In vitro heterogeneity of porcine adipose tissue-derived stem cells.

Tissue-specific adult stem cells (ASC) are heterogeneous and characterized by a mix of progenitor cells that produce cells at various stages of differentiation, and ultimately different terminally differentiated cells. Understanding the heterogeneity of ASCs may lead to the development of improved protocols of cell isolation and optimized cell therapy clinical protocols. Using a combination of enzymatic and explant culture protocols, we obtained pADSC population, which is composed by two distinct morphologies: fibroblast-like cells (FLCs) and endothelial-like cells (ELCs). Both cell sub-types efficiently formed colonies, expressed CD90+/CD105+/CD44+, and differentially expressed such markers such as Nestin, Vimentin, Fibronectin, Cytokeratin, Connexin 43, CD31, CD34 and CD146 as well as the pluripotent stem cell markers Oct-4, Nanog and Sox2. Mixed populations of pADSCs did not lose their multipotentiality and the cells were able to undergo osteogenic, chondrogenic, adipogenic and myogenic differentiation. Furthermore, the mixed population spontaneously formed capillary tube structures. Our findings suggest that different subpopulations can be isolated from adipose tissue and that the ADSCs need to be better evaluated using a wide panel of different markers related to cell differentiation, which is important for stem cell therapy and regenerative medicine, particularly for advanced stem cells therapies - products that are currently under investigation or even use.

In vitro heterogeneity of porcine adipose tissue-derived stem cells

Tissue-specific adult stem cells (ASC) are heterogeneous and characterized by a mix of progenitor cells that produce cells at various stages of differentiation, and ultimately different terminally differentiated cells. Understanding the heterogeneity of ASCs may lead to the development of improved protocols of cell isolation and optimized cell therapy clinical protocols. Using a combination of enzymatic and explant culture protocols, we obtained pADSC population, which is composed by two distinct morphologies: fibroblast-like cells (FLCs) and endothelial-like cells (ELCs). Both cell sub-types efficiently formed colonies, expressed CD90+/CD105+/CD44+, and differentially expressed such markers such as Nestin, Vimentin, Fibronectin, Cytokeratin, Connexin 43, CD31, CD34 and CD146 as well as the pluripotent stem cell markers Oct-4, Nanog and Sox2. Mixed populations of pADSCs did not lose their multipotentiality and the cells were able to undergo osteogenic, chondrogenic, adipogenic and myogenic differentiation. Furthermore, the mixed population spontaneously formed capillary tube structures. Our findings suggest that different subpopulations can be isolated from adipose tissue and that the ADSCs need to be better evaluated using a wide panel of different markers related to cell differentiation, which is important for stem cell therapy and regenerative medicine, particularly for advanced stem cells therapies – products that are currently under investigation or even use.

In vitro heterogeneity of porcine adipose tissue-derived stem cells

Tissue-specific adult stem cells (ASC) are heterogeneous and characterized by a mix of progenitor cells that produce cells at various stages of differentiation, and ultimately different terminally differentiated cells. Understanding the heterogeneity of ASCs may lead to the development of improved protocols of cell isolation and optimized cell therapy clinical protocols. Using a combination of enzymatic and explant culture protocols, we obtained pADSC population, which is composed by two distinct morphologies: fibroblast-like cells (FLCs) and endothelial-like cells (ELCs). Both cell sub-types efficiently formed colonies, expressed CD90+/CD105+/CD44+, and differentially expressed such markers such as Nestin, Vimentin, Fibronectin, Cytokeratin, Connexin 43, CD31, CD34 and CD146 as well as the pluripotent stem cell markers Oct-4, Nanog and Sox2. Mixed populations of pADSCs did not lose their multipotentiality and the cells were able to undergo osteogenic, chondrogenic, adipogenic and myogenic differentiation. Furthermore, the mixed population spontaneously formed capillary tube structures. Our findings suggest that different subpopulations can be isolated from adipose tissue and that the ADSCs need to be better evaluated using a wide panel of different markers related to cell differentiation, which is important for stem cell therapy and regenerative medicine, particularly for advanced stem cells therapies – products that are currently under investigation or even use.

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model.

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction.

Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.

