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

Heart failure is characterised by decreased cardiac output, which results in the development of both peripheral hypoperfusion and pulmonary congestion and can lead to the development of acute pulmonary edema. The primary objective in treating a patient with decompensated heart failure is hemodynamic stabilization, which is usually achieved by inotropic support. Classic inotropic agents provide short-term hemodynamic improvement, but their use has been correlated with poor prognosis. Levosimendan, a new calcium sensitizer, offers hemodynamic and symptomatic improvement without increasing cAMP and intracellular calcium concentrations. This agent improves contractility without increasing the risk of cardiac events such as arrhythmias. By combining a positive inotropic action mediated via calcium sensitization and a vasodilatory effect via ATP-dependent potassium channels, it appears to be superior than classic positive inotropic agents. Furthermore, it seems to have prolonged benefit in heart failure patients, and it also has anti-inflammatory and antiapoptotic properties. In conclusion, levosimendan seems to be a particularly promising agent for the treatment of decompensated heart failure, as in addition to improving cardiac output, it has a more favorable side-effect profile than classic inotropic agents, and it affects multiple pathways with key role in the pathophysiology of heart failure.
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PMID:Levosimendan: a novel agent in heart failure. 1822 Oct 85

The use of classic inotropic agents activating the beta-receptor-cyclic adenosine monophosphate (cAMP) pathway (ie, dobutamine or milrinone) should be restricted to a "rescue" therapy in patients with acute heart failure and signs of peripheral hypoperfusion (hypotension, renal dysfunction) that is refractory to volume replacement, diuretics, and vasodilators. This approach is largely supported by observations from clinical trials suggesting that both short-term treatment of acute heart failure without an essential requirement of inotropic support as well as long-term inotropic therapy in patients with severe chronic heart failure with classical inotropic agents can increase arrhythmia and mortality. Vice versa, beta-receptor blockade, whenever tolerated, improves survival in patients with severe stable heart failure, further supporting the concept that beta-receptor stimulation has adverse long-term effects. Positive inotropic therapy stimulating the beta-receptor-cAMP pathway should, therefore, be used with caution, given the potential harmful effects. Levosimendan, a novel calcium sensitizer, has recently attracted substantial clinical interest and may be superior to classical inotropes with respect to improving cardiac mechanical efficiency and avoiding adverse effects such as increasing myocardial oxygen uptake or cardiomyocyte death. Earlier clinical studies have suggested a beneficial effect on survival compared with dobutamine or placebo in patients with acute heart failure (LIDO , RUSSLAN , and CASINO trials). However, more recent data from two large clinical trials (SURVIVE and REVIVE trials) did not confirm these beneficial effects on mortality. Therefore, additional data are required with respect to the optimum dosing of levosimendan and patient selection to reach a definitive conclusion about the role of levosimendan in the management of patients with acute heart failure.
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PMID:Update on inotropic therapy in the management of acute heart failure. 1822 96

Levosimendan is a vasodilator used in the treatment of acute heart failure. In the present study, the effect of hepatic impairment on the pharmacokinetics of levosimendan and its 2 metabolites, OR-1855 and OR-1896 (pharmacologically active), was investigated in 12 healthy subjects and 12 subjects with moderate hepatic impairment due to alcoholic cirrhosis of the liver but with no heart failure. In addition, the effect of acetylator status on the pharmacokinetics of levosimendan, OR-1855, and OR-1896 was evaluated. Safety and tolerability of levosimendan were also assessed. Levosimendan was given as an intravenous infusion of 0.1 microg/kg/min for 24 hours. Levosimendan showed similar C(max), AUC, and elimination half-life (t(1/2)), with a mean (+/-SEM) t(1/2) of 0.9 +/- 0.0 hours in healthy subjects and 0.8 +/- 0.1 hours in hepatically impaired subjects, respectively (not significant). The t(1/2) of OR-1855 was 61 +/- 5 hours in healthy subjects and 82 +/- 3 hours (P < .01) in subjects with hepatic impairment. The t(1/2) of OR-1896 was 62 +/- 5 hours and 91 +/- 5 hours (P < .01), respectively. However, the AUCs of OR-1855 and OR-1896 were similar in healthy volunteers and hepatically impaired subjects. The effect of acetylator status was seen as higher C(max) and AUC of OR-1855 in slow acetylators. Correspondingly, higher C(max) and AUC of OR-1896 were observed in rapid acetylators. Levosimendan was well tolerated in both study groups. In conclusion, the pharmacokinetics of the parent drug levosimendan was unaltered in subjects with moderate hepatic impairment, whereas the elimination of the metabolites was prolonged. However, because the maximum duration of levosimendan infusion is 24 hours, dosing adjustments of levosimendan may not be required in subjects with impaired hepatic function.
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PMID:Pharmacokinetics of intravenous levosimendan and its metabolites in subjects with hepatic impairment. 1830 24

