance imaging (MRI)-based 3D computational models with fluid-structure Interactions (FSI) for human atherosclerotic carotid plaques; b) perform mechanical analysis using 3D FSI models to identify critical stress/strain conditions which may be used for possible plaque rupture predictions. Data, Model, and Methods. Histological, ex vivo/ in vivo MRI data of human carotid plaques were provided by the University of Washington Medical School and Washington University Medical School. Blood flow was assumed to be laminar, Newtonian, viscous and incompressible. The Navier-Stokes equations with arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations for the flow model. The vessel and plaque components were assumed to be hyperelastic, isotropic, nearly-incompressible and homogeneous. The nonlinear Mooney-Rivlin model was used to describe the nonlinear properties of the materials with parameter values chosen to match available experimental data. The fully-coupled FSI models were solved by a commercial finite element software ADINA to obtain full 3D flow and stress/strain distributions for analysis. Validation of the computational models and Adina software were provided by comparing computational solutions with analytic solutions and experimental data. Several novel methods were introduced to address some fundamental issues for construction of in vivo MRI-based 3D FSI models: a) an automated MRI segmentation technique using a Bayes theorem with normal probability distribution was implemented to obtain plaque geometry with enclosed components; b) a pre-shrink process was introduced to shrink the in vivo MRI geometry to obtain the no-load shape of the plaque; c) a Volume Component-Fitting Method was introduced to generate a 3D computational mesh for the plaque model with deformable complex geometry, FSI and inclusions; d) a method using MRI data obtained under in vitro pressurized conditions was introduced to determine vessel material properties. Results. The effects of material properties on flow and wall stress/strain behaviors were evaluated. The results indicate that a 100% stiffness increase may decrease maximal values of maximum principal stress (Stress-P1) and maximum principal strain (Strain-P1) by about 20% and 40%, respectively; flow Maximum-Shear-Stress (FMSS) and flow velocity did not show noticeable changes. By comparing ex vivo and in vivo data of 10 plaque samples, the average axial (25%) and inner circumferential (7.9%) shrinkages of the plaques between loaded and unloaded state were obtained. Effects of the shrink-stretch process on plaque stress/strain distributions were demonstrated based on six adjusted 3D FSI models with different shrinkages. Stress-P1 and Strain-P1 increased 349.8% and 249% respectively with 33% axial stretch. The effects of a lipid-rich necrotic core and fibrous cap thickness on structure/flow behaviors were investigated. The mean values of wall Stress-P1 and Strain-P1 from lipid nodes from a ruptured plaque were significantly higher than those from a non-ruptured plaque (112.3 kPa, 0.235 & 80.1 kPa, 0.185), which was 40.2% and 26.8% higher, respectively (p<0.001). High stress/strain concentrations were found at the thin fibrous cap regions. These results indicate that high stress concentrations and thin fibrous cap thickness might be critical indicators for plaque vulnerability. Conclusion. In vivo image-based 3D FSI models and mechanical image analysis may have the potential to provide quantitative risk indicators for plaque vulnerability assessment.

INTRODUCTION: The“vulnerable plaque" is defined as the“precursor lesion" that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo.

