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

Preventing the progression of established heart failure can be difficult, as multiple factors contribute to the continual decline of cardiac function. Blunting the activated neurohormonal response to a decreased systolic function is a proven means of slowing progression of CHF. Preventing further CAD and cardiac ischemia may also prove to be an effective mechanism. Two trials with HMGCoA reductase inhibitors lend support to this hypothesis. Studies using ACE inhibitors may also support this notion. Since a major portion of heart failure in the USA is caused by CAD, preventing CHF progression may be related to the prevention of CAD. Using ACE inhibitors and lipid-lowering agents, in addition to standard measures of CAD risk factor modification, may prove useful in future trials to retard the progression of heart failure. Further research and clinical trials involving this method of CHF prevention are warranted.
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PMID:Role of secondary prevention in congestive heart failure due to coronary artery disease. 989 17

In cardiovascular pharmacotherapy, the main focus is now on statins (HMG-CoA-reductase inhibitors) because of their antihyperlipidaemic and antiatherogenic effect. They are suggested to be beneficial also in senile dementia, stroke and osteoporosis and they can reduce incidence of ventricular arrhythmias in patients with cardioverter-defibrillator. In chronic heart failure, statins should be used with caution since reduced cholesterol levels relate to impaired survival. As an alternative to statins and fibrates, niacin therapy may be considered. ACE inhibitors are of proven benefit for patients with left ventricular dysfunction after acute myocardial infarction; however, in long-term treatment, their protective activity is not superior to that of beta-blockers, diuretics and clonidine. Ca-channel antagonists slightly increase the incidence of cardiovascular complications but reduce the incidence of stroke in high-risk patients. Biventricular pacing has been used with success in patients with severe heart failure and conduction disturbances, and the first permanent artificial ventricle was implanted to a patient with irreversible terminal heart failure in summer 2000. Cardiospecific troponin I may be an uninvasive marker of a procoagulant status indicating e.g. graft failure after cardiac transplantation; T-cadherin belongs to the cell-adhesion molecules and has a role in maintenance of cellular contacts which are critical for the vessel wall architecture. Etamoxir, originally developed for the treatment of diabetes II, has recently been shown to be a potential novel drug for heart failure. Routine use of nitric oxide after congenital heart surgery lessens the risk of pulmonary hypertensive crises.
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PMID:[Cardiology 2000]. 1137 23

Statins are competitive inhibitors of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase and are the most commonly used drugs to treat hyperlipidaemia. Muscle toxicity is an adverse effect reported with a low incidence and rarely associated with acute renal failure due to rhabdomyolysis. We describe two patients with chronic renal failure treated with pravastatin and simvastatin who suffered rhabdomyolysis and acute renal failure. One patient started pravastatin several days after cessation of bezafibrate and developed acute renal failure without needing dialysis. The other was treated with simvastatin three years ago and suffered rhabdomyolysis when renal function was impaired after indomethacin was prescribed for backache. He needed hemodialysis because of acute cardiac failure and died from a respiratory infection while on mechanical ventilation. Myopathy was reversible in both patients. We recommend starting statins with the lower doses in chronic renal failure and monitoring muscle enzymes when renal function changes or when new drugs with potential interactions are prescribed.
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PMID:[Rhabdomyolysis and acute renal failure secondary to statins]. 1198 93

Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are of proven clinical benefit in coronary heart disease, at least in those patients who do not have overt chronic heart failure (CHF). However, as there have been no prospective clinical trials of statins in CHF patients, the question arises as to whether the benefits observed in the absence of CHF can be necessarily inferred in those patients in whom CHF is established. In this review, the evidence base stating support of the use of statins in CHF is presented, as well as theoretical considerations as to why these agents may not necessarily be of benefit in this setting. The beneficial potential of statins clearly relates to their plaque stabilization properties and associated improvements in endothelial function, which together should reduce the risk of further infarction and, perhaps, the ischemic burden on the failing ventricle. Furthermore, these agents may have beneficial effects independent of lipid lowering. These include actions on neoangiogenesis, downregulation of AT(1) receptors, inhibition of proinflammatory cytokine activity and favorable modulation of the autonomic nervous system. The potential adverse effects of statins in CHF include reduction in levels of coenzyme Q10 (which may further exacerbate oxidative stress in CHF) and loss of the protection that lipoproteins may provide through binding and detoxifying endotoxins entering the circulation via the gut. In support of these possibilities are epidemiologic data linking a lower serum cholesterol with a poorer prognosis in CHF. These uncertainties indicate the need for a definitive outcome trial to assess the efficacy and safety of statins in CHF, despite their current widespread, non-evidence based use in this population.
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PMID:Statins and chronic heart failure: do we need a large-scale outcome trial? 1202 Apr 81

Nitroglycerin (glyceryl trinitrate, GTN), originally manufactured by Alfred Nobel, has been used to treat angina and heart failure for over 130 years. However, the molecular mechanism of GTN biotransformation has remained a mystery and it is not well understood why "tolerance" (i.e., loss of clinical efficacy) manifests over time. Here we purify a nitrate reductase that specifically catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from GTN, leading to production of cGMP and relaxation of vascular smooth muscle both in vitro and in vivo, and we identify it as mitochondrial aldehyde dehydrogenase (mtALDH). We also show that mtALDH is inhibited in blood vessels made tolerant by GTN. These results demonstrate that the biotransformation of GTN occurs predominantly in mitochondria through a novel reductase action of mtALDH and suggest that nitrite is an obligate intermediate in generation of NO bioactivity. The data also indicate that attenuated biotransformation of GTN by mtALDH underlies the induction of nitrate tolerance. More generally, our studies provide new insights into subcellular processing of NO metabolites and suggest new approaches to generating NO bioactivity and overcoming nitrate tolerance.
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PMID:Identification of the enzymatic mechanism of nitroglycerin bioactivation. 1206 Jul 25

There are a number of theoretical reasons as to why 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) should be prescribed to patients with chronic heart failure (CHF). These agents are proven to prevent coronary heart disease, the major etiological factor in the development of CHF. Potential additional effects of these agents include inhibition of proinflammatory cytokine activity and other potential beneficial effects on cardiac remodeling. However, there are also possible adverse effects of this strategy, supported by the overriding observation that low plasma lipid levels portend a poorer prognosis in patients with established CHF. Potential mechanisms by which statins may directly confer adverse effects include a reduction in levels of the antioxidant ubiquinone and an increase in blood endotoxin levels, both of which may contribute to CHF disease progression. Given these uncertainties, an answer to the question of whether or not therapy for CHF should include statins requires a definitive clinical trial. The importance of such a trial is further highlighted by the already commonplace usage of statins amongst patients with CHF.
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PMID:Should patients with chronic heart failure be treated with "statins"? 1263 77

Endothelial dysfunction plays an important role in a number of cardiovascular diseases. An important pathogenetic factor for the development of endothelial dysfunction is lack of nitric oxide (NO), which is a potent endothelium-derived vasodilating substance. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), originally designed to lower plasma cholesterol levels, seem to ameliorate endothelial dysfunction by a mechanism so far only partly understood. However, statins increase nitric oxide synthase activity. It has been speculated that this and other "side effects" of statin treatment are due to inhibition of Rho, an intracellular signalling protein that initiates Rho kinase transcription. Moreover, statins possess anti-inflammatory characteristics. Some statins have proven to lower plasma levels of C-reactive protein, which is induced by pro-inflammatory cytokines. Other statins have been demonstrated to directly inhibit pro-inflammatory cytokine induction. Finally, some data suggest that statins might be able to counterbalance an increased production of oxygen free radicals. Since chronic heart failure is accompanied not only by endothelial dysfunction, but also by pro-inflammatory cytokine activation and enhanced formation of oxygen free radicals, it is tempting to speculate that statins might be an ideal candidate to treat certain features of this disease. The doses needed to achieve the desired effects might be much lower than those needed to treat hypercholesterolemia.
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PMID:Statins and the role of nitric oxide in chronic heart failure. 1265 63

In recent years, rapid growth in the understanding of the pathophysiology of chronic heart failure has allowed for insights into many potential new therapeutic strategies. Yet until now, despite sound biological basis for efficacy and success in early-Phase studies, novel agents have not stood up to the scrutiny of late-Phase clinical trials. Indeed, remarkably negative results have been observed for vasopeptidase inhibitors, endothelin receptor antagonists and agents which block immune activation. However, efficacy data from other novel agents are still awaited, including the selective aldosterone receptor antagonist eplerenone, arginine vasopressin inhibitors, erythropoietin and hydroxy-methyl-glutaryl coenzyme A reductase inhibitors. Other classes of drugs which may enter clinical development include cardiac metabolic agents, matrix metalloproteinase inhibitors and advanced glycation end product antagonists. That the mortality and morbidity of patients with chronic heart failure remain unacceptably high makes the ongoing commitment to exploration of new drug therapies for the condition critical.
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PMID:New developments in the pharmacological treatment of chronic heart failure. 1272 Apr 87

Cardiac hypertrophy is an initial physiological adaptive response by the heart to pressure overload. However, if pressure overload persists, frequently, the heart decompensates and develops 'pathophysiological' hypertrophy. This leads to increased mortality and morbidity and is an independent risk factor for heart failure. Because cardiac myocytes convert this pressure overload into intracellular biochemical signals, blocking this critical signaling pathway may be an important therapeutic target to prevent cardiac hypertrophy. Small GTP-binding proteins, in particular Rac1, have been suggested to play a key role in the development of cardiac hypertrophy. Recently, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also called statins, have been shown to inhibit cardiac hypertrophy independent of their cholesterol lowering property. Statins block the isoprenylation and activation of members of the Rho family, such as RhoA and Rac1. Rac1 also regulates NADPH oxidase, which is a major source of reactive oxygen species (ROS) in cardiovascular cells. Growing evidence suggests that ROS may be involved in the process of cardiac hypertrophy and recent research has shown that statins attenuate oxidative stress through inhibition of Rac1. Overall, these pleiotropic effects of statins will give new insights into the process of cardiac hypertrophy.
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PMID:A novel pleiotropic effect of statins: prevention of cardiac hypertrophy by cholesterol-independent mechanisms. 1457 63

Cardiac hypertrophy is a physiological adaptive response by the heart to pressure overload. However, after prolonged periods, this initial adaptive response becomes maladaptive, leading to increased mortality and morbidity from heart failure. Recently, 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been shown to inhibit cardiac hypertrophy by cholesterol-independent mechanisms. Statins block the isoprenylation and activation of members of the Rho guanosine triphosphatase (GTPase) family, such as RhoA and Rac1. Since Rac1 is a requisite component of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is a major source of reactive oxygen species (ROS) in cardiovascular cells, the ability of statins to inhibit Rac1-mediated oxidative stress makes an important contribution to their inhibitory effects on cardiac hypertrophy.
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PMID:Statins and myocardial hypertrophy. 1523 20


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