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

Angiotensin-converting enzyme inhibitors improve long-term survival in patients with left ventricular dysfunction after a myocardial infarction, but their mechanism of action is not entirely clear. The neurohormonal effects may be important in this respect, as well as an early hemodynamic unloading induced by these drugs. The primary objective was to assess the effect of trandolapril on plasma levels of atrial natriuretic peptide. A secondary objective was to assess the effects of trandolapril on selected neurohormones, vasoactive peptides and enzymes, which may be important in the development of left ventricular remodeling and heart failure following an acute myocardial infarction. A total of 119 patients with an acute myocardial infarction and a wall motion index < or =1.2 (16-segment echocardiographic model) were randomized to double blind treatment with trandolapril or placebo within 3-7 days after the onset of infarction. Blind treatment was discontinued 21 days after the index infarction. Venous blood samples were collected at rest, before randomization and on the day after treatment was discontinued. At the end of the study, there were no differences in plasma levels of atrial natriuretic peptide between the two treatment groups. Angiotensin-converting enzyme activity was suppressed and plasma renin activity was higher in the trandolapril group. No differences in plasma levels of N-terminal pro-atrial natriuretic peptide, brain natriuretic peptide, aldosterone, noradrenaline, adrenaline, vasopressin, big endothelin-1 and neuropeptide Y were found between the two treatment groups. There were positive correlations between several markers of neurohormonal activation at baseline and variables expressing left ventricular dysfunction and clinical heart failure. Neurohormonal activation is related to left ventricular dysfunction. The effects of 2-3 weeks of angiotensin-converting enzyme inhibition on neurohormonal activation does not predict the already established beneficial long-term effects after myocardial infarction. Thus, early modulation of circulatory neurohormone levels may not be a major mechanism for the efficacy of angiotensin-converting enzyme inhibitors in these patients. Selected plasma hormone markers may still be used to identify patients who might get the greatest benefit from treatment.
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PMID:Early neurohormonal effects of trandolapril in patients with left ventricular dysfunction and a recent acute myocardial infarction: a double-blind, randomized, placebo-controlled multicentre study. 1116 38

The incidence of chronic heart failure has increased, with a corresponding increase in morbidity and mortality, and has made a substantial financial impact on our society. Improved therapy for heart failure has resulted in a significant prolongation of survival, a decreased number of hospitalizations, and an enhanced quality of life for many patients. It can reasonably be expected, therefore, that adherence to a rational medical regimen for these patients might decrease costs as well. Management of patients with severe heart failure begins with identifying the etiology and educating the patients and their families. Angiotensin-converting enzyme inhibitors are the cornerstone of therapy but only after diagnostic tests are performed to establish the etiology and extent of myocardial dysfunction. Because cardiac transplantation is a therapeutic option for only a limited number of patients, other surgical and medical therapies have to be viewed as the mainstay of a treatment strategy.
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PMID:Treatment of advanced heart failure. 1117 88

Angiotensin-converting enzyme (ACE) inhibitors are now accepted as part of the routine management of patients with heart failure. Their use has been mandated in all the new major mortality trials to test the efficacy of beta-blockers in heart failure. Morbidity and mortality remain high in those with heart failure even with the benefits proven for both these groups of agents. In spite of the evidence for benefit of ACE inhibitors they are persistently used in lower doses in clinical practice than tested in the large-scale trials. This was so prevalent as to allow the conduct of a substantial study, the ATLAS trial, to compare high and low dose ACE inhibition. Its equivocal findings have allowed different interpretations. Clinical experience would suggest that starting with a low dose is appropriate but the dose should be titrated then without undue delay to the levels used in the trials wherever possible. The evidence for benefit with these drugs had been obtained largely in patients with impaired systolic function. However the AIRE study selected patients with clinical evidence of heart failure after myocardial infarction rather than with impaired systolic function. A substantial and long-term benefit was found from ACE inhibition. A cohort of patients had ventricular function assessed and as anticipated almost one half had preserved systolic function. Whilst the absolute benefit in lives saved was greater in the higher risk/low ejection fraction group, the relative risk reduction was not significantly different between those with preserved or impaired systolic function. The publication of the HOPE trial, although not a study of patients with heart failure, has clarified the situation considerably for those taking day to day care of patients. The HOPE study selected patients on the basis of high cardiovascular risk excluding those with known impaired systolic function. Although not an entry requirement for the study, ejection fraction was measured in a substantial majority and was above 40% indicating preservation of systolic function. The ACE inhibitor ramipril markedly reduced the combined end-point of cardiovascular death, stroke and myocardial infarction. Importantly there was a highly significant 20% risk reduction in the rate of myocardial infarction, a prospectively defined end-point, over the average four and a half year follow-up. Taken together with the retrospectively derived evidence from the heart failure trials there is now compelling evidence that the ACE inhibitors prevent myocardial infarction. The majority of patients with clinical heart failure have underlying ischaemic heart disease. Prevention of myocardial infarction and control of blood pressure are two key factors in the management of these patients irrespective of systolic ventricular function. The ACE inhibitors like the beta-blockers therefore have a pivotal role in their management. A challenge to current clinical trials is to determine whether these properties are shared to the same degree by the angiotensin antagonists or if even further gains in benefit can come from their combination. The neutral findings of the ELITE II study comparing the angiotensin antagonist, losartan, with the ACE inhibitor, captopril, have heightened interest in the on-going trials addressing these issues.
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PMID:ACE inhibitors in heart failure: an update. 1119 59

