Shaddy Robert, Gong Jianjian, Garito Tania, Solar-Yohay Susan, Zhang Sijia, Prescott Margaret F, Bonnet Damien, Kantor Paul F, Burch Michael, Mao Chad, Cilliers Antoinette, Canter Charles, Law Yuk, Grutter Giorgia, Wang Jou Kou, Jeewa Aamir, Rossano Joseph
Children's Hospital Los Angeles and the Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Novartis Pharmaceuticals, East Hanover, New Jersey, USA.
ESC Heart Fail. 2025 Aug;12(4):3042-3052. doi: 10.1002/ehf2.15326. Epub 2025 May 12.
The PANORAMA-HF trial demonstrated significant N-terminal pro-B-type natriuretic peptide (NT-proBNP) reductions in paediatric patients with left ventricular systolic dysfunction with sacubitril/valsartan or enalapril treatment over 52 weeks. This post hoc analysis aims to correlate changes in NT-proBNP levels with clinical outcomes in PANORAMA-HF patients receiving either sacubitril/valsartan or enalapril. Additionally, NT-proBNP reductions in the paediatric population were compared with a subset of adult heart failure with reduced ejection fraction (HFrEF) patients from the PARADIGM-HF trial.
This post hoc analysis utilized data from Part 2 of the PANORAMA-HF trial. Associations between baseline NT-proBNP levels, changes post-baseline and the risk of HF clinical events in paediatric patients on sacubitril/valsartan or enalapril were assessed. The paediatric HF population from PANORAMA-HF was categorized into age groups (AG): AG1 (aged 6 to <18 years), AG2a (aged 2 to <6 years) and AG3a (aged 1 month to <2 years). The Cox proportional hazard model evaluated the relationship between NT-proBNP and clinical outcomes. Analysis of 361 paediatric patients (sacubitril/valsartan, n = 179; enalapril, n = 182) demonstrated overall higher baseline NT-proBNP levels in younger AGs. At Week 52, both treatment groups exhibited reduced NT-proBNP levels across all AGs. Reductions were comparable between sacubitril/valsartan and enalapril, with a numerically greater reduction observed in adult patients versus children. Strong associations between NT-proBNP levels and HF clinical outcomes were observed in paediatric populations in PANORAMA-HF and in adult DCM patients with HFrEF in PARADIGM-HF. Doubling of NT-proBNP levels was associated with a ≥1.7-fold increased risk of HF clinical events, while halving of the levels correlated with a 52% reduction in the risk of clinical events.
This is the first prospective, randomized large-scale study to demonstrate a strong correlation between NT-proBNP levels and risks of HF clinical events in paediatric patients with HF.
PANORAMA-HF试验表明，在接受沙库巴曲缬沙坦或依那普利治疗52周的左心室收缩功能障碍儿科患者中，N末端B型利钠肽原（NT-proBNP）显著降低。这项事后分析旨在将NT-proBNP水平的变化与接受沙库巴曲缬沙坦或依那普利治疗的PANORAMA-HF患者的临床结局相关联。此外，还将儿科人群中NT-proBNP的降低情况与PARADIGM-HF试验中射血分数降低的成人心力衰竭（HFrEF）患者亚组进行了比较。
这项事后分析利用了PANORAMA-HF试验第2部分的数据。评估了基线NT-proBNP水平、基线后变化与接受沙库巴曲缬沙坦或依那普利治疗的儿科患者发生心力衰竭临床事件风险之间的关联。将PANORAMA-HF试验中的儿科心力衰竭人群分为年龄组（AG）：AG1（6至<18岁）、AG2a（2至<6岁）和AG3a（1个月至<2岁）。Cox比例风险模型评估了NT-proBNP与临床结局之间的关系。对361例儿科患者（沙库巴曲缬沙坦组，n = 179；依那普利组，n = 182）的分析表明，年龄较小的AG组患者基线NT-proBNP水平总体较高。在第52周时，两个治疗组在所有AG组中的NT-proBNP水平均有所降低。沙库巴曲缬沙坦组和依那普利组的降低幅度相当，成人患者的降低幅度在数值上大于儿童患者。在PANORAMA-HF试验的儿科人群以及PARADIGM-HF试验中患有HFrEF的成人扩张型心肌病（DCM）患者中，均观察到NT-proBNP水平与心力衰竭临床结局之间存在密切关联。NT-proBNP水平翻倍与心力衰竭临床事件风险增加≥1.7倍相关，而水平减半与临床事件风险降低52%相关。
这是第一项前瞻性、随机大规模研究，证明了NT-proBNP水平与儿科心力衰竭患者心力衰竭临床事件风险之间存在密切关联。