A robust fully automatic lumen segmentation method for in vivo intracoronary optical coherence tomography

Abstract Introduction: Intravascular optical coherence tomography (IVOCT) is an in-vivo imaging modality based on the introduction of a catheter in a blood vessel for viewing its inner wall using electromagnetic radiation. One of the most developed automatic applications for this modality is the lumen area segmentation, however on the evaluation of these methods, the slices inside bifurcation regions, or with the presence of complex atherosclerotic plaques and dissections are usually discarded. This paper describes a fully-automatic method for computing the lumen area in IVOCT images where the set of slices includes complex atherosclerotic plaques and dissections. Methods The proposed lumen segmentation method is divided into two steps: preprocessing, including the removal of artifacts and the second step comprises a lumen detection using morphological operations. In addition, it is proposed an approach to delimit the lumen area for slices inside bifurcation region, considering only the main branch. Results Evaluation of the automatic lumen segmentation used manual segmentations as a reference, it was performed on 1328 human IVOCT images, presenting a mean difference in lumen area and Dice metrics of 0.19 mm2 and 97% for slices outside the bifurcation, 1.2 mm2 and 88% in the regions with bifurcation without automatic contour correction and 0.52 mm2 and 90% inside bifurcation region with automatic contour correction. Conclusion This present study shows a robust lumen segmentation method for vessel cross-sections with dissections and complex plaque and bifurcation avoiding the exclusion of such regions from the dataset analysis.

Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect.

Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (≈25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibody-containing perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to impaired viscoelastic ductility. Total and PDI-associated expressions of ß1-integrin, and levels of reduced cell-surface ß1-integrin, were diminished after PDI antibody treatment, implicating ß1-integrin as a likely pecPDI target during vessel repair. Indeed, focal adhesion kinase phosphorylation, a downstream ß1-integrin effector, was decreased by PDI antibody. Thus, the upregulated pecPDI pool tunes matrix/cytoskeleton reshaping to counteract inward remodeling in vascular pathophysiology.

Clinical performance of a novel ultrathin strut, low-dose, sirolimus-eluting stent with abluminal-only biodegradable polymeric coating for patients undergoing percutaneous coronary intervention in the daily practice.

BACKGROUND: The present study aimed to evaluate the clinical performance, in the daily practice of a busy catheterization laboratory, of a novel drug-eluting stent (DES) built with an ultra-thin-strut metallic platform, eluting sirolimus at low doses, abluminal coated with biodegradable polymers, and mounted in a low-compliant delivery system. METHODS: Prospective, single-arm study, comprising all consecutive patients undergoing percutaneous coronary intervention (PCI) with the Inspiron™ sirolimus-eluting stent (SES) (Scitech, Aparecida de Goiania, Brazil). The primary endpoint was the occurrence of major adverse cardiac events (MACE) [cardiac death, non-PCI related myocardial infarction (MI), or target vessel revascularization (TVR)]. RESULTS: A total of 470 patients were included, from which 51.3% were diabetics, 33.8% had triple-vessel disease, 15.3% had heart failure, 38.9% had at least one bifurcation treated, 19.8% were treated for a bare metal stent restenosis, and 61.9% had at least one type C lesion; one or more of these features were found in 96.0%. At 300 days, the rate target lesion revascularization was 5.4% and the rate of MACE was 8.1%. The incidence of definite or probable stent thrombosis was 0.4%, with no cases between 30 and 300 days. CONCLUSIONS: The novel stent is associated with excellent short and mid-term clinical outcomes in patients treated with PCI in the daily practice.

A bifurcation identifier for IV-OCT using orthogonal least squares and supervised machine learning.

Intravascular optical coherence tomography (IV-OCT) is an in-vivo imaging modality based on the intravascular introduction of a catheter which provides a view of the inner wall of blood vessels with a spatial resolution of 10-20 µm. Recent studies in IV-OCT have demonstrated the importance of the bifurcation regions. Therefore, the development of an automated tool to classify hundreds of coronary OCT frames as bifurcation or nonbifurcation can be an important step to improve automated methods for atherosclerotic plaques quantification, stent analysis and co-registration between different modalities. This paper describes a fully automated method to identify IV-OCT frames in bifurcation regions. The method is divided into lumen detection; feature extraction; and classification, providing a lumen area quantification, geometrical features of the cross-sectional lumen and labeled slices. This classification method is a combination of supervised machine learning algorithms and feature selection using orthogonal least squares methods. Training and tests were performed in sets with a maximum of 1460 human coronary OCT frames. The lumen segmentation achieved a mean difference of lumen area of 0.11 mm(2) compared with manual segmentation, and the AdaBoost classifier presented the best result reaching a F-measure score of 97.5% using 104 features.

