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[Pathophysiologic aspects and modern treatment of congestive heart failure].

Congestive heart failure is a clinical syndrome with inadequate cardiac output and increased venous pressure, characterized by hyperfunction of the sympatho-neuro-endocrine system, favoring maximal vasoconstriction in non-essential organs and retention of salt and water. Identification of the cause of heart failure and its correction is the best treatment. The suppression of precipitant factors is also essential. Traditionally the treatment of congestive heart failure is based on diuretics, restriction of salt intake, and digitalis. The conventional vasodilators are effective in the short term, but they have a marked tendency to tachyphylaxis. The inhibitors of angiotensin-converting enzyme are, through their specific action on neuro-endocrine dysregulation, the most important advance in recent years. Of the non-glycosidic inotropic agents used in severe heart failure, the new inhibitors of phosphodiesterase need further testing. In certain cases, permanent synchronous pacing has to be considered.

Angiotensin-Converting Enzyme Inhibitors↗

The kidney in congestive heart failure.

Congestive heart failure (CHF) is characterized by activation of (i) vasopressor and antinatriuretic influences (ii) and by counter-activation of vasodilator natriuretic systems. The former comprise the sympathoadrenal, renin-angiotensin-aldosterone and arginine vasopressin systems, and possibly endothelin and withdrawal of endothelium dependent relaxing factor respectively. The latter include the prostaglandins (PGE-2, PGI-2), dopamine and atrial natriuretic factor. The response of the kidney to chronic heart failure, i.e. vasoconstriction and antinatriuresis, resembles the renal reaction to volume depletion. The adverse renal effects of ACE inhibitors in some patients with advanced congestive heart failure may be explained by lowering of renal perfusion pressure and dependence of glomerular filtration rate on angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗

Exercise for patients with congestive heart failure.

Congestive heart failure is a widely prevalent sequel to myocardial infarction and other chronic conditions (including ischaemia without infarction, hypertension, various infections, toxic metabolic and endocrine disorders). Exercise tolerance is severely limited; the cardiac ejection fraction is often less than 20% and the peak oxygen intake may be less than 10 ml/kg x min, with a resulting deterioration in the quality of life. Possible factors contributing to the poor tolerance of exercise include: (i) disturbances of myocardial function (damage to the ventricular wall; decreased inotropic response, mitral valve regurgitation and increased diastolic pressures); (ii) peripheral vascular factors (decreased metaboreceptor discharge, reduced vasodilator response, increased activity of sympathetic afferents and less efficient distribution of cardiac output); (iii) hormonal disturbances (increases of catecholamines, renin/angiotensin/aldosterone, antidiuretic and natriuretic factors, endothelin and decreased endothelium-relaxing factor); (iv) impaired muscle function (loss of lean tissue, increase of type II fibres, increased impedance to perfusion, enzyme changes); (v) ventilatory disturbances (increased oxygen cost of activity, pulmonary congestion, increased ventilatory drive, mismatching of ventilation and perfusion, increased anaerobic effort); and (vi) psychological factors (anxiety, depression and iatrogenic limitation of effort). The prognosis with conventional treatment is poor, but patients with stable congestive heart failure respond favourably to a progressive exercise programme. Reported gains depend on the cause of congestive failure, initial status, study duration and compliance, and the type of training programme. Most studies to date have been short term (4 to 16 weeks), and relatively few have adopted a randomised controlled design. Suggested bases for the enhancement of aerobic performance of up to 20% include an increased intensity of peak effort, an enhanced matching of ventilation to perfusion, improved cardiac function, a strengthening of skeletal muscle and an increase of aerobic enzyme activity in the muscles. A few studies have continued for a year or longer and it appears that the gains realised over the first 16 weeks of training can be sustained for this period; the quality of life is enhanced, but data are as yet insufficient to judge effects upon mortality rates. Useful clinical information can be obtained from a 6-minute walk, but the choice for more precise evaluation lies between a measurement of ventilatory threshold or peak oxygen intake. Given initial muscle wasting, prescribed exercise should include both aerobic activity and resisted muscle exercises.

Cardiovascular System↗

Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure.

