OCT-BASED THREE DIMENSIONAL MODELING OF STENT DEPLOYMENT

Stent deployment has been widely used to treat narrowed coronary artery. Its acute outcome in terms of stent under expansion and malapposition depends on the extent and shape of calcifications. However, no clear understanding as to how to quantify or categorize the impact of calcification. We have conducted ex vivo stenting characterized by the optical coherence tomography (OCT). The goal of this work is to capture the ex vivo stent deployment and quantify the effect of calcium morphology on the stenting. A three dimensional model of calcified plaque was reconstructed from ex vivo OCT images. The crimping, balloon expansion and recoil process of the Express stent were characterized. Three cross-sections with different calcium percentages were chosen to evaluated the effect of the calcium in terms of stress/strain, lumen gains and malapposition. Results will be used to the pre-surgical planning

MECHANICAL PERFORMANCE OF PLLA STENT

Stent implantation is widely used to treat blocked lumen. Stents were meshed structure made of polymers and metal alloys, including stainless steel, cobalt chrome and nitinol [1]. Clinical studies had demonstrated that stents helped to scaffold the diseased lesion up to one year when tissue adapted to the stented environment [2]. However, the permanently implanted stents inside artery were associated with complications such as stent fracture, tissue inflammation, in-stent restenosis and thrombosis [3]. Currently, biodegradable stents are attracting more attention due to its potential long-term efficacy in treating blocked lumens. The detailed characterizations of biodegradable stents are essential for the desired clinical outcomes. In this work, the mechanical performance of Absorb GTI™ Bioresorbable stent made of PLLA (Poly-L-Lactide Acid) was studied using finite element method (FEM). Both the stent crimping and deployment were quantified towards the optimization of its scaffolding capacity in a limited time

Um papel para organismos de arqueia no desenvolvimento de placas ateroscleróticas vulneráveis e matriz mixomatosa

PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02); between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03), and between chlamydial bodies and foam cells (r = 0.42; P = 0.03). The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions.PROPOSTA: Placas vulneráveis são caracterizadas por matriz mixomatosa, centro lipídico necrótico, espécies reativas de oxigênio e alto níveis de microorganismos. Micróbios aeróbicos como Chlamydophila pneumoniae e Mycoplasma pneumoniae usualmente não sobrevivem em meio de estresse oxidativo. Arquéias são microorganismos anaeróbicos com poderosas enzimas anti-oxidantes que permitem detoxificação de radicais livres e a presença delas poderia favorecer a sobrevivência de micróbios aeróbicos. Pesquisamos por elementos de arquéia em placas vulneráveis e sua possível associação com degeneração mixomatosa da matriz e aumento do número de clamídias e micoplasmas. MÉTODOS: Vinte e nove amostras de 13 produtos de aterotomia de lesões grandes e excêntricas de óstio ou bifurcação de coronárias foram estudadas pela microscopia óptica e eletrônica. Agentes compatíveis com arquéia, clamídia e micoplasma foram semiquantificados pela microscopia eletrônica e correlacionados com quantidade de tecido fibromuscular, matriz mixomatosa e células xantomatosas. Seis casos foram também submetidos à reação em cadeia da polimerase com oligonucleotídeos de arquéia. RESULTADOS: Os 13 casos foram positivos para estruturas sugestivas de arquéia, micoplasma ou clamídia, em pelo menos uma amostra. Houve correlação positiva entre intensidade de matriz mixomatosa versus arquéia (r=0.44, p=0.02); arquéia versus micoplasma (r=0.41, p=0.03) e clamídia versus células xantomatosas r=0,42; 0.03). PCR foi positiva para DNA de arqueia em 4 dos 6 fragmentos. DISCUSSÃO: DNA e formas compatíveis com arquéia estão presentes em placas vulneráveis e podem ter papel fundamental na proliferação de micoplasma e clamídia. Este parece ser o primeiro relato de arquéia aparentemente patogênica em lesões de órgãos internos humanos

Impact of stenting and oral sirolimus on endothelium-dependent and independent coronary vasomotion

