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1.
J Surg Res ; 257: 294-305, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871430

RESUMO

BACKGROUND: Drug-eluting stents impair post-angioplasty re-endothelialization thus compromising restenosis prevention while heightening thrombotic risks. We recently found that inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) effectively mitigated both restenosis and thrombosis in rodent models. This motivated us to determine how PERK inhibition impacts re-endothelialization. METHODS: Re-endothelialization was evaluated in endothelial-denuded rat carotid arteries after balloon angioplasty and periadventitial administration of PERK inhibitor in a hydrogel. To study whether PERK in smooth muscle cells (SMCs) regulates re-endothelialization by paracrinally influencing endothelial cells (ECs), denuded arteries exposing SMCs were lentiviral-infected to silence PERK; in vitro, the extracellular vesicles isolated from the medium of PDGF-activated, PERK-upregulating human primary SMCs were transferred to human primary ECs. RESULTS: Treatment with PERK inhibitor versus vehicle control accelerated re-endothelialization in denuded arteries. PERK-specific silencing in the denuded arterial wall (mainly SMCs) also enhanced re-endothelialization compared to scrambled shRNA control. In vitro, while medium transfer from PDGF-activated SMCs impaired EC viability and increased the mRNA levels of dysfunctional EC markers, either PERK inhibition or silencing in donor SMCs mitigated these EC changes. Furthermore, CXCL10, a paracrine cytokine detrimental to ECs, was increased by PDGF activation and decreased after PERK inhibition or silencing in SMCs. CONCLUSIONS: Attenuating PERK activity pharmacologically or genetically provides an approach to accelerating post-angioplasty re-endothelialization in rats. The mechanism may involve paracrine factors regulated by PERK in SMCs that impact neighboring ECs. This study rationalizes future development of PERK-targeted endothelium-friendly vascular interventions.


Assuntos
Angioplastia com Balão/efeitos adversos , Reestenose Coronária/prevenção & controle , Miócitos de Músculo Liso/efeitos dos fármacos , Inibidores de Proteínas Quinases/administração & dosagem , Reepitelização/efeitos dos fármacos , eIF-2 Quinase/antagonistas & inibidores , Angioplastia com Balão/instrumentação , Animais , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Artérias Carótidas/cirurgia , Reestenose Coronária/etiologia , Modelos Animais de Doenças , Stents Farmacológicos/efeitos adversos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Humanos , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Comunicação Parácrina/efeitos dos fármacos , Comunicação Parácrina/genética , RNA Interferente Pequeno/metabolismo , Ratos , Reepitelização/genética , eIF-2 Quinase/genética
2.
Arq Bras Cardiol ; 115(1): 80-89, 2020 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32813829

RESUMO

Background The use of drug-eluting stents (DESs), compared with bare-metal stents (BMSs), in percutaneous coronary intervention (PCI) has reduced the rate of restenosis, without an impact on mortality but with an increase in costs. Medical literature lacks randomized studies that economically compare these 2 stent types within the reality of the Brazilian Unified Public Health System (SUS). Objective To estimate the incremental cost-effectiveness ratio (ICER) between DES and BMS in SUS patients with single-vessel coronary artery disease. Methods Over a 3-year period, patients with symptomatic single-vessel coronary artery disease were randomized in a 1:2 ratio to receive a DES or BMS during PCI, with a 1-year clinical follow-up. The evaluation included in-stent restenosis (ISR), target lesion revascularization (TLR), major adverse events, and cost-effectiveness for each group. P-values <0.05 were considered significant. Results In the DES group, of 74 patients (96.1%) who completed the follow-up, 1 developed ISR (1.4%), 1 had TLR (1.4%), and 1 died (1.4%), with no cases of thrombosis. In the BMS group, of 141 patients (91.5%), ISR occurred in 14 (10.1%), TLR in 10 (7.3%), death in 3 (2.1%), and thrombosis in 1 (0.74%). In the economic analysis, the cost of the procedure was R$ 5,722.21 in the DES group and R$ 4,085.21 in the BMS group. The effectiveness by ISR and TLR was 8.7% for DES and 5.9% for BMS, with an ICER of R$ 18,816.09 and R$ 27,745.76, respectively. Conclusions In the SUS, DESs were cost-effective in accordance with the cost-effectiveness threshold recommended by the World Health Organization (Arq Bras Cardiol. 2020; 115(1):80-89).