Congestive heart failure is a condition associated with increased plasma norepinephrine levels. Moreover, norepinephrine has been recently demonstrated to affect glucose homeostasis by decreasing insulin sensitivity. In the present study, eight patients suffering from chronic congestive heart failure and 10 healthy age- and body mass index-matched subjected were submitted to both an oral glucose tolerance test (OGTT; 75 g) and a euglycemic hyperinsulinemic glucose clamp. During the 360 minutes of the glucose clamp, insulin was infused at three different rates (25, 50, and 100 mU/kg/h), while D-3H glucose infusion allowed determination of glucose turnover. In basal conditions, patients versus controls had similar plasma glucose (5.2 +/- 0.1 v 4.9 +/- 0.2 mmol/L,P = NS), but higher plasma insulin (125.7 +/- 9.2 v 35.7 +/- 3.3 pmol/L,P less than .01), norepinephrine (5.39 +/- 0.13 v 1.47 +/- 0.22 nmol/L,P less than .001), and free fatty acid (FFA) (927 +/- 79 v 792 +/- 88 mumol/L,P less than .05) levels. In patients, basal plasma norepinephrine correlated with FFA levels (r = .65, P less than .025). After loading glucose, plasma glucose and insulin levels were still significantly higher in patients than controls. Euglycemic hyperinsulinemic glucose clamp produced a lower insulin-mediated inhibition of endogenous (hepatic) glucose production (HGP) and a greater increase in both glucose disappearance rate (Rd) and glucose metabolic clearance rate (gMCR) in patients than in controls during the first two insulin infusion rates (25 and 50 mU/kg/h). By contrast, these differences disappeared during the highest insulin infusion rate (100 mU/kg/h). Insulin-mediated decrease in plasma FFA levels was also lower in patients than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Immediate and long-term pathophysiologic mechanisms underlying the genesis of sudden cardiac death in patients with congestive heart failure.

Congestive heart failure is the most important predisposing factor to the occurrence of sudden death in patients with cardiovascular disease. As left ventricular dysfunction deteriorates and symptoms of heart failure become evident, ambulatory ventricular arrhythmias become increasingly frequent and complex, and sudden cardiac death becomes an increasingly common occurrence. When the left ventricular ejection fraction has declined to less than 30 percent and symptoms of heart failure become refractory to treatment with digitalis and diuretics, 35 to 50 percent of patients will die of a lethal cardiac arrhythmia within three years. A number of factors interact to determine the occurrence of malignant ventricular arrhythmias in patients with congestive heart failure. Myocardial fibrosis and enhanced left ventricular wall stress may alter the electrophysiologic properties of the myocardium, but these factors may not be sufficient to explain the development of lethal rhythm disturbances. Neurohormonal activation may exacerbate the frequency and complexity of ambulatory arrhythmias in these patients, but such activation can persist for long periods without fatal electrophysiologic sequelae. Recent investigations suggest that electrolyte depletion may provide an important immediate precipitating cause for the occurrence of fatal ventricular tachyarrhythmias in the patient with severe left ventricular dysfunction whose susceptibility is markedly heightened by preexisting structural, hemodynamic, or neurohormonal factors. Further work is needed to determine if prophylactic therapy directed at preventing electrolyte depletion can favorably modify the long-term outcome of these severely ill patients.

Arrhythmias, Cardiac↗

Markedly increased serum aspartate aminotransferase activity in congestive heart failure.

Congestive heart failure usually features a mild to moderate increase in aspartate aminotransferase (AST) activity. A marked increase in AST may occur rarely and is usually preceded by prolonged shock or hypotensive episodes and is accompanied by hyperbilirubinemia. I report two patients with congestive heart failure in whom the AST activity was greater than 8000 U/L. No prior episodes of shock or hypotension occurred in these patients and the accompanying increase in bilirubin was slight. In both cases, the enzyme activity decreased sharply with improvement in the patients' circulatory status. Recognition of this entity is important to distinguish it from viral or drug-induced hepatitis.

Aged↗

The relationship of the sympathetic nervous system and the renin-angiotensin system in congestive heart failure.

Congestive heart failure is a complex clinical syndrome characterized by circulatory and metabolic abnormalities. It has been apparent for more than 25 years that the sympathetic nervous system and the renin-angiotensin-aldosterone system are markedly activated in the late stages of heart failure. These two systems interact to facilitate sympathetic drive and promote salt and water retention. Circumstantial evidence is now accumulating to indicate that excessive sympathetic drive and angiotensin II activity may contribute to the pathophysiology of heart failure. These observations suggest that a dual strategy of modulating sympathetic nervous system activity to the heart while blocking angiotensin II activity may provide a rational therapeutic approach to the treatment of heart failure. Xamoterol, a beta 1 partial agonist, may enhance myocardial contractile force in the steady state, while acting to inhibit excessive sympathetic drive during exercise or severe heart failure. The concomitant use of a converting-enzyme inhibitor would be expected to blunt the detrimental effects of excessive angiotensin II activity. Modulation of adrenergic drive coupled with inhibition of marked angiotensin II activity may be potentially more effective in the treatment of congestive heart failure than either strategy used alone.

