Rationale and design of the hemodynamic, echocardiographic and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: A randomized controlled trial in patients hospitalized with heart failure (horizon-hf) trial

John E A Blair, Cezar Macarie, Witold Ruzyllo, Antonella Bacchieri, Giovanni Valentini, Maria Bianchetti, Peter Pang, Matthew E. Harinstein, Hani N. Sabbah, Gerasimos S. Filippatos, Mihai Gheorghiade

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Current 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 Results: This 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 ≤ 35%) admitted to the hospital with worsening HF. Three cohorts of 40 patients each were randomized after an initial stabilization period of

Original languageEnglish (US)
Pages (from-to)231-240
Number of pages10
JournalAmerican Journal of Therapeutics
Volume15
Issue number3
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Randomized Controlled Trials
Heart Failure
Hemodynamics
Blood Pressure
Placebos
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Left Ventricular Dysfunction
Left Ventricular Function
Stroke Volume
Myocardial Ischemia
Cardiac Arrhythmias
Necrosis
Animal Models
Heart Rate
Kidney
Istaroxime

Keywords

  • Acute heart failure syndromes
  • Diastolic function
  • Echocardiography
  • Hemodynamics
  • Inotropes
  • Lusitropic agents
  • Myocardial integrity
  • Neurohormones
  • Renal function
  • Systolic function

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Rationale and design of the hemodynamic, echocardiographic and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent : A randomized controlled trial in patients hospitalized with heart failure (horizon-hf) trial. / Blair, John E A; Macarie, Cezar; Ruzyllo, Witold; Bacchieri, Antonella; Valentini, Giovanni; Bianchetti, Maria; Pang, Peter; Harinstein, Matthew E.; Sabbah, Hani N.; Filippatos, Gerasimos S.; Gheorghiade, Mihai.

In: American Journal of Therapeutics, Vol. 15, No. 3, 05.2008, p. 231-240.

Research output: Contribution to journalArticle

Blair, John E A ; Macarie, Cezar ; Ruzyllo, Witold ; Bacchieri, Antonella ; Valentini, Giovanni ; Bianchetti, Maria ; Pang, Peter ; Harinstein, Matthew E. ; Sabbah, Hani N. ; Filippatos, Gerasimos S. ; Gheorghiade, Mihai. / Rationale and design of the hemodynamic, echocardiographic and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent : A randomized controlled trial in patients hospitalized with heart failure (horizon-hf) trial. In: American Journal of Therapeutics. 2008 ; Vol. 15, No. 3. pp. 231-240.
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AU - Bacchieri, Antonella

AU - Valentini, Giovanni

AU - Bianchetti, Maria

AU - Pang, Peter

AU - Harinstein, Matthew E.

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AU - Filippatos, Gerasimos S.

AU - Gheorghiade, Mihai

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