Assuntos
Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Brasil , Reestenose Coronária/prevenção & controle , Análise Custo-Benefício , Stents Farmacológicos/efeitos adversos , Humanos , Desenho de Prótese , Saúde Pública , Fatores de Risco , Stents/efeitos adversos , Resultado do Tratamento
4.
J Vasc Res ; 57(2): 65-75, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32036370

RESUMO

AIMS: Percutaneous coronary intervention is routinely performed to treat occlusive coronary artery disease. Coronary perforation is a potential complication and can be treated with a stent graft. Current stent grafts are associated with high restenosis rates. We tested the safety and feasibility of biodegradable stent grafts in pig and rabbit models. METHODS AND RESULTS: Stent grafts were examined in pig coronaries with repeated OCT imaging for 42 days. Novel biodegradable coatings were applied on a bare metal stent by either an electrospinning (ES) or dip coating (DC) method. A completely biodegradable system was made by ES coating a magnesium-based stent. A commercially available stent graft served as a control. ES devices showed less restenosis (44.3 ± 8.8 vs. 59.1 ± 11.1% in controls, p < 0.05) and smaller reduction in minimum lumen area (44.3 ± 13.4 vs. 64.4 ± 13.6% in controls, p < 0.05) at day 42. DC devices occluded during follow-up. ES devices showed recanalization through the graft wall at day 42. Feasibility of the ES and DC devices was evaluated in pig coronary aneurysms and rabbit aortic perforation models and sealed aneurysms and perforations without complications. CONCLUSIONS: Recanalization of the graft wall improves biocompatibility. Biodegradable stent grafts may present an alternative to permanent implants by showing reduced restenosis at day 42.


Assuntos
Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/efeitos adversos , Stents/efeitos adversos , Implantes Absorvíveis , Animais , Reestenose Coronária/prevenção & controle , Modelos Animais , Coelhos , Suínos
5.
Cardiovasc Res ; 116(3): 505-519, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31397850

RESUMO

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent restenosis (ISR) is a major drawback for intracoronary stenting, while graft failure is the limiting factor for coronary artery bypass graft surgery (CABG), especially using veins. Conversely, internal thoracic artery (ITA) is known to maintain long-term patency in CABG. Understanding the biology and pathophysiology of ISR and vein graft failure (VGF) and mechanisms behind ITA resistance to failure is crucial to combat these complications in CAD treatment. This review intends to provide an overview of the biological mechanisms underlying stent and VGF and of the potential therapeutic strategy to prevent these complications. Interestingly, despite being different modalities of revascularization, mechanisms of failure of stent and saphenous vein grafts are very similar from the biological standpoint.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/terapia , Reestenose Coronária/prevenção & controle , Vasos Coronários/cirurgia , Oclusão de Enxerto Vascular/prevenção & controle , Artéria Torácica Interna/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Veia Safena/transplante , Stents , Animais , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Reestenose Coronária/metabolismo , Reestenose Coronária/patologia , Reestenose Coronária/fisiopatologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Oclusão de Enxerto Vascular/metabolismo , Oclusão de Enxerto Vascular/patologia , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Artéria Torácica Interna/metabolismo , Artéria Torácica Interna/fisiopatologia , Neointima , Fatores de Risco , Veia Safena/metabolismo , Veia Safena/fisiopatologia , Fatores de Tempo , Falha de Tratamento , Grau de Desobstrução Vascular
6.
EuroIntervention ; 15(17): 1527-1533, 2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-31659986

