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Control of atrial natriuretic peptide secretion in patients with severe congestive heart failure.

Congestive heart failure (CHF) is marked by activation of multiple hormone systems that increased peripheral vasoconstriction and produce sodium and water retention. Plasma atrial natriuretic peptide (ANP) levels are frequently elevated in patients with severe CHF and may act to counterbalance these hormonal actions. To determine whether CHF patients maintain a physiological response to the presumed major stimulus to ANP secretion, atrial stretch, 22 CHF patients and 8 normal volunteers were studied. Atrial distention was produced in 10 CHF patients with a mannitol infusion and in 12 with lower body positive pressure. Eight normal volunteers also underwent a mannitol infusion. Both stimuli provoked increases in plasma ANP levels in the CHF patients, and the relative increase in plasma ANP after mannitol was similar in the CHF patients and the normal volunteers. We conclude that ANP secretion responds to atrial stretch in CHF patients, suggesting maintenance of the physiological release of this peptide.

Adult↗

The role of continuous positive airway pressure in the treatment of congestive heart failure.

Congestive heart failure (CHF) is a serious medical condition frequently associated with sleep-related breathing disorders, which remain underdiagnosed and undertreated. Recent studies have provided important insight into the pathophysiology of sleep apnea syndrome in patients with CHF, with potential therapeutic implications. In addition to abolition of sleep apnea, continuous positive airway pressure (CPAP) treatment can improve cardiac function and relieve symptoms of CHF. Postulated mechanisms include beneficial hemodynamic effects on ventricular remodeling, unloading of fatigued respiratory muscles, and neurohormonal modulation. Although medium-term studies using CPAP to treat sleep-related breathing disorders associated with CHF have been encouraging, more definitive data from ongoing large clinical trials are necessary to clarify its therapeutic role.

Heart Failure↗

Mammalian cardenolides as biomarkers in congestive heart failure.

Congestive heart failure (CHF) afflicts over 5 million individuals in the United States, and most die within 5 yr of diagnosis. Because of the high morbidity and mortality associated with CHF, the search for biomarkers to predict, diagnose, and manage this disease has intensified. Calcium homeostasis and alterations in intracellular concentrations of this cation have been implicated in both hypertrophy as well as the adaptive mechanisms observed in CHF. In this article, we discuss the roles of the sodium pump and the endogenous mammalian cardenolides and their involvement in the pathophysiology of this disease in view of the regulation of intracellular calcium. Understanding the mechanisms for the release of mammalian cardenolides in plasma, the alterations in sodium pump isoforms and function, and the modulation of pathways involving calcium in hypertrophy and CHF may assist in the development of new biological markers capable of predicting the disease before significant progression and irreversible heart failure.

Animals↗

Adverse cardiovascular effects of NSAIDs in patients with congestive heart failure.

Congestive heart failure (CHF) is a complex clinical syndrome, especially in the elderly, which results from cardiac dysfunction. Epidemiological studies have shown a gradual increase in age-adjusted hospitalisation rates for CHF and overall population prevalence of CHF during the last 2 decades in Western countries. The healthcare costs associated with CHF are considerable and are likely to increase in the near future. Hence, identification of risk factors which could induce or exacerbate CHF is of major importance. NSAIDs are frequently prescribed in elderly patients for several rheumatological and nonrheumatological indications. Numerous adverse reactions, mainly related to the gastrointestinal tract and kidney function, have been described for NSAIDs. In addition, some case reports have suggested a causal relation between the use of NSAIDs and the onset of CHF. The pathophysiology of CHF and the pharmacological properties of NSAIDs support this hypothesis. In particular, the inhibition of prostaglandin synthesis may adversely affect cardiovascular homeostasis in patients with a propensity to develop CHF. Notwithstanding the adverse effects, however, the prescription of NSAIDs in elderly patients is often desirable and justifiable. Therefore, further pharmaco-epidemiological research is needed to quantify the risk for CHF attributable to the use of NSAIDs and to identify patients who are particularly susceptible to the adverse cardiovascular effects of these agents. In these patients, it may be advisable to avoid the use of NSAIDs.

Aging↗

Underutilisation of ACE inhibitors in patients with congestive heart failure.