BACKGROUND: There is no consensus regarding the impact of stenting on long-term endothelial function. There have been reports of increased endothelial dysfunction with sirolimus-eluting stents as compared to bare metal stenting (BMS). OBJECTIVE: This study aims to assess the impact of BMS and the effect of oral sirolimus on endothelial function. METHODS: Forty-five patients were randomized into three groups: BMS + high-dose oral sirolimus (initial dose of 15 mg, followed by 6 mg/day for four weeks); BMS + low-dose sirolimus (6 mg followed by 2 mg daily for four weeks); and BMS without sirolimus. Changes in vasoconstriction or vasodilation in a 15 mm segment starting at the distal stent end in response to acetylcholine and nitroglycerin were assessed by quantitative angiography. RESULTS: The groups had similar angiographic characteristics. The percent variation in diameter in response to acetylcholine was similar in all groups at the two time points (p = 0.469). Four hours after stenting, the target segment presented an endothelial dysfunction that was maintained after eight months in all groups. In all groups, endothelium-independent vasomotion in response to nitroglycerin was similar at four hours and eight months, with increased target segment diameter after nitroglycerin infusion (p = 0.001). CONCLUSION: The endothelial dysfunction was similarly present at the 15 mm segment distal to the treated segment, at 4 hours and 8 months after stenting. Sirolimus administered orally during 4 weeks to prevent restenosis did not affect the status of endothelium-dependent and independent vasomotion.FUNDAMENTO: Não há consenso sobre o impacto do implante de stent sobre a função endotelial no longo prazo. Há relatos de disfunção endotelial aumentada com stent com sirolimus quando comparado com o stent metálico convencional (BMS). OBJETIVO: Este estudo visa a avaliar o impacto do BMS e o efeito do sirolimus por via oral sobre a função endotelial. MÉTODOS: Quarenta e cinco pacientes foram randomizados em três grupos: BMS + altas doses de sirolimus oral (dose inicial de 15 mg, seguida de 6 mg/dia durante quatro semanas); BMS + baixa dose de sirolimus (6 mg, seguida de 2 mg por dia durante quatro semanas) e BMS sem sirolimus. Mudanças na vasoconstrição ou vasodilatação, em um segmento de 15 milímetros começando pelo extremo distal do stent em resposta a acetilcolina e nitroglicerina, foram avaliadas por angiografia quantitativa. RESULTADOS: Os grupos apresentaram características angiográficas semelhantes. A variação percentual de diâmetro em resposta a acetilcolina foi semelhante em todos os grupos, nos dois momentos (p = 0,469). Quatro horas após o implante de stent, o segmento alvo apresentou uma disfunção endotelial que se manteve após oito meses em todos os grupos. Em todos os grupos, a vasomotricidade independente de endotélio em resposta a nitroglicerina foi semelhante, às quatro horas e aos oito meses, com diâmetro do segmento alvo aumentado após a infusão de nitroglicerina (p = 0,001). CONCLUSÃO: A disfunção endotelial esteve igualmente presente no segmento distal de 15 milímetros do segmento tratado, às 4 horas e aos 8 meses após implante do stent. O sirolimus administrado por via oral durante quatro semanas para evitar a reestenose não afetou o estado de vasomotricidade endotélio dependente e independente.Universidade Federal de São Paulo (UNIFESP) Hospital do Rim e HipertensãoUNIFESP, Hospital do Rim e HipertensãoSciEL

Atheromas that cause fatal thrombosis are usually large and frequently accompanied by vessel enlargement

Several lines of clinical evidence show that AMI frequently occurs at sites with mild to moderate degree of coronary stenosis. The degree of luminal stenosis depends on plaque deposition and degree of vessel remodeling, features poorly assessed by coronary angiography. This postmortem study tested the hypothesis that the size of coronary atheroma and the type of remodeling distinguish culprit lesion responsible for fatal AMI from equi-stenotic nonculprit lesion in the same coronary tree. The main coronary branches from 36 consecutive patients with fatal AMI were studied. The culprit lesion (Group 1) and an equi-stenotic nonculprit segment (Group 2) obtained in measurements of another coronary branch from the same patient were compared. Morphometry and plaque composition was assessed in both groups. Compared to Group 2, Group 1 had larger areas of: plaque $9.6 vs. 4.7 mm^2$, vessel $12.7 vs. 7.4 mm^2$ and lumen $1.7 vs. 1.2 mm^2$; (P<.01). Positive remodeling was more frequent in Group 1 than Group 2: 21/30 (70%) vs. 8/26 (31%). Plaque area correlated positively with lipid core and macrophages and negatively with fibrosis and smooth muscle cells. Atherosclerotic plaques that cause fatal thrombosis are more frequently positively remodeled and tend to be larger than nonculprit plaques with the same degree of cross-sectional stenosis. We tested whether arterial remodeling and plaque size vary between segments containing a fatal thrombosed plaque versus an equi-stenotic nonculprit plaque. Culprit vessel segments had higher cross-sectional areas of intimal plaque and of vessel wall than equi-stenotic nonculprit plaques. The cross-sectional area of the vessel correlated positively with both the lipid core area and $CD68^+$ macrophage content, and negatively with fibrosis area and smooth muscle cell content. These results add elements explaining limitations of angiography in identifying plaques and provide new insights into the role of remodeling in plaque instability.Other Research Uni

