**5.1 Reduced blood flow—"no flow, no growth" is a possible etiology of hypoplastic left heart syndrome**

Reduced blood flow through the left side of the developing heart is the most prevalent hypothesis in the causation of HLHS. Abnormal blood flow has a negative effect on the shear forces applied to the developing heart which in turn impacts the growth of the left ventricle. Any experimental manipulation to decrease left ventricular preload during embryonic development by either obstructing the left atrioventricular canal flow [39], inserting a balloon in the left atrium [25], or by placing an occluder in the foramen ovale [40] resulted in cardiac phenotypes of HLHS in chick embryos and fetal lambs. This hypothesis is further supported by the observation of the HLHS phenotypes in human fetuses with foramen ovale restriction [41] and premature closure of foramen ovale (**Figure 6**).