A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting stent in porcine coronary arteries.

BACKGROUND: Permanent polymers in first generation drug-eluting stent (DES) have been imputed to be a possible cause of persistent inflammation, remodeling, malapposition and late stent thrombosis. We aim to describe the in vivo experimental result of a new polymer-free DES eluting sirolimus from stent-plus-balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix, Biosensors). METHODS: In 10 juvenile pigs, 23 coronary stents were implanted in the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day follow-up, optical coherence tomography (OCT) and histology were used to evaluate neointimal hyperplasia and healing response. RESULTS: According to OCT analysis, Focus np stents had a greater lumen area and less neointimal hyperplasia response than BMS and Biomatrix had. Histomorphometry results showed less neointimal hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition in Biomatrix stent compared to Focus np and BMS. CONCLUSIONS: The new polymer-free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28-day follow-up in this porcine coronary model. This new polymer-free DES is promising and warrants further clinical studies.

Aterectomia rotacional em artérias com calcificação extrema ou falha em dilatação prévia: aspectos técnicos e evolução tardia após intervenção coronária percutânea / Rotational atherectomy in arteries with extreme calcification or previous failed dilation: technical aspects and late outcomes after percutaneous coronary intervention

A aterectomia rotacional com incorporação de novas estratégias ablativas tem sido proposta para o preparo de lesões extremamente calcificadas. Entretanto, pouco se conhece a respeito da adoçãodessas novas estratégias na prática contemporânea e sobre a evolução tardia dos pacientes submetidos aesse tratamento. Objetivamos avaliar os aspectos técnicos da aterectomia e a evolução tardia dos pacientesquanto à ocorrência de eventos cardiovasculares adversos maiores (ECAM). Métodos: Estudo retrospectivo e unicêntrico, incluindo todos os pacientes submetidos à aterectomiarotacional como parte do tratamento de lesões coronárias com calcificação extrema ou falha de dilataçãoem procedimento prévio, no período de julho de 2012 a novembro de 2014. Foram definidos como ECAM: óbito, infarto agudo do miocárdio com onda Q ou nova revascularização do vaso-alvo.Resultados: Foram submetidos à aterectomia 29 pacientes com idade média de 69,5 ± 7,6 anos. A médiada relação oliva/vaso foi de 0,54 ± 0,07; a velocidade de rotação inicial adotada foi de 161.000 ± 13.928 e a taxa de utilização de cutting balloon pós-aterectomia foi de 45,1%. Sucesso angiográfico foi obtido em todos os procedimentos. Na evolução tardia, a mediana de tempo de seguimento foi de 13,2 meses (intervalo interquartil: 4,0 a 17,4 meses). Foram registrados um óbito por causa não cardíaca e duas novas revascularizações do vaso-alvo. A média do tempo de sobrevivência livre de ECAM foi de 29,7 ± 2,1 meses.Conclusões: A aterectomia rotacional contemporânea incorporou estratégias menos agressivas de ablação,com elevada taxa de sucesso imediato e baixa ocorrência de ECAM na evolução tardia...

Rotational atherectomy with new ablative strategies have been proposed for the treatment of extremely calcified lesions prior to stent implantation. Nevertheless, few data are available about the adoption of these new strategies in contemporary practice and about late outcomes of patients undergoing this therapy. Methods: From July 2012 to November 2014, a retrospective single center registry was conducted, including all patients undergoing rotational atherectomy as part of the treatment of coronary arteries with heavy calcification or previous failed dilation. We evaluated technical aspects of atherectomy and late outcomes of patients for the occurrence of major adverse cardiovascular events (MACE), defined as death, Q-wave myocardial infarction or repeat target vessel revascularization.Results: Twenty-nine patients with a mean age of 69.5 ± 7.6 years, underwent atherectomy. The averageburr-to-artery ratio was 0.54 ± 0.07, the initial rotational speed was 161.000 ± 13.928 and the rate of cuttingballoon utilization after atherectomy was 45.1%. Angiographic success was achieved in all procedures. The median follow-up time was 13.2 months (IQ: 4.0-17.4) and there were three events: 1 death of non cardiac cause and 2 new target vessel revascularizations. The mean MACE-free survival time was 29.7 ± 2.1 months. Conclusions: Contemporary rotational atherectomy incorporates less aggressive strategies of ablation with high rates of acute success and low occurrence of major adverse cardiovascular events during late follow-up...

