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PubMed1995

Pulmonary and renal neutral endopeptidase EC 3.4.24.11 in rats with experimental heart failure.

Congestive heart failure is characterized by avid sodium retention and a blunted renal response to exogenous and endogenous atrial natriuretic peptide. Inhibition of neutral endopeptidase EC 3.4.24.11, the main enzyme that degrades natriuretic peptides, produces a natriuretic response in different models of congestive heart failure. This raises the possibility that an increase in either the expression or activity of neutral endopeptidase is responsible for these phenomena. In the present study, we examined (1) the renal effects of SQ-28,603, a neutral endopeptidase inhibitor, in rats with moderate and severe congestive heart failure induced by an aortocaval fistula compared with sham controls, and (2) neutral endopeptidase expression and activity in the lungs and kidneys of these rats. Infusion of SQ-28,603 (40 mg/kg IV) induced a significant natriuretic response in normal rats and rats with moderate congestive heart failure. This response was blunted in rats with severe congestive heart failure. Surprisingly, renal neutral endopeptidase mRNA levels, assessed by quantitative reverse transcriptase-polymerase chain reaction; protein levels, assessed by Western blotting; and activity, assessed by gelatin gels, were comparable in all groups. Pulmonary neutral endopeptidase mRNA levels decreased by 45% in rats with severe congestive heart failure but not in rats with mild congestive heart failure. In addition, pulmonary neutral endopeptidase immunoreactivity levels and activity were significantly decreased in congestive heart failure in correlation with the severity of the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

PubMedDate not supplied

Mortality of the institutionalized old-old hospitalized with congestive heart failure.

BACKGROUND: Congestive heart failure is a major cause of mortality and morbidity in the elderly but the disease impact on the oldest and sickest population has not been defined. OBJECTIVES: To review the mortality and hospital readmission rate of institutionalized elderly persons with congestive heart failure and to examine the relation of baseline characteristics to subsequent clinical outcomes. METHODS: This was a retrospective analysis based on chart review of 231 residents of the Philadelphia (Pa) Geriatric Center (63 congregate housing tenants and 168 nursing home residents) 80 years and older, hospitalized with congestive heart failure from 1989 to 1995. Patients' demographic data and clinical, electrocardiographic, and echocardiographic findings were obtained from their initial (index) hospitalization records. Subsequent outcomes were obtained from their outpatient (nursing home or office) records. RESULTS: Thirteen percent died during the index hospitalization but the total mortality during the follow-up period was 87%. One hundred forty-six patients (63%) died in the first year with a mean +/- SD survival of 4+/-4 months and a readmission rate of 3.9 per patient-year. Eighty-five patients survived the first year with a readmission rate of 1.2 per patient-year and 54 patients subsequently died, with a mean +/- SD survival of 28+/-12 months. The first-year decedents and survivors were comparable in sex, age, medical history, and electrocardiographic findings. However, patients who died in the first year, compared with survivors, were more likely to be nursing home residents (81% vs 59%), have New York Heart Association class IV heart failure (54% vs 32%), have impaired left ventricular function by echocardiogram (53% vs 32%), and have renal insufficiency (32% vs 11%). CONCLUSIONS: Very elderly persons with congestive heart failure had a guarded long-term prognosis. Nursing home residency, class IV heart failure, impaired left ventricular function, and renal insufficiency were associated with higher risk for early death and repetitive hospitalizations.

Aged↗

PubMedDate not supplied

Exercise as a treatment modality for congestive heart failure.

Chronic congestive heart failure is a clinical syndrome that affects nearly 5 million people in the United States alone. Patients with this condition have symptoms of dyspnea and exertional fatigue that often limit their daily activities and decrease their quality of life. There has recently been a paradigm shift in the management of congestive heart failure. Current strategies are focusing on improving the central cardiopulmonary abnormalities, such as decreased ejection fraction and increased capillary wedge pressure, and interventions aimed at improving the numerous peripheral changes that occur with congestive heart failure. Exercise as a treatment modality has been shown to affect many of these peripheral changes, specifically abnormalities in the skeletal muscle, peripheral blood flow, and neurohormonal milieu, which improve with appropriate exercise regimes. Exercise also reduces the symptoms of exertional fatigue, improves quality of life, and increases survival. This article reviews the current experience with exercise and congestive heart failure and discusses strategies used to implement an exercise program for patients.

