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

Levosimendan is a novel compound recently approved for the management of acute heart failure in Sweden and several European countries. Levosimendan exerts dual mechanisms of action associated with dose-dependent increases in cardiac output and decreases in pulmonary capillary wedge pressures. A positive inotropic effect is achieved through calcium sensitization, an effect of levosimendan binding to troponin C in a calcium-dependent manner. This mode of enhanced contractile force generation is achieved without an increase in myocardial oxygen consumption, intracellular calcium concentrations, or an adverse effect on diastolic function. The vasodilatory effect observed in cardiac, pulmonary and systemic vasculature occurs as a result of K-ATP channel activation, a mechanism which may also confer anti-ischemic properties. It remains unclear whether calcium sensitization or K-ATP channel activation is of greater clinical significance. Clinical studies utilizing fixed-dose infusions of 6 to 24 h in patients with left ventricular systolic dysfunction demonstrate greater safety and hemodynamic efficacy than placebo or dobutamine. This has translated into improved comparative survival at 31 days and potentially 180 days. Two additional prospective, outcome studies are being completed to confirm the beneficial effect on morbidity and mortality. Hypo-tension and decreased hematologic indices are the most common adverse effects requiring monitoring. No relevant drug interactions have been noted with chronic oral heart failure medications. Levosimendan's unique safety and efficacy profile suggests it is a rationale alternative to conventional inotropes, and potentially a useful first line agent for management of acute decompensated heart failure. Its role in other clinical scenarios, such as for cardiac surgery, diastolic dysfunction and outpatient infusion therapy, continues to evolve.
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PMID:Levosimendan: dual mechanisms for acute heart failure...and beyond? 1633 39

Congestive heart failure is a long standing health issue. Traditionally, heart failure has been treated with a wide array of drugs such as diuretics, digitalis, catecholamine and non catecholamine inotropics, although treatment with these drugs bears adverse effects, such as the generation of arrhythmia and even death. A new class of drugs has recently exerted a positive impact on the treatment of patients with heart failure; these are the calcium sensitizers that enhance myocardial contractility without increasing cytosolic calcium. Levosimendan is a calcium sensitizer that, besides increasing contractility, has a vasodilating effect due to the activation of K(ATP) channels, being both mechanisms responsible for an advantageous therapeutic option. Different studies have proven the efficiency and safety profile of the drug on various scenarios and populations; thereby considering levosimendan a real and safe alternative treatment for patients with acute or chronic ventricular failure that need intravenous pharmacological support.
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PMID:[Levosimendan: a new strategy in the treatment of heart failure]. 1636 78

Treatment of heart failure (HF) has changed in recent years, despite the paucity of new approved drugs. Current treatment is directed not only towards improving symptoms, but also to preventing the development from asymptomatic systolic dysfunction to symptomatic heart failure, to preventing cardiac remodelling, renal dysfunction and to reducing mortality. The main families of drugs currently used are: cardiac glycosides, diuretics, angiotensin-converting enzyme inhibitors (ACEI), beta-blocking drugs (BB), angiotensin-II receptor blockers (ARB) and aldosterone receptor antagonists. The combination isosorbide dinitrate + hydralazine is hardly used due to its side effects and none of the new positive inotropic drugs has been approved in chronic HF, because all of them increase mortality. Levosimendan is a new positive inotropic agent approved for acute HF by an intravenous route, with a favourable effect on prognosis vs placebo and vs dobutamine (which worsens the prognosis). The approved oral drugs can be given at the same time if the patient tolerates them, because their beneficial effect is additive. Mortality in two years in mild to moderate HF is 34% with glycosides + diuretics. It falls to 22% when an ACEI is added, to 14% when a BB is added and to 10% when an aldosterone antagonist is added. ARB can be given instead of an ACEI or be added to the other drugs.
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PMID:[Heart failure. Current pharmacologic treatment]. 1640 Sep 75

In acute heart failure the myocardial function is acutely reduced and the oxygenation of the tissues becomes inadequate. Traditional inotropic drugs improve the haemodynamics and give symptomatic relief, but the evidence of injurious effects on morbidity and mortality restricts their use. The need for new inotropic drugs which can also reduce morbidity and mortality is for that reason obvious. Levosimendan is such a new drug in a new class (Ca2+ sensitizers) of positive inotropic drugs with favourable effects compared to existing treatment possibilities.
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PMID:[Levosimendan--an alternative to conventional inotropic treatment of patients with acute heart failure?]. 1643 Aug 7

Aortic valve replacement in patients suffering from low-gradient aortic stenosis and congestive heart failure is associated with high operative mortality, and the perioperative use of inotropes is common. Levosimendan is a calcium sensitizer with positive inotropic and vasodilatory effects and has been developed for treatment of decompensated heart failure. Although its use in patients with low-gradient aortic stenosis is not established, we hypothesized that it might have beneficial effects on outcome after aortic valve replacement. We report on a high-risk operation in a 73-year-old man with low-gradient aortic stenosis, congestive heart failure and coronary artery disease. Levosimendan was administered perioperatively (0.1 mg/kg/min 16 hours prior to the operation without a loading dose) and allowed rapid recovery of the patient, who required only brief treatment in the intensive care unit. No levosimendan-specific adverse events were observed, in particular no hypotension. The excellent postoperative result was maintained after the patient was discharged from hospital.
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PMID:Successful administration of levosimendan in a patient with low-gradient low-output aortic stenosis. 1648 28

