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

There is no evidence that loop diuretics improve ventricular remodeling in patients with heart failure. Aldosterone receptor antagonists, which have an effect on natriuresis and diuresis, especially in conjunction with an angiotensin converting enzyme-inhibitor, have been shown to improve ventricular remodeling in patients with left ventricular systolic dysfunction. The mechanisms for this beneficial effect and a reduction in death due to progressive heart failure seen in the randomized aldosterone evaluation study (RALES) is likely related to the effect of aldosterone receptor antagonism on myocardial collagen formation and ventricular hypertrophy. Further proof of this hypothesis should be forthcoming from the results of the Eplerenone Heart Failure Efficacy and Survival Study (EPHESUS) early in 2003 in which the aldosterone receptor antagonist eplerenone is being evaluated in patients with systolic left ventricular dysfunction post myocardial infarction.
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PMID:Do diuretics and aldosterone receptor antagonists improve ventricular remodeling? 1255 63

Recent preclinical and clinical studies indicate that aldosterone, independent of angiotensin II and elevated blood pressure, may play a role in health and disease. In addition to its role in fluid and electrolyte balance and circulatory homeostasis, more recent studies have identified aldosterone as a critical mediator of vascular damage. In animal studies, aldosterone is implicated in cardiac and vascular fibrosis, renal disease, and cerebrovascular damage. These lesions are prevented by specific aldosterone receptor blockade. In clinical studies, aldosterone receptor antagonism is associated with decreased hospitalization, symptomatology, and mortality, and improvement of endothelial dysfunction in patients with chronic heart failure. A better understanding of aldosterone's actions in nonepithelial tissues should pave the way to better protection of organs at risk such as the kidneys, heart, and brain.
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PMID:Aldosterone and specific aldosterone receptor antagonists in hypertension and cardiovascular disease. 1264 11

Based upon the results of the RALES trial and accumulating evidence about the role of aldosterone and aldosterone receptor antagonism in various disease states, the authors anticipate that aldosterone receptor antagonists will become standard therapy, along with ACE inhibitors and beta-adrenergic receptor blocking agents, in patients with heart failure that is caused by systolic left ventricular dysfunction. Furthermore, the prospect of the use of these agents in other disease states that have implicated an activated rennin-angiotensin-aldosterone cascade, such as diastolic dysfunction, aging, and atherosclerosis, remains to be tested. Until further data from well-designed, prospective, randomized trials are available, the use of aldosterone receptor antagonists should be restricted to patients with severe or progressive heart failure caused by systolic left ventricular dysfunction in whom serum creatinine level is < or = 2.0 mg/dL and serum potassium levels are < 5.0 meq/L at baseline.
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PMID:Aldosterone as a target in congestive heart failure. 1269 33

In studies of animals, increases in aldosterone are associated with myocardial necrosis and fibrosis, and treatment with spironolactone, an antagonist of aldosterone, improved clinical outcomes in patients with heart failure. In the present study, we explored nitric oxide (NO), a signaling molecule involved in cardiac function, as a potential mediator of aldosterone's effects on the heart. Levels of both inducible NO synthase (iNOS) and NO from isolated rat neonatal cardiomyocytes pretreated with IL-1 were found to be decreased with exposure to aldosterone or dexamethasone in a dose-dependent manner. Spironolactone increased iNOS expression and prevented inhibition by aldosterone, consistent with a mineralocorticoid receptor-mediated mechanism for iNOS down-regulation. Aldosterone had no effect on iNOS mRNA levels, indicating a posttranscriptional mechanism for the inhibition of iNOS. Neutralization of TGF-beta 1 using a specific antibody reversed aldosterone-dependent iNOS and NO down-regulation. In summary, aldosterone inhibited IL-1-induced iNOS expression posttranscriptionally by a TGF-beta -dependent mechanism. The decrease in NO synthesis could have relevance to known cardiac effects of aldosterone.
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PMID:Aldosterone inhibits inducible nitric oxide synthase in neonatal rat cardiomyocytes. 1269 75

In recent years, rapid growth in the understanding of the pathophysiology of chronic heart failure has allowed for insights into many potential new therapeutic strategies. Yet until now, despite sound biological basis for efficacy and success in early-Phase studies, novel agents have not stood up to the scrutiny of late-Phase clinical trials. Indeed, remarkably negative results have been observed for vasopeptidase inhibitors, endothelin receptor antagonists and agents which block immune activation. However, efficacy data from other novel agents are still awaited, including the selective aldosterone receptor antagonist eplerenone, arginine vasopressin inhibitors, erythropoietin and hydroxy-methyl-glutaryl coenzyme A reductase inhibitors. Other classes of drugs which may enter clinical development include cardiac metabolic agents, matrix metalloproteinase inhibitors and advanced glycation end product antagonists. That the mortality and morbidity of patients with chronic heart failure remain unacceptably high makes the ongoing commitment to exploration of new drug therapies for the condition critical.
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PMID:New developments in the pharmacological treatment of chronic heart failure. 1272 Apr 87

