MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis

Background In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease. Methods We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database. Results We found 190 miRNAs with great abundance in patients with CD, of which 26 miRNAs regulate the gene expression of enzymes known to catalyze epigenetic modifications involved in essentials pathophysiological processes, such as chromatin architecture reorganization, immune response regulation including CD4+ T cells polarization, integrity of gut mucosa, gut microbiota composition and tumorigenesis. Conclusion The integrated analysis of miRNAs with a high relative abundance in patients with CD showed a combined and superimposed gene expression regulation of enzymes associated with relevant epigenetic mechanisms and that could explain, in part, the pathogenesis of CD

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

Concordancia de la motilidad segmentaria evaluada por ecocardiograma transtorácico y resonancia magnética cardíaca en pacientes con infarto agudo de miocardio

Resumen: Introducción: La evaluación de la contractilidad segmentaria es un marcador importante para determinar la extensión de la enfermedad coronaria manifestada a través de un evento isquémico cardiaco. La resonancia magnética cardíaca es el patrón estándar para evaluar dicha motilidad; sin embargo, debido al elevado número de exámenes, la disponibilidad de equipos de resonancia magnética y el costo de los exámenes de resonancia magnética, el uso del ecocardiograma transtorácico es el método diagnóstico de elección. Objetivo: Evaluar la concordancia de la evaluación de la motilidad de diferentes segmentos miocárdicos y de agrupación de segmentos por territorios de irrigación arterial obtenidos por resonancia magnética cardiaca y ecocardiograma transtorácico en pacientes hospitalizados por infarto agudo de miocardio. Métodos: A un grupo de pacientes que llegaron al servicio de emergencia por infarto agudo de miocardio, se les realizó ecocardiograma transtorácico y resonancia magnética cardiaca y se compararon los resultados. La resonancia magnética cardiaca fue el valor de referencia a comparar para fracción de eyección y contractilidad segmentaria. Las pruebas comparativas se hicieron a un 95% de confianza mediante el coeficiente de Kappa-Cohen para evaluar la concordancia entre las medidas. Resultados: No se encontraron diferencias entre la fracción de eyección del ventrículo izquierdo medida por ecocardiograma transtorácico y resonancia magnética cardiaca. Los territorios irrigados por las arterias coronarias descendente anterior y circunfleja tenían una concordancia mediana y buena. En aquellos asociados con la arteria coronaria derecha la concordancia fue baja y media. Conclusiones: La evaluación de la fracción de eyección por ecocardiograma transtorácico no difiere de la evaluación por resonancia magnética cardiaca. En la evaluación de la motilidad segmentaria, la resonancia magnética cardiaca es mejor que el ecocardiograma. Abstract: Introduction: The evaluation of segmental contractility is an important marker to determine the extent of the coronary disease manifested by an ischaemic event. Cardiac magnetic resonance is the standard pattern to evaluate this contractility. However, due to lower availability of magnetic resonance equipment, as well as the increased cost of magnetic resonance tests, the use of the transthoracic echocardiogram is the diagnostic method of choice. Objective: The aim of the study is to compare the evaluation of the motility of different myocardial segments and segments grouped by coronary artery supply territories obtained by cardiac magnetic resonance and transthoracic electrocardiogram performed on patients admitted to hospital with acute myocardial infarction. Methods: A cardiac magnetic resonance and transthoracic electrocardiogram was performed on a group of patients that arrived in the Emergency Department due to an acute myocardial infarction, and the results were compared. The cardiac magnetic resonance was the reference value to compare for the ejection fraction and segmental contractility. Comparative tests were performed with 95% confidence limits using a Kappa-Cohen coefficient to evaluate the agreement between the measurements. Results: No differences were found between the left ventricular ejection fraction measured by cardiac magnetic resonance and transthoracic electrocardiogram. There was average and good agreement in the coronary and circumflex artery supply territories, respectively. In those associated with the right coronary artery, the concordance was low and average. Conclusions: There was no difference between the evaluation of the ejection fraction by transthoracic electrocardiogram or that by cardiac magnetic resonance. In the evaluation of segmental motility, cardiac magnetic resonance was better than transthoracic electrocardiogram. Palabras clave: Ecocardiografía, Resonancia magnética cardiaca, Infarto agudo de miocardio, Keywords: Transthoracic echocardiogram, Cardiac magnetic resonance, Acute myocardial infarctio

