RESUMEN
AIM: The microRNAs (miRs) are small non-coding RNAs which regulate expression of multiple genes involved in atherogenesis. MicroRNA are also present in circulation. The aims of this study were: 1) assessment of expression level of miR-1, miR-208a and miR-423-5p in plasma in patients with STEMI, stable CAD and healthy individuals; 2) evaluation of correlation between plasma miRs and left ventricle ejection fraction, end- systolic and end-diastolic diameters and troponin release in patients with STEMI. METHODS: Study group consisted of 26 patients: 1) acute MI group (N.=17); 2) stable CAD group (N.=4); and 3) subjects with no history of CAD (control group, N.=5). Expression of miR-423-5p, miR-208 and miR-1 was measured in plasma before PCI, 6, 12 and 24 hours later. Expression level ofmiRs was measured using TaqMan® MicroRNA Assays. Expression was assessed by Pfaffl method, and miR-39 was used for normalization of the results. RESULTS: In stable CAD in comparison to control group the expression level of miR-1, miR-208a and miR-423-5p did not show significant differences. Also there was no significant increase of number of miR copies at 6, 12 and 24 hours after PCI. There was a significantly higher number of miR-423-5p copies in patients with acute MI before the pPCI. After 6, 12 and 24 hours post-procedure the expression level was similar to the control group and significantly lower than the baseline level. Conversely, the expression level of miR-1 and miR-208a were not significantly different than in the control group. In patients with acute MI there were no significant correlations between the expression level of miRs and any of the echocardiographic parameters of LV as well as level of troponin I at any time-point of the follow-up. CONCLUSION: Early in acute myocardial infarction the expression of miR-423-5p in plasma is significantly increased with subsequent normalization within 6 hours. Potentially it is an early marker of myocardial necrosis.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , MicroARNs/genética , Infarto del Miocardio/genética , Estudios de Casos y Controles , Ecocardiografía , Femenino , Estudios de Seguimiento , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Necrosis , Factores de Tiempo , Troponina I/metabolismoRESUMEN
AIM: Aim of the study was to evaluate the association between circulating endothelial progenitor cells (EPCs) and angiographic outcomes after implantation of GenousTM stent in patients with non-ST-segment elevation acute coronary syndromes (ACS) (NSTE-ACS) undergoing urgent percutaneous coronary intervention (PCI). METHODS: Sixty patients treated with EPC-capture stent (N.=30) or bare metal stents (BMS) (N.=30) receiving 80 mg atorvastatin and dual antiplatelet therapy (DAT) for 12 months. Restenosis was assessed after 6 months by quantitative coronary angiography (QCA) and major acute coronary events (MACE) evaluated after 6 and 12 months. INCLUSION CRITERIA: de novo lesion >70% in native vessel, diameter 2.5-4 mm, lesion length <30 mm. EXCLUSION CRITERIA: diabetes, previous revascularization, significant left main stenosis, chronic total occlusions (CTO) and multivessel disease. RESULTS: Majority of patients in EPC-capture stent and BMS groups presented with NSTEMI (73.3% and 70%, respectively). Mean stent length was 20.1±8 and 19.9±10 mm, diameter 3±0.97 and 3.1±0.88 mm in respective groups. The binary restenosis was significantly lower in GenousTM (13 vs. 26.6%, P=0.04). Risk of MACE after 6 and 12 months were comparable in both groups. There was no stent thrombosis. Numbers of circulating EPCs were significantly approximately 2-fold higher during the ACS than after 6 months. Mobilization of EPCs during acute ischemia was significantly lower in patients who developed restenosis after 6 months (3 vs. 4.5 cells/µL, P=0.002) and it was negatively correlated with late-loss after 6 months (R=-0.42; P<0.03). CONCLUSION: Use of GenousTM stents in NSTE-ACS is associated with lower restenosis rate than BMS at 6 months. There was no ST through 1 year. The number of circulating EPCs is inversely correlated with in-stent late loss (LL).
