RESUMO
Spontaneous coronary artery dissection (SCAD) is diagnosed in a very small percentage of patients with suspected acute coronary syndromes who undergo emergency coronary angiography. Although fibromuscular dysplasia (FMD) is known to coexist in patients with SCAD, the vascular sites of FMD and their frequency have not yet been clarified. We retrospectively reviewed the medical records of 16 patients who were diagnosed with and treated for SCAD at our hospital between 1 January 2011 and 31 January 2023. We have summarized their baseline and clinical characteristics and medical variables, including coronary and upper extremity angiography and in-hospital outcomes. One of our patients had concurrent cardiac tamponade requiring pericardial drainage, and another went into hemorrhage shock the following day from dissection of the gastric retroperitoneal artery. Characteristic angiographic features of partial or diffuse nonatherosclerotic stenosis were observed mainly in the distal parts of the coronary arteries or their branches. Notably, in six patients with SCAD who underwent upper extremity angiography, FMD of the brachial artery was revealed. For the first time, to our knowledge, we found a high prevalence of multifocal FMD of the brachial artery in patients with SCAD.
Assuntos
Anomalias dos Vasos Coronários , Displasia Fibromuscular , Doenças Vasculares , Humanos , Estudos Retrospectivos , Vasos Coronários/diagnóstico por imagem , Artéria Braquial/diagnóstico por imagem , Displasia Fibromuscular/diagnóstico , Displasia Fibromuscular/diagnóstico por imagem , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia , Angiografia Coronária , Extremidade Superior , Anomalias dos Vasos Coronários/diagnóstico , Anomalias dos Vasos Coronários/diagnóstico por imagemRESUMO
TAVI is an established therapy for patients with severe aortic stenosis. Rapid or control pacing is necessary for TAVI, and most centers are familiar with right ventricular (RV) pacing. Although there are several reports on the efficacy and safety of LV pacing, they are still few. In addition, LV pacing has not been studied for different LV guidewires. Our aim is to study the effectiveness of left ventricular (LV) pacing and the thresholds of LV guidewires in patients who underwent transcatheter aortic valve implantation (TAVI). We retrospectively analyzed 252 consecutive patients who underwent trans-femoral TAVI (TF-TAVI) with LV pacing in our institute between December 2017 and November 2020. We excluded 48 patients from the total cohort due to TAVI with RV pacing, and the remaining 204 patients were analyzed (52 males, mean age 85 ± 5 years). Among them, 202 patients (99.0%) had successful LV pacing. In the two patients with failed LV pacing, SAFARI2™ Small was used. The CONFIDA™ group (n = 34) showed a significantly lower threshold than the SAFARI2™ group (n = 163) (median 3.0 vs. 5.0 V; P = 1.1 × 10-7). LV pacing with Lunderquist® was successful in all patients (n = 7). LV pacing in TAVI was an effective and safe strategy. CONFIDA™ wire may be particularly well suited for LV pacing in TAVI.
Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Estudos Retrospectivos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitrated derivative of guanosine 3',5'-cyclic monophosphate (cGMP) formed endogenously under conditions associated with production of both reactive oxygen species and nitric oxide. It acts as an electrophilic second messenger in the regulation of cellular signaling by inducing a post-translational modification of redox-sensitive protein thiols via covalent adduction of cGMP moieties to protein thiols (protein S-guanylation). Here, we demonstrate that 8-nitro-cGMP potentially S-guanylates thiol groups of cGMP-dependent protein kinase (PKG), the enzyme that serves as one of the major receptor proteins for intracellular cGMP and controls a variety of cellular responses. S-Guanylation of PKG was found to occur in a site specific manner; Cys42 and Cys195 were the susceptible residues among 11 Cys residues. Importantly, S-guanylation at Cys195, which is located in the high-affinity cGMP binding domain of PKG, causes persistent enzyme activation as determined by in vitro kinase assay as well as by an organ bath assay. In vivo, S-guanylation of PKG was demonstrated to occur in mice without any specific treatment and was significantly enhanced by lipopolysaccharide administration. These findings warrant further investigation in terms of the physiological and pathophysiological roles of S-guanylation-dependent persistent PKG activation.
Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Guanina/metabolismo , Nucleotídeos Cíclicos/metabolismo , Proteínas/metabolismo , Animais , Ativação Enzimática , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/enzimologia , Miocárdio/metabolismoAssuntos
Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral , Cateterismo Cardíaco , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Anuloplastia da Valva Mitral/efeitos adversos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Resultado do TratamentoRESUMO
Endothelial and vascular smooth muscle dysfunction of epicardial coronary arteries play a pivotal role in the pathogenesis of vasospastic angina (VSA). However, coronary microvascular (MV) function in patients with VSA is not fully understood. In the present study, subjects without coronary obstruction were divided into two groups according to the acetylcholine provocation test: VSA group (n = 29) and non-VSA group (n = 21). Hyperemic MV resistance (hMR) was measured using a dual-sensor (Doppler velocity and pressure)-equipped guidewire, and guidewire-derived hemodynamic parameters were compared. There were no between-group differences in clinical demographics, including potential factors affecting MV function (e.g., diabetes). Although coronary flow velocity reserve was similar between the two groups [2.4 ± 1.0 (VSA group) vs. 2.4 ± 0.9 (non-VSA group); P = 0.8], coronary vessel resistance and hMR were significantly elevated in the VSA group compared with the non-VSA group (2.6 ± 3.1 vs. 1.2 ± 0.8, P = 0.04; 1.9 ± 0.6 vs. 1.6 ± 0.5, P = 0.03, respectively). Coronary vasospasm, older age, E/e', and estimated glomerular filtration rate were significantly associated with MV dysfunction [defined as ≥ median value of hMR (1.6)] in univariate analysis. Coronary vasospasm most strongly predicted higher hMR in multivariate logistic regression analysis (odds ratio, 4.61; 95% confidence interval, 0.98-21.60; P = 0.053). In conclusion, coronary MV resistance is impaired in patients with VSA compared with non-VSA patients, whereas coronary flow velocity reserve is maintained at normal levels in both groups. In vivo assessment of hMR might be a promising index of coronary MV dysfunction in patients with VSA.
Assuntos
Angina Pectoris/fisiopatologia , Vasoespasmo Coronário/fisiopatologia , Microcirculação , Resistência Vascular , Acetilcolina/farmacologia , Idoso , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hiperemia/fisiopatologia , Fluxometria por Laser-Doppler , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Cardiovascular disease (CVD), the most common morbidity resulting from atherosclerosis, remains a frequent cause of death. Efforts to develop effective therapeutic strategies have focused on vascular inflammation as a critical pathology driving atherosclerosis progression. Nonetheless, molecular mechanisms underlying this activity remain unclear. Here, we ask whether angiopoietin-like protein 2 (Angptl2), a proinflammatory protein, contributes to vascular inflammation that promotes atherosclerosis progression. APPROACH AND RESULTS: Histological analysis revealed abundant Angptl2 expression in endothelial cells and macrophages infiltrating atheromatous plaques in patients with cardiovascular disease. Angptl2 knockout in apolipoprotein E-deficient mice (ApoE(-/-)/Angptl2(-/-)) attenuated atherosclerosis progression by decreasing the number of macrophages infiltrating atheromatous plaques, reducing vascular inflammation. Bone marrow transplantation experiments showed that Angptl2 deficiency in endothelial cells attenuated atherosclerosis development. Conversely, ApoE(-/-) mice crossed with transgenic mice expressing Angptl2 driven by the Tie2 promoter (ApoE(-/-)/Tie2-Angptl2 Tg), which drives Angptl2 expression in endothelial cells but not monocytes/macrophages, showed accelerated plaque formation and vascular inflammation because of increased numbers of infiltrated macrophages in atheromatous plaques. Tie2-Angptl2 Tg mice alone did not develop plaques but exhibited endothelium-dependent vasodilatory dysfunction, likely because of decreased production of endothelial cell-derived nitric oxide. Conversely, Angptl2(-/-) mice exhibited less severe endothelial dysfunction than did wild-type mice when fed a high-fat diet. In vitro, Angptl2 activated proinflammatory nuclear factor-κB signaling in endothelial cells and increased monocyte/macrophage chemotaxis. CONCLUSIONS: Endothelial cell-derived Angptl2 accelerates vascular inflammation by activating proinflammatory signaling in endothelial cells and increasing macrophage infiltration, leading to endothelial dysfunction and atherosclerosis progression.