American Heart Association↗

PubMed2001

Impact of a guideline-based disease management team on outcomes of hospitalized patients with congestive heart failure.

BACKGROUND: Congestive heart failure is the most common reason for hospitalization in the United States, and guidelines to improve the quality of care for patients with congestive heart failure have been developed. However, adherence is typically low. We hypothesized that a guideline-based care management team would result in greater quality and efficiency of care than guidelines alone. METHODS: A faculty cardiologist and nurse care manager at an academic medical center reviewed each patient's data and made guideline-based recommendations. Hospital length of stay, total costs, and use of recommended guidelines were compared between 173 patients before team implementation but with available guidelines, 283 care-managed patients, and 126 concurrent non-care-managed patients. RESULTS: Care-managed patients achieved higher rates of use of angiotensin-converting enzyme inhibitor than baseline or non-care-managed patients (95%, 60%, and 75%, respectively; P<.001), as well as increased adherence to guidelines for daily weight monitoring and assessment of left ventricular function. Hospital length of stay was lower (median, 3, 4, and 5 days, respectively; P<.001) as were costs of hospitalization (median, $2934, $3209, and $4830, respectively; P<.01). These differences persisted after adjustment for severity of illness. CONCLUSIONS: When compared with dissemination of guidelines alone, an active care management approach was associated with significant improvements in quality and efficiency of care for hospitalized patients with congestive heart failure.

Aged↗

PubMed1998

[Present day opinion about beta block treatment of congestive heart failure].

The congestive heart failure is an important clinical problem because of its frequency of appearance and poor prognosis. A new groups of drugs are to be found to change the negative natural course of this disease. Beta adrenolytic agents are on focus now because of promising results of small and great clinical trials and wider knowledge about the pathophysiology of congestive heart failure. This paper presents the present day knowledge about the role of the beta blockers therapy in the congestive heart failure treatment.

Adrenergic beta-Antagonists↗

PubMed2002

[Chronic simultaneous stimulation of both ventricles, a new treatment option for severe congestive heart failure].

Dilated congestive heart failure due to systolic left ventricle dysfunction frequently leads to intraventricular conduction disturbances with a prolonged QRS complex (> 120 ms). The prolonged conduction time in the ventricles causes electrical asynchrony of the ventricles and contributes to a further reduction of systolic function, changes of filling and relaxation intervals, and promotes mitral valve insufficiency. Chronic simultaneous stimulation of both the right and left ventricle in patients with severe heart failure improves functional status, quality of life, and exertion tolerance. At present the implantation of a biventricular pacemaker is time consuming because the positioning of the lead in a left ventricular epicardial vein is difficult. As congestive heart failure is frequently associated with an increased risk of ventricular fibrillation, the combined implantation of a biventricular stimulator and an implantable automatic defibrillator is sometimes necessary. Preliminary calculations show that about 750 patients per year with severe congestive heart failure are eligible for a biventricular stimulator.

Cardiac Pacing, Artificial↗

PubMed1997

Plasma N-terminal atrial natriuretic factor: a predictor of survival in patients with congestive heart failure.

