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1.
Am J Med ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31422111

RESUMO

BACKGROUND: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. RESULTS: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). CONCLUSION: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.

2.
Rev. esp. cardiol. (Ed. impr.) ; 71(4): 243-249, abr. 2018. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-171751

RESUMO

Introducción y objetivos. Una red para la atención del infarto agudo de miocardio con elevación del segmento ST (IAMCEST) activada por no cardiólogos reduce los retrasos en la atención, pero pueden aumentar los falsos positivos. El objetivo es evaluar la prevalencia, los predictores y el impacto de los diagnósticos falsos positivos dentro de la red catalana para la atención del IAMCEST (Codi Infart). Métodos. Se incluyó a los pacientes atendidos por el Codi Infart entre enero de 2010 y diciembre de 2011. Se consideró activación apropiada si se cumplían los criterios clínicos y electrocardiográficos de IAMCEST. Las activaciones apropiadas se clasificaron como falso positivo según 2 definiciones no excluyentes: a) «angiográfica» si no se identificó una arteria causal, y b) «clínica» si el diagnóstico al alta no era IAMCEST. Resultados. Se incluyó un total de 5.701 activaciones. La activación resultó apropiada en el 87,8% de las veces. Los falsos positivos angiográficos fueron el 14,6% y los clínicos, el 11,6%. El sexo femenino, el bloqueo de rama izquierda y el antecedente de infarto de miocardio se asociaron con el falso positivo. Utilizando la definición clínica, se observó una tasa de falsos positivos mayor en los hospitales sin sala de hemodinámica y los pacientes con complicaciones durante el primer contacto. La mortalidad hospitalaria y a los 30 días fue similar entre los falsos y los verdaderos positivos. Conclusiones. La evolución clínica es similar entre los pacientes con falsos positivos y aquellos con verdaderos positivos. La identificación de predictores de falsos positivos justifica una evaluación cuidadosa para optimizar el uso de las redes de IAMCEST (AU)


Introduction and objectives. ST-segment elevation myocardial infarction (STEMI) network activation by a noncardiologist reduces delay times but may increase the rate of false-positive STEMI diagnoses. We aimed to determine the prevalence, predictors, and clinical impact of false-positive activations within the Catalonian STEMI network (Codi Infart). Methods. From January 2010 through December 2011, all consecutive patients treated within the Codi Infart network were included. Code activations were classified as appropriate if they satisfied both electrocardiogram and clinical STEMI criteria. Appropriate activations were classified as false positives using 2 nonexclusive definitions: a) “angiographic” if a culprit coronary artery was not identified, and b) “clinical” if the discharge diagnosis was other than STEMI. Results. In total, 5701 activations were included. Appropriate activation was performed in 87.8% of the episodes. The rate of angiographic false positives was 14.6%, while the rate of clinical false positives was 11.6%. Irrespective of the definition, female sex, left bundle branch block, and previous myocardial infarction were independent predictors of false-positive STEMI diagnoses. Using the clinical definition, hospitals without percutaneous coronary intervention and patients with complications during the first medical contact also had a false-positive STEMI diagnoses rate higher than the mean. In-hospital and 30-day mortality rates were similar for false-positive and true-positive STEMI patients after adjustment for possible confounders. Conclusions. False-positive STEMI diagnoses were frequent. Outcomes were similar for patients with a true-positive or false-positive STEMI diagnosis treated within a STEMI network. The presence of any modifiable predictors of a false-positive STEMI diagnosis warrants careful assessment to optimize the use of STEMI networks (AU)


Assuntos
Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Angiografia Coronária/estatística & dados numéricos , Eletrocardiografia/estatística & dados numéricos , Cateterismo Cardíaco/estatística & dados numéricos , Angioplastia Coronária com Balão/estatística & dados numéricos , Reações Falso-Positivas , Sensibilidade e Especificidade , Procedimentos Clínicos/organização & administração , Tratamento de Emergência/métodos
3.
Rev Esp Cardiol (Engl Ed) ; 71(4): 243-249, 2018 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28711360

