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

The appreciation that congestive heart failure is not merely a disorder of myocardium has led to a substantial alteration in the treatment of this disease. The use of angiotensin-converting enzyme inhibitors is increasing as their well-demonstrated mortality and symptomatic benefits become better publicized and known. Although diuretics and digoxin continue to remain standard additions to angiotensin-converting enzyme inhibitors for the therapy of congestive heart failure, investigations of these and other agents continue. For example, acceptance of beta-blockade as a potentially beneficial therapeutic intervention increased in the past year with the publication of the Cardiac Insufficiency Bisoprolol Study (CIBIS), the largest controlled trial to date. Similarly, survival studies of vasodilators and positive inotropic agents such as vesnarinone are ongoing. Even the effects of exercise in severely ill patients (who were previously advised to be sedentary) are being studied. With the understanding that heart failure is a systemic disease and that controlled trials are needed because many of our assumptions prove to be incorrect, we can expect continued improvement in the management of heart failure.
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PMID:New approaches to managing congestive heart failure. 761 78

Analysis of heart rate variability (HRV) provides a non-invasive index of autonomic nervous system activity. HRV has been shown to be reduced in heart failure. Preliminary data indicate that beta blockers improve clinical status in patients with heart failure, but HRV improvement remains to be demonstrated. Fifty-four patients from the randomized double-blind, placebo-controlled Cardiac Insufficiency Bisoprolol Study were included in the HRV study. The bisoprolol daily dose was 5 mg once daily. We assessed HRV during 24-hour Holter recordings before randomization and after 2 months of treatment. HRV as measured in the time domain by root-mean-square successive differences (rMSSD), the percentage of adjacent RR differences >50 ms (pNN50), and the SD of RR intervals (SDNN), and in the frequency domain by high-frequency (0.16 to 0.40 Hz) and low-frequency (0.04 to 0.15 Hz) power. Most patients were in New York Heart Association functional class III. The mean left ventricular ejection fraction was 27 +/- 7%, and heart failure was idiopathic or ischemic. After 2 months, the patients receiving bisoprolol had a reduced mean heart rate compared with that in placebo patients (p=0.0004). Bisoprolol increased 24-hour rMSSD (p=0.04) and 24-hour pNN50 (p=0.04), daytime SDNN (p=0.05), and daytime high-frequency power (p=0.03) power. Bisoprolol induced a significant increase in HRV parameters related to parasympathetic activity in heart failure. Increased vagal tone may contribute to the protective effect of beta blockers and may have prognostic implications.
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PMID:Effects of bisoprolol on heart rate variability in heart failure. 861 Jun 12

The use of Beta-blockers for treatment of chronic heart failure due to idiopathic dilated cardiomyopathy has now begun to be accepted among cardiologists after having been used sporadically for 19 years. Pooled data from several minor controlled trials performed during the last 13 years which have shown consistent improvement of myocardial function, specifically in patients with idiopathic dilated cardiomyopathy, have recently been confirmed by two major trials using the selective beta-blockers metoprolol (MDC trial) and bisoprolol (CIBIS trial). There was a decrease of 34% in the combined number of deaths and patients needing a heart transplantation (P = 0.058) in the MDC trial. Bisoprolol, as well as reducing the overall mortality significantly, was found, in a retrospective subgroup analysis, to reduce mortality in idiopathic dilated cardiomyopathy. The MDC trial showed improvement in ejection fraction by 7 units compared with placebo and 13 units compared with baseline after 12 months treatment (P < 0.0001). There was also an increase in exercise time compared with placebo at 12 months follow-up. There was a 39% reduction in the number of readmissions to hospital due to heart failure and arrhythmias (P < 0.04) and a 32% reduction in the CIBIS trial (P < 0.01). Possible mechanisms for improvement after beta-blockers are improvement in myocardial energetic balance, protection against calcium overload or normalization of myocardial catecholamine kinetics. The role of upregulation of beta-adrenergic receptors remains controversial since this could not be seen in the action of all beta-blockers. The question of whether mortality can be reduced remains unsolved and will require large prospective trials which are now in progress.
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PMID:Adrenergic beta-blocking agents in congestive heart failure due to idiopathic dilated cardiomyopathy. 868 79

The effect of beta-blockade on heart-rate variability was assessed at different heart rates in 52 patients with heart failure included in the randomized, placebo-controlled, Cardiac Insufficiency Bisoprolol Study (CIBIS). Scatterplots of R-R intervals display beat-to-beat variability by plotting each R-R interval against the preceding interval. Scatterplot dispersion at different R-R intervals provides a measure of beat-to-beat heart-rate variability at different heart rates. A 24-hour Holter tape was performed at baseline and after 2 months of treatment with bisoprolol or matched placebo. Geometric measurements of scatterplots were used to determine beat-to-beat dispersion for different R-R intervals. Bisoprolol and placebo groups were well matched at base-line. After 2 months of treatment, bisoprolol significantly increased beat-to-beat variability at the longest R-R intervals (p < 0.05); however, there was no change in scatterplot dispersion at the shortest R-R intervals. This suggests that beta-blockade increases parasympathetic or decreases sympathetic tone or both in heart failure patients only at the slowest heart rates.
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PMID:Effects of beta-blockade with bisoprolol on heart rate variability in advanced heart failure: analysis of scatterplots of R-R intervals at selected heart rates. 870