Intravascular ultrasound guidance to minimize the use of iodine contrast in percutaneous coronary intervention: the MOZART (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy) randomized controlled trial.

OBJECTIVES: The aim of this study was to evaluate the impact of intravascular ultrasound (IVUS) guidance on the final volume of contrast agent used in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: To date, few approaches have been described to reduce the final dose of contrast agent in PCIs. We hypothesized that IVUS might serve as an alternative imaging tool to angiography in many steps during PCI, thereby reducing the use of iodine contrast. METHODS: A total of 83 patients were randomized to angiography-guided PCI or IVUS-guided PCI; both groups were treated according to a pre-defined meticulous procedural strategy. The primary endpoint was the total volume contrast agent used during PCI. Patients were followed clinically for an average of 4 months. RESULTS: The median total volume of contrast was 64.5 ml (interquartile range [IQR]: 42.8 to 97.0 ml; minimum, 19 ml; maximum, 170 ml) in the angiography-guided group versus 20.0 ml (IQR: 12.5 to 30.0 ml; minimum, 3 ml; maximum, 54 ml) in the IVUS-guided group (p < 0.001). Similarly, the median volume of contrast/creatinine clearance ratio was significantly lower among patients treated with IVUS-guided PCI (1.0 [IQR: 0.6 to 1.9] vs. 0.4 [IQR: 0.2 to 0.6, respectively; p < 0.001). In-hospital and 4-month outcomes were not different between patients randomized to angiography-guided and IVUS-guided PCI. CONCLUSIONS: Thoughtful and extensive use of IVUS as the primary imaging tool to guide PCI is safe and markedly reduces the volume of iodine contrast compared with angiography-alone guidance. The use of IVUS should be considered for patients at high risk of contrast-induced acute kidney injury or volume overload undergoing coronary angioplasty. (Minimizing cOntrast utiliZation With IVUS Guidance in coRonary angioplasTy [MOZART]; NCT01947335).

Catheter-based induction of renal ischemia/reperfusion in swine: description of an experimental model.

Several techniques to induce renal ischemia have been proposed: clamp, PVA particles, and catheter-balloon. We report the development of a controlled, single-insult model of unilateral renal ischemia/reperfusion (I/R) without contralateral nephrectomy, using a suitable model, the pig. This is a balloon-catheter-based model using a percutaneous, interventional radiology procedure. One angioplasty balloon-catheter was placed into the right renal artery and inflated for 120 min and reperfusion over 24 h. Serial serums were sampled from the inferior vena cava and urine was directly sampled from the bladder throughout the experiment, and both kidneys were excised after 24 h of reperfusion. Analyses of renal structure and function were performed by hematoxylin-eosin/periodic Acid-Schiff, serum creatinine (SCr), blood urea nitrogen (BUN), fractional excretion of ions, and glucose, SDS-PAGE analysis of urinary proteins, and serum neutrophil gelatinase-associated lipocalin (NGAL). Total nitrated protein was quantified to characterize oxidative stress. Acute tubular necrosis (ATN) was identified in every animal, but only two animals showed levels of SCr above 150% of baseline values. As expected, I/R increased SCr and BUN. Fractional sodium, potassium, chloride, and bicarbonate excretion were modulated during ischemia. Serum-nitrated proteins and NGAL had two profiles: decreased with ischemia and increased after reperfusion. This decline was associated with increased protein excretion during ischemia and early reperfusion. Altogether, these data show that the renal I/R model can be performed by percutaneous approach in the swine model. This is a suitable translational model to study new early renal ischemic biomarkers and pathophysiological mechanisms in renal ischemia.

