A pictorial account 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.

Morphogenesis of the Mammalian Aortic Arch Arteries

“…For a number of these stages, however, only one specimen was available for analysis ( Table 1 ). Due to the limited availability of intact human embryos for research, some published studies do rely on using one embryo per stage, making the assumption that these are representative of normal ( Hikspoors et al, 2022 ) or make comparisons to other databases ( Rana et al, 2014 ). The human embryos used in our study were all genotyped and found to be karyotypically normal, and with the expected morphology when compared to published studies of human developmental anatomy ( Congdon, 1922 ; Rana et al, 2014 ).…”

Evaluation of cardiovascular morphology and associated anomalies in patients with crossed pulmonary arteries on multidetector computed tomography angiography

“…Identification of this anomaly suggests the coexistence of a variety of congenital cardiac defects, especially aortic arch anomalies and outflow tract malformations. While it is well established that the distal outflow tract separates into the intrapericardial trunks and the right and left pulmonary arteries develop extrapericardially, it is possible that the undue rotation of the aortopulmonary septum can produce crossing of the pulmonary arteries 11 …”

Flow-Mediated Factors in the Pathogenesis of Hypoplastic Left Heart Syndrome

“…Our approach to creating this model was guided by two observations: (i) the HLHS heart in utero displays an intact ventricular septum, normally aligned great vessels, and concordant atrioventricular connections; and (ii) that this contrasts with the chick embryo model, in which left atrial ligation is performed during cardiogenesis and structural abnormalities other than left heart hypoplasia, such as ventricular septal defects, can occur (in approximately a quarter of surgically manipulated embryos) [ 18 , 32 ]. Therefore, we hypothesized that the insult leading to left heart growth failure likely occurs in the fetal period after the early cardiac developmental events have occurred (i.e., after looping, convergence, wedging, and septation events have taken place by weeks 8–9 of gestation [ 33 , 34 ]).…”

“…In the clinical setting, HLHS has been detected as early as 12 weeks of gestation with ultrasound [ 36 ]. This is still 3–4 weeks after the completion of cardiogenesis [ 33 , 34 ] during a period when the heart is growing rapidly. The left atrium embolization model demonstrates that HLHS can occur after cardiogenesis, but does not exclude it from occurring or being initiated earlier.…”