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

Despite favorable improvements in mortality, heart failure (HF) remains a problematic illness due to the ever-present burden of hospitalization. Clearly, novel treatment strategies are needed. This review focuses on two newer pharmacologic targets: arginine vasopressin and aldosterone. Arginine vasopressin receptor antagonists will most likely serve as an adjunct to or replacement of standard diuretic therapy in selected patients. The safety and efficacy of chronic therapy with oral arginine vasopressin receptor antagonists in large groups of congestive HF patients is currently under investigation. Aldosterone antagonism is emerging as a treatment of severe congestive HF. Recent large-scale clinical trials using aldosterone antagonists have proven that those with HF or left ventricular dysfunction postmyocardial infarction derive a survival benefit from aldosterone antagonism. Whether aldosterone antagonism should be prescribed in all patients with HF is unclear; however, in carefully selected and managed patients, aldosterone antagonism is helpful.
 ...
PMID:Novel therapies for heart failure: vasopressin and selective aldosterone antagonists. 1572 67

Vasoactive neurohormonal systems (eg, sympathetic nervous system [SNS], renin-angiotensin-aldosterone system, and arginine vasopressin [AVP]) are defense mechanisms designed to preserve arterial volume and circulatory homeostasis during periods of low cardiac output. Neurohormonal systems, which are normally stimulated under conditions of acute volume depletion, are activated by the low cardiac output and arterial pressure. However, sustained and chronic activation of these systems, as occurs in congestive heart failure (CHF), can cause progressive ventricular remodeling and worsening heart failure. Vasoconstriction, water retention, and increased blood volume are results of the activation of the SNS, the renin-angiotensin pathway, and AVP secretion. These effects can accelerate progression of CHF, contributing to increased morbidity and mortality. AVP regulates vascular tone and free-water reabsorption, respectively, through the vasopressin V(1a) and V(2) receptor subtypes and therefore is a potential neurohormonal target in the treatment of CHF.
 ...
PMID:Neurohormonal activation in congestive heart failure and the role of vasopressin. 1584 52

Although multiple advancements have been made in the treatment of heart failure (HF), mortality rates remain alarmingly high. The accepted arsenal of therapeutics includes a diuretic, digitalis, a beta-blocking agent and an inhibitor of the renin-angiotensin-aldosterone system. Despite the employment of a vast array of agents, nearly 300,000 patients in the US die annually with HF as a primary or contributory cause of death. Additional molecular targets are being evaluated in preclinical and clinical settings including vasopeptidase inhibitors, endothelin-1 receptor antagonists, arginine vasopressin antagonists, selective aldosterone blockers, TNF-alpha blockers and matrix metalloproteinase inhibitors. Although these approaches hold promise as viable therapeutics, a thorough evaluation of clinical benefit from these agents requires additional trials. Future disease-modifying approaches will also undoubtedly include cell transplantation and gene therapy. It is likely that notable advances in HF treatment will come from agents that attenuate myocardial remodelling. Indeed, maintenance or improvement of cardiac structure can attenuate HF development and improve mortality.
 ...
PMID:Emerging therapies for heart failure. 1598 48

The recrudescence of interest in manipulation of the arginine vasopressin system and especially of V2 vasopressin receptor blockade in heart failure stems from the limited efficacy and possible detrimental effects of loop diuretics. The "braking phenomenon," hypertrophy of the collecting duct cells, and altered pharmacodynamics contribute to loop diuretic resistance in heart failure. Selective (tolvaptan) and nonselective (conivaptan) V2 vasopressin receptor antagonists now known as "vaptans" promote free-water excretion that is labeled aquaresis and correct hyponatremia in patients with severe heart failure. A large mortality study with tolvaptan in heart failure is presently ongoing.
 ...
PMID:Vasopressin antagonists in heart failure. 1603 44

Anaemia is common in patients with diabetes and associated with an increased risk of diabetic complications. Although the role of anaemia in heart failure is established, we hypothesize that anaemia also contributes to an increased risk of cardiac dysfunction in patients with Type II diabetes. In the present study, 228 consecutive adults with diabetes were investigated using transthoracic echocardiography. Echocardiographic parameters were correlated with the Hb (haemoglobin) level and adjusted for other risk factors for cardiac dysfunction using multivariate analysis. More than one in five patients (23%) had anaemia, which was an independent risk factor for cardiac dysfunction on echocardiography. Over one-third of all patients with evidence of abnormal cardiac function (diastolic and/or systolic dysfunction) on echocardiography had anaemia compared with <5% of patients with normal echocardiographic findings. Most patients with anaemia had cardiac dysfunction (94%), with the major abnormality being diastolic dysfunction associated with an increased left ventricular mass and impaired relaxation indices. A continuous association between diastolic function and Hb was also observed in patients without anaemia. In patients with a history of cardiovascular disease, systolic dysfunction was twice as common in patients with anaemia. Anaemia was also correlated with plasma markers of cardiac risk, including BNP (brain natriuretic peptide), CRP (C-reactive protein) and AVP (arginine vasopressin). Notably, the predictive utility of these markers was eliminated after adjusting for Hb. Consequently, the inexpensive measurement of Hb may be a useful tool to identify diabetic patients at increased risk of cardiac dysfunction.
 ...
PMID:Diastolic dysfunction is associated with anaemia in patients with Type II diabetes. 1618 Nov 49