Congestive heart failure (CHF) is associated with substantial morbidity and mortality, and is the only major cardiovascular disease increasing in prevalence. Despite abundant evidence to support their efficacy and cost-effectiveness, angiotensin-converting enzyme (ACE) inhibitors are sub-optimally used in patients with CHF. This paper reviews the evidence for the sub-optimal use of ACE inhibitors in patients with CHF, the factors contributing to this, and its implications for health systems. A systematic review of all articles assessing practice patterns (specifically the use of ACE inhibitors in CHF) identified by MEDLINE, search of bibliographies, and contact with content experts was undertaken. 37 studies have documented the use of ACE inhibitors in patients with CHF. Studies assessing use among all patients with CHF document 33% to 67% (median 51%) of all patients discharged from hospital and 10% to 36% (median 26%) of community dwelling patients were prescribed ACE inhibitors. Rates of ACE inhibitor use range from 43% to 90% (median of 71%) amongst those discharged from hospital having known systolic dysfunction, and from 67% to 95% (median of 86%) for those monitored in specialty clinics. Moreover, the dosages used in the 'real world' are substantially lower than those proven efficacious in randomised, controlled trials, with evaluations reporting only a minority of patients achieving target doses and/or an overall mean dose achieved to be less than one-half of the target dose. Factors predicting the use and optimal dose administration of ACE inhibitors are identified, and include variables relating to the setting (previous hospitalisation, specialty clinic follow-up), the physician (cardiology specialty versus family practitioner or general internist, board certification), the patient (increased severity of symptoms, male, younger), and the drug (lower frequency of administration). In light of the substantial evidence for reductions in morbidity and mortality, clearly, the prescription of ACE inhibitors is sub-optimal. Wide variability in ACE inhibitor use is noted, with higher rates consistently reported among patients having systolic dysfunction confirmed by an objective assessment--an apparent minority of the those having CHF. Optimisation of the prescription of proven efficacious therapies has the potential to confer a substantial reduction in the total cost of care for patients with CHF by reducing hospitalisations and lengths of hospital stays. It is likely that only multifaceted programs targeted toward the population at large will yield benefits to the healthcare system, given the widespread nature of the sub-optimal prescription of therapies proven effective in the management of patients with CHF.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical and economic factors in the treatment of congestive heart failure.

Congestive heart failure (CHF) is a disease of massive clinical and economic importance throughout the developed world. Approximately 1% of the population are affected, with incidence and prevalence of CHF increasing with age. The major aetiological factor is ischaemic heart disease and, despite advances in treatment, mortality from CHF remains appallingly high, and comparable to that of many malignancies. The majority of patients with CHF require treatment with a diuretic, though there is now clear evidence that the addition of an angiotensin converting enzyme (ACE) inhibitor will not only improve symptoms but also reduce mortality and delay the progression of the disease. The vast economic impact of CHF is now becoming fully appreciated, with the majority of expenditure on hospital admissions. The earlier and more widespread use of ACE inhibitors in the treatment of CHF would be highly cost effective, with substantial savings in hospitalisation costs, though new and effective treatments are still urgently required.

Age Distribution↗

The role of dopaminergic agonists in congestive heart failure.

Congestive Heart Failure is a clinical syndrome characterised by myocardial dysfunction and sympathetic activation. Plasma norepinephrine (NE) levels have been related to the poorest survival. Large-scale clinical trials have proved the clinical benefits of Angiotensin Converting Enzyme inhibitors in reducing the risk of death and hospitalisation. However, mortality remains high in the treated group underlining the need to explore new therapeutic approaches. Specific activation of peripheral dopamine receptors exerts profound hemodynamic effects and neurohormonal control such as peripheral and renal vasodilation, diuresis and natriuresis and inhibition of NE release. Z1046, a mixed D1/D2-like agonist, reduces peripheral and renal vascular resistance increasing renal blood flow. In anaesthetised dogs the compound strongly reduces plasma NE without increasing plasma renin activity and plasma aldosterone. The inhibition of NE could be the basis of Z1046 potent cardioprotective effect observed in a dog model of myocardial ischemia and reperfusion, in which the severity of ventricular arrhythmias was markedly reduced, resulting in higher survival. These findings suggest that chronic oral treatment with specific dopaminergic agonists is able to alleviate the hemodynamic burden on the myocardium, and to suppress the sympatho-adrenal activity.

