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

The aims of the treatment of heart failure are to improve the quality of life and slow the progression of cardiac disease. Improvement of quality of life is best assessed by questionnaire; progression of the disease is assessed by measuring mortality and morbidity. The agenda for the future is to establish intermediate markers for progression of cardiac disease that can be substituted for morbidity and mortality, and thus improve the efficiency and shorten the follow-up of clinical trials. At present, polypharmacy is required to achieve optimal improvements in quality and duration of life. Furthermore, some drugs may favorably affect one end point and adversely affect the other; for example, beta-blockers may exert adverse short-term effects on quality of life but may slow progression of the disease. Certain inotropic drugs may reduce symptoms but shorten life expectancy. Angiotensin-converting enzyme (ACE) inhibitors have exerted favorable effects on both quality of life and mortality, but the magnitude of these benefits has been disappointingly small. Persistent angiotensin-induced vasoconstriction and endocrine effects, despite ACE inhibition, is one possible explanation. The Valsartan in Heart Failure Trial (Val-HeFT) has been designed to test the efficacy and safety of the AT(1) receptor blocker (ARB) valsartan in combination with ACE inhibitors and all other prescribed therapies in patients with heart failure. The study is powered to detect a mortality benefit and should therefore establish the role of ARBs in this patient group. When this trial and other ongoing studies are completed, we will be more able to define the role of ARBs in the treatment of heart failure.
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PMID:Improving outcomes in congestive heart failure: Val-HeFT. Valsartan in Heart Failure Trial. 1044 91

Angiotensin-converting enzyme (ACE) inhibitors were introduced in the early 1980s as a novel class of agents to treat hypertension. Since that time, they have been proven to be a powerful tool in the treatment of symptomatic left ventricular systolic dysfunction. In this article we will summarize the results from clinical trials using ACE inhibitors in the treatment of heart failure and after myocardial infarction. We will discuss some of the mechanisms postulated to account for the beneficial effects associated with ACE inhibitor treatment. Finally, we will highlight some recent controversies in the use of ACE inhibitors.
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PMID:Angiotensin-converting enzyme inhibitors: congestive heart failure and beyond. 1047 85

Rationale The epidemiology of heart failure and patient management procedures may vary from one country to another. This study was designed to analyse the spectrum of patients hospitalized in France for heart failure. Patients and Methods A registry involving 120 departments (cardiology, general medicine and geriatrics) and 1058 patients.Results The patients' median age was 76 years, and the male/female ratio was 55/45. Echocardiography was performed in 77% of the cases: the left ventricular ejection fraction was <30% in 22%, between 30 and 40% in 25% and greater than 40% in 53%. Angiotensin-converting enzyme (ACE) inhibitors were prescribed to, respectively, 78% and 63% of patients with ejection fractions above and below 40%. Conclusion In France, patients hospitalized for heart failure tend to be old and are often women; about one in two have relatively preserved left ventricular systolic function. ACE inhibitor prescription seems to be more frequent than currently reported. This survey confirms the clear gap between the populations in clinical trials and those in routine clinical practice.
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PMID:A national survey of heart failure in French hospitals. The Myocardiopathy and Heart Failure Working Group of the French Society of Cardiology, the National College of General Hospital Cardiologists and the French Geriatrics Society. 1073 20

Angiotensin-converting enzyme (ACE) inhibitors protect the hearts of patients with different levels of cardiac disorder. The greatest benefit seems to be achieved in subjects with most severe heart failure. Moreover, ACE inhibition is protective also in patients without manifested heart failure but with severe systolic left ventricular dysfunction. Data are presented that ACE inhibitors can alter the composition of the myocardium also in control: healthy animals. In rats and rabbits with non-diseased heart, chronic ACE inhibition reduced fibrotic tissue concentration in the left ventricle. We speculate that if this were applied to humans, ACE inhibition may prove to be of potential benefit in subjects with normal systolic function but with a trend to left ventricular filling abnormalities caused by increased ventricular stiffness. In these patients reduction of myocardial fibrotic tissue might prevent deterioration of diastolic function.
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PMID:Effect of angiotensin-converting enzyme inhibitors on non-diseased myocardium of experimental animals: potential clinical implications. 1085 52