RESUMO

INTRODUCTION AND OBJECTIVES: ST-segment elevation myocardial infarction (STEMI) network activation by a noncardiologist reduces delay times but may increase the rate of false-positive STEMI diagnoses. We aimed to determine the prevalence, predictors, and clinical impact of false-positive activations within the Catalonian STEMI network (Codi Infart). METHODS: From January 2010 through December 2011, all consecutive patients treated within the Codi Infart network were included. Code activations were classified as appropriate if they satisfied both electrocardiogram and clinical STEMI criteria. Appropriate activations were classified as false positives using 2 nonexclusive definitions: a) "angiographic" if a culprit coronary artery was not identified, and b) "clinical" if the discharge diagnosis was other than STEMI. RESULTS: In total, 5701 activations were included. Appropriate activation was performed in 87.8% of the episodes. The rate of angiographic false positives was 14.6%, while the rate of clinical false positives was 11.6%. Irrespective of the definition, female sex, left bundle branch block, and previous myocardial infarction were independent predictors of false-positive STEMI diagnoses. Using the clinical definition, hospitals without percutaneous coronary intervention and patients with complications during the first medical contact also had a false-positive STEMI diagnoses rate higher than the mean. In-hospital and 30-day mortality rates were similar for false-positive and true-positive STEMI patients after adjustment for possible confounders. CONCLUSIONS: False-positive STEMI diagnoses were frequent. Outcomes were similar for patients with a true-positive or false-positive STEMI diagnosis treated within a STEMI network. The presence of any modifiable predictors of a false-positive STEMI diagnosis warrants careful assessment to optimize the use of STEMI networks.


Assuntos
Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Codificação Clínica/estatística & dados numéricos , Estudos de Coortes , Angiografia Coronária/estatística & dados numéricos , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Espanha
4.
Rev. esp. cardiol. (Ed. impr.) ; 70(12): 1067-1073, dic. 2017. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-169305

RESUMO

Introducción y objetivos: El tratamiento óptimo de pacientes con insuficiencia cardiaca aguda (ICA) y síndrome cardiorrenal tipo 1 (SCR-1) no está bien definido. La hipoperfusión arterial y la congestión venosa tienen un papel fundamental en la fisiopatología del SCR-1. El antígeno carbohidrato 125 (CA125) ha emergido como marcador indirecto de sobrecarga de volumen en la ICA. El objetivo de este estudio es evaluar la utilidad del CA125 para el ajuste del tratamiento diurético de pacientes con SCR-1. Métodos: Ensayo clínico multicéntrico, abierto y paralelo, que incluye a pacientes con ICA y creatinina ≥ 1,4 mg/dl al ingreso, aleatorizados a: a) estrategia convencional: titulación basada en la evaluación clínica y bioquímica habitual, o b) estrategia basada en CA125: dosis altas de diuréticos si CA125 > 35 U/ml y bajas en caso contrario. El objetivo principal es el cambio en la función renal a las 24 y las 72 h tras el comienzo del tratamiento. Como objetivos secundarios: a) cambios clínicos y bioquímicos a las 24 y las 72 h, y b) cambios en la función renal y eventos clínicos mayores a 30 días. Resultados: Los resultados de este estudio aportarán datos relevantes sobre la utilidad del CA125 para guiar el tratamiento diurético en el SCR-1. Además, permitirá ampliar el conocimiento de la fisiopatología de esta compleja entidad clínica. Conclusiones: La hipótesis del presente estudio es que las concentraciones de CA125 aumentadas pueden identificar a una población de pacientes con SCR-1 para quienes una estrategia diurética más intensa puede ser beneficiosa. Por el contrario, las concentraciones bajas de esta glucoproteína seleccionarían a los pacientes para los que serían perjudiciales las dosis altas de diuréticos (AU)


Introduction and objectives: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Methods: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4 mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72 hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72 hours, and b) renal function changes and major clinical events at 30 days. Results: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. Conclusions: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses (AU)


Assuntos
Humanos , Insuficiência Cardíaca/terapia , Nefropatias/complicações , Biomarcadores , Diuréticos/uso terapêutico , Insuficiência Cardíaca/complicações , Análise Estatística
6.
J Am Heart Assoc ; 6(5)2017 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-28468789