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, the development of remodeling, left ventricular (LV) dysfunction, and ischemic events, both when administered alone as long-term treatment in patients with impaired LV function and/or heart failure (HF) and as short-term treatment, early after acute myocardial infarction (AMI) and/or HF. The few data available on the use of ACE inhibitors in the elderly after AMI are conflicting. Nothing is known about the effects of ACE inhibitors in elderly postinfarction patients with preserved LV function: these patients have a remarkable medium- to long-term mortality and HF incidence after infarction. The aim of this study is to evaluate, in patients with AMI aged > or =65 years, the effects of Perindopril on the combined outcome of death, hospitalization for HF, and heart remodeling, considered to be a > or =8% increase in LV end-diastolic volume (LVEDV). Secondary objectives include the same factors listed in the primary end points but considered separately. In addition, safety of the drug, ventricular remodeling, and adaptation are being evaluated. A total of 1100 patients with AMI (first episode or reinfarction), aged > or =65 years, and preserved or only moderately depressed LV (LV ejection fraction > or =40%), are to be enrolled and randomly assigned to treatment (8 mg for 12 months of Perindopril or placebo, in double-blind conditions). Clinical assessment is performed at fixed times, and periodic evaluations of (1) ventricular shape, dimensions, and function by quantitative 2-D echocardiography, and (2) heart rate variability and arrhythmias by ambulatory electrocardiographic monitoring are anticipated. The results and conclusions will be available by 2002 year.
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PMID:PREAMI: Perindopril and Remodelling in Elderly with Acute Myocardial Infarction: study rationale and design. 1130 Mar 69

Angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of therapy for congestive heart failure (CHF). Because ischemic heart disease is the most common cause of CHF, aspirin is frequently given concomitantly with ACE inhibitors in patients with CHF. Increased bradykinin levels, with the consequent enhanced synthesis of vasodilatory prostaglandins, appear to mediate a significant benefit of ACE inhibitor therapy in these patients. In contrast, aspirin inhibits cyclooxygenase, and thereby suppresses prostaglandin production. Thus, these counteracting effects on prostaglandins may result in antagonism between ACE inhibitor and aspirin therapy in heart failure patients. Several early reports questioned the safety of aspirin in CHF, and the potential antagonistic interaction between ACE inhibitors and aspirin in patients with heart failure has become the focus of both increasing research and intense debate. This article briefly highlights the theoretic considerations underlying this interaction, and reviews the available evidence for such an interaction from clinical trials.
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PMID:The angiotensin-converting enzyme inhibitor and aspirin interaction in congestive heart failure: fear or reality? 1130 80

Hospital admission for congestive heart failure is extremely common and quite expensive, although it is frequently preventable. New drugs and therapies have been reported to reduce admissions, decrease morbidity and mortality, and improve the quality of life for these patients. Patients with an ejection fraction less than 40 percent (decreased systolic function) should be treated with medication to improve symptoms and prevent progression of heart failure. Angiotensin-converting enzyme (ACE) inhibitors are a mainstay of treatment in patients who can tolerate them; in patients who cannot take these drugs, angiotensin II receptor blocking agents offer an alternative. Patients with New York Heart Association class II or III heart failure should also receive a beta blocker (metoprolol, carvedilol or bisoprolol). Recent research has shown that treatment with spironolactone improves mortality and hospital readmission rates. An exercise program should also be recommended for all patients with heart failure unless their condition is unstable.
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PMID:Reducing readmissions for congestive heart failure. 1132 25

Patients with chronic heart failure (CHF) have an increased risk for sudden death. This increased risk has been associated with increased QT dispersion (QTd), a reflection of the heterogeneity in ventricular repolarization. Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease heart size as well as decreasing morbidity and mortality in moderate-to-severe CHF. The aim of this study was to determine if ACE therapy is associated with a decrease in QTd, a marker for increased electrical instability. Ninety-seven patients were evaluated. The normalized QTd after 2 months of ACE therapy decreased from 16 +/- 4 to 12 +/- 3, a 25% reduction in dispersions. QTd also decreased from 61 +/- 14 to 47 +/- 12 (P < .001) and QTc dispersions decreased from 71 +/- 18 to 52 +/- 14 (P < .001). After 2 months of ACE inhibitor therapy, heart rate slowed significantly (RR intervals 765 +/- 198 before and 838 +/- 186 after ACE). There was a negative correlation between ejection fraction and QTd (r = -0.8; P < .001). The study also found no correlation between ACE level, percent converting enzyme inhibition, and QTd. The effects of ACE therapy appear early on in terms of repolarization changes. The reduction in QTd may explain the reduced sudden death mortality in patients with heart failure who are treated with ACE inhibitor therapy.
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PMID:Effect of angiotensin-converting enzyme therapy on QT interval dispersion. 1132 7

