Hemodynamic, Echocardiographic, and Neurohormonal Effects of Istaroxime, a Novel Intravenous Inotropic and Lusitropic Agent. A Randomized Controlled Trial in Patients Hospitalized With Heart Failure

Mihai Gheorghiade*, John E.A. Blair, Gerasimos S. Filippatos, Cezar Macarie, Witold Ruzyllo, Jerzy Korewicki, Serban I. Bubenek-Turconi, Maurizio Ceracchi, Maria Bianchetti, Paolo Carminati, Dimitrios Kremastinos, Giovanni Valentini, Hani N. Sabbah

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Objectives: We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF). Background: Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase. Methods: One hundred twenty patients admitted with HF and reduced systolic function were instrumented with a pulmonary artery catheter within 48 h of admission. Three sequential cohorts of 40 patients each were randomized 3:1 istaroxime:placebo to a continuous 6-h infusion. The first cohort received 0.5 μg/kg/min, the second 1.0 μg/kg/min, and the third 1.5 μg/kg/min istaroxime or placebo. Results: All doses of istaroxime lowered pulmonary capillary wedge pressure (PCWP), the primary end point (mean ± SD: -3.2 ± 6.8 mm Hg, -3.3 ± 5.5 mm Hg, and -4.7 ± 5.9 mm Hg compared with 0.0 ± 3.6 mm Hg with placebo; p < 0.05 for all doses). Istaroxime significantly decreased heart rate (HR) and increased systolic blood pressure (SBP). Cardiac index increased and left ventricular end-diastolic volume decreased significantly only with 1.5 μg/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 μg/kg/min. There were no changes in neurohormones, renal function, or troponin I. Adverse events were not life threatening and were dose related. Conclusions: In patients hospitalized with HF, istaroxime improved PCWP and possibly diastolic function. In contrast to available inotropes, istaroxime increased SBP and decreased HR. (A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function [HORIZON-HF]; NCT00616161).

Original languageEnglish (US)
Pages (from-to)2276-2285
Number of pages10
JournalJournal of the American College of Cardiology
Volume51
Issue number23
DOIs
StatePublished - Jun 10 2008

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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