Human Cardiac Development in the First Trimester

With rapid advances in medical imaging, fetal diagnosis of human congenital heart disease is now technically feasible in the first trimester. Although the first human embryological studies were recorded by Hippocrates in 300 to 400 BC, present-day knowledge of normal human cardiac development in the first trimester is still limited. In 1886, 2 articles by Dr His described the development of the heart on the basis of dissections of young human embryos. Free-hand wax models were made that illustrated the external developmental anatomy. These wax plate reconstruction methods were used by many other investigators until the early 1900s.1 Subsequently, serial histological sections of human embryos have been used to further investigate human cardiac development.2–6 Using an analysis of histological sections and scaled reproductions of human embryos, Grant2 showed a large cushion in the developing heart at 6\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{6}{7}\) \end{document} weeks (Carnegie stage [CS] 14) and separate atrioventricular (AV) valves at 9\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\frac{1}{7}\) \end{document} weeks (CS 22). At the end of 8 weeks (CS 8), separate aortic and pulmonary outflows were observed. Orts-Llorca et al5 used 3-dimensional (3D) reconstructions of transverse sections of human embryos to define the development of the truncus arteriosus and described completion of septation of the truncus arteriosus in 14- to 16-mm embryos, equivalent to an estimated gestational age (EGA) of 8 weeks (CS 18). Given the complex tissue remodeling associated with cardiac chamber formation and inflow/outflow tract and valvular morphogenesis, the plane of sectioning often limited the information that can be gathered on developing structures in the embryonic heart. These technical limitations, in conjunction with limited access to human embryo specimens, have meant that much of our understanding of early cardiac development in the human embryo is extrapolated from studies in model organisms.7–10 With possible species differences in developmental timing and variation in cardiovascular anatomy, …