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

Results of uncontrolled studies suggest that the duration of action of an ACE inhibitor may be an important determinant of renal impairment when using these agents to treat patients with heart failure. To determine whether there is experimental evidence for this hypothesis, we compared the effects of intermittent (captopril, 25 mg i.v. bolus twice daily) and continuous (captopril. 25 mg bolus, then 50 mg/day by constant infusion) ACE inhibition in an ovine model where heart failure was induced by rapid left ventricular pacing (LVP). Six sheep underwent three 4-day periods of LVP with intermittent, continuous, or no treatment (control) given in random order from the onset of LVP. Despite evidence that intermittent captopril administration allowed significant recovery of serum ACE activity (4.6 +/- 1.2 vs. 1.1 +/- 0.5 pmol/L before and after captopril bolus on day 4, p less than 0.001) and restitution of arterial pressure between successive boluses (48 +/- 7 vs. 41 +/- 4 mm Hg, p less than 0.01), there was no difference in the renal effects of intermittent and continuous ACE inhibition (creatinine clearance was 44 +/- 14 and 47 +/- 8 ml/min on day 4 of the intermittent and continuous phase, respectively). Nevertheless, there was a significant correlation between the decline in arterial pressure and fall in creatinine clearance induced by ACE inhibition (r = 0.65, p less than 0.05), with evidence that drug accumulation may potentiate hypotension and renal impairment should arterial pressure be reduced below the threshold for renal autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal effects of ACE inhibition in ovine heart failure: a comparison of intermittent and continuous ACE inhibition. 170 5

Treatment of patients with heart failure due to major ventricular systolic dysfunction should aim not only at symptomatic but also at prognostic improvement. If correction of the underlying problem is not possible, treatment should slow down the progression of cardiac failure and eliminate triggers for sudden cardiac death due to electromechanical dissociation or arrhythmias. In every patient with chronic congestive heart failure screening for myocardial ischemia and complete revascularization is mandatory, if possible. In patients with coronary artery disease and diminished systolic function, beta-blockade may improve prognosis by reducing ischemic events and sudden cardiac death. The incidence of life-threatening arrhythmias in patients with heart failure may be reduced by eliminating facilitating factors like electrolyte disturbances, altered autonomic tone and raised intracardiac pressure rather than by antiarrhythmic medical treatment itself. One of the most important prognostic aspects in treatment is the interference with the development of the cardiomyopathy of overload, uniformly observed in chronic congestive heart failure. Modification of mechanical and neuroendocrine stimuli may postpone myocardial hypertrophy and interstitial hyperplasia as a consequence of altered gene expression. Early treatment with ACE inhibitors and in certain patients with betablockers are the most promising strategies to delay the progression of the disease. In contrast, positive inotropic drugs, including digitalis and phosphodiesterase inhibitors, do not improve prognosis. Calcium antagonists should also be used with restriction, as Verapamil and Diltiazem, but also Nifedipine may adversely affect the outcome in congestive heart failure patients.
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PMID:[Prognostic aspects in the treatment of chronic heart insufficiency]. 173

We conclude from our studies and data from the literature that ACE inhibitors belong to the proper basic therapy of cardiac failure because of their marked influence on progression and death by pump failure. The therapeutic gain per 100 patients treated for one year exceeds that of other medications used commonly for secondary prophylaxis.
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PMID:[The effect of captopril on the progression of heart insufficiency]. 173 1

In severe chronic heart failure, myocardial beta-adrenoceptors are downregulated and G-proteins inhibiting adenylate cyclase activity are augmented. Because of these biochemical changes, all positive inotropic drugs that need cAMP for their contractile effects lose their efficacy. Among the positive inotropic drugs used today for treatment of heart failure, only cardiac glycosides remain effective without development of tolerance as long as enough contractile myocardium is left. Controlled studies with phosphodiesterase III inhibitors (milrinone and enoximone) have revealed an unfavorable prognosis in these patients in comparison to placebo. Thus, these drugs are not indicated in chronic heart failure. In higher classes of chronic heart failure, therapy should always be a combination of diuretics, digitalis, and ACE-inhibitors.
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PMID:[Positive inotropic substances--therapeutic perspectives]. 179 36

In 33 patients with heart failure (NYHA II-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:00 to 22:00 h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 +/- 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 +/- 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p less than 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 +/- 0.1 mmol/L) reached statistical significance (p less than 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 +/- 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.
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PMID:Circadian rhythm of blood pressure in congestive heart failure and effects of ACE inhibitors. 181 90

The impact of treatment on prognosis of patients with chronic congestive heart failure depends not only on pharmacological therapy but also on nonpharmacological aspects of patient management. Patient compliance, life style changes, salt and fluid restriction, detailed patient information and measures of self control greatly affect therapeutic efficacy. Reasons for hospitalizations and emergency room visits: In an analysis of 82 admissions of patients for decompensated chronic congestive heart failure we found poor compliance with drug treatments or dietary instructions as causally related factors in 30 patients, uncontrolled hypertension in 22 patients, acute infection in 18 and acute myocardial ischemia in 18 patients. More than half of the patients had weight gain before decompensation, that had not been adequately answered by changes in medication. Inadequate patient information: Inadequate knowledge about necessary life style changes at the time of hospital discharge is often found in patients with chronic heart failure. Less than 50% of these patients remembered correctly the instructions on key issues of necessary life style changes and diet. Drug treatment of heart failure: Recent controlled drug trials have not gained enough weight in therapeutic decisions of physicians treating heart failure patients. While ACE-inhibitors have been shown to improve longevity in congestive heart failure only 6% of patients with heart failure are treated with these drugs, while 5% are treated with calcium antagonists which have not been proven to be of symptomatic or prognostic benefit and may be harmful as well in this disease. Inadequate dosage in patients with chronic renal failure or in elderly patients as well as inadequate choice of drugs lead to side effects in a considerable percentage of patients.
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PMID:[Effects of patient information, compliance and medical control on prognosis in chronic heart failure]. 182 Feb 95

