Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study sought to identify confounding factors for the interpretation of copeptin levels in healthy individuals. The natriuretic peptides are recognized as diagnostic and prognostic tools in HF (heart failure). Interpretation of BNP (brain natriuretic peptide) and NTproBNP (N-terminal pro-BNP) levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called copeptin is comparable with the natriuretic peptides in the diagnosis and prognosis of HF and as a prognostic biomarker after AMI (acute myocardial infarction). Copeptin, derived from the C-terminal portion of the precursor to AVP (arginine vasopressin), is secreted stoichiometrically with vasopressin, hence it can be used as a surrogate marker of the AVP system. In the present study, 706 healthy volunteers were recruited from a local HF screening study. Participants with a history of cardiovascular disease and those with echocardiographic abnormalities were excluded from the study. Copeptin and NTproBNP levels were assayed using in-house immunoluminometric assays. Median copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4-44.3) compared with 3.2 (1.0-14.8) pmol/l; P<0.001]. In males, copeptin was correlated with eGFR (estimated glomerular filtration rate; r(s)=-0.186, P<0.001). In females, the correlation of copeptin with eGFR was weak (r(s)=-0.097, P=0.095). DT (deceleration time) and left atrial size correlated with higher copeptin levels (r(s)=0.085, P=0.029 and r(s)=0.206, P<0.001 respectively). Only gender (P<0.001), eGFR (P<0.001), left atrial size (P=0.04) and DT (P=0.02) remained independently predictive of plasma copeptin. The present study suggests that gender and renal function specific partition values should be used to interpret copeptin values in future studies of this biomarker in HF or ischaemic heart disease.
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PMID:Gender and renal function influence plasma levels of copeptin in healthy individuals. 1864 34

Impaired urinary dilution leading to water retention and hyponatremia may occur in patients with cardiac failure, cirrhosis, pregnancy, hypothyroidism, glucocorticoid and mineralocorticoid deficiency. The mechanisms for these defects predominantly involve the non-osmotic stimulation of arginine vasopressin release with upregulation of aquaporin 2 water channel expression and trafficking to the apical membrane of the principal cells of the collecting duct. These perturbations are reversed by V2 vasopressin receptor antagonists. In contrast, urinary concentration defects leading to polyuria are vasopressin-resistant. They may involve several factors, such as impaired counter-current concentration secondary to downregulation of Na-K-2Cl co-transporter. Vasopressin-resistant downregulation of aquaporin 2 expression has also been described as a factor in impaired urinary concentration.
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PMID:Molecular mechanisms of clinical concentrating and diluting disorders. 1865 7

Increased synthesis of arginine vasopressin (AVP) plays a critical role in fluid retention and hyponatremia in patients with heart failure. The AVP receptor antagonists constitute a new class of agents that are promising in the management of hyponatremia and congestion. Three of these agents--conivaptan, tolvaptan, and lixivaptan--have been studied in clinical settings. All are effective in inducing aquaresis (ie, electrolyte-free water excretion) and normalizing serum sodium concentration. They are well tolerated without causing electrolyte disorders, hypotension, or renal impairment. Conivaptan has been approved by the US Food and Drug Administration for short-term intravenous treatment of euvolemic hyponatremia of variable etiology but has not been adequately studied in heart failure. The addition of tolvaptan to standard therapy in hospitalized patients with heart failure has led to symptomatic improvement and decreased body weight, but there is no long-term clinical benefit. Early data on lixivaptan in heart failure suggest a dose-dependent aquaresis effect, and larger studies are under way.
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PMID:Vasopressin and vasopressin antagonists in heart failure and hyponatremia. 1876 79

In the Adhere (Acute Decompensated Heart Failure Registry) National Registry, hyponatremia (serum sodium <130 mEq/l) at clinical presentation was noted in 5% of patients with HF. The enhanced release of arginine vasopressin (AVP) can lead to hyponatremia by binding to the V2 receptor results in free-water retention and hyponatremia. Given the central role of AVP in causing hyponatremia in patients with congestive heart failure, decreasing vasopressin activity has been a therapeutic focus. With no current therapy to decrease production of AVP, attention was turned to decreasing the effect of AVP by blocking the receptor.
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PMID:AVP receptor antagonists in patients with CHF. 1876 39

