Clinical and echocardiographic changes after intermittent levosimendan infusion in patients with advanced heart failure

Abstract Aims To evaluate the short-term clinical, structural, and functional cardiac changes following intermittent levosimendan infusion and their prognostic implications in patients with advanced heart failure (AdHF). Methods In this prospective, multicentre, observational study, patients with AdHF treated with intermittent levosimendan infusion (12.5 mg at a rate of 0.1 μg/kg/min, without a bolus) were enrolled. Clinical, laboratory, and comprehensive echocardiographic assessments were performed at baseline, 48 hours, and 30 days post-infusion. The primary endpoint was to evaluate the extent of clinical and cardiac structure and function changes during the first 30 days after levosimendan infusion. Secondary outcome of interest was the association of cardiac changes and a composite endpoint of decompensated HF, urgent HF rehospitalization, cardiogenic shock, cardiac arrest and cardiovascular death at 6 months. Results A total of 37 patients with AdHF were included (mean age 71.1 + 9.0 years; 59.5% male). A non-significant trend reduction in mean arterial pressure values was observed over time (81.3 + 9.5 mmHg vs. 80.9 + 7.7 mmHg after 48 hours vs. 79.1 + 6.9 mmHg at 30 days, p-value for trend = 0.079). NT-proBNP levels significantly decreased at 48 hours and rose again by 30 days [from 1802 (1127–4436) ng/L to 1060 (830–3864) ng/L at 48 hours and 1661 (1015–4245) ng/L at 30 days, p-value for trend = 0.006). The main left ventricular (LV) and right ventricular (RV) structure and function parameters improved at 48 hours but returned to baseline or a slight improvement by 30 days (LV ejection fraction: 30.9 + 11.3% vs. 32.2 + 11.2%, vs. 30.9 + 11.3%, p-value for trend = 0.001; LV global longitudinal strain: -8.0 + 3.5% vs. -9.2 + 3.5% vs. -8.0 + 3.3%, p-value for trend 0.001; tricuspid annular plane systolic excursion: 16.9 + 3.1 mm vs. 17.7 + 3.4 vs. 17.0 + 3.5, p-value for trend 0.007; systolic pulmonary artery pressure: 48.7 + 15.8 mmHg vs. 41.6 + 12.7 mmHg vs. 46.1 + 15.0, p-value for trend 0.001). Overall, 17 (45.9%) patients experienced CV events. After accounting for confounders, ΔLV global longitudinal strain (GLS) after 48h (adjusted odds ratio (OR) 0.26, 95% confidence interval (CI) 0.10–0.67, p = 0.006) and ΔRV free wall longitudinal strain (FWLS) (adjusted OR 0.75, 95% CI 0.57–0.99, p = 0.041) were significantly associated with a lower risk of events. Conclusions In patients with AdHF, intermittent levosimendan infusion resulted in early improvements in NT-proBNP levels and biventricular function, which tended to wane by 30 days. Early enhancements in LV-GLS and RV-FWLS were independently associated with better clinical outcomes, suggesting their potential role as markers to guide patient selection and therapeutic response.