Animals↗

Epidemiology and clinical aspects of congestive heart failure.

Congestive heart failure (CHF) is an increasing problem for healthcare systems in all developed countries. The prevalence is increasing partly due to ageing of the population, but also due to improved survival from acute cardiac disease such as myocardial infarction. Advances in diagnostic techniques and better understanding of the pathophysiology offer many opportunities for substantial improvement in the management of CHF. This article reviews the current epidemiology of CHF and the related diagnostic issues.

Heart Failure↗

Diagnosis and outpatient management of congestive heart failure.

Congestive heart failure causes substantial patient morbidity and mortality in the United States. Symptoms and physical findings can be helpful in diagnosis but have limited sensitivity and specificity. Objective measurement of ventricular function is essential in virtually all patients in whom a diagnosis of heart failure is suspected. Reversible causes of heart failure must be sought. Outpatient management includes education and counseling, emphasis on and assessment of compliance with diet, and pharmacologic 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. Diuretic therapy 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 the results of the medical history and physical examination. Routine serial testing of ventricular function and exercise performance is discouraged.

Ambulatory Care↗

[Trends in pharmacological treatment of congestive heart failure].

Congestive heart failure (CHF) is growing epidemiologic and clinical problem, and is the only common cardiovascular condition that is increasing in incidence, prevalence and mortality. During last years numerous clinical trial have been conduced evaluating the effect of various treatment procedures on clinical endpoints in patients with CHF. The major risk factor for CHF are hipertension and atherosclerotic vascular diseases, and now it is clear that aggressive treatment of hypertension and hyperlipidemia can be effective in preventing CHF. Treatment strategies for CHF are aimed at preventing and delaying progression of the disease and improving survival. In the treatment of CHF diuretics are at present the first drugs line for patients with fluid retention and are necessary to relieve symptoms but cannot halt progression or improve the prognosis of CHF. Angiotensin-converting enzyme inhibitors (ACE inhibitors) therapy has been shown to decrease mortality and progression of CHF and should be used early in patients with left ventricular dysfunction whether they have symptomatic or asymptomatic CHF. Digoxin therapy is associated with decrease in the risk of worsening CHF irrespective of rhythm, systolic function, severity of CHF or therapy with ACE inhibitors. In patients with symptomatic CHF due to systolic dysfunction the addition of diuretics and digoxin appears to reducing worsening CHF without improving survival. Other than digoxin oral inotropic agents (amrinone, pimobendan, vesnarinone, ibopamine) increase mortality in patients with CHF and have not improved symptom status and other clinical endpoints during long-term therapy. Hydralazine and isosorbide dinitrate administrated in combination are less effective alternative to ACE inhibitors. Beta-blockers and particular carvedilol may prolong survival and decrease worsening CHF when used in combination with digoxine, diuretics and ACE inhibitors. Beta-blockers therapy improve hemodynamics, LVEF and functional status patients with CHF and the ideal candidate for this therapy is stable patients with NYHA II-III CHF due to nonischemic cause. Calcium antagonists do not appear to be useful in patients with CHF, although amlodipine and mibefradil appears to be safe for treatment of angina or hypertension in this group. On the basis of current data, antiarrhythmic agents should not be given to patients with CHF free from arrhythmia but those with sustained ventricular tachycardia or ventricular fibrillation amiodaron appears to be safe.

Adrenergic beta-Antagonists↗

From digoxin to angiotensin-converting enzyme inhibitors: issues in pharmacotherapy for congestive heart failure.

Congestive heart failure (CHF) is a disease with high mortality rates and increasing prevalence in the United States. As our understanding of the pathophysiologic characteristics of this disease has progressed, so has our pharmacologic approach to treatment. Digoxin was the first documented drug used in the treatment of CHF, and since that time, the efficacy of its use has been the source of great controversy. A more recent treatment option is the use of angiotensin-converting enzyme (ACE) inhibitors, the first drug class shown to increase survival rates in CHF. Although controversy remains, ACE inhibitors appear to be gaining favor over digoxin in the pharmacologic approach to treatment. This article provides a pathophysiologic review of CHF as it is understood today, the rationale behind the use of digoxin and ACE inhibitors, and a challenge for the future in the pharmacotherapy of CHF.

