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1.
J Am Soc Echocardiogr ; 29(9): 819-826.e4, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27288090

RESUMO

BACKGROUND: Transthoracic echocardiography (TTE), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI) have been widely used to monitor aortic diameters, with no consensus as to the best measurement approach. Thus, the aim of this study was to establish the best measurement methods by two-dimensional (2D) TTE, MDCT, and MRI to achieve comparable aortic diameters. METHODS: One hundred forty patients with severe aortic valvular disease or aortic dilatation were prospectively evaluated using 2D TTE and MDCT (n = 70) or MRI (n = 70). The aorta was measured at three different levels: sinuses of Valsalva, sinotubular junction, and ascending aorta. Three different measurements were made by 2D TTE-inner edge to inner edge, leading edge to leading edge (L-L), and outer edge to outer edge-and then compared with the inner edge-to-inner edge and outer edge-to-outer edge measurements of cusp-to-cusp and cusp-to-commissure diameters by MDCT or MRI. Inter- and intraobserver variability was analyzed. RESULTS: Aortic diameters by 2D TTE, MDCT, and MRI showed excellent inter- and intraobserver variability using all conventions. Significant underestimation was observed of all aortic diameters assessed by 2D TTE using the inner edge-to-inner edge convention compared with those obtained by MDCT or MRI (P < .0001). However, excellent accuracy was observed by 2D TTE when the L-L convention was used and compared with the internal diameter by MDCT and MRI (mean differences, 0.6 ± 2.6 mm [P = .158] for MDCT and 0.4 ± 3.5 mm [P = .852] for MRI). Cusp-to-cusp diameters were slightly larger than cusp-to-commissure diameters. The diameter by 2D TTE using the L-L convention correlated best with the noncoronary cusp-to-right coronary cusp diameter determined by both MDCT and MRI. CONCLUSIONS: Aortic root and ascending aortic diameters measured by 2D TTE using the L-L convention showed accurate and reproducible values compared with internal diameters assessed by MDCT or MRI. This approach permits a multimodality follow-up of patients with aortic diseases and avoids disparities in measurements obtained by different conventions.


Assuntos
Aorta/diagnóstico por imagem , Aorta/patologia , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/patologia , Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Idoso , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
Heart ; 102(8): 626-32, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26848186

RESUMO

OBJECTIVE: This study aimed to determine aortic disease severity in patients with Loeys-Dietz syndrome (LDS). METHODS: Thirty-three patients with LDS diagnosed and followed up at our unit were included. After reviewing all family trees, 25 deceased family members with clear clinical suspicion of having had LDS were also included. Clinical presentation, aortic dilation rate by echocardiography and age at aortic surgery, dissection or death were determined. RESULTS: Median aortic diameter at diagnosis was 36 mm, 43% of the patients aged >40 years had a z-score <2. Median aortic root dilation rate was 0.67 mm/year (maximum 2.0 mm/year) over a median follow-up of 2 years (IQR 1.0-4.0). In the global cohort, 31/58 patients reached a clinical endpoint; 19% death, median age: 52 years; 14% dissection, median age: 36 years; 21% aortic surgery, median age: 53 years. As expected, probands had a higher z-score (2.9 vs 1.5, p=0.019) and more often required aortic surgery (33.4% vs 18.2%, p=0.035) compared with family members. TGFBR2 carriers had a higher z-score compared with TGFBR1 carriers (3.2 vs 1.5, p=0.034) and younger age at aortic surgery (HR 4.9, 95% CI 1.5 to 123, p=0.026). Craniofacial severity index was inversely correlated with age at first event (r=-0.765, p=0.045). CONCLUSIONS: Although paediatric patients were not properly represented in our cohort, our patients with LDS presented a significant heterogeneity in the severity of aortic disease with large intrafamilial and interfamilial variability, aortic root aneurysm were less frequent and aortic complications less premature than previously depicted. Furthermore, aortic dilation rate was similar to that reported in Marfan syndrome and aortic root diameters appear to be larger in TGFBR2 carriers.