In the 1980s and early 1990s, evidence suggesting a pivotal role for chronic neurohormonal stimulation in the pathophysiology of heart failure began to emerge, which has now produced a dramatic change in the way heart failure is viewed and treated. Preclinical data and results from clinical trials revealed that blocking the actions or generation of norepinephrine or angiotensin II positively affected the course of left ventricular dysfunction and myocardial failure, despite the fact that this inhibition had minimal or negative effects on hemodynamics. Angiotensin-converting enzyme (ACE) inhibitors have been used for heart failure for many years, but only recently have beta-blockers been recommended as part of standard treatment for heart failure. The negative inotropic effects of beta-blockers are well known; these agents must be used with caution in patients with heart failure. However, after several months of treatment, left ventricular ejection fraction (LVEF) gradually increases, and a reversal of the pathological remodeling associated with chronic heart failure occurs: left ventricular mass decreases, chamber shape becomes more elliptical, and mitral regurgitation decreases. Data from clinical trials have shown that long-term beta-adrenergic blockade halts the progression of pump dysfunction, substantially improves left ventricular function, and reduces morbidity and mortality rates in patients with mild-to-moderate heart failure. This article provides a detailed rationale for the use of beta-blockers in patients with chronic heart failure, based on the current understanding of pathophysiology and recent clinical trial data.
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PMID:Mechanistic and clinical rationales for using beta-blockers in heart failure. 1090 93

Congestive heart failure causes substantial morbidity and mortality. Symptoms and physical findings can help in diagnosis, but have limited sensitivity and specificity. Objective measurement of ventricular function is essential in virtually all patients in whom heart failure is suspected; reversible causes of heart failure must be sought. Out-patient management includes education and counseling, emphasis on and assessment of compliance with diet, and pharmacological treatment. Angiotensin-converting enzyme inhibitors are the mainstay of treatment but are underused, and maximal doses are not given, apparently because of concern about side-effects. Diuretics should be administered only as needed to manage fluid overload. Calcium channel blockers are relatively contraindicated in patients with impaired ventricular function. Patient follow-up should be guided by results of the medical history and physical examination. Routine serial testing of ventricular function and exercise performance is discouraged.
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PMID:[Diagnosis and treatment of heart failure within the community]. 1091 71

Endogenous peptidases participate in a major way in the formation of peptide pressor substances such as angiotensin II (A II) and endothelin (ET) as well as in the degradation of depressor substances, e.g. atrial natriuretic peptide (ANP) or bradykinin. They include on the one hand the angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE), on the other hand kinase II for bradykinin and neutral endopeptidase 24.11 (NEP) for ANP. Inhibition of these enzymatic reactions leads to a decline of vasopressors A II and ET and conversely delays the break-down of vasodilatating bradykinin and ANP. The main haemodynamic consequence of this double inhibition is a reduced peripheral vascular resistance and decline of the blood pressure. The concurrent block of both systems (dual inhibition) is more effective than the isolated block of one substance. The first dual endopeptidase inhibitors were ACE inhibitors blocking the conversion of angiotensin I to A II and inhibiting at the same time the degradation of bradykinin by kininase II which is identical with ACE. At present further substances were synthetized with a dual inhibitory effect e.g. on ECE and on NEP (phosphoramidone, thiorphan, ecadatril etc.). Under experimental conditions they have a long-term antihypertensive effect on the vascular wall and heart muscle. The development of another dual ACE and NEP inhibitor has reached already the stage of clinical tests and the first clinical studies. The preparation omapatrilate in amounts of 2.5-80 mg significantly reduced the BP in a dose-dependent way in mild and medium advanced essential hypertension. Normalization of the blood pressure, i.e. a drop below 140/90 mm Hg, was achieved with omapatrilate monotherapy in as many as 83% of patients with hypertension stage I and in 53% patients with essential hypertension stage II. The drop of blood pressure after 20-80 mg/day depended on the degree of hypertension and was comparable or better than monotherapy with lisonopril 20 mg/day or amlodipine 10 mg/day. Treatment with omapatrilate was well tolerated. Dual peptidase inhibitors interfering with the formation of pressor substances and with the degradation of depressor substances seem to be a perspective class of antihypertensives also useful in the treatment of other cardiovascular diseases (heart failure, primary pulmonary hypertension). Before its final inclusion in the therapeutic pattern, further comparative and clinical mortality studies must be implemented.
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PMID:[Dual endopeptidase inhibitors--a new direction in the development of hypertensive agents]. 1104 16

