Haemodynamic effects of istaroxime in SCAI stage B HF-related cardiogenic shock: Insights from the SEISMiC trial

Aims: The haemodynamic effects of istaroxime in SCAI stage B cardiogenic shock (CS) due to acute decompensated heart failure (ADHF) have not been evaluated. We assessed the impact of istaroxime on specific invasively-obtained haemodynamic measures. Methods and results: In the SEISMiC extension study, 30 patients with ADHF-related SCAI stage B CS were randomized to 60-h intravenous infusion of either placebo (n = 11) or istaroxime at maximum 0.5–1.0 μg/kg/min (n = 19). In this post hoc analysis, invasively-obtained haemodynamic measures, simulated group-averaged pressure-volume (PV) loops, and end-systolic elastance (Ees), derived from individual-patient PV relationships, were compared between istaroxime- and placebo-treated patients. Compared with placebo, patients randomized to istaroxime for 48–60 h had greater increases in aortic pulsatility index (API) and left ventricular (LV) stroke work index (LVSWI) at 6, 12, 24, and 48 h; and greater increase in pulmonary artery (PA) compliance and reduction in PA elastance at 48 h. At group-averaged PV loop analysis, LV contractility remained stable and right ventricular (RV) contractility tended to deteriorate over time with placebo, whereas LV contractility improved and RV contractility tended to be stabilized with istaroxime. Greater increases in both LV Ees and RV Ees were observed with istaroxime versus placebo from baseline to 48 h. Conclusions: In patients with ADHF-pre-CS, istaroxime at doses up to 1.0 μg/kg/min for up to 60 h was associated with sustained improvements in measures of LV performance (API and LVSWI), in parallel with increase in PA compliance and reduction in PA elastance at 48 h. As compared with placebo, istaroxime improved LV contractility and preserved RV contractility, which deteriorated on placebo, over time.