TY - JOUR
T1 - Effects of istaroxime on diastolic stiffness in acute heart failure syndromes
T2 - Results from 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
AU - Shah, Sanjiv J.
AU - Blair, John E.A.
AU - Filippatos, Gerasimos S.
AU - MacArie, Cezar
AU - Ruzyllo, Witold
AU - Korewicki, Jerzy
AU - Bubenek-Turconi, Serban I.
AU - Ceracchi, Maurizio
AU - Bianchetti, Maria
AU - Carminati, Paolo
AU - Kremastinos, Dimitrios
AU - Grzybowski, Jacek
AU - Valentini, Giovanni
AU - Sabbah, Hani N.
AU - Gheorghiade, Mihai
N1 - Funding Information:
The HORIZON-HF study was funded by Sigma-Tau i.f.r., SpA (Rome, Italy). The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents.
PY - 2009/6
Y1 - 2009/6
N2 - Background Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of the Na+/K+ adenosine triphosphatase and stimulation of sarcoplasmic reticulum calcium adenosine triphosphatase activity. We analyzed data from HORIZON-HF, a randomized, controlled trial evaluating the short-term effects of istaroxime in patients hospitalized with heart failure and left ventricular ejection fraction ≤35% to test the hypothesis that istaroxime improves diastolic stiffness in acute heart failure syndrome. Methods One hundred twenty patients were randomized 3:1 (istaroxime/placebo) to a continuous 6-hour infusion of 1 of 3 doses of istaroxime or placebo. All patients underwent pulmonary artery catheterization and comprehensive 2-dimensional/Doppler and tissue Doppler echocardiography at baseline and at the end of the 6-hour infusion. We quantified diastolic stiffness using pressure-volume analysis and tissue Doppler imaging of the lateral mitral annulus (E'). Results Baseline characteristics were similar among all groups, with mean age 55 ± 11 years, 88% men, left ventricular ejection fraction 27% ± 7%, systolic blood pressure (SBP) 116 ± 13 mm Hg, and pulmonary capillary wedge pressure (PCWP) 25 ± 5 mm Hg. Istaroxime administration resulted in an increase in E' velocities, whereas there was a decrease in E' in the placebo group (P = .048 between groups). On pressure-volume analysis, istaroxime decreased end-diastolic elastance (P = .0001). On multivariate analysis, increasing doses of istaroxime increased E' velocity (P = .043) and E-wave deceleration time (P = .001), and decreased E/E' ratio (P = .047), after controlling for age, sex, baseline ejection fraction, change in PCWP, and change in SBP. Conclusions Istaroxime decreases PCWP, increases SBP, and decreases diastolic stiffness in patients with acute heart failure syndrome.
AB - Background Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of the Na+/K+ adenosine triphosphatase and stimulation of sarcoplasmic reticulum calcium adenosine triphosphatase activity. We analyzed data from HORIZON-HF, a randomized, controlled trial evaluating the short-term effects of istaroxime in patients hospitalized with heart failure and left ventricular ejection fraction ≤35% to test the hypothesis that istaroxime improves diastolic stiffness in acute heart failure syndrome. Methods One hundred twenty patients were randomized 3:1 (istaroxime/placebo) to a continuous 6-hour infusion of 1 of 3 doses of istaroxime or placebo. All patients underwent pulmonary artery catheterization and comprehensive 2-dimensional/Doppler and tissue Doppler echocardiography at baseline and at the end of the 6-hour infusion. We quantified diastolic stiffness using pressure-volume analysis and tissue Doppler imaging of the lateral mitral annulus (E'). Results Baseline characteristics were similar among all groups, with mean age 55 ± 11 years, 88% men, left ventricular ejection fraction 27% ± 7%, systolic blood pressure (SBP) 116 ± 13 mm Hg, and pulmonary capillary wedge pressure (PCWP) 25 ± 5 mm Hg. Istaroxime administration resulted in an increase in E' velocities, whereas there was a decrease in E' in the placebo group (P = .048 between groups). On pressure-volume analysis, istaroxime decreased end-diastolic elastance (P = .0001). On multivariate analysis, increasing doses of istaroxime increased E' velocity (P = .043) and E-wave deceleration time (P = .001), and decreased E/E' ratio (P = .047), after controlling for age, sex, baseline ejection fraction, change in PCWP, and change in SBP. Conclusions Istaroxime decreases PCWP, increases SBP, and decreases diastolic stiffness in patients with acute heart failure syndrome.
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U2 - 10.1016/j.ahj.2009.03.007
DO - 10.1016/j.ahj.2009.03.007
M3 - Article
C2 - 19464414
AN - SCOPUS:67049100043
SN - 0002-8703
VL - 157
SP - 1035
EP - 1041
JO - American heart journal
JF - American heart journal
IS - 6
ER -