OBJECTIVES: We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF). BACKGROUND:Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase. METHODS:One hundred twenty patients admitted with HF and reduced systolic function were instrumented with a pulmonary artery catheter within 48 h of admission. Three sequential cohorts of 40 patients each were randomized 3:1istaroxime:placebo to a continuous 6-h infusion. The first cohort received 0.5 microg/kg/min, the second 1.0 microg/kg/min, and the third 1.5 microg/kg/min istaroxime or placebo. RESULTS: All doses of istaroxime lowered pulmonary capillary wedge pressure (PCWP), the primary end point (mean +/- SD: -3.2 +/- 6.8 mm Hg, -3.3 +/- 5.5 mm Hg, and -4.7 +/- 5.9 mm Hg compared with 0.0 +/- 3.6 mm Hg with placebo; p < 0.05 for all doses). Istaroxime significantly decreased heart rate (HR) and increased systolic blood pressure (SBP). Cardiac index increased and left ventricular end-diastolic volume decreased significantly only with 1.5 microg/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 microg/kg/min. There were no changes in neurohormones, renal function, or troponin I. Adverse events were not life threatening and were dose related. CONCLUSIONS: In patients hospitalized with HF, istaroxime improved PCWP and possibly diastolic function. In contrast to available inotropes, istaroxime increased SBP and decreased HR. (A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function [HORIZON-HF]; NCT00616161).
RCT Entities:
OBJECTIVES: We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF). BACKGROUND:Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase. METHODS: One hundred twenty patients admitted with HF and reduced systolic function were instrumented with a pulmonary artery catheter within 48 h of admission. Three sequential cohorts of 40 patients each were randomized 3:1 istaroxime:placebo to a continuous 6-h infusion. The first cohort received 0.5 microg/kg/min, the second 1.0 microg/kg/min, and the third 1.5 microg/kg/min istaroxime or placebo. RESULTS: All doses of istaroxime lowered pulmonary capillary wedge pressure (PCWP), the primary end point (mean +/- SD: -3.2 +/- 6.8 mm Hg, -3.3 +/- 5.5 mm Hg, and -4.7 +/- 5.9 mm Hg compared with 0.0 +/- 3.6 mm Hg with placebo; p < 0.05 for all doses). Istaroxime significantly decreased heart rate (HR) and increased systolic blood pressure (SBP). Cardiac index increased and left ventricular end-diastolic volume decreased significantly only with 1.5 microg/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 microg/kg/min. There were no changes in neurohormones, renal function, or troponin I. Adverse events were not life threatening and were dose related. CONCLUSIONS: In patients hospitalized with HF, istaroxime improved PCWP and possibly diastolic function. In contrast to available inotropes, istaroxime increased SBP and decreased HR. (A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function [HORIZON-HF]; NCT00616161).
Authors: Mihai Gheorghiade; Muthiah Vaduganathan; Andrew Ambrosy; Michael Böhm; Umberto Campia; John G F Cleland; Francesco Fedele; Gregg C Fonarow; Aldo P Maggioni; Alexandre Mebazaa; Mandeep Mehra; Marco Metra; Savina Nodari; Peter S Pang; Piotr Ponikowski; Hani N Sabbah; Michel Komajda; Javed Butler Journal: Heart Fail Rev Date: 2013-03 Impact factor: 4.214
Authors: Marco Metra; Luca Bettari; Valentina Carubelli; Silvia Bugatti; Alessandra Dei Cas; Francesca Del Magro; Valentina Lazzarini; Carlo Lombardi; Livio Dei Cas Journal: Drugs Date: 2011-03-26 Impact factor: 9.546
Authors: Hashim Khan; Marco Metra; John E A Blair; Mark Vogel; Matthew E Harinstein; Gerasimos S Filippatos; Hani N Sabbah; Herve Porchet; Giovanni Valentini; Mihai Gheorghiade Journal: Heart Fail Rev Date: 2009-02-24 Impact factor: 4.214
Authors: John R Teerlink; Marco Metra; Valerio Zacà; Hani N Sabbah; Gadi Cotter; Mihai Gheorghiade; Livio Dei Cas Journal: Heart Fail Rev Date: 2009-12 Impact factor: 4.214