Beta-blocking agents reduce mortality and improve symptoms in patients with dilated cardiomyopathy (DCM). There have been reports that diltiazem, a calcium-blocking agent, is also effective in such patients. We prospectively compared the effects of the beta-blocking agent bisoprolol with those of the calcium-blocking agent diltiazem in 18 patients (11 males and 7 females, age 14 to 68) with DCM. The 18 patients, (10 in New York Heart Association functional class III and 8 in class IV) were randomly assigned to 2 groups. Bisoprolol was administered as the first drug in 10 patients and diltiazem was administered in 8. Cross-over to bisoprolol was also performed in 3 patients. At the end of the study, among the 13 patients who had been given bisoprolol, 9 showed a good response (efficacy rate: 69%). In contrast, only 3 of the 8 patients who received diltiazem showed a good response (efficacy rate: 37.5%). Among the patients in NYHA class III, all 7 (100%) who were treated with bisoprolol responded but only 2 of the 4 (50%) treated with diltiazem responded (p < 0.05). Among the patients in class IV, 2 of 6 (33%) responded to bisoprolol and 1 of 4 (25%) responded to diltiazem (not significant). These results suggest that diltiazem, like bisoprolol, has a beneficial effect in patients with DCM, with a greater effect in class III patients. However, we conclude that diltiazem should usually be used as a second choice to improve heart failure in DCM, and as the first medication only in those with contraindications to beta-blocking agents.
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PMID:Comparison of the therapeutic effects of the beta-blocking agent bisoprolol and the calcium-blocking agent diltiazem in patients with heart failure due to dilated cardiomyopathy. 893 39

Clinical research in chronic heart failure has recently focused on the stimulated neuro-hormonal compensatory mechanisms that could contribute to auto-aggravation of the disease. On the basis of such a hypothesis, and apart from the inhibition of the renin angiotensin system, the antagonism of beta-receptors has evolved as a promising approach for improving quality of life and prognosis. However, the definite proof of beta-adrenoceptor blockade induced benefit on survival remains to be demonstrated. On the basis of CIBIS I data, the objective of the Cardiac Insufficiency Bisoprolol Study II (CIBIS II) is to evaluate effects of the selective beta-1 adrenoceptor blocker, bisoprolol, on mortality (primary endpoint) in patients with ischaemic or non-ischaemic chronic heart failure. Eligible patients will be symptomatic ambulatory patients with left ventricular ejection fraction < or = 35% in NYHA functional class III or IV, receiving a background treatment of diuretics and angiotensin converting enzyme inhibitors. A total of 2,500 patients are planned to be included with a mean follow up of at least 3 years. Secondary endpoints include hospitalisations, cardiovascular mortality and combination of both as well as permanent treatment withdrawal. Bisoprolol will be titrated up to 10 mg, starting with 1.25 mg daily. Randomization began in November 1995. CIBIS II results will represent a basis for definite conclusions on the evaluation of beta-adrenoceptor blockade induced benefit with bisoprolol in chronic heart failure.
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PMID:Design of the cardiac insufficiency bisoprolol study II (CIBIS II). The CIBIS II Scientific Committee. 910 60

In heart failure the chronic sympathetic stimulation alters the cardiac beta-adrenergic pathway. This alteration leads to a diminished contractile response to stimulation of the cardiac beta 1 receptor. A blockade of the beta 1 receptor partly restores the physiologic response to sympathetic stimulation at rest and during exercise. Several mechanisms resulting from the competitive blockade of the beta 1 receptor may be important. The major effect of beta-blockers seems to be triggered by a reduction of the heart rate at rest resulting in an increase of the left ventricular ejection fraction on the average by 7-8%. Patients with heart failure who are treated with a beta-blocker experience initially a slight decrease of the left ventricular function. beta-blocker therapy should therefore be initiated only in patients with stable heart failure. The starting dose of the beta-blocker has to be very small, e.g, 5 mg Metoprolol, 1.25 mg Bisoprolol or 3.125 mg Carvedilol. In a stepwise fashion the dose has to be increased to a full beta blocking effect over a period of 4-8 weeks. Despite a careful dose titration only 90% of the patients tolerate this regimen. Patients with high resting heart rates and/or dilated cardiomyopathy will have the greatest benefit. The two main reasons for withdrawal of the beta-blocker are deterioration of heart failure or symptomatic hypotension. Symptomatic improvement and a significant increase of exercise capacity appear gradually and can be measured only after more than 1 month duration of therapy. Three multicenter studies (MDC. CIBIS I, Carvedilol) evaluated the influence of beta-blockers on prognosis of heart failure. The MDC trial demonstrated a slower progression of heart failure with Metoprolol. The MDC and the CIBIS I trial could not show a significant improvement of prognosis. The larger trial with carvedilol was the first study to demonstrate a decreased mortality in patients who initially tolerate the beta-blocker therapy. One major concern in that study is the evaluation and classification of patients in the run-in phase who do not tolerate the beta-blocker. Definite studies (BEST, CIBIS II; COMET; RESOLVED; MERIT) are designed to answer these problems and to evaluate the effect of beta-blockers on mortality. Until the results of these studies are available the main goal of treatment with beta-blockers remains symptomatic improvement. Further, there is good evidence for an additional increase in life expectancy. In order to achieve optimal medical treatment and to avoid side-effects careful clinical evaluation and management of the patients is mandatory during therapy with beta-blockers.
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PMID:[Therapy of heart failure with beta-blockers?]. 913 18