RESUMO

BACKGROUND: Autologous adipose tissue-derived mesenchymal stem cells (ATMSCs) therapy is a promising strategy to improve post-myocardial infarction outcomes. In a porcine model of acute myocardial infarction, we studied the long-term effects and the mechanisms involved in allogeneic ATMSCs administration on myocardial performance. METHODS AND RESULTS: Thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. After reperfusion, allogeneic ATMSCs or culture medium (vehicle) were intracoronarily administered. Follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated, n=10; ATMSCs-treated, n=9) or long term (60 days after acute myocardial infarction vehicle-treated, n=7; ATMSCs-treated, n=7). At short term, infarcted myocardium analysis showed reduced apoptosis in the ATMSCs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; P=0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor, granulocyte macrophage colony-stimulating factor, and stromal-derived factor-1α gene expression; and increased M2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; P=0.016). In long-term groups, increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in ATMSCs-treated animals, compared to vehicle (87.9±28.7 versus 57.4±17.7 mL/min per gram at 7 days; P=0.034 and 99±22.6 versus 43.3±14.7 22.6 mL/min per gram at 60 days; P=0.0001, respectively). At day 60, higher vascular density was detected at the border zone in the ATMSCs-treated animals (118±18 versus 92.4±24.3 vessels/mm2 in vehicle; P=0.045). Cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. CONCLUSIONS: In this porcine acute myocardial infarction model, allogeneic ATMSCs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. No effect on left ventricular volumes or ejection fraction was observed.


Assuntos
Tecido Adiposo/citologia , Circulação Coronária , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais , Infarto do Miocárdio/cirurgia , Disfunção Ventricular Esquerda/cirurgia , Função Ventricular Esquerda , Proteínas Angiogênicas/metabolismo , Animais , Células Cultivadas , Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Citocinas/metabolismo , Modelos Animais de Doenças , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Imagem por Ressonância Magnética , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/metabolismo , Tomografia Computadorizada Multidetectores , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia , Neovascularização Fisiológica , Imagem de Perfusão/métodos , Recuperação de Função Fisiológica , Regeneração , Sus scrofa , Fatores de Tempo , Transfecção , Transplante Homólogo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
7.
Rev Esp Cardiol (Engl Ed) ; 70(12): 1067-1073, 2017 Dec.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28341415

RESUMO

INTRODUCTION AND OBJECTIVES: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. METHODS: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. RESULTS: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. CONCLUSIONS: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.


Assuntos
Acetazolamida/uso terapêutico , Antígeno Ca-125/sangue , Síndrome Cardiorrenal/tratamento farmacológico , Clortalidona/uso terapêutico , Diuréticos/uso terapêutico , Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Proteínas de Membrana/sangue , Desequilíbrio Hidroeletrolítico/tratamento farmacológico , Doença Aguda , Síndrome Cardiorrenal/sangue , Síndrome Cardiorrenal/complicações , Creatinina/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Humanos , Planejamento de Assistência ao Paciente , Desequilíbrio Hidroeletrolítico/sangue , Desequilíbrio Hidroeletrolítico/etiologia
9.
Int J Cardiol ; 232: 70-75, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28087172

RESUMO

BACKGROUND: Therapeutic hypothermia (HT) in out-of-hospital cardiac arrest STEMI patients aims to improve their neurological prognosis, but it has been associated with slow coronary flow and cardiac thrombotic events. We sought to serially assess endothelial function during the first 48h after admission in out-of-hospital cardiac arrest STEMI patients, under therapeutic hypothermia (HT). METHODS: From January 2015 to August 2015, eighteen consecutive out-of-hospital cardiac arrest STEMI patients eligible for primary PCI received HT at admission and were included in the study (HT group). During the same time period, eight consecutive patients with large anterior STEMI who received primary PCI but not HT were included as control group. Serial endothelial function by measuring flow-mediated dilatation (FMD) in the brachial artery, biomarkers of endothelial function and oxidative stress were assessed during the first 48h after admission in both groups. RESULTS: HT group showed worse FMD as compared to the control group (p<0.001). Glutathione peroxidase-3 (GPx-3) values were higher in control as compared to HT group (p=0.019), without any interaction between time of observation and HT (p=0.864). A significant interaction between time and HT was found in the levels of sVCAM-1, which reached an earlier peak in control than in HT group (p=0.019). ET-1 values generally increase overtime (p=0.005), but without any main effect of HT (p=0.175). CONCLUSIONS: HT is associated with endothelial dysfunction in out-of-hospital cardiac arrest STEMI patients during the first 48h after admission. This vascular dysfunction may be related to increased oxidative stress due to deficiency of GPx-3 in HT patients.


