Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease

Abstract

Although the genetic origins underpinning congenital heart disease (CHD) have been extensively studied, genes, by themselves, do not entirely predict phenotypes, which result from the complex interplay between genes and the environment. Consequently, genes merely suggest the potential occurrence of a specific phenotype, but they cannot predict what will happen in reality. This task can be revealed by metabolomics, the most promising of the “omics sciences”. Though metabolomics applied to CHD is still in its infant phase, it has already been applied to CHD prenatal diagnosis, as well as to predict outcomes after cardiac surgery. Particular metabolomic fingerprints have been identified for some of the specific CHD subtypes. The hallmarks of CHD-related pulmonary arterial hypertension have also been discovered. This review, which is presented in a narrative format, due to the heterogeneity of the selected papers, aims to provide the readers with a synopsis of the literature on metabolomics in the CHD setting.

A Noninvasive Circulating Signature of Combined Right Ventricular Pressure and Volume Overload in Tetralogy of Fallot/Pulmonary Atresia/Major Aortopulmonary Collateral Arteries

“…To our knowledge, no normative plasma proteomic data exist in children and minimal data exist in other forms of congenital heart disease and few have used the state-of-the-art discovery MS profiling over 1,000 proteins as we have. 16,18,25 The longitudinal follow-up of these patients is another strength of this study and attempts to overcome some of the challenges inherent to the small sample size and lack of controls. The patient population most similar to our study was evaluated by Xuan et al They profiled the plasma proteome in children with TOF preoperatively with age-matched controls.…”

“…8–14 Circulating proteins of ventricular stretch, cardiac remodeling, oxidative stress, and inflammation are showing promise in guiding heart failure therapy in adult ischemic heart disease. 15 There are emerging data on circulating biomarkers to understand the mechanisms of heart failure in children with congenital heart disease including metabolic profiling to identify ventricular remodeling in aortic valve abnormalities, 16 defects in amino acid metabolism in Fontan circulation implicating altered energy metabolism 17 and altered extracellular matrix (ECM) proteins in interstage infants with single ventricle heart disease. 18 We investigated circulating biomarkers of the systemic response characterizing the transition from early RV pressure overload to late RV pressure and volume overload with chronic diastolic dysfunction in children with TOF/PA/MAPCAs which could be used in conjunction with imaging to determine the optimal timing for surgical intervention.…”

Idiopathic Pulmonary Arterial Hypertension in Paediatrics Represents Still a Serious Challenge: A Case Series Study

“…Overall, notwithstanding the progress in medical therapy, IPAH continues to represent a serious challenge, particularly in the paediatric population, with the need for lung transplantation and significant mortality in a relatively short time. However, metabolomics, a recent technique, could be of hope, which reveals the complex cascade of metabolic reactions underpinning a number of pathologies including PH/PAH [ 37 ]. In the meantime, due to the rarity of the disease, multicentre studies trying to enroll as many patients as possible are needed to shed light on its still obscure characteristics [ 38 ].…”

Potential Impact of a Pregnant Woman’s Microbiota on the Development of Fetal Heart Defects: A Review of the Literature

“…Following previous discussions on the influence of maternal microflora on the development of fetal heart defects, it is worth highlighting new findings in the field of metabolomics. The research described in the article ‘Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease’ [ 35 ] sheds light on the complex metabolic interactions that may be key to understanding this phenomenon.…”