Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus.

BACKGROUND: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

[Female gender is an independent predictor of in-hospital mortality in patients with ST segment elevation acute myocardial infarction treated with primary angioplasty]. / El género femenino es un predictor independiente de la mortalidad intrahospitalaria en pacientes con infarto agudo de miocardio con elevación del segmento ST revascularizado mediante una angioplastia primaria.

OBJECTIVE: The aim of this study was to determine the influence of gender on in hospital outcome in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary angioplasty (PA). DESIGN AND SCOPE: Prospective study of a cohort of patients consecutively admitted to the Coronary Unit of a tertiary hospital in the period of January to October 2004 with the diagnoses of IAMEST and treated with PA. PATIENTS: Consecutive sample of 86 patients with this diagnosis divided into two groups based on sex: 52 men and 34 women. MAIN VARIABLES OF INTEREST: In both groups, we analyzed the baseline clinical-demographic characteristics, extension of the coronary disease (ECD), success of the PA, appearance of heart failure (HF) and in-hospital mortality in the first 28 days after admission. We analyzed predictors of mortality in a multivariate model. RESULTS: The women were older (70+/-8 versus 65+/-11; p=0.02) and had greater prevalence of diabetes (37% versus 18%; p=0.002) and hypertension (58% versus 37%; p<0.001) than the men while the men had greater frequency of smoking (34% versus 22%; p=0.001). There were no differences in the presence of hyperlipidemia, ECD or the success of PA. Women had a higher incidence of HF on admission (22% versus 12%; p=0.01) and in-hospital mortality (17% versus 8%; p=0.002). In the multivariate analyses, female sex and HF on admission continued to be predictors of in-hospital mortality. CONCLUSIONS: In our study, female gender was an independent predictor of in-hospital mortality in patients with IAMEST treated with PA.

El género femenino es un predictor independiente de la mortalidad intrahospitalaria en pacientes con infarto agudo de miocardio con elevación del segmento ST revascularizado mediante una angioplastia primaria / Female gender is an independent predictor of in-hospital mortality in patients with ST segment elevation acute myocardial infarction treated with primary angioplasty

Objetivo. Analizar la influencia del sexo en el pronóstico intrahospitalario del infarto agudo de miocardio con elevación del segmento ST (IAMEST) revascularizado mediante una angioplastia primaria (AP). Diseño y ámbito. Estudio prospectivo de una cohorte de pacientes consecutivamente ingresados en la Unidad Coronaria de un hospital terciario durante el periodo de enero a octubre de 2004, con diagnóstico de IAMEST y tratados con AP. Pacientes. Muestra consecutiva de 86 pacientes con dicho diagnóstico dividida en dos grupos en función del sexo: 52 hombres y 34 mujeres. Variables de interés principales. En ambos grupos analizamos las características clínico-demográficas basales, la extensión de la enfermedad coronaria (EEC), el éxito de la AP, la aparición de insuficiencia cardiaca (IC) y la mortalidad intrahospitalaria en los primeros 28 días tras el ingreso. Se analizaron predictores de mortalidad en un modelo multivariado. Resultados. Las mujeres presentaron mayor edad (70 ± 8 frente a 65 ± 11; p = 0,02) y prevalencia de diabetes (37% frente a 18%; p = 0,002) y de hipertensión arterial (58% frente a 37%; p < 0,001) que los hombres, mientras que estos presentaron mayor frecuencia de tabaquismo (34% frente a 22%; p = 0,001). No hubo diferencias en la presencia de hiperlipidemia, la EEC o el éxito de la AP. Las mujeres presentaron mayor incidencia de IC al ingreso (22% frente a 12%; p = 0,01) y de mortalidad intrahospitalaria (17% frente a 8%; p = 0,002). En el análisis multivariado, el sexo femenino y la IC al ingreso permanecieron como predictores de mortalidad intrahospitalaria. Conclusiones. En nuestro estudio, el sexo femenino fue un predictor independiente de mortalidad intrahospitalaria en pacientes con IAMEST tratados con AP

