Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The double-blind, placebo-controlled, multinational trial Xamoterol in Severe Heart Failure randomized 290 patients treated with captopril and 217 treated with enalapril to xamoterol or placebo. At the end of the 100-day follow-up period, the cumulative probability of survival in patients with coronary artery disease or with dilated cardiomyopathy decreased in the captopril group (90.3%) when compared with the enalapril group (97.2%). The excess mortality in the captopril group could not be related to the indexes of the severity of heart failure, such as baseline exercise duration, functional class, cardiothoracic ratio, ejection fraction or dose of diuretic drugs. Furthermore, the excess in mortality was seen in all subsets of patients examined as well as across countries. Examination of the dosing regimen used, however, suggests that insufficient daily dosage of captopril or the inadequate schedule of administration, or both, might be responsible for different degrees of angiotensin-converting enzyme inhibition between the enalapril and captopril groups and hence for the difference in mortality. It is important in future clinical trials to determine to what extent complete circadian angiotensin-converting enzyme inhibition is necessary to provide the full benefit of this therapy in heart failure.
 ...
PMID:Difference in mortality between patients treated with captopril or enalapril in the Xamoterol in Severe Heart Failure Study. 205 42

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.
 ...
PMID:Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy--echocardiographical follow-up. 167 61

The use of beta-receptor antagonists in the treatment of heart failure is controversial. Available data do not allow general recommendations regarding their use. In dilated cardiomyopathy, several studies suggest that long-term treatment in individual patients reduces symptoms and increases exercise capacity. Short-term treatment is usually not beneficial, except in patients with ischemically induced left ventricular dysfunction. In heart failure, post myocardial infarction and in chronic ischemic heart disease, no proper long-term study has been performed to evaluate its effects. However, patients with acute myocardial infarction tolerate beta blockers, despite the presence of left ventricular dysfunction and long-term prognosis is improved. Newer agents, some with ancillary properties, such as intrinsic activity and vasodilatation, may have advantages. In the future we need a better description of the cardiac status in our patients in order to be able to select those that will respond favorably to beta-receptor antagonists. The mechanisms by which some patients improve are still obscure. Protection against receptor downregulation, restoration of receptor density, protection against cardiotoxicity of catecholamines, and improvement in ischemic systolic and diastolic left ventricular function are all possible. The fear that beta-receptor antagonists are dangerous in heart failure is in most instances not warranted, but an initial deterioration may have to be accepted in order to gain long-term beneficial effects. Ongoing studies in both idiopathic cardiomyopathy and in postinfarction failure will hopefully help us to define the use of beta-adrenoceptor antagonists in the future.
 ...
PMID:Beta receptor antagonists in the treatment of heart failure. 167 62

In addition to the underlying pathophysiological processes that cause myocarditis and dilated cardiomyopathy, structural, biochemical, neurohormonal and haemodynamic influences and interrelations promote progression of the heart failure syndrome. Independent of their symptomatic benefits, diuretics, digitalis, ACE inhibitors, PDE inhibitors and dopamine agonists exert specific influences on factors that retard or accelerate progression of congestive heart failure (CHF). Important factors that indicate or promote progression of CHF are discussed here, with special emphasis on therapeutic options. Interference with baroreceptor function (digitalis, ACE inhibitors), the RAA system (ACE inhibitors), the sympathetic nerve system (dopamine agonists, ACE inhibitors, digitalis) can potentially retard progression of CHF, while other therapeutic options, such as PDE inhibitors and diuretics, might accelerate progression of left ventricular dysfunction and CHF.
 ...
PMID:Therapeutic alternatives in dilated cardiomyopathy--a review of current options. 168 Jun 88

