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)

Chronic congestive heart failure primarily of ischemic origin remains a leading cause of morbidity and mortality in the United States and other leading countries. The current main stream of therapy is, however, palliative and uses a complex regimen of drugs, the actions of which are not understood completely. On the other hand, unfavorable remodeling after cardiac injuries of multiple causes has been thought to lead to cardiac contractile dysfunction in heart failure, and a body of scientific evidence points to a central role of intrinsic defects in intracellular calcium handling in cardiomyocytes that arise from the distorted functions of several key regulatory molecules on plasma membrane or sarcoplasmic reticulum (SR), a muscle-specific intracellular membrane complex that stores calcium at high concentration. Accordingly, the initial appetite to use gene transfer strategies to modulate calcium regulatory proteins was to validate molecular targets for the development of new pharmaceuticals; however, remarkable therapeutic efficacies found in an initial series of studies using various heart failure animal models immediately promoted us to seek ways to directly apply gene transfer to cure clinical heart failure. The first part of this article reviews our up-to-date knowledge of various functional components to regulate calcium handling in cardiomyocytes, including beta-adrenergic receptor, L-type calcium channel, ryanodine receptor (RyR) and its associated proteins, sarco-endoplasmic reticulum calcium ATPase (SERCA), and phospholamban (PLN), and their abnormalities in failing hearts. A series of new somatic gene transfer attempts targeting calcium handling in cardiomyocytes are discussed thereafter.
 ...
PMID:Gene therapy targeted at calcium handling as an approach to the treatment of heart failure. 1573 5

Chronic congestive heart failure has become a significant medical burden in the adult and a growing problem in the pediatric age group. While the etiologies of heart failure differ between children and adults, applied medical therapies are generally the same. In this regard, over the last decade, beta-adrenergic receptor blockade has become an important component in drug therapy of congestive heart failure in the adult population. A third-generation beta-blocker, carvedilol, has now been shown in adult trials to be efficacious in the treatment of heart failure and has been shown to be superior to other similarly used beta-blockers. Carvedilol use has been adapted into pediatric heart failure practice although data supporting its efficacy in infants and children are scarce. This review will describe the application of carvedilol in the adult, as it pertains to pediatric practice, review the existing pediatric literature and describe our institution's experience with carvedilol in heart failure therapy.
 ...
PMID:The use of carvedilol in pediatric heart failure. 1672 34

Congestive heart failure with preserved left ventricular systolic function has emerged as a growing epidemic medical syndrome in developed countries, which is characterized by high morbidity and mortality rates. Rapid and accurate diagnosis of this condition is essential for optimizing the therapeutic management. The diagnosis of congestive heart failure is challenging in patients presenting without obvious left ventricular systolic dysfunction and additional diagnostic information is most commonly required in this setting. Comprehensive Doppler echocardiography is the single most useful diagnostic test recommended by the ESC and ACC/AHA guidelines for assessing left ventricular ejection fraction and cardiac abnormalities in patients with suspected congestive heart failure, and non-invasively determined basal or exercise-induced pulmonary capillary hypertension is likely to become a hallmark of congestive heart failure in symptomatic patients with preserved left ventricular systolic function. The present review will focus on the current clinical applications of spectral tissue Doppler echocardiography used as a reliable noninvasive surrogate for left ventricular diastolic pressures at rest as well as during exercise in the diagnosis of heart failure with preserved left ventricular systolic function. Chronic congestive heart failure, a disease of exercise, and acute heart failure syndromes are characterized by specific pathophysiologic and diagnostic issues, and these two clinical presentations will be discussed separately.
 ...
PMID:Current clinical applications of spectral tissue Doppler echocardiography (E/E' ratio) as a noninvasive surrogate for left ventricular diastolic pressures in the diagnosis of heart failure with preserved left ventricular systolic function. 1738 87

Chronic congestive heart failure (CHF) is a common consequence of heart muscle or valve damage and remains a major cause of morbidity and mortality worldwide. There are increasing interests to treat cardiac failure by stem cell-based therapy. Many types of stem cells or progenitor cells have been suggested for cellular therapy of heart failure. While stem cell-based therapy was initially thought to be achieved by transdifferentiation of stem cells into myocardial cells including cardiomyocytes it has become clear that this may be rather an infrequent event. Instead cardiac regeneration may result from vascular differentiation of stem cells or even from stem cell-mediated reverse remodelling. Thus the term stem cell-mediated cardiac regeneration covers the spectrum from stem cell transdifferentiation into cardiomyocytes to cell-mediated pharmacotherapy. In this review we revise stem cell-based cardiac regeneration both in experimental models and in clinical application. We have limited our discussion on some selected types of stem cells, with particular emphasis on their differentiation potential, current status and perspectives on their future applications.
 ...
PMID:Do stem cells in the heart truly differentiate into cardiomyocytes? 1771 88