Assuntos
Endotélio Vascular/fisiopatologia , Hipotermia Induzida/métodos , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Vasodilatação/fisiologia , Angiografia Coronária , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/etiologia , Parada Cardíaca Extra-Hospitalar/terapia , Prognóstico , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia
10.
Am J Cardiol ; 118(11): 1631-1635, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27665208

RESUMO

Decision-making in acute chest pain remains challenging despite normal (below ninety-ninth percentile) high-sensitivity troponin (hs-cTn). Some studies suggest that undetectable hs-cTn, far below the ninety-ninth percentile, might rule out acute coronary syndrome. We investigated clinical data in comparison to undetectable hs-cTnT. The study comprised 682 patients (November 2010 to September 2011) presenting at the emergency department with chest pain and normal hs-cTnT (<14 ng/l). The main end point was major adverse cardiac events (MACE: death, myocardial infarction, readmission for unstable angina, or revascularization) at a 4-year median follow-up; secondary end point was 30-day MACE. A clinical score was built by assigning points according to hazard ratios of the independent predictive variables: 1 point (male and effort-related pain) and 2 points (recurrent pain and prior ischemic heart disease). The negative predictive values of the clinical score and undetectable hs-cTnT (<5 ng/l), were tested. A total of 72 (10.6%) patients suffered long-term MACE. The C-statistics of the clinical score for long-term (0.75) and 30-day (0.88) MACE were higher than with the TIMI(Thrombolysis In Myocardial Infarction) risk (0.68, 0.77) or GRACE(Global Registry of Acute Coronary Events) (0.50, 0.47) scores. Likewise, the negative predictive values of score = 0 (97.5%, 100%) and ≤1 point (95.9%, 100%) were higher than using undetectable hs-cTnT (91.9%, 98.1%). Both clinical scores of 0 and ≤1 better classified patients at risk of MACE (p = 0.0001, log-rank test) than hs-cTnT <5 ng/l (p = 0.06). In conclusion, clinical data can guide decision-making and perform at least equally well as undetectable hs-cTnT, in patients presenting at the emergency department with chest pain and normal hs-cTnT.


Assuntos
Dor Aguda/sangue , Dor no Peito/sangue , Tomada de Decisão Clínica , Troponina T/sangue , Dor Aguda/diagnóstico , Dor Aguda/epidemiologia , Biomarcadores/sangue , Dor no Peito/diagnóstico , Dor no Peito/epidemiologia , Diagnóstico Diferencial , Eletrocardiografia , Serviço Hospitalar de Emergência , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Espanha/epidemiologia
11.
Eur J Intern Med ; 35: 89-94, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27423981

RESUMO

BACKGROUND: Comorbid elderly patients with non-ST-elevation myocardial infarction (non-STEMI) are underrepresented in randomized trials and undergo fewer cardiac catheterizations according to registries. Our aim was to compare the conservative and invasive strategies in these patients. METHODS: Randomized multicenter study, including 106 patients (January 2012-March 2014) with non-STEMI, over 70years and with comorbidities defined by at least two of the following: peripheral artery disease, cerebral vascular disease, dementia, chronic pulmonary disease, chronic renal failure or anemia. Patients were randomized to invasive (routine coronary angiogram, n=52) or conservative (coronary angiogram only if recurrent ischemia or heart failure, n=54) strategy. Medical treatment was identical. The main endpoint was the composite of all-cause mortality, reinfarction and readmission for cardiac cause (postdischarge revascularization or heart failure), at long-term (2.5-year follow-up). Analysis of cumulative event rate (incidence rate ratio=IRR) and time to first event (hazard ratio=HR), were performed. RESULTS: Cardiac catheterization/revascularization rates were 100%/58% in the invasive versus 20%/9% in the conservative arm. There were no differences between groups in the main endpoint (invasive vs conservative: IRR=0.946, 95% CI 0.466-1.918, p=0.877) at long-term. The invasive strategy, however, tended to improve 3-month outcomes in terms of mortality (HR=0.348, 95% CI 0.122-0.991, p=0.048), and of mortality or ischemic events (reinfarction or postdischarge revascularization) (HR=0.432, 95% CI 0.190-0.984, p=0.046). This benefit declined during follow-up. CONCLUSIONS: Invasive management did not modify long-term outcome in comorbid elderly patients with non-STEMI. The finding of a tendency towards an improvement in the short-term needs confirmation in larger studies (clinicaltrials.govNCT1645943).