BACKGROUND: Congestive heart failure results in biatrial stretch, which stimulates myocyte release of atrial natriuretic factor (1-126). The N-terminal fragment, proatrial natriuretic factor(1-98), (proANF), is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply because of prolonged in vitro stability. Proatrial natriuretic factor has been shown to be predictive of clinical status in patients with congestive heart failure. This retrospective analysis was undertaken to evaluate the relationship between N-terminal atrial natriuretic factor(1-98) and survival in patients with stable congestive heart failure. METHODS AND RESULTS: Proatrial natriuretic factor was sampled from 316 patients (mean age, 68 (+/-) 11 years; 71% men) recruited from an outpatient heart failure clinic. The mean ejection fraction was 34 (+/-) 13%. Seventy-three deaths were registered during the period of data collection (42 months). Deaths per proANF quartile (n = 79) were as follows: 2 (2.5%) in quartile I. 13 (16.5%) in quartile II, 21 (26.6%) in quartile III, and 37 (46.8%) in quartile IV. The odds ratio estimates for death adjusted for age and sex were 7.6, 13.9, and 33.9 for the second, third, and fourth quartiles, respectively. Survival curves constructed according to proANF quartiles demonstrate significant differences in mortality rates. The correlation with death was greater for proANF as compared with left ventricular end-diastolic diameter (P < .001), systolic pulmonary artery pressure (P < .005), or ejection fraction (P < .05). CONCLUSION: These data indicate that the concentration of proANF is related to prognosis in patients with heart failure and that moderate elevation is associated with markedly decreased survival. Analysis should be of practical value in the assessment of prognosis in this heterogeneous population.

Adolescent↗

PubMed1995

A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure.

BACKGROUND: Congestive heart failure is the most common indication for admission to the hospital among older adults. Behavioral factors, such as poor compliance with treatment, frequently contribute to exacerbations of heart failure, a fact suggesting that many admissions could be prevented. METHODS: We conducted a prospective, randomized trial of the effect of a nurse-directed, multidisciplinary intervention on rates of readmission within 90 days of hospital discharge, quality of life, and costs of care for high-risk patients 70 years of age or older who were hospitalized with congestive heart failure. The intervention consisted of comprehensive education of the patient and family, a prescribed diet, social-service consultation and planning for an early discharge, a review of medications, and intensive follow-up. RESULTS: Survival for 90 days without readmission, the primary outcome measure, was achieved in 91 of the 142 patients in the treatment group, as compared with 75 of the 140 patients in the control group, who received conventional care (P = 0.09). There were 94 readmissions in the control group and 53 in the treatment group (risk ratio, 0.56; P = 0.02). The number of readmissions for heart failure was reduced by 56.2 percent in the treatment group (54 vs. 24, P = 0.04), whereas the number of readmissions for other causes was reduced by 28.5 percent (40 vs. 29, P not significant). In the control group, 23 patients (16.4 percent) had more than one readmission, as compared with 9 patients (6.3 percent) in the treatment group (risk ratio, 0.39; P = 0.01). In a subgroup of 126 patients, quality-of-life scores at 90 days improved more from base line for patients in the treatment group (P = 0.001). Because of the reduction in hospital admissions, the overall cost of care was $460 less per patient in the treatment group. CONCLUSIONS: A nurse-directed, multidisciplinary intervention can improve quality of life and reduce hospital use and medical costs for elderly patients with congestive heart failure.

Aged↗

PubMed1984

Magnesium deficiency in congestive heart failure.

In congestive heart failure several compensatory mechanisms are operating, and may cause severe disturbances of both the internal and external electrolyte balance. The medical treatment prescribed in congestive heart failure also leads to changes in the handling of electrolytes. These combined effects may prove critical to the patient, especially with regard to the emergence of cardiac arrhythmias.

Cardiac Output↗

PubMed2003

[Plasma levels of brain natriuretic peptide, cyclic 3'5'-guanosine monophosphate, endothelin 1, and noradrenaline in patients with chronic congestive heart failure].

Chronic congestive heart failure (CHF) is a complex clinical syndrome characterized by marked neurohormonal activation which may lead to further decompensation of the circulatory system. This study was undertaken to establish the role of certain hormones in pathogenesis of congestive heart failure. Plasma levels of brain natriuretic peptide (BNP), cyclic 3'5'-guanosine monophosphate (c-GMP), endothelin 1 (ET-1), and noradrenaline (NA) were examined in patients in patients with CHF and with decompensation of circulatory system. The survey was made in 92 patients with CHF, among them there were 42 females aged 50-76 years (mean 66 years) and 50 males aged 53-76 years (mean 68 years). All patients were divided into 3 groups according to NYHA classification. On admission blood samples were taken from all patients to determine plasma levels of BNP, c-GMP, ET-1, and NA. Then patients received captopril and furosemide. Next blood samples were taken between 5 and 7 day of the treatment, after entire remission symptoms of decompensation. Plasma levels of BNP, c-GMP, ET-1, and NA were estimated with radioimmunoassay. Our study showed that plasma levels of ET-1, BNP, c-GMP, and NA were increased in patients with CHF. 5-7 days of the treatment with ACE inhibitor and diuretic caused significant decrease of ET-1, BNP, and c-GMP levels, but did not influence NA plasma levels. Determination of ET-1, BNP, c-GMP, and NA plasma levels may be a noninvasive method useful in estimation of degree of CHF and efficacy of the treatment.

