Category: Heart Failure

A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: Conclusionsβ-blocker used in most of the successful studies, newer nonspecific p-blockers such as bucindolol and carvedilol have advantages over metoprolol partly due to their peripheral vasodilatory properties. canada health and care mall

Although several studies have suggested the probability of a decrease in mortality with P-blockers even in addition to the effect of ACE inhibitors, to our knowledge, the only large study showing an improvement in mortality has been with carvedilol. …Read the rest of this article

Although the long-term use of carvedilol may result in tolerance to its a-blockade properties analogous to that produced by prazosin, this does not seem to affect its beneficial long-term effects as shown by Packer et al in their 1996 report on the effect of carvedilol on 1,094 patients with mixed ischemic and idiopathic DCM with mild, moderate, and severe CHF. The Data and Safety Monitoring Board recommended termination of that study because the mortality over 12 months was 7.8% in the placebo group and 3.2% in the carvedilol group, a 59% reduction. There was also a 27% reduction in risk of hospitalization for cardiovascular causes.
Not yet available in the United States is nebivolol, a novel β-blocker that can improve left ventricular contractile function. In a South African 3-month placebo-controlled trial in 24 patients, most of whom had idiopathic DCM, the ejection fraction and stroke volume increased with a fall in end-diastolic pressure as well as mass and end-diastolic and systolic volumes. …Read the rest of this article

A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: β-Blockers and ACE Inhibitorsβ-Blockers and ACE Inhibitors
Angiotensin II causes an increase in adrenergic neurotransmitter activity, and ACE inhibitors can decrease norepinephrine in venous blood and are therefore said to be antiadrenergic and like β-blockers, can increase β-receptor density.
During the acute stages of CHF, an increase in the renin-angiotensin system is necessary to maintain pressure. However, chronically high angiotensin levels increase afterload, which depresses myocardial function. Stimulation can stimulate the renin-angiotensin system, and β-blockers can suppress renin output. The decrease in angiotensin II will decrease vasoconstriction, thereby attenuating any elevation in afterload. Therapy with β-blockers plus ACE inhibitors inhibits the renin-angiotensin system by two different pathways and suggests that they would have an additive benefit in CHF. …Read the rest of this article

Conventional hemodynamic criteria cannot predict who will respond to β-blockers. Histologic criteria are more predictive. In 1993, Yamada et al reported that almost all patients with interfascicular fibrosis responded well, while only one third with intercellular fibrosis responded.
In 1995, Yamada et al53 reported that the extent of myocardial fibrosis could be estimated by means of their signal averaging criteria which, in turn, could predict the effectiveness of long-term metoprolol therapy with a sensitivity of 85% and specificity of 91%.
Heart Rate and Prognosis with β-Blockers
Although Schwartz et al claimed that a basic rapid heart rate was the best predictor of success with β-blockers, Swedberg et a found that rapid heart rates gave no better prediction of success than those with average heart rates. …Read the rest of this article

A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: Ischemic vs Idiopathic DCM and β-BlockersTwo of the negative studies had a duration of only 1 month, during which time there may be temporary deterioration. Although a few patients have immediate improvement, it usually takes 2 months for an increase in ejection fraction, and 6 months to a year for maximum response. After many months, a larger dose may produce an even greater increase in ejection fraction. Sackner-Bernstein and colleagues in a 1995 abstract, showed that of 18 patients whose CHF worsened during the initial 3 to 5 weeks of β-blocker therapy, subsequent improvement occurred over the next 4 months similar to the patients who had had no early worsening. Fortunately, to our knowledge, there are no reported deaths directly attributable to this acute intolerance that occurs in as high as 7% of patients. buy yasmin online
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The normal heart has about 80% β1 and 20% β2-receptors. In CHF, it is not surprising that there are about 60% &beta:-receptors and 40% &beta:2-receptors, because theβ2-receptor response is relatively unchanged. However, by β2-stimulation tests in heart failure, there may also be a 30% decrease in their responsiveness. Therefore some downregulation may occur even with β2-receptors. However, metoprolol may also counteract β2-downregulation because it has been shown to cause an increase in β-responsiveness  β-Receptor upregulation may not be the most important mechanism for the effect of β-blockers because the time course or degree of clinical improvement does not correlate with the degree of upregulation. Also, with carvedilol, a p-blocker with vasodilator and atypical p-agonist properties, there was an increase in the ejection fraction of about 10% with no increase in β-receptor density. However, metoprolol in a similar group of patients caused an increase in P-receptor density. …Read the rest of this article

A Review of Why and How We May Use β-Blockers in Congestive Heart Failure: Long-term sympathetic stimulationWith long-term sympathetic stimulation, the ability of noradrenergic sympathetic nerve endings of the heart to synthesize norepinephrine is attenuated. In animals, sympathetic blockade can restore the ability to make norepinephrine.
Upregulation and Downregulation of β-Receptors
Repeated or prolonged exposure to β-agonists causes the β-receptors to become desensitized by chemical uncoupling to binding proteins. Uncoupling makes β-receptors nonreactive when tested by the chemical reaction used to mark their presence. P-Receptor density, ie, the total number of β-receptors, can also be decreased by prolonged exposure to the norepinephrine caused by heart failure and is independent of the decreased sensitivity caused by uncoupling. The decrease in β-receptor density is what is usually meant by downregulation. …Read the rest of this article