INTRODUÇÃO: Os suportes vasculares bioabsorvíveis (SVB) surgiram com a finalidade de aumentar a segurança tardia das intervenções coronárias percutâneas (ICP). Estes dispositivos liberam o fármaco antiproliferativo no local da obstrução e são absorvidos com o passar do tempo. A utilização do ultrassom intracoronário (USIC) pode ajudar na avaliação do processo de absorção deste dispositivo. OBJETIVOS: Primário: avaliar e comparar, pelo USIC, o volume e a área da luz, do vaso e do SVB imediatamente após o implante da prótese, e, tardiamente, aos 6 e 18 meses. Objetivos secundários: avaliar e comparar, pelo USIC, o volume e área da placa imediatamente após o implante da prótese, e, tardiamente, aos 6 e 18 meses e os diâmetros do vaso, lúmen e SVB após ICP e no seguimento. Percentual de estenose e perda tardia do lúmen pela angiografia no seguimento e incidência de eventos cardíacos adversos maiores (ECAM) até os 18 meses. MÉTODO: Trata-se de um estudo prospectivo, não randomizado com a inclusão de 20 pacientes que foram submetidos ao implante do SVB DESolve®. Foi realizado o USIC após o procedimento e aos 6 e 18 meses de seguimento. RESULTADOS: Dos 20 pacientes selecionados, um paciente recusou realizar o USCI aos 6 meses e dois não realizaram o exame aos 18 meses, sendo excluídos do estudo. Totalizando 17 pacientes analisados. A idade média foi de 58,59 ± 8,73 anos e 70,6% eram do sexo masculino. O quadro clínico predominante era de angina estável. A via de acesso preferencial foi a radial, todos os pacientes foram submetidos à pré e pós-dilatação e o sucesso angiográfico ocorreu em todos os casos. No seguimento, houve aumento significativo na área (6,41 ± 1,35 mm2 vs. 7,35 ± 1,53 mm2, p < 0,002), volume (101,19 ± 20,9 mm3 vs. 118,51 ± 26,6 mm3, p = 0,001) e diâmetros do dispositivo, pelo USIC, aos 6 meses quando comparado ao procedimento índice. Não houve alteração significativa nas áreas, nos volumes e nos diâmetros do vaso e lúmen, em qualquer comparação no seguimento. A perda tardia foi de 0,22 ± 0,30 mm aos 6 e de 0,33 ± 0,44 mm aos 18 meses. Não houve nenhum caso de reestenose angiográfica e trombose do dispositivo. No seguimento, não houve casos de ECAM. CONCLUSÕES: A ICP com a utilização do SVB DESolve® para o tratamento da doença arterial coronária não complexa demonstrou resultados promissores. Houve aumento do volume e área do dispositivo aos 6 meses e uma supressão eficaz da hiperplasia intimal sem ECAM no seguimento. / INTRODUCTION: The bioresorbable vascular scaffolds (BVS) emerged in order to increase late safety of percutaneous coronary interventions (PCI). These devices release the antiproliferative drug to the site of obstruction and are absorbed over time. The use of intravascular ultrasound (IVUS) can help in the evaluation of this device absorption process. OBJECTIVES: The primary endpoint was to evaluate and compare, through IVUS, the volume and the area of the lúmen, the vessel and the device immediately after its implantation, and later at 6 and 18 months. The secondary endpoints were to evaluate and compare, through IVUS, the volume and the area of the plaque immediately after its implantation, and later at 6 and 18 months and diameters of the vessel, lúmen and BVS after PCI and at follow-up. Percentage of stenosis and late lúmen loss by angiography and incidence of major adverse cardiac events (MACE) up to 18 months. METHOD: This is a prospective, non-randomized study, with the inclusion of 20 patients who underwent implantation of DESolveTM. IVUS was performed after the procedure and at 6 and 18 months of follow-up. RESULTS: Of the 20 patients selected, one patient refused to perform the USCI at 6 months and two did not undergo the exam at 18 months and were excluded from the study. In total, 17 patients were analyzed. The average age was 58.59 ± 8.73 years and 70,6% were male. The most common clinical presentation was stable angina. The preferred vascular acess was to radial, all patients underwent pre- and post-dilation and angiographic success occurred in all cases. At follow-up there was a significant increase in area (6,41 ± 1,35 mm2 vs. 7,35 ± 1,53 mm2, p < 0,002), volume (101,19 ± 20,9 mm3 vs. 118,51 ± 26,6 mm3, p = 0,001) and diameters of the device, by IVUS, at 6 months when compared to the index procedure. There was no significant change in the areas, volumes and diameters of the vessel and lúmen, in any comparison at follow-up. The late loss was 0,22 ± 0,30 mm at 6 and 0,33 ± 0,44 mm at 18 months. There were no cases of restenosis and scaffold thrombosis. During follow-up there was no case of MACE. CONCLUSIONS: PCI with the use of DESolve scaffold for the treatment of non-complex coronary artery disease has shown promising results. There was an increase in the volume and area of the device at 6 months and an effective suppression of intimal hyperplasia without MACE at follow-up.

