Transforming pediatric heart failure: Efficacy of low-dose sacubitril/valsartan

Aims: Pediatric heart failure is a significant cause of illness and death in children. We aimed to assess sacubitril/valsartan's effectiveness and find the proper dosage for pediatric patients. Methods: Patients unresponsive to traditional medicines for at least 12 months prescribed sacubitril/valsartan from January 2020 to March 2023 were reviewed. The initial dose was 0.2 mg/kg bid, gradually increasing in 0.1 mg/kg increments. The target dose was determined based on blood pressure fluctuations at 70/50 mmHg. Clinical efficacy and quantity-effect relationship were evaluated using echocardiography, NT-proBNP, and the concentration of valsartan, sacubitril, sacubitrilat. Results: A total of 23 pediatric patients with dilated cardiomyopathy and advanced heart failure were enrolled. Mean sacubitril/valsartan dose was 1.84 mg/kg/day. After 6 months, LVEF increased significantly (38.09% to 45% at 3 months, 52% at 6 months; p < 0.001). LV size reduced to 4.4 cm (IQR, 4.1-5.2) and 4.5 cm (IQR, 4-5.1) at 3 and 6 months, respectively, from 4.6 cm (IQR, 4.2-5.6) at baseline (both P < 0.05). NT-proBNP levels reduced by 5.7 at 3 months (p < 0.05) and 5.38 at 6 months (p < 0.001). Sacubitrilat is the active form of Sacubitril. The highest concentration of sacubitrilat was observed at approximately 1.6 mg/kg. The maintenance dose correlated positively with time (p < 0.001) and valsartan/sacubitril concentration (p < 0.05). Conclusion: Low dose sacubitril/valsartan is effective in children with heart failure, with dosage adjustments to avoid hypotension. Adjusted dosing can increase EF and reduce heart size, offering new possibilities for pediatric heart failure treatment.