Currently, 90% of patients with congenital heart disease survive into adulthood. In this population, heart failure (HF) represents a major cause of morbi-mortality, and patients with a systemic right ventricle (SRV) or a single ventricle (SV) are particularly at risk. Sacubitril/Valsartan is an established therapy for heart failure in adults; however, data regarding its use in congenital cardiology remain limited.

This prospective, multicenter, observational study conducted over 12 months, aimed to evaluate efficacy and safety of Sacubitril/Valsartan in patients with a SRV or a SV dysfunction (systemic ventricular ejection fraction ≤ 40%) and New York Heart Association (NYHA) class II–III despite optimal HF therapy. The primary endpoint was the comparison of maximal oxygen uptake (peak VO ₂ ) before initiation and after 12 months of treatment.

A total of 50 patients were included, 33 men (71.7%), 41.3 ± 9.6years. Hence, 43 patients (86%) had a SRV, including 32(64%) D-transposition of the great arteries and 11 (22%) congenitally corrected transposition of the great arteries. Among the 7 patients (14%) with a SV, 4 (8%) had a left ventricle. After 12 months of treatment at the maximum tolerated dose, no improvement in peak VO ₂ was observed: 17.3 mL/kg/min [14–21.6] vs 17.5 mL/kg/min [14.4–21.8] ( P = 0.656). However, improvement was noticed in NYHA class (2.19 ± 0.6 vs 1.72 ± 0.6; P ≤ 0.001), NT-proBNP (998 pg/mL [451–1751] vs 639 pg/mL [365.5–1174.5]; P = 0.002), right ventricular fractional area change (27.71 ± 6.9% vs 31.6 ± 6.9%; P ≤ 0.001), and tricuspid regurgitation grade (2.13 ± 0.9 vs 1.70 ± 0.7; P ≤ 0.001). Sacubitril/Valsartan was discontinued in 1 (2%) patient due to symptomatic arterial hypotension. In the remaining patients, the treatment led to a decrease in blood pressure (BP) without clinical consequences (119 ± 13.3 mmHg vs 107.1 ± 12.7 mmHg systolic BP; P ≤ 0.001 and 71.1 ± 10 mmHg vs 65.1 ± 8.7 mmHg diastolic BP; P ≤ 0.001). The increase in serum creatinine (80 μmol/L [71.6–88 vs 87 μmol/L [76–92]; P = 0.016) did not compromise continuation of therapy. No predictive factors of treatment response were identified.

This first prospective study did not demonstrate an improvement in peak VO ₂ with Sacubitril/Valsartan in heart failure patients with a SRV or SV. However, due to improvements in NYHA class, NT-proBNP levels, echocardiographic parameters, along with good treatment tolerability, further studies are needed in this specific issue.