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

Patients with chronic heart failure (HF) are characterized by systemic inflammation, as evident by raised circulating levels of several inflammatory cytokines with increasing levels according to the degree of disease severity. In addition to the myocardium itself, several tissues and cells can contribute to this inflammation, including leukocytes, platelets, tissue macrophages and endothelial cells. Although the mechanisms for the systemic inflammation is unknown, both infectious (e.g., endotoxins) and non-infectious (e.g., oxidative stress and hemodynamic overload) events could be operating, also including activation of Toll-like receptors as well as interaction with the neurohormone system. A growing body of evidence suggests that this systemic inflammation in chronic HF may play a role in the development and progression of this disorder, not only by promoting myocardial dysfunction, but also by inducing pathogenic consequences in other organs and tissues, thereby contributing to additional aspects of the HF syndrome such as cachexia, endothelial dysfunction and anemia. Although this inappropriate immune activation and inflammation could represent a new target for therapy in patients with chronic HF, the anti-tumor necrosis factor trials have been disappointing, and future research in this area will have to more precisely identify the most important mechanisms and actors in the immunopathogenesis of chronic HF in order to develop better immunomodulating agents for this disorder.
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PMID:Systemic inflammation in heart failure--the whys and wherefores. 1681 81

Early mobilization and aggressive physical therapy are essential in patients who receive left ventricular assist devices (LVADs) due to long-term, end-stage heart failure. Some of these patients remain ventilator dependent for quite some time after device implantation. We report our regimen of mobilization with the aid of a portable ventilator, in patients with cardiac cachexia and LVAD implantation. Further, we describe the specific physical therapy interventions used in an LVAD patient who required prolonged mechanical ventilation after device implantation. The patient was critically ill for 5 weeks before the surgery and was ventilator dependent for 48 days postoperatively. There were significant functional gains during the period of prolonged mechanical ventilation. The patient was able to walk up to 600 feet by the time he was weaned from the ventilator and transferred out of the intensive care unit. He underwent successful heart transplantation 6 weeks after being weaned from the ventilator We believe that improving the mobility of LVAD patients who require mechanical ventilation has the potential both to facilitate ventilator weaning and to improve the outcomes of transplantation.
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PMID:Early mobilization of LVAD recipients who require prolonged mechanical ventilation. 1687 12

Cachexia is a process that accompanies many chronic diseases, and consists of a combination of wasting of lean body mass, increased energy expenditure, and a paradoxical loss of appetite. Cachexia both worsens quality of life and negatively affects treatment of the underlying disease. Conditions as diverse as cancer, renal failure, and heart failure show a remarkable similarity in their associated cachexia, exhibiting changes in metabolism and endocrinology, including marked increases in levels of cytokines that accompany these diseases. So far, it has been difficult to treat disease-associated cachexia successfully. One treatment that has shown promise in animal trials, however, involves antagonism of the central melanocortin system, an anorexigenic pathway in the hypothalamus and brainstem. Humans who have genetic mutations involving pro-opiomelanocortin or the melanocortin 4 receptor in this pathway exhibit increased appetite and increased lean body mass. Recent research has shown that in rodent models of cancer and renal failure, administration of melanocortin 4 receptor antagonists results in an attenuation of symptoms of cachexia, including maintenance of appetite, lean body mass, and basal energy expenditure. Although this research needs to be substantiated in humans, it provides a promising direction for treating the wasting that is associated with a variety of disease states.
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PMID:Therapy insight: Use of melanocortin antagonists in the treatment of cachexia in chronic disease. 1693 26

Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of caloric restriction were obscured by the varied diet composition of the participants. The Dahl salt-sensitive rat which develops gradual, hypertension-associated diastolic dysfunction was used in this study to assess the impact of caloric restriction upon decompensated pressure-overload hypertrophy. Male Dahl salt-sensitive rats were provided either a low-salt diet or a high-salt diet to initiate heart failure progression. A further subset of high-salt rats underwent 15% calorie restriction, with salt load held constant. Parameters measured included serial systolic blood pressure, body weight, and changes of left ventricular systolic and diastolic parameters and ventricular geometry by echocardiography. After 18 weeks, fasting glucose, blood lipids, heart weight, kidney weight, lung weight, plasma interleukin-6 and TNF-alpha, and cardiac lipid peroxidation were measured. Low-salt rats did not develop heart failure. While high-salt rats displayed features of decompensated pressure-overload hypertrophy, moderate calorie restriction remarkably reduced morbidity. Compared to the high-salt fed group, the high-salt, calorie-restricted group showed reduced blood pressure, delayed onset of cachexia, lower fasting hyperlipidemia, lower cardiac, renal and lung weight, less plasma IL-6 and TNF-alpha, less cardiac oxidative damage, and improved diastolic chamber function and cardiac index. Modest calorie restriction, independent of salt intake, reduced pathogenesis in this well described model of decompensated pressure-overload hypertrophy.
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PMID:Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. 1693 90

Although the adverse health consequences of obesity in the general population have been well documented, recent evidence suggests that obesity is associated with better outcomes in patients with heart failure (HF). Studies of patients with HF that specifically examined the impact of body mass index (BMI) on outcomes have suggested the existence of an "obesity paradox." However, closer examination of these studies raises important questions on the validity of the paradox. First, the diagnosis of HF in obese patients, particularly when made using clinical variables, may not be accurate; the obese patients in these studies may actually be "healthier" than their nonobese comparators. Second, the deleterious effects of cachexia, rather than the salutary ones of obesity, are likely the main reason for the inverse correlation between BMI and HF outcome, especially once the underlying biologic mechanisms behind cachexia and obesity in patients with HF are considered. Furthermore, few studies have specifically examined the more severely obese population (BMI >35 kg/m(2)) when assessing outcomes, and those that have suggest that severely obese patients may have worse outcomes than patients with normal weights or those who are mildly obese. Therefore, a "U-shaped" outcome curve according to BMI for patients with HF may actually exist, in which mortality is greatest in cachectic patients; lower in normal, overweight, and mildly obese patients; but higher again in more severely obese patients. Further prospective studies assessing the impact of more marked degrees of obesity on outcomes in patients with HF are needed to more conclusively determine whether the obesity paradox truly exists.
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PMID:The obesity paradox: fact or fiction? 1699 80

The 350,000 maintenance hemodialysis (MHD) patients in the United States have an unacceptably high mortality rate of >20%/year. Almost half of all deaths are assumed to be cardiovascular. Markers of kidney disease wasting (KDW) such as hypoalbuminemia, anorexia, body weight and fat loss, rather than traditional cardiovascular risk factors, appear to be the strongest predictors of early death in these patients. The KDW is closely related to oxidative stress (SOX). Such SOX markers as serum myeloperoxidase are associated with pro-inflammatory cytokines and poor survival in MHD patients. Identifying the conditions that modulate the KDW/SOX-axis may be the key to improving outcomes in MHD patients. Dysfunctional lipoproteins such as a higher ratio of the high-density lipoprotein inflammatory index (HII) may engender or aggravate the KDW, whereas functionally intact or larger lipoprotein pools, as in hypercholesterolemia and obesity, may mitigate the KDW in MHD patients. Hence, a reverse epidemiology or "bad-gone-good" phenomenon may be observed. Diet and gene and their complex interaction may lead to higher proportions of pro-inflammatory or oxidative lipoproteins such as HII, resulting in the aggravation of the SOX and inflammatory processes, endothelial dysfunction, and subsequent atherosclerotic cardiovascular disease and death in MHD patients. Understanding the factors that modulate the KDW/SOX complex and their associations with genetic polymorphism, nutrition, and outcomes in MHD patients may lead to developing more effective strategies to improve outcomes in this and the 20 to 30 million Americans with chronic disease states such as individuals with chronic heart failure, advanced age, malignancies, AIDS, or cachexia.
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PMID:The kidney disease wasting: inflammation, oxidative stress, and diet-gene interaction. 1701 6

