Guideline-Directed Medical Therapy and Clinical Outcomes in Adults with Fontan Palliation and Systemic Ventricular Systolic Dysfunction.

BACKGROUND: The role of guideline-directed medical therapy (GDMT) in adults with Fontan palliation and systemic ventricular (SV) systolic dysfunction remains uncertain. OBJECTIVES: To evaluate the association between GDMT intensity and clinical outcomes, and to assess the impact of GDMT uptitration on SV systolic function and congestion. METHODS: We conducted a retrospective cohort study of adults (≥18 years) with Fontan palliation and SV systolic dysfunction (SV ejection fraction <50%) (2003-2024). GDMT intensity was quantified using a standardized GDMT score. Outcomes were all-cause mortality and cardiovascular adverse events (composite hospitalization, transplantation, or death). Changes in SV systolic function and NT-proBNP were evaluated in patients with serial follow-up. GDMT uptitration was defined as increase in GDMT score between baseline and 1-year encounter. RESULTS: Among 182 patients (age 27±9 years, 61% male), mean GDMT score was 1.71±1.53. Overall, 24% died and 47% experienced cardiovascular events. Higher GDMT score was independently associated with lower mortality (HR 0.68, 95%CI 0.40-0.89, p=0.001) and fewer cardiovascular events (HR 0.74, 95%CI 0.53-0.95, p=0.02). These associations were consistent across subgroups. Among patients with follow-up data, GDMT uptitration was associated with greater improvement in SV ejection fraction (+14% vs +3%, p=0.01), longitudinal strain (+19% vs +9%, p=0.007), and NT-proBNP (-28% vs -15%, p=0.009). CONCLUSIONS: In adults with Fontan circulation and SV systolic dysfunction, higher GDMT intensity is associated with improved survival and reduced cardiovascular events. GDMT uptitration is associated with improved ventricular function and reduced congestion, suggesting a potential role for optimized medical therapy in this high-risk population.