Atherosclerosis is an inflammatory disease, occurring preferentially in arterial regions with disturbed flow. We have shown that disturbed flow induces inflammation in endothelial cells (ECs) by producing bone morphogenic protein-4 (BMP4). Moreover, chronic BMP4 infusion induces endothelial dysfunction and systemic hypertension in mice. Here, we examined which BMP receptors (BMPR) mediate BMP4 action in ECs. Western blot, immunostaining and RT-PCR studies using human and bovine ECs, mouse aortas and human coronary arteries (HCA) showed that BMPRI (ALK2 and 6) and BMP-RII were expressed in ECs. As a functional test, ECs were treated with a BMPRII siRNA to knockdown expression. BMPRII knockdown blocked a well-known BMP4 response - smad1/5/8 phosphorylation, as expected. Unexpectedly, BMPRII knockdown itself significantly stimulated ICAM-1 and VCAM-1 expression and monocyte adhesion in a BMP4-independent manner. Inflammatory responses caused by BMPRII knockdown were blocked by inhibitors of NADPH oxidase and NFκ B. From these results, we hypothesized that BMP-RII knockdown in ECs would cause inflammation, which is a critical event in atherosclerosis initiation and progression. Genetic mutations of BMPRII have been linked to primary pulmonary hypertension. However, it is not known whether BMP-RII is regulated by atherosclerotic conditions and plays a role in non-pulmonary vessels causing inflammation and atherosclerosis. We examined BMPRII levels in HCA by immunostaining. While non-diseased arteries showed intense staining of BMPRII, the expression decreased as lesions became more advanced. BMPRII was virtually undetectable in the most advanced lesions. These findings suggested a potential link between pro-atherosclerotic conditions and BMP-RII levels. We tested this hypothesis by treating ECs with pro-inflammatory cytokines found in atheromas: TNFα decreased BMPRII by 2-fold. In contrast, statins increased BMPRII by 4-fold. In summary, we demonstrate for the first time that BMPRII can be down- or up-regulated by pro- or anti-atherogenic conditions, respectively, and it is dramatically decreased in HCA with advanced plaques. Moreover, BMPRII knockdown in ECs induces inflammation, a critical atherogenic step. We propose that focal inflammation initiated by disturbed flow, together with circulating pro-atherogenic risk factors, may lead to a vicious cycle of BMPRII down-regulation causing secondary inflammation and atheroma progression.

Thesis (Ph. D.)--University of Canterbury, 2006. / Typescript (photocopy). Includes bibliographical references (leaves 233-271). Also available via the World Wide Web.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Over the past few years, the involvement between oral pathogens and vascular disease has been investigated, with growing attention to the pathogenesis and progression of atherosclerosis. Oral bacteria have been detected in atherosclerotic plaques at a variable frequency; however, the connection between oral health and vascular and oral bacterial profiles of these patients is not clearly established. The aim of this study was to evaluate the presence of oral bacteria DNA in the mouth and atherosclerotic plaques, in addition to assess the patientâs caries and periodontal disease history. Thirty samples of supragingival and subgingival plaque, saliva and atherosclerotic plaques of 13 patients with carotid stenosis or aortic aneurysm were evaluated, through Real Time Polymerase Chain Reaction, for the presence/absence of Streptococcus mutans, Prevotella