Although the drug-eluting stent (DES) has dramatically reduced the rate of coronary restenosis, it still occurs in up to 20% of patients with a DES. Monitoring drug delivery could be one way to decrease restenosis rates. We demonstrate real-time photoacoustic imaging and spectroscopy (PAIS) using a wavelength-tunable visible laser and clinical ultrasound scanner to track cardiac drug delivery. The photoacoustic signal was initially calibrated using porcine myocardial samples soaked with a known concentration of a drug surrogate (Dil). Next, an in situ coronary artery was perfused with DiI for 20 min and imaged to monitor dye transport in the tissue. Finally, a partially DiI-coated stent was inserted into the porcine brachiocephalic trunk for imaging. The photoacoustic signal was proportional to the DiI concentration between 2.4 and 120 mu g/ml, and the dye was detected over 1.5 mm from the targeted coronary vessel. Photoacoustic imaging was also able to differentiate the DiI-coated portion of the stent from the uncoated region. These results suggest that PAIS can track drug delivery to cardiac tissue and detect drugs loaded onto a stent with sub-mm precision. Future work using PAIS may help improve DES design and reduce the probability of restenosis. (C) 2017 Society of Photo-Optical Instrumentation Engineers (SPIE)

FUNDAMENTOS: Com a expressiva ampliação do uso dos stents farmacológicos (SF), nos diversos cenários em que se apresenta a doença arterial coronária (DAC), e diante de todas as evoluções das diferentes formas de tratamento, levantou-se o questionamento sobre a propriedade de indicação da intervenção coronária percutânea (ICP), à busca do discernimento sobre quais pacientes (P) com DAC apresentam o melhor balanço risco/benefício. Visando a sistematizar as indicações para procedimentos de RM, e tomando como referência as Diretrizes Internacionais baseadas nos principais estudos e ensaios clínicos desta área, em 2009, pela primeira vez, ACC/AHA/SCAI/AATS publicaram um documento sugerindo, frente aos diversos cenários clínicos e anatômicos da DAC, critérios de propriedade de indicação para os procedimentos de RM, permitindo classificá-los quanto à indicação em: A - apropriado, PA - pode ser apropriado ou RA - raramente apropriado. OBJETIVOS: O objetivo primário foi avaliar o grau de propriedade de indicação da ICP com SF nos pacientes do Registro DESIRE, no período de Janeiro de 2012 a Dezembro de 2013, correlacionando com a ocorrência de eventos cardíacos maiores (ECAM) (óbito, infarto e revascularização da lesão-alvo), num seguimento clínico de dois anos. Os objetivos secundários foram: comparar o grau de propriedade de indicação da ICP entre pacientes com apresentação clínica estável versus aqueles com síndrome coronária aguda (SCA); e a ocorrência isolada de óbito cardíaco (OC), infarto agudo do miocárdio não-fatal (IM), revascularização da lesão-alvo (RLA) e trombose do stent no período de follow-up. CASUÍSTICA E MÉTODOS: Foram incluídos todos os pacientes, consecutivamente tratados no HCor-ASS com ICP e implante de pelo menos um SF, entre 01/01/2012 a 31/12/2013. A coleta de dados foi feita do banco de dados do Registro DESIRE, em cujo programa constam dados pormenorizados das características clínicas, angiográficas e informações técnicas da intervenção, incluindo complicações, de cada um dos P registrados, além dos dados evolutivos obtidos nos períodos definidos após o procedimento-índice (1, 6, 12 meses e anualmente a partir de então). Fez-se a validação desses critérios, usando-se o aplicativo SCAI-QIT®, que permite a definição, ao serem incluídas as variáveis do P, do grau de propriedade de indicação para o implante do SF. Este aplicativo é facilmente acessado via internet, no seguinte site: http://scai-qit.org/. Após ser feita a classificação dos critérios de propriedade de indicação, os dados foram analisados estatisticamente, para obtenção dos objetivos e resultados do estudo em questão. RESULTADOS: Dentre os 1.108 P do Registro DESIRE analisados, usando-se o aplicativo SCAI-QIT®, observou-se que: 375 (33,8%) tiveram indicações Apropriada (Grupo I); 480 (43,3%) tiveram indicação Pode Ser Apropriada (Grupo II) e 215 (19,4%) tiveram indicação Raramente Apropriada (Grupo III). No Grupo I, 22,7% tinham isquemia silenciosa, 13,3% angina estável, 36,8 % SCAssST e 27,2% SCAcsST. No Grupo II, 34,0% tinha isquemia silenciosa, 11,9% angina estável, 33,3% SCAssST e 20,8% SCAcsST. No