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

Gallstone ileus: management options and results on a series of 40 patients Íleo biliar: opciones terapéuticas y resultados en una serie de 40 casos

Introduction: controversy remains about the management of gallstone ileus. While some authors propose enterotomy, others defend the one-stage procedure (simultaneously fistula repair). The objective of the present study was to analyze management options and comparative study their results. Material and methods: retrospective and descriptive study with revision of clinical stories of patients with the diagnosis of gallstone ileus between 1987 and 2008. All the following variables were recorded: dates of hospital admission, surgery and discharge, age, sex, pathological antecedents, preoperative or intraoperative diagnosis, treatment, location of the fistula and location of the obstruction. End-result variables were: postoperative complications, mortality, complications during the follow-up and biliary complications. Results: a total of 40 patients were included of 46,648 admissions. Age, comorbidity, and intraoperative diagnosis were related with poorer short- and long-outcomes. The percentage of postoperative complications was similar for groups with and without fistula repair. Mortality was higher in the group with fistula repair (15vs. 25%). Biliary complications were more frequent in the group without fistula repair (11 vs. 0%). Sex, location of the fistula and location of the obstruction did not be related with the prognosis. Conclusion: one-stage procedure is related with higher mortality rate than enterotomy alone. Nevertheless, fistula repair reduces the number of biliary complications during the follow-up.<br>Introducción: todavía existe gran controversia sobre el mejor tratamiento del íleo biliar. Algunos autores proponen la enterotomía aislada, mientras otros defienden la reparación de la fístula bilioentérica en el mismo acto quirúrgico. El objetivo del presente estudio fue analizar las opciones terapéuticas en estos pacientes y estudiar sus resultados. Material y métodos: estudio retrospectivo y descriptivo, con revisión de las historias clínicas de los pacientes diagnosticados de íleo biliar desde 1987 hasta 2008. Se recogieron las fechas de ingreso, de intervención y del alta, edad, sexo, antecedentes patológicos, diagnóstico preoperatorio o intraoperatorio, tratamiento, lugar de la fístula y lugar de la obstrucción. Como variables de resultado se utilizaron las complicaciones postoperatorias, mortalidad, complicaciones en el seguimiento y complicaciones biliares. Resultados: se incluyeron 40 pacientes sobre 46.648 ingresos. La edad, la comorbilidad y el diagnóstico intraoperatorio se relacionaron con peores resultados a corto y largo plazo. El porcentaje de complicaciones postoperatorias fue similar para el grupo con abordaje de la fístula y para el grupo con enterotomía aislada. La mortalidad fue superior en el grupo con abordaje de la fístula (15 frente a 25%). Las complicaciones biliares fueron más frecuentes en el grupo sin abordaje de la fístula biliar (11 frente a 0%). El sexo, lugar de la fístula o el lugar de la obstrucción no demostraron diferencias. Conclusión: la cirugía en un solo tiempo se relaciona con mayor mortalidad que la enterotomía aislada. No obstante, añadir la reparación de la fístula reduce el número de complicaciones biliares en el seguimiento

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.)