Adrenergic beta-Agonists↗

Long-term effect of social relationships on mortality in patients with congestive heart failure.

Congestive heart failure is a major cause of morbidity and mortality within the Western world, and yet psychosocial impact of this disease is under-researched. The aim of this study was to evaluate the possible effects of social relationships (perceived social support and perceived social isolation) on mortality risk in 119 patients with stable, symptomatic congestive heart failure. Fifty-one deaths were registered during the six-year follow-up period, all from cardiac causes. Analysis using proportional hazard models indicated that social isolation was a significant predictor of mortality (relative risk, 1.36; confidence interval, 1.04 to 1.78; p < 0.03), controlling for neuroticism, heart failure severity, functional status, gender, and age. The small sample size was a limitation of the study; therefore, further research is required in order to confirm these findings and to illuminate the mechanisms behind the relationships between social isolation and mortality.

Aged↗

Captopril does not acutely modulate plasma endothelin-1 concentration in human congestive heart failure.

Congestive heart failure (CHF) is a syndrome characterized by increased levels of angiotensin II (Ang II) and endothelin-1 (ET-1). In vitro, Ang II stimulates ET-1 release. The purpose of the study was to assess the effect of a single dose of an angiotensin-converting enzyme inhibitor (ACEI) captopril versus placebo on plasma endothelin concentration in human congestive heart failure. Captopril (25 mg, given orally) was compared with placebo in a group of 20 patients with systolic dysfunction in a double-blind randomized study. Plasma irET concentration was significantly increased in CHF patients compared with normal subjects (5.59 pg/ml +/- 0.35 vs. 3.58 pg/ml +/- 0.99, p < 0.0002). Despite the decrease in systolic blood pressure and the increase in plasma renin activity, suggesting a significant blockade of the renin-angiotensin system, no difference in plasma irET-1 was observed between captopril and placebo. Our results suggest that captopril does not acutely influence irET-1 plasma concentration in human CHF. These data do not support the hypothesis that the acute vasodilator effect of a single dose of 25 mg of captopril given daily orally involves modulation of the increased plasma concentration of endothelin observed in CHF.

Adult↗

Drug suppression of the angiotensin system in congestive heart failure.

Congestive heart failure is frequently associated with elevated systemic vascular resistance. Lowering resistance can improve cardiac performance and alleviate symptoms. The angiotensin-converting enzyme inhibitors offer a new way to lower resistance and have certain advantages, including the inhibition of compensatory mechanisms. However, skillful use of these compounds demands a thorough understanding of their pharmacologic properties and of the pathophysiology of congestive heart failure.

Angiotensin II↗

Congestive heart failure.

Congestive heart failure is important to the physician who treats elderly patients because of its incidence, prevalence, and high morbidity and mortality and because it often necessitates repeated hospitalizations. Presentation may be atypical and the condition may be precipitated by many of the ills that occur routinely in geriatric practice. Diastolic dysfunction may complicate diagnostic evaluation. Many of the symptoms respond gratifyingly to therapy. Congestive heart failure ranks among the most treatable of the geriatric syndromes. The physician who cares for older patients should be constantly alert for its presence and should keep abreast of the current therapies available and acquire experience in their use.

Aged↗

Interrelationship of magnesium and congestive heart failure.

Congestive heart failure is a most arrhythmogenic disease that is responsible for many unexpected sudden deaths. Reduction of sudden cardiac death rates among patient populations receiving long-term diuretic therapy, when given potassium- and magnesium-sparing diuretics as well as magnesium supplements, substantiates the premise that maintenance of adequate magnesium status is important in the prevention and management of cardiovascular diseases that predispose to congestive heart failure.

Animals↗

Lymphocyte G proteins reflect response to treatment in congestive heart failure.