Development of a closed-artery catheter-based myocardial infarction in pigs using sponge and lidocaine hydrochloride infusion to prevent irreversible ventricular fibrillation.

The objectives of this study were to develop a robust, homogeneous, viable and inexpensive model of closed-artery catheter-based model of myocardial infarction (MI) in pigs without major cardiac dysfunction. Suitable animal models that mimic human cardiovascular conditions are of paramount importance to understand the effects of novel therapeutic strategies to improve tissue perfusion and prevent cardiac deterioration post-MI. Pigs (N = 21, BW = 17 ± 1 kg) receiving continuous iv lidocaine hydrochloride were subjected to percutaneous intracoronary implant of foam sponge into the proximal left circumflex coronary artery. Intraprocedure mortality was 23.8%. ST segment elevation and increased serum Troponin T and CK-MB were documented in all animals. Thirty days after occlusion, echocardiography (95% IC [9.3-12.4%]) and anatomopathological (95% CI [9.3-12.6%]) analyses confirmed a significant and reproducible MI. Taken together, we provide evidence for a suitable closed-artery catheter-based method to produce MI in pigs accompanied by tissue hypoperfusion and absence of overt heart failure.

Estudo Pré-Clínico de Stent com Polímero Biodegradável e Liberação Abluminal de Sirolimus / Preclinical Study of a Biodegradable Polymer-based Stent with Abluminal Sirolimus Release

Fundamento: Stents recobertos com polímeros bioabsorvíveis e fármacos apenas na face abluminal podem ser mais seguros que stents farmacológicos com polímeros permanentes. Objetivo: Relatar os resultados experimentais com o stent Inspiron(r), um stent recoberto com polímero bioabsorvível e com liberação de sirolimus apenas da face abluminal, recentemente aprovado para uso clínico. Métodos: Foram implantados 45 stents nas artérias coronárias de 15 porcos e, no 28° dia pós-implante, foram obtidos os resultados angiográficos, de ultrassonografia intracoronária e de histomorfologia. Cinco grupos foram avaliados: Grupo I (nove stents sem recobrimento); Grupo II (nove stents com polímero bioabsorvível nas faces luminal e abluminal); Grupo III (oito stents com polímero bioabsorvível na face abluminal); Grupo IV (nove stents com polímero bioabsorvível e sirolimus nas faces luminal e abluminal); e Grupo V (dez stents com polímero bioabsorvível e sirolimus na face abluminal exclusivamente). Resultados: Observamos, para os Grupos I, II, III, IV e V respectivamente: porcentual de estenose de 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 e 26 ± 15 (p = 0,443); perda luminal tardia (em mm) de 1,02 ± 0,60; 1,24 ± 0,48; 1,11 ± 0,54; 0,72 ± 0,44 e 0,78 ± 0,39 (p = 0,253); área neointimal (em mm2) de 2,60 ± 1,99; 2,74 ± 1,51; 2,74 ± 1,30; 1,30 ± 1,14 e 0,97 ± 0,84 (p = 0,001; Grupos IV e V versus Grupos I, II e III) e porcentual de área neointimal de 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 e 15 ± 12 (p = 0,001; Grupo IV e V versus Grupo I, II e III). Os escores de injúria e inflamação foram baixos e sem diferenças entre os grupos. Conclusão: O stent Inspiron(r) foi seguro e inibiu significativamente a hiperplasia ...

