We included patients hospitalised for AHF with left ventricular ejection fraction ≤40% and E/e' > 10. Patients were randomised to a 24 h
intravenous infusion of placebo or
istaroxime at doses of 0.5 μg/kg/min (cohort 1: placebo n = 19;
istaroxime n = 41) or 1.0 μg/kg/min (cohort 2: placebo n = 20,
istaroxime n = 40). The primary endpoint of change in E/e' ratio from baseline to 24 h decreased with
istaroxime vs. placebo (cohort 1: -4.55 ± 4.75
istaroxime 0.5 μg/kg/min vs. -1.55 ± 4.11 placebo, P = 0.029; cohort 2: -3.16 ± 2.59
istaroxime 1.0 μg/kg/min vs. -1.08 ± 2.72 placebo, P = 0.009). Both
istaroxime doses significantly increased stroke volume index and decreased heart rate. Systolic blood pressure increased with
istaroxime, achieving significance with the high dose. Self-reported dyspnoea and N-terminal pro-
brain natriuretic peptide improved in all groups without significant differences between
istaroxime and placebo. No significant differences in cardiac
troponin absolute values or clinically relevant arrhythmias were observed during or after
istaroxime infusion. Serious cardiac adverse events (including arrhythmias and
hypotension) did not differ between placebo and
istaroxime groups. The most common adverse events were
injection site reactions and gastrointestinal events, the latter primarily with
istaroxime 1.0 μg/kg/min.
CONCLUSIONS: In patients hospitalised for AHF with reduced ejection fraction, a 24 h infusion of
istaroxime improved parameters of diastolic and systolic cardiac function without major cardiac adverse effects.