Assuntos
Angiopoietinas/metabolismo , Aterosclerose/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Mediadores da Inflamação/metabolismo , Vasculite/metabolismo , Idoso de 80 Anos ou mais , Proteína 2 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Angiopoietinas/deficiência , Angiopoietinas/genética , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Transplante de Medula Óssea , Células Cultivadas , Quimiotaxia de Leucócito , Dieta Hiperlipídica , Modelos Animais de Doenças , Progressão da Doença , Dislipidemias/metabolismo , Dislipidemias/fisiopatologia , Células Endoteliais/imunologia , Células Endoteliais/patologia , Endotélio Vascular/imunologia , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Integrina alfa5beta1/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Monócitos/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Óxido Nítrico/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Placa Aterosclerótica , Transdução de Sinais , Fatores de Tempo , Vasculite/genética , Vasculite/imunologia , Vasculite/patologia , Vasculite/prevenção & controle , VasodilataçãoRESUMO
Peri-procedural myocardial damage (MD) is associated with increased risk of major in-hospital complications and adverse clinical events. The aim of this study was to evaluate the effects of on-clopidogrel platelet aggregation and CYP2C19-reduced-function gene variants on elective percutaneous coronary intervention (PCI)-related MD. We measured changes in serum high-sensitive troponin T (hs-TnT) levels, CYP2C19 genotype, and on-clopidogrel platelet aggregation (PA) using VerifyNow(®) P2Y12 system in 91 patients who received stent implantation (stent group). The control group comprised 30 patients who did not receive PCI. Blood samples were obtained before and 24 h after PCI or coronary angiography (CAG). Patients of the stent group were divided into high and low MD groups based on the median value of hs-TnT level at 24 h after PCI. Serum hs-TnT levels were significantly higher 24 h after PCI (86.8 ± 121.5 pg/ml) compared with before PCI (9.4 ± 5.3, p < 0.001), whereas the levels were identical before and 24 h after CAG in the control group. Simple logistic regression analysis demonstrated that MD correlated with age (p = 0.014), estimated GFR (p = 0.003), hemoglobin A1c (p = 0.015), baseline serum hs-TnT (p = 0.049), and stent length (p < 0.001). Multiple logistic regression analysis identified old age, high hemoglobin A1c level, and long stent, but not CYP2C19 reduced-function allele or high on-clopidogrel PA, as independent predictors of elective PCI-related MD. The present study demonstrated no significant relation between peri-procedural MD and high on-clopidgrel PA associated with CYP2C19 reduced-function allele in patients undergoing elective PCI.
