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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of both experimental studies and clinical trials indicate that prolonged activation of the sympathetic nervous system can adversely affect the course of heart failure, and that this deleterious effect can be attenuated with the use of beta-blocking agents. Studies with beta-1 selective agents such as metoprolol and bisoprolol, have demonstrated that beta-blockers can reduce the risk of worsening heart failure but have shown little or equivocal effect on survival. In contrast, recent trials with non-selective vasodilating beta-blockers (i.e. carvedilol) have reported a reduction in the risk of both death and hospitalization. It is uncertain, however, whether these survival effects represent a class effect of beta-blockers or a specific effect of carvedilol. Carvedilol antagonizes several biological mechanisms (not blocked by metoprolol or bisoprolol) that may be important in mediating the progression of heart failure. In three meta-analyses, the survival effects of non-selective vasodilating beta-blockers (primarily carvedilol) were greater than those of beta-1 selective non-vasodilating beta-blockers. A clear answer to the question as to whether mortality reduction is a class effect of beta-blockers will be provided by several large-scale survival trials, which are currently in progress.
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PMID:Do beta-blockers prolong survival in chronic heart failure? A review of the experimental and clinical evidence. 951 51

This study was aimed at investigating in chronic heart failure (CHF) the effects that beta-blockade with carvedilol may have on lung function, and their relationship with left ventricular (LV) performance and peak exercise oxygen uptake (VO2p). CHF causes disturbances in ventilation and pulmonary gas transfer (stress failure of alveolar-capillary membrane) that participate in limiting VO2p. Carvedilol improves LV function and not VO2p. Twenty-one NYHA functional class II-III patients were randomized (2 to 1) to carvedilol (25 mg bid., 14 patients) or placebo (7 patients) for 6 months. Rest forced expiratory volume (FEV1), vital capacity (VC), total lung capacity (TLC), carbon monoxide diffusing capacity (DLCO), its alveolar-capillary membrane component (DM), pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure, EDP), LV diastolic (EDD) and systolic (ESD) dimensions, stroke volume (SV), ejection fraction (EF), fiber shortening velocity (VCF) were measured at baseline and at 3 and 6 months. VO2p, peak ratio of dead space to tidal volume (VD/VTp), ventilatory equivalent for CO2 production (VE/VCO2), VO2 at anaerobic threshold (VO2at) were also determined. FEV1, VC, TLC, DLCO, DM were impaired in CHF compared to 14 volunteers, and did not vary with treatment. Carvedilol reduced EDP, EDD, ESD, and increased EF, SV, VCF, without affecting VO2p, VO2at, VD/VTp, VE/VCO2, at 3 and 6 months. Placebo was ineffective. In CHF, carvedilol exerts neutral effects on ventilation and pulmonary gas transfer and ameliorates LV function at rest. This proves that antifailure treatment may not be similarly effective on cardiac and pulmonary function; and does not contradict the possibility that persistence of lung impairment may contribute to lack of improvement in exercise performance with carvedilol.
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PMID:[A failed improvement in pulmonary function and exercise capacity with carvedilol in congestive heart failure despite an excellent effect on left ventricular function]. 955 74

This study investigated the effects of carvedilol on right ventricular (RV) volume and systolic function in chronic heart failure patients. Carvedilol treatment resulted in a significant improvement of RV ejection fraction and systolic performance, which paralleled the improvement of systolic function demonstrated in the left ventricle.
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PMID:Effects of carvedilol on right ventricular function in chronic heart failure. 959 16

The data from animal and human in-vivo studies suggest that cardiac function is dependent in part on the normal function of the GH/IGF-1 axis (growth hormone/insulin-like growth factor-1). The syndrome of heart failure appears to be associated with a perturbation of the GH/IGF-1 axis. So far encouraging results from phase II clinical trials evaluating the effects of long-term growth hormone treatment in patients with moderate to severe chronic congestive heart failure due to dilated cardiomyopathy have been published. In these studies growth hormone (i.e., DNA-derived recombinant human growth hormone) was not used alone but in addition to standard optimal therapy for chronic heart failure. The following rationale is the basis of this new approach for the treatment of chronic congestive heart failure due to dilated cardiomyopathy. According to Laplace's Law, cardiac wall stress(i.e., the force acting per unit of cross-sectional area of the ventricular wall) is directly related to intraventricular pressure and ventricular radius and inversely related to ventricular wall thickness. Cardiac (ventricular) wall stress if increased in dilated cardiomyopathy (mainly because of the dilatation of the ventricles and to a minor extent because of the relative reduction in ventricular thickness). Growth hormone seems to be capable of increasing ventricular wall thickness in dilated cardiomyopathy, thus, reducing cardiac wall stress which in turn leads to an improvement in systolic cardiac performance. Recombinant human growth hormone as a pharmacologic treatment is not only an expensive but also risky therapeutic modality (e.g., potential risk of inducing colonic carcinoma, de-novo leukemias, relapses of leukemias and central nervous system tumors). Given these prerequisites and a receptivity for cost effectiveness and risk-benefit analyses, it seems as if subcutaneous recombinant human growth hormone-as an additional therapeutic substance in conjunction with one of the widely accepted drugs for end-stage chronic congestive heart failure due to dilated cardiomyopathy-e.g., angiotensin converting-enzyme inhibitors, diuretics, nitrates, digoxin, and beta-adrenergic receptor blockers (Carvedilol) could either become a bridge to transplantation (i.e., supporting patients awaiting transplantation) or an alternative to the very expensive cardiac transplantation. There are three reasons for this hypothesis. First, the fact that end-state dilated cardiomyopathy along with ischemic heart disease are the main indications for heart transplantation in adults; second, the worldwide small supply of human donor organs for heart transplantation; and, third, the urgent need to find alternative cost-effective and risk-beneficial therapeutic modalities.
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PMID:[Therapy of terminal dilated cardiomyopathy with growth hormone]. 969 12