Physicians must aggressively treat heart failure in the early stages to prevent disease progression and improve survival. Early treatment implies early diagnosis of left ventricular (LV) dysfunction, before the onset of symptoms. Patients with risk factors for the development of heart failure, especially coronary disease or hypertension, should undergo echocardiography to evaluate LV function. Patients with LV systolic dysfunction should be further evaluated to determine the type of cardiac dysfunction, uncover correctable etiologic factors, determine prognosis, and guide treatment. Angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking drugs improve survival and are integral to the treatment plan. Physicians should prescribe an ACE inhibitor as initial therapy for all patients with LV systolic dysfunction unless there are specific contraindications. The combination of hydralazine and isosorbide dinitrate is an acceptable alternative therapy for patients who cannot take ACE inhibitors. Diuretics should be used if there are signs or symptoms of volume overload. Beta-adrenergic blocking drugs should be added to therapy in stable patients with mild to moderate heart failure after optimal treatment with ACE inhibitors, diuretics, or other vasodilators. Digoxin should be used routinely in patients with severe heart failure and should be added to therapy in patients with mild to moderate heart failure who remain symptomatic despite optimal doses of ACE inhibitors and diuretics. Spironolactone should be added, but electrolytes should be closely monitored. Warfarin anticoagulation should be considered in patients with a left ventricular ejection fraction (LVEF) of 35% or less. Until survival data exist, angiotensin receptor blockers (ARBs) should not be used as initial therapy or as sole therapy but can be used for ACE-intolerant patients or can be added to standard heart failure therapy. Outpatient use of intravenous inotropic therapy should be avoided. Patients with severe heart failure should have peak oxygen consumption measured to quantify functional impairment, determine prognosis, and identify the need for advanced heart failure therapy. Patients who remain symptomatic while receiving optimal standard therapy should be referred early to a specialized heart failure center.
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PMID:Chronic Heart Failure. 1109 88

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been described in chromosome 17q23 of the human genome. Subjects with the genotype DD have markedly higher plasma ACE levels than those with genotype II; although ACE concentration in plasma is not rate-limiting for the production of angiotensin II, it has been suggested that the renin-angiotensin system may have an enhanced role in cardiovascular homeostasis in subjects with DD genotype or D allele. Meta-analysis confirmed the association of the D allele with an increased risk of myocardial infarction and stroke, but these relations are still uncertain with longevity and renal deterioration. Otherwise, I allele seems to be related with an improved response to physical training. The I/D polymorphism of the ACE gene is not a marker for any form of hypertension, though some conflicting results have been described. Nevertheless this polymorphism may have an influence on the antihypertensive response, particularly when using ACE inhibitors (ACEI). For example, blood pressure normalization with captopril in patients suffering from cardiac failure would be more effective in II genotype; conversely, both regression in left ventricular hypertrophy and improvement in diastolic filling would be greater after long-term treatment with enalapril in patients with essential hypertension and DD genotype. Conflicting results were also described using ACEI as a renoprotective therapy. This review therefore supports the justification for further evaluation in appropriately powered studies.
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PMID:Angiotensin I-converting enzyme gene polymorphism and drug response. 1109 39

New therapeutic strategies as well as the development of drugs with more specific targets have been fueled by disappointments in the treatment of adult heart failure. Calcium sensitizers, vesnarinone and angiotensin channel blockers will be addressed in this manuscript. The physiologic and pharmacologic principles that justify their use in the management of heart failure are reviewed. Calcium sensitizers increase myocardial contractility and in part they bypass the adenylyl cyclase cascade, which gives them a more favorable energy profile. Vesnarinone is a quinolinone derivative with ion channel modulation properties, which result in a positive inotropic effect and prolongation of the action potential. In addition vesnarinone has immunomodulatory properties. Angiotensin-converting enzyme inhibitors are the cornerstones for the treatment of heart failure. The discovery of some putative drawbacks to ACE inhibition has challenged this supremacy. Angiotensin receptor blockers have been developed hoping to overcome these deficiencies. Myocardial developmental differences highlight the shortcomings of attempting to extrapolate data on drugs and cellular physiology in adults to children. Studies are needed addressing standards of care, quality of life, morbidity and mortality, neurohumoral activation, its modulation and the consequences of these therapies in pediatric heart failure.
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PMID:New drugs in the treatment of heart failure. 1111 51


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