Coronary Microvascular Dysfunction in Heart Failure
Coronary microvascular dysfunction, including endothelial dysfunction due to chronic oxidant stress, has emerged as a major therapeutic target in adult heart failure in ischemic heart disease. Emerging data suggests microvascular dysfunction may have its origin during childhood. The impact of cyanosis and vascular shear stress seen in congenital heart disease (CHD) on coronary microvascular function and its role in the development of pediatric heart failure is unknown. We sought to elucidate the mechanisms underlying microvascular dysfunction in children with the most severe forms of CHD, and develop novel therapies for treatment and prevention using state-of-the-art 3D vascular imaging and primary patient cardiac endothelial cells.
Oxidant stress damages endothelial mitochondrial and impairs mitophagy.
3D vascular imaging shows simplification of the coronary microvascular tree in children with Fontan failure.