RESUMO

AIMS: Drug-coated balloons (DCB) may avoid stent-associated long-term complications. This trial compared the clinical outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) treated with either DCB or stents. METHODS AND RESULTS: A total of 210 patients with NSTEMI were enrolled in a randomised, controlled, non-inferiority multicentre trial comparing a paclitaxel iopromide-coated DCB with primary stent treatment. The main inclusion criterion was an identifiable culprit lesion without angiographic evidence of large thrombus. The primary endpoint was target lesion failure (TLF; combined clinical endpoint consisting of cardiac or unknown death, reinfarction, and target lesion revascularisation) after nine months. Secondary endpoints included total major adverse cardiovascular events (MACE) and individual clinical endpoints. Mean age was 67±12 years, 67% were male, 62% had multivessel disease, and 31% were diabetics. One hundred and four patients were randomised to DCB, 106 to stent treatment. In the stent group, 56% of patients were treated with BMS, 44% with current-generation DES. In the DCB group, 85% of patients were treated with DCB only whereas 15% underwent additional stent implantation. During a follow-up of 9.2±0.7 months, DCB treatment was non-inferior to stent treatment with a TLF rate of 3.8% versus 6.6% (intention-to-treat, p=0.53). There was no significant difference between BMS and current-generation DES. The total MACE rate was 6.7% for DCB versus 14.2% for stent treatment (p=0.11), and 5.9% versus 14.4% in the per protocol analysis (p=0.056), respectively. CONCLUSIONS: In patients with NSTEMI, treatment of coronary de novo lesions with DCB was non-inferior to stenting with BMS or DES. These data warrant further investigation of DCB in this setting, in larger trials with DES as comparator (ClinicalTrials.gov Identifier: NCT01489449).


Assuntos
Angioplastia Coronária com Balão/métodos , Fármacos Cardiovasculares/administração & dosagem , Reestenose Coronária/prevenção & controle , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Paclitaxel/administração & dosagem , Sirolimo/administração & dosagem , Stents , Idoso , Idoso de 80 Anos ou mais , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/epidemiologia , Feminino , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Desenho de Prótese , Resultado do Tratamento , Ultrassonografia de Intervenção
7.
J Mater Chem B ; 7(46): 7314-7325, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31674636

RESUMO

Vascular stent interventional therapy, as a regular and effective therapy, has been widely used to treat coronary artery diseases. However, adverse events occur frequently after stent intervention, especially restenosis and late stent thrombosis. The targeted implanting site will suffer from severe atherosclerosis, which is considered as a chronic inflammatory disease. Meanwhile, with the over-expanding use of endovascular mechanical intervention, vascular injury has become an increasingly common issue. Lesions and newly induced vascular injury result in inflammatory and oxidative stress; meanwhile, activated macrophages and granulocytes generate high levels of reactive oxygen species (ROS), contributing to endothelial dysfunction and neointima hyperplasia. Therefore, attenuating oxidative stress and reducing ROS generation in the inflammatory response represent reasonable strategies to inhibit intimal hyperplasia and restenosis. Herein, we have developed a multifunctional surface for the MgZnYNd alloy with tannic acid (TA) coating, and the pH dependence of the coating deposition is also demonstrated. The phenolic hydroxyl groups on the coatings endow the modified surface with excellent antioxidant functions. We found that the coating can be recycled, and the scavenging activity hardly weakened within five cycles. Also, the TA coating has a promising strong antioxidant activity as it shows a radical scavenging activity over 80% in long term. Moreover, the TA coating possesses platelet-repellent capability. No significant inflammatory response was observed for the TA modified sample in the rat subcutaneous implantation test. Combining these performances, we envision that the vascular stent modified with TA coating can have great potential in various applications by virtue of its simplicity and effectiveness.


Assuntos
Ligas/química , Antioxidantes/química , Plaquetas/efeitos dos fármacos , Fluoretos/química , Stents , Taninos/química , Animais , Compostos de Bifenilo/química , Proliferação de Células , Reestenose Coronária/prevenção & controle , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Inflamação , Neodímio/química , Estresse Oxidativo , Picratos/química , Adesividade Plaquetária , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/química , Trombose/prevenção & controle , Zinco/química
8.
Aging (Albany NY) ; 11(19): 8604-8622, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596731

