Yet there is convincing evidence supporting an intrinsic wall abnormality that predisposes to aneurysm with BAV. First-degree relatives of patients with BAV, who do not have BAV themselves, have dilated and stiffer aortic roots than controls, which is consistent with a heritable aortopathy. A flow-mediated mechanism and this heritable, intrinsic vessel wall abnormality, however, are not mutually exclusive. Even with Marfan syndrome, the quintessential connective tissue disorder, blood flow plays an important role in disease progression; beta-adrenergic blockade, by blunting the systolic impulse of blood flow in the aortic root, slows the rate of aortic dilation and reduces complications in patients with Marfan syndrome. Unlike Marfan syndrome, however, BAV is associated with asymmetric AsAo aneurysms that bulge toward the right-anterior quadrant, where we have demonstrated asymmetrically elevated systolic WSS, suggesting that blood flow may have a pronounced role in their pathogenesis. Further understanding of the systolic hemodynamics may elucidate why only a subgroup of BAV patients have dilated aortas, and why right-left aortic leaflet fusion, which was the predominant fusion pattern in our BAV patients, is associated with rapid aortic dilation.