1,721,281 research outputs found
Cardiac inotropes: current agents and future directions
No full textIntrinsic inotropic stimulation of the heart is central to the regulation of cardiovascular function, and exogenous inotropic therapies have been used clinically for decades. Unfortunately, current inotropic drugs have consistently failed to show beneficial effects beyond short-term haemodynamic improvement in patients with heart failure. To address these limitations, new agents targeting novel mechanisms are being developed: (i) istaroxime has been developed as a non-glycoside inhibitor of the sodium-potassium-ATPase with additional stimulatory effects on the sarcoplasmic reticulum calcium pump (SERCA) and has shown lusitropic and inotropic properties in experimental and early clinical studies; (ii) from a mechanistic point of view, the cardiac myosin activators, directly activating the acto-myosin cross-bridges, are most appealing with improved cardiac performance in both animal and early clinical studies; (iii) gene therapy approaches have been successfully employed to increase myocardial SERCA2a; (iv) nitroxyl donors have been developed and have shown evidence of positive lusitropic and inotropic, as well as potent vasodilatory effects in early animal studies; (v) the ryanodine receptor stabilizers reduce pathological leak of calcium from the sarcoplasmic reticulum with initial promising pre-clinical results; and finally, (vi) metabolic energy modulation may represent a promising means to improve contractile performance of the heart. There is an urgent clinical need for agents that improve cardiac performance with a favourable safety profile. These current novel approaches to improving cardiac function provide the hope that such agents may soon be available
Heart failure
No full textHeart failure is common in adults, accounting for substantial morbidity and mortality worldwide. Its prevalence is increasing because of ageing of the population and improved treatment of acute cardiovascular events, despite the efficacy of many therapies for patients with heart failure with reduced ejection fraction, such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists, and advanced device therapies. Combined angiotensin receptor blocker neprilysin inhibitors (ARNIs) have been associated with improvements in hospital admissions and mortality from heart failure compared with enalapril, and guidelines now recommend substitution of ACE inhibitors or ARBs with ARNIs in appropriate patients. Improved safety of left ventricular assist devices means that these are becoming more commonly used in patients with severe symptoms. Antidiabetic therapies might further improve outcomes in patients with heart failure. New drugs with novel mechanisms of action, such as cardiac myosin activators, are under investigation for patients with heart failure with reduced left ventricular ejection fraction. Heart failure with preserved ejection fraction is a heterogeneous disorder that remains incompletely understood and will continue to increase in prevalence with the ageing population. Although some data suggest that spironolactone might improve outcomes in these patients, no therapy has conclusively shown a significant effect. Hopefully, future studies will address these unmet needs for patients with heart failure. Admissions for acute heart failure continue to increase but, to date, no new therapies have improved clinical outcomes
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Acute decompensated heart failure update
No full textAcute decompensated heart failure (ADHF) continues to increase in prevalence and is associated with substantial mortality and morbidity including frequent hospitalizations. The American Heart Association is predicting that more than eight million Americans will have heart failure by 2030 and that the total direct costs associated with the disease will rise from 70 billion in 2030. The increase in the prevalence and cost of HF is primarily the result of shifting demographics and a growing population. Although many large, randomized, controlled clinical trials have been conducted in patients with chronic heart failure, it was not until recently that a growing number of studies began to address the management of ADHF. It is the intent of this review to update the clinician regarding the evaluation and optimal management of ADHF
Medical treatment of heart failure with reduced ejection fraction: the dawn of a new era of personalized treatment?
No full textRecent trials have shown the efficacy of new drugs for the medical therapy of heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduced hospitalizations for heart failure (HF), HF events, and cardiovascular death in patients with HFrEF or hospitalized for HF. Iron repletion with ferric carboxymaltose (FCM) improved symptoms, functional capacity, and quality of life in chronic HFrEF patients, and decreased the risk of subsequent HF hospitalizations in subjects with acutely decompensated HF. New-generation potassium binders may allow initiation and up-titration of renin-angiotensin-aldosterone system inhibitors (RASis). Lastly, the guanylate cyclase stimulator vericiguat and the myosin activator omecamtiv mecarbil reduced the primary endpoint in two major controlled trials. These results open novel pathways for the treatment of HFrEF. This review discusses new opportunities of an individualized approach to HFrEF pharmacotherapy, where new compounds expand a spectrum of drugs that target primarily neuroendocrine activation. SGLT2i can be safely applied once daily at a fixed dose to the vast majority of patients with HFrEF, including those with moderate renal dysfunction and/or systolic blood pressure as low as 95-100mmHg. Additional medications are suitable for more specific phenotypes, with ivabradine providing benefit in patients with sinus rhythm and heart rates >= 70 b.p.m., FCM in the presence of iron deficiency, and potassium-lowering agents to implement RASi when hyperkalaemia occurs. Vericiguat and omecamtiv mecarbil also have potential for tailored approaches towards the haemodynamic status. Thus, a new era is starting for a more personalized medical treatment of HFrEF
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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