Current knowledge of the mechanisms contributing to progression of heart failure suggests that therapies that limit or interfere with the consequences of neurohormonal activation and improve myocardial energetics appear to be most beneficial. Carvedilol, a nonselective beta-adrenergic blocker with peripheral vasodilating properties, reduces mortality, slows progression of disease, and improves quality of life in patients with heart failure when added to standard therapy. When administered according to recommended guidelines, carvedilol is well tolerated. Clinical guidelines on the use of carvedilol in heart failure are provided.
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PMID:Carvedilol: therapeutic application and practice guidelines. 969 47

Carvedilol is a novel cardiovascular drug of proven efficacy in the treatment of hypertension, angina, and heart failure. Several mechanisms may account for the beneficial effects of carvedilol in patients with heart failure. As with other beta-blockers, blockade of cardiac beta-adrenergic receptors (both beta1 and beta2), and hence reduction of cardiac work load and oxygen consumption, plays an important role in the actions of this agent. Additional benefit is provided by vasodilation (alphal-adrenergic blockage) at peripheral resistance vessels, which decreases preload and after-load, thereby further reducing cardiac work and wall tensions. In addition, potential advantages of carvedilol resulting from alpha1-adrenergic blockade are likely because alpha1-adrenergic receptors mediate cardiac remodeling by inducing hypertrophy. Finally, carvedilol is a potent antioxidant and is unique among beta-blockers in this respect. In recent years, evidence has accumulated in support of the role played by reactive oxygen radicals in chronic pathological states of the myocardium. In this article, the role of oxygen radicals in heart failure is discussed with special reference to apoptosis, a phenomenon believed to be involved in progressive cardiac myocyte loss in ischemic or myopathic heart diseases. The potential role of the antioxidant actions of carvedilol, especially in prevention of apoptotic cell death, is highlighted as a novel mechanism of action in heart failure.
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PMID:Novel mechanisms in the treatment of heart failure: inhibition of oxygen radicals and apoptosis by carvedilol. 971 19

The model for heart failure has changed radically over the past 20 years. No longer a simple hemodynamic paradigm of pump dysfunction, heart failure is now characterized as a complex clinical syndrome with release of many neurohormones and cytokines, which are believed to be most responsible for progression of disease. This change in our understanding of the pathophysiology of heart failure has important therapeutic implications. Drugs designed to influence the myocardial contractile state have been found over the past few decades to have either a neutral or an adverse effect on long-term survival, whereas agents designed to block the renin-angiotensin-aldosterone and other neurohormonal systems have proved to be remarkably effective treatment. Recently, drugs designed to block excessive sympathetic nervous system activity have been demonstrated in well-controlled studies to be safe and effective forms of therapy for heart failure. Carvedilol, a nonselective beta-adrenergic blocker with alpha1-blocking and antioxidant properties, is associated with prevention of progression of heart failure as manifested by improvement in left ventricular (LV) function, reduction in heart size, and improved survival in patients with New York Heart Association functional Class II and III symptoms. This improvement is observed equally in patients with ischemic and non-ischemic heart failure. It is tempting to speculate that beta-adrenergic blockers prevent the progression of heart failure by reducing LV mass and LV chamber size. In essence, carvedilol, and perhaps other beta-adrenergic blockers, appear to abrogate relentless LV remodeling which is typically associated with progression of heart failure. The combination of angiotensin-converting enzyme inhibitors and beta-adrenergic blockers may be particularly effective in this regard, although more data on beta-adrenergic blockers in patients with advanced heart failure are needed. Data from experimental heart failure animal models also suggest that endothelin (ET) subtype A (ET(A)) receptor blockers have the potential to lessen the pace of progressive LV remodeling. As our understanding of the neuroendocrine response to diminished cardiac performance improves, novel and even more imaginative neurohormonal and cytokine antagonists are likely to emerge as important new treatments for both hypertension and heart failure.
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PMID:Neurohumoral activation and progression of heart failure: hypothetical and clinical considerations. 973 91