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Angiografia Coronária , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Idoso , Idoso de 80 Anos ou mais , Angioplastia Coronária com Balão , Cateterismo Cardíaco , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Espanha , Resultado do Tratamento
12.
Resuscitation ; 106: 108-12, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27449822

RESUMO

BACKGROUND: Mild therapeutic hypothermia (MTH) is associated with an increased risk of both thrombotic and bleeding events. Although little is known about the use of Glycoprotein IIb-IIIa inhibitors (GPi) in this setting, the early action and the intravenous administration of these agents in patients who cannot swallow might potentially translate into clinical benefits in patients with acute coronary syndromes (ACS). AIMS: To assess the incidence of bleeding/thrombotic events in patients with ACS under MTH after an Out-of-hospital cardiac arrest (OHCA) who received GPi or not. METHODS AND RESULTS: From January 2010 to September 2015, 110 patients were treated with MTH after an OHCA. Among them, 88 (80%) had an ACS and 71 patients (80.6%) underwent percutaneous coronary intervention (PCI). In 17 (24%) GPi were administered in the cath-lab. During hospitalization, 11.7% in the GPi and 9.25%in the non GPi group presented thrombotic events (stent thrombosis, deep vein thrombosis, pulmonary embolism) without significant differences between groups (p= 0.762). The incidence of any bleeding (64.7% vs. 14.8%; p<0.0001), and major bleeding (41.1% vs. 3.7; p<0.0001) was significantly higher in patients receiving GPi. Finally, in-hospital mortality did not differ between groups (24% vs. 35, 2%; p=0.385). CONCLUSIONS: In this study, the use of GPi in patients with ACS undergoing PCI under MTH was associated with an increased bleeding risk without reduction of thrombotic events. According to these results, the use of GPi should be carefully considered in this setting.


Assuntos
Síndrome Coronariana Aguda/terapia , Hipotermia Induzida/efeitos adversos , Inibidores da Agregação de Plaquetas/administração & dosagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Síndrome Coronariana Aguda/complicações , Síndrome Coronariana Aguda/mortalidade , Adulto , Anticoagulantes/uso terapêutico , Reanimação Cardiopulmonar , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/complicações , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos
13.
Angiogenesis ; 19(2): 155-71, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26850053

RESUMO

After endothelial injury, the transcription factor Krüppel-like factor 6 (KLF6) translocates into the cell nucleus to regulate a variety of target genes involved in angiogenesis, vascular repair and remodeling, including components of the membrane transforming growth factor beta (TGF-ß) receptor complex such as endoglin and activin receptor-like kinase 1. The membrane metalloproteinase 14 (MMP14 or MT1-MMP) targets endoglin to release soluble endoglin and is involved in vascular inflammation and endothelial tubulogenesis. However, little is known about the regulation of MMP14 expression during vascular wounding. In vitro denudation of monolayers of human endothelial cell monolayers leads to an increase in the KLF6 gene transcriptional rate, followed by an upregulation of MMP14 and release of soluble endoglin. Concomitant with this process, MMP14 co-localizes with endoglin in the sprouting endothelial cells surrounding the wound border. MMP14 expression at mRNA and protein levels is increased by ectopic KLF6 and downregulated by KLF6 suppression in cultured endothelial cells. Moreover, after wire-induced endothelial denudation, Klf6 (+/-) mice show lower levels of MMP14 in their vasculature compared with their wild-type siblings. Ectopic cellular expression of KLF6 results in an increased transcription rate of MMP14, and chromatin immunoprecipitation assays show that KLF6 interacts with MMP14 promoter in ECs, this interaction being enhanced during wound healing. Furthermore, KLF6 markedly increases the transcriptional activity of different reporter constructs of MMP14 gene promoter. These results suggest that KLF6 regulates MMP14 transcription and is a critical player of the gene expression network triggered during endothelial repair.