Few studies have been conducted that focus on survival as the end point of medical therapy of CHF. No vigorous studies have been conducted in dogs. It is generally accepted that diuretic therapy is an essential component of the therapy of CHF in cardiomyopathic dogs. Significant symptomatic improvement is afforded by diuretics, and acute death may be prevented. In this context diuretics can be said to improve survival. However, diuretics do not alter the natural progression of cardiomyopathy and in this context do not favorably influence long-term survival. Digitalis glycosides have been shown in humans to improve various parameters of CHF in a subset of patients with either atrial fibrillation or third heart sounds. In dogs, these gallop heart rhythms due to third heart sounds are usually associated with myocardial failure due to dilated cardiomyopathy. In spite of symptomatic improvement, no study has demonstrated an unequivocal favorable effect of digoxin on survival of patients with dilated cardiomyopathy. Likewise, there is no convincing evidence of an adverse effect on survival. Newer, powerful inotropes, such as milrinone, often demonstrate impressive short-term improvements in left ventricular function, clinical signs, and exercise tolerance in patients with CHF. However, their long-term benefits are much less impressive, they are arrhythmogenic, and they have not been shown to prolong survival. In fact, long-term milrinone therapy in humans has had an unfavorable influence on mortality. Vasodilators offer the potential advantage of increasing left ventricular performance without an associated increase in myocardial oxygen demand and cardiac rhythm disturbances. The only vigorous survival study that unequivocally demonstrated improved survival of patients with advanced CHF due to myocardial failure, including dilated cardiomyopathy, was the Consensus Trial. Survival of patients receiving enalapril was significantly better than those receiving placebo. In fact, the trial was stopped prematurely by the ethical review committee when it became obvious that the results favored the enalapril group. Although the use of beta-adrenergic blocking drugs in cardiomyopathic patients with CHF is controversial and associated with a risk of short-term deterioration of left ventricular function, their use in human medicine is gaining acceptance. Although hemodynamic and clinical evidence of improvement has been demonstrated along with withdrawal-associated deterioration, the only study purporting a beneficial effect on survival used retrospective controls.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effect of medical therapy on survival of patients with dilated cardiomyopathy. 168 46

The human heart contains both beta 1-adrenoceptors and a considerable number of beta 2-adrenoceptors, both of which bring about positive inotropic and chronotropic effects of beta-adrenoceptor agonists in vitro and in vivo. In chronic heart failure, the decrease in beta-adrenoceptor function is related to the severity of the disease. However, both cardiac beta 1- and beta 2-adrenoceptors seem to be differentially affected depending on the type of heart failure and its aetiology. beta 1-adrenoceptor function decreases in all forms of chronic heart failure. beta 2-adrenoceptor function, on the other hand, decreases in mitral valve disease, tetralogy of Fallot and end-stage ischaemic cardiomyopathy, and seems to be unaltered (or only mildly uncoupled) in end-stage dilated cardiomyopathy, and possibly in aortic valve disease. Since the human heart has few spare beta-adrenoceptors and these decline with increasing degree of heart failure, beta-adrenoceptor agonists (but only non-selective full agonists) may be of therapeutic use only if the heart needs acute inotropic support; in long-term treatment they may be not effective, since tolerance develops. On the other hand, for long-term treatment selective beta 1-adrenoceptor antagonists may be beneficial since they protect the heart from the deleterious effects of chronic exposure to high (cardiac derived) noradrenaline and simultaneously may restore the previously reduced beta-adrenoceptor function.
 ...
PMID:Pathophysiology of the beta-adrenoceptor system in chronic heart failure: consequences for treatment with agonists, partial agonists or antagonists? 168 17

Beta-blockers were initially given to patients with chronic heart failure due to ischemic heart disease and resting tachycardia. The prompt effect on severe backward heart failure was directly associated with an immediate fall in heart rate. This observation led to long-term administration to patients with idiopathic dilated cardiomyopathy and, later, to patients with ischemic cardiomyopathy and secondary cardiomyopathies as well. Due to marked down-regulation of beta receptors, patients with heart failure are extremely sensitive to beta blockade. A test dose of metoprolol 5 mg b.i.d. for 2 days is recommended to select patients for long-term beta-blockade, followed by careful titration with increment in dose over 6 weeks. One important effect of beta-blockade in the early phase of treatment is a reduction in the myocardial energy demand early after the onset of long-term treatment. After 1 month of treatment with beta-blockers, marked improvement of diastolic function is observed. This effect might be attributed to inhibition of calcium overload. After 3 months of treatment, an increase in ejection fraction can be observed, which might be attributed to upregulation of beta receptors. The withdrawal of long-term treatment was followed by a deterioration of heart function in 61% of patients and improvement was seen after reinstitution of beta-blockade. There was an increase in cardiac index and stroke work index at rest as well as during supine exercise. A marked fall in left ventricular filling pressure at rest and unchanged filling pressure during supine exercise was noted, while exercise capacity increased by 25%. A similar pattern was seen in patients with ischemic cardiomyopathies and other secondary cardiomyopathies. However, the increase in ejection fraction in the ischemic cardiomyopathy group was lower (0.06) compared to the groups with dilated cardiomyopathy and other secondary cardiomyopathies (0.18).
 ...
PMID:Beta-adrenergic blockade in dilated cardiomyopathy, ischemic cardiomyopathy, and other secondary cardiomyopathies. 168 23

