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.

Abstract

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, HORIZON-HF Investigators
• Journal: American heart journal (Am Heart J) Vol. 157 Issue 6 Pg. 1035-41 (Jun 2009) ISSN: 1097-6744 [Electronic] United States
• PMID: 19464414 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Cardiovascular Agents
• Etiocholanolone
• Sodium-Potassium-Exchanging ATPase
• Istaroxime

Topics

• 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