Grupo III, 82,3% tinham isquemia silenciosa, 4,2% angina estável, 0% SCAssST e 13,5% SCAcsST. A ocorrência de IM (definido como aumento da CKMB massa >3X o percentil 99) foi de 9,6%, 9,6%% e 7,0% (p= 0,652) nos Grupos I, II e III, respectivamente. A RLA foi de 1,9%, 2,1% e 0,9% (p= 0,592) e a taxa de trombose do stent foi 0,3%, 0,6% e 1,4% (p=0,406). Comparando os 3 grupos não foi estatisticamente significativo as taxas de OC e ECAM no follow-up de 2 anos. CONCLUSÕES: Os resultados deste estudo demonstram que apesar das taxas de PCI em pacientes estáveis e instáveis, destoarem das esperadas e das já documentadas, isso não teve relevância nos eventos maiores e sobrevida dos pacientes no follow-up clínico. / BACKGROUND: With the significant expansion of the use of drug-eluting stents in different scenarios as presented coronary artery disease (CAD), and before all the developments of different forms of treatment, rose the questioning on the indication of ownership of percutaneous coronary intervention (PCI), the pursuit of insight into which patients (P) with CAD have the best balance risk/benefit. Aiming to systematize indications for coronary revascularization procedures, and by reference to the International Guidelines based on the main studies and clinical trials in this area, in 2009 for the first time, ACC/AHA/SCAI/AATS published a paper suggesting, compared to various clinical and anatomical scenarios of CAD, criteria for appropriate indication of coronary revascularization procedures, allowing to classify them as the indicated in: A - Appropriate, PA - May be appropriate or RA - Rarely appropriate. OBJECTIVES: The primary objective was to evaluate the degree of appropriateness of the ICP with pharmacological stents in patients of DESIRE Registry, in the period from January 2012 to December 2013, correlating with the occurrence of major cardiac events (MACE)(death, myocardial infarction and target vessel revascularization), in the clinical follow-up of two years. The secondary objective were: to compare the degree of appropriateness of PCI indication among patients with clinical presentation satble versus those with acute coronary syndrome to isolated occurrence of cardiac death, myocardial infarction (MI), new target lesion revascularization (TLR) and stent thrombosis in follow-up period. METHODS: We included all patients consecutively treated in HCor-ASS with ICP and implantation of at least one drug-eluting stent, between 01/01/2012 to 31/12/2013. Data collection was made of the DESIRE Registry data base in whose program includes these full details of clinical features, and technical information of the intervention, including complications, each of registered patients in addition to the rolling data over defined periods after the index procedure (1, 6 12 months and annually thereafter). It was made the validation of these criteria, using the application SCAI-QIT, which allows definition, when the patient variables are include, the degree of appropriateness implantation of drug-eluting stent. This application is easily accessed via the internet, at the following site: http://scai-qit.org/. After being made the classification of statement of appropriateness criteria, data were statistically analyzed to obtain the objectives and results of the study in question. RESULTS: Among the 1.108 P of DESIRE Registry analyzed using the SCAI-QIT® application, it was observed that: 375 (33,8%) had Appropriate(Group I) indication; 480 (43,3%) had May be appropriate (Group II) indication and 215 (19,4%) had Rarely appropriate (Group II) indication. In Group I, 22,7% had silent ischemia, 13,3% stable angina, 36,8% SCAssST e 27,2% SCAcsST. In Group II, 34,0% had silent ischemia, 11,9% stable angina, 33,3% SCAssST e 20,8% SCAcsST. No Group III, 82,3% had silent ischemia, 4,2% stable angina, 0% SCAssST e 13,5% SCAcsST. The occurrence of MI (defined as increase of CKMB mass >3x the 99 percentile) was 9,6%, 9,6%% and 7,0% (p= 0,652) in Groups I, II e III, respectively. The TLR was 1,9%, 2,1% and 0,9% (p= 0,592) and stent thrombosis rate was 0,3%, 0,6% and 1,4% (p=0,406). Comparing the 3 groups was not statistically significant the rates of mortality and mace in follow-up of 2 years. CONCLUSIONS: The results of this study demonstrate that despite PCI in stable and unstable patients, diverges the expected and already documented, it had no relevance in major events and survival of patients in the clinical follow-up.