RESUMO

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, particularly among older adults. Despite the advent of medical technology, restenosis is still an issue after interventional procedures. Tryptophan metabolite 5-methoxytryptophan (5-MTP) has recently been shown to protect against systemic inflammatory responses. This study aimed to investigate the function and mechanisms of 5-MTP in interventional procedure-induced restenosis. We found that after mouse femoral artery denudation with a guide wire, 5-MTP accelerated recovery of endothelium in the denuded area and reduced vascular leakage and intimal thickening. 5-MTP increased endothelial cell proliferation in the denuded arteries and rescued TNF-α-reduced endothelial cell proliferation and migration, likely via maintaining vascular endothelial growth factor receptor 2 activation. In contrast, 5-MTP preserved differentiated phenotype of medial vascular smooth muscle cells (VSMCs) and decreased VSMC proliferation and migration. Furthermore, 5-MTP maintained expression levels of critical transcription factors for VSMC marker gene expressions via attenuated activation of p38 MAPK and NFκB-p65. Our findings uncover a novel protective mechanism of 5-MTP in restenosis. In response to denudation injury, 5-MTP attenuates intimal hyperplasia via concerted but opposing actions on endothelial cells and VSMCs. Taken together, our results suggest that 5-MTP is a valuable therapeutic target for arterial injury-induced restenosis.


Assuntos
Reestenose Coronária , Endotélio Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Triptofano/análogos & derivados , Animais , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Reestenose Coronária/metabolismo , Reestenose Coronária/prevenção & controle , Camundongos , Fatores de Proteção , Triptofano/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Adv Ther ; 36(9): 2296-2309, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31372962

RESUMO

INTRODUCTION: High on-treatment residual platelet reactivity (HRPR) was associated with greater atherosclerosis burden. We examined whether intrinsic hypercoagulability (IHC) could be attributed to that association in patients treated by drug-eluting stents. METHODS: This retrospective observation enrolled a total of 891 coronary artery disease (CAD) subjects. Platelet and coagulant reactivity was measured by thrombelastography. At least 24 h after a 300-mg dose of clopidogrel, adenosine diphosphate (ADP)-induced maximum amplitude of clot strength (MAadp) > 47 mm represented HRPR. Thrombin-induced platelet-fibrin clot strength (MAthrombin) and blood fibrinogen surrogated intrinsic coagulability. Using mediation analysis to evaluate the effect of IHC on the relationship between the number of narrowed coronaries and HRPR on clopidogrel. RESULTS: More HRPR on clopidogrel and higher intrinsic coagulability were observed in more severe coronary atherosclerosis, especially in the three-vessel disease. After adjustment for confounding factors, the number of narrowed coronaries (ORadj = 1.343, 95% CI 1.063-1.695, p = 0.013), MAthrombin (ORadj = 1.106, 95% CI 1.058-1.157, p < 0.001), and fibrinogen (ORadj = 1.003, 95% CI 1.001-1.005, p = 0.012) were all independent positive predictors for HRPR. MAthrombin and fibrinogen were meaningful mediators for the significant positive association of the number of narrowed vessels and HRPR on clopidogrel, which were enhanced by around 30% and 43%, respectively, for this effect. CONCLUSIONS: This is the first study to demonstrate that the positive correlation between the number of stenotic coronaries and HRPR on clopidogrel may be partly attributed to IHC, which may enhance the risk stratification, guide more precise coagulation in multi-vessel disease after drug-eluting stents, and therefore deserve further study.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Stents Farmacológicos/estatística & dados numéricos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Trombofilia/etiologia , Idoso , Clopidogrel , Reestenose Coronária/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/farmacologia , Estudos Retrospectivos , Tromboelastografia/métodos , Ticlopidina/uso terapêutico
12.
Cardiovasc Revasc Med ; 20(7): 577-582, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153846

RESUMO

BACKGROUND: The advent of bioresorbable vascular scaffolds (BVS) was considered as a potential improvement in percutaneous coronary intervention (PCI) after the groundbreaking development of drug eluting stents (DES). However, the clinical performance, long-term safety and efficacy of BVS in complex coronary lesions remain uncertain. COMPARE ABSORB, a multicenter, single blind, prospective randomized trial, aims to compare the clinical outcomes between the Absorb BVS and Xience everolimus-eluting metallic stent (EES) in patients with coronary artery disease and a high risk of restenosis. DESIGN: COMPARE ABSORB is designed to enroll 2100 patients at up to 45 European sites. Enrolled patients will possess high risk for restenosis due to clinical profile or coronary lesion complexity and will undergo elective or emergent PCI. Once included in the study, patients will receive either Absorb BVS or Xience EES. Specific advice on implantation technique including mandatory pre-dilatation, sizing and post-dilatation (PSP), will be used in the Absorb BVS arm. The primary endpoint is target lesion failure (TLF), a device-oriented composite endpoint (cardiac death, target vessel myocardial infarction and clinically-indicated target lesion revascularization). The trial is powered to assess non-inferiority of Absorb BVS compared with Xience EES with a predetermined non-inferiority margin of 4.5% at 1 year after index procedure. The clinical follow-up will continue for 7 years. CONCLUSIONS: The prospective COMPARE ABSORB randomized trial (ClinicalTrials.govNCT02486068) will help to assess the long-term safety and efficacy of Absorb BVS compared with Xience EES in the treatments of patients with complex coronary artery disease and a high attendant risk of restenosis.


