Hemodynamic, Echocardiographic, and Neurohormonal Effects of Istaroxime, a Novel Intravenous Inotropic and Lusitropic Agent: A Randomized Controlled Trial in Patients Hospitalized With Heart Failure
J Am Coll Cardiol, 2008; 51:2276-2285. View citation
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 µg/kg/min, the second 1.0 µg/kg/min, and the third 1.5 µg/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 µg/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 µg/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.
