Abstract
Congenital heart defects are the most common malformations in humans, affecting approximately
1% of newborn babies. While genetic causes of congenital heart disease have been studied,
only less than 20% of human cases are clearly linked to genetic anomalies. The cause
for the majority of the cases remains unknown. Heart formation is a finely orchestrated
developmental process and slight disruptions of it can lead to severe malformations.
Dysregulation of developmental processes leading to heart malformations are caused
by genetic anomalies but also environmental factors including blood flow. Intra-cardiac
blood flow dynamics plays a significant role regulating heart development and perturbations
of blood flow lead to congenital heart defects in animal models. Defects that result
from hemodynamic alterations recapitulate those observed in human babies, even those
due to genetic anomalies and toxic teratogen exposure. Because important cardiac developmental
events, such as valve formation and septation, occur under blood flow conditions while
the heart is pumping, blood flow regulation of cardiac formation might be a critical
factor determining cardiac phenotype. The contribution of flow to cardiac phenotype,
however, is frequently ignored. More research is needed to determine how blood flow
influences cardiac development and the extent to which flow may determine cardiac
phenotype.
Keywords
blood flow - congenital heart defects - cardiac development