Assuntos
Endoglina/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Metaloproteinase 14 da Matriz/genética , Proteínas Proto-Oncogênicas/metabolismo , Regulação para Cima , Lesões do Sistema Vascular/enzimologia , Lesões do Sistema Vascular/genética , Animais , Sequência de Bases , Simulação por Computador , Endoglina/genética , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fator 6 Semelhante a Kruppel , Metaloproteinase 14 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Solubilidade , Transcrição Genética , Regulação para Cima/genética , Lesões do Sistema Vascular/patologia , Cicatrização
14.
Eur Heart J Acute Cardiovasc Care ; 5(5): 399-406, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26136512

RESUMO

BACKGROUND: The additional diagnostic and prognostic information provided by delta high-sensitivity troponin T (hs-cTnT) in patients with acute chest pain and hs-cTnT elevation remains unclear. METHODS: The study group consisted of 601 patients presenting at the emergency department with non-ST-segment elevation acute chest pain and hs-cTnT elevation after two determinations (admission and within the first six hours). Maximum hs-cTnT and delta hs-cTnT (absolute or percentage change between the two measurements) were considered. Cutoff values were optimized using the quartile distribution for the endpoints. The endpoints were diagnostic (significant stenosis in the coronary angiogram) and prognostic (death or recurrent myocardial infarction at one year). RESULTS: Regarding the diagnostic endpoint, 114 patients showed a normal angiogram. Both maximum hs-cTnT ⩾80 ng/ml (OR 2.5, 95% CI 1.3-4.8, P=0.005) and delta hs-cTnT ⩾20 ng/l (OR 2.1, 95% CI 1.1-4.0, P=0.02) median value cutoffs were related to significant coronary stenosis. Furthermore, the combination of hs-cTn <80 ng/l and delta hs-cTn <20 ng/l showed the lowest probability of significant coronary stenosis (OR 0.3, 95% CI 0.1-0.4, P=0.001). During follow-up, 86 patients experienced the prognostic endpoint. After full adjustment for clinical data, maximum hs-cTnT ⩾30 ng/l, first quartile cutoff, was related to the outcome (HR 1.8, 95% CI 1.0-3.4, P=0.05), while delta hs-cTnT, either absolute or percentage change, lacked prognostic value. CONCLUSIONS: Maximum hs-cTnT captures all the prognostic information provided by hs-cTnT in non-ST-segment elevation acute chest pain. Low maximum and low delta hs-cTnT are associated with a normal coronary angiogram, which could make the final diagnosis challenging in some cases.


Assuntos
Dor no Peito/diagnóstico , Dor no Peito/metabolismo , Troponina T/metabolismo , Idoso , Dor no Peito/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
J Cell Biochem ; 117(2): 448-57, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26221761

RESUMO

Platelets are important in hemostasis, but also detect particles and pathogens in the circulation. Phagocytic and endocytic activities of platelets are widely recognized; however, receptors and mechanisms involved remain poorly understood. We previously demonstrated that platelets internalize and store phospholipid microvesicles enriched in human tissue factor (TF+MVs) and that platelet-associated TF enhances thrombus formation at sites of vascular damage. Here, we investigate the mechanisms implied in the interactions of TF+MVs with platelets and the effects of specific inhibitory strategies. Aggregometry and electron microscopy were used to assess platelet activation and TF+MVs uptake. Cytoskeletal assembly and activation of phosphoinositide 3-kinase (PI3K) and RhoA were analyzed by western blot and ELISA. Exposure of platelets to TF+MVs caused reversible platelet aggregation, actin polymerization and association of contractile proteins to the cytoskeleton being maximal at 1 min. The same kinetics were observed for activation of PI3K and translocation of RhoA to the cytoskeleton. Inhibitory strategies to block glycoprotein IIb-IIIa (GPIIb-IIIa), scavenger receptor CD36, serotonin transporter (SERT) and PI3K, fully prevented platelet aggregation by TF+MVs. Ultrastructural techniques revealed that uptake of TF+MVs was efficiently prevented by anti-CD36 and SERT inhibitor, but only moderately interfered by GPIIb-IIIa blockade. We conclude that internalization of TF+MVs by platelets occurs independently of receptors related to their main hemostatic function (GPIIb-IIIa), involves the scavenger receptor CD36, SERT and engages PI3-Kinase activation and cytoskeletal assembly. CD36 and SERT appear as potential therapeutic targets to interfere with the association of TF+MVs with platelets and possibly downregulate their prothrombotic phenotype.


