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

Oral antidiabetic agents were introduced into clinical practice during the 1950s. Biguanides and sulfonylureas are still used extensively today and their safety and tolerability profiles are well defined. Developments and refinements within these classes have included the introduction of second- and third-generation sulfonylureas, the introduction of modified-release preparations, and the emergence of fixed-dose preparations with metformin and with novel drugs. The latter include the thiazolidinediones, agents with a putative genomic mechanism of action that have been under intense scrutiny since the emergence of severe hepatotoxicity with troglitazone. Recent concerns about thiazolidinediones have centred on the issue of oedema and the risk of precipitating heart failure in vulnerable patients. Only prolonged exposure will determine the long-term safety of thiazolidinediones. Rapid-acting non-sulfonylurea secretagogues appear to be effective and perhaps safer than sulfonylureas in some groups of patients with certain comorbidities (e.g., those with renal impairment). alpha-Glucosidase inhibitors have an excellent safety record and acarbose has been shown to retard the progression from impaired glucose tolerance to Type 2 diabetes. However, their use is limited by tolerability issues.
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PMID:Comparative safety of newer oral antidiabetic drugs. 1704 9

It is known that the angiotensin receptor blockers (ARBs) have organ protective effects in patients with heart failure or renal impairment. Several studies have revealed that the ARB telmisartan has an organ protective effect, but there have been few studies directly comparing the effects of telmisartan and calcium antagonists, since most clinical studies on telmisartan have been conducted in treated patients or patients on combination therapy. The present study was conducted to compare the renal and vascular protective effects of telmisartan monotherapy and calcium antagonist monotherapy in untreated hypertensive patients. Forty-three patients with untreated essential hypertension were randomized to receive amlodipine (n=22) or telmisartan (n=21), which were respectively administered at doses of 5 mg and 40 mg once daily in the morning for 24 weeks. The patients were examined before and after treatment to assess changes of renal function, flow-mediated dilation (a parameter of vascular endothelial function), and brachial-ankle pulse wave velocity (baPWV; a parameter of arteriosclerosis). Before treatment, there were no significant differences in these parameters between groups. The decreases of urinary albumin excretion and baPWV, and the increase of flow-mediated dilation were significantly greater in the telmisartan group than the amlodipine group, while the antihypertensive effects were not significantly different between the two groups. In conclusion, these results suggest that telmisartan is more effective at protecting renal function and vascular endothelial function, and at improving arteriosclerosis than the calcium channel blocker in patients with essential hypertension.
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PMID:Renal and vascular protective effects of telmisartan in patients with essential hypertension. 1713 11

Renal insufficiency is becoming an increasingly common and devastating comorbidity in both acute and chronic heart failure settings. Part of the problem is due to the lack of insight into the underlying pathophysiology of salt and water balance leading to the congestive states. This review summarizes our current understanding regarding the cause and consequences of renal insufficiency in patients with heart failure, and addresses some of the limitations of current therapeutic strategies. Based on these limitations, this paper will explore the ongoing efforts to develop novel drug therapeutics to prevent or ameliorate renal impairment in patients with heart failure. These include natriuretic peptides and other vasodilators, adenosine receptor antagonists, and vasopressin receptor antagonists all currently undergoing late-stage clinical trials.
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PMID:Current and novel pharmacological approaches to renal insufficiency in heart failure. 1716 87

