@article{3120834,
    title = "Treatment with 24 hour istaroxime infusion in patients hospitalised for acute heart failure: a randomised, placebo-controlled trial",
    author = "Carubelli, V. and Zhang, Y. and Metra, M. and Lombardi, C. and Felker, G.M. and Filippatos, G. and O'Connor, C.M. and Teerlink, J.R. and Simmons, P. and Segal, R. and Malfatto, G. and La Rovere, M.T. and Li, D. and Han, X. and Yuan, Z. and Yao, Y. and Li, B. and Lau, L.F. and Bianchi, G. and Zhang, J. and the Istaroxime ADHF Trial Group",
    journal = "European Journal of Heart Failure",
    year = "2020",
    volume = "22",
    number = "9",
    pages = "1684-1693",
    publisher = "John Wiley and Sons Ltd",
    doi = "10.1002/ejhf.1743",
    keywords = "amino terminal pro brain natriuretic peptide;  istaroxime;  placebo;  troponin;  etiocholanolone;  istaroxime, abdominal pain;  acute heart failure;  adult;  Article;  cardiogenic shock;  cohort analysis;  controlled study;  double blind procedure;  drug effect;  drug withdrawal;  dyspnea;  female;  heart death;  heart failure;  heart left ventricle ejection fraction;  heart rate;  heart stroke volume;  hospital patient;  human;  inflammation;  injection site reaction;  kidney artery embolism;  major clinical study;  male;  multicenter study;  nausea;  phase 2 clinical trial;  priority journal;  randomized controlled trial;  self report;  systolic blood pressure;  vomiting;  heart failure;  heart left ventricle function, Double-Blind Method;  Etiocholanolone;  Heart Failure;  Humans;  Stroke Volume;  Ventricular Function, Left",
    abstract = "Aim: Istaroxime is a first-in-class agent which acts through inhibition of the sarcolemmal Na+/K+ pump and activation of the SERCA2a pump. This study assessed the effects of a 24 h infusion of istaroxime in patients hospitalised for acute heart failure (AHF). Methods and results: 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. © 2020 European Society of Cardiology"
}