Patients with worsening heart failure (HF) requiring hospitalization commonly have a history of progressive fluid retention, decreased renal function, and hyponatremia. For these patients, diuretics have traditionally been the mainstay of treatment, but they are associated with electrolyte abnormalities and impaired renal function. Previous studies have shown that levels of the endogenous arginine vasopressin (AVP) hormone are elevated in patients with HF and may be the contributing factor to fluid retention and hyponatremia, and probably progression of HF. Vasopressin antagonists represent a unique class of therapeutic agents because of their potential role in both the short- and long-term treatment of patients hospitalized with worsening HF. As "aquaretics," AVP antagonists offer the possibility of added efficacy in relieving congestion and improving symptoms with minimal adverse effects in combination with standard medical therapy. Some AVP receptor antagonists have shown promising results in animal studies and small-scale clinical trials. The purpose of this review was to update the current status of studies with the available AVP antagonists.
 ...
PMID:Overview of vasopressin receptor antagonists in heart failure resulting in hospitalization. 1639 90

In heart failure, as the heart gets worse, often so do the kidneys, complicating the treatment of heart failure and worsening the prognosis. This article addresses challenges in the use of diuretics, angiotensin-converting enzyme (ACE) inhibitors, and other therapies in the cardiorenal syndrome, as well as novel therapies that hold promise, such as arginine vasopressin antagonists, adenosine A1 receptor antagonists, and ultrafiltration.
 ...
PMID:Addressing the challenges of cardiorenal syndrome. 1684 71

Increased arginine vasopressin (AVP) secretion in heart failure may lead to vasoconstriction, left ventricular remodeling, and water retention-actions that promote afterload, preload, and hyponatremia and thereby cause disease progression. Interfering with AVP-mediated signaling pharmacologically may be beneficial in heart failure. Selective antagonism of the vasopressin 2 (V2) receptor may facilitate a safe diuresis and normalize low serum sodium levels, as demonstrated in preliminary clinical trials. Pure V2 antagonism, however, may stimulate AVP secretion and enhance V1a signaling, while pure V1a receptor antagonism may lead to unwanted V2 stimulation and secondary water retention and volume expansion. Combined V1a and V2 receptor antagonism could potentially prove advantageous as a therapy for heart failure by acting synergistically to facilitate diuresis and improve hemodynamics.
 ...
PMID:Vasopressin receptor antagonists: mechanisms of action and potential effects in heart failure. 1678 9

The neurohormone arginine vasopressin (AVP) is a promising target in the treatment of heart failure because AVP promotes congestion and hyponatremia, each of which is associated with poor outcomes. Diuretics are standard therapy for heart failure, but they have several limitations, including worsening renal function and hyponatremia. Blocking AVP leads to effective aquaresis, improvements in hemodynamics and renal function parameters, weight loss, and normalization of serum sodium, without changes in blood pressure or heart rate. In placebo-controlled trials in the inpatient and outpatient setting, the AVP receptor antagonist tolvaptan reduced body weight and edema and normalized serum sodium in patients with heart failure.
 ...
PMID:The clinical effects of vasopressin receptor antagonists in heart failure. 1678 10

This article discusses the pathophysiology of sodium and water retention in edematous disorders with a particular focus on cardiac failure, cirrhosis, and pregnancy. The body fluid volume hypothesis, which emphasizes the dominant role of arterial baroreceptors in renal sodium and water excretion, is reviewed. With arterial underfilling, either due to a decrease in cardiac output or peripheral arterial vasodilation, the normal central inhibition of the sympathetic nervous system activity and baroreceptor-mediated, nonosmotic arginine vasopressin (AVP) release is attenuated. The resultant increase in renal adrenergic activity stimulates the renin-angiotensin-aldosterone system. Although the resultant increase in systemic vascular resistance compensates for the primary arterial underfilling, this activation of the neurohumoral axis results in diminished sodium and water delivery to the renal collecting duct sites of aldosterone, AVP, and natriuretic peptide action. This diminished distal sodium and water delivery will be discussed as an important factor in the failure to escape from the sodium-retaining effects of aldosterone, the resistance to the natriuretic and diuretic effects of natriuretic peptides, and the diminished maximal solute-free water excretion in patients with edema. The role of the nonosmotic AVP release in water retention and hypo-osmolality/hyponatremia has been demonstrated in patients and experimental animals by administering nonpeptide, orally active vasopressin V2 receptor antagonists. These agents have been found to increase solute-free water excretion in patients with water-retaining, hyponatremic edema as well as in experimental animals.
 ...
PMID:Water and sodium retention in edematous disorders: role of vasopressin and aldosterone. 1684 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>