Cardiac complications are the leading cause of mortality in patients with chronic renal failure. Secondary carnitine deficiency, which is frequently observed in hemodialysis patients, has been associated with cardiac hypertrophy and heart failure and may impair myocardial fatty acid oxidation. In chronic kidney disease, impaired carnitine homeostasis also may affect myocardial metabolism. In this study, myocardial function and substrate oxidation in conjunction with carnitine deficiency were investigated in experimental renal failure. Uremia was induced in male Sprague-Dawley rats via a two-stage five-sixths nephrectomy. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C nuclear magnetic resonance at 3 and 6 wk of uremia. Renal impairment as assessed by serum creatinine was more severe initially and was associated with a significant deficiency in serum free carnitine (43%; P < 0.001) and elevated acyl carnitine/free carnitine ratio. Myocardial tissue carnitine concentrations, however, were unaffected. A moderate degree of cardiac hypertrophy (10 to 14%; P < 0.05) was observed in uremia without evidence of dysfunction or changes in myocardial substrate utilization. It is concluded that renal dysfunction is associated with cardiac hypertrophy in the presence of normal myocardial carnitine levels, despite a significant depletion in serum carnitine. This may be a factor in maintaining normal cardiac function and metabolism.
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PMID:Myocardial function, energy provision, and carnitine deficiency in experimental uremia. 1718 87

Patients with heart failure in the "real world" are often elderly and with multiple comorbid diseases. These conditions create a dilemma for the physician responsible for the treatment of heart failure and are associated with a substantial underutilization of evidence-based treatments. Clarifying the prognostic impact of comorbidities in heart failure could provide more precise risk stratification and optimize the management of these patients. The negative prognostic impact of concomitant diseases has been shown in several studies: in the TEMISTOCLE study, carried out in Italy on patients hospitalized for heart failure in Internal Medicine and Cardiology wards, the presence of comorbidities was associated with higher in-hospital mortality and prolonged length of stay. In the IN-CHF registry, enrolling out patients with heart failure in a cardiological setting, the rate of coexisting diseases is not very high according to the epidemiological characteristics of this population. Renal impairment, particularly in patients >70 years old, and chronic obstructive pulmonary disease (COPD) are frequent comorbid diseases in heart failure. Renal impairment has been recognized as an independent risk factor for morbidity and mortality in heart failure while the role of COPD is controversial. Patients with renal dysfunction and COPD have largely been excluded from randomized controlled trials for safety reasons, so data are scarce. In the IN-CHF registry the prevalence of elderly patients with renal impairment (serum creatinine > or = 2 mg/dl and age > or = 70 years) is 5.1%; this subgroup of patients has an increased risk for both 1-year death (28.1 vs 11.2%) and hospital admission (34.9 vs 22.5%) compared with the remaining population. The prescription pattern has been evaluated in the last years (2003-2005) and shows that angiotensin system inhibitors (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) as well as beta-blockers are less prescribed in these patients (78.9 vs 86.1% and 42.2 vs 55.9%, respectively). The prevalence of patients with COPD in the registry was 13.2%: considerable differences in COPD prevalence estimates exist in the general population depending on many factors such as method for diagnosis or lack of agreement on diagnostic criteria. COPD patients were older and with more severe symptoms; with respect to the pharmacological treatment, beta-blockers are significantly less prescribed in COPD patients while a similar proportion of patients are receiving angiotensin system antagonists. The adjusted analysis shows that COPD in not an independent predictor of 1-year mortality in this population while it is independently associated with 1-year all-cause hospitalization. Non-cardiovascular hospital admissions seem to be more influenced by the presence of this comorbidity than cardiovascular admissions.
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PMID:[Heart failure: critical patients]. 1797 26

Renal impairment is often observed in acute heart failure (HF), which is an independent prognostic factor. It is important to identify high-risk patients, who need close follow-up and intensive care for renal protection. This study was conducted to identify the factors associated with the subsequent occurrence of HF-related renal dysfunction in patients, who were admitted to the hospitals due to acute HF symptoms. We evaluated 254 consecutive patients with acute HF. HF-related renal dysfunction was defined when highest serum creatinine level was greater than 1.2 mg/dl and the serum creatinine level increased by more than 50% compared with the baseline value during the admission. Forty patients with acute HF (16%) had subsequent renal dysfunction after admission. Elevated serum C-reactive protein (CRP) levels (> or = 5 mg/dl, odds ratio 2.51, p = 0.008 by univariate analysis, odds ratio 2.43, p = 0.019 by multivariate analysis) during the first week after admission and over-reduction of body weight (> or = 4.5 kg, odds ratio 2.68, p = 0.005 by univariate analysis, odds ratio 2.53, p = 0.010 by multivariate analysis) by acute HF treatment were significantly associated with this phenomenon. Patients with high CRP levels (> or = 5 mg/dl) during the first week after admission showed a significantly greater elevation of serum creatinine levels as compared to the levels before admission than those with low CRP levels (< 5 mg/dl). In conclsion, higher serum levels of CRP could predict the subsequent renal impairment in patients admitted with the worsening of HF symptoms.
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PMID:Elevated serum C-reactive protein levels as a predictive indicator for subsequent renal impairment in patients with acute heart failure. 1807 40

