Heart-mind interactions in advanced heart failure treated with intermittent levosimendan
R Fernandes Da Silva, R Louro, P Correia, R Viana, M Paralta De Figueiredo, A Raquel Clerigo, A Batista, P Ameixa, D Veladas, S Alexandrino, T Grenho, K Congo, B Picarra, R Rocha, M TrincaAbstract
Background
Intermittent levosimendan is increasingly used in patients with advanced heart failure to improve symptoms and reduce recurrent decompensations. Although its hemodynamic and biomarker effects are well established, little is known about its impact on psychological well-being and its relationship with biological response and clinical outcomes.
Purpose
To evaluate psychological, echocardiographic and biomarker responses to levosimendan in patients with advanced heart failure, and to explore the association between mental health improvement, biological response and adverse heart failure–related outcomes.
Methods
We conducted a study in patients with advanced heart failure treated with levosimendan, predominantly administered as destination therapy. Longitudinal changes in the Hospital Anxiety and Depression Scale (HADS), including depressive (HADS-D) and anxiety (HADS-A) subscales, as well as echocardiographic parameters and laboratory biomarkers were evaluated. Assessments were performed prior to levosimendan initiation and at the latest available follow-up in patients receiving ongoing or completed levosimendan therapy. A composite outcome of heart failure hospitalization and all-cause mortality was assessed. Group comparisons and correlation analyses were performed using non-parametric methods.
Results
Thirty-three patients were included (mean age 69.7 ± 14.6 years; 45.5% ischemic etiology). Levosimendan was associated with significant psychological improvement, with depressive symptoms decreasing by 2.4 points (p = 0.005), anxiety symptoms by 2.7 points (p = 0.020) and total HADS score by 5.1 points (p = 0.001). Left ventricular ejection fraction increased by 3.8%, and NT-proBNP decreased by 2179 pg/mL. Improvement in depressive symptoms correlated positively with improvement in systolic function (Spearman ρ = 0.603, p = 0.038). Median follow-up was 279 days (IQR 148–532). During follow-up, 13 of 32 patients (40.6%) experienced the composite outcome. Patients free from adverse events showed a median NT-proBNP reduction of 1372 pg/mL, along with a parallel trend toward greater improvement in LVEF, whereas those with events exhibited a median increase of 1440 pg/mL (p = 0.025).
Conclusions
In this cohort of patients with advanced heart failure, intermittent levosimendan was associated with clinically meaningful improvements in psychological well-being alongside favorable biological responses. The observed association between improvement in depressive symptoms and recovery of left ventricular systolic function highlights a potential heart–mind interaction in levosimendan response and supports the relevance of psychological assessment in the management of advanced heart failure.