Angiotensin-Converting Enzyme Inhibitors↗

An overview of intermittent inotropic therapy for severe congestive heart failure.

Congestive heart failure (CHF) is a major problem in the field of medicine in the U.S. Over 4 million people in the U.S. have CHF with 400,000 new cases per year. This diagnosis creates 6 million hospital days with a Medicare cost of billions of dollars. There are limited options for patients >65 years of age who have resistant heart failure on maximum medical therapy. There is considerable debate surrounding intermittent inotropic therapy. This paper is a review of the literature regarding this form of therapy; 20 studies are described. All but one of these studies disclose beneficial effects. The major criticism of these studies is that they are small and not randomized or placebo controlled. Larger well controlled studies are needed to determine the effect and safety of this treatment. Researchers must develop and evaluate all forms of therapy fairly to help decrease hospitalizations, decrease mortality, and improve quality of life.

Journal Article↗

Pathophysiology of congestive heart failure.

Congestive heart failure is a syndrome common in the United States, especially in elderly patients. The most common etiology is coronary artery disease. A number of general factors contribute to the heart failure syndrome, including loss of muscle, decreased myocardial contractility, pressure or volume overload, or restricted filling. All of these factors may play a role in a given patient as, for example, with coronary artery disease. Although systolic dysfunction with a reduced ejection fraction is the most common heart failure syndrome, up to 40% of patients may have a relatively preserved ejection fraction with diastolic dysfunction. As the heart begins to fail, a number of compensatory mechanisms are activated. These include increased heart rate, the Frank-Starling mechanism, increased catecholamines, activation of the renin-angiotensin system, and release of atrial natriuretic peptides. Although these mechanisms are initially helpful to the cardiovascular system, they frequently overshoot, initiating a vicious cycle. For example, with a decrease in cardiac output, there is a reflex increase in systemic vascular resistance in order to maintain perfusion pressure. This increase in resistance, however, acts as a load on the left ventricle and further reduces cardiac output. The best evidence for the existence of this vicious cycle is the beneficial change in hemodynamics produced by vasodilator drugs and the ACE inhibitors. Thus, an understanding of pathophysiology allows for the selection of rational therapy. An unresolved problem in heart failure patients is how best to reduce the high incidence of sudden death, which is one of the major challenges for the future.

Aged↗

What is the experience of men and women with congestive heart failure?

Congestive heart failure (CHF) is increasing in incidence and prevalence in both men and women in Canada. Research findings to date have been inconsistent with respect to whether gender differences influence quality of life, treatment and survival. There is a paucity of qualitative research describing the experience of patients with CHF This qualitative case study approach used semistructured interviews with women and men with New York Heart Association (NYHA) class three or four CHF who were referred to a CHF clinic. In addition to quality of life measures, data related to medical history, medical management and NYHA scores were collected to offer a thorough description of these clients' experiences. Three hypotheses were generated from 13 themes that emerged. First, the psychosocial impact of CHF outweighs the physical impact. Second, sex differences exist in relation to living with CHF with men being more accepting of CHF and more likely to experience social isolation and loss than women, while women are more likely to describe fear. Third, the experience of CHF is influenced by age with physical experiences and depression mentioned more frequently in younger age groups. Findings from this study have generated nursing implications and recommendations for further research.

Activities of Daily Living↗

Economic implications of treatment guidelines for congestive heart failure.