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.

Stenting remains a common treatment option for atherosclerotic arteries. The main drawback of early stent platforms was restenosis, which has been combated by drug eluting stents; however, these stents have suffered from a higher incidence of late stage thrombosis. To address current stenting limitations, the major research focuses have been the development of the next generation of drug eluting stents and first generation bioabsorbable stents. The main objective of this dissertation was the design and development of a new class of bioabsorbable stent composed of elastin mimetic protein polymers. The first phase explored different stent design schemes and fabrication strategies. Successfully fabricated stents were then mechanically tested to ensure they possessed sufficient mechanical strength. Additionally, described herein is the potential to modulate the properties of the elastin mimetics through different crosslinking strategies. We have demonstrated that chemical crosslinking allows for the tailoring of the physical, mechanical, drug delivery, and endothelialization properties of these materials. The potential for drug delivery from this elastin mimetic stent was benchmarked as was the potential to endothelialize these stents. Furthermore, we developed the necessary delivery systems to allow for deployment in the rat aorta model.

FUNDAMENTOS: Com a expressiva ampliação do uso dos stents farmacológicos (SF), nos diversos cenários em que se apresenta a doença arterial coronária (DAC), e diante de todas as evoluções das diferentes formas de tratamento, levantou-se o questionamento sobre a propriedade de indicação da intervenção coronária percutânea (ICP), à busca do discernimento sobre quais pacientes (P) com DAC apresentam o melhor balanço risco/benefício. Visando a sistematizar as indicações para procedimentos de RM, e tomando como referência as Diretrizes Internacionais baseadas nos principais estudos e ensaios clínicos desta área, em 2009, pela primeira vez, ACC/AHA/SCAI/AATS publicaram um documento sugerindo, frente aos diversos cenários clínicos e anatômicos da DAC, critérios de propriedade de indicação para os procedimentos de RM, permitindo classificá-los quanto à indicação em: A - apropriado, PA - pode ser apropriado ou RA - raramente apropriado. OBJETIVOS: O objetivo primário foi avaliar o grau de propriedade de indicação da ICP com SF nos pacientes do Registro DESIRE, no período de Janeiro de 2012 a Dezembro de 2013, correlacionando com a ocorrência de eventos cardíacos maiores (ECAM) (óbito, infarto e revascularização da lesão-alvo), num seguimento clínico de dois anos. Os objetivos secundários foram: comparar o grau de propriedade de indicação da ICP entre pacientes com apresentação clínica estável versus aqueles com síndrome coronária aguda (SCA); e a ocorrência isolada de óbito cardíaco (OC), infarto agudo do miocárdio não-fatal (IM), revascularização da lesão-alvo (RLA) e trombose do stent no período de follow-up. CASUÍSTICA E MÉTODOS: Foram incluídos todos os pacientes, consecutivamente tratados no HCor-ASS com ICP e implante de pelo menos um SF, entre 01/01/2012 a 31/12/2013. A coleta de dados foi feita do banco de dados do Registro DESIRE, em cujo programa constam dados pormenorizados das características clínicas, angiográficas e informações técnicas da intervenção, incluindo complicações, de cada um dos P registrados, além dos dados evolutivos obtidos nos períodos definidos após o procedimento-índice (1, 6, 12 meses e anualmente a partir de então). Fez-se a validação desses critérios, usando-se o aplicativo SCAI-QIT®, que permite a definição, ao serem incluídas as variáveis do P, do grau de propriedade de indicação para o implante do SF. Este aplicativo é facilmente acessado via internet, no seguinte site: http://scai-qit.org/. Após ser feita a classificação dos critérios de propriedade de indicação, os dados foram analisados estatisticamente, para obtenção dos objetivos e resultados do estudo em questão. RESULTADOS: Dentre os 1.108 P do Registro DESIRE analisados, usando-se o aplicativo SCAI-QIT®, observou-se que: 375 (33,8%) tiveram indicações Apropriada (Grupo I); 480 (43,3%) tiveram indicação Pode Ser Apropriada (Grupo II) e 215 (19,4%) tiveram indicação Raramente Apropriada (Grupo III). No Grupo I, 22,7% tinham isquemia silenciosa, 13,3% angina estável, 36,8 % SCAssST e 27,2% SCAcsST. No Grupo II, 34,0% tinha isquemia silenciosa, 11,9% angina estável, 