Insights and perspectives into clinical biomarker discovery in pediatric heart failure and congenital heart disease-a narrative review.

Abstract

Heart failure (HF) in the pediatric population is a multi-factorial process with a wide spectrum of etiologies and clinical manifestations, that are distinct from the adult HF population, with congenital heart disease (CHD) as the most common cause. CHD has high morbidity/mortality with nearly 60% developing HF during the first 12 months of life. Hence, early discovery and diagnosis of CHD in neonates is pivotal. Plasma B-type natriuretic peptide (BNP) is an increasingly popular clinical marker in pediatric HF, however, in contrast to adult HF, it is not yet included in pediatric HF guidelines and there is no standardized reference cut-off value. We explore the current trends and prospects of biomarkers in pediatric HF, including CHD that can aid in diagnosis and management. As a narrative review, we will analyze biomarkers with respect to diagnosis and monitoring in specific anatomical types of CHD in the pediatric population considering all English PubMed publications till June 2022. We present a concise description of our own experience in applying plasma BNP as a clinical biomarker in pediatric HF and CHD (tetralogy of fallot vs. ventricular septal defect) in the context of surgical correction, as well as untargeted metabolomics analyses. In the current age of Information Technology and large data sets we also explored new biomarker discovery using Text Mining of 33M manuscripts currently on PubMed. (Multi) Omics studies from patient samples as well as Data Mining can be considered for the discovery of potential pediatric HF biomarkers useful in clinical care. Future research should focus on validation and defining evidence-based value limits and reference ranges for specific indications using the most up-to-date assays in parallel to commonly used studies.