intermedia, Porphyromonas gingivalis and Treponema denticola. For edentulous patients, the variables of supragingival and subgingival plaques were not considered. All patients were submitted to oral exams using the DMTF (decayed, missing and filled teeth) and PSR (Periodontal Screening and Recording) indexes for dental and periodontal evaluation, respectively, and histopathological analysis of the atherosclerotic plaques was performed. Most of the patients were edentulous (76.9%). Streptococcus mutans, Prevotella intermedia, Porphyromonas gingivalis and Treponema denticola were detected in 100.0%, 92.0%, 15.3% and 30.7% of the oral samples, respectively. Streptococcus mutans was the most prevalent targeted bacteria in atherosclerotic plaques (p<0,05), detected in 100% of the samples, followed by Prevotella intermedia (7.1%), and the vascular samples were negative for Porphyromonas gingivalis and Treponema denticola. There was a statistically significant difference (p<0,05) between the presence of Porphyromonas gingivalis and Treponema denticola in the oral cavity and vascular samples. In conclusion, Streptococcus mutans was found at a high frequency in oral and vascular samples, even in edentulous patients, and its presence in atherosclerotic plaques suggests the possible involvement of this bacteria with the disease progression. / Nos Ãltimos anos, a relaÃÃo entre patÃgenos orais e doenÃa vascular tem sido investigada, com crescente atenÃÃo para a etiopatogÃnese e progressÃo da aterosclerose. BactÃrias orais tÃm sido detectadas em placas aterosclerÃticas, com variÃvel frequÃncia, porÃm, a relaÃÃo entre saÃde bucal e perfis bacterianos vasculares e orais dos pacientes nÃo està claramente estabelecida. Foi objetivo deste estudo avaliar a presenÃa de DNA de bactÃrias orais na boca e placas aterosclerÃticas, alÃm de avaliar histÃrico de cÃrie e doenÃa periodontal dos pacientes. Trinta amostras de placa dental supragengival, subgengival, saliva, e placas aterosclerÃticas de 13 pacientes com estenose de carÃtida ou aneurisma de aorta foram avaliadas, atravÃs de ReaÃÃo em Cadeia da Polimerase em Tempo Real, para presenÃa/ausÃncia de Streptococcus mutans, Prevotella intermedia, Porphyromonas gingivalis e Treponema denticola. Para pacientes desdentados totais, nÃo foram consideradas as variÃveis de placa supragengival e subgengival. Todos os pacientes foram submetidos a exames de CPO-D (dentes permanentes cariados, perdidos e obturados) e PSR (registro periodontal simplificado) para avaliaÃÃo dentÃria e periodontal, respectivamente, bem como anÃlise histopatolÃgica das placas aterosclerÃticas. A maioria dos pacientes eram edÃntulos (76,9%). Streptococcus mutans, Prevotella intermedia, Porphyromonas gingivalis e Treponema denticola foram detectados em 100,0%, 92,0%, 15,3% e 30,7% das amostras orais, respectivamente. O micro-organismo mais prevalente em placas aterosclerÃticas foi o Streptococcus mutans (p<0,05), presente em 100,0% das amostras, seguido de Prevotella intermedia (7,1%), e as amostras vasculares foram negativas para Porphyromonas gingivalis e Treponema denticola. Observou-se diferenÃa estatisticamente significante (p<0,05) com relaÃÃo à presenÃa de Porphyromonas gingivalis e Treponema denticola em cavidade oral e amostra vascular. Em conclusÃo, Streptococcus mutans foi encontrado em alta frequÃncia em amostras orais e vasculares, mesmo de pacientes desdentados, e sua presenÃa em placas aterosclerÃticas sugere o possÃvel envolvimento desse patÃgeno na progressÃo da doenÃa.

