Sacubitril/ valsartan in patients with congenital heart disease: a systematic review and meta-analysis

Abstract Introduction Heart failure (HF) is a one of the main complications among patients with congenital heart disease (CHD), leading to significant morbidity and mortality. While the efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNi) in the general HF population is well-documented, data specific to the CHD cohort remain limited. Purpose To comprehensively assess the efficacy of ARNi in this unique patient population, we conducted a meta-analysis synthesizing available evidence on ARNi use in patients with CHD. Methods Following PRISMA guidelines, we systematically explored PubMed, SCOPUS, and Cochrane databases up to November 30, 2024. We gathered data on N-terminal pro b-type natriuretic peptide (NT-proBNP) pre and post the administration of sacubitril/ valsartan, New York Heart Association (NYHA) class improvement and death/ transplantation during follow up in the total cohort. Regarding systemic RV, fractional area change (FAC), global longitutinal strain (GLS) of the systematic RV and subpulmonic left ventricle (LV), 6-minute walking distance (6MWD) and maximal oxygen consumption (VO2) pre and post the administration of sacubitril/ valsartan were collected. Results This meta-analysis comprised 10 studies including 444 patients with CHD (mean age was 25.7 ± 18.3 years, 32.6% males) and 158 with systematic RV, who were administered sacubitril/ valsartan. During a mean follow up period of 11.9 ± 8 months, at least one grade of NYHA improvement was reported in 30% (95% CI: 0.14-0.49, I2=84.2%) of the patients with a parallel significant decrease in NT-proBNP levels with a Standardized Mean Difference (SMD) of -0.67 (95% CI -1.00, -0.33, I²=55.2%) (Figure 1). Mortality or need for transplantation was observed in 6% of the patients. In patients with systematic RV, sacubitril/ valsartan administration led to a significant NT-proBNP reduction (SMD -0.64, 95% CI: -1.04, -0.24, I2=52.9%) (Figure 2). Functional capacity of these patients was also improved, with at least one grade of NYHA improvement being reported in 27% (95% CI: 0.11-0.47, I2=78.4%) of the patients and a significantly increase in 6MWD (SMD 1.02, 95% CI: 0.20, 1.83, I2=85.4%) No significant difference was demonstrated in VO2 measurements (SMD -0.21, 95% CI: -0.54, 0.12, I2=0.0%). Echocardiographic parameters were also significantly improved, FAC (SMD 0.52, 95% CI: 0.09, 0.96, I2=65.1%), GLS of systematic RV (SMD 1.22, 95% CI: 0.30, 2.15, I2=89.1%) and GLS of subpulmonary LV (SMD 0.47, 95% CI: 0.01, 0.93, I2=63.8%). Conclusion ARNIs seem to have a beneficial impact in patients with CHD and HF, particularly those with a systemic RV. ARNIs in intention to treat cohorts improved functional capacity, NT-proBNP levels and echocardiographic parameters. Further controlled studies of ARNIs on CHD patients are clearly warranted.