Antidiuretic hormone, also known as arginine vasopressin, is a hormone with a multitude of physiologic activities including the control of urinary free water excretion. Antidiuretic hormone also plays a role in vasoconstriction and has 3 receptors that have been identified. Vasopressin analogs and antagonists have been extensively studied in animal models as well as in humans. Because heart failure is associated with a state of water retention, several vasopressin antagonists have been evaluated for their potential aquaretic effect. Diuretics remain the mainstay of treatment in acute and chronic volume overload but are not shown to improve survival. In fact, they are associated with numerous side effects including hypotension, electrolyte abnormalities, worsening renal function, and activation of renin-angiotensin-aldosternone system. Tolvaptan, conivaptan, and lixivaptan are some of the vasopressin antagonists that have been studied in heart failure. The results were initially encouraging with alleviation of symptoms and effective aquaresis without worsening of hyponatremia or renal function, but yet failed to show any effect on mortality in heart failure. With an increasing number of more selective orally active vasopressin antagonists, further studies are underway to establish the role of "Vaptans" in the treatment of heart failure and other disease states with volume overload and hyponatremia.
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PMID:Vasopressin and vasopressin receptor antagonists in heart failure. 1909 65

Tolvaptan is an oral, once-daily nonpeptide arginine vasopressin V(2)-receptor antagonist under development for the treatment of hyponatremia and congestive heart failure. In Phase II clinical trials, tolvaptan, in addition to standard therapy, increased fluid loss, resulting in decreased body weight and improved edema and serum sodium without affecting blood pressure, heart rate or renal function in patients with heart failure. The compound appeared to be well tolerated and dose-dependent adverse events were generally realated to its pharmacological activity, such as thirst and dry mouth. In patients with hyponatremia, tolvaptan appears to be more effective than fluid restriction at improving sodium levels without an increase in adverse events. An international Phase III outcome study; Efficacy of Vasopressin antagonism in hEaRt failurE outcome Study with Tolvaptan (EVEREST), evaluating the long-term efficacy and safety of tolvaptan in patients hospitalized with worsening heart failure, is currently ongoing.
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PMID:Tolvaptan for the treatment of hyponatremia and congestive heart failure. 1980 53

Tolvaptan is an orally administered, nonpeptide, selective arginine vasopressin V(2) receptor antagonist that increases free water clearance, thereby correcting low serum sodium levels. SALT-1 and -2, two identical, randomized, double-blind, placebo-controlled, multicentre trials, included patients with hypervolaemic or euvolaemic hyponatraemia (serum sodium <135 mmol/L) associated with heart failure, cirrhosis or the syndrome of inappropriate antidiuretic hormone secretion. In both trials, patients receiving (in addition to standard medical treatment) tolvaptan 15-60 mg once daily (titrated according to response) for up to 30 days (n = 95 and 118) experienced significantly greater improvements than those receiving placebo (n = 89 and 114) for the co-primary endpoints of the change in average daily area under the curve for the serum sodium level from baseline to day 4 and from baseline to day 30. This beneficial effect of tolvaptan on serum sodium levels in SALT-1 and -2 was observed in patients with mild (serum sodium <135 mmol/L) and in those with marked (serum sodium <130 mmol/L) hyponatraemia at baseline. Tolvaptan was also superior to placebo in increasing serum sodium levels from baseline to day 7 in a subgroup of 323 patients with hyponatraemia (serum sodium <134 mmol/L) in the randomized, double-blind, multicentre EVEREST trials, which included patients who were hospitalized for worsening heart failure. Tolvaptan was generally well tolerated in clinical trials. The most frequently reported adverse events were thirst and dry mouth, which result from the pharmacodynamic effects of the drug.
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PMID:Tolvaptan. 2020 86