Renal dysfunction is a frequent and progressive complication of chronic heart failure and is a powerful predictor of cardiovascular mortality. It is intimately associated with cardiovascular disease even in its earliest stages. Although cardiovascular and renal disease share many risk factors, the prognostic implications do not simply reflect widespread atherosclerotic vascular disease as this appears to be as important in those with heart failure secondary to idiopathic dilated cardiomyopathy as it is in those with coronary artery disease. There may be a role in the progression of heart failure, as the deleterious effects of even "mild" renal impairment seem to be borne out in predicting outcome, in a broad range of heart failure patients including those with heart failure and preserved systolic function. Renal dysfunction is both an indication for, as well as frequently limiting intervention with intensive disease modifying therapy. Although renal impairment is common in heart failure and these patients are at higher risk for adverse events including death, they are under represented in clinical trials.
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PMID:Broken pump or leaky filter? Renal dysfunction in heart failure a contemporary review. 1819 Dec 40

Diabetes as the dominant cause of ESRD is also the major cause of renal anaemia. However, most patients with diabetic kidney disease will succumb to co-morbid vascular disease or heart failure before developing severe renal impairment. In these patients, anaemia is also common finding, with a 2-3 times greater prevalence and earlier onset than in patients with renal impairment from other causes. We have recently shown that at least one in five outpatients with type 1 or type 2 diabetes in tertiary referral clinics have anaemia, in whom it constitutes a significant additional burden. Impaired renal erythropoietin release in response to declining haemoglobin levels appears to be the major contributor to anaemia in diabetes. This may be due to the predominance of damage to cells and vascular architecture of the renal tubulointerstitium associated with diabetic nephropathy that may be apparent, like albuminuria, before demonstrable changes in renal function. In addition, systemic inflammation, autonomic neuropathy and reduce red cell survival may also compound anaemia in diabetes. While anaemia may be considered a marker of diabetic kidney disease, reduced haemoglobin levels, even within the normal range, identify diabetic patients with an increased risk of hospitalisation and mortality. Anaemia may also be significant in determining the outcome of heart failure and hypoxia-induced organ damage in patients with diabetes. Upcoming studies will determine whether correction of anaemia in diabetes will lead to improved outcomes in these patients.
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PMID:Anaemia in diabetes: an emerging complication of microvascular disease. 1822 May 87

The cardiorenal syndrome refers to the interdependence of cardiocirculatory aberrations and renal dysfunction that signify a worsening in heart failure outcome. Biochemically, it appears covertly as an abnormality in renal function and when progressive, is manifested by symptom exacerbation and worsening renal impairment during application of therapy to ameliorate such symptoms. The pathways leading to these distinct impairments involve not only hemodynamic deterioration but also neurohormonal, inflammatory, and intrinsic renal mechanisms that produce this syndrome. Traditional therapy with diuretics typically worsens the cardiorenal syndrome, and vasodilator or inotropic therapy has not been shown to help either. New therapeutic avenues involving vasopressin antagonists, adenosine antagonists, and ultrafiltration are being investigated. In the absence of underlying primary renal parenchymal disease, mechanical ventricular assist devices or cardiac transplantation achieve reversal of the progressive cardiorenal syndrome, indicating the sentinel role of interrupting the cardiocirculatory aberrations that accompany this clinical manifestation.
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PMID:The progressive cardiorenal syndrome in heart failure: mechanisms and therapeutic insights. 1864 89

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


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