Chronic heart failure is a complex catabolic state that carries a devastating prognosis. The transition from stable disease to cardiac cachexia is not well understood. Mechanisms that maintain the wasting process involve neurohormones and pro-inflammatory cytokines, which contribute to an imbalance in anabolic and catabolic pathways. A decrease in food intake alone rarely triggers the development of a wasting process, but dietary deficiencies in micronutrients and macronutrients contribute to the progression of the disease. Malabsorption from the gut as a result of bowel wall edema and decreased bowel perfusion also plays an important role. This article describes the complex interplay of hormonal systems in energy balance in patients with chronic heart failure as well as other factors such as malabsorption and dietary deficiencies that contribute to the wasting process. Finally, therapeutic approaches are discussed. These include dietary advice, ongoing studies, and future possibilities.
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PMID:Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure. 1703 72

We have demonstrated a potent and specific lipolytic effect of natriuretic peptides (NP) in human and primates' fat cells. The lipolytic effect of NP is mediated through intracellular production of cGMP and activation of the cGMP-dependent kinase 1alpha. Local infusion of atrial-NP (ANP), directly within the subcutaneous adipose tissue through a microdialysis catheter, increases lipolysis and stimulates blood flow through its vasodilating effect in lean healthy men. This effect is blunted in overweight men and can be recovered by endurance training. Intravenous infusion of physiological doses of ANP induces lipid mobilization. Higher concentrations of ANP that are encountered during heart failure also stimulate lipid oxidation. ANP activates lipolysis and free fatty acids release from adipose tissue during endurance exercise. This effect is paradoxically amplified when exercise is performed under beta-blockade treatment, because of an enhanced cardiac release of ANP. No gender differences in ANP-induced lipid mobilization during exercise have been found. Heart failure is associated with high circulating levels of NP that could participate to the progression toward cachexia. On contrary, a negative correlation between NP levels and body mass index is found in obese persons. The molecular basis of this inverse correlation is not yet demonstrated from a functional standpoint. Further studies are needed to clearly define the pathophysiological role of NP in obesity and heart failure.
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PMID:[Physiological and pathophysiological features of the control of lipolysis and lipid mobilization by natriuretic peptides]. 1714 64

The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.
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PMID:Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice. 1725 28

Muscle wasting and weakness are common in many disease states and conditions including aging, cancer cachexia, sepsis, denervation, disuse, inactivity, burns, HIV-acquired immunodeficiency syndrome (AIDS), chronic kidney or heart failure, unloading/microgravity, and muscular dystrophies. Although the maintenance of muscle mass is generally regarded as a simple balance between protein synthesis and protein degradation, these mechanisms are not strictly independent, but in fact they are coordinated by a number of different and sometimes complementary signaling pathways. Clearer details are now emerging about these different molecular pathways and the extent to which these pathways contribute to the etiology of various muscle wasting disorders. Therapeutic strategies for attenuating muscle wasting and improving muscle function vary in efficacy. Exercise and nutritional interventions have merit for slowing the rate of muscle atrophy in some muscle wasting conditions, but in most cases they cannot halt or reverse the wasting process. Hormonal and/or other drug strategies that can target key steps in the molecular pathways that regulate protein synthesis and protein degradation are needed. This review describes the signaling pathways that maintain muscle mass and provides an overview of some of the major conditions where muscle wasting and weakness are indicated. The review provides details on some therapeutic strategies that could potentially attenuate muscle atrophy, promote muscle growth, and ultimately improve muscle function. The emphasis is on therapies that can increase muscle mass and improve functional outcomes that will ultimately lead to improvement in the quality of life for affected patients.
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PMID:Therapeutic approaches for muscle wasting disorders. 1725 13


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