Aged↗

PubMed1985

Combination therapy with diltiazem and propranolol: precipitation of congestive heart failure.

Although congestive heart failure has been reported with the combination of a beta blocker and either verapamil or nifedipine, it has not previously been reported for combination therapy that includes diltiazem. The following case documents the occurrence of clinical congestive failure in a patient with baseline left ventricular dysfunction and severe angina pectoris. Although the patients had tolerated propranolol therapy for years without difficulty, and high-dose diltiazem monotherapy with an excellent clinical response, the combination of diltiazem and propranolol resulted in the development of congestive heart failure. Thus, although generally well tolerated, given the suitable scenario of reduced left ventricular function, the combination of diltiazem and a beta blocker may adversely affect left ventricular performance.

Angina Pectoris↗

PubMed1996

Beta-adrenoceptor blocking agents for the treatment of heart failure.

Congestive heart failure is associated with high morbidity and mortality. Modification of neurohormonal activation by use of angiotensin converting enzyme inhibitors has been shown to decrease symptoms and prolong survival. More recent evidence has suggested that beta-adrenoceptor blocking agent therapy may be also beneficial in patients with congestive heart failure, possibly by down-regulating the activation of the adrenergic system. A large number of randomized trials of beta-adrenoceptor blocking agents in heart failure have been performed. These studies demonstrated improvement in symptoms of congestive heart failure, functional classification, and reduction in the number of patients requiring cardiac transplantation. beta-adrenoceptor blocking agents have not been shown to decrease mortality, however, the current trials have been too small to be conclusive in this regard.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

Pharmacotherapy in congestive heart failure: drug absorption in the management of congestive heart failure: loop diuretics.

Congestive heart failure is a disease state distinguished by the regular presence of both renal and hepatic abnormalities in drug handling. One such abnormality involves flaws in the process of drug absorption. In most instances, congestive heart failure-related abnormalities in drug absorption are of inconsequential significance. However, this is not the case with loop diuretics. Loop diuretic action ordinarily tracks the rate and extent of absorption if a sufficient amount of diuretic has been given to exceed the threshold for diuretic effect. In congestive heart failure, both the rate and absolute amount of loop diuretic absorbed can be reduced as a function of the heart failure state itself. In this setting, drug dissolution characteristics can assume added significance. Furosemide is the loop diuretic with the widest intra- and interpatient variability of absorption. Alternatively, the loop diuretic torsemide is rapidly and fairly completely absorbed independent of the heart failure state. This pattern of absorption establishes it as the preferred loop diuretic in the otherwise diuretic-resistant heart failure patient. However, the exact role of torsemide in the outpatient management of congestive heart failure remains to be determined.

Diuretics↗

PubMed2001

Effects of chronic clonidine administration on sympathetic nerve traffic and baroreflex function in heart failure.

Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0+/-1.1 years (mean+/-SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (-46.8% and -26.7%, respectively; P<0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested.

Baroreflex↗

PubMedDate not supplied

Endothelin in heart failure.