INTRODUÇÃO: Os suportes vasculares bioabsorvíveis (SVB) surgiram com a finalidade de aumentar a segurança tardia das intervenções coronárias percutâneas (ICP). Estes dispositivos liberam o fármaco antiproliferativo no local da obstrução e são absorvidos com o passar do tempo. A utilização do ultrassom intracoronário (USIC) pode ajudar na avaliação do processo de absorção deste dispositivo. OBJETIVOS: Primário: avaliar e comparar, pelo USIC, o volume e a área da luz, do vaso e do SVB imediatamente após o implante da prótese, e, tardiamente, aos 6 e 18 meses. Objetivos secundários: avaliar e comparar, pelo USIC, o volume e área da placa imediatamente após o implante da prótese, e, tardiamente, aos 6 e 18 meses e os diâmetros do vaso, lúmen e SVB após ICP e no seguimento. Percentual de estenose e perda tardia do lúmen pela angiografia no seguimento e incidência de eventos cardíacos adversos maiores (ECAM) até os 18 meses. MÉTODO: Trata-se de um estudo prospectivo, não randomizado com a inclusão de 20 pacientes que foram submetidos ao implante do SVB DESolve®. Foi realizado o USIC após o procedimento e aos 6 e 18 meses de seguimento. RESULTADOS: Dos 20 pacientes selecionados, um paciente recusou realizar o USCI aos 6 meses e dois não realizaram o exame aos 18 meses, sendo excluídos do estudo. Totalizando 17 pacientes analisados. A idade média foi de 58,59 ± 8,73 anos e 70,6% eram do sexo masculino. O quadro clínico predominante era de angina estável. A via de acesso preferencial foi a radial, todos os pacientes foram submetidos à pré e pós-dilatação e o sucesso angiográfico ocorreu em todos os casos. No seguimento, houve aumento significativo na área (6,41 ± 1,35 mm2 vs. 7,35 ± 1,53 mm2, p < 0,002), volume (101,19 ± 20,9 mm3 vs. 118,51 ± 26,6 mm3, p = 0,001) e diâmetros do dispositivo, pelo USIC, aos 6 meses quando comparado ao procedimento índice. Não houve alteração significativa nas áreas, nos volumes e nos diâmetros do vaso e lúmen, em qualquer comparação no seguimento. A perda tardia foi de 0,22 ± 0,30 mm aos 6 e de 0,33 ± 0,44 mm aos 18 meses. Não houve nenhum caso de reestenose angiográfica e trombose do dispositivo. No seguimento, não houve casos de ECAM. CONCLUSÕES: A ICP com a utilização do SVB DESolve® para o tratamento da doença arterial coronária não complexa demonstrou resultados promissores. Houve aumento do volume e área do dispositivo aos 6 meses e uma supressão eficaz da hiperplasia intimal sem ECAM no seguimento. / INTRODUCTION: The bioresorbable vascular scaffolds (BVS) emerged in order to increase late safety of percutaneous coronary interventions (PCI). These devices release the antiproliferative drug to the site of obstruction and are absorbed over time. The use of intravascular ultrasound (IVUS) can help in the evaluation of this device absorption process. OBJECTIVES: The primary endpoint was to evaluate and compare, through IVUS, the volume and the area of the lúmen, the vessel and the device immediately after its implantation, and later at 6 and 18 months. The secondary endpoints were to evaluate and compare, through IVUS, the volume and the area of the plaque immediately after its implantation, and later at 6 and 18 months and diameters of the vessel, lúmen and BVS after PCI and at follow-up. Percentage of stenosis and late lúmen loss by angiography and incidence of major adverse cardiac events (MACE) up to 18 months. METHOD: This is a prospective, non-randomized study, with the inclusion of 20 patients who underwent implantation of DESolveTM. IVUS was performed after the procedure and at 6 and 18 months of follow-up. RESULTS: Of the 20 patients selected, one patient refused to perform the USCI at 6 months and two did not undergo the exam at 18 months and were excluded from the study. In total, 17 patients were analyzed. The average age was 58.59 ± 8.73 years and 70,6% were male. The most common clinical presentation was stable angina. The preferred vascular acess was to radial, all patients underwent pre- and post-dilation and angiographic success occurred in all cases. At follow-up there was a significant increase in area (6,41 ± 1,35 mm2 vs. 7,35 ± 1,53 mm2, p < 0,002), volume (101,19 ± 20,9 mm3 vs. 118,51 ± 26,6 mm3, p = 0,001) and diameters of the device, by IVUS, at 6 months when compared to the index procedure. There was no significant change in the areas, volumes and diameters of the vessel and lúmen, in any comparison at follow-up. The late loss was 0,22 ± 0,30 mm at 6 and 0,33 ± 0,44 mm at 18 months. There were no cases of restenosis and scaffold thrombosis. During follow-up there was no case of MACE. CONCLUSIONS: PCI with the use of DESolve scaffold for the treatment of non-complex coronary artery disease has shown promising results. There was an increase in the volume and area of the device at 6 months and an effective suppression of intimal hyperplasia without MACE at follow-up.