The combination of an angiotensin II receptor antagonist and a thiazide has been used extensively in the treatment of patients with overt heart failure. The effect of this combination on the vascular wall early in the disease, however, has not been investigated. To evaluate this effect, the vascular status of 3-month-old cardiomyopathic hamsters was assessed after daily administration of a combination of losartan (25 mg/kg, p.o.) and hydrochlorothiazide (6.5 mg/kg, p.o.) over an 8-week period. Age-matched golden hamsters were used as healthy controls. The contractile response of aortic rings to endothelin-1 was significantly higher in cardiomyopathic hamsters than in control animals. Concentration-response curves for the endothelin-1-induced contraction were displaced to the right after hydrochlorothiazide+losartan treatment (toward the curves for healthy controls); however, E(max) from treated hamsters was significantly reduced when compared to E(max) from untreated cardiomyopathic animals (1.016+/-0.073 vs. 1.346+/-0.153 g, P<0.05, n=6). No significant differences in the EC50 values from these curves were observed between hydrochlorothiazide+losartan treated and untreated cardiomyopathic animals (2.90+/-0.95 vs. 1.10+/-0.85 nM, P>0.05). The acetylcholine-induced relaxation observed in cardiomyopathic animals was not improved after treatment with hydrochlorothiazide+losartan or hydrochlorothiazide alone, but the combination of these drugs increased significantly the basal production of nitric oxide (NO). Angiotensin-converting enzyme activity increased in plasma (from 29.9+/-1.23 to 41.16+/-1.82 nmol x mg(-1) x min(-1), n=8, P<0.05) but decreased in the aorta (from 0.33+/-0.02 to 0.25+/-0.017 nmol x mg(-1) x min(-1), n=6, P<0.05) after treatment with hydrochlorothiazide+losartan. In addition, the combination of these drugs reduced the heart-to-body mass ratio (3.96+/-0.07 for treated vs. 5.01+/-0.20 mg/g for untreated animals, n=7, P<0.05), and the thickness of the aortic media (0.076+/-0.003 for treated vs. 0.149+/-0.009 mm for untreated animals, n=8, P<0.05). Although hydrochlorothiazide alone lowered systolic blood pressure to the same level achieved with both drugs in combination (from 166+/-10 for untreated cardiomyopathic animals to 84+/-1 mm Hg for hydrochlorothiazide+losartan, and 80+/-5 mm Hg for hydrochlorothiazide alone, P<0.05), no significant reduction in heart-to-body mass ratio was observed in animals treated with the diuretic alone (P>0.05). In conclusion, in this model of heart failure, chronic hydrochlorothiazide+losartan administration normalizes the vascular responses to endothelin-1, improves basal vascular tone, and prevents the development of cardiac and vascular hypertrophy.
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PMID:Chronic administration of losartan plus hydrochlorothiazide improves vascular status in young cardiomyopathic hamsters. 1140 35

The syndrome of congestive heart failure may result from either systolic or diastolic dysfunction of the left ventricle. Diastolic left ventricle dysfunction is particularly common in the geriatric age group, and is associated with left ventricular hypertrophy resulting from aging and hypertension. The clinical differentiation of these two patterns is important in understanding the pathophysiologic process and in selecting appropriate therapy. Angiotensin-converting enzyme (ACE) inhibitors are useful in systolic dysfunction, both in improving clinical manifestations of reduced cardiac output and in actually prolonging survival. ACE inhibitors are also beneficial in diastolic heart failure by promoting regression of left ventricular hypertrophy, thus improving diastolic physiological function. Calcium antagonists improve diastolic function by reducing blood pressure of hypertensive subjects, reducing left ventricular mass, and theoretically, by facilitating the energy-dependent transport of calcium ions from the actin-myosin complex into the sarcoplasmic reticulum. However, because of the negative inotropic properties of the calcium antagonists, they should be used cautiously, if used at all, in patients with significant systolic dysfunction, at least until the results of clinical trials using these drugs in systolic congestive heart failure are available.
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PMID:Aspects of the Use of Angiotensin-Converting Enzyme Inhibitors and Calcium Antagonists in Treatment of Heart Failure in the Older Patient. 1141 83

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with heart failure and coronary artery disease. Recently, there has been growing concern about the possible interaction between ACE inhibitors and aspirin. Numerous investigators have addressed this issue; however, results are equivocal. Most researchers used a statistical test of interaction, but the use of this method has been criticized. To assess the interaction between ACE inhibitors and aspirin properly, an additive model-more specifically, the Rothman Synergy Index-should be used. Further investigation with this model, however, is needed.
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PMID:Quantifying the interaction between angiotensin-converting enzyme inhibitors and aspirin: are we using the right method? 1160 71


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