Objective. The aim of this study was to determine the influence of gender on in hospital outcome in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary angioplasty (PA). Design and scope. Prospective study of a cohort of patients consecutively admitted to the Coronary Unit of a tertiary hospital in the period of January to October 2004 with the diagnoses of IAMEST and treated with PA. Patients. Consecutive sample of 86 patients with this diagnosis divided into two groups based on sex: 52 men and 34 women. Main variables of interest. In both groups, we analyzed the baseline clinical-demographic characteristics, extension of the coronary disease (ECD), success of the PA, appearance of heart failure (HF) and in-hospital mortality in the first 28 days after admission. We analyzed predictors of mortality in a multivariate model. Results. The women were older (70 ± 8 versus 65 ± 11; p = 0.02) and had greater prevalence of diabetes (37% versus 18%; p = 0.002) and hypertension (58% versus 37%; p < 0.001) than the men while the men had greater frequency of smoking (34% versus 22%; p = 0.001). There were no differences in the presence of hyperlipidemia, ECD or the success of PA. Women had a higher incidence of HF on admission (22% versus 12%; p = 0.01) and in-hospital mortality (17% versus 8%; p = 0.002). In the multivariate analyses, female sex and HF on admission continued to be predictors of in-hospital mortality. Conclusions. In our study, female gender was an independent predictor of in-hospital mortality in patients with IAMEST treated with PA

New pharmacologic options in the treatment of acute coronary syndromes and myocardial ischemia-reperfusion injury: potential role of levosimendan.

Modern and effective therapeutic possibilities have improved the management and outcomes in acute coronary syndromes and acute myocardial infarction. However, substantial morbidity and mortality still remain. Myocardial ischemia-reperfusion injury may contribute to additional damage to myocardial necrosis and apoptosis. Therefore, it has been focused on attention and field of therapeutic actions in the last years. The main mechanisms involved in the pathogenesis of ischemia-reperfusion injury are depressed energy metabolism, elevated oxidative damage, and altered calcium homeostasis. In experimental trials, a variety of drugs have proved effectiveness for the prevention and treatment of the ischemia-reperfusion injury. However, its efficacy, not always confirmed, has not yet been established in clinical practice. On the basis of the strong evidence linking potassium ATP dependent channels opening in the myocardium and its proved cardioprotective role during ischemia, these channels have been pointed out as possible and promising pharmacological targets in this setting. Some evidences suggest that the calcium sensitizing agent levosimendan may have of beneficial and exerts cardioprotective effects on myocardial ischemia and ischemia-reperfusion injury. Further investigation is warranted on this novel application of levosimendan.

[Systemic inflammatory response syndrome: incidence and influence on outcome in acute myocardial infarction treated with primary angioplasty]. / Síndrome de respuesta inflamatoria sistémica: incidencia e influencia pronóstica en el infarto agudo de miocardio tratado con angioplastia primaria.

OBJECTIVE: To assess the incidence, clinical profile and influence on outcome of systemic inflammatory response syndrome (SIRS) in patients with acute myocardial infarction (AMI) treated with primary angioplasty (PA). DESIGN: Prospective observational study. SCOPE: A 12-beds coronary care unit at a university hospital. PATIENTS AND METHODS: Patients with AMI treated with PA, admitted in 2004 were studied. PRINCIPAL VARIABLES OF INTEREST: Age, gender, anterior localization of AMI, smoking, arterial hypertension, diabetes mellitus, troponin Ic levels, time delays until PA, heart failure, left ventricular ejection fraction (LVEF), in-hospital length of stay and mortality. RESULTS: Ninety patients were included. SIRS was diagnosed in 15 patients (16.6%), who were older (72 +/- 7 vs 66 +/- 9 years; p = 0,01). These patients had a greater frequency of diabetes mellitus (42% vs 17%; p = 0.01), higher troponin Ic levels (80 +/- 12 vs 68 +/- 19 ng/ml; p = 0.02), lower LVEF (41 +/- 8% vs 51 +/- 12%; p = 0.002), longer in-hospital length of stay (18 +/- 5 vs 7 +/- 3 days, p = 0.001), and higher in-hospital mortality (10 vs 3%, p = 0.03) compared with patients without SIRS. Diabetes mellitus (OR: 1.7; 95% CI: 1.2-1.9) and lower ejection fraction (OR: 2.3; 95% CI: 1.5-3.1) were the independent predictors of the presence of systemic inflammatory response syndrome. In multivariant analysis SIRS was an independent predictor of mortality in AMI patients treated with PA (OR: 3.3; 95% CI: 1.3-6). CONCLUSIONS: Systemic inflammatory response syndrome may be present in AMI patients treated with PA and its presence is associated to a worse outcome and longer in-hospital stay.