Application of ex vivo cryo-imaging technique for three-dimensional finite element analysis of atherosclerotic plaque rupture

PublishedCryo-imaging is an ex vivo vascular imaging modality that acquires serial 2D fluorescence and bright-field images at 20μm increments without sacrifice to tissue morphology. These features make Cryo-imaging an attractive approach for rendering high-resolution 3D volumes that may serve as a basis for finite element analysis (FEA) studies of plaque rupture. This work demonstrates the first use of Cryo-imaging for the imaging of a human coronary vessel and the subsequent rendering of a 3D FE model that clearly delineates critical anatomical features of atherosclerotic plaque. FEA is then performed to assess the plaque rupture conditions that result in a thrombotic episode

Impact of Drug Release Kinetics on Vascular Response to Different Zotarolimus-Eluting Stents Implanted in Patients With Long Coronary Stenoses

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Serial Assessment of Vessel Interactions After Drug-Eluting Stent Implantation in Unprotected Distal Left Main Coronary Artery Disease Using Frequency-Domain Optical Coherence Tomography

ObjectivesThis study sought to assess stent-vessel interactions after drug-eluting stent (DES) implantation in unprotected left main coronary artery (ULM) by frequency-domain optical coherence tomography (FD-OCT).BackgroundPercutaneous coronary intervention using DES in ULM has been increasingly performed in routine practice. Recently, FD-OCT assessments of DES-vessel interactions have been used as surrogates for DES safety; however, there are no FD-OCT studies in ULM.MethodsWe prospectively enrolled 33 consecutive patients with ULM disease treated with sirolimus- (n = 11) and everolimus-eluting stents (n = 22). FD-OCT assessments were performed post-percutaneous coronary intervention and at 9-month follow-up. Three different segments of ULM were compared: distal (DIS), bifurcation (BIF), and ostial-body (BODY). The primary endpoints were percentages of uncovered and malapposed struts at 9-month follow-up, and the secondary endpoint was neointimal hyperplasia area.ResultsWe analyzed 25,873 stent struts. Significant differences were demonstrated for percentage of uncovered struts (3.4%, 11.7%, and 18.7%, respectively for DIS, BIF, and BODY; p < 0.05 for all the comparisons). Malapposition was also more common in BODY (5.3%) than in DIS (0.6%) and BIF (2.0%) segments (p < 0.05 for BODY vs. DIS, and BODY vs. BIF). Equivalent neointimal hyperplasia areas were demonstrated in all segments. Acute malapposition rates led to different patterns of DES-vessel interactions at 9-month follow-up.ConclusionsDistinct patterns of DES-vessel interactions were demonstrated in different segments of ULM. Acute stent strut malapposition affects these findings

Deep learning segmentation of fibrous cap in intravascular optical coherence tomography images

Thin-cap fibroatheroma (TCFA) is a prominent risk factor for plaque rupture. Intravascular optical coherence tomography (IVOCT) enables identification of fibrous cap (FC), measurement of FC thicknesses, and assessment of plaque vulnerability. We developed a fully-automated deep learning method for FC segmentation. This study included 32,531 images across 227 pullbacks from two registries. Images were semi-automatically labeled using our OCTOPUS with expert editing using established guidelines. We employed preprocessing including guidewire shadow detection, lumen segmentation, pixel-shifting, and Gaussian filtering on raw IVOCT (r,theta) images. Data were augmented in a natural way by changing theta in spiral acquisitions and by changing intensity and noise values. We used a modified SegResNet and comparison networks to segment FCs. We employed transfer learning from our existing much larger, fully-labeled calcification IVOCT dataset to reduce deep-learning training. Overall, our method consistently delivered better FC segmentation results (Dice: 0.837+/-0.012) than other deep-learning methods. Transfer learning reduced training time by 84% and reduced the need for more training samples. Our method showed a high level of generalizability, evidenced by highly-consistent segmentations across five-fold cross-validation (sensitivity: 85.0+/-0.3%, Dice: 0.846+/-0.011) and the held-out test (sensitivity: 84.9%, Dice: 0.816) sets. In addition, we found excellent agreement of FC thickness with ground truth (2.95+/-20.73 um), giving clinically insignificant bias. There was excellent reproducibility in pre- and post-stenting pullbacks (average FC angle: 200.9+/-128.0 deg / 202.0+/-121.1 deg). Our method will be useful for multiple research purposes and potentially for planning stent deployments that avoid placing a stent edge over an FC.Comment: 24 pages, 9 figures, 2 tables, 2 supplementary figures, 3 supplementary table