• John E A Blair, Cezar Macarie, Witold Ruzyllo, Antonella Bacchieri, Giovanni Valentini, Maria Bianchetti, Peter S Pang, Matthew E Harinstein, Hani N Sabbah, Gerasimos S Filippatos, Mihai Gheorghiade, and HORIZON-HF investigators.
• Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
• Am J Ther. 2008 May 1;15(3):231-40.

BackgroundCurrent inotropes have inodilator properties and, although are frequently used in acute heart failure syndromes, do not improve outcomes, likely from reduction in systolic blood pressure and increasing in arrhythmias, causing worsened myocardial ischemia and end-organ damage. Istaroxime is a novel agent that, in animal models, has both inotropic (inhibition of the Na/K ATPase channel) and lusitropic (stimulation of sarcoplasmic reticulum calcium ATPase activity) effects. HORIZON-HF is designed to test the hypothesis that istaroxime is effective in improving central hemodynamics and left ventricular (LV) function, without lowering systolic blood pressure, increasing heart rate, and worsening renal function or myocardial necrosis.Methods And ResultsThis was a phase 2, randomized, double-blind, placebo-controlled, multicenter dose escalation exploratory study comparing 3 different doses of istaroxime to placebo in patients with LV systolic dysfunction (LV ejection fraction ConclusionsThe novel inotropic and lusitropic agent, istaroxime, was tested in acute heart failure syndromes using a comprehensive assessment of cardiovascular function in addition to hemodynamic measurements.

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