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Síndrome Coronario Agudo/fisiopatología , Síndrome Coronario Agudo/terapia , Reestenosis Coronaria/etiología , Stents Liberadores de Fármacos , Células Endoteliales , Células Madre , Anciano , Angioplastia Coronaria con Balón/métodos , Atorvastatina , Materiales Biocompatibles Revestidos , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/prevención & control , Stents Liberadores de Fármacos/efectos adversos , Femenino , Estudios de Seguimiento , Sistema de Conducción Cardíaco/fisiopatología , Ácidos Heptanoicos/administración & dosificación , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Estudios Prospectivos , Pirroles/administración & dosificación , Radiografía , Factores de Riesgo , Stents/efectos adversos , Resultado del TratamientoRESUMEN
Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the peripheral blood, including hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, circulating angiogenic cells and pluripotent very small embryonic-like cells; however, the contribution of circulating cells to the myocardial and endothelial repair is still unknown. The number and function of these cells is impaired in patients with diabetes and other cardiovascular risk factors, but can be improved by physical exercise and use of statins. The mobilization of SPCs in acute coronary syndromes and stable coronary artery disease seems to predict the clinical outcomes in selected groups of patients. Interpretation of the findings has to incorporate other factors that modulate the process of mobilization, such as coexisting diseases, age and medications. This review discusses the mobilization of SPCs in acute ischemia (MI, stroke), as well as in stable cardiovascular disease, and highlights the possibility of using the SPC as a marker of cardiovascular risk.
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Enfermedades Cardiovasculares/terapia , Movilización de Célula Madre Hematopoyética , Enfermedades Cardiovasculares/patología , Ejercicio Físico , HumanosRESUMEN
Although regenerative medicine is searching for pluripotent stem cells that could be employed for therapy, various types of more differentiated adult stem and progenitor cells are in meantime being employed in clinical trials to regenerate damaged organs (for example, heart, kidney or neural tissues). It is striking that, for a variety of these cells, the currently observed final outcomes of cellular therapies are often similar. This fact and the lack of convincing documentation for donor-recipient chimerism in treated tissues in most of the studies indicates that a mechanism other than transdifferentiation of cells infused systemically into peripheral blood or injected directly into damaged organs may have an important role. In this review, we will discuss the role of (i) growth factors, cytokines, chemokines and bioactive lipids and (ii) microvesicles (MVs) released from cells employed as cellular therapeutics in regenerative medicine. In particular, stem cells are a rich source of these soluble factors and MVs released from their surface may deliver RNA and microRNA into damaged organs. Based on these phenomena, we suggest that paracrine effects make major contributions in most of the currently reported positive results in clinical trials employing adult stem cells. We will also present possibilities for how these paracrine mechanisms could be exploited in regenerative medicine to achieve better therapeutic outcomes. This approach may yield critical improvements in current cell therapies before true pluripotent stem cells isolated in sufficient quantities from adult tissues and successfully expanded ex vivo will be employed in the clinic.
Asunto(s)
Micropartículas Derivadas de Células/fisiología , Péptidos y Proteínas de Señalización Intercelular/uso terapéutico , Comunicación Paracrina , Células Madre Pluripotentes/citología , Medicina Regenerativa , Trasplante de Células Madre , Adulto , Diferenciación Celular , HumanosRESUMEN
We intended to estimate how the zero coronary artery calcium (CAC) score in symptomatic patients with intermediate probability of coronary artery disease predicts the absence of obstructive non-calcified coronary plaques (NCAPs). CAC scoring and coronary arteries were evaluated by means of 64-multislice CT coronary angiography (CCTA). In 166 subject with CAC=0, Non-obstructive NCAPs (less than 50%) were found in 17 patients (10.2%), while significant stenosis were diagnosed in 3 (2%). In the female insignificant stenoses were more frequent (12%) than in men (6%), however, all 3 cases with significant stenosis were male. In our study, where CCTA has been used as diagnostic method for CAD diagnosing, the prevalence of non-calcified plaques in CAC=0 subjects is relatively high. Our study confirms a relatively low incidence of significant coronary stenosis in this subset of CAD-suspected subjects.