Assuntos
Síndrome de Loeys-Dietz/genética , Síndrome de Loeys-Dietz/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Dissecção Aórtica/genética , Dissecção Aórtica/patologia , Aneurisma Aórtico/genética , Aneurisma Aórtico/patologia , Aneurisma Aórtico/cirurgia , Criança , Anormalidades Craniofaciais/genética , Dilatação Patológica/genética , Dilatação Patológica/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Síndrome de Loeys-Dietz/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Proteínas Serina-Treonina Quinases/genética , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Índice de Gravidade de Doença , Adulto Jovem
3.
Heart ; 102(5): 376-82, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26802099

RESUMO

OBJECTIVE: To assess the usefulness of hand-held cardiac ultrasound (HCU) performed by family doctors (FDs) in primary care, with web-based remote expert support interpretation, in a cohort of patient with symptoms or physical examination signs suggestive of cardiovascular disease. METHODS: This prospective observational study included 1312 consecutive patients, in three remote primary care areas, with symptoms or physical examination signs suggestive of cardiovascular disease. In 859 patients (group A), FDs had indicated conventional echocardiography (CE), and in 453 (Group B) the study was performed to complement the physical examination. HCU was carried out by 14 FDs after a short training period. The scans and preliminary FD reports were uploaded on a web-based program for remote expert support interpretation in <24 h. RESULTS: Experts considered HCU to be inconclusive in 116 (8.8%) patients. FD and expert agreement on diagnosis was moderate (K=0.40-0.70) except in mitral stenosis (K=0.29) and in left atrial dilation (K=0.38). Diagnostic agreement between expert interpretation and CE was good (K=0.66-0.85) except in mitral stenosis (K=0.43). After remote expert interpretation, conventional echocardiograms were finally requested by FDs in only 276 (32.1%) patients, and discharges increased by 10.2%. Furthermore, significant heart diseases were diagnosed in 32 (7%) patients of group B. CONCLUSIONS: HCU performed at the point of care by FDs with remote expert support interpretation using a web-based system is feasible, rapid and useful for detecting significant echocardiographic abnormalities and reducing the number of unnecessary echocardiographic studies.


Assuntos
Diagnóstico por Computador/métodos , Ecocardiografia Doppler em Cores/métodos , Cardiopatias/diagnóstico por imagem , Médicos de Família , Testes Imediatos , Atenção Primária à Saúde , Consulta Remota/métodos , Serviços de Saúde Rural , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Doppler em Cores/instrumentação , Educação Médica Continuada , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Cardiopatias/terapia , Humanos , Capacitação em Serviço , Internet , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Médicos de Família/educação , Sistemas Automatizados de Assistência Junto ao Leito , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Espanha , Transdutores , Procedimentos Desnecessários , Adulto Jovem
6.
J Am Coll Cardiol ; 58(9): 977-86, 2011 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-21723061

RESUMO

OBJECTIVES: The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease. BACKGROUND: In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI). METHODS: Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 µg HGF and 2 to 8 µg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging. RESULTS: The IGF-1/HGF activated c-kit positive-CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive-CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI. CONCLUSIONS: In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.


Assuntos
Vasos Coronários/fisiologia , Fator de Crescimento de Hepatócito/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/fisiologia , Células-Tronco/metabolismo , Animais , Diferenciação Celular/fisiologia , Sobrevivência Celular/fisiologia , Vasos Coronários/citologia , Quimioterapia Combinada , Feminino , Fator de Crescimento de Hepatócito/fisiologia , Humanos , Injeções Intra-Arteriais , Fator de Crescimento Insulin-Like I/fisiologia , Miócitos Cardíacos/citologia , Células-Tronco/citologia , Suínos
7.
Front Biosci (Schol Ed) ; 2(2): 641-52, 2010 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-20036974

RESUMO

For a long time the heart has been considered a terminally differentiated organ without any regenerative potential. The latter has been classically based on the terminally differentiated nature of cardiomyocytes and the absence of a pool of tissue-specific stem cells. This view has been radically changed due to the discovery of resident cardiac stem and progenitor cells in the adult mammalian heart. However, at minimum, 5 apparently different cardiac stem and/or progenitor cell types have been described so far. Thus, we have changed from a view of the heart as a static tissue to an organ with the highest number of tissue-specific stem cell populations. Most likely, the different putative adult cardiac stem and progenitor cells represent different developmental and/or physiological stages of a unique resident adult cardiac stem cell. Notably, it is not yet known the origin of all these cells. A better understanding of the origin, biology and physiology of the myocardial stem and progenitor cells will impact the development of regenerative medicine as an effective therapy for heart disease and failure.


Assuntos
Biomarcadores/metabolismo , Coração/embriologia , Miócitos Cardíacos/citologia , Células-Tronco/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/metabolismo , Adulto , Proteínas de Homeodomínio/metabolismo , Humanos , Recém-Nascido , Proteínas com Homeodomínio LIM , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Células-Tronco/classificação , Células-Tronco/citologia , Fatores de Transcrição
8.
Am J Physiol Heart Circ Physiol ; 297(6): H2015-25, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19783773