Assuntos
Doença da Artéria Coronariana/genética , Citocromo P-450 CYP2C19/genética , DNA/genética , Procedimentos Cirúrgicos Eletivos/métodos , Miocárdio/metabolismo , Intervenção Coronária Percutânea , Polimorfismo Genético , Idoso , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/cirurgia , Citocromo P-450 CYP2C19/metabolismo , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Período Pré-OperatórioRESUMO
Despite current standards of care aimed at achieving targets for low-density lipoprotein cholesterol (LDL-C), many patients remain at high residual risk of cardiovascular events. We sought to assess the LDL-C-dependent differences in culprit intravascular ultrasound (IVUS) morphologies and clinical characteristics in patients with acute coronary syndrome (ACS). Eighty-six consecutive ACS patients whose culprit lesions imaged by preintervention IVUS were divided into two groups based on the fasting LDL-C level on admission: a low-LDL-C group (LDL-C <2.6 mmol/l, n = 45) and a high-LDL-C group (LDL-C ≥2.6 mmol/l, n = 41). Patients with stable angina with LDL-C <2.6 mmol/l (n = 30) were also enrolled as an age- and gender-matched control. The low-LDL-C ACS group was significantly older (72 ± 12 vs 64 ± 14 years, P = 0.007) and more diabetic (47 % vs 15 %, P = 0.001). Importantly, IVUS morphologies were comparable between low- and high-LDL-C ACS groups (all P not significant), whereas culprit plaque was more hypoechoic and less calcified in the low-LDL-C ACS group than in the low-LDL-C stable angina group. Furthermore, compared with the low-LDL-C ACS nondiabetic group, the low-LDL-C ACS diabetic group was more obese, more triglyceride rich (1.3 ± 0.6 vs 0.9 ± 0.4 mmol/l, P = 0.003), and more endothelially injured, but no different for the culprit IVUS morphologies. In multivariate analysis, diabetes was independently associated with a low LDL-C level on admission in patients with ACS. There was no relationship between the LDL-C level at onset and culprit-plaque IVUS morphologies in ACS patients, although culprit plaque in the low-LDL-C ACS group was more vulnerable than in the low-LDL-C stable angina group. In patients with low-LDL-C levels, diabetes with atherogenic dyslipidemia might be the key residual risk.
Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , LDL-Colesterol/sangue , Vasos Coronários/diagnóstico por imagem , Dislipidemias/sangue , Ultrassonografia de Intervenção , Síndrome Coronariana Aguda/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angina Estável/diagnóstico por imagem , Angina Estável/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Comorbidade , Estudos Transversais , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Placa Aterosclerótica , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
PURPOSE: Mechanical circulatory support (MCS) using a venoarterial extracorporeal membrane oxygenation (VA-ECMO) device or a catheter-type heart pump (Impella) is critical for the rescue of patients with severe cardiogenic shock. However, these MCS devices require large-bore cannula access (14-Fr and larger) at the femoral artery or vein, which often requires surgical decannulation. METHODS: In this retrospective study, we evaluated post-closure method using a percutaneous suture-mediated vascular closure system, Perclose ProGlide/ProStyle (Abbott Vascular, Lake Bluff, IL, Perclose), as an alternative procedure for MCS decannulation. Closure of 83 Impella access sites and 68 VA-ECMO access sites performed using Perclose or surgical method between January 2018 and March 2023 were evaluated. RESULTS: MCS decannulation using Perclose was successfully completed in all access sites without surgical hemostasis. The procedure time of ProGlide was shorter than surgical decannulation for both Impella and VA-ECMO (13 min vs. 50 min; p < 0.001, 21 min vs. 65 min; p < 0.001, respectively). There were no significant differences in the 30-day survival rate and major adverse events by decannulation including arterial dissection requiring endovascular treatment, hemorrhage requiring a large amount of red blood cell transfusion, and access site infection. CONCLUSION: Our results suggest that the post-closure technique using the percutaneous suture-mediated closure system appears to be a safe and effective method for large-bore MCS decannulation.
Assuntos
Cateterismo Periférico , Oxigenação por Membrana Extracorpórea , Coração Auxiliar , Técnicas Hemostáticas , Punções , Dispositivos de Oclusão Vascular , Humanos , Estudos Retrospectivos , Masculino , Feminino , Resultado do Tratamento , Pessoa de Meia-Idade , Idoso , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/instrumentação , Fatores de Tempo , Técnicas Hemostáticas/instrumentação , Técnicas Hemostáticas/efeitos adversos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/instrumentação , Remoção de Dispositivo/efeitos adversos , Técnicas de Sutura/instrumentação , Técnicas de Sutura/efeitos adversos , Artéria Femoral , Choque Cardiogênico/terapia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Choque Cardiogênico/diagnóstico , Fatores de Risco , Hemorragia/etiologia , Hemorragia/prevenção & controleRESUMO
Subclinical leaflet thrombosis (SLT) can be one of the causes of transcatheter heart valve (THV) failure after transcatheter aortic valve implantation (TAVI). We sought to clarify the formation process of SLT and thrombogenicity during the perioperative period of TAVI. This multicenter, prospective, single-arm interventional study enrolled 26 patients treated with edoxaban for atrial fibrillation and who underwent TAVI for severe aortic stenosis between September 2018 and September 2022. We investigated changes in maximal leaflet thickness detected by contrast-enhanced computed tomography between 1 week and 3 months after TAVI in 18 patients and measured the thrombogenicity by Total Thrombus-formation Analysis System (T-TAS) and flow stagnation volume by computational fluid dynamics (CFD) (n = 11). SLT was observed in 16.7% (3/18) at 1 week, but decreased to 5.9% (1/17) at 3 months after TAVI. Patients with SLT at 1 week had a significantly decreased maximal leaflet thickness compared to those without SLT. Thrombogenicity assessed by T-TAS decreased markedly at 1 week and tended to increase at 3 months. The stagnation volume assessed by CFD was positively associated with a higher maximum leaflet thickness. This study showed the course of leaflet thrombus formation and visualization of stagnation in neo-sinus of THV in the acute phase after TAVI.