Congestive heart failure is a complex disease that results from pumping failure of the cardiac muscle and adaptational processes of the cardiovascular system to correct for the reduced blood supply to the organism. It is associated with increased vasoconstriction and impaired vasodilation in response to physical activity. The elevated vasoconstrictor tone is caused by the activation of compensatory mechanisms including the sympathetic nervous system and stimulation of the release of neurohormones like angiotensin II, catecholamines, and vasopressin. Furthermore, the vascular endothelium is importantly involved in the regulation of vascular tone as it releases a variety of vasoactive substances that act locally and systemically. In congestive heart failure, there is a marked imbalance between the diminished release or the increased inactivation of vasodilators on the one hand, ie, nitric oxide, and the elevated production, release, or reduced inactivation of vasoconstrictors such as endothelin-1 on the other hand. In addition to its very potent vasoconstrictor effects, endothelin-1 possesses antinatriuretic and mitogenic properties that are a common feature of substances that are involved in development of the deleterious consequences that render congestive heart failure a lethal disease. The spectrum of action of the endothelin system and the advent of specific antagonists for its receptors have made this system a very interesting target for clinical research and possibly for future therapeutic approaches.

Animals↗

PubMed1996

Medical treatment of end-stage heart failure.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Adrenergic beta-Antagonists↗

PubMed2001

Digitalis for treatment of congestive heart failure in patients in sinus rhythm.

BACKGROUND: Digitalis glycosides have been in clinical use in the treatment of congestive heart failure for more than 200 years. In recent years several trials have been conducted to address concerns about efficacy and toxicity. Although a systematic review of the literature was recently published, an update is required to include more current trials. OBJECTIVES: To examine the effectiveness of digitalis glycosides in treating congestive heart failure in patients with normal sinus rhythm. To examine the effect of digitalis in patients taking diuretics, ACE inhibitors, and beta blockers; patients with varying severity and duration of disease; patients with prior exposure to digitalis vs. no prior exposure; and patients with diastolic vs. systolic dysfunction. SEARCH STRATEGY: Electronic databases were searched between 1966 and 2000. Dissertation Abstracts and annual meeting abstracts of the American Heart Association, American College of Cardiology, and European Society of Cardiology were searched from 1996-2000. In addition, reference lists provided by the pharmaceutical industry (Glaxo Wellcome Inc.) were searched. SELECTION CRITERIA: Included were randomized placebo-controlled trials of 20 or more adult patients of either sex with symptomatic congestive heart failure who were studied for seven weeks or more. Excluded were trials in which the prevalence of atrial fibrillation was 2% or greater, or in which any arrhythmia that might compromise cardiac function or any potentially reversible cause of heart failure such as acute ischemic heart disease or myocarditis was present. DATA COLLECTION AND ANALYSIS: Articles selected from the searches described above were reviewed by one of the coauthors, and validated by staff from the central office of the Heart Collaborative Review Group in Bristol, UK. MAIN RESULTS: Eleven articles meeting the defined criteria were identified, and major endpoints of mortality, hospitalization, and clinical status, based respectively upon on 8, 4, and 10 of these selected studies, were recorded and analyzed. The data show that there is no difference in mortality between treatment and control groups, whereas digitalis therapy is associated with a lower rate of hospitalization and of clinical deterioration. REVIEWER'S CONCLUSIONS: The literature indicates that digitalis has a useful role in the treatment of patients with congestive heart failure who are in normal sinus rhythm.

Cardiotonic Agents↗

PubMed1999

Class III drugs and congestive heart failure: focus on the congestive heart failure-survival trial of antiarrhythmic therapy.

Patients with congestive heart failure frequently have ventricular arrhythmias on ambulatory electrocardiographic recordings and sudden cardiac death is seen in almost 50% of such patients. Many antiarrhythmic agents have been approved to suppress the arrhythmia in an effort to improve survival. Some sodium-channel blockers not only failed to improve survival but have been shown to be harmful. This led to the development of potassium-channel blockers, such as d-sotalol, amiodarone, dofetilide, and azimilide. d-Sotalol was associated with excess mortality in patients with left ventricular dysfunction; amiodarone seems to be potentially beneficial; and dofetilide has a neutral effect on mortality. The Sudden Cardiac Death Heart Failure Trial (SCD HEFT) is testing the implantable cardioverter defibrillator (ICD) against amiodarone and placebo. The ICDs appear to be superior to antiarrhythmic drugs in certain high-risk patients, although not proved in unstratified patients with heart failure.

Amiodarone↗