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 principal complication of the atrial arrythmias is the thrombo-embolic accident, notably the cerebro-vascular accident. The efficacity of the oral anticoagulants in reducing cerebro-vascular accidents has been demonstrated in numerous studies. This is significantly superior to that obtained with the anti-platelet drugs. However, the anti-vitamin K drugs (warfarin) carry a risk of serious haemorrhage of around 5% per year. This restricts the proposal of this treatment to patients with an elevated risk of vascular accidents: age, diabetes, previous cerebro-vascular accidents, and cardiac failure are the risk factors. Nevertheless, the risk of haemorrhage is responsible for an under prescription of the anticoagulants in the elderly. This explains the interest aroused by alternative therapeutics: the results of trials on ximelagatran, a direct anti-thrombin, are promising. In patients with an arrythmia, cardioversion carries a thrombo-embolic risk of around 1%. This risk is reduced by prior anticoagulant treatment. The procedure for this treatment is orientated by a trans-oesophageal echocardiogram. The incertitude of the duration of anticoagulant therapy without cardioversion calls for respect of the arrythmia. The treatment of this is limited to control of the cardiac rhythm and anticoagulant treatment.
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PMID:[Antithrombotic therapy in atrial arrhythmia]. 1513 39

The vast majority of acute coronary syndrome (ACS) trials conducted over the past two decades support the view that women have persistently higher mortality and morbidity despite the introduction of new medical therapies and devices. Even after adjustment for older age, higher prevalence of diabetes, hypertension, heart failure, smaller vessel size, and late presentation, some studies still point to a persistent sex disadvantage. Even in contemporary practice, women continue to have longer delays in presentation and treatment. Selection bias in unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) trials allows inclusion of large numbers of women with clinically insignificant coronary disease and may mistakenly shift results toward apparent benefit of a less aggressive approach. This bias causes further difficulty in determining efficacy and safety of new antithrombotic agents such as direct thrombin inhibitors and glycoprotein IIb/IIa inhibitors across the spectrum of ACS. In trials of UA/NSTEMI, use of objective evidence of ischemia such as elevated troponin levels, would greatly assist the determination of efficacy and benefit in women. Enrollment of more women in clinical trials and timely sex-specific analysis would promote a better understanding of the role of female gender in ACS and would facilitate better care of all patients.
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PMID:Acute coronary syndromes in women: is treatment different? Should it be? 1518 98

Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.
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PMID:Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation. 1519 37

Atrial fibrillation and heart failure are growing epidemics in the developed world and often coexist. From clinical trials, warfarin is highly effective in reducing stroke in patients with atrial fibrillation. Equally important is the fact that in spite of well-designed trials, translation of the results of the data from the trials into clinical practice has been less than optimal. One of the reasons is that warfarin is a difficult drug to use. Thus there has been a concerted effort to develop an alternative to warfarin. Ximelagatran and Dabigatran, both direct thrombin inhibitors, are the furthest along in clinical development. Ximelagatran, while highly effective as an anticoagulant and safe with regard to bleeding, has been associated with liver function abnormalities; the importance of which needs resolution. Dabigatran is much earlier in development and is currently of unproven value. It is highly likely that alternatives to warfarin for stroke prevention will be available in the future and will likely result in a higher utilization rate of anticoagulants in patients with atrial fibrillation.
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PMID:Stroke prevention in atrial fibrillation: anticoagulants and antithrombotics. 1553 73

