Trend of echocardiographic parameters, ventricular-arterial coupling and biomarkers in advanced heart failure outpatients undergoing intermittent therapy with levosimendan
G Togni, L Fazzini, O Zucchetti, G Reijans, L Guida, M Lampus, R Pugliese, I Moretti, S D'isa, L Di Odoardo, E Sciatti, M Gori, M Senni, E D'eliaAbstract
Background
Despite major advances in heart failure (HF) therapy, a subset of patients progresses to advanced HF (advHF). Levosimendan, a calcium-sensitizing inodilator with cardioprotective properties, is used as intermittent intravenous therapy to prevent decompensation, reduce hospitalizations and improve functional status. Yet, data on its long-term efficacy are limited.
Purpose
To evaluate short- and long-term changes in echocardiographic parameters, ventricular–arterial coupling (VAC), and biomarkers in advHF outpatients treated with intermittent levosimendan, comparing levosimendan-naïve patients with those on long-term levosimendan therapy.
Methods
Single-center, prospective, observational study conducted between May 2024 and September 2025. AdvHF patients received levosimendan every 3–4 weeks (0.05–0.2 μg/kg/min, 12.5 mg over 48 h, no bolus). Evaluations were performed at baseline (T0), 48 h (T48), and 21 days (T1). Levosimendan-naïve patients (≤3 cycles at enrollment) underwent additional follow-up at a median of 12 months. Left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LVGLS), stroke volume (SV), natriuretic peptides (BNP, NT-proBNP), sST2, and VAC (Ea/Ees, single-beat Chen method) were assessed. Paired Wilcoxon tests were used.
Results
Twenty-seven patients were included (median age 69 years, 74% male, median LVEF 30%). Sixteen patients were levosimendan-naïve and eleven were on chronic intermittent therapy with levosimedan for more than 1 year. LVEF showed a transient increase at 48 h in both groups, returning towards baseline by day 21 (p<0.02 for T0–T48) (Figure 1). LVGLS and SV did not change significantly. VAC showed a borderline improvement at 48 h only in naïve patients, with rebound at day 21. In the long-term treatment group, NT-proBNP decreased significantly at 48 h with partial rebound at day 21 (p<0.01). In naïve patients, BNP decreased at 48 h and rebounded by day 21, while NT-proBNP remained unchanged (Figure 2). sST2 was stable in all analyses. At long-term follow-up in naïve patients, significant reductions in NT-proBNP (2559→1085 pg/mL, p=0.0137) and BNP (406→306 pg/mL, p=0.0178) were observed, along with a significant increase in LVEF (30%→34%, p=0.0243). VAC and SV showed a non-significant improving trend.
Conclusion
In advHF outpatients, intermittent levosimendan therapy is associated with favorable short-term haemodynamic and biomarker responses, more evident in levosimendan-naïve patients. In this subgroup, therapeutic benefits appear to persist over time, with sustained improvements in LVEF and natriuretic peptides, supporting the role of intermittent levosimendan as an effective strategy in selected advHF patients.Figure 1.Trend of LVEF and SV.For image description, please refer to the figure legend and surrounding text.Figure 2.Trend of Biomarkers.For image description, please refer to the figure legend and surrounding text.