Investigating the use of novel and established cardiac biomarkers in conjunction with enhanced imaging modalities to improve early diagnosis and monitoring of heart failure in children with congenital heart disease and cardiomyopathy

Abstract

Introduction
Paediatric heart failure is a common clinical syndrome that may be experienced by children with congenital heart disease (CHD) and/or cardiomyopathy. It is characterised by clinical signs/symptoms which reflect the underlying pathophysiology based on one of three main clinical states: pulmonary over-circulation, pressure overload, and ventricular failure. Current diagnosis relies on clinical assessment and echocardiogram imaging as cardiac biomarkers have been predominantly scientific to date. As there is significant mortality and morbidity associated with paediatric heart failure, it is important to identify and manage heart failure symptoms early in children with CHD and cardiomyopathy. This prospective cohort study aimed to recruit children with congenital heart disease or cardiomyopathy at risk of heart failure. The primary aim was to determine if circulating blood biomarkers can be used to diagnose and/or monitor heart failure in children. It also compared the blood biomarkers to clinical assessment tools for heart failure, imaging on echocardiogram and MRI, and activity measurements.

Methods
Children and young people with a diagnosis of single ventricle physiology, cardiomyopathy or left to right shunt physiology were approached by the study team if they were receiving routine clinical care in the cardiology department of Royal Belfast Hospital for Sick Children between March 2022 and December 2023. Once recruited to the study, all were offered appointments to undergo detailed echocardiogram imaging, blood sampling and clinical assessment. Children with single ventricle physiology were also invited to partake in exercise testing and MRI scanning. The research fellow performed a Modified Ross score on all participants at each study appointment. Blood samples were obtained by the research fellow and stored in WWIEM laboratory for ELISA analysis which was later performed by the research fellow for sST2 and Tetranectin. Blood samples were also processed by BHSCT for NT-proBNP and Troponin T. All echocardiograms were performed by one of three senior cardiac clinical physiologists, and the imaging was analysed offline by the research fellow and a supervising paediatric cardiology consultant. The MRI examinations were supervised and analysed by a paediatric cardiology consultant. Exercise testing was performed by the research fellow and a senior cardiac clinical physiologist. All data was stored anonymously by the research fellow in an encrypted spreadsheet and analysed once all study activities had been completed.

Results
105 children were recruited to the study between 29/03/2022 and 07/12/2023. Study follow up continued until the participant had a third study appointment, or up to, and including 19/06/2024, depending on which was later. There were 63 participants with single ventricle physiology, 21 participants with left to right shunts and 21 participants with cardiomyopathy. Overall, there were few participants in the single ventricle and cardiomyopathy subgroups with clinical evidence of heart failure. There was more evidence of clinical heart failure in the left to right shunt group, but this group was limited by low numbers and poor attendance at follow up study appointments.
There was no single echocardiographic or biomarker variable which consistently added diagnostic or prognostic benefit in all study participants. However, the Modified Ross score appears to have a significant role in heart failure status assessment in all three of the subgroups.

Conclusion
This study found that most children recruited had minimal signs and symptoms of heart failure which limited its ability to identify or monitor heart failure using biomarkers and enhanced imaging modalities. It did demonstrate the usefulness of the Modified Ross score in all three patient subgroups as it reflected participants’ heart failure status throughout. It consistently correlated with imaging, biochemical and demographic data that reflect ventricular function and signs and symptoms of heart failure. There may be a role for the Modified Ross score in monitoring all children with CHD and cardiomyopathy at risk of heart failure. Further work should focus on monitoring this group of patients at risk of paediatric heart failure, from birth to adulthood, to truly understand the role of biomarkers and imaging in identifying and monitoring heart failure.

Date of Award	Dec 2026
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Royal Belfast Hospital for Sick Children’s
Supervisor	Chris Watson (Supervisor) & Frank Casey (Supervisor)