Síndrome de respuesta inflamatoria sistémica: incidencia e influencia pronóstica en el infarto agudo de miocardio tratado con angioplastia primaria / Systemic inflammatory response syndrome: incidence and influence on outcome in acute myocardial infarction treated with primary angioplasty

Objetivo. Analizar la incidencia y efecto sobre la mortalidad del síndrome de respuesta inflamatoria sistémica (SRIS) en el infarto agudo de miocardio (IAM) tratado con angioplastia primaria (AP). Diseño. Estudio observacional prospectivo. Ámbito. Unidad de coronarias con 12 camas en un hospital universitario. Pacientes. Pacientes con IAM tratados con AP ingresados durante el año 2004. Variables de interés principales. Edad, sexo, localización anterior del IAM, tabaquismo, hipertensión arterial, diabetes mellitus, niveles de troponina Ic, tiempos de retraso hasta la AP, presencia de insuficiencia cardíaca, fracción de eyección del ventrículo izquierdo (FEVI), estancia y mortalidad intrahospitalaria. Resultados. Se incluyeron 90 pacientes, en 15 (16,6%) se diagnosticó SRIS. Éstos presentaron mayor edad (72 ± 7 frente a 66 ± 9 años; p = 0,01), mayor frecuencia de diabetes mellitus (42% frente a 17%; p = 0,01), niveles más elevados de troponina Ic (80 ± 12 frente a 68 ± 19 ng/ml; p = 0,02), FEVI más baja (41 ± 8% frente a 51 ± 12%; p = 0,002), mayor estancia hospitalaria (18 ± 5 frente a 7 ± 3 días, p = 0,001) y mortalidad intrahospitalaria (10% frente a 3%, p = 0,03) que los pacientes sin diagnóstico de SRIS. Fueron variables predictivas independientes de la presencia de SRIS la diabetes mellitus (OR: 1,7; IC 95%: 1,2-1,9) y una menor FEVI (OR: 2,3; CI 95%: 1,5-3,1). El análisis multivariante mostró que la presencia de SRIS fue variable independiente predictora de mortalidad en los pacientes con IAM tratados con AP (OR: 3,3; IC 95%: 1,3-6). Conclusiones. El SRIS se presenta, con relativa frecuencia, en pacientes con IAM tratados con AP y se asocia con una estancia hospitalaria más larga y un peor pronóstico

Objective. To assess the incidence, clinical profile and influence on outcome of systemic inflammatory response syndrome (SIRS) in patients with acute myocardial infarction (AMI) treated with primary angioplasty (PA). Design. Prospective observational study. Scope. A 12-beds coronary care unit at a university hospital. Patients and methods. Patients with AMI treated with PA, admitted in 2004 were studied. Principal variables of interest. Age, gender, anterior localization of AMI, smoking, arterial hypertension, diabetes mellitus, troponin Ic levels, time delays until PA, heart failure, left ventricular ejection fraction (LVEF), in-hospital length of stay and mortality. Results. Ninety patients were included. SIRS was diagnosed in 15 patients (16.6%), who were older (72 ± 7 vs 66 ± 9 years; p = 0,01). These patients had a greater frequency of diabetes mellitus (42% vs 17%; p = 0.01), higher troponin Ic levels (80 ± 12 vs 68 ± 19 ng/ml; p = 0.02), lower LVEF (41 ± 8% vs 51 ± 12%; p = 0.002), longer in-hospital length of stay (18 ± 5 vs 7 ± 3 days, p = 0.001), and higher in-hospital mortality (10 vs 3%, p = 0.03) compared with patients without SIRS. Diabetes mellitus (OR: 1.7; 95% CI: 1.2-1.9) and lower ejection fraction (OR: 2.3; 95% CI: 1.5-3.1) were the independent predictors of the presence of systemic inflammatory response syndrome. In multivariant analysis SIRS was an independent predictor of mortality in AMI patients treated with PA (OR: 3.3; 95% CI: 1.3-6). Conclusions. Systemic inflammatory response syndrome may be present in AMI patients treated with PA and its presence is associated to a worse outcome and longer in-hospital stay

