Myocardial and metabolic effects of intermittent levosimendan in advanced heart failure

Abstract Background Patients with advanced heart failure frequently remain symptomatic despite guideline-directed medical therapy. Levosimendan is often used as a supportive treatment in this setting, but its effects beyond short-term hemodynamic stabilization are not well characterized, particularly regarding myocardial remodeling and metabolic profile. Purpose To evaluate the multidimensional effects of intermittent levosimendan therapy on cardiac structure and function, biomarkers, renal function, and iron metabolism in patients with advanced heart failure, and to explore characteristics of patients showing meaningful ventricular remodeling. Methods We conducted a study in patients with advanced heart failure treated with levosimendan. Clinical, laboratory, and echocardiographic assessments were performed at baseline and at follow-up. Changes between baseline and follow-up were analyzed using paired parametric or non-parametric tests as appropriate. A responder phenotype was defined as an absolute increase in left ventricular ejection fraction of at least 5%. Results Twenty-six patients had paired echocardiographic data available. Median follow-up was 279 days (IQR 148–532). Levosimendan therapy was associated with a significant improvement in left ventricular ejection fraction (median 24.5% vs. 28.0%, p=0.005). A significant increase in transferrin saturation was observed (from 20.2% to 27.0%, p = 0.048), along with an improvement in renal function (p = 0.05). Right ventricular function, diastolic filling pressures, natriuretic peptides, and mitral regurgitation showed consistent favorable trends. Hemoglobin, ferritin, and CA-125 remained stable during therapy. Seven patients (27%) met criteria for ventricular remodeling responders. Responders showed greater improvement in transferrin saturation compared with non-responders, suggesting a potential metabolic component associated with myocardial recovery. Conclusion In patients with advanced heart failure, intermittent levosimendan therapy is associated with significant improvement in systolic function and iron metabolism, alongside consistent favorable trends across renal, diastolic, and structural parameters. These findings support a broader biological effect of levosimendan beyond transient hemodynamic support and support a link between myocardial remodeling and iron metabolism.