Assuntos
Estenose da Valva Aórtica , Fibrilação Atrial , Trombose , Substituição da Valva Aórtica Transcateter , Humanos , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Substituição da Valva Aórtica Transcateter/efeitos adversos , Trombose/etiologia , Feminino , Masculino , Idoso de 80 Anos ou mais , Idoso , Estudos Prospectivos , Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/patologia , Índice de Gravidade de Doença , Piridinas/uso terapêutico , TiazóisRESUMO
Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice transplanted with wild-type tissue. RT-PCR analysis revealed that mouse Angptl2 expression in perivascular adipose tissue was significantly increased by aging, hypercholesterolemia, and endovascular injury, all risk factors for coronary heart disease (CHD). Immunohistochemical and RT-PCR analysis of tissues from patients with CHD and from non-CHD patients indicated that ANGPTL2 expression in epicardial adipose tissue was unchanged. Interestingly, that analysis also revealed a positive correlation in ANGPTL2 and ADIPONECTIN expression in epicardial adipose tissue of non-CHD patients, a correlation not seen in CHD patients. However, in epicardial adipose tissue from CHD patients, ANGPTL2 expression was positively correlated with that of TNF-α, a correlation was not seen in non-CHD patients. These findings suggest that pro-inflammatory adipokines cooperatively accelerate CHD development and that maintaining a balance between pro- and anti-inflammatory adipokines likely protects non-CHD patients from developing CHD. Overall, our studies demonstrate that perivascular adipose tissue-secreted Angptl2 accelerates vascular inflammation and the subsequent CVD development.
Assuntos
Tecido Adiposo/metabolismo , Angiopoietinas/metabolismo , Neointima/metabolismo , Lesões do Sistema Vascular/metabolismo , Adiponectina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína 2 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Angiopoietinas/genética , Animais , Criança , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Citocinas/genética , Citocinas/metabolismo , Feminino , Artéria Femoral/metabolismo , Artéria Femoral/patologia , Expressão Gênica , Humanos , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hiperplasia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Neointima/patologia , Ativação Transcricional , Lesões do Sistema Vascular/patologiaRESUMO
OBJECTIVES: The present study used iMap IVUS system to compare neointimal tissue components between DES and bare-metal stents (BMSs). BACKGROUND: Drug-eluting stents (DESs) can cause impaired arterial healing, which constitutes the most important pathological substrate underlying late DES thrombosis. Intravascular ultrasound (IVUS)-based tissue characterization allows for the in vivo identification of neointimal tissue components. METHODS AND RESULTS: Follow-up IVUS data after coronary stenting (9.8 ± 9.4 months from index procedures) was obtained from consecutive 61 lesions (34 in DES, 27 in BMS). The iMap tissue components (fibrotic, lipidic, necrotic, and calcified) were measured in every recorded frame and expressed as percentages of mean neointimal cross-sectional area for the stented segment. Patients' characteristics were comparable between DES and BMS. When compared with BMSs, smaller (2.9 ± 0.4 mm vs. 3.2 ± 0.4 mm, P = 0.004) and longer (34 ± 18 mm vs. 26 ± 14 mm, P = 0.03) DESs were implanted. When compared with BMS group, minimum lumen area at follow-up was significantly greater in DES group (3.9 ± 1.8 mm(2) vs. 3.1 ± 1.5 mm(2) , P < 0.04), mainly attributable to suppression of neointimal hyperplasia (1.7 ± 0.8 mm(2) vs. 3.1 ± 1.5 mm(2) , P < 0.0001). The iMap analyses showed that neointima after DES placement was composed of smaller fibrotic component (67 ± 8% vs. 78 ± 7%, P < 0.0001), larger necrotic (14 ± 4% vs. 9 ± 3%, P < 0.0001) and calcified (15 ± 6% vs. 7 ± 4%, P < 0.0001) components compared with BMS. Logistic regression analysis showed that only intra-DES neointima was a significant predictor of necrotic neointima at follow-up. CONCLUSIONS: DES implantation would be associated with iMap-derived necrotic and less-fibrotic neointimal formation. In vivo iMap evaluation of neointimal tissue may provide useful information in detecting impaired healing after stenting.