It was first reported by our group in 1975 that heart failure due to idiopathic dilated cardiomyopathy (IDC) could be improved by long term treatment with a beta-blocker, starting at a low dose and continuing with a stepwise up-titration. Since then, many studies have been performed in patients with heart failure of various aetiologies and the beneficial effects of long term beta-blockade have been confirmed. About 3000 patients have been included in randomised studies in which beta-blockade, given for more than 2 months, mostly elicited significant improvements in functional class, exercise capacity, cardiac function, quality of life and/or morbidity. When started at a very low dose (one-tenth to one-twentieth of the doses generally used in angina or hypertension), the treatment is well tolerated in most patients. In these studies, various types of beta-blockers were used, including beta1-selective blockers and nonselective blockers with additional properties (vasodilator and antioxidative) such as metoprolol, bisoprolol, bucindolol and carvedilol. Several large studies have also reported benefits on mortality and morbidity. In the Metoprolol in Dilated Cardiomyopathy (MDC) trial, metoprolol treatment in patients with IDC resulted in a 34% reduction of the primary combined endpoint, total number of deaths and need for cardiac transplantation. In the Cardiac Insufficiency Bisoprolol Study (CIBIS), in patients with idiopathic as well as ischaemic cardiomyopathy, there was a nonsignificant 20% reduction in mortality. In the US carvedilol studies (n = 1094), also in patients with ischaemic and idiopathic cardiomyopathy, carvedilol reduced mortality by 65%, which was highly significant. A nonsignificant reduction in mortality was observed in the Australia-New Zealand (ANZ) Heart Failure Study with carvedilol. In all these studies there was a reduction in hospitalisations, with all drugs being generally well tolerated. It can thus be concluded that the beneficial effects of beta-blockers on cardiac function and morbidity have been documented in a large number of studies in selected groups of patients. The treatment has been accepted in some countries by the regulatory authorities. Larger, placebo-controlled studies are needed to convincingly demonstrate a reduction in total mortality as observed in the pooling of the 4 US carvedilol studies. Such studies are in progress for various beta-blockers, which may lead to acceptance of their routine clinical use in patients with congestive heart failure.
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PMID:The role of beta-blockers in left ventricular dysfunction and heart failure. 933 58

With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of heart failure, especially lethal arrhythmias and sudden cardiac death, focus has returned to the potential benefits of beta-adrenergic blockade. In patients with myocardial infarction and left ventricular (LV) dysfunction, particularly those prone to life-threatening arrhythmias, beta-blocker therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of angiotensin-converting enzyme (ACE) inhibition, beta blockade has improved cardiac function and LV contractility in nonischemic heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the Metoprolol in Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency Bisoprolol Study (CIBIS) found beta blockade to be associated with decreased mortality rates in patients with nonischemic heart failure. Of the 3 large randomized mortality trials now under way, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) is specifically designed to investigate the effects of beta blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic heart failure. Unresolved issues to be addressed include whether: (1) beta-blocker therapy in heart failure can improve survival and/or reduce the incidence of sudden cardiac death; (2) beta blockade is equally effective in ischemic and nonischemic heart failure; (3) any specific beta blocker may be better tolerated initially and cause fewer adverse effects; and (4) all beta blockers result in improved exercise tolerance and quality of life.
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PMID:Clinical studies on beta blockers and heart failure preceding the MERIT-HF Trial. Metoprolol CR/XL Randomized Intervention Trial in Heart Failure. 937 51

The use of beta-blocker therapy in heart failure was contraindicated for many years because it was considered to block necessary sympathetic compensatory responses to reduced cardiac function. However, early studies provided promising results in terms of improved symptoms and work capacity and reduced heart size. Small-scale studies have been completed over the past 20 years but until large-scale, long-term, randomized trials were conducted, the potential of beta-blockers in heart failure was not confirmed. The results of randomized trials published to date have included over 3,000 patients and the results show improvements in left ventricular function and heart rate. Significant improvements in New York Heart Association classification were also shown. Although no conclusive effect on mortality was shown, the first Cardiac Insufficiency Bisoprolol Study (CIBIS) indicated a trend toward improved survival during long-term treatment with bisoprolol. Ongoing studies have been specifically designed to investigate the effects of beta-blockers on survival. One of these trials, CIBIS II, which was terminated early in 1998 because of a positive effect on survival, is expected to report in late summer 1998. Such trials will also examine the different mechanisms of action of beta-blockers in heart failure and the influence of causes on the effects of beta-blockade.
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PMID:Over 20 years' experience of beta-blockade in heart failure. 971 21


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