33,3% SCAssST e 20,8% SCAcsST. No Grupo III, 82,3% tinham isquemia silenciosa, 4,2% angina estável, 0% SCAssST e 13,5% SCAcsST. A ocorrência de IM (definido como aumento da CKMB massa >3X o percentil 99) foi de 9,6%, 9,6%% e 7,0% (p= 0,652) nos Grupos I, II e III, respectivamente. A RLA foi de 1,9%, 2,1% e 0,9% (p= 0,592) e a taxa de trombose do stent foi 0,3%, 0,6% e 1,4% (p=0,406). Comparando os 3 grupos não foi estatisticamente significativo as taxas de OC e ECAM no follow-up de 2 anos. CONCLUSÕES: Os resultados deste estudo demonstram que apesar das taxas de PCI em pacientes estáveis e instáveis, destoarem das esperadas e das já documentadas, isso não teve relevância nos eventos maiores e sobrevida dos pacientes no follow-up clínico. / BACKGROUND: With the significant expansion of the use of drug-eluting stents in different scenarios as presented coronary artery disease (CAD), and before all the developments of different forms of treatment, rose the questioning on the indication of ownership of percutaneous coronary intervention (PCI), the pursuit of insight into which patients (P) with CAD have the best balance risk/benefit. Aiming to systematize indications for coronary revascularization procedures, and by reference to the International Guidelines based on the main studies and clinical trials in this area, in 2009 for the first time, ACC/AHA/SCAI/AATS published a paper suggesting, compared to various clinical and anatomical scenarios of CAD, criteria for appropriate indication of coronary revascularization procedures, allowing to classify them as the indicated in: A - Appropriate, PA - May be appropriate or RA - Rarely appropriate. OBJECTIVES: The primary objective was to evaluate the degree of appropriateness of the ICP with pharmacological stents in patients of DESIRE Registry, in the period from January 2012 to December 2013, correlating with the occurrence of major cardiac events (MACE)(death, myocardial infarction and target vessel revascularization), in the clinical follow-up of two years. The secondary objective were: to compare the degree of appropriateness of PCI indication among patients with clinical presentation satble versus those with acute coronary syndrome to isolated occurrence of cardiac death, myocardial infarction (MI), new target lesion revascularization (TLR) and stent thrombosis in follow-up period. METHODS: We included all patients consecutively treated in HCor-ASS with ICP and implantation of at least one drug-eluting stent, between 01/01/2012 to 31/12/2013. Data collection was made of the DESIRE Registry data base in whose program includes these full details of clinical features, and technical information of the intervention, including complications, each of registered patients in addition to the rolling data over defined periods after the index procedure (1, 6 12 months and annually thereafter). It was made the validation of these criteria, using the application SCAI-QIT, which allows definition, when the patient variables are include, the degree of appropriateness implantation of drug-eluting stent. This application is easily accessed via the internet, at the following site: http://scai-qit.org/. After being made the classification of statement of appropriateness criteria, data were statistically analyzed to obtain the objectives and results of the study in question. RESULTS: Among the 1.108 P of DESIRE Registry analyzed using the SCAI-QIT® application, it was observed that: 375 (33,8%) had Appropriate(Group I) indication; 480 (43,3%) had May be appropriate (Group II) indication and 215 (19,4%) had Rarely appropriate (Group II) indication. In Group I, 22,7% had silent ischemia, 13,3% stable angina, 36,8% SCAssST e 27,2% SCAcsST. In Group II, 34,0% had silent ischemia, 11,9% stable angina, 33,3% SCAssST e 20,8% SCAcsST. No Group III, 82,3% had silent ischemia, 4,2% stable angina, 0% SCAssST e 13,5% SCAcsST. The occurrence of MI (defined as increase of CKMB mass >3x the 99 percentile) was 9,6%, 9,6%% and 7,0% (p= 0,652) in Groups I, II e III, respectively. The TLR was 1,9%, 2,1% and 0,9% (p= 0,592) and stent thrombosis rate was 0,3%, 0,6% and 1,4% (p=0,406). Comparing the 3 groups was not statistically significant the rates of mortality and mace in follow-up of 2 years. CONCLUSIONS: The results of this study demonstrate that despite PCI in stable and unstable patients, diverges the expected and already documented, it had no relevance in major events and survival of patients in the clinical follow-up.