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Calcio/análisis , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/epidemiología , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/epidemiología , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: Occlusive coronary artery disease (CAD) is associated with left ventricular (LV) remodeling, LV systolic dysfunction, and heart failure. The BEAUTIFUL Echo substudy aimed to evaluate the effects of heart rate reduction with ivabradine on LV size (primary end-point: change in LV end-systolic volume index [LVESVI]) and function and the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: The substudy was carried out in 86 centers participating in the BEAUTIFUL study. 2D echocardiography was performed at baseline, and after 3 and 12 months in patients with stable CAD and LV systolic dysfunction receiving ivabradine or placebo at the same time-points. All data were read and analyzed centrally. Of 525 patients completing the study, 426 had adequate echocardiographic readings (n = 220 ivabradine; n = 206 placebo). Treatment with ivabradine was associated with a decrease in the primary end-point LVESVI (change from baseline to last value, -1.48 ± 13.00 mL/m(2)) versus an increase with placebo (1.85 ± 10.54 mL/m(2)) (P=0.018). There was an increase in LV ejection fraction with ivabradine (2.00 ± 7.02%) versus no change with placebo (0.01 ± 6.20%) (P=0.009). Reduction in LVESVI was related to the degree of heart rate reduction with ivabradine. There were no differences in any other echocardiographic parameters or NT-proBNP. Change in LVESVI was related to the log change in NT-proBNP in the ivabradine group only (r = 0.18, P = 0.006). CONCLUSIONS: Our observations suggest that ivabradine may reverse detrimental LV remodeling in patients with CAD and LV systolic dysfunction.
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Benzazepinas/farmacología , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Anciano , Método Doble Ciego , Femenino , Humanos , Ivabradina , Masculino , UltrasonografíaRESUMEN
The bone marrow (BM) niche contains small heterogenous populations of cells which may contribute to cardiac and endothelial repair, including committed lineages [endothelial progenitor cells (EPCs), multipotent mesenchymal stromal cells (MSCs) and more primitive very small embryonic-like cells (VSELs) expressing pluripotent stem cell (PSC) markers (Oct-4, Nanog, SSEA-1)]. VSELs are present in BM, peripheral blood and some solid organs in mice and were recently identified in peripheral blood in patients with acute coronary syndromes and stroke. VSELs can be expanded in vitro and differentiated into cells from all three germ layers. This population of cells displays the morphology of primitive PSC (small size, open type chromatin, large nucleus, narrow rim of cytoplasm) and express PSC markers. The isolation of human VSELs is based on their size and presence of several surface markers (CXCR4, CD133, CD34) and lack of markers of hematopoietic lineage (lin, CD45). In acute myocardial infarction and ischemic stroke VSELs are rapidly mobilized into peripheral blood, and express increased levels of PSC markers as well as early cardiac (GATA-4, Nkx2.5/Csx), neural (GFAP, nestin, beta-III-tubulin, Olig1, Olig2, Sox2, Musashi) and endothelial lineage markers (VE-cadherin, von Willebrand factor). The number of VSELs mobilized in acute myocardial infarction is inversely correlated with left ventricular ejection fraction and the release of cardiac necrosis markers. Mobilization of these cells is also reduced in patients with diabetes and in the elderly. BM-derived VSELs were expanded and after cardiogenic pre-differentiation injected intramyocardially in mice models of myocardial infarction leading to improved left ventricular contractility. VSELs are probably progeny of epiblast cells which migrated to the BM and developing organs during embryonic development. The cells are present in a quiescent state in the adult BM and solid organs and might serve as a reserve pool of resident stem cells. VSELs are promising candidates for further pre-clinical and clinical studies on cellular cardiovascular therapy.
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Síndrome Coronario Agudo/cirugía , Células Madre Embrionarias/trasplante , Miocitos Cardíacos/trasplante , Accidente Cerebrovascular/cirugía , Ingeniería de Tejidos/métodos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/patología , Animales , Células Madre Embrionarias/patología , Humanos , Ratones , Miocitos Cardíacos/patología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/patologíaRESUMEN
OBJECTIVES: Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline. METHODS: BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%). RESULTS: A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%). CONCLUSIONS: Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients.
