Heart failure reviews
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Heart failure reviews · Dec 2009
ReviewA novel approach to improve cardiac performance: cardiac myosin activators.
Decreased systolic function is a central factor in the pathogenesis of heart failure, yet there are no safe medical therapies to improve cardiac function in patients. Currently available inotropes, such as dobutamine and milrinone, increase cardiac contractility at the expense of increased intracellular concentrations of calcium and cAMP, contributing to increased heart rate, hypotension, arrhythmias, and mortality. These adverse effects are inextricably linked to their inotropic mechanism of action. ⋯ A first-in-human study in healthy volunteers with the lead cardiac myosin activator, CK-1827452, as well as preliminary results from a study in patients with stable chronic heart failure, have extended these findings to humans, demonstrating significant increases in systolic ejection time, fractional shortening, stroke volume, and cardiac output. These studies suggest that cardiac myosin activators offer the promise of a safe and effective treatment for heart failure. A program of clinical studies are being planned to test whether CK-1827452 will fulfill that promise.
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Heart failure reviews · Dec 2009
ReviewVasodilators in the treatment of acute heart failure: what we know, what we don't.
Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebo-controlled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. ⋯ They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients' outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1-2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice.
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Heart failure reviews · Dec 2009
ReviewRelaxin, a pleiotropic vasodilator for the treatment of heart failure.
Relaxin is a naturally occurring peptide hormone that plays a central role in the hemodynamic and renovascular adaptive changes that occur during pregnancy. Triggering similar changes could potentially be beneficial in the treatment of patients with heart failure. The effects of relaxin include the production of nitric oxide, inhibition of endothelin, inhibition of angiotensin II, production of VEGF, and production of matrix metalloproteinases. ⋯ An initial pilot study has shown favorable hemodynamic effects in patients with heart failure, including reduction in ventricular filling pressures and increased cardiac output. The ongoing RELAX-AHF clinical program is designed to evaluate the effects of relaxin on the symptoms and outcomes in a large group of patients admitted to hospital for acute heart failure. This review will summarize both the biology of relaxin and the data supporting its potential efficacy in human heart failure.
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Levosimendan is a new cardiac enhancer that exerts positive inotropic effects on the failing heart mediated by calcium sensitization of contractile proteins as well as peripheral vasodilatory effects mediated by opening of ATP-sensitive potassium channels in vascular smooth-muscle cells. Levosimendan is the most well-studied calcium sensitizer in the real clinical practice, producing greater hemodynamic and symptomatic improvement in patients with acute heart failure syndromes (AHFS) than those with traditional inotropes. ⋯ However, in patients with a previous history of CHF and on beta-blocker on admission, levosimendan seems to have a beneficial effect on short-term mortality. According to the recent guidelines of the European Society of Cardiology, levosimendan is indicated in patients with symptomatic low cardiac output HF secondary to cardiac systolic dysfunction without severe hypotension (Class IIa, Level of Evidence B).