Troponinosis en los servicios de urgencias / Troponiosis in the emergency services

No disponible

[Plasma homocysteine levels in Spanish patients with coronary artery disease]. / Concentraciones de homocisteína en plasma en pacientes españoles con enfermedad arterial coronaria.

OBJECTIVE: A rise in plasma levels of the amino acid homocysteine (HCY) is a possible risk factor in cardiovascular disease. The mechanisms proposed to explain how HCY can increase the risk of vascular disease include its direct effect on the vascular endothelium and its role in increasing the risk of thrombosis. The present work has been designed to determine HCY levels in patients with coronary artery disease (CAD) residents in the Canary Islands and to establish whether hyperhomocysteinemia can be considered as an risk factor. METHODS: The sample studied consisted of 132 patients with, angiographically demonstrated, CAD and 18 controls with normal coronary arteries. Biochemical parameters determined included: HCY, vitamin B12, vitamin B6, folic acid, creatinine, cholesterol and its fractions, triglycerides, glucose and fibrinogen. RESULTS: Mean levels of HCY were not significantly different between the cases and controls (p = 0.37). In the distribution of HCY levels into quintiles there was no significant association between the quintiles and the occurrence of CAD (p = 0.57). Multiple logistic regression analysis in which the risk factors were compared with quintiles 2, 3, 4 and 5 of HCY did not reveal a significant relation between HCY levels and risk of CAD. CONCLUSIONS: This study questions the previously accepted consideration that hyperhomocysteinemia is a risk factor of CAD. Controlled intervention trials are, therefore, necessary to clarify the possible association between total HCY levels and cardiovascular disease.

Concentraciones de homocisteína en plasma en pacientes españoles con enfermedad arterial coronaria / Plasma homocysteine levels in spanish patients with coronary artery disease

Objetivo: El aumento de las concentraciones séricas del aminoácido homocisteína (HCY) es un posible factor de riesgo de enfermedades cardiovasculares. Los mecanismos propuestos para explicar porqué la HCY puede hacer aumentar el riesgo de enfermedades vasculares son un efecto directo sobre el endotelio vascular y su intervención en el aumento del riesgo de trombosis. El presente estudio ha sido diseñado para conocer la homocisteinemia de pacientes residentes en las Islas Canarias con enfermedad arterial coronaria (EAC), y comprobar si la hiperhomocisteinemia es un factor de riesgo. Métodos: Se incluyeron 132 pacientes afectos de EAC demostrada angiográficamente y 18 controles con arterias coronarias normales. Se determinaron los valores de HCY, vitamina B12, vitamina B6 , ácido fólico, creatinina, colesterol con sus diferentes fracciones, triglicéridos, glucosa y fibrinógeno. Resultados: Las concentraciones medias de HCY no difirieron significativamente (p= 0,37) entre los casos y los sujetos de control. La distribución de los niveles de HCY por quintiles no parece estar asociada sobre la producción de EAC (p= 0,57). El análisis de regresión logística múltiple de los factores de riesgos comparado con los quintiles 2, 3, 4 y 5 de HCY no demostró evidencia significativa entre la concentración de HCY y el riesgo de EAC. Conclusiones: Este estudio añade incertidumbre de que la hiperhomocisteinemia sea factor de riesgo para EAC. Es necesario realizar estudios controlados de intervención clínica, algunos de los cuales están en marcha, para intentar aclarar las interrelaciones entre la HCY total y las enfermedades cardiovasculares (AU)

[Right ventricular cardiomyopathy: a diagnosis to bear in mind]. / Miocardiopatía ventricular derecha: un diagnóstico a tener en cuenta.