Assuntos
Plaquetas/fisiologia , Antígenos CD36/metabolismo , Micropartículas Derivadas de Células/metabolismo , Citoesqueleto/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Tromboplastina/metabolismo , Células Cultivadas , Ativação Enzimática , Humanos , Integrina beta3/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Agregação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Transporte Proteico , Transdução de Sinais , Proteína rhoA de Ligação ao GTP/metabolismo
16.
J Mol Cell Cardiol ; 80: 146-55, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25619946

RESUMO

The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p<0.01 and 181.0/mL vs. 62.0/mL; p<0.01). Endothelial progenitor cells peaked at 30 days post-infarction (201.0/mL vs. 369.5/mL; p<0.01), as did VCAM-1 (573.7 ng/mL vs. 701.8 ng/mL; p<0.01). At 180 days post-infarction, circulating endothelial cells and VWF decreased, compared to baseline. In stroke patients, the number of endothelial progenitor cells - but not circulating endothelial cells - was higher than in controls (90.0/mL vs. 37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however, VCAM-1 peaked (628.1/mL vs. 869.1/mL; p<0.01) but there was no significant change in endothelial progenitor cells (90/mL vs. 78/mL; p<0.34). At 180 days after stroke, circulating endothelial cells and VWF decreased, compared to baseline. Cultured endothelial progenitor cells from controls and myocardial infarction patients had endothelial phenotype characteristics and exhibited functional differences in adhesion and Ca(2+) influx, but not in proliferation and vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization of endothelial progenitor cells peaked at 30 days after the ischemic event. Although a similar VCAM-1 kinetic was observed in stroke patients, endothelial progenitor cells did not increase. Endothelial progenitor cells had mature endothelial capabilities in vitro.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Infarto do Miocárdio/metabolismo , Acidente Vascular Cerebral/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Contagem de Células , Células Cultivadas , Células Endoteliais/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/etiologia , Fenótipo , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator de von Willebrand/metabolismo
17.
Pflugers Arch ; 467(8): 1711-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25208915

RESUMO

Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to the process of intimal hyperplasia which constitutes a common pathological lesion in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell migration and proliferation. Using human VSMCs from vessels in which unwanted remodeling is a relevant clinical complication, we explored the contribution of the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional contribution of Kv1.3 and Kv1.5 channels were studied in contractile and proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced proliferation were observed in all vascular beds studied. When investigating the signaling pathways modulated by the blockade of Kv1.3 channels, we found that anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were occluded by selective inhibition of MEK/ERK and PLCγ signaling pathways, but were unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the anti-proliferative effects of Kv1.3 blockers indicates that they have a role in the late signaling events essential for the mitogenic response to growth factors. These findings establish the involvement of Kv1.3 channels in the PM of human VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR blockers, our results provide the basis for the development of novel, more specific therapies.


Assuntos
Proliferação de Células , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Canal de Potássio Kv1.3/antagonistas & inibidores , Canal de Potássio Kv1.3/genética , Canal de Potássio Kv1.3/metabolismo , Canal de Potássio Kv1.5/genética , Canal de Potássio Kv1.5/metabolismo , Potenciais da Membrana , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Fenótipo , Inibidores de Fosfodiesterase/farmacologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Tempo
18.
Heart ; 100(20): 1591-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24947318