Comparison of segmental contractility evaluated by transthoracic echocardiogram and cardiac magnetic resonance in patients with acute myocardial infarction

Introducción: La evaluación de la contractilidad segmentaria es un marcador importante para determinar la extensión de la enfermedad coronaria manifestada a través de un evento isquémico cardiaco. La resonancia magnética cardíaca es el patrón estándar para evaluar dicha motilidad; sin embargo, debido al elevado número de exámenes, la disponibilidad de equipos de resonancia magnética y el costo de los exámenes de resonancia magnética, el uso del ecocardiograma transtorácico es el método diagnóstico de elección. Objetivo: Evaluar la concordancia de la evaluación de la motilidad de diferentes segmentos miocárdicos y de agrupación de segmentos por territorios de irrigación arterial obtenidos por resonancia magnética cardiaca y ecocardiograma transtorácico en pacientes hospitalizados por infarto agudo de miocardio. Métodos: A un grupo de pacientes que llegaron al servicio de emergencia por infarto agudo de miocardio, se les realizó ecocardiograma transtorácico y resonancia magnética cardiaca y se compararon los resultados. La resonancia magnética cardiaca fue el valor de referencia a comparar para fracción de eyección y contractilidad segmentaria. Las pruebas comparativas se hicieron a un 95% de confianza mediante el coeficiente de Kappa-Cohen para evaluar la concordancia entre las medidas. Resultados: No se encontraron diferencias entre la fracción de eyección del ventrículo izquierdo medida por ecocardiograma transtorácico y resonancia magnética cardiaca. Los territorios irrigados por las arterias coronarias descendente anterior y circunfleja tenían una concordancia mediana y buena. En aquellos asociados con la arteria coronaria derecha la concordancia fue baja y media.Introduction: The evaluation of segmental contractility is an important marker to determine the extent of the coronary disease manifested by an ischaemic event. Cardiac magnetic resonance is the standard pattern to evaluate this contractility. However, due to lower availability of magnetic resonance equipment, as well as the increased cost of magnetic resonance tests, the use of the transthoracic echocardiogram is the diagnostic method of choice. Objective: The aim of the study is to compare the evaluation of the motility of different myocardial segments and segments grouped by coronary artery supply territories obtained by cardiac magnetic resonance and transthoracic electrocardiogram performed on patients admitted to hospital with acute myocardial infarction. Methods: A cardiac magnetic resonance and transthoracic electrocardiogram was performed on a group of patients that arrived in the Emergency Department due to an acute myocardial infarction, and the results were compared. The cardiac magnetic resonance was the reference value to compare for the ejection fraction and segmental contractility. Comparative tests were performed with 95% confidence limits using a Kappa-Cohen coefficient to evaluate the agreement between the measurements. Results: No differences were found between the left ventricular ejection fraction measured by cardiac magnetic resonance and transthoracic electrocardiogram. There was average and good agreement in the coronary and circumflex artery supply territories, respectively. In those associated with the right coronary artery, the concordance was low and average. Conclusions: There was no difference between the evaluation of the ejection fraction by transthoracic electrocardiogram or that by cardiac magnetic resonance. In the evaluation of segmental motility, cardiac magnetic resonance was better than transthoracic electrocardiogram

Global variations in heart failure etiology, management, and outcomes

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper–middle-income, lower–middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a β-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper–middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower–middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper–middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower–middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper–middle-income countries (ratio = 2.4), similar in lower–middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper–middle-income countries (9.7%), then lower–middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower–middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally

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.)

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN