Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Archéologie, Identités et Tourisme Circuit touristique des Pétroglyphes de la Ovejería (San Pedro de Colalao, Tucumán, Argentina)

El turismo es una actividad en desarrollo que a nivel mundial está avanzando y se está diversificando a una velocidad alarmante (Nielsen et al. 2003). Dentro de este avance de la "industria sin chimeneas", el patrimonio cultural adquiere un valor de mercancía convertible en moneda (Ballart 1997) generando altas expectativas económicas a las comunidades que lo contienen. Actualmente, ante la falta de una planificación adecuada sobre la protección del patrimonio por parte del Estado (Nacional y Provincial), las comunidades y agrupaciones indígenas están demostrando un mayor interés en relación a la protección y conservación cultural (Endere y Curtoni 2003) y reclamando una mayor participación en los beneficios económicos para revertir su situación de exclusión y de marginalidad en la que viven actualmente.Le tourisme progresse au niveau international et se diversifie à grande vitesse (Nielsen et al. 2003). Dans ce progrès de l’« industrie sans cheminée », le patrimoine culturel acquiert une valeur de marchandise génératrice de ressources (Ballart, 1997), produisant de grands bénéfices économiques pour les communautés qui le possè- dent. Actuellement, devant le manque de planification convenable pour la défense du patrimoine de la part de l’État (national et provincial), communautés et groupes indigènes démontrent un intérêt accru pour la protection et la conservation de leur culture (Endere & Curtoni, 2003), réclamant davantage de participation aux revenus économiques afin de changer la situation d’exclusion et de marginalité où ils se trouvent aujourd’hui.International tourism is most rapidly progressing and diversifying (Nielsen et al. 2003). In the progression of the “industry without chimney stacks”, cultural heritage acquires a market value that can produce considerable economic benefits for communities possessing such a heritage. At present, confronted with a lack of suitable State (both national and provincial) planning to defend their heritage, communities and indigenous groups are the situation of exclusion and marginality that they feel they are in today. showing an increased interest in protecting and preserv- ing their culture (Endere & Curtoni 2003). They demand an increased share of economic revenues in order to change.Fil: Corbalan, Mario. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; ArgentinaFil: Rodriguez Curletto, Silvina Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; ArgentinaFil: del Bel, Ezequiel. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Estudios Sociales. Universidad Nacional de Tucumán. Instituto Superior de Estudios Sociales; Argentin

Changes in cyclic AMP dependent protein kinase and active stiffness in the rat volume overload model of heart hypertrophy

Objective: The aim was to clarify the role of cyclic AMP dependent protein kinase (PKA) and changes in mechanical heart function during development of cardiac hypertrophy induced by volume overload. Methods: Protein and DNA contents, PKA activity, and peak systolic stress-strain relationships in hearts from animals submitted to aortocaval shunt were assessed as a function of time. Sham operated (control) rats were used as controls. Results: Heart weight to body weight ratio and cardiac protein content per heart increased from d 7 (p<0.005 and p<0.01, respectively) reaching their highest values by d 56; the same occurred with cardiac DNA content. PKA activity·g-1 tissue in soluble extracts of hearts from rats with aortocaval shunt increased by 2.7-fold on d 2 (p<0.005), reached a ninefold peak increase by d 7 (p<0.0001) and declined to fourfold by d 56 with respect to control values. The end peak systolic stress-strain relation slopes were: control, 368(SEM 14) g·cm-2 (n = 16); aortoca

Occurrence of dioctophymosis in canines within a riparian zone of the Río de la Plata watercourse, in Ensenada, Buenos Aires Province, Argentina

Dioctophymosis is a parasitic disease occasioned by the so-called "giant kidney worm", Dioctophyme renale, a nematode with an indirect life cycle. This parasite´s definitive host is the mink, Mustela vison, though numerous wild and domestic mammals as well as man can serve as final hosts. The worms also can be in ectopic locations in the body. We surveyed 692 canines by ecography, urine sampling, surgery, necropsy, and clinical examination and diagnosed 244 cases of dioctophymosis (35.3%). Of the cases of dioctophymosis identified, 30.7% were obtained by ecography, 45.9% by urinalysis, and 17.6% by both those techniques -in addition to positive findings through surgery (2.5%), necropsy (2.5%), and the spontaneous elimination of the parasites (0.8%). Cases of dioctophymosis were observed in animals as young as 4 months of age up to 15 years. The frequency of D. renale diagnosis throughout the sampling period varied significantly. There was a statistically significant association between risk factors (swimming in the river, eating frogs, fish or eels, drinking ditch water) and the prevalence of infection. It was discussed the period missing after infection in canines.Facultad de Ciencias Veterinaria

Association of beta2 adrenergic receptor polymorphisms and related haplotypes with triglyceride and LDL-cholesterol levels.

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between beta(2)-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the beta(2)-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the beta(2)-AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5'LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5'LC-Arg19 homozygous (P=0.03 and P=0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5'LC-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5'LC-Cys(19)Arg(16)Gln(27) haplotype

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)