Forskolin, a diterpene derivative of the Indian plant Coleus forskhohlii, proved to be a marked positive inotropic and vasodilatory compound in animal experiments with a mechanism of action distinct from catecholamines, cardiac glycosides, and phosphodiesterase-inhibiting compounds. The cardiovascular effects of forskolin seem to be mediated by a direct stimulatory action at the catalytic unit of sarcolemmal adenylate cyclase. The aim of the present study was to clarify the cardiovascular profile of this compound in 12 patients with stage III (NYHA) congestive cardiomyopathy. The effects of forskolin were investigated by invasive techniques using the thermodilution catheter method and compared to the beta 1-receptor agonist dobutamine and the vasodilator sodium nitroprusside in an intraindividual comparison. Forskolin dose-dependently reduced cardiac pre- and afterload values, and led to a reduction in systolic, diastolic, and mean pulmonary artery pressure as well as pulmonary wedge pressure by greater than 50% concomitant with an increase in cardiac output. There was a slight increase in heart rate. Cardiac stroke volume and stroke volume index was increased by approximately 70%. The cardiovascular effects of dobutamine and nitroprusside were less pronounced; however, it seemed that a similar hemodynamic profile could be achieved by the combination of both dobutamine and sodium nitroprusside. In view of the rapid development of tolerance toward beta 1-receptor stimulation, forskolin, with its receptor-independent mechanism of action, may be advantageous for the treatment of severe heart failure, especially in patients with catecholamine-insensitive heart failure.
 ...
PMID:Cardiovascular effects of forskolin (HL 362) in patients with idiopathic congestive cardiomyopathy--a comparative study with dobutamine and sodium nitroprusside. 169 72

The antiarrhythmic properties of amiodarone at the ventricular level were discovered in the early 1970s. The unanimously recognised efficacy of amiodarone includes a weak negative inotropic effect and compensatory vasodilatory properties, making amiodarone particularly suitable for treating the potentially malignant arrhythmias associated with organic disease. In a review of 611 hospitalised patients on amiodarone, and 353 patients in whom the drug had been prescribed, over a 52-month period in our 60-bed department, we noted that amiodarone was prescribed in 53% of patients for arrhythmias and in 47% of patients for coronary insufficiency. Ventricular arrhythmias represented 13% of the rhythmic indications. These indications differ from those in the USA. The efficacy (70 to 90%) of amiodarone in ventricular extrasystoles has been shown in open studies. In coronary patients, the antiarrhythmic activity of amiodarone is superior to that of propranolol. However, there has been no controlled study because the need for a loading dosage, and the electrocardiographic effects render such studies difficult. After myocardial infarction, ventricular arrhythmias constitute a significant risk factor independently of prognosis; amiodarone may be useful in this indication, and studies of the European Myocardial Infarction Amiodarone Trial (EMIAT) type will examine its value here. Since 1973, it has been recognised that amiodarone can prevent ventricular tachycardia in 55 to 89% of patients in the clinical situation. After a long-standing controversy, the positive predictive value of programmed stimulation has finally been agreed on. In hypertrophic cardiomyopathy, retrospective studies suggest a reduction in mortality in patients treated with amiodarone. By contrast, the value of amiodarone in dilated cardiomyopathy requires more intensive investigation. We consider amiodarone to be indicated in ventricular arrhythmic complexes, particularly if they are associated with an ejection fraction of less than 35% and/or atrial fibrillation. The value of amiodarone in arrhythmias associated with heart failure needs to be evaluated. In conclusion, amiodarone is a powerful antiarrhythmic agent but, because of the possibility of dose- and duration-dependent side effects, evaluation of the risk: benefit ratio in each indication is needed.
 ...
PMID:The value of oral amiodarone in the treatment of ventricular arrhythmias in heart disease. 171 68

We analyzed our 10-year cumulative experience of 40 consecutive patients with idiopathic dilated cardiomyopathy and associated ventricular tachyarrhythmias, treated with implantable cardioverter defibrillators. Dilated cardiomyopathy was defined as left ventricular ejection fraction (EF) less than or equal to 50% with no defineable etiology. Patient characteristics included: 24 male, mean age 52 years, mean EF = 33%, New York Heart Association Class I-III, presenting syndrome--cardiac arrest (n = 28), syncope/near syncope (n = 12). At 2.5 years mean follow-up, there were 16 deaths: one operative, three sudden, two incessant ventricular tachycardia/ventricular fibrillation (VT/VF), six heart failure, and four noncardiac. The actuarial mortality at 1 and 4 years was 0% and 14% for sudden death, 11% and 34% for cardiac death. The projected mortality was 52% and 78% for same time intervals (P less than 0.01). No useful baseline variable predicted who would or would not receive an ICD shock in follow-up. ICD therapy appears effective in reducing sudden death mortality in this high risk population.
 ...
PMID:Long-term follow-up of patients with nonischemic dilated cardiomyopathy and ventricular tachyarrhythmias treated with implantable cardioverter defibrillators. 172 Nov 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>