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

Background and Objective: 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 administration has shown benefit in advanced HF due to acquired heart disease, but currently, there are no data on ACHD. We aimed to evaluate the effects of this treatment in ACHD patients with advanced heart failure, focusing on both clinical status and objective outcome measures. Materials and Methods: We conducted a single-center retrospective analysis of ACHD patients aged >18 years with advanced HF who received ≥ three intermittent levosimendan infusions (either 12.5 mg once monthly or 6.25 mg every two weeks over a 6 h infusion) between March 2020 and January 2025 at a tertiary ACHD center. 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-pro-B-natriuretic peptide (nt-proBNP) values, 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 well-tolerated, with no treatment-limiting adverse events. Two patients (16%) required hospitalization for HF during follow-up compared with 8 (66%) in the year preceding treatment. The incidence of HF hospitalizations decreased from 0.83 to 0.20 events per person-year during follow-up (p = 0.03), although findings should be interpreted cautiously given the small sample size and retrospective design. NYHA functional class improved significantly (p = 0.005). While no significant changes were observed in NT-proBNP or left ventricular ejection fraction, patients with a systemic right ventricle (sRV) showed an increase in right ventricular fractional area change (27 ± 7.4% to 30.6 ± 7%, p = 0.02); however, this observation should be regarded as exploratory given the limited sample size. Two deaths occurred, consistent with the severity of the underlying disease and not directly attributable to levosimendan and the Fontan patient received a successful heart and liver transplant. Conclusions: In a small, real-world cohort of ACHD and advanced HF, intermittent levosimendan administration was safe and associated with improved symptoms, reduced HF hospitalizations, and signals of enhanced systemic right ventricular function. These hypothesis-generating findings may help inform future multicenter studies in ACHD patients with advanced HF, suggesting a potential role for intermittent levosimendan in selected patients, while highlighting the need for prospective, adequately powered studies to confirm its efficacy and better define optimal patient selection.