RESUMO

OBJECTIVES: High-sensitivity troponin (hs-cTn) is substituting conventional cTn for evaluation of chest pain. Our aim was to assess the impact on patient management and outcome. METHODS: A total of 1372 consecutive patients presenting at the emergency department with non-ST-elevation acute chest pain were divided into two periods according to the cTn assay used, conventional (n=699, March 2008 to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies were similar and according to guidelines. The primary endpoint was major adverse cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by unstable angina or postdischarge revascularisation). RESULTS: There were minor differences in baseline characteristics. In the hs-cTn period, more patients elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs 55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and, therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6 months, 135 patients suffered MACE, including 54 deaths. After adjusting for a Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99; 95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95), though the risk of longer hospitalisation stay increased at the index episode (OR=1.35, 95% CI 1.07 to 1.71, p=0.02). CONCLUSIONS: hs-cTn simplified chest pain triage on avoiding a more complex evaluation with non-invasive tests in the chest pain unit, but prompted longer hospitalisations and more invasive procedures without impacting on the 6-month outcomes.


Assuntos
Dor no Peito/sangue , Dor no Peito/terapia , Troponina/sangue , Doença Aguda , Idoso , Feminino , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade
19.
Eur J Clin Invest ; 44(1): 83-92, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24350923

RESUMO

BACKGROUND: Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. DESIGN: Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. RESULTS: Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies. CONCLUSIONS: The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Animais , Modelos Animais de Doenças , Sobrevivência de Enxerto , Células-Tronco Mesenquimais/metabolismo , Microscopia Confocal , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Volume Sistólico , Suínos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo
20.
Circ Res ; 112(1): 113-27, 2013 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-23048070

RESUMO

RATIONALE: Activin receptor-like kinase-1 (ALK1) is an endothelial transforming growth factor ß receptor involved in angiogenesis. ALK1 expression is high in the embryo vasculature, becoming less detectable in the quiescent endothelium of adult stages. However, ALK1 expression becomes rapidly increased after angiogenic stimuli such as vascular injury. OBJECTIVE: To characterize the molecular mechanisms underlying the regulation of ALK1 on vascular injury. METHODS AND RESULTS: Alk1 becomes strongly upregulated in endothelial (EC) and vascular smooth muscle cells of mouse femoral arteries after wire-induced endothelial denudation. In vitro denudation of monolayers of human umbilical vein ECs also leads to an increase in ALK1. Interestingly, a key factor in tissue remodeling, Krüppel-like factor 6 (KLF6) translocates to the cell nucleus during wound healing, concomitantly with an increase in the ALK1 gene transcriptional rate. KLF6 knock down in human umbilical vein ECs promotes ALK1 mRNA downregulation. Moreover, Klf6(+/-) mice have lower levels of Alk1 in their vasculature compared with their wild-type siblings. Chromatin immunoprecipitation assays show that KLF6 interacts with ALK1 promoter in ECs, and this interaction is enhanced during wound healing. We demonstrate that KLF6 is transactivating ALK1 gene, and this transactivation occurs by a synergistic cooperative mechanism with specificity protein 1. Finally, Alk1 levels in vascular smooth muscle cells are not directly upregulated in response to damage, but in response to soluble factors, such as interleukin 6, released from ECs after injury. CONCLUSIONS: ALK1 is upregulated in ECs during vascular injury by a synergistic cooperative mechanism between KLF6 and specificity protein 1, and in vascular smooth muscle cells by an EC-vascular smooth muscle cell paracrine communication during vascular remodeling.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Receptores de Ativinas Tipo I/metabolismo , Células Endoteliais/metabolismo , Artéria Femoral/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Lesões do Sistema Vascular/metabolismo , Cicatrização , Receptores de Ativinas Tipo I/genética , Receptores de Activinas Tipo II/genética , Animais , Sítios de Ligação , Modelos Animais de Doenças , Células Endoteliais/patologia , Artéria Femoral/lesões , Artéria Femoral/patologia , Regulação da Expressão Gênica , Células HEK293 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-6/metabolismo , Fator 6 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/deficiência , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Comunicação Parácrina , Regiões Promotoras Genéticas , Transporte Proteico , Proteínas Proto-Oncogênicas/deficiência , Proteínas Proto-Oncogênicas/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Fator de Transcrição Sp1/metabolismo , Fatores de Tempo , Transcrição Genética , Ativação Transcricional , Transfecção , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/patologia
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