Heart failure monitor最新文献

Recent studies have identified the importance of biologically active molecules, such as neurohormones, as mediators of disease progression in heart failure. More recently, it has become apparent that, in addition to neurohormones, another portfolio of biologically active molecules, termed cytokines, are also expressed in the setting of heart failure. This article will review recent clinical material that suggests that tumor necrosis factor, a pro-inflammatory cytokine, may contribute to disease progression in heart failure by virtue of the direct toxic effects that this molecule exerts on the heart and circulation. In addition, this article reviews the existing clinical literature, which suggests that cytokine antagonism is safe and potentially effective in patients with heart failure.

In many forms of cardiomyopathic left ventricular (LV) dysfunction, there is a rapid myocardial expression of pro-inflammatory cytokines such as interleukin 1, interleukin 6 and tumour necrosis factor-alpha (TNF-alpha) which mediate, via specific receptors, various processes such as gene expression, cell growth or apoptosis. In the initial stages of myocarditis, the myocardial expression of proinflammatory cytokines appears to be part of an inflammatory process. In many other conditions such as ischaemic cardiomyopathy and chronic LV pressure or volume overload, myocardial expression of proinflammatory cytokines is triggered by an elevation of LV wall stress. Myocardial expression of cytokines contributes to depression of contractile performance and adverse LV remodelling. Cytokine-induced depression of contractile performance appears to result from sphingosine production, which interferes with myocardial calcium handling. In transgenic mice, the rate of progression of LV dilatation appears to correlate with the intensity of myocardial TNF-alpha overexpression. In heart failure patients, cytokine concentrations are elevated not only in the myocardium but also in plasma. Cytokines are, therefore, responsible not only for autocrine and paracrine signalling within the myocardium but also for endocrine signalling throughout the body, especially affecting striated muscle mass with induction of muscle wasting and cachexia. The source of cytokine production in heart failure remains uncertain and several mechanisms have been proposed including endotoxin-induced immune activation due to bowel oedema, myocardial production due to haemodynamic overload and peripheral extramyocardial production due to tissue hypoperfusion and hypoxia. The latter seems to be the most likely mechanism, possibly modulated by the presence of bacterial endotoxins released from the gut. Numerous drugs have meanwhile been shown to influence this cardioinflammatory response to heart failure either by reducing basal levels of cytokines (e.g. amlodipine, pentoxifylline, beta-blockers) or by reducing endotoxin-induced cytokine gene expression (e.g. ouabain, amiodarone, adenosine, angiotensin converting enzyme inhibitors, angiotensin II-receptor blockers). Direct blockade of the deleterious actions of elevated plasma levels of cytokines recently became possible through intravenous infusion of a soluble TNF-alpha receptor fusion protein, which resulted in an increase in exercise tolerance and LV performance.

There is now conclusive evidence that most patients with heart failure due to left ventricular systolic dysfunction should be treated with angiotensin converting enzyme (ACE) inhibitors and beta-blockers. They will also need diuretics for the control of fluid retention. There is also a powerful case for adding spironolactone to the treatment of patients with more severe symptoms. Many doctors would also use digoxin and, especially if coronary disease is present, aspirin or warfarin. Most patients also have other chronic diseases, such as diabetes, arthritis, depression and dyspepsia, and each of these may provoke the prescription of yet another agent. Many patients will receive prescriptions to treat the side-effects of their therapy. Finding a sure path through the morass of pharmacotherapy is a daunting task. Polypharmacy is having a negative impact on new drug research in an area where there are in fact remarkably few really effective treatments and the therapeutic problem is only partially solved. This paper discusses some of the issues surrounding polypharmacy in heart failure and how to resolve them, using an illustrative case history. It highlights the potential benefits of polypharmacy with effective drugs and the gross over-use of ineffective treatments in heart failure. The major problem with polypharmacy in heart failure is not the heart failure treatment itself, but the drugs for other concomitant conditions, the effectiveness of which is often not supported by an appropriate evidence base and for which alternative, less noxious management strategies often exist. Polypharmacy may be deleterious not only because of the increased potential for side-effects and drug interactions but also because taking unnecessary therapy reduces compliance with effective drugs.

Congestive chronic heart failure (CHF) is a progressive disorder in which a complex interaction of haemodynamic, neurohormonal and metabolic disturbances leads to subsequent immune activation. The greatest attention has been given to the concept that the progression of heart failure is due to neurohormonal abnormalities and this has led to substantial therapeutic benefits for CHF. The aim of this review is to describe a number of the interactions between neurohormonal pathways and metabolic problems relevant in CHF. Besides the renin-angiotensin-aldosterone-system, steroid and thyroid hormones, growth factors, insulin and inflammatory cytokines (e.g. tumour necrosis factor-alpha [TNF-alpha]) are considered. TNF-alpha is potentially a key molecule with enormous interactive opportunities within a regulatory network of energy metabolism, immune function and neuroendocrine and hormonal function. The most dramatic metabolic problem in heart failure patients is the development of cardiac cachexia. Currently, no specific therapy exists and the prognosis is poor. There are promising approaches (counteracting TNF-alpha or applying anabolic growth factors) but these are not without risk and are expensive, and their application may, therefore, be limited to certain subgroups of patients. In the future, it will not be enough to monitor cardiac function and symptomatic status in heart failure patients. Rather, the patients' metabolic status may need to be taken, as well as an assessment of peak oxygen consumption, body composition and hormonal status.

Heart failure is an important public health problem and one for which morbidity and mortality remain high despite treatment with angiotensin converting enzyme (ACE) inhibitors. A large number of clinical trials examining the effects of beta-blockers in the treatment of heart failure have now been performed. Two large-scale clinical trials have recently confirmed significant survival benefits with these agents, with effects that are additive to those achieved with ACE inhibitor therapy. These trials have now established beta-blocker therapy as an important part of standard heart failure treatment. The clinical use of beta-blockers in patients with heart failure requires careful translation of the randomized controlled trials into everyday clinical practice. Patient selection is key to the safe use of beta-blockers. Patients who may be suitable for beta-blockade therapy include those with mild-moderate heart failure due to left ventricular systolic impairment, those who are receiving adequate dose of diuretics and ACE inhibitors and those whose clinical condition is stable at the time of initiation of the beta-blocker. Survival benefits have been demonstrated with bisoprolol, carvedilol and metoprolol. Whether different beta-blockers have important clinical differences with regard to clinical end-points is as yet uncertain. beta-Blockers should be initiated at low dose, with titration of dose over several weeks and careful clinical monitoring for potential adverse effects, such as hypotension or worsening congestion. This careful application of the clinical trials into clinical practice will allow the safe use of this effective treatment for patients with chronic heart failure.