The effect of torasemide and furosemide therapy was compared in 50 patients who had chronic heart failure and symptoms [NYHA class II-III] despite long-term therapy with both low-dose furosemide and angiotensin-converting enzyme inhibitors. In this randomized 6-month, open-label trial, baseline and follow-up echocardiograms and neurohumoral assays were obtained in 25 group F patients (continued same dose of oral furosemide at 20-40 mg/day) and in 25 group T patients (received torasemide at 4-8 mg/day in place of furosemide). At 6 months, parameters were unchanged in group F whereas the group T patients had a lower left ventricular end-diastolic diameter (p<0.005) and left ventricular mass index (p<0.005) with improved Doppler filling parameters, decreased plasma B-type natriuretic concentration (p<0.001) and increased plasma concentrations of active renin (p<0.005) and aldosterone (p<0.001). The magnitude of these changes appeared dose dependent and it is suggested these favorable effects of switching from furosemide to torasemide may be related to aldosterone receptor blockade.
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PMID:Effects of torasemide on left ventricular function and neurohumoral factors in patients with chronic heart failure. 1273 74

Although the role of the systemic renin-angiotensin-aldosterone system in the pathophysiology of heart failure is well-known for years, the impact of a local cardiac aldosterone system has been recognized recently. Aldosterone promotes cardiac hypertrophy and fibrosis in hypertension and heart failure and is involved in left ventricular remodeling after myocardial infarction. Plasma aldosterone levels in patients with heart failure are an indicator of a worse prognosis. Although ACE inhibitor therapy in these patients reduces plasma aldosterone levels, this effect is only transitory, a phenomenon referred to as "aldosterone escape". Even maximally recommended doses of ACE inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure, and those patients with increased aldosterone levels during ACE inhibition have impaired exercise capacity. The RALES study has demonstrated convincingly that in patients with heart failure, addition of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to ACE inhibition markedly reduces mortality and prevents worsening heart failure. While reduction of excessive extracellular matrix turnover leading to decreased fibrosis appears to be the most important effect of spironolactone in heart failure, other mechanisms such as regression of hypertrophy, improvement of endothelial function, enhanced renal sodium excretion and antiarrhythmic actions may contribute. In RALES, low-dose spironolactone did not confer a substantial risk of hyperkalemia, however, with broader use of spironolactone in heart failure, cases of hyperkalemia associated with the use of this drug increase. Close control of serum potassium and creatinine and estimation of creatinine clearance are mandatory, especially in the presence of additional factors impairing renal function. The new and more selective aldosterone antagonist eplerenone which is devoid of some side effects of spironolactone, has been shown to be effective in hypertension and holds great promise as future therapeutic agent in patients with heart failure.
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PMID:Aldosterone antagonism in addition to angiotensin-converting enzyme inhibitors in heart failure. 1278 71

Heart failure affects more than 350,000 Canadians and costs over $1 billion annually for inpatient care alone. Consensus guidelines have been developed to guide care and improve quality of life based on current evidence or best practice. This article will provide a brief overview of medications and lifestyle modifications described in guidelines developed by the American College of Cardiology/American Heart Association, the Canadian Cardiovascular Society, the Heart Failure Society of America, and the European Society of Cardiology. Medications for treating heart failure can be divided into two groups: those with a mortality benefit (angiotensin converting enzyme inhibitor, beta-blockers, and selective aldosterone receptor antagonists), and those that improve symptoms (diuretics and cardiac glycosides). Nursing implications include careful assessment of volume status, vital signs, monitoring electrolyte and renal function, as well as spacing of medications. Nurses play a key role in assisting patients to identify their lifestyle habits that require modifications, ultimately improving their quality of life and decreasing hospital readmissions. Education focusing on self-care activities, diet, rest, and exercise enables patients to retain a sense of control in their lives.
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PMID:Heart failure: an overview of consensus guidelines and nursing implications. 1280 36

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.
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PMID:Structural pathways and prevention of heart failure and sudden death. 1293 Feb 59

Recent studies suggest that aldosterone may play a larger role than once appreciated in normal physiologic function and cardiovascular disease. Some of the adverse cardiovascular effects that have been described include cardiac and vascular fibrosis, vascular necrosis and inflammation, impaired endothelial function, reduced fibrinolysis, hypertension, left ventricular hypertrophy (LVH), congestive heart failure, and cardiac arrhythmias. In light of these findings, the ability to block the actions of aldosterone has gained increased therapeutic importance. Eplerenone is a selective aldosterone receptor blocker that displays little interaction with androgen and progesterone receptors. Eplerenone has already been approved for the treatment of systemic hypertension and has been evaluated in numerous hypertension subgroups, including patients with low plasma renin activity; diabetes; LVH; uncontrolled blood pressure while receiving monotherapy with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta-blockers; and in black patients. Results of these trials indicate that eplerenone lowers blood pressure and reduces end-organ damage. Further proof of the therapeutic importance of mineralocorticoid receptor blockade comes from the eplerenone post acute myocardial infarction survival and efficacy study (EPHESUS). In this large-scale clinical outcome trial, eplerenone was shown to reduce total mortality by 15% as well as the combined endpoint of cardiovascular mortality/cardiovascular hospitalization by 13% when administered at a mean of 7.3 days post myocardial infarction to patients with evidence of systolic left ventricular dysfunction and symptoms of heart failure. Eplerenone is well tolerated, with an adverse effect profile comparable to placebo. The advent of selective aldosterone blockers, such as eplerenone, should prove to be of great therapeutic value in hypertension control and prevention of cardiovascular disease and associated end-organ damage.
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PMID:Eplerenone: a selective aldosterone blocker. 1293 Dec 52


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