Assuntos
Implantes Absorvíveis , Angioplastia Coronária com Balão/instrumentação , Doença da Artéria Coronariana/terapia , Reestenose Coronária/prevenção & controle , Metais , Stents , Adolescente , Adulto , Idoso , Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Reestenose Coronária/mortalidade , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Desenho de Prótese , Fatores de Proteção , Medição de Risco , Fatores de Risco , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Lancet ; 394(10194): 230-239, 2019 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-31204115

RESUMO

BACKGROUND: The optimal technique of percutaneous coronary intervention in patients at high bleeding risk is not known. The hypothesis of the DEBUT trial was that percutaneous coronary intervention with drug-coated balloons is non-inferior to percutaneous coronary intervention with bare-metal stents for this population. METHODS: The DEBUT trial is a randomised, single-blind non-inferiority trial done at five sites in Finland. Patients were eligible if they had an ischaemic de-novo lesion in a coronary artery or bypass graft that could be treated with drug-coated balloons, at least one risk factor for bleeding, and a reference vessel diameter of 2·5-4·0 mm. Those with myocardial infarction with ST-elevation, bifurcation lesions needing a two-stent technique, in-stent restenosis, and flow-limiting dissection or substantial recoil (>30%) of the target lesion after predilation were excluded. After successful predilation of the target lesion, patients were randomly assigned (1:1), by use of a computer-generated random sequence, to percutaneous coronary intervention with a balloon coated with paclitaxel and iopromide or a bare-metal stent. The primary outcome was major adverse cardiac events at 9 months. Non-inferiority was shown if the absolute risk difference was no more than 3%. All prespecified analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01781546. FINDINGS: Between May 22, 2013, and Jan 16, 2017, 220 patients were recruited for the study and 208 patients were assigned to percutaneous coronary intervention with drug-coated balloon (n=102) or bare metal stent (n=106). At 9 months, major adverse cardiac events had occurred in one patient (1%) in the drug-coated balloon group and in 15 patients (14%) in the bare-metal stent group (absolute risk difference -13·2 percentage points [95% CI -6·2 to -21·1], risk ratio 0·07 [95% CI 0·01 to 0·52]; p<0·00001 for non-inferiority and p=0·00034 for superiority). Two definitive stent thrombosis events occurred in the bare metal stent group but no acute vessel closures in the drug-coated balloon group. INTERPRETATIONS: Percutaneous coronary intervention with drug-coated balloon was superior to bare-metal stents in patients at bleeding risk. The drug-coated balloon-only coronary intervention is a novel strategy to treat this difficult patient population. Comparison of this approach to the new generation drug-eluting stents is warranted in the future. FUNDING: B Braun Medical AG, AstraZeneca, and Competitive State Research Funding of the Kuopio University Hospital Catchment Area.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/patologia , Reestenose Coronária/prevenção & controle , Feminino , Hemorragia/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Método Simples-Cego , Stents , Moduladores de Tubulina/administração & dosagem
14.
JAMA Cardiol ; 4(7): 659-669, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31111862

