A Pictorial Account of Heart Development: Spatial and Temporal Aspects of The Human Embryonic Heart Between 3.5 and 8 Weeks of Development

Abstract

Heart development is topographically complex and requires visualization to understand its progression. No comprehensive 3-dimensional primer of human cardiac development is currently available. We prepared detailed reconstructions of 12 hearts between 3.5 and 8 weeks post fertilization, using Amira® 3D-reconstruction and Cinema4D®-remodeling software. The models were visualized as calibrated interactive 3D-PDFs. We describe the developmental appearance and subsequent remodeling of 70 different structures incrementally, using sequential segmental analysis. Pictorial timelines of structures highlight age-dependent events, while graphs visualize growth and spiraling of the wall of the heart tube. The basic cardiac layout is established between 3.5 and 4.5 weeks. Septation at the venous pole is completed at 6 weeks. Between 5.5 and 6.5 weeks, as the outflow tract becomes incorporated in the ventricles, the spiraling course of its subaortic and subpulmonary channels is transferred to the intrapericardial arterial trunks. The remodeling of the interventricular foramen is complete at 7 weeks.

Development of the Human Arterial Valves: Understanding Bicuspid Aortic Valve

“…This was later confirmed using molecular markers [CD31; (19)]. At this stage, the forming valves have a considerable length within the middle part of the septating outflow tract, coinciding with the boundary between the arterial and ventricular components (33). By around the 50th day of gestation (CS20), the sinus walls are becoming apparent but are still surrounded by a cuff of the myocardium, whilst by 52 dpc (CS21; 23mm CRL), the leaflets are short and thick with only a slit-like sinus.…”

“…This expression was downregulated by 37 dpc (CS16) of development and thus could not be used to track them within the developing arterial valves. However, the characteristic condensed mesenchyme within the outflow cushions, which is shown to be made up of NCCs in the mouse, is apparent in the human outflow cushions from approximately 32 dpc (CS14) (33).…”

“…Since the arterial valve leaflets form from the distal ends of the outflow cushions (15,50), it may be possible to determine where they will form from as early as 33 dpc (CS15) as the lumen narrows and the overlying endocardium takes on a distinct cobble-stone appearance. However, at 37 dpc (CS16), the mesenchyme of the distal cushions, where the leaflets will form, swells relative to the more proximal regions of the cushions (33). The first appearance of valve structures from the cushions is at approximately 41 dpc (CS17), with the sinuses first apparent as shallow depressions between the arterial wall and the developing valve ( 16) (Figures 2, 3).…”

A Reassessment of the anatomical features of multiple ventricular septal defects

“…11 Evidence is now also becoming available to show that the changes observed in the murine heart provide an accurate framework for understanding human cardiac development. 12 These changes now permit us to provide an equally solid framework to underpin the categorisation of both solitary and multiple ventricular septal defects.…”

“…This is equivalent to around 5 weeks of development in the human, representing stage 13 in the system developed by the Carnegie Institute. 12 At this stage, the apical components of the developing ventricles are beginning to expand from the inlet and outlet parts of the heart tube by a process known as "ballooning". 13 As the apical components extend centrifugally, so the muscular part of the ventricular septum develops between them.…”