Congestive heart failure (CHF) is the most common cause of cardiovascular hospital admission. A significant proportion of the costs of CHF is due to hospitalizations. The present study evaluated the economic impact of a modest increase in the use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, spironolactone and digoxin on CHF hospitalizations. Patients with CHF were identified through the Canadian Institute for Health Information (CIHI) database. The efficacy of ACE inhibitors, beta-blockers, spironolactone and digoxin in the first year of treatment were retrieved from the Survival and Ventricular Enlargement (SAVE) trial, a meta-analysis, the Randomized Aldactone Evaluation Study (RALES) and the Digitalis Investigation Group (DIG) trial, respectively. Cost of CHF hospitalization was based on the National List of Provincial Costs. Costs of drug treatment were based on the 2002 Alberta Health and Wellness Drug Benefit list. Physician visits for drug titration were also included in the model. A total of 85,679 patients with CHF were identified with a total of 106,130 hospital discharges. A 10% increase in use of ACE inhibitors, beta-blockers, spironolactone and digoxin would incur in a total cost due to avoidable hospital admissions of 0.4 million dollars, 1.3 million dollars, 3.7 million dollars and 1.2 million dollars, respectively. Similarly, the costs of drug treatment would be 2.2 million dollars, 1.3 million dollars, 0.3 million dollars and 0.5 million dollars, respectively. An increase in the use of the above medications would save 6.6 million dollars due to avoidable hospital admissions. The total cost of drug treatment was 4.3 million dollars, giving a net savings of 2.3 million dollars in the first year. The implementation of evidence-based therapy for CHF treatment is not only clinically efficacious, but also economically attractive.

Adrenergic beta-Antagonists↗

[Conventional surgery for congestive heart failure].

Congestive heart failure is a major public health problem in western countries. Although substantial efforts have been made in the last decades in the prevention, diagnosis and treatment of cardiovascular disease, the incidence of end-stage dilated cardiomyopathy is still increasing. Heart transplantation represents the most effective therapy in this setting, but due to shortage of donors, it remains a realistic option just for a very small number of patients. Therefore, conventional surgical treatment for end-stage heart disease has gained increasing attention in recent years and a variety of surgical interventions have been improved or optimized to manage the multifactorial pathophysiology of the heart failure picture. The aim of this review is to report our experience with more than 500 patients with advanced dilated cardiomyopathy, treated with conventional surgical procedures such as myocardial revascularization, left ventricular restoration, mitral valve repair and surgical ablation of atrial fibrillation. Indications, results, controversial issues and future perspectives will be discussed.

Adult↗

New therapeutic strategies in the management of congestive heart failure.

Congestive heart failure is a syndrome with multiple causes and manifestations. While rheumatic heart disease and hypertension are in decline, coronary artery disease is the leading cause in patients referred for evaluation of heart failure. Decrease in cardiac contractility and general neurohormonal activation, which trigger alterations in mechanical and biochemical factors in cardiac muscle and bring derangements of haemodynamics, are now considered as excessively early compensatory mechanisms which can be regarded as deleterious in patients with heart failure. Therapeutic principles illustrated in this article emphasize the importance of basic research and clinical observations derived from trials set the stage for therapeutic interventions. The approach to the patient with silent myocardial dysfunction must be treated so as to have the greatest beneficial impact on the prognosis of this disease.

Drug Therapy, Combination↗

Circulatory regulation at rest and exercise and the functional assessment of patients with congestive heart failure.

Congestive heart failure occurs when myocardial dysfunction is advanced. Although clinical manifestations and diminished functional capacity can be traced back to the poor cardiac contractile state, there are major modifying influences from a complex series of compensatory responses. These particularly involve the heart, vessels, kidneys, sympathetic nervous system, the renin-angiotensin system, and other hormone systems. Functional capacity is, therefore, determined by the sum of the effects of the original cardiac insult and the effects, beneficial and adverse, of the secondary events. Functional capacity relates closely to prognosis only in the most severely disabled patients. The latter is mainly related to the extent of ventricular dysfunction, and there can be independent contributions from arrhythmias and sympathetic activity. Measures of resting parameters of cardiac contractility, hemodynamics, or neurohumoral responses are, therefore, of no value in predicting functional capacity but can be useful in examining outlook or examining mechanisms of disease and therapy. Exercise measurements are necessary because adequate resting performance can disguise major limitations in cardiac reserve. Measurement of functional capacity can be used to quantify the effects of therapy on daily living and to give an indication of the overall response of the body to major cardiac inadequacy. Limitation of exercise capacity, the earliest symptom of heart failure, can be quantified during a graded exercise test. Measurements of cardiac output and hemodynamic variables during exercise quantify the extent to which the cardiovascular system can increase performance to meet the demands of exercise. Work capacity and maximum oxygen capacity indicate the limits of physical performance, whereas determination of the anaerobic threshold indicates the highest level of exercise at which cardiorespiratory mechanisms are able to provide adequate oxygen supply to maintain aerobic metabolism in working skeletal muscle.

Autonomic Nervous System↗