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20054号 / 医博第4162号 / 新制||医||1018(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 湊谷 謙司, 教授 富樫 かおり, 教授 木村 剛 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13515号 / 論医博第2265号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 湊谷 謙司, 教授 石見 拓, 教授 江木 盛時 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Até o momento, pouco se sabe sobre a influência da modificação na composição do ateroma nas bordas dos stents e a ocorrência de alterações na geometria vascular. Este estudo objetiva correlacionar, utilizando de maneira seriada (pós-implante do stent e reestudo aos nove meses) o ultrassom monocromático e a Histologia Virtual®, as modificações na composição dos ateromas nas bordas proximais e distais de stents nãofarmacológicos e farmacológicos e as alterações ocorridas nas dimensões do vaso, luz e placa que possam explicar a ocorrência da reestenose nestes segmentos. Estudo prospectivo, de centro único, que randomizou (1:1) pacientes com síndrome coronária aguda para receberem stents nãofarmacológicos (Driver®, n=20 pacientes) ou farmacológicos (Cypher®, n=20 pacientes). Após a realização do procedimento, todos os pacientes submeteram-se a avaliação com ultrassom e Histologia Virtual®, que foi repetido ao final de nove meses de seguimento. O objetivo primário foi avaliar as modificações na área do vaso, luz e placa ao ultrassom e na composição do ateroma pela Histologia Virtual® no período entre o implante e o reestudo, buscando correlacionar as alterações no ateroma com as modificações na geometria vascular. Observou-se que na borda proximal, stents farmacológicos e não-farmacológicos tem um comportamento semelhante na avaliação ultrassonográfica, com tendência a remodelamento expansivo da área do vaso para compensar o crescimento na área da placa. Por outro lado, na borda distal, há menor crescimento da área da placa entre os pacientes tratados com stents farmacológicos, resultando em maior área da luz no reestudo de nove meses. Do ponto de vista da análise com Histologia virtual, nos dois grupos e em ambas as bordas houve redução do componente fibroso e núcleo necrótico com aumento no conteúdo fibrolipidico. Observou-se ainda importante correlação entre a variação do componente fibrótico e o aumento na área da placa (r=0.78, p=0.01). O uso de stents farmacológicos não se correlaciona com \"efeito de borda\". Ao contrário, parece haver menor crescimento da placa na borda distal destas endopróteses quando comparadas às sem fármaco. A modificação na composição do ateroma, com aumento do conteúdo fibro-lipídico pode explicar em parte estes achados. / To the present, little is known about the correlation between modifications in plaque composition at stent edges and the changes in vessel geometry. This study sought to evaluate, by serial grey-scale intravascular ultrasound (IVUS) and Virtual Histology(TM), the modifications in plaque composition at the edges of drug-eluting and bare-metal stents and the correlation of these findings with changes in the measuremntes of vessel, lumen and plaque area at those segments. Single-center, prospective and randomized (1:1) evaluation of 40 patients with acute coronary syndrome treated with bare-metal (Driver(TM), n=20 patients) or drug-eluting stents (Cypher(TM), n=20 patients). Following stent deployment, all individuals underwent gray scale IVUS and Virtual Histology(TM) evaluation, which were repeated at nine months. Primary endpoint included the modification in vessel, lumen and plaque area and in the composition of the plaque in the mean time between the baseline and follow-up procedure. Additionally, we tried to determine a correlation between plaque composition variation and changes in vessel geometry. At the proximal edge of both drug-eluting and bare-metal stents there was a trend to positive vessel remodeling which compensated the modest increase in plaque area. At the distal edge, patients treated with drug-eluting stents had less plaque growth resulting in a larger lumen area at follow-up. By Virtual Histology, there was a marked reduction in the % of fibrotic tissue and necrotic core in both edges of the two stents and a positive, strong correlation was seen between increase in % of fibrofatty component and augmentation in plaque area(r=0.78, p=0.01). The use of drug-eluting stents was not associated with \"edge effect\". On the contrary, patients treated with these devices experienced less plaque growth, especially at the distal edge of the stents. Modifications in plaque composition, with increase in fibrofatty content, might partially explain these findings.