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Despite considerable research progress in the treatment of heart failure over the past 2 decades, severe chronic heart failure (CHF) remains a syndrome with a high mortality, hence the continuing search for new agents to improve both patients symptoms and survival. Especially positive inotropic agents were thought to be beneficial, since it was hoped that they would improve myocardial contractility and thus left ventricular ejection fraction. Although this is the case, many agents also lead to increased myocardial oxygen consumption, which is deleterious in the setting of severe heart failure. Furthermore, long-term survival has even been shown to be decreased in trials that assessed phosphodiesterase inhibitors, or either ß- or dopaminergic agonists, and many studies had to be stopped early due to excess mortality in the treatment arms. A common theme with these different agents is positive inotropism through catecholaminergic receptor or post-receptor pathway stimulation, which increases intracellular calcium. Of interest is the novel concept of increased calcium-sensitization of myofilaments, which does not depend on cAMP or ß-receptors, and leads to increased contractility without a concomitant increase in myocardial oxygen consumption. Indeed, 24-hour i.v. infusion of the calcium-sensitizer levosimendan has been shown to be safe and effective in patients with severe heart failure, where it led to reduced mortality when compared to dobutamine. In this presentation an overview of positive inotropic substances will be given and their indication for treatment of heart failure according to current guidelines will be discussed.
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