Several clinical studies suggest substantial limitations of currently available positive inotropic substances, including beta1-adrenoceptor agonists and phosphodiesterase III inhibitors in the short- and long-term treatment of heart failure. The reasons for these detrimental effects are related to the mechanism of action of these drugs, including increases in intracellular Ca2+ with subsequent increases in myocardial oxygen demand and arrhythmogenesis. Levosimendan, a myofilament Ca2+ sensitizer with inotropic effects, increases myocardial performance without substantial changes in oxygen consumption and with neutral effects on heart rhythm. In addition, levosimendan has vasodilatory effects that are achieved by stimulation of adenosine triphosphate-dependent potassium channels. This action may be of specific interest in the setting of myocardial ischemia. To date, levosimendan is approved in 31 countries worldwide, and more patients with heart failure have participated in randomized controlled trials with levosimendan than with any other intravenous inotropic agent.
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PMID:Levosimendan, a new inotropic and vasodilator agent. 1650 4

The treatment of heart failure continues to pose a real challenge for clinicians. This condition is sometimes reversible and therapy should therefore pursue this outcome. In the context of coronary ischemic syndromes, myocardial stunning can cause heart failure and even cardiogenic shock, with important prognostic repercussions. Myocardial stunning is mainly due to calcium overload in the cytosol of myocardial cells, the loss of myofilaments and their reduced sensitivity to calcium. Enhanced immune activation with inflammatory phenomena also plays an important role in the pathophysiology of cardiac dysfunction. Increasing evidence has shown that the myocardial ATP-dependent potassium channel (K(ATP)) plays an important role in many myocardial cell functions and that it is involved in ischemia-reperfusion injury and myocardial stunning. K(ATP) is thus considered a therapeutic target in this setting. Currently used inotropic drugs improve contractility by increasing intracellular concentrations of free calcium, but they increase myocardial consumption of energy and even produce arrhythmia; therefore, in this clinical context, they do not seem to be 'pathophysiologically correct' drugs. Levosimendan, a new calcium-sensitizing agent, increases contractility by enhancing the sensitivity of myofilaments to calcium by binding to the C cardiac troponin in cardiac muscle in a calcium-dependent way. Levosimendan also exerts a coronary and systemic vasodilatory effect through its K(ATP) channel-opening properties and may exert other cardioprotective actions through this mechanism. Levosimendan produces positive hemodynamic effects without increasing myocardial oxygen demand or causing arrhythmias. Intravenous levosimendan is generally well tolerated and has been approved by several European countries, and recently recommended in European Society of Cardiology guidelines, as inotropic therapy for the short-term treatment of acute severe decompensated heart failure in adults. Randomized, double-blind trials have shown that levosimendan is not only more clinically and hemodynamically effective but also that it significantly reduces morbidity and mortality when compared with dobutamine or placebo. Clinical trials addressing the use and efficacy of intravenous levosimendan in acute heart failure in patients with systolic dysfunction or cardiogenic shock due to myocardial stunning are scarce. Beneficial effects on myocardial contractility in patients with myocardial stunning have only been shown in small clinical trials. A positive experience with levosimendan in a small series of patients with cardiogenic shock complicating ST-elevation myocardial infarction suggests that the use of this drug in cardiogenic shock should be further evaluated.
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PMID:Pharmacologic treatment of heart failure due to ventricular dysfunction by myocardial stunning: potential role of levosimendan. 1655 60

Recent upsurge in referral of patients with high perioperative risk or compromised left ventricular function for cardiac surgery has lead to an increasing use of pharmacologic support in the form of vasodilator and inotropic therapy to achieve improvement of tissue perfusion in the perioperative period or to support weaning from cardiopulmonary bypass. Traditionally, perioperatively used inotropic agents, epinephrine, dobutamine, and milrinone, are limited by significant increases in myocardial oxygen consumption, proarrhythmia, or neurohormonal activation. Levosimendan, a new inodilator for the treatment of decompensated heart failure, has also shown promise in elective therapy of cardiac surgical patients with high perioperative risk or compromised left ventricular function, as well as in rescue therapy of patients with difficult weaning from cardiopulmonary bypass. This review article briefly discusses the pharmacology of levosimendan and evaluates current best available evidence to assess the safety and efficacy of levosimendan usage in cardiac surgery.
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PMID:Levosimendan in cardiac surgery: current best available evidence. 1656 21

Levosimendan is a novel inotropic agent indicated for patients with decompensated heart failure. It has well recognised mechanisms of action. Its use however, has not been described in patients with end-stage renal failure. This report describes the use of levosimendan in a post-operative coronary artery bypass graft patient with decompensated heart failure and end-stage renal failure previously receiving dialysis six days per week. Levosimendan proved to be a safe and useful agent when used as a continuous intravenous infusion initially at 0.05 microg/kg/min then increasing up to 0.2 microg/kg/min for a total of 42 hours.
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PMID:Levosimendan following coronary artery bypass grafting in a patient with end-stage renal failure: a case report. 1656 97

Levosimendan is a new calcium sensitizer and K-ATP channel opener. Compared with other inodilators, it improves myocardial contractility without increasing oxygen requirements and induces peripheral and coronary vasodilation with a potential anti-stunning, anti-ischaemic effect. The documentation regarding levosimendan is one of the largest ever on the safety and efficacy of a new pharmacological agent in acute heart failure syndromes. Recent experiences in small-scale studies and randomized clinical trials have led to greater interest in the use of this drug for the support of impaired cardiac function also in patients with ischaemic heart disease and cardiogenic or septic shock. It is also demonstrated that this drug could be used as bridge therapy for the peri-operative phase of cardiac surgery in both adult and paediatric populations. This review summarizes the evidence from published scientific literature regarding the use of levosimendan in various clinical settings.
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PMID:Evidence-based use of levosimendan in different clinical settings. 1728 1


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