Cardiac Transcriptome Remodeling and Impaired Bioenergetics in Single-Ventricle Congenital Heart Disease

JACC Basic Transl Sci. 2023 Jan 11;8(3):258-279. doi: 10.1016/j.jacbts.2022.09.013. eCollection 2023 Mar.


The mechanisms responsible for heart failure in single-ventricle congenital heart disease are unknown. Using explanted heart tissue, we showed that failing single-ventricle hearts have dysregulated metabolic pathways, impaired mitochondrial function, decreased activity of carnitine palmitoyltransferase activity, and altered functioning of the tricarboxylic acid cycle. Interestingly, nonfailing single-ventricle hearts demonstrated an intermediate metabolic phenotype suggesting that they are vulnerable to development of heart failure in the future. Mitochondrial targeted therapies and treatments aimed at normalizing energy generation could represent a novel approach to the treatment or prevention of heart failure in this vulnerable group of patients.

Keywords: cardiac metabolism; cardiometabolic remodeling; heart failure; hypoplastic left heart syndrome; mitochondria; oxidative phosphorylation; single ventricle.