Acute Chagas' disease corresponds to the initial period of a Trypanosoma cruzi infection. Levosimendan is a positive inotropic drug with vasodilatory properties that is indicated for acute heart failure. We describe two cases of myocarditis due to acute Chagas' disease, resulting from oral intake of sugar cane juice infected with T. cruzi and resulting complications. Both developed acute decompensated heart failure refractory to Dobutamine. We describe for the first time in the medical literature the use of Levosimendan for myocarditis due to acute Chagas' disease, with excellent clinical and hemodynamic results.
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PMID:The use of Levosimendan for myocardiopathy due to acute Chagas' disease. 1866 34

Levosimendan is a calcium-sensitizing agent with effective inotropic properties. It has been shown to improve cardiac function, hemodynamic performance, and survival in adults with severe heart failure. However, the effect of Levosimendan in pediatric cardiac surgery has not yet been investigated. Thus, we report on our experience with the intraoperative application of Levosimendan in seven infants (body weight range 2.6-6.3 kg) with severe myocardial dysfunction after complex congenital heart surgery. During the administration of Levosimendan, the heart rate, mean arterial blood pressure, and central venous pressure did not change. The mean arterial lactate level significantly decreased 24 and 48 h after the first infusion compared to baseline. Central venous oxygen saturation increased significantly 24 and 48 h after the onset of Levosimendan infusion. We found intraoperatively administered Levosimendan to be well tolerated in the seven infants with severe myocardial dysfunction after complex congenital heart surgery. Levosimendan is a new rescue drug which has beneficial effects, even in pediatric cardiac surgery.
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PMID:First experiences with intraoperative Levosimendan in pediatric cardiac surgery. 1881 47

Levosimendan reduces symptoms and improves hemodynamics in patients with acutely decompensated chronic heart failure (ADCHF). The aim of this study was to investigate (1) the association of changes induced by low-dose dobutamine stress echocardiography in 2-dimensional strain parameters with the corresponding changes in the left ventricular (LV) ejection fraction (EF) and LV outflow tract velocity time integral (VTI) in patients with ADCHF and (2) whether LV contractile reserve assessed by conventional and speckle-tracking echocardiography is associated with clinical and neurohumoral improvement after levosimendan treatment. Twenty-eight consecutive patients with ADCHF (mean age 65 +/- 10 years, mean New York Heart Association class 3.6 +/- 0.3, mean EF 22 +/- 6%) were studied using dobutamine stress echocardiography before 24-hour infusion of levosimendan. The LV EF, VTI, and mean longitudinal, circumferential, and radial strain and strain rate using speckle-tracking imaging were measured. Twenty-one patients (75%) had evidence of contractile reserve (LV EF increase >10% and VTI increase >20% after peak dobutamine dose). Patients with versus without contractile reserve demonstrated greater improvements in New York Heart Association class (mean change -1.0 +/- 0.5 vs -0.5 +/- 0.3, p = 0.01) and reductions in B-type natriuretic peptide levels (-34 +/- 30% vs +4 +/- 31%, p <0.01) 48 hours after treatment. On multivariate analysis, mean longitudinal systolic strain rate reserve (peak longitudinal strain rate minus longitudinal strain rate at rest) was the best predictor of improvement in New York Heart Association class (p = 0.039) and B-type natriuretic peptide level (p = 0.042) after levosimendan among the reserve of LV fractional shortening, the EF, VTI, and longitudinal, circumferential, and radial strain and strain rate. In conclusion, dobutamine-induced changes in longitudinal systolic strain rate are associated with clinical and neurohumoral improvement after levosimendan treatment in patients with ADCHF.
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PMID:Usefulness of dobutamine-induced changes of the two-dimensional longitudinal deformation predict clinical and neurohumoral improvement in men after levosimendan treatment in acutely decompensated chronic heart failure. 1894 Feb 97