Assuntos
Doença da Artéria Coronariana/terapia , Vasos Coronários/diagnóstico por imagem , Stents Farmacológicos , Metais , Neointima , Intervenção Coronária Percutânea/instrumentação , Stents , Ultrassonografia de Intervenção , Idoso , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Estudos Transversais , Feminino , Fibrose , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Necrose , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/diagnóstico por imagem , CicatrizaçãoRESUMO
OBJECTIVE: Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). METHODS AND RESULTS: Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl(2)-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. CONCLUSIONS: Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.
Assuntos
Angiopoietinas/metabolismo , Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Macrófagos/metabolismo , Proteína 2 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Angiopoietinas/deficiência , Angiopoietinas/genética , Animais , Aorta Abdominal/imunologia , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/imunologia , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/prevenção & controle , Transplante de Medula Óssea , Cloreto de Cálcio , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Genótipo , Humanos , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , FenótipoRESUMO
Background: Coronary cannulation after TAVR is sometimes difficult due to an overlap between native and neo-commissures, especially in Evolut devices with a supra-annular position. The Evolut C-tab corresponds to a neo-commissure, and the hat marker is in a fixed position. Therefore, the orientation of the hat marker can be adjusted to minimise overlaps. Aims: We investigated whether the HAt marker-guided SHaft rotation method (HASH, stylised as the #rotation method) is effective in facilitating coronary artery access after transcatheter aortic valve replacement (TAVR) with an Evolut system. Methods: We retrospectively analysed 95 patients who underwent electrocardiogram-gated cardiac computed tomography after TAVR. In the #rotation method, the hat marker of the delivery catheter was adjusted to face the greater curvature of the descending thoracic aorta in the left anterior oblique view. Its orientation was maintained while the system passed through the aortic arch. Results: In total, 60 and 35 patients underwent TAVR with the #rotation and non-#rotation methods, respectively. A ±15° angle between the native and neo-commissures was more frequent in the #rotation group (p=0.001). Favourable angles and appropriate frame orientation for access to the left coronary artery were significantly more frequent in the #rotation group than in the non-#rotation group (p<0.001 and p=0.001). Although the #rotation method showed a higher rate of favourable angles and frames in the right coronary artery, statistically significant differences were not found. Conclusions: The #rotation method is useful for improving commissural post alignment in TAVR with Evolut devices, especially in the ostium of the left coronary artery.
