Chronic intermittent levosimendan infusion as destination therapy in advanced heart failure: a single center experience

Background

Patients with advanced heart failure (AHF) ineligible for heart transplantation or long-term left ventricular assist devices have poor prognosis and limited therapeutic options. Due to its prolonged metabolite activity, levosimendan is an attractive option for intermittent outpatient inotropic support.

Purpose

To assess clinical outcomes in AHF patients receiving intermittent levosimendan as destination therapy (DT) in a real-world population.

Methods

Consecutive AHF patients receiving intermittent levosimendan infusions (0.1 μg/kg/min every 4 weeks) as DT at a tertiary heart failure (HF) clinic between 2019-2024 were included. The primary outcome was 1-year all-cause death. Unplanned HF hospitalizations and ICD shocks and/or malignant arrhythmias during the year preceding and the year following levosimendan initiation were compared within each patient. Patients were stratified by MAGGIC score tertiles to compare predicted and observed mortality. Survival analyses were performed via KM estimates with log-rank testing. Predictors of 1-year mortality were assessed using Cox proportional hazards regression.

Results

37 AHF patients (age 75 ± 8 years, 78% male) were included. Median left ventricular ejection fraction (LVEF) was 22% (IQR 19–27), 29 patients (78.4%) were NYHA III-IV. Median MAGGIC score was 33 (IQR 28-37). The main etiology was ischemic cardiomyopathy (23 patients, 62.1%).

Median follow-up was 505 days (IQR 169–1048). Overall, 1-year mortality was 29.7%. Compared with the previous year, levosimendan was associated with a significant reduction in HF hospitalizations (81.1% vs 48.6% patients; total events 57 vs 24, p < 0.001), without differences in ICD shocks and/or malignant arrhythmias (8.1% vs 16.2% patients; total events 3 vs 7, p = 0.447). At 6-month echocardiographic follow-up, mitral regurgitation severity improved (moderate-severe: 91.9% vs 56.8%, p = 0.036). MAGGIC stratification showed lower-than-predicted mortality in low–intermediate MAGGIC score subgroups, while observed mortality exceeded predicted risk in the high-score tertile (log-rank 0.0276, Figure 1). Patients in the high MAGGIC score subgroup exhibited higher rates of HF hospitalization (≥3 HF hospitalization in the last year: 60% vs 14.8% patients, p = 0.040), more malignant ventricular arrhythmias (30% vs 0%, p = 0.022), higher diuretic requirements (total daily furosemide dose: 200 vs 52.5 mg, p = 0.040), lower LVEF (18.6 vs 24.6%, p = 0.010), and left ventricular end-diastolic volume (LVEDV 267.9 vs 205.4 mL, p = 0.011), compared with the low-intermediate subgroup. At multivariable Cox analysis, the high MAGGIC score subgroup independently predicted 1-year mortality (HR 4.21, 95% CI 1.20–14.8).

Conclusions

In patients with AHF, intermittent levosimendan was associated with fewer unplanned HF hospitalizations at 1 year. A high MAGGIC score identified subjects with limited survival benefit, highlighting the need for careful patient selection.MAGGIC observed vs predicted 1-yr deathFor image description, please refer to the figure legend and surrounding text.