Background: Bioabsorbable polymer stents with drug elution only on the abluminal surface may be safer than durable polymer drug-eluting stents. Objective: To report the experimental findings with the Inspiron(tm) stent - a bioabsorbable polymer-coated stent with sirolimus release from the abluminal surface only, recently approved for clinical use. Methods: 45 stents were implanted in the coronary arteries of 15 pigs. On day 28 after implantation, angiographic, intracoronary ultrasonographic and histomorphological data were collected. Five groups were analyzed: Group I (nine bare-metal stents); Group II (nine coated with bioabsorbable polymer on the luminal and abluminal surfaces); Group III (eight stents coated with bioabsorbable polymer on the abluminal surface); Group IV (nine stents with bioabsorbable polymer and sirolimus on the luminal and abluminal surfaces); and Group V (ten stents with bioabsorbable polymer and sirolimus only on the abluminal surface). Results: The following results were observed for Groups I, II, III, IV and V, respectively: percentage stenosis of 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 and 26 ± 15 (p = 0.443); late lumen loss (in mm) of 1.02 ± 0.60; 1.24 ± 0.48; 1.11 ± 0.54; 0.72 ± 0.44 and 0.78 ± 0.39 (p = 0.253); neointimal area (in mm2 )) of 2.60 ± 1.99; 2.74 ± 1.51; 2.74 ± 1.30; 1.30 ± 1.14 and 0.97 ± 0.84 (p = 0.001; Groups IV and V versus Groups I, II and III); and percentage neointimal area of 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 and 15 ± 12 (p = 0.001; Groups IV and V versus Groups I, II and III). Injury and inflammation scores were low and with no differences between the groups. Conclusion: The Inspiron(tm) stent proved to be safe and was able to significantly inhibit the neointimal hyperplasia observed on day 28 after implantation in porcine coronary arteries. .

Preclinical study of a biodegradable polymer-based stent with abluminal sirolimus release.

BACKGROUND: Bioabsorbable polymer stents with drug elution only on the abluminal surface may be safer than durable polymer drug-eluting stents. OBJECTIVE: To report the experimental findings with the Inspiron™ stent - a bioabsorbable polymer-coated stent with sirolimus release from the abluminal surface only, recently approved for clinical use. METHODS: 45 stents were implanted in the coronary arteries of 15 pigs. On day 28 after implantation, angiographic, intracoronary ultrasonographic and histomorphological data were collected. Five groups were analyzed: Group I (nine bare-metal stents); Group II (nine coated with bioabsorbable polymer on the luminal and abluminal surfaces); Group III (eight stents coated with bioabsorbable polymer on the abluminal surface); Group IV (nine stents with bioabsorbable polymer and sirolimus on the luminal and abluminal surfaces); and Group V (ten stents with bioabsorbable polymer and sirolimus only on the abluminal surface). RESULTS: The following results were observed for Groups I, II, III, IV and V, respectively: percentage stenosis of 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 and 26 ± 15 (p = 0.443); late lumen loss (in mm) of 1.02 ± 0.60; 1.24 ± 0.48; 1.11 ± 0.54; 0.72 ± 0.44 and 0.78 ± 0.39 (p = 0.253); neointimal area (in mm(2)) of 2.60 ± 1.99; 2.74 ± 1.51; 2.74 ± 1.30; 1.30 ± 1.14 and 0.97 ± 0.84 (p = 0.001; Groups IV and V versus Groups I, II and III); and percentage neointimal area of 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 and 15 ± 12 (p = 0.001; Groups IV and V versus Groups I, II and III). Injury and inflammation scores were low and with no differences between the groups. CONCLUSION: The Inspiron™ stent proved to be safe and was able to significantly inhibit the neointimal hyperplasia observed on day 28 after implantation in porcine coronary arteries.

Tendências da Utilização da Via de Acesso Transradial em Mais de Uma Década: A Experiência do InCor / Trends in the Use of the Transradial Approach in More Than a Decade: The InCor's Experience

Introdução: A utilização da via radial para a realização de cateterismo cardíaco diagnóstico e intervenção coronária percutânea varia entre os diversos centros de hemodinâmica. Descrevemos as tendências do uso dessa via de acesso ao longo dos últimos 14 anos num serviço terciário. Métodos: Foram identificados procedimentos coronarianos consecutivos realizados de 1999 a 2013, em um único centro, em pacientes com idade ≥ 35 anos. Dados como idade, sexo, fonte provedora de recursos (Sistema de Saúde Público ou Saúde Suplementar/Privado) e complexidade do procedimento (diagnóstico ou terapêutico) foram retrospectivamente analisados. Resultados: Foram incluídos 103.253 procedimentos, dos quais o Sistema Único de Saúde (SUS) foi o provedor de recursos em 77% dos casos. A média de idades dos pacientes foi 62,2 ± 11,3 e 58,8% eram do sexo masculino. A via radial foi utilizada em 6.402 (6,2%) dos procedimentos, apresentando ascensão significativa ao longo do tempo, mais evidente quando analisada comparativamente nos seis períodos de experiência do serviço: 0,2%, 0,6%, 3,1%, 2,1%, 6,9% e 24,4%, respectivamente (p < 0,01). Porcentuais ainda maiores do uso da via radial foram encontrados, restringindo-se aos procedimentos realizados pelo SUS e quando apenas os cateterismos cardíacos diagnósticos foram contabilizados. Houve também mudança no perfil da via de acesso, ainda que de menor monta, no setor de Saúde Suplementar/Privado. Conclusões: Demonstramos a progressiva modificação do perfil de utilização das vias de acesso para a realização de cateterismo cardíaco diagnóstico e intervenção coronária percutânea de um centro de grande porte ao longo do tempo. Esses dados são condizentes...