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Benzazepinas/uso terapéutico , Fármacos Cardiovasculares/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Insuficiencia Cardíaca/tratamiento farmacológico , Anciano , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Complicaciones de la Diabetes , Método Doble Ciego , Quimioterapia Combinada , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Ivabradina , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Disfunción Ventricular Izquierda/tratamiento farmacológico , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Bone marrow-derived cells which may be involved in cardiac repair/regeneration after ischaemic injury must undergo mobilisation into peripheral blood with subsequent homing and engraftment into the target organ. Mobilisation of the heterogeneous population of stem/progenitor cells in endothelial injury or myocardial ischaemia has been described recently. The number of circulating stem/progenitor cells reflects the endothelial damage, and turnover may be a surrogate marker reflecting the burden of cardiovascular risk factors and prognostic markers in stable coronary heart disease and acute coronary syndromes. Acute coronary syndromes are associated with increased levels of inflammatory and haematopoietic cytokines which, in turn, can mobilise progenitor cells from the bone marrow. Myocardial infarction increases the number of endothelial progenitor cells and other less well-defined subpopulations, such as CD34/c-kit(+) and CD34/CXCR4(+) cells, which may take part in cardiac repair after ischaemic injury. Data on mobilisation of stem/progenitor cells in acute coronary syndromes are summarised here. Cell types, mechanisms of mobilisation, homing and engraftment are discussed and their relevance to clinical outcomes.
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Síndrome Coronario Agudo/fisiopatología , Movimiento Celular/fisiología , Enfermedad Coronaria/fisiopatología , Células Madre/citología , Síndrome Coronario Agudo/sangre , Animales , Diferenciación Celular , Enfermedad Coronaria/sangre , Vasos Coronarios/fisiología , Citocinas/fisiología , Endotelio Vascular/fisiología , Humanos , Ratones , Miocardio , Ratas , Regeneración/fisiología , Células Madre/fisiologíaRESUMEN
AIMS: A fibrinolytic agent more effective than streptokinase available for bolus injection with reasonable cost-effectiveness is a desirable goal. Pilot studies with bolus pegulated staphylokinase (PEG-Sak) have revealed excellent Thrombolysis In Myocardial Infarction (TIMI) 3 60-minute flow. METHODS AND RESULTS: We evaluated patients with acute ST-elevation myocardial infarction within 6 hours of chest pain onset to determine a dose of PEG-Sak that had at least equal efficacy to recombinant tissue plasminogen activator (rt-PA) while maintaining an acceptable safety profile. After the initial study of 38 patients, of whom 27 received PEG-Sak, enrollment was temporarily halted because 3 patients receiving PEG-Sak had intracranial hemorrhage: 1 at a dose of 0.15 mg/kg and 2 at a dose of 0.05 mg/kg. Overall, 378 patients were studied across a PEG-Sak dose range from 0.01 mg/kg to 0.015 mg/kg, and 122 patients received accelerated rt-PA. At the lowest dose of PEG-Sak studied, 0.01 mg/kg, there was suggestive evidence of attenuation of efficacy; the point estimate for TIMI 3 flow was 24% (95% CI 9%-38%). At doses of 0.01875 to 0.0375 mg/kg (n = 314), TIMI 3 flow rates were 33% (95% CI 27%-38%), whereas the TIMI 3 flow was 41% (95% CI 20%-61%) at the highest PEG-Sak dose studied, 0.05 mg/kg (n = 23), which was similar to that found with rt-PA, 41% (95% CI 32%-50%). CONCLUSION: The efficacy of PEG-Sak, coupled with its ease of administration, provide further impetus for further study in acute myocardial infarction.
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Fibrinolíticos/administración & dosificación , Metaloendopeptidasas/administración & dosificación , Infarto del Miocardio/tratamiento farmacológico , Estreptoquinasa/administración & dosificación , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Adulto , Anciano , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Alterations of the immune system are now believed to play crucial role in the pathogenesis of atherosclerosis. The aim of this study was analysis of soluble forms of selectin-P and interleukin-8 levels in patients with different form of coronary heart disease. MATERIALS AND METHODS: In the study took part 18 patients with stable coronary heart disease, 20 patients with unstable coronary heart disease and 15 healthy persons from control group. Soluble selectin-P and interleukin-8 levels were measured in EDTA plasma with the use of enzyme immunoassay ELISA. RESULTS: The level of soluble selectin-P was significantly higher in unstable coronary heart disease patients in comparison to the stable coronary heart disease patients (P < or = 0.01) and nonsignificantly higher in comparison to the control group. The level of interleukin-8 were significantly higher in unstable coronary heart disease patients in comparison to the stable coronary heart disease patients (P < or = 0.01) and in comparison to the control group (P < or = 0.02). CONCLUSION: Our findings suggest that soluble form of selectin-P and interleukin-8 may be useful clinical predictors of unstable coronary heart disease. The assessment of the risk for the development of coronary heart disease requires further serial investigation.