There has not been a year that would not have brought something new, often upheaval in the field of cardiovascular pharmacotherapy during last decades. This overview addresses the perspectives that may be expected in the treatment of cardiovascular diseases in the coming years. As for the field of dyslipidemy treatment there are some new options of blocking cholesterol resorption at the enterocyte level opening up in the field of dyslipidemy treatment (e.g. brush border transport system inhibitors, inhibitors of esterification or bind to apolipoprotein), further big revolution may be foreseen in the field of the stimulation of peroxysomal receptors controlling the lipids and glycides metabolism. It is also the field of antithrombotic drugs where we encounter the series of innovative approaches as the inhibitors of receptors facilitating the thrombocyte adhesion, new direct thrombin inhibitors or tissue factor blockers. There is no significant advance in the field of arrhythmias pharmacology, that field is completely posessed by electro-impulse therapy and ablative methods. On the contrary, great perspectives may be foreseen in the field of heart failure therapy. Along with the new methods moderating hyperactivated regulation mechanisms (e.g. renin or vasopeptidases inhibitors) promising is the field of the new inotropics active without increasing the supply of calcium (calcium sensitizers, the stimulators of sarcoplasmatic calcium ATPase). In the field of diuretics there may be expected the introduction of adiuretin blockers (akvaretics). Finally the last promising field is represented by the drugs intervening the metabolism of non-cellular matrix which are expected primarily to have a positive influence on the ventricle remodellation.
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PMID:[New trends in pharmacotherapy of cardiovascular diseases]. 1565 Nov 41

Symptomatic prehospital therapy of patients suffering from an ST elevation myocardial infarction basically does not differ from in-hospital care regarding pain relief, beta-blockers, antiplatelets, and thrombin antagonists as well as therapy of elevated blood pressure and acute heart failure. Precondition of a targeted and adequate treatment, however, is the twelve-lead ECG whose reliability does not differ from the ECG in the hospital. Biomarkers have no role in the prehospital setting. Out-of-hospital thrombolysis, which has been proven to be superior to later in-hospital initiation, can be used as a safe strategy for reperfusion. Only the prehospital phase offers a chance to treat the majority of patients within the first 2 h after symptom onset, a time window where thrombolysis results in equal or even better outcomes with respect to mortality, if compared to percutaneous intervention. Therefore, prehospital thrombolysis should be routinely applied in areas with a weak infrastructure and few and less experienced facilities for intervention but should also be considered a principal way for earliest start of reperfusion therapy. There is increasing evidence supporting the "rescue PCI" concept in patients in whom thrombolysis has failed. By contrast, the role of "facilitated PCI" still has to be defined.
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PMID:[Prehospital care of patients with acute ST elevation myocardial infarction]. 1633 63

Heart failure is an enormously important clinical problem that, if not faced, may overwhelm health care resources. Primary and secondary cardiomyopathies cause the majority of cases of clinical heart failure, which is thus better approached from the utility point of view of myocardial failure. Furthermore, the risk of thromboembolic complications presenting in such disease may be higher than in ischemic cardiomyopathy. Intracardiac thrombi and mural endocardial plaques (from the organization of thrombi) are present at necropsy in more than 50% of patients with dilated cardiomyopathy (DCM). Several studies have shown that systemic and pulmonary emboli are more frequent in patients with ventricular thrombi or plaques. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. Platelet activation, thrombin activation and fibrinolytic activity are increased in patients with DCM compared to normal subjects. However, these markers reflecting coagulation activation in patients with left ventricle thrombus are comparable to those in patients without thrombus in the left ventricle. The pathophysiology and clinical issues concerning the susceptibility to develop left ventricular (LV) thrombosis and its complications like cerebrovascular disease in patients with DCM are summarized and the most recent articles present in the medical literature are reviewed.
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PMID:Review of dilated cardiomyopathies. Dilated cardiomyopathies and altered prothrombotic state: a point of view of the literature. 1646 24