Heart failure (HF) is associated with substantial cost, morbidity, and mortality. One of the common complications associated with HF, as well as with its treatment, is the development of hyponatremia. Hyponatremia is due to the nonosmotic release of arginine vasopressin (AVP) along with neurohormonal activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. Hyponatremia in patients with HF is associated with poor outcomes and can limit the use of diuretic therapy. Given that AVP is the primary stimulus for the development of hyponatremia in these patients, therapies that target AVP action would seem a logical choice in the therapeutic regimen for HF. Drugs that antagonize the action of AVP at the vasopressin V(2) receptor, which is primarily responsible for water resorption in the kidney, are now available and have been studied in patients with HF. These drugs (termed vaptans) have been associated with improvements in serum sodium concentration, urine output, body weight, and mental functioning but have shown no long-term mortality benefit in patients with HF. The role of vaptans in the HF armament will require further studies that center on the proper timing and indications for their use as well as their cost-efficacy.
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PMID:Hyponatremia in heart failure: the role of arginine vasopressin and its antagonism. 2065 16

The nonosmotic release of arginine vasopressin, concurrent with the activation of the sympathetic nervous system and renin-angiotensin-aldosterone system, is thought to represent the maladaptive response that is central to the pathophysiology of heart failure (HF). The degree of neurohormonal activation correlates with the severity of the disease and can predict the outcomes. However, quantification of components of neurohormonal axis (e.g., serum arginine vasopressin level) is mainly reserved for research purposes rather than routine practice. The results of several recent HF trials have shed light on the differential role of blood urea nitrogen (BUN) and creatinine in predicting the outcomes in this setting. These studies suggest that BUN could indeed represent a surrogate marker for "renal response" to neurohormonal activation in this setting, above and beyond its role in the estimation of renal function. In this report, the relevant physiologic mechanisms underlying urea and water transport in the kidney are first reviewed. Then, the activation of the neurohormonal axis and the impact of its components on renal urea transport, independent of changes in renal function, are explained. Finally, the unique role of BUN as a biomarker of neurohormonal activation in the setting of HF is discussed, and the potential clinical implication of this novel concept is emphasized. In conclusion, this review explains the pathophysiologic basis for the emerging role of BUN as a biomarker in HF.
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PMID:Emergence of blood urea nitrogen as a biomarker of neurohormonal activation in heart failure. 2072 48

Heart failure is one of the most common, costly, disabling and growing diseases (McMurray and Pfeffer in Lancet 365(9474):1877-1889, 2005). Hyponatremia, conventionally defined as a serum-sodium concentration equal or less than 135 mmol/l (American Heart Association in Heart disease and stroke statistics--2007 update. American Heart Association, Dallas, 2007; Stewart et al. in Eur J Heart Fail 4:361-371, 2002), is a common phenomenon in patients with heart failure, with an incidence of 20-25% (Krumholz et al. in Arch Intern Med 157:e99-e104, 1997; Rosamond et al. in Circulation 117(4):e25-e146, 2008; Adrogue and Madias in N Engl J Med 342:1581-1589, 2000) and seems to be of prognostic importance in patients with heart failure (Luca et al. in Am J Cardiol 96:19L-23L, 2005; Gheorghiade et al. in Eur Heart J 28:980-988, 2007; Gheorghiade et al. in Arch Intern Med 167:1998-2005, 2007). So far treatment strategies have been limited and burdened by side effects. The development of hyponatremia in the setting of heart failure is related to the arginine vasopressin (AVP) dysregulation. Thus, AVP receptor antagonists are a promising approach to treatment. However, several questions remain: whether there is a cause-and-effect mechanism, if the correction of hyponatremia improves outcomes, and defining the specific cut-off level of serum-sodium that should be used to define hyponatremia. In this review, we aim to summarize the literature on hyponatremia in patients with heart failure within several aspects: incidence in clinical trials and registries, prognostic value, underlying mechanisms, therapeutic options, and possible future perspectives.
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PMID:Significance of hyponatremia in heart failure. 2083 81


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