Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure.
OBJECTIVE
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).
Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. m-gheorghiade@northwestern.edu
Mihai
M
Gheorghiade
John E A
JE
Blair
Gerasimos S
GS
Filippatos
Cezar
C
Macarie
Witold
W
Ruzyllo
Jerzy
J
Korewicki
Serban I
SI
Bubenek-Turconi
Maurizio
M
Ceracchi
Maria
M
Bianchetti
Paolo
P
Carminati
Dimitrios
D
Kremastinos
Giovanni
G
Valentini
Hani N
HN
Sabbah
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects; D005043:Etiocholanolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D006760:Hospitalization; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D014463:Ultrasonography
D002316:Cardiotonic Agents; D005043:Etiocholanolone; D000254:Sodium-Potassium-Exchanging ATPase; C468128:Istaroxime