| 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. | |
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MedLine Citation:
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PMID: 19464414 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Randomized Controlled Trial Date: 2009-04-23 |
Journal Detail:
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Title: American heart journal Volume: 157 ISSN: 1097-6744 ISO Abbreviation: Am. Heart J. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-05-25 Completed Date: 2009-06-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370465 Medline TA: Am Heart J Country: United States |
Other Details:
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Languages: eng Pagination: 1035-41 Citation Subset: AIM; IM |
Affiliation:
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Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. sanjiv.shah@northwestern.edu |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00616161 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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