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Enfermedad Coronaria/inmunología , Interleucina-8/sangre , Selectina-P/sangre , Anciano , Angina Inestable/inmunología , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Southern Poland Epidemiological Survey (SPES) was carried out in 1997 in the former Katowice and Bielsko voivodeships with the aim of cardiovascular disease prevention. One of the objectives of SPES was to establish the prevalence of the risk factors for atherosclerosis. This paper describes a group of 41,927 adults (24,985 women and 16,942 men) with no signs and symptoms of ischaemic heart disease who participated in the study, comprising 83.7% of all the examined cohort. Hypercholesterolemia and hypertension, present in 55.8% and 45.3% of subjects respectively, were found to be the main risk factors in both men and women. Hypercholesterolemia was more prevalent in older age groups. 33.7% of women and 46.3% of men were overweight, 23.9% and 17% respectively were obese. 22.4% of women and 31.9% of men were active smokers. Smoking was more common in younger age groups. 25.3% of women and 21.5% of men had a positive family history for ischaemic heart disease before the age of 60 years. High prevalence of classical risk factors in the examined group indicates that population strategy should be introduced in primary prevention of cardiovascular disease in this area.
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Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/etiología , Adulto , Áreas de Influencia de Salud , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Existing drug therapies for paroxysmal supraventricular tachycardia (PSVT) have potentially serious adverse effects. Dofetilide, a pure class III antiarrhythmic agent, may offer an effective and safe alternative for treating PSVT. This study compared the efficacy and safety of dofetilide with that of propafenone and placebo in the prevention of PSVT. METHODS: This multicenter, randomized, placebo-controlled, parallel-group study compared the effectiveness of oral dofetilide 500 microg given twice daily with that of propafenone 150 mg given 3 times a day and placebo in preventing the recurrence of PSVT in 122 symptomatic patients. Episodes of PSVT were documented by symptom diaries and Hertcard (Hertford Medical, Hertfordshire, UK) event recorders. RESULTS: After 6 months of treatment, patients taking dofetilide, propafenone, and placebo had a 50%, 54%, and 6% probability, respectively, of remaining free of episodes of PSVT (P <.001 for both dofetilide and propafenone vs placebo). Both dofetilide and propafenone also decreased the frequency of episodes of PSVT; the median numbers of episodes in the dofetilide- and propafenone-treated groups were 1 and 0.5, respectively, compared with 5 in the placebo-treated group. Dofetilide was well tolerated; no proarrhythmia occurred. Three patients taking propafenone had serious treatment-related adverse effects that required drug discontinuation. CONCLUSIONS: Dofetilide and propafenone were equally effective in preventing the recurrence of or decreasing the frequency of PSVT.
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Antiarrítmicos/uso terapéutico , Fenetilaminas/uso terapéutico , Propafenona/uso terapéutico , Sulfonamidas/uso terapéutico , Taquicardia Supraventricular/prevención & control , Administración Oral , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to-moderate heart failure, but little is known about their effects in severe heart failure. METHODS: We evaluated 2289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic, and who had an ejection fraction of less than 25 percent. In a double-blind fashion, we randomly assigned 1133 patients to placebo and 1156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention, or were receiving intravenous vasodilators or positive inotropic drugs were excluded. RESULTS: There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected a 35 percent decrease in the risk of death with carvedilol (95 percent confidence interval, 19 to 48 percent; P=0.00013, unadjusted; P=0.0014, adjusted for interim analyses). A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24 percent decrease in the combined risk of death or hospitalization with carvedilol (95 percent confidence interval, 13 to 33 percent; P<0.001). The favorable effects on both end points were seen consistently in all the subgroups we examined, including patients with a history of recent or recurrent cardiac decompensation. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (P=0.02). CONCLUSIONS: The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.