Arrhythmogenic right ventricular cardiomyopathy is a entity of unknown etiology, that is pathologically characterized by right ventricular myocardial atrophy and fibroadipous tissue replacement. We present the case of a 65-year-old male patient with the diagnosis of chronic liver disease, whose study lead a diagnosis of Arrhythmogenic right ventricular cardiomyopathy.

Miocardiopatia Ventricular Derecha: un diagnostico a tener en cuenta / Right Ventricular Cardiomyopathy: a diagnosis to bear in mind

La miocardiopatía arritmogénica ventricular derecha es una entidad de etiopatogenia desconocida, que patológicamente se caracteriza por atrofia miocárdica ventricular derecha y sustitución por tejido fibroadiposo. Presentamos un paciente de 65 años de edad diagnosticado de hepatopatía crónica, cuyo estudio llevó al diagnóstico de miocardiopatía arritmogénica ventricular derecha. (AU)

[Infectious endocarditis of prosthetic valves due to Staphylococcus capitis: a new case]. / Endocarditis infecciosa sobre válvulas protésicas causada por Staphylococcus capitis: un nuevo caso.

We present the case of a male patient with aortic and mitral valve bioprostheses who developed infectious endocarditis due to Staphylococcus capitis, which has recently been described as an agent producing infectious endocarditis in native and prosthetic cardiac valves. The patient's course evolved unfavorably, despite specific antibiotic treatment, leading to the surgical replacement of the valve, which completely resolved the problem. This case points out that, although rare, in infectious endocarditis due to Staphylococcus capitis its pathogenicity is significant.

Synthesis and Reactivity with beta-Lactamases of "Penicillin-like" Cyclic Depsipeptides.

Several 7-carboxy-3-amido-3,4-dihydro-2H-1-benzopyran-2-ones have been synthesized as potential beta-lactamase substrates and/or mechanism-based inhibitors. Substituted o-tyrosine precursors were prepared by the Sörensen method and then heated in vacuo to give the lactones. These compounds are cyclic analogues of aryl phenaceturates which are known to be beta-lactamase substrates. The goal of incorporating the scissile ester group into a lactone was to retain the leaving group tethered to the acyl moiety at the acyl-enzyme stage of turnover by serine beta-lactamases, in a manner similar to that during penicillin turnover. Further, in two cases, a functionalized methylene group para to the leaving group phenoxide oxygen was incorporated. These molecules possess a latent p-quinone methide electrophile which could, in principle, be unmasked during enzymic turnover and react with an active site nucleophile. All of these compounds were found to be substrates of class A and C beta-lactamases, the first delta-lactones with such activity. Generally, k(cat) values were smaller than for the analogous acyclic depsipeptides, which suggests that the tethered leaving group may obstruct the attack of water on the acyl-enzymes. Further exploration of this structural theme might lead to quite inert acyl-enzymes and thus to significant inhibitors. Despite the apparent advantage offered by the longer-lived acyl-enzymes, the functionalized compounds were no better as irreversible inhibitors than comparable acyclic compounds [Cabaret, D.; Liu, J.; Wakselman, M.; Pratt, R. F.; Xu, Y. Bioorg. Med. Chem. 1994, 2, 757-771]. Thus, even tethered quinone methides, at least when placed as dictated by the structures of the present compounds, were unable to efficiently trap a nucleophile at serine beta-lactamase active sites.

[The adult respiratory distress syndrome as a complication of the APSAC treatment of acute myocardial infarct. Apropos a case]. / Síndrome de distrés respiratorio del adulto como complicación del tratamiento del infarto agudo de miocardio con APSAC. A propósito de un caso.

Thrombolytic therapy has shown to be effective in acute myocardial infarction, and its benefits on left ventricular function and later survival are well known. However it is not a therapy free of complications and side effects. Allergic reactions, anafilaxia, hypotension, and several kinds of hemorrhages have been reported. Adult respiratory distress syndrome after streptokinase administration has been also described, and one case, recently communicated, after APSAC therapy. We present the case of a male with acute myocardial infarction who developed adult respiratory distress syndrome after APSAC therapy, with different outcome than the first case published in the literature. Finally, we discussed the mechanisms by means these drugs can produce such a complication.