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.

Background: Drug eluting stents (DES) are preferred over bare metal stents (BMS) for native coronary artery revascularization unless contraindicated. However, the preferred stent choice for saphenous venous graft (SVG) percutaneous coronary interventions (PCI) is unclear due to conflicting results. Methods: PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through June 2018. Seven studies (n = 1639) comparing DES versus BMS in SVG-PCI were included. Endpoints were major adverse cardiac events (MACE), cardiovascular mortality, all-cause mortality, myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), in-stent thrombosis, binary in-stent restenosis, and late lumen loss (LLL). Results: Overall, during a mean follow up of 32.1 months, there was no significant difference in the risk of MACE, cardiovascular mortality, all-cause mortality, MI, stent thrombosis, TVR and TLR between DES and BMS. However, short-term follow up (mean 11 months) showed lower rate of MACE (OR 0.66 [0.51, 0.85]; p = 0.002), TVR (OR 0.47 [0.23, 0.97]; p = 0.04) and binary in-stent restenosis (OR 0.14 [0.06, 0.37]; p < 0.0001) in DES as compared with BMS. This benefit was lost on long-term follow up with a mean follow up 35.5 months. Conclusion: In this meta-analysis of SVG-PCI, DES use was associated with similar MACE, cardiovascular mortality, all-cause mortality, MI, in-stent thrombosis, TVR and TLR compared with BMS during long-term follow up. There was high incidence of MACE noted in both DES and BMS suggesting a need for exploring novel strategies to treat SVG disease to improve clinical outcomes.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24474号 / 医博第4916号 / 新制||医||1062(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 石見 拓, 教授 永井 洋士, 教授 大鶴 繁 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p>Mathematical and computational modeling allow for the rationalization of complex phenomenon observed in our reality. Through the careful selection of assumptions, the intractable task of simulating reality can be reduced to the simulation of a practical system whose behavior can be replicated. The development of computational models allow for the full comprehension of the defined system, and the model itself can be used to evaluate the results of thousands of simulate experiments to aid in the rational design process.</p> <p>Biomedical engineering is the application of engineering principles to the field of medicine and biology. This discipline is composed of numerous diverse subdisciplines that span from genetic engineering to biomechanics. Each of these subdisciplines is concerned with its own complex and seemingly chaotic systems, whose behavior is difficult to characterize. The development and application of computational modeling to rationalize these systems is often necessary in this field and will be the focus of this thesis.</p> <p>This thesis is centered on the development and application of mathematical and computational modeling in three diverse systems in biomedical engineering. First, computational modeling is employed to investigate the behavior of key proteins in the post-synapse centered around learning and memory. Second, computational modeling is utilized to characterize the drug release rate from implantable drug delivery depots, and produce a tool to aid in the tailoring of the release rate. Finally, computational modeling is utilized to understand the motion of particles through an inertial focusing microfluidics chip and optimize the size selective capture efficiency.</p> <p> </p>

The study applies in vivo technique for profiling hemodynamics and wall shear stress (WSS) distribution in human coronary arteries. The methodology involves fusion of 2D Intra Vascular Ultra Sound and Bi-plane angiograms to reproduce the 3D arterial geometry. This geometry is then used in a Computational Fluid Dynamics (CFD) module for flow modeling. The Walburn and Schneck constitutive relation was used to represent the non-Newtonian blood rheology. The methodology is applied to study the relationship between WSS and Neointimal Hyperplasia (NIH) in two groups of diabetic patients after being treated separately with bare metal stents (BMS) and Sirolimus Eluting Stents (SES). The stent assignments were blinded until the end of the study. The study was repeated for the patients after 9 months. The predicted WSS ranged from (0.1- 8 N/m2) and was categorized into five classes: low ( < 1 N/m2); low-normal (1-2 N/m2); normal (2-3 N/m2); high-normal (3-4 N/m2); high ( > 4 N/m2). The results indicate NIH in 5 of the patients treated with BMS and none in SES cases. These results correlate with our predicted WSS distribution.