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily and is involved in the regulation of bone metabolism and vascular calcification. Increased serum OPG levels have been reported in patients with stable angina pectoris and survivors of myocardial infarction with heart failure. The purpose of the present study was to determine serum OPG levels in young survivors of acute myocardial infarction (MI), and the relationship between OPG, homocysteine, sCD40L and coagulation factors in blood. Fifty-eight patients with verified MI, 40-60 years of age, were recruited 1-4 years after the acute event into an age- and sex- matched case control study with controls recruited from the general population. Serum OPG levels were similar in cases (2.41 ng/ml, 2.11-2.77 ng/ml) (mean, 95% CI) and controls (2.43 ng/ml, 2.11-2.79 ng/ml) (p = 0.92). Significant correlation between OPG and homocysteine was found in patients (r = 0.30, p = 0.02) and controls (r = 0.35, p = 0.007). A significant negative correlation was found between OPG and sCD40L in patients (r = -0.51, p < 0.001), but not in controls (r = 0.001, p = 0.96). No associations were found between serum OPG and markers of coagulation activation. The present study shows that serum OPG level was not increased in young survivors of uncomplicated myocardial infarction. Serum OPG levels were not associated with thrombin generation assessed by thrombin-antithrombin complexes (TAT), but a positive association between serum OPG and homocysteine was found.
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PMID:Serum osteoprotegerin in young survivors of myocardial infarction. 1667 81

Thrombin activates protease-activated receptor-1 (PAR-1) and engages signaling pathways that influence the growth and survival of cardiomyocytes as well as extracellular matrix remodeling by cardiac fibroblasts. This study examines the role of Shc proteins in PAR-1-dependent signaling pathways that influence ventricular remodeling. We show that thrombin increases p46Shc/p52Shc phosphorylation at Tyr(239)/Tyr(240) and Tyr(317) (and p66Shc-Ser(36) phosphorylation) via a pertussis toxin-insensitive epidermal growth factor receptor (EGFR) transactivation pathway in cardiac fibroblasts; p66Shc-Ser(36) phosphorylation is via a MEK-dependent mechanism. In contrast, cardiac fibroblasts express beta(2)-adrenergic receptors that activate ERK through a pertussis toxin-sensitive EGFR transactivation pathway that does not involve Shc isoforms or lead to p66Shc-Ser(36) phosphorylation. In cardiomyocytes, thrombin triggers MEK-dependent p66Shc-Ser(36) phosphorylation, but this is not via EGFR transactivation (or associated with Shc-Tyr(239)/Tyr(240) and/or Tyr(317) phosphorylation). Importantly, p66Shc protein expression is detected in neonatal, but not adult, cardiomyocytes; p66Shc expression is induced (via a mechanism that requires protein kinase C and MEK activity) by Pasteurella multocida toxin, a Galpha(q) agonist that promotes cardiomyocyte hypertrophy. These results identify novel regulation of individual Shc isoforms in receptor-dependent pathways leading to cardiac hypertrophy and the transition to heart failure. The observations that p66Shc expression is induced by a Galpha(q) agonist and that PAR-1 activation leads to p66Shc-Ser(36) phosphorylation identifies p66Shc as a novel candidate hypertrophy-induced mediator of cardiomyocyte apoptosis and heart failure.
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PMID:Distinct signaling functions for Shc isoforms in the heart. 1669 71

Fondaparinux is a synthetic pentasaccharide that inhibits thrombin formation and thrombus development via selective antithrombin mediated inhibition of factor Xa. The complete bioavailability (100%) and elimination half-life of approximately 17 hours allows once-daily administration of fondaparinux. In a well designed trial (ARTEMIS) in acute medical patients aged > or = 60 years, fondaparinux was significantly more effective than placebo in terms of reducing the incidence of venous thromboembolism (VTE) up to day 15. The beneficial effect of fondaparinux therapy was observed in all subgroups of patients irrespective of underlying illness (e.g. acute heart failure or acute respiratory disease) in a predefined subgroup analysis of the ARTEMIS trial. Similarly, in a retrospective analysis of the trial, age and renal function did not appear to affect the incidence of VTE in fondaparinux and placebo recipients. Fondaparinux was generally well tolerated in this clinical trial. In patients receiving fondaparinux, the incidence of major bleeding was similar to that in patients receiving placebo and the incidence of minor bleeding was <3%.
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PMID:Fondaparinux: use in thromboprophylaxis of acute medical patients. 1818 32


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