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

Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive beta blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of beta-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with beta blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of beta blockers indicates that early initiation can be safely achieved and can improve patient outcomes.
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PMID:Early initiation of beta blockade in heart failure: issues and evidence. 1622 71

B-type natriuretic peptide (BNP) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure. Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels. The aim of this study is to compare the efficacy of a BNP-guided approach vs. standard care on beta-blocker titration in heart failure patients. Forty-one patients with heart failure were randomized into a clinical trial. Bisoprolol was started, and the dose was regularly up-titrated. BNP was measured monthly. The clinical group had beta-blocker dosage increased according to standard care, whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus standard care. The primary outcome was mean beta-blocker dose achieved after 3 months. BNP levels, left ventricular ejection fraction, clinical score, quality of life, and hospitalization were collected in all patients. BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD (5.9+/-4.3 mg vs. 4.4+/-3.4 mg, p=0.22). Left ventricular ejection fraction was significantly improved in both groups by 7.3% (95% confidence interval, 4.1%-10.4%; p<0.0001). A trend toward better quality of life was seen in the BNP group.
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PMID:BNP-guided therapy not better than expert's clinical assessment for beta-blocker titration in patients with heart failure. 1623 Aug 66

Hyperthyroidism is associated with low exercise tolerance despite high cardiac output and sometimes with the development of heart failure. L-type calcium channels may play a role in the mechanism, but this has not been fully understood. We examined the effects of thyroid hormone on gene expression and function of L-type calcium channels in rat ventricles by the ribonuclease protection assay and whole-cell patch-clamp technique, respectively. The effects of bisoprolol, beta-blocking agent, on the regulation of calcium channel by thyroid hormone was also studied. In hyperthyroid animals, the mRNA of the calcium channel alpha1c subunit was reduced on day 4, compared with that in euthyroid animals, and remained low on day 8. Bisoprolol did not affect the thyroid hormone mediated decrease in alpha1c subunit mRNA. While L-type calcium current was greater in hyperthyroid than euthyroid myocytes on day 4, it was smaller on day 8. In addition, the isoproterenol-induced increase in calcium current in euthyroid rats was attenuated in hyperthyroid rats. Acetylcholine decreased calcium current in hyperthyroid myocytes, but not in euthyroid myocytes. In conclusion, L-type calcium current was increased by thyroid hormone in rat ventricular myocytes by the activation of the adenylate cyclase cascade, despite a decreased calcium channel gene expression. These genomic and non-genomic modifications may play an important role in the association of high cardiac output with low exercise tolerance, and in the development of heart failure in hyperthyroidism.
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PMID:Genomic and non-genomic regulation of L-type calcium channels in rat ventricle by thyroid hormone. 1623 92

Combined therapy with optimum doses of a beta-blocker and an angiotensin-converting enzyme inhibitor (ACE-I) is the mainstay for the treatment of chronic heart failure (CHF). However, patients cannot be started on full doses of both drugs and treatment has to be initiated one way or the other. The Cardiac Insufficiency Bisoprolol Study (CIBIS) III was the first trial investigating the optimum sequence of initiating treatment of CHF, in terms of mortality and morbidity. CIBIS III compared randomised, open-label initial monotherapy with bisoprolol or enalapril for six months, followed by their combination for six to 24 months, in 1,010 patients at least 65 years of age, with stable, mildly or moderately symptomatic, systolic CHF. The two strategies were similarly efficacious in terms of the combined primary endpoint of mortality or all-cause hospitalisation, and showed similar safety. The bisoprolol-first approach showed a 28% lower mortality at the end of the monotherapy phase (p=0.24) and a 31% lower mortality at the end of the first year (p=0.06), but a 25% increase in worsening of CHF events (p=0.23). The main conclusion is that, CHF therapy may be started with bisoprolol or enalapril in patients like those in CIBIS III. However, it may be argued that the primary therapeutic goal in the early phase of CHF should be improved survival, whereas the long-term aim, achievable during combined therapy with optimum doses of several drugs, should be improved quality of life, physical function, morbidity and survival. In such case, the CIBIS III findings would tend to support starting CHF therapy with bisoprolol rather than enalapril in stable patients with mild or moderate symptoms.
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PMID:Implications of CIBIS III: a commentary. 1652 41

The basis of modern chronic heart failure (CHF) treatment is a combination of optimum doses of a beta-blocker and an angiotensin-converting enzyme inhibitor (ACEI); however, patients cannot be started on full doses of both drugs and treatment has to be initiated one way or the other. By tradition and according to guideline recommendations, an ACEI is usually initiated first, followed by a beta-blocker after a varying time period based on clinical judgement. Early beta-blockade has several theoretical advantages, and two surrogate end point studies have indicated that initiation of CHF treatment with a beta-blocker may be superior to an ACEI. The Cardiac Insufficiency Bisoprolol III trial was the first trial investigating the optimum sequence of initiating treatment of CHF in terms of mortality and morbidity. The results indicated that, in stable, mildly to moderately symptomatic patients with systolic CHF, initiation of therapy with the beta-blocker bisoprolol followed by the ACEI enalapril was similarly efficacious to the opposite sequence in terms of combined mortality and all-cause hospitalisation. However, initiating therapy with bisoprolol showed a trend towards better survival, but also towards further worsening of CHF. This review aims to put these recent findings into clinical perspective.
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PMID:Treatment of early heart failure: an ACEI or a beta-blocker first? 1663 87

