Association between NT-proBNP changes and clinical outcomes in paediatric patients with heart failure: Insights from PANORAMA-HF and PARADIGM-HF

Robert Shaddy; Jianjian Gong; Tania Garito; Susan Solar-Yohay; Sijia Zhang; Margaret F Prescott; Damien Bonnet; Paul F Kantor; Michael Burch; Chad Mao; Antoinette Cilliers; Charles Canter; Yuk Law; Giorgia Grutter; Jou Kou Wang; Aamir Jeewa; Joseph Rossano; PANORAMA‐HF investigators

doi:10.1002/ehf2.15326

Association between NT-proBNP changes and clinical outcomes in paediatric patients with heart failure: Insights from PANORAMA-HF and PARADIGM-HF

ESC Heart Fail. 2025 May 12. doi: 10.1002/ehf2.15326. Online ahead of print.

Authors

Robert Shaddy¹, Jianjian Gong², Tania Garito³, Susan Solar-Yohay², Sijia Zhang⁴, Margaret F Prescott², Damien Bonnet⁵, Paul F Kantor¹, Michael Burch⁶, Chad Mao⁷, Antoinette Cilliers⁸, Charles Canter⁹, Yuk Law¹⁰, Giorgia Grutter¹¹, Jou Kou Wang¹², Aamir Jeewa¹³, Joseph Rossano¹⁴; PANORAMA‐HF investigators

Affiliations

¹ Children's Hospital Los Angeles and the Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
² Novartis Pharmaceuticals, East Hanover, New Jersey, USA.
³ Novartis Pharma AG, Basel, Switzerland.
⁴ Novartis Pharma, Shanghai, China.
⁵ M3C-Necker, Congenital and Paediatric Cardiology Department, Hospital Necker-Enfants Malades, University of Paris Cité, Paris, France.
⁶ Great Ormond Street Hospital for Children, London, UK.
⁷ Children's Healthcare of Atlanta and Emory University, Atlanta, Georgia, USA.
⁸ Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa.
⁹ Washington University School of Medicine, St Louis, Missouri, USA.
¹⁰ Seattle Childrens Hospital, Seattle, Washington, USA.
¹¹ IRCCS Bambino Gesu Children Hospital, Rome, Italy.
¹² National Taiwan University Hospital, Taipei City, Taiwan.
¹³ The Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁴ Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania, USA.

PMID: 40353367
DOI: 10.1002/ehf2.15326

Abstract

Aims: 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.

Methods and results: 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.

Conclusions: 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.

Keywords: Left ventricular systolic dysfunction; NT‐proBNP; Paediatric heart failure; Sacubitril/valsartan.

Grants and funding

Novartis Pharma AG, Basel, Switzerland