Clinical trials in heart failure (HF) tend to randomize patients according to demographic characteristics and severity of left ventricular dysfunction, without taking account of the precise diagnosis. This article reviews results from recent trials suggesting that the etiology of HF, and particularly whether it is ischemic or nonischemic, may influence the long-term prognosis and the response to treatment. Some studies, but not all, suggest that nonischemic HF has a better prognosis than ischemic HF. The data on the benefits of angiotensin-converting enzyme inhibitors in ischemic versus nonischemic HF are conflicting. Carvedilol, and recently, bisoprolol have been shown to reduce mortality in ischemic and nonischemic HF, whereas metoprolol has, to date, improved prognosis only in dilated cardiomyopathy. Better responses to digoxin, amlodipine and amiodarone have been reported in non-ischemic HF. There is at present no clear explanation for the apparent therapeutic differences between ischemic and nonischemic HF. Absence of a rigorous definition of "nonischemic HF" in many studies makes interpretation of the results difficult. Further studies to clarify the effects of etiology of HF on the response to treatment could be particularly important for preventing progression to more advanced stages, in which any type of drug therapy may have limited value in prolonging survival. An individualized therapeutic approach, based on etiology of HF and possibly other factors such as plasma drug levels or the levels of neurohormones, could result in major progress in treating HF patients.
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PMID:Etiology and response to drug treatment in heart failure. 980 21

The prognosis remains poor for patients with congestive heart failure (CHF), despite reduced mortality rates resulting from the addition of angiotensin converting enzyme inhibitors to traditional treatment regimens. Because much of the myocardial damage that occurs in patients with CHF may be related to sympathetic activation, interest in the use of beta blockers has grown. Recent studies have shown the benefits of beta blocker therapy in many patients with heart failure. Carvedilol, the first beta blocker labeled in the United States specifically for the treatment of heart failure, has been shown to improve left ventricular ejection fraction and may reduce mortality.
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PMID:Carvedilol: the new role of beta blockers in congestive heart failure. 982 60

Heart failure is a common clinical problem in patients with cardiovascular disease. Mortality remains high despite conventional therapy. The morbidity associated with heart failure accounts for numerous hospitalizations and significant health care expenditures. Therapy has been directed at relieving symptoms, augmenting exercise capacity, reducing hospitalizations and improving survival. Randomized clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors achieve these therapeutic goals and exert a favourable influence on disease progression. Recent clinical trials evaluating metoprolol, bisoprolol and carvedilol have clearly established that judicious use of beta-adrenergic blockers in heart failure patients who have been stabilized favourably influences the natural history of the disease, even when given as additional therapy to patients already receiving ACE inhibitors. Carvedilol is a non-selective beta-adrenergic blocking drug with vasodilatory properties that has been recently approved by the U.S. Food and Drug Administration for use in patients with NYHA functional class II or III heart failure. It was the only agent to produce a statistically significant survival benefit in a pre-specified analysis that included all the patients randomized into the multicentre U.S. Carvedilol Heart Failure Trials Program, irrespective of disease aetiology. As with trials looking at ACE inhibitor therapy, studies involving beta-blocker therapy in patients with heart failure have evaluated the effects of these drugs on hospitalization, NYHA functional class, exercise capacity and survival. In the U.S. Carvedilol Heart Failure Trials Program, the risk of hospitalization for any cause was reduced by 29%, the risk of hospitalization for a cardiovascular cause was reduced by 28% and the risk of dying was reduced by 65%. Thus, carvedilol has been shown in randomized clinical trials to improve the quantity of life and, at least in terms of the incidence of hospitalization, to improve the qualify of life as well. Randomized trials have consistently reported a favourable change in NYHA functional class in patients treated with beta-adrenergic blocking drugs: the majority of patients became less symptomatic. In the U.S. Carvedilol trials, patients and physicians reported (separately) an improvement in global status, and less deterioration when treatment was randomized to carvedilol. The positive influence of such therapy is reflected in a reduction in hospitalizations. In summary, patients with NYHA class II or III who have been stabilized with ACE inhibitors and diuretics can expect an improvement in the quality as well as the quantity of life with beta-blocker therapy.
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PMID:Beta-blockers in heart failure. Do they improve the quality as well as the quantity of life? 988 8


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