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Antagonistas Adrenérgicos beta/uso terapéutico , Carbazoles/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Propanolaminas/uso terapéutico , Antagonistas Adrenérgicos beta/efectos adversos , Anciano , Carbazoles/efectos adversos , Carvedilol , Enfermedad Crónica , Método Doble Ciego , Femenino , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Propanolaminas/efectos adversos , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Riesgo , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
Results of the studies published or reported within the last 2 years provide convincing evidence that beta-blockers can decrease mortality in patients with chronic symptomatic heart failure because of left ventricular systolic dysfunction. The Cardiac Insufficiency Bisoprolol Study (CIBIS)-II and Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) trials showed a 34% reduction in all-cause death with bisoprolol and metoprolol therapy in patients with class II-III heart failure. Data from Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS), with a 35% mortality reduction, extended this benefit to class IV patients treated with carvedilol who do not require intravenous diuretics or positive inotropes. Ongoing beta-blocker studies address new topics, such as treatment of older patients, in whom diastolic heart failure may be more common, and direct comparison of different drugs. Although the use of beta-blockers for heart failure tends to increase, implementation of the knowledge from the trials in clinical practice still remains a challenge.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Insuficiencia Cardíaca/terapia , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Diminished activity of 5,10 methylenetetrahydrofolate reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose to coronary artery disease (CAD). In a case-control study we determined the prevalence of two common MTHFR polymorphisms, C677T and A1298C, in 161 male patients under the age of 50 years with angiographically documented CAD and compared it to that in 211 healthy controls. Genotyping was also performed in a random population sample, consisting of 149 men and 121 women at an average age of 40 years. The studied group had classic risk factors of atherosclerosis but did not differ in fasting plasma homocysteine, folic acid, and vitamin B12 levels in either the control group or population sample. The frequency of the 1298C allele was significantly higher in CAD (0.304) than in controls (0.199) or the population sample (0.235). Allele 1298C showed a significant association with early-onset CAD both in homozygotes and in heterozygous carriers. These findings were further supported by comparisons with the population sample. Homozygosity for allele 677T showed a tendency to associate with CAD. Allele 1298C of MTHFR is associated with early-onset CAD (carriers- RR = 1.71, 95% CI: 1.13-2.59; homozygotes- RR = 3.09, 95% CI: 1.36-7.02), even when blood homocysteine levels are not elevated.
Asunto(s)
Enfermedad Coronaria/enzimología , Enfermedad Coronaria/genética , Homocisteína/sangre , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH , Adolescente , Adulto , Edad de Inicio , Alelos , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Enfermedad Coronaria/epidemiología , Femenino , Ácido Fólico/sangre , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Homocigoto , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Infarto del Miocardio/enzimología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/genética , Polimorfismo Genético , Prevalencia , Factores de RiesgoRESUMEN
OBJECTIVE: QT interval prolongation and increased spatial QT dispersion are important factors increasing the risk in coronary heart disease. The authors studied the spontaneous beat-to-beat variability of ventricular repolarization (RT intervals) in normal subjects and in patients after myocardial infarction (MI) in order to define the determinants of abnormal temporal dispersion. METHODS: Seventy-six patients with a history of MI (17 female, 59 male, aged 52 +/- 10 years) comprised the study group. Forty-seven patients had preserved left ventricular ejection fraction (EF > or = 40%, MI-A) and 29 patients had left ventricular dysfunction (EF < 40%, MI-B). Twenty healthy volunteers (6 female, 14 male, aged 25 +/- 5 years) were included as the control group. An ECG signal of 512 heartbeats was recorded in the supine position. After analogue-to-digital conversion (16 bit, 2 kHz), the fiducial points of the R wave and T wave were determined. The RR and RT variability (V) assessed in the time domain as the standard deviations of RR and RT (ms), as well as the coefficients of scatterplots of RR and RT intervals. RESULTS: As expected, the standard deviation of RR was significantly reduced in MI patients. The magnitude of RTV in the time domain was similar in the controls and in both subgroups of MI patients. The complexity of heart rate variability (HRV) was slightly, but significantly, reduced in the MI-B group, but not significantly in the MI-A heart group. The complexity of RTV behaved in the opposite manner, being increased in both MI subgroups with the lower mean in the MI-B patients. The different behaviour of HRV and RTV was indicated by the increased ratio of RR/RT coefficients, which reached a significantly greater value in the MI-B group. CONCLUSION: The authors have described different patterns of scatterplot of short-term HRV and RTV in normal subjects, which confirmed that RTV is a less complex phenomenon than HRV. In patients after MI, the complexity of HRV diminishes, while the complexity of RTV increases. These opposing changes are more pronounced in patients with left ventricular dysfunction. A possible prognostic value of this feature is unknown and remains to be elucidated in future prospective studies.