Progression of heart failure ("expected mortality") and sudden cardiac death ("unexpected mortality"), presumably secondary to ventricular arrhythmia, are the major causes for the poor prognosis in chronic heart failure (CHF). Limitations of this classification ultimately stem from inaccuracies in establishing the mechanism of death at the time of death. Elucidation of the determinants of patients prone to sudden death and the effects of treatment modalities on the rate of sudden death remain hidden. Unexpected mortality is probably secondary to arrhythmic death but denotes only that death occurred within some brief interval (arbitrarily less than one hour in most studies) and does not exclude other causes. The demonstrated benefit of ACE inhibitors for improving total mortality as illustrated by the findings of the VHeFT, Captopril Multicenter and CONSENSUS, and the improved event-free survival shown by Munich Mild Heart Failure Trial for low-dose captopril argues strongly for their use in patients with CHF. These agents are confirmed to reduce the risk of death from pump failure; the effects on sudden death are less clear. Although many favorable effects contribute to improved hemodynamics, neuroendocrine and electrolyte status as discussed, at present, it is not possible to predict the precise mechanism by which these agents extend life and whether they reduce the frequency of "sudden" deaths.
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PMID:Can angiotensin converting enzyme (ACE) inhibitors influence the risk of sudden cardiac death in patients with heart failure? 182 Feb 99

In 1984 we demonstrated in an animal model of chronic congestive heart failure due to rapid right ventricular pacing in chronically instrumented dogs, that the inhibition of the renin-angiotensin-aldosterone system by captopril from the onset of pacing has beneficial effects on hemodynamic and neurohumoral mechanisms. In contrast to control animals, dogs on a chronic therapy with the ACE-inhibitor showed no significant increase in peripheral vascular resistance, a reduced decline of cardiac output and no significant increase of mean pulmonary arterial pressure. Chronic ACE-inhibition led to a significant reduction of the secretion of aldosterone, to an attenuation of the activation of the sympathetic activity and to a prevention of inappropriate stimulation of vasopressin secretion. This was associated with a reduction in symptoms and a lack of fluid retention, whereas control animals developed pleural infusions and ascites. Similar beneficial effects have been demonstrated in rats following myocardial infarction during a long-term therapy with captopril on hemodynamic parameters, heart size, and survival. Thus, early inhibition of the renin-angiotensin-aldosterone system in heart failure may be an attractive approach for treatment in patients with ventricular dysfunction even before symptoms develop.
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PMID:[ACE inhibition: mechanisms of cardioprotection in chronic experimental heart failure]. 183 Sep 9

Epidemiologic studies have revealed that in arterial hypertension left ventricular hypertrophy is an important risk factor for cardiac failure. Accordingly antihypertensive therapy should aim at preventing or regressing left ventricular hypertrophy. Reduction of blood pressure does not necessarily induce reversal of left ventricular hypertrophy. Vasodilators like hydralazine and minoxidil, which lead to augmented plasma levels of norepinephrine, were not able to diminish left ventricular hypertrophy. In contrast, a sympatholytic therapy with methyldopa caused a reversal of left ventricular muscle mass. These experimental findings in spontaneously hypertensive rats led to the hypothesis that catecholamines control the onset and progression of myocardial hypertrophy mostly independent of blood pressure. This hypothesis was supported by the experimental findings, that subhypertensive dosages of norepinephrine induce left ventricular hypertrophy and that this hormone promotes alpha-receptor mediated growth of isolated myocytes. Recent studies have revealed that also the renin-angiotension-system has trophic effect on the myocardium. Clinical investigations have documented regression of cardiac hypertrophy due to antihypertensive therapy with sympatholytic drugs, ACE-inhibitors, calcium-channel blockers and beta-receptor blockers. Diuretics failed to decrease left ventricular muscle mass along with blood pressure normalization.
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PMID:[ACE inhibition: mechanisms of cardioprotection in heart hypertrophy]. 183 Sep 11

1. There is a body of circumstantial and direct evidence supporting the existence and functional importance of a tissue based RAS at a variety of sites. 2. The relation between circulatory and tissue based systems is complex. The relative importance of the two in determining haemodynamic effects is unknown. 3. Despite the wide range of ACE inhibitors already available, it remains unclear whether there are genuine differences related to tissue specificity. 4. Pathological states such as chronic cardiac failure need to be explored with regard to the contribution of tissue based ACE activities in generating acute and chronic haemodynamic responses to ACE inhibitors. 5. The role of tissue vs plasma ACE activity may be clarified by study of the relation between drug concentration and haemodynamic effect, provided that the temporal dissociation is examined and linked to circulating and tissue based changes in ACE activity, angiotensin peptides and sympathetic hormones.
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PMID:Tissue and plasma angiotensin converting enzyme and the response to ACE inhibitor drugs. 184 31


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