RESUMO
OBJECTIVE: To investigate whether and how the endoplasmic reticulum (ER) stress-induced, CCAAT/enhancer-binding protein-homologous protein (CHOP)-mediated pathway regulates myocardial ischemia/reperfusion injury. METHODS AND RESULTS: Wild-type and chop-deficient mice underwent 50 minutes of left coronary artery occlusion followed by reperfusion. Expression of chop and spliced x-box binding protein-1 (sxbp1) mRNA was rapidly and significantly increased in reperfused myocardium of wild-type mice. chop-deficient mice exhibited markedly reduced injury size after reperfusion compared with wild-type mice, accompanied by a decreasing number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cardiomyocytes. Interestingly, myocardial inflammation, as assessed by expression of inflammatory cytokines and chemokines and numbers of infiltrated inflammatory cells, was also attenuated in chop-deficient mice. Moreover, expression of interleukin-6 mRNA in response to lipopolysaccharide was enhanced by simultaneous stimulation with thapsigargin, a potent ER stressor, in wild-type cardiomyocytes but not in chop-deficient cardiomyocytes. Finally, we found that superoxide was produced in reperfused myocardium and that intravenous administration of edaravone, a free radical scavenger, immediately before reperfusion significantly suppressed the superoxide overproduction and subsequent expression of sxbp1 and chop mRNA, followed by reduced injury size in wild-type mice. CONCLUSIONS: The ER stress-induced, CHOP-mediated pathway, which is activated in part by superoxide overproduction after reperfusion, exacerbates myocardial ischemia/reperfusion injury by inducing cardiomyocyte apoptosis and myocardial inflammation.
Assuntos
Apoptose , Retículo Endoplasmático/metabolismo , Inflamação/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Fator de Transcrição CHOP/deficiência , Animais , Antipirina/análogos & derivados , Antipirina/farmacologia , Apoptose/efeitos dos fármacos , Células Cultivadas , Quimiocinas/metabolismo , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Edaravone , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/imunologia , Sequestradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/imunologia , Miocárdio/patologia , Splicing de RNA , RNA Mensageiro/metabolismo , Fatores de Transcrição de Fator Regulador X , Estresse Fisiológico , Superóxidos/metabolismo , Tapsigargina/farmacologia , Fatores de Tempo , Fator de Transcrição CHOP/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Transcatheter aortic valve implantation (TAVI) represents the standard of care for relieving aortic stenosis in high-risk patients for surgery. The transfemoral approach is preferable with respect to invasiveness, but is often difficult in patients with complex vascular structures. Recently, the clinical application of advanced visualization and guidance technology with three-dimensional computed tomography (3D-CT) during TAVI has received considerable attention. Herein we report successful transfemoral TAVI in a patient with a right-sided aortic arch and chronic aortic dissection without vascular complications by 3D-CT/fluoroscopy fusion imaging guidance.
Assuntos
Dissecção Aórtica , Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Fluoroscopia , Humanos , Tomografia Computadorizada por Raios X , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.
Assuntos
Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/terapia , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/terapia , Terapia por Exercício/métodos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Humanos , Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Razão de Chances , Aptidão Física , Projetos Piloto , Fatores de Risco , Fatores SexuaisRESUMO
AIM: Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: This prospective, observational, multicenter study enrolled 104 consecutive Japanese patients undergoing elective PCI. We examined the CYP2C19 genotype, platelet function tests, the levels of coagulation and inflammatory biomarkers and the serum levels of high-sensitivity troponin T (hs-TnT) before, immediately after and one, two and 28 days after PCI. RESULTS: A total of 68 (65%) of the 104 enrolled patients were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet aggregation (PA), measured using light transmittance aggregometry and the VerifyNow(®) P2Y12 system, and the platelet reactivity index (PRI) were significantly higher at all time points in the carriers than in the noncarriers (pï¼0.05), whereas there were no differences in the levels of the coagulation and inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression analyses identified on-clopidogrel PA and PRI as being significant predictors of carriers of the CYP2C19 reduced-function allele. CONCLUSIONS: The present study suggests that platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of DAPT in patients undergoing elective PCI.
Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Coagulação Sanguínea/genética , Inflamação/genética , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/genética , Polimorfismo Genético/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Biomarcadores/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Citocromo P-450 CYP2C19 , Feminino , Genótipo , Heterozigoto , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária , Estudos ProspectivosRESUMO
BACKGROUND: Some plaques lead to ST-segment elevation myocardial infarction (STEMI), whereas others cause non-ST-segment elevation acute coronary syndrome (NSTEACS). We used angiography and intravascular ultrasound (IVUS) to investigate the difference of culprit lesion morphologies in ACS. METHODS: Consecutive 158 ACS patients whose culprit lesions were imaged by preintervention IVUS were enrolled (STEMI=81; NSTEACS=77). IVUS and angiographic findings of the culprit lesions, and clinical characteristics were compared between the groups. RESULTS: There were no significant differences in patients' characteristics except for lower rate of statin use in patients with STEMI (20% vs 44%, p=0.001). Although angiographic complex culprit morphology (Ambrose classification) and thrombus were more common in STEMI than in NSTEACS (84% vs 62%, p=0.002; 51% vs 5%, p<0.0001, respectively), SYNTAX score was lower in STEMI (8.6 ± 5.4 vs 11.5 ± 7.1, p=0.01). In patients with STEMI, culprit echogenicity was more hypoechoic (64% vs 40%, p=0.01), and the incidence of plaque rupture, attenuation and "microcalcification" were significantly higher (56% vs 17%, p<0.0001; 85% vs 69%, p=0.01; 77% vs 61%, p=0.04, respectively). Furthermore, the maximum area of ruptured cavity, echolucent zone and arc of microcalcification were significantly greater in STEMI compared with NSTEACS (1.80 ± 0.99 mm(2) vs 1.13 ± 0.86 mm(2), p=0.006; 1.52 ± 0.74 mm(2) vs 1.21 ± 0.81 mm(2), p=0.004; 99.9 ± 54.6° vs 77.4 ± 51.2°, p=0.01, respectively). Quantitative IVUS analysis showed that vessel and plaque area were significantly larger at minimum lumen area site (16.6 ± 5.4 mm(2) vs 14.2 ± 5.5 mm(2), p=0.003; 13.9 ± 5.1 mm(2) vs 11.6 ± 5.2 mm(2), p=0.003, respectively). CONCLUSION: Morphological feature (outward vessel remodeling, plaque buildup and IVUS vulnerability of culprit lesions) might relate to clinical presentation in patients with ACS.
Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária/normas , Infarto do Miocárdio/diagnóstico por imagem , Ultrassonografia de Intervenção/normas , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagemRESUMO
BACKGROUND: The prevalence, clinical features, and long-term outcome of patients with non-ST-segment elevation acute coronary syndrome (NSTE ACS) associated with coronary spasm are not fully investigated. METHODS AND RESULTS: This observational multicenter study enrolled 1601 consecutive patients with suspected NSTE-ACS who underwent cardiac catheterization between January 2001 and December 2010. A culprit lesion was found in 1152 (72%) patients. In patients without a culprit lesion, the acetylcholine provocation test was performed in 221 patients and was positive in 175 patients. In the other patients, coronary spasm was verified in 145 patients during spontaneous attack. Spasm-induced NSTE-ACS was diagnosed in 320 (20%) patients. Multivariable analysis identified age <70 years (odds ratio [OR] 2.19, 95% CI 1.58 to 3.04), estimated glomerular filtration rate >60 mL/min per 1.73 m(2) (OR 1.72, 95% CI 1.16 to 2.56), and lack of hypertension (OR 2.55, 95% CI 1.90 to 3.41), dyslipidemia (OR 2.76, 95% CI 2.05 to 3.73), diabetes mellitus (OR 2.49, 95% CI 1.78 to 3.48), previous myocardial infarction (OR 5.37, 95% CI 2.89 to 10.0), and elevated cardiac biomarkers (OR 2.84, 95% CI 2.11 to 3.83) as significant correlates of spasm-induced NSTE-ACS (P<0.01 for all variables). Transient ST-segment elevation during spontaneous attack (variant angina) was observed in 119 patients with spasm-induced NSTE-ACS. Variant angina was more common in nondyslipidemic men among patients with spasm-induced NSTE-ACS. CONCLUSIONS: The study showed frequent involvement of coronary spasm in the pathogenesis of NSTE-ACS. Variant angina was observed in one third of patients with spasm-induced NSTE-ACS. Coronary spasm should be considered even in patients with less coronary risk factors and nonobstructive coronary arteries.