RESUMO

Importance: Stenting small-vessel lesions has an increased adverse cardiovascular event risk. Very thin-strut or ultrathin-strut drug-eluting stents might reduce this risk, but data are scarce. Objective: To assess the outcome of all-comer patients with small coronary vessel lesions treated with 3 dissimilar types of drug-eluting stents. Design: This is a prespecified substudy of the Comparison of Biodegradable Polymer and Durable Polymer Drug-eluting Stents in an All Comers Population (BIO-RESORT) trial, an investigator-initiated, randomized, patient-blinded comparative clinical drug-eluting stent trial. Patients treated with ultrathin-strut sirolimus-eluting stents, very thin-strut everolimus-eluting stents, or previous-generation thin-strut zotarolimus-eluting stents were enrolled from December 2012 to August 2015. This multicenter trial was conducted in 4 Dutch centers for cardiac intervention. Of all 3514 all-comer BIO-RESORT participants, 1506 patients with treatment in at least 1 small-vessel lesion (reference vessel <2.5 mm) were included. Data were analyzed between September 2018 and February 2019. Main Outcomes and Measures: Target lesion failure at 3-year follow-up, a composite of cardiac death, target vessel-related myocardial infarction, or target lesion revascularization, analyzed by Kaplan-Meier methods. Results: In 1452 of 1506 participants (96.4%) (1057 men [70.2%]; 449 women [29.8%]; mean [SD] age, 64.3 [10.4] years), follow-up was available. Target lesion failure occurred in 36 of 525 patients (7.0%) treated with sirolimus-eluting stents, 46 of 496 (9.5%) with everolimus-eluting stents, and 48 of 485 (10.0%) with zotarolimus-eluting stents (sirolimus-eluting vs zotarolimus-eluting hazard ratio [HR], 0.68; 95% CI, 0.44-1.05; P = .08; everolimus-eluting vs zotarolimus-eluting HR, 0.93; 95% CI, 0.62-1.39; P = .72). There was a difference in target lesion revascularizations between sirolimus-eluting and zotarolimus-eluting stents (2.1% vs 5.3%; HR, 0.40; 95% CI, 0.20-0.81; P = .009) that emerged after the first year of follow-up (1.0% vs 3.7%; P = .006); multivariate analysis showed that sirolimus-eluting stent implantation was independently associated with a lower target lesion revascularization rate at 3-year follow-up (adjusted HR, 0.42; 95% CI, 0.20-0.85; P = .02). In the everolimus-eluting stents, the revascularization rate was 4.0% (vs zotarolimus-eluting, HR, 0.74; 95% CI, 0.41-1.34; P = .31). There was no significant between-stent difference in cardiac death, target vessel myocardial infarction, or stent thrombosis. Conclusions and Relevance: Patients stented in small coronary vessels experienced fewer repeated revascularizations if treated with ultrathin-strut sirolimus-eluting stents vs previous generation thin strut zotarolimus-eluting stents. Further research is required to evaluate the potential effect of particularly thin stent struts. Trial Registration: ClinicalTrials.gov identifier: NCT01674803.


Assuntos
Reestenose Coronária/prevenção & controle , Stents Farmacológicos , Implantes Absorvíveis , Vasos Coronários , Everolimo/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Intervenção Coronária Percutânea/instrumentação , Desenho de Prótese , Fatores de Risco , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Resultado do Tratamento
15.
Int J Cardiol ; 290: 64-69, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30971372

RESUMO

INTRODUCTION: Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known. METHODS: All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint. RESULTS: 2745 patients were included, mean age 68 ±â€¯11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer. CONCLUSIONS: The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications.


Assuntos
Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/tendências , Intervenção Coronária Percutânea/tendências , Desenho de Prótese/tendências , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/diagnóstico por imagem , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/prevenção & controle , Stents Farmacológicos/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese/efeitos adversos , Sistema de Registros , Fatores de Risco , Resultado do Tratamento
16.
IUBMB Life ; 71(5): 632-642, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30597731

RESUMO

Vascular smooth muscle cell (VSMC) hyperproliferation is the main pathological process in various cardiovascular diseases, such as vascular restenosis. This process may be repressed by RING finger protein 10 (RNF10) in metabolic syndrome (MetS) rats. The aim of this study is to evaluate the inhibitory effects and molecular mechanisms of RNF10 on VSMC hyperproliferation. Neointimal hyperplasia in MetS and high-glucose-induced VSMC hyperproliferation were measured after infection with adenoviruses encoding RNF10 (Ad-RNF10), short hairpin RNF10 (Ad-shRNF10), or green fluorescent protein (Ad-GFP). In vivo and in vitro, we found that overexpression of RNF10 significantly affected neointima formation and VSMC proliferation, and displayed further inhibitory activity by promoting mesenchyme homeobox 2 (Meox2) and suppressing activating protein 1 (AP-1). In contrast, Ad-shRNF10 had an opposite effect on neointimal hyperplasia and VSMC hyperproliferation in vivo and in vitro. Our study indicated that RNF10 inhibited the hyperproliferation with the activities of Meox2 and AP-1 proteins. RNF10 may be a next drug target for treating vascular restenosis and other related cardiovascular diseases. © 2018 IUBMB Life, 71(5):632-642, 2019.


