1,721,036 research outputs found
The Paragon-HF trial: The sacubitril/valsartan in heart failure with preserved ejection fraction
No full textHeart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril-valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous post hoc analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence
The PARAGON-HF Trial: Toward Extension to Patients With HF Middle Range Ejection Fraction
No full textRecent advances in pharmacological treatment of heart failure
Full text linkBackground: Over the last years, several trials offered new evidence on heart failure (HF) treatment. Design and results: For HF with reduced left ventricular ejection fraction, type 2 sodium—glucose cotransporter inhibitors, aside from sacubitril—valsartan, demonstrated extraordinary efficacy in ameliorating patients' prognosis. Some new molecules (eg vericiguat, omecamtiv mecarbil and ferric carboxymaltose) correct iron deficiency and have shown to be capable of furthering reducing the burden of HF hospitalisation. Finally, there is new evidence on the possible therapeutic approaches of HF patients with mid-range or preserved left ventricular ejection fraction. Conclusions: This review aimed to revise the main novelties in the field of HF therapy and focus on how the daily clinical approach to patient treatment is changing
Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development
Full text linkThe liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium-glucose cotransporters sodium-glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin-angiotensin-aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective
Unresolved issues in left ventricular postischemic remodeling and progression to heart failure
No full text: In the past decades, myocardial infarction periacute mortality markedly declined since coronary reperfusion therapy has been adopted. Despite immediate benefits of coronary blood flow restoration, the percentage of new onset heart failure has increased over time suggesting that ischemia can run detrimental consequences beyond the immediate anoxic hit. By accepting to aggregate all types of heart failure regardless of underlying cause, the current practice did not help to shed light on the complex postischemic cardiac biology indicating that heart failure is somewhat unavoidable. In the ischemic sequel, the activated mechanisms aim to repair the infarcted zone and to compensate for the lost myocyte functions, thus allowing the heart to maintain the efficient cardiac output for vital organs. The variety of underlying preexisting conditions, as well as the multifaceted components of cardiac molecular structure, cellular state, and electrophysiological postischemic events pave the way for long-term adverse cardiac remodeling. We focused our attention on multiple factors, which include myocyte loss, hypertrophy, hyperplasia, extracellular matrix changes linked to myocardial fibrosis and scar, metabolic imbalance, as well as immunologic response occurring in the acute myocardial aftermath. Moreover, we reported both current pharmacological strategies and future perspectives that might be useful in clinical practice. Furthermore, we discussed the cardiac magnetic resonance as the most promising noninvasive imaging tool, which could be helpful in identifying the amount of myocardial damage. Despite the redundancy of molecular pathogenic mechanisms making it impossible to estimate the proportionate contributions in generating the heart failure phenotype, a deeper understanding will contribute to more customized patient management
2019 ESC Guidelines on diabetes, pre-diabetes and cardiovascular diseases: what's new? The cardiologist's point of view
No full textSustainable and Energy-Efficient Industrial Systems: Modelling the Environmental Impact of Logistics Facilities
Full text linkIn the last decade industrial systems have been affected by increased challenges, and among those the need for more sustainable production and logistics has been called into question by both practitioners and academia. Within industrial networks, logistics facilities traditionally represent key nodes as they have a direct impact on both companies’ service levels and logistics costs. Recently, their complexity has dramatically increased due to their ever-demanding requirements and pressures from stakeholders and society. In this context, companies have started to search for solutions for greener warehousing processes and energy efficiency improvements. Still, on the academic side, a limited number of studies have been found addressing the quantification of logistics facilities’ environmental performance, the impact of the green warehousing practices in place, and the related effects on warehouse consumption and emission reduction. This paper aims to address this research gap by proposing a simulation-based approach where multiple scenarios of a real logistics facility are discussed, grounded on a conceptual framework that offers a roadmap towards sustainable and energy-efficient warehousing. Different scenarios are outlined, and the related performances are examined in terms of energy consumption and CO2eq emissions. Implications of the results are discussed and streams for future investigation are identified
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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