Levosimendan increases the sensitivity of the cardiac fibrils to calcium, favorably affects hemodynamics in patients with heart failure. It is a positive inotrope and a peripheral vasodilator. The elimination half-life of the compound is about 1 hour. The drug decreases pulmonary capillary wedge pressure, increases cardiac output with the improvement in left ventricular ejection fraction leading to symptomatic improvement which includes decreased dyspnea and fatigue. Levosimendan can be used safely with diuretics, nitrates, beta-blockers, digoxin, and angiotensin-converting enzyme inhibitors. The most common adverse effects of levosimendan are headache and hypotension. Prolongation of the QTc interval does not appear to increase the incidence of arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointes. Levosimendan is a novel agent in the treatment of decompensated heart failure, representing a newer class of medications aimed at increasing calcium sensitivity. Its properties holds promise for the treatment of heart failure but further large-scale studies will be needed to determine its precise efficacy, safety, as well as the compound's long-term impact on mortality.
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PMID:Levosimendan and calcium sensitization of the contractile proteins in cardiac muscle: impact on heart failure. 1908 50

Levosimendan is a new cardiac enhancer that exerts positive inotropic effects on the failing heart mediated by calcium sensitization of contractile proteins as well as peripheral vasodilatory effects mediated by opening of ATP-sensitive potassium channels in vascular smooth-muscle cells. Levosimendan is the most well-studied calcium sensitizer in the real clinical practice, producing greater hemodynamic and symptomatic improvement in patients with acute heart failure syndromes (AHFS) than those with traditional inotropes. Immunomodulatory and anti-apoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal responses in AHFS. Recent mortality trials showed that levosimendan does not improve short- and long-term prognosis in AHFS in comparison to dobutamine or placebo. However, in patients with a previous history of CHF and on beta-blocker on admission, levosimendan seems to have a beneficial effect on short-term mortality. According to the recent guidelines of the European Society of Cardiology, levosimendan is indicated in patients with symptomatic low cardiac output HF secondary to cardiac systolic dysfunction without severe hypotension (Class IIa, Level of Evidence B).
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PMID:Levosimendan: from basic science to clinical practice. 1910 96

Acute heart failure is a common clinical problem faced in cardiac surgery operating rooms and intensive care units. Levosimendan, an inotropic and vasodilating agent used widely in cases of acute heart failure for "cardiological" patients, has not gained global acceptance in its application for heart-operated ones. Herein, we are presenting a series of studies and patents concerning this medication, which, in general, support the use of levosimendan during and after heart surgery, despite the relatively high cost of administration. However, trials with larger samples of patients have to be performed in order to definitively establish this medication as a routinely administered drug for acute congestive heart failure after heart surgery.
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PMID:Levosimendan for heart-operated patients: what is the state of the art? 1914 2

Severe heart failure represents a major source of morbidity and mortality. Poor right ventricular function is an independent prognostic marker for mortality in patients with chronic heart failure. In this study, levosimendan (L) and dobutamine (D) in patients with severe chronic biventricular failure were compared. Forty consecutive patients, who were judged for inotropic therapy by their primary physicians, with acutely decompensated systolic heart failure and having moderate-to-severe right ventricular dysfunction with right ventricular fractional area change of <or= 24%m were randomized to L and D in a 2:1 fashion. Echocardiographic parameters including tricuspid annular motion and clinical issues were considered. Mean age and sex distribution were not different between the two groups. After the infusion, ejection fraction improved and systolic pulmonary artery pressure decreased significantly in both arms. Longitudinal systolic function of tricuspid annulus improved significantly better in patients with L compared to patients with D (15%+/-12% vs. 2%+/-6% improvement, P<0.001). Furthermore, L improved both 24-h urine output and creatinine, whereas D showed only a small, but significant improvement in urine output without any improvement in the creatinine levels. Levosimendan seems to offer more beneficial effects compared to dobutamine in a specific group of patients with biventricular failure.
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PMID:Comparative effects of levosimendan and dobutamine on right ventricular function in patients with biventricular heart failure. 1916 63


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