Asunto(s)
Potenciales de Acción , Ritmo Circadiano , Enfermedad Coronaria/fisiopatología , Electrocardiografía , Frecuencia Cardíaca , Ventrículos Cardíacos/fisiopatología , Potenciales de Acción/fisiología , Adolescente , Adulto , Anciano , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Enoxaparin inhibits smooth muscle cell proliferation in experimental models. Intimal hyperplasia has been found to be the principal cause of restenosis after coronary stent implantation. We sought to determine whether the intramural delivery of enoxaparin before stenting of de novo lesions decreases restenosis. METHODS AND RESULTS: One hundred patients who were undergoing stenting were randomly assigned to either local administration of enoxaparin during predilation with reduced systemic heparinization or stenting with standard, systemic heparinization. All patients were treated with the same type of stent (NIR). The primary study end point was late luminal loss. The secondary end points were major adverse cardiac events, target lesion revascularization, and angiographic restenosis at 6 months. Angiographic follow-up at 6 months was completed in all except 1 patient. Late luminal loss was reduced to 0.76+/-0.42 mm in the local enoxaparin delivery group versus 1. 07+/-0.49 mm in the systemic heparinization group (P:<0.001). Restenosis, using a binary definition, occurred in 10% of patients in the enoxaparin group and in 24% of patients in the systemic heparinization group (P:<0.05). Target lesion revascularization rates occurred in 8% of the enoxaparin group and 22% of the systemic heparinization group (P:<0.05). There were no deaths and no emergent CABGs were performed. The only subacute stent closure and non-Q-wave infarction occurred in a patient assigned to the systemic heparinization group. CONCLUSIONS: This is the first prospective randomized trial in which the local delivery of a drug, enoxaparin, resulted in significant reduction in late luminal loss and restenosis after stent implantation in de novo coronary lesions.
Asunto(s)
Enoxaparina/administración & dosificación , Oclusión de Injerto Vascular/prevención & control , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/cirugía , Stents , Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Vías de Administración de Medicamentos , Sistemas de Liberación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Polonia , Estudios Prospectivos , Stents/efectos adversos , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
UNLABELLED: The aim of our study was to determine the quality of life in elderly patients after PTCA using the SF 36 questionnaire measuring post procedural physical and mental health. STUDY GROUP: 71 pts > 65 years (M-46, F-25), mean age 70.92 +/- 3.49, post PTCA were examined with SF 36 questionnaire. CONTROL GROUP: 73 pts < 65 years (M-61, F-12) mean age 53.6 +/- 7.37, post PTCA. The mean follow-up time was 19.3 +/- 3.2 month in the study group and 18.8 +/- 8.5 month in the control group (NS). The mean physical component summary score was 67.2 vs 69.7 points (NS) in the control group. The mean mental component summary score was 72.3 vs 74.4 points (NS) respectively. There were no significant differences between the groups in the following multi item domains: general health, vitality, social functioning, emotional role functioning and mental health, except physical functioning: 73.5 vs 76.3 points, p < 0.008 respectively. Additional questions asked revealed high satisfaction with performed PTCA, similar in both groups: 65 pts (91.6%) vs 71 pts (98.6%) (NS). 70 (99%) elderly pts considered this method most valuable and would undergo this procedure eagerly again, if necessary. During the observation 21 (29.6%) elderly pts required hospitalization because of the chest pain, 2 pts (2.8%) had nonfatal myocardial infarction and 3 pts (4.2%) underwent surgical revascularisation (CABG). In the control group 12 pts (16.4%) were re-hospitalized, 1 pt (1.4%) required CABG and no acute cardiac events were observed. Smoking was continued significantly more frequently in the younger pts: 12 (16.4%) vs 2 (2.8%) p = 0.05. 72 (98.6%) younger pts and 60 (84.5%) elderly pts reported regular cholesterol level control (NS). Our data suggest that PTCA in elderly pts with symptomatic coronary artery disease, is well tolerated and reflects positively in their quality of life after the procedure.