Document Detail


Effects of istaroxime on diastolic stiffness in acute heart failure syndromes: 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.
MedLine Citation:
PMID:  19464414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 < or = 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.
Authors:
Sanjiv J Shah; 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; Jacek Grzybowski; Giovanni Valentini; Hani N Sabbah; Mihai Gheorghiade;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial     Date:  2009-04-23
Journal Detail:
Title:  American heart journal     Volume:  157     ISSN:  1097-6744     ISO Abbreviation:  Am. Heart J.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-25     Completed Date:  2009-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370465     Medline TA:  Am Heart J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1035-41     Citation Subset:  AIM; IM    
Affiliation:
Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. sanjiv.shah@northwestern.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00616161
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Aged
Cardiovascular Agents / pharmacology*
Diastole
Etiocholanolone / analogs & derivatives*,  pharmacology,  therapeutic use
Female
Heart / drug effects*
Heart Failure / drug therapy*,  therapy
Hospitalization
Humans
Male
Middle Aged
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
Stroke Volume
Chemical
Reg. No./Substance:
0/3-((2-aminoethoxy)imino)androstane-6,17-dione; 0/Cardiovascular Agents; 53-42-9/Etiocholanolone; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase

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