Background: The use of the radial approach for diagnostic cardiac catheterization and percutaneous coronary interventions varies among different interventional cardiology centers in the world. We describe the trends in the use of this approach over the past 14 years at a tertiary hospital. Methods: Consecutive coronary procedures performed from 1999 to 2013 at a single center, in patients aged ≥ 35 years were identified. Age, gender, resource provider (Public or Private Healthcare System) and the complexity of the procedure (diagnostic or therapeutic) were retrospectively analyzed. Results: 103,253 procedures were included. The Brazilian Public Healthcare Service (SUS - Sistema Único de Saúde) was the resource provider in 77% of the cases. Mean age of patients was 62.2 ± 11.3 years and 58% were male. The radial approach was used in 6,402 (6.2%) procedures, showing a significant rise over time, which was more evident when analyzed comparatively for the six timepoints of service experience: 0.2%; 0.6%; 3.1%; 2.1%; 6.9%, and 24.4% respectively (p < 0.01). Even larger percentages of radial approach were observed when only the procedures performed by the SUS and diagnostic cardiac catheterizations were taken into account. There were also changes in the profile of vascular access, even though smaller, in the Private Healthcare System. Conclusions: We demonstrated progressive changes in the profile of the use of access routes for diagnostic cardiac catheterization and percutaneous coronary interventions at a large center over time. These data are consistent with the global trend and are significantly robust, especially when the last sextile is analyzed...

Remoção Precoce do Introdutor Arterial Após Intervenção Coronária Percutânea por Via Femoral: Estudo de Segurança e Eficácia / Early Removal of the Arterial Sheath After Percutaneous Coronary Intervention Using the Femoral Approach: Safety and Efficacy Study

Introdução: Avaliamos a segurança e eficácia do uso de protamina, guiada pelo tempo de coagulação ativado, para a remoção imediata do introdutor arterial femoral em pacientes submetidos à intervenção coronária percutânea com heparina não fracionada, com o objetivo de propor um algoritmo para a prática clínica. Métodos: Estudo prospectivo, com pacientes consecutivos, com angina estável ou com síndrome coronariana aguda de baixo ou moderado risco. Comparamos os pacientes com a retirada precoce do introdutor arterial àqueles nos quais o introdutor foi retirado de acordo com o protocolo convencional. A decisão pela remoção precoce ou convencional do introdutor foi deixada a critério do operador. Resultados: O grupo de remoção precoce (n = 149) apresentou menor tempo de manuseio do sítio de punção que o grupo de remoção convencional (58,3 ± 21,4 minutos vs. 355 ± 62,9 minutos; p < 0,01), principalmente devido à redução do tempo até a retirada do introdutor (42,3 ± 21,1 minutos vs. 338,6 ± 61,5 minutos; p < 0,01), sem impacto sobre a duração da compressão femoral (16,0 ± 3,6 minutos vs. 16,4 ± 5,1 minutos; p = 0,49). Não houve trombose hospitalar de stent e nem diferença significativa na incidência de eventos vasculares ou hemorrágicos. A incidência de outras hemorragias, que levaram à hospitalização prolongada, foi menor no grupo de remoção precoce (1,3% vs. 5,1%; p = 0,05). Conclusões: O uso seletivo de uma abordagem, para a remoção imediata do introdutor femoral guiada pelo tempo de coagulação ativado e a administração de protamina, é seguro e eficaz em pacientes submetidos à intervenção coronária...