Assuntos
Proteínas de Transporte/metabolismo , Proliferação de Células , Reestenose Coronária/prevenção & controle , Hiperplasia/prevenção & controle , Síndrome Metabólica/fisiopatologia , Músculo Liso Vascular/citologia , Neointima , Proteínas do Tecido Nervoso/metabolismo , Adenoviridae/fisiologia , Infecções por Adenoviridae/virologia , Angioplastia Coronária com Balão/efeitos adversos , Animais , Proteínas de Transporte/genética , Movimento Celular , Células Cultivadas , Reestenose Coronária/etiologia , Reestenose Coronária/patologia , Dieta Hiperlipídica/efeitos adversos , Hiperplasia/etiologia , Hiperplasia/patologia , Masculino , Síndrome Metabólica/etiologia , Músculo Liso Vascular/metabolismo , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
17.
Colloids Surf B Biointerfaces ; 174: 587-597, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30504039

RESUMO

We report a multistep strategy of biochemical surface modifications that resulted in the synthesis of new, effective and biocompatible intravascular implants coating with immobilized anti-CD133 antibodies, that proved to be the most effective in endothelial progenitor cells capture and reduced smooth muscle cells growth. Biomolecules were immobilized on differently functionalized surfaces. The distribution, nanostructural characteristics and intramolecular interactions of anti-CD133 molecules as well as their ability to bind EPCs was evaluated. We also tempted to build a molecular model of the CD133 protein to study antigen-antibody interactions. CD133 protein is expressed in endothelial progenitor cells (EPCs). Absence of preferential interaction site on CD133, but rather a presence of a small binding area, may be the specificity of reconnaissance sequence, thus importantly increasing the probability of CD133 protein binding. After all, regarding our molecular model, we are convinced that specific, and large enough interactions between anti-CD133 coating stent surface and CD133 present on EPCs will reduce risk of restenosis by favoring the endothelial growth. Additionally, the safety study of the vivo performance of modified titania based surface was performed using small animal models. No allergological or toxical local or systemic adverse effects of the developed coatings were noted.


Assuntos
Antígeno AC133/imunologia , Anticorpos Imobilizados/imunologia , Adesão Celular , Proliferação de Células , Células Progenitoras Endoteliais/fisiologia , Miócitos de Músculo Liso/citologia , Stents , Animais , Anticorpos Imobilizados/química , Anticorpos Monoclonais/imunologia , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Reestenose Coronária/prevenção & controle , Células Progenitoras Endoteliais/citologia , Feminino , Cobaias , Humanos , Masculino , Ratos , Ratos Wistar
18.
J Invasive Cardiol ; 31(1): 10-14, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30418164

RESUMO

OBJECTIVES: Early endothelialization of drug-eluting stent (DES) is a major challenge to reduce the risk of stent thrombosis and the duration of dual-antiplatelet therapy (DAPT) in high bleeding-risk patients. The aim of the present study is to evaluate very early strut coverage with optical coherence tomography (OCT) of the Synergy stent (Boston Scientific) at 1 month in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients. METHODS: This substudy of the EARLY trial prospectively included NSTE-ACS patients treated with the Synergy DES. OCT analysis of the Synergy stent was performed during a staged PCI of additional lesions at 1 month. The primary endpoint was the percentage of covered struts assessed with OCT at 1 month. RESULTS: Twenty-four patients were included, with a mean stent length of 35.9 ± 10.1 mm per patient. The rate of covered struts was 78.5% out of 3839 struts analyzed. Nineteen patients (79.2%) had at least 70% of their struts covered. The average neointimal thickness was 0.0508 ± 0.016 mm. CONCLUSIONS: In NSTE-ACS patients undergoing culprit percutaneous coronary intervention with the Synergy stent, the rate of covered struts at 1 month was 78.5%. This rapid coverage is in line with the results of clinical trials demonstrating the safety of short-duration DAPT in selected patients who are at high bleeding risk and treated with new-generation DES options.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Angioplastia Coronária com Balão/métodos , Reestenose Coronária/diagnóstico por imagem , Stents Farmacológicos , Infarto do Miocárdio/cirurgia , Tomografia de Coerência Óptica/métodos , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão/instrumentação , Angiografia Coronária/métodos , Reestenose Coronária/prevenção & controle , Everolimo/farmacologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Neointima/diagnóstico por imagem , Estudos Prospectivos , Desenho de Prótese , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Int J Pharm ; 554: 212-223, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30408532