Chronic congestive heart failure is a highly prevalent and progressive disorder associated with excess morbidity and mortality; it has huge economic impact. Left heart failure may be systolic or may occur as isolated diastolic dysfunction. The diastolic form predominates in older people. Sleep disorders are frequent in both types. Most systematic studies have been performed in patients with systolic heart failure. Prospective studies show the presence of obstructive and central sleep apnea, periodic limb movements, and significant alterations in sleep architecture, characterized by poor efficiency, excess stage 1 and arousals, and lack of deep sleep. Both obstructive sleep apnea and central sleep apnea occur in patients with heart failure and have been shown to be associated with excess mortality. Obstructive sleep apnea is best treated with continuous positive airway pressure (CPAP) devices. Central sleep apnea is also best treated with CPAP, but only about 50% of the patients are considered responders. Survival improves when heart failure patients are effectively treated with CPAP for both central and obstructive sleep apnea. A new positive airway pressure device, a pressure support servo-ventilator, is the next best choice for heart failure patients whose central sleep apnea does not respond to CPAP. Nocturnal oxygen should be used for patients whose central sleep apnea does not respond to positive pressure devices. Both periodic limb movements and insomnia could have adverse hemodynamic consequences for the failing heart. There are no guidelines or long-term studies regarding treatment of these conditions in heart failure. For restless legs syndrome with or without periodic limb movements, pramipexole and ropinirole have been approved. Treatment of insomnia comorbid with heart failure depends on the cause. In the absence of any known cause, a trial of ramelteon is the first choice.
 ...
PMID:Sleep dysfunction in heart failure. 1878 5

Congestive heart failure, chronic kidney insufficiency and anemia are often present in the same patient. We have coined this triad the cardio-renal anemia syndrome. We suggest that congestive heart failure can often cause chronic renal failure, with both diseases producing anemia. The anemia exacerbates the chronic heart failure, which then worsens the chronic renal failure, causing further anemia, in a vicious cycle. Together with early detection and treatment of the chronic heart failure, correction of the associated anemia with a combination of subcutaneous erythropoietin and intravenous iron will often alleviate the chronic heart failure and slow down or stop the progression of the associated chronic kidney insufficiency.
 ...
PMID:The cardio-renal anemia syndrome. 1892 82

Chronic congestive heart failure (CHF) is associated with an increase in cytokines and inflammatory markers, particularly in elderly patients in whom chronic inflammation is generally present per se. In the present pilot study, neutrophil gelatinase-associated lipocalin (NGAL), a recently discovered cytokine, was analyzed together with different clinical and laboratory parameters in a small cohort of 46 elderly patients with CHF of various degrees. NGAL levels in the cohort were found to be significantly higher than in healthy age-balanced controls (458.5 [62.5-1212.4] vs. 37.8 [15.9-46.5] ng/mL; p = 0.0001). Furthermore, NGAL values increased in parallel with the clinical severity of CHF (New York Heart Association [NYHA] classification), the highest levels being reached in class IV patients (p = 0.0001). After a 2-year follow up, Kaplan-Meier curves indicated that patients with baseline NGAL > 783 ng/mL (best receiver operating characteristic [ROC]-derived cut-off value) had a significantly higher mortality (p = 0.001; log-rank test) and 4.08 hazards ratio (95% confidence interval [CI], 1.29-12.96) for death than the other subjects considered. Although preliminary, our findings suggest that NGAL plays a pivotal role in the systemic adaptation to chronic heart failure in elderly patients. Moreover, they indicate, for the first time, that measurement of NGAL may be of important prognostic value in the assessment of survival, thus extending the predictive properties of this cytokine beyond the clinical field of renal disease.
 ...
PMID:Increased plasma neutrophil gelatinase-associated lipocalin levels predict mortality in elderly patients with chronic heart failure. 1919 11

Chronic congestive heart failure (CHF) and acute decompensated heart failure (ADHF) refractory to medical therapy represent therapeutic challenges. In such patients, attempts to reduce pulmonary and systemic congestion frequently produce deterioration of renal function. In studies of patients with chronic severe CHF refractory to medical therapy (including loop diuretics), isolated ultrafiltration was frequently able to relieve congestive symptoms by precise removal of extracellular water and sodium, and in some cases was able to restore responsiveness to loop diuretics. Randomized controlled trials comparing isolated ultrafiltration and medical therapy (mainly loop diuretics) in patients with ADHF failed to demonstrate the superiority of isolated ultrafiltration over diuretic therapy with respect to renal function and mortality. Isolated ultrafiltration reduced length of hospital stay in several studies. At this time, there is insufficient evidence to support the use of isolated ultrafiltration as initial therapy of ADHF.
 ...
PMID:Role of isolated ultrafiltration in the management of chronic refractory and acute decompensated heart failure. 2766 47

Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients.
 ...
PMID:A perspective on diuretic resistance in chronic congestive heart failure. 2872 76


<< Previous 1 2