Efficacy and safety of sacubitril/valsartan in pediatric heart failure: A prospective study

Abstract

Introduction

Pediatric heart failure is associated with significant morbidity and mortality and can be a source of major disability for the child and their family. Therapeutic options are limited, and managing this condition presents multiple challenges. Although the use of sacubitril/valsartan is well established in adults heart failure, its efficacy and safety in children remain uncertain. Its clinical effects and safety profile are not yet well established in the paediatric population.

Method

This prospective, observational, multicenter study included symptomatic children aged between 1 month and 18 years with systemic ventricular dysfunction (LVEF ≤ 45% or RF ≤ 22.5%) who were symptomatic (NYHA > = 2 or ROSS > = 2) from March 2024 to March 2025. Patients were assessed at baseline and 3 months after initiating sacubitril/valsartan. The primary endpoint was clinical improvement using the Global Rank End Point, which is a hierarchical composite clinical score. Secondary endpoints included NT-proBNP, quality of life (PGIS and Ped Q life), NYHA and Ross classifications, ultrasound parameters mainly LVEF and global longitudinal strain, and potential treatment-related side effects.

Results

A total of 20 patients were included. Mean age was 5.3 years (range: 1–15 years) 13 children (65%) were girls, 9 (45%) had primitive cardiomyopathy 8 (40%) had secondary cardiomyopathy (metabolic abnormality5%neuromuscular disease5% Dilated cardiomyopathy post myocarditis 20% ischemic heart disease 10%) and 3 (15%) had congenital heart disease. At 3 months follow up, the primary endpoint showed significant improvement: 65% (n = 13) progressed favorably (category 5) 10% (n = 2) remained stable (Category 4) 5% (n = 1) worsened (Category 3) 10% (n = 2) had poor progression (Category 2-A) 10% (n = 2) died from non-cardiac causes (Category1) (Table 1) Secondary endpoints also demonstrated statistically significant improvements in NT-proBNP (P = 0.00008) quality of life (P < 0.05) PedQ Life (P < 0.05) and echographic parameters: left ventricular, global longitudinal strain (P < 0.05) LVEF (P < 0.05) and NYHA and ROSS scores also improved significantly. The treatment was well tolerated, with 35% (n = 7) experiencing non-serious adverse effects (hyperkalemia hypotension nausea). No treatment discontinuations occurred.

Conclusion

These findings suggest that sacubtril/valsartan is well tolerated in pediatric heart failure and is associated with improvement in quality of life and left ventricular function and It may represent a promising therapeutic alternative for this population.