RESUMO

Nanoparticles (NPs) can be used to locally deliver anti-restenosis drugs when they are infused directly to the injured arteries after intervention procedures such as angioplasty. However, the efficacy of transferring NPs via infusion to the arterial wall is limited, at least partially, due to poor NP retention on the inner artery wall. To improve NP retention, angioplasty balloons coated with drug-loaded NPs were fabricated via either layer-by-layer (LbL) electrostatic coating or acrylic-based hydrogel (AAH) coating techniques. Three types of NPs, namely poly (lactide-co-glycolide) (PLGA), biodegradable photo-luminescent PLGA and urethane doped polyester were studied. The transfer efficacy of NPs from various coatings to the arterial wall were further evaluated to find the optimal coating conditions. The ex vivo NP transfer studies showed significantly more NPs being transferred to the rat arterial wall after the angioplasty procedure by the AAH coating (95% transfer efficiency) compared to that of the LbL technique (60%) and dip coating (20%) under flow conditions (10 dyn/cm2). Our results suggest that the AAH coating of drug-loaded NPs on the angioplasty balloon could potentially provide superior retention of drug-loaded NPs onto the arterial wall for a better local delivery of drug-loaded NPs to effectively treat arterial diseases.


Assuntos
Angioplastia Coronária com Balão/métodos , Reestenose Coronária/prevenção & controle , Sistemas de Liberação de Medicamentos , Nanopartículas , Animais , Artérias/metabolismo , Doenças Cardiovasculares/terapia , Substâncias Luminescentes/química , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos , Uretana/química
20.
Disabil Rehabil ; 41(24): 2881-2887, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-29991296

RESUMO

Purpose: The purpose of this study is to evaluate the effects of rehabilitation exercise on coronary artery of the patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).Methods: We searched Medline, EMBASE, Cochrane CENTRAL databases, ISI Web of Science databases, Chinese Biological Medicine Data Base, Chinese knowledge resources, and Wan Fang database. Two researchers independently screened the literature databases, and assessed methodological qualities using the Physiotherapy Evidence Database scale and extracted data.Results: The coronary restenosis rate in rehabilitation exercise group was 10.8% (23/212), and that in the control group was 21% (48/229). Patients with rehabilitation exercise showed a significant reduction in restenosis rate, compared to the control group ((pooled OR: 0.46, 95% CI: 0.26-0.82, p < 0.01); heterogeneity: Chi2=3.86, df =5 (p = 0.57); I2=0%). In addition, the late luminal loss per stent in the rehabilitation exercise group was significantly smaller than that in the control group ((pooled MD: -0.33, 95% CI: -0.52 to -0.13, p < 0.01); heterogeneity: Chi2=0.27, df =1 (p = 0.60); I2=0%).Conclusions: Appropriate rehabilitation exercise reduces the incidence of coronary restenosis after PCI in patients with CHD and contributes to a significant reduction in late luminal loss in the stented coronary segment.Implications for RehabilitationAppropriate rehabilitation exercise can reduce the incidence of coronary restenosis after percutaneous coronary intervention in patients with coronary heart disease.Appropriate rehabilitation exercise contributes to a reduction in late luminal loss in the stented coronary segment.


Assuntos
Doença da Artéria Coronariana/cirurgia , Reestenose Coronária/prevenção & controle , Terapia por Exercício/métodos , Intervenção Coronária Percutânea/reabilitação , Humanos , Resultado do Tratamento
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