Pharmacology of new agents for acute heart failure syndromes

Mihai Gheorghiade*, John R. Teerlink, Alexandre Mebazaa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Current therapies for acute heart failure syndromes (AHFS) target hemodynamics by decreasing congestion or increasing myocardial contraction. Several new agents for AHFS use novel mechanisms of action that focus on new treatment targets, such as those providing anti-ischemic and antistunning effects, blocking vasopressin receptors, or blocking endothelin-1 receptors. For example, levosimendan acts as a calcium sensitizer and adenosine triphosphate-dependent potassium (KATP) channel opener that increases contraction, causes vasodilation, and provides cardioprotective effects. This is accomplished by its dual mechanism of action. Levosimendan binds to cardiac troponin C, thereby enhancing calcium myofilament responsiveness and increasing myocardial contraction without increasing intracellular calcium levels. Thus, contraction is increased with no significant increase in myocardial oxygen consumption. The opening of KATP channels by levosimendan causes vasodilation and exerts anti-ischemic and antistunning effects on the myocardium. Other new agents target neurohormonal pathways. Tezosentan is an antagonist of endothelin-1 receptors A and B. By inhibiting endothelin-1 receptors, tezosentan may counteract the activities of endothelin-1, which include vasoconstriction, proarrhythmic activities, potentiation of other neurohormones, and mediation of increased vascular permeability. Tolvaptan is a vasopressin V2-receptor antagonist that functions as an aquaretic (ie, it increases urine volume and serum sodium with little or no sodium loss). Therefore, by using novel mechanisms of action, these agents may provide new opportunities for helping patients with AHFS.

Original languageEnglish (US)
Pages (from-to)68-73
Number of pages6
JournalAmerican Journal of Cardiology
Volume96
Issue number6 SUPPL.
DOIs
StatePublished - Sep 19 2005

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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