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 g/kg/min, the second 1.0 g/kg/min, and the third 1.5 g/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 g/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 g/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) (JAm Coll Cardiol 2008;51:2276–85) © 2008 by the American College of Cardiology Foundation

Hemodynamic, echocardiographic and neurohormonal effects of istaroxime,a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure

FERRARI, Roberto;
2008

Abstract

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 g/kg/min, the second 1.0 g/kg/min, and the third 1.5 g/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 g/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 g/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) (JAm Coll Cardiol 2008;51:2276–85) © 2008 by the American College of Cardiology Foundation
2008
M., Gheorghiade; Je, Blair; Gs, Filippatos; C., Macarie; W., Ruzyllo; J., Korewicki; SI Bubenek, Turconi; M., Ceracchi; M., Bianchetti; P., Carminati; D., Kremastinos; G., Valentini; Hn, Sabbah; Ferrari, Roberto; HORIZON HF, Investigators
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1378832
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 128
  • ???jsp.display-item.citation.isi??? 104
social impact