Congestive heart failure is associated with chronotropic and inotropic hyporesponsiveness to adrenergic stimulation. A decrease in Gs alpha or an increase in Gi alpha is associated with a decrease in adenylyl cyclase activity. The current study assessed G proteins in response to treatment with direct-acting vasodilators and correlated changes in lymphocyte beta-adrenergic receptor components with changes in hemodynamic variables. Twenty-three patients with severe chronic congestive heart failure (New York Heart Association functional classes III and IV) were studied. Patients were grouped as responders (n = 10) or nonresponders (n = 13) on the basis of clinical assessment of functional status from questionnaires. Therapy was associated with an increase in cardiac index, a decrease in mean arterial pressure, and a decrease in systemic vascular resistance in all patients. Left ventricular filling pressure significantly decreased in responders (26 +/- 2 mm to 13 +/- 3 mm, p < 0.05) but did not change significantly in nonresponders. Similarly, mean right atrial pressure significantly decreased in responders (11 +/- 2 mm Hg to 4 +/- 1 mm Hg, p < 0.05) but did not change in nonresponders. Plasma norepinephrine increased significantly only in nonresponders (679 +/- 100 pg/ml to 1233 +/- 201 pg/ml, p < 0.05). Whereas lymphocyte beta-adrenergic receptor density and Gs did not significantly change, Gi increased after treatment only in the nonresponder group (23 +/- 5 to 51 +/- 11 fmol/mg, p < 0.05). A poor response to direct-acting vasodilators can be distinguished by reactive increases in plasma norepinephrine and lymphocyte Gi in the absence of a decrease in either left- or right-sided filling pressures.

Aged↗

Mechanisms of abnormal transmembrane signaling of the beta-adrenergic receptor in congestive heart failure.

Congestive heart failure is associated with blunted cardiac adrenergic responsiveness, clinically manifested by diminished chronotropic, inotropic, and lusitropic responses to beta-adrenergic stimulation. Recent advances in our understanding of the multiple components of the beta-adrenergic receptor complex and of the mechanisms by which these components interact with each other have led to insights beyond the mere evaluation of beta-receptors to account for adrenergic hyporesponsiveness in congestive heart failure. In addition to a reduction in beta-adrenergic receptors, the failing heart appears to show key abnormalities in the guanine nucleotide-binding proteins that link the beta-receptor to its biochemical effector. A reduction in the stimulatory protein and in the extent to which the stimulatory protein is linked to the beta-receptor are demonstrable in peripheral circulating lymphocytes and in cardiac tissue. These abnormalities are at least partially reversible.

Adenylyl Cyclases↗

[Neurohormonal factors in congestive heart failure].

Congestive heart failure is characterized by peripheral circulatory abnormalities including arterial and venous vasoconstriction and redistribution of regional blood flow. These peripheral factors are consecutive to a neurohumoral activation of sympathetic, renin-angiotensin-aldosterone and arginine-vasopressin systems. Clinical consequences of these neurohumoral changes are: excessive increase of aortic impedance and myocardial work, salt and water retention a processus which is angiotensin II-dependent, and eventually, hyponatremia. A growing body of evidences suggests that pharmacological blockade of this neurohumoral activation improves clinical and hemodynamic status in patients with congestive heart failure.

Arginine Vasopressin↗

The role of the sympathetic nervous system in congestive heart failure.

Congestive heart failure is usually accompanied by cardiovascular signs of an increased sympathetic and a decreased parasympathetic efferent activity. A current hypothesis for these autonomic changes holds the baroreceptor mechanisms mainly responsible for this complex neural reflex pattern together with a decreased responsiveness of cardiac vagal afferent ffibers. An alternative hypothesis is proposed here. Afferent sympathetic fibers with sensory endings in the atria and in the pulmonary veins are progressively excited by volume load. In cats with a chronic spinal section at C8, breathing spontaneously, an infusion of saline induces a reflex tachycardia through a sympatho-sympathetic neural circuit. In chronic dogs with intact cardiovascular innervation, the stimulation of aortic or cardiac sympathetic afferent fibers elicits an excitatory sympathetic reflex leading to hypertension and tachycardia; in addition, the sensitivity of baroreflexes is markedly reduced. Therefore, in congestive heart failure, especially in the absence of hypotension, the reflex excitation of the sympathetic outflow and the inhibition of the vagal efferent activity directed to the heart could be due to reflex mechanisms mediated by sympathetic cardiovascular afferents.

Animals↗

Congestive heart failure.

Congestive heart failure in adults should be conceptualized and dealt with as a clinical syndrome. It is neither a diagnosis nor a disease as such. Patients with heart failure present with clusters of symptoms that define sets of systemic congestion, pulmonary congestion, and inadequate cardiac output. Some have potentially correctable anatomic or metabolic defects, others have myocardial failure, and some have both as underlying causes of the syndrome. A careful analysis of the symptom clusters may provide important clues to the underlying etiologic diagnosis, which should be established before initiating therapy for heart failure.

Adult↗