Intermittent Levosimendan Administration for Advanced Heart Failure Treatment in Adults with Congenital Heart Disease

Background: Heart failure (HF) is a major cause of morbidity in adults with congenital heart disease (ACHD), who may also have limited access to transplant. Intermittent levosimendan has shown benefit in advanced HF due to acquired heart disease, but currently there are no data in ACHD. Methods: We conducted a retrospective analysis of ACHD patients aged >18 years with advanced HF who received ≥3 intermittent levosimendan infusions between March 2020 and January 2026 at a tertiary ACHD centre. Clinical outcomes during follow-up were compared with those in the year preceding treatment. Primary endpoints included safety and HF-related adverse events, particularly HF hospitalizations. Secondary endpoints included changes in New York Heart Association (NYHA) class, NT-proBNP levels, and ventricular systolic function assessed by echocardiography. Results: Twelve patients (median age 44.6 years, 25% female) were included, with heterogeneous congenital diagnoses and advanced HF. Five patients had a systemic right ventricle (sRV) and one had a single ventricle with previous Fontan palliation. During a median follow-up of 1.3 years, intermittent levosimendan was generally well tolerated, with no treatment-limiting adverse events. HF hospitalization incidence significantly decreased from 0.83 events/person-year before treatment to 0.20 events/person-year during follow-up (p=0.03). NYHA functional class improved significantly (p=0.005). While no significant changes were observed in NT-proBNP or left ventricular ejection fraction, patients with an sRV demonstrated a significant improvement in right ventricular fractional area change (27±7.4% to 30.6±7%, p=0.02). Two deaths occurred, consistent with the severity of underlying disease and not directly attributable to levosimendan. Conclusions: In this real-world cohort of ACHD patients with advanced HF, intermittent levosimendan administration was safe and associated with improved symptoms, reduced HF hospitalizations, and enhanced systemic right ventricular function. These findings support the potential role of intermittent levosimendan as a therapeutic option in selected ACHD patients and underscore the need for prospective, adequately powered studies to confirm efficacy and define optimal patient selection.