1. Changes in sodium currents (I(Na)) in heart failure contribute to cardiac electrophysiological alterations and, thereby, to ventricular arrhythmias. Bisoprolol has anti-arrhythmic effects, but its direct effect on I(Na) in cardiac cells remains unclear. Accordingly, in the present study we investigated the effects of bisoprolol on ventricular I(Na) in diastolic heart failure (DHF) and normal rats. 2. The DHF model was produced by abdominal aortic coarctation for 4 weeks and single ventricular myocytes were isolated by enzymatic dissociation. The electrophysiological actions of bisoprolol on I(Na) currents were investigated using a whole-cell patch-clamp technique. 3. The membrane capacitance of rats in the DHF group was significantly greater than that of the control group and the current-voltage curve was simultaneously shifted downward. Bisoprolol concentration-dependently decreased I(Na) in ventricular myocytes of both groups (at -45 mV), with IC(50) values of 19.53 +/- 0.06 and 40.78 +/- 0.03 micromol/L in the control and DHF groups, respectively. 4. In both groups, the current-voltage curves were shifted upwards, whereas activation potentials, peak currents and reversal potentials showed no significant changes. At -45 mV, the descent ratio of current densities in the DHF group was lower than that of the control group. In both groups, inactivation curves were shifted to more negative potentials, but activation curves and recovery curves were not altered. Changes in the half-inactivation voltage, V(0.5), and the slope of the inactivation curve, S, were similar for both groups. 5. In conclusion, bisoprolol concentration-dependently decreases I(Na) in ventricular myocytes of DHF and normal rats, which could be responsible, at least in part, for its anti-arrhythmic effects.
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PMID:Bisoprolol inhibits sodium current in ventricular myocytes of rats with diastolic heart failure. 1760 May 46

Bisoprolol fumarate is a highly selective beta-1 receptor blocker. Bisoprolol has been extensively studied in three large mortality trials in stable chronic heart failure (CHF) patients. The CIBIS trial enrolled 641 patients and demonstrated the good tolerability of bisoprolol in a large CHF population, without evidence for any harmful effect. The CIBIS-II study was the first large randomized, double-blind, placebo-controlled study demonstrating in 2647 patients a dramatic reduction in mortality with a beta-blocking agent in CHF patients. CIBIS-III demonstrated in 1010 patients the equivalence of 2 different therapeutic strategies in de novo CHF patients. There was no difference in morbidity and mortality between sub-groups of patients receiving first bisoprolol or enalapril. These three trials also demonstrated the good tolerability of bisoprolol fumarate. Other studies were either limited in number of patients or not randomized. However, these studies confirmed the good tolerability of bisoprolol in CHF patients, even in elderly population. Bisoprolol fumarate is a selective beta-1 receptor blocker that significantly reduced morbidity and mortality in stable CHF patients. Bisoprolol is well tolerated with few significant side effects in different large trials.
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PMID:Bisoprolol in the treatment of chronic heart failure. 1796 74

Clinical trials have consistently shown the benefits of beta-blocker treatment in patients with chronic heart failure (HF). As a result, bisoprolol, carvedilol, and metoprolol succinate are now indicated for the treatment of all patients with chronic HF who do not have major contraindications. Bisoprolol is the first beta-blocker shown to improve survival in an outcome trial. In the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), all-cause mortality and sudden death were reduced in patients treated with bisoprolol compared with those on placebo (11.8% vs 17.3%; p < 0.0001 and 3.6% vs 6.3%, p < 0.002; respectively) regardless of age, NYHA functional class, and co-morbidities. Further studies have shown both the efficacy of bisoprolol on secondary endpoints and patients subgroups as well its high cost effectiveness. More recently, CIBIS-III has shown similar efficacy and safety of the initiation of HF treatment with either bisoprolol or enalapril, with a tendency to a survival advantage with bisoprolol. Nowadays, the role of bisoprolol, as well as that of carvedilol and metoprolol succinate, in HF treatment is firmly established and research is mainly focused on implementation of treatment and better dosing. This article will summarize evidence for the efficacy of bisoprolol in the treatment of HF.
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PMID:Bisoprolol in the treatment of chronic heart failure: from pathophysiology to clinical pharmacology and trial results. 1847 78

Simulation of chronic heart failure in rats led to an increase in heart rate variability and decrease in heart rate. All beta-blockers also promoted the heart rate variability augmentation in ill animals. The most potent effects on heart rate variability were produced by pindolol, atenolol, and propranolol. Bisoprolol and metoprolol affected heart rate and heart rate variability in less extent, and nebivolol normalized a part of heart rate variability parameters.
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PMID:Heart rate variability in rats with experimental chronic heart failure and long-term exposure to beta-adrenoblockers. 1951 16

Beta-blockers, once considered contraindicated in patients with heart failure, are now the standard of care in such patients. This change is the result of several large-scale clinical trials, including Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF), and the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, that have demonstrated significant morbidity and mortality benefits of beta-blockers in patients with heart failure caused by left ventricular systolic dysfunction. beta-blockade also improves quality of life and causes regression of cardiac remodeling, a phenomenon characteristic of chronic heart failure. This article provides an overview of the history of beta-blockade in the treatment of heart failure, beginning with the early misconception that beta-blockers are detrimental to patients with heart failure. Mechanistic and early clinical trials are reviewed, along with the results from CIBIS-II, MERIT-HF, and COPERNICUS. Barriers to the use of beta-blocker therapy also are discussed.
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PMID:Beta-blockers in heart failure: how far have we progressed? 1966 3


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