Abstract 4365011: Safety and Efficacy of Istaroxime in Acute Heart Failure Related Pre-Cardiogenic Shock: An Updated Systematic Review and Meta Analysis of Randomized Controlled Trials

Background: Acute heart failure (AHF) with pre-cardiogenic shock carries substantial morbidity and mortality. Istaroxime, a novel intravenous inotrope that enhances both cardiomyocyte contractility and relaxation without adrenergic overstimulation, has demonstrated favourable haemodynamic and echocardiographic effects in early randomized trials. We sought to update the evidence including the newly reported SEISMiC trial to better define istaroxime’s role in AHF pre-cardiogenic shock. Methods: We performed a systematic search of PubMed, Web of Science, SCOPUS, and the Cochrane Library for RCTs comparing istaroxime versus placebo in adult hospitalized AHF patients with pre-cardiogenic shock (SBP <90 mmHg without hypoperfusion or persistent hypotension 70–100 mmHg for ≥2 h). Data were extracted independently by two reviewers. Continuous endpoints (e.g., SBP change) were pooled using random effects inverse variance meta analysis and reported as mean differences (MD) with 95% confidence intervals (CI); dichotomous outcomes used risk ratios (RR). Heterogeneity was assessed with I 2 . Results: Five studies comprising 360 patients were identified. For change in systolic blood pressure at 24 h, pooled MD was +5.4 mmHg (95% CI 2.6, 8.3; p <0.001; I 2 = 0%), favouring istaroxime. Heart rate decreased by −3.1 bpm (95% CI −5.2, −0.9; p = 0.005; I 2 = 0%). Stroke volume index improved (MD +3.0 mL/m 2 ; 95% CI 2.4, 3.6; p <0.0001; I 2 = 0%). In the SEISMiC trial, istaroxime (1.0–1.5 µg/kg/min) significantly increased SBP area-under-the-curve at 6 h (difference +22.2 mmHg; p = 0.017) and 24 h (difference +82.5 mmHg; p = 0.025) without excess serious adverse events. No significant increase in arrhythmias or myocardial injury markers was observed (RR for worsening HF events 1.2; 95% CI 0.7, 2.1; p = 0.45; I 2 = 5%). Conclusions: Istaroxime demonstrates consistent, clinically meaningful improvements in blood pressure, cardiac output, and diastolic function with a favourable safety profile in AHF pre-cardiogenic shock. The inclusion of the SEISMiC trial strengthens the evidence base, supporting further large scale Phase III investigations.