RESUMO

cAMP inhibits proliferation in most cell types, triggering different and sometimes opposing molecular pathways. p85alpha (phosphatidylinositol 3-kinase regulatory subunit) is phosphorylated by cAMP/PKA in certain cell lineages, but its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are unknown. In the present study, we evaluated 1) the role of p85alpha in the integration of cAMP/PKA-dependent signaling on the regulation of VSMC and EC growth in vitro; and 2) the effects of PKA-modified p85alpha on neointimal hyperplasia and endothelial healing after balloon injury in vivo. Plasmid constructs carrying wild-type and PKA-modified p85alpha were employed in VSMCs and ECs in vitro and after balloon injury in rat carotid arteries in vivo. cAMP/PKA reduced VSMC proliferation through p85alpha phosphorylation. Transfected PKA-activated p85alpha binds p21ras, reducing ERK1/2 activation and VSMC proliferation in vitro. In contrast, EC proliferation inhibition by cAMP is independent from PKA modification of p85alpha and ERK1/2 inhibition; indeed, PKA-activated p85alpha did not inhibit per se ERK1/2 activation and proliferation in ECs in vitro. Interestingly, cAMP reduced both VSMC and EC apoptotic death through p85alpha phosphorylation. Accordingly, PKA-activated p85alpha triggered Akt activation, reducing both VSMC and EC apoptosis in vitro. Finally, compared with controls, vascular gene transfer of PKA-activated p85alpha significantly reduced neointimal formation after balloon injury in rats, without inhibiting endothelial regeneration of the injured arterial segment. In conclusions, PKA-activated p85alpha integrates cAMP/PKA signaling differently in VSMCs and ECs. By reducing neointimal hyperplasia without inhibiting endothelial regeneration, it exerts a protective effect against restenosis after balloon injury.


Assuntos
Lesões das Artérias Carótidas/enzimologia , Proliferação de Células , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Células Endoteliais/enzimologia , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Animais , Apoptose , Lesões das Artérias Carótidas/genética , Lesões das Artérias Carótidas/patologia , Cateterismo , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/patologia , Ativação Enzimática , Hiperplasia , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fosfatidilinositol 3-Quinases/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Transfecção , Proteínas ras/metabolismo
9.
Am J Physiol Heart Circ Physiol ; 292(6): H2935-43, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17293493

RESUMO

Drug-eluting stents are increasingly used to reduce in-stent restenosis and adverse cardiac events after percutaneous coronary interventions. However, the race for the ideal drug-eluting stent is still on, with special regard to the best stent-coating system and the most effective and less toxic drug. Fludarabine, a nucleoside analog, has both anti-inflammatory and antiproliferative cellular effects. The aim of the present study was to assess the cellular and molecular effects of fludarabine on vascular smooth muscle cell (VSMC) growth in vitro and in vivo and the feasibility and efficacy of a fludarabine-eluting stent. To study the biomolecular effects of fludarabine on VSMC proliferation in vitro, rat VSMCs were grown in the presence of 50 microM fludarabine or in the absence of the same. To evaluate the in vivo effect of this drug, male Wistar rats underwent balloon injury of the carotid artery, and fludarabine was locally delivered at the time of injury. Finally, fludarabine-eluting stents were in-laboratory manufactured and tested in a rabbit model of in-stent restenosis. Fludarabine markedly inhibited VSMC proliferation in cell culture. Furthermore, fludarabine reduced neointimal formation after balloon angioplasty in a dose-dependent manner, and fludarabine-eluting stents reduced neointimal hyperplasia by approximately 50%. These in vitro and in vivo cellular effects were specifically associated with the molecular switch-off of signal transducer and activator of transcription (STAT)-1 activation, without affecting other STAT proteins. Fludarabine abolishes VSMC proliferation in vitro and reduces neointimal formation after balloon injury in vivo through specific inhibition of STAT-1 activation. Fludarabine-eluting stents are feasible and effective in reducing in-stent restenosis in rabbits.


Assuntos
Fármacos Cardiovasculares/farmacologia , Lesões das Artérias Carótidas/prevenção & controle , Estenose das Carótidas/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Fator de Transcrição STAT1/metabolismo , Stents , Vidarabina/análogos & derivados , Angioplastia com Balão/efeitos adversos , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/uso terapêutico , Lesões das Artérias Carótidas/etiologia , Lesões das Artérias Carótidas/patologia , Estenose das Carótidas/etiologia , Estenose das Carótidas/patologia , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Hiperplasia , Janus Quinase 2/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fosforilação , Desenho de Prótese , RNA Antissenso/genética , RNA Antissenso/metabolismo , Coelhos , Ratos , Ratos Wistar , Fator de Transcrição STAT1/genética , Stents/efeitos adversos , Fatores de Tempo , Transfecção , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/patologia , Vidarabina/administração & dosagem , Vidarabina/farmacologia , Vidarabina/uso terapêutico
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