Fetal Cardiology

Embryology, Genetics, Physiology, Echocardiographic Evaluation, Diagnosis, and Perinatal Management of Cardiac Diseases, Third Edition

Simcha Yagel, Norman H. Silverman, Ulrich Gembruch, Simcha Yagel, Norman H. Silverman, Ulrich Gembruch

• Publisher: CRC Press
• Year: 2018
• ISBN:
  9780429865732
• Edition: 3
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

The third edition of this established reference is the product of the combined efforts of many professionals – obstetricians, pediatric cardiologists, sonographers, molecular biologists, and medical physicists – and is a comprehensive guide intended for anyone interested in scanning the fetal cardiac system.

1

Cardiac morphogenesis

Adriana C. Gittenberger-de Groot, Monique R.M. Jongbloed, Marco C. de Ruiter, Margot M. Bartelings, and Robert E. Poelmann

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 double-sided 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 two- or 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.

The various converging fields of research have sometimes resulted in a confusing use of terminology, which is not easily solved,9 and which will undoubtedly continue with future new discoveries. This chapter describes in brief the major events in cardiac development.10 There is a focus specifically on the continuous recruitment of myocardium from the second heart field11,12 and on extracardiac cellular contributions13 to the heart and their modulatory role.14 Genetic and epigenetic causal pathways will be briefly discussed. (For all abbreviations of genes and gene products, see Table 1.1; for all embryological and anatomical abbreviations, see Table 1.2.)

Table 1.1Mentioned genes and gene products

14-3-3 epsilon: Eluted in the 14th fraction on positions 3.3

Actc: Cardiac muscle α actin

Acvr2b: Activin A receptor type B

Alk2: Activing receptor-like kinase

BMP: Bone morphogenetic protein

CHD7: Chromodomain helicase DNA binding protein 7

Cited2: cbp/300-interacting transactivator 2

DSCAM: Down syndrome cell adhesion molecule

eNOS: Endothelial nitric oxide synthase

ET1: Endothelin-1

FGF: Fibroblast growth factor

GATA: Transcription factors binding to the GATA sequence

GJA1: Gap junction α-1 protein

HAND2: Heart and neural crest derivatives

HCN4: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Isl1: Insulin gene enhancer protein 1

Irx4: Iroquois homeobox protein

KLF2: Krüppel-like factor-2

Lrp2: Low-density lipoprotein-related protein-2

Mef2c: Myocyte-specific enhancer factor

MHC: Myosin heavy chain

MYH 6,7:...