ABSTRACT

Introduction Cardiovascular development and the regulatory mechanisms underlying this major embryonic event have become essential knowledge for the fetal cardiologist. The increased potential of ultrasound technology to detect morphology of the growing heart requires more insight into the morphogenetic and epigenetic pathways essential for normal and abnormal development. This area is now expanding with the possibilities of acquiring data from patients by human exome screening, transcriptome analysis, single nuleotide polymorphism (SNIP) technology, and chromatin remodeling.1-3 It is essential to link these genetic, epigenetic, and environmental clues from patient material to advance our understanding of the complicated interactive processes that govern heart development. The crucial processes in human cardiac development take place within the first 6 weeks of embryogenesis and, as such, cannot be pursued using in vivo diagnostics. It is, therefore, still imminent that essential knowledge is incorporated from animal models such as (transgenic) mouse, chicken, and, more recently, zebrafish, as basic principles of heart formation can be compared between various animal models and human development, even profiting from an evolutionary-developmental approach.4,5 One has to take into account, however, important species differences such as, for instance, a doublesided aortic arch in fish and reptiles, a right-sided aortic arch system in birds, as compared to a left-sided system in mammals,6 a persisting left-sided caval vein in mice, and the lack of cardiac septation in fish and many reptiles with only a twoor three-chambered heart tube as a final result. The influence of hemodynamics on the developing system has long been underestimated or neglected because of insufficient refined technology to study this in vivo in the developing embryo. Currently, newly designed techniques including microparticle image velocimetry have opened up this research field.7,8 For the fetal cardiologist, particle image velocimetry is a very interesting new development, as noninvasive techniques such as echo-Doppler add physiologic insight to morphology.