Introduction: We evaluated the safety and efficacy of protamine administration, guided by activated clotting time, for the immediate femoral arterial sheath removal in patients undergoing percutaneous coronary intervention with unfractionated heparin in order to propose an algorithm for clinical practice. Methods: Prospective study with consecutive patients with stable angina or low-to-moderate risk acute coronary syndrome. We compared patients with an early removal of the arterial sheath to those whose sheath removal was based on a standard protocol. Results: The early removal group (n = 149) had lower access manipulation time than the conventional group (58.3 ± 21.4 minutes vs. 355.0 ± 62.9 minutes; p < 0.01), mainly due to a reduced time to sheath removal (42.3 ± 21.1 minutes vs. 338.6 ± 61.5 minutes; p < 0.01), with no impact on the duration of femoral compression (16.0 ± 3.6 minutes vs. 16.4 ± 5.1 minutes; p = 0.49). There was no stent thrombosis during hospitalization and no significant differences in the incidence of major vascular or bleeding events. The incidence of other bleeding events leading to a prolonged in-hospital length of stay was lower in the early removal group (1.3% vs. 5.1%; p = 0.05). Conclusions: The selective use of an approach for immediate femoral sheath removal, based on activated clotting time guidance and protamine administration, is a safe and effective option in patients undergoing percutaneous coronary intervention by femoral access...

Impacto da insuficiência renal aguda na evolução hospitalar após tratamento percutâneo do infarto agudo do miocárdio / Impact of acute renal failure on in-hospital outcomes following percutaneous treatment of acute myocardial infarction

INTRODUÇÃO: A insuficiência renal aguda (IRA) é uma complicação possível após intervenção coronária percutânea (ICP). O objetivo deste estudo foi avaliar a ocorrência e o impacto prognóstico da IRA pós-ICP em pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IMCSST). MÉTODOS: Registro unicêntrico, que analisou a evolução hospitalar de 501 pacientes admitidos com IMCSST submetidos à ICP primária, de resgate ou tardia. Foram avaliados a incidência e os preditores de IRA pós-ICP. RESULTADOS: A idade média foi 60,7 ± 12,6 anos e 67% eram do gênero masculino. A população apresentava características de alto risco cardiovascular, sendo 30% diabéticos e 7,4% com doença renal crônica (DRC) preexistente. A artéria descendente anterior foi a principal artéria culpada (49,4%) e 15% dos pacientes se apresentaram em Killip III ou IV. A IRA ocorreu em 24,7% dos pacientes, que, quando comparados àqueles sem IRA, eram significativamente mais idosos, diabéticos, com DRC e insuficiência cardíaca, além de apresentarem maior elevação enzimática e menor fração de ejeção. A mortalidade hospitalar foi maior nos pacientes que desenvolveram IRA (29% vs. 4,8%; P < 0,01). Os preditores independentes de IRA foram idade > 76 anos, DRC prévia, Killip III ou IV, necessidade de cirurgia vascular ou transfusão sanguínea. CONCLUSÕES: A disfunção renal aguda após ICP no IMCSST foi uma complicação frequente e associada com aumento da mortalidade hospitalar.

BACKGROUND: Acute renal failure (ARF) is a possible complication after percutaneous coronary intervention (PCI). The objective of this study was to evaluate the occurrence and prognostic impact of ARF after PCI in patients with ST segment elevation myocardial infarction (STEMI). METHODS: Single-center registry evaluating in-hospital outcomes of 501 patients admitted with STEMI undergoing primary, rescue or late PCI. The incidence and predictors of ARF after PCI were evaluated. RESULTS: Mean age was 60.7 ± 12.6 years and 67% were male. The population had high cardiovascular risk characteristics, with 30% of diabetics and 7.4% with preexisting chronic kidney disease (CKD). The left anterior descending artery was the culprit vessel in 49.4% of the cases and 15% of patients had Killip class III or IV. ARF was observed in 24.7% of patients, who were significantly older, had more diabetes, history of CKD or heart failure, had higher enzyme elevation and lower ejection fraction when compared to those without ARF. In-hospital mortality was higher in patients who developed ARF (29% vs. 4.8%; P < 0.01). Independent predictors of ARF were age > 76 years, previous CKD, Killip class III or IV, need of vascular surgery or blood transfusion. CONCLUSIONS: Acute renal failure after PCI in STEMI was a frequent complication and was associated with increased in-hospital mortality.