Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-06-23T18:29:13.317Z Has data issue: false hasContentIssue false

Chapter 9.1 - Structural heart disease

Embryology

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

Mark D. Kilby
Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson
Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes
Affiliation:
Department of Obstetrics, Leiden University Medical Center
Get access

Summary

Introduction

The prenatal detection of structural cardiac malformations has greatly benefited from the advances in echo Doppler technology and the in depth-training of specialists in this area. This opens up new possibilities, now and in the future, for developing in-utero therapy. It also necessitates a better knowledge of the underlying mechanisms and the developmental timing that lead to structural congenital heart disease (CHD), based on a marked progress involving genetic and epigenetic causes. Gene mutations are discovered in the fetus and parents and pathways can be unraveled using mouse transgene technology. Epigenetic causes are also receiving attention, but have thus far been underestimated as approximately 85% of CHD is determined to have a multifactorial background that combines a genetic susceptibility with epigenetic influences. Studies in animal models including chicken, quail, zebrafish, and even more primitive Chordates contribute relevant data. In essence cardiac development shows basic similarities of the major processes involved in between species, therefore, mechanisms unraveled in animal models can be reliably used in understanding normal human cardiac development and CHD [1].

This chapter provides an update on recent advances in heart development (Figure 9.1.1) in which it is important to distinguish a first heart field (FHF) and a second heart field (SHF). As will be explained the contribution of the SHF is very important for most of the structural CHD which we can detect in the fetus and neonate. After a general introduction into embryology the most common heart malformations will be grouped in a developmental context and a small separate paragraph on each specific malformation will be provided. As heart development is a very complicated process with many interacting mechanisms, the grouping of the malformations in a developmental concept should be seen as an approximation in which FHF and SHF components interact to enable, for instance, septation and valve formation (Table 9.1.1).

Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
, pp. 100 - 112
Publisher: Cambridge University Press
Print publication year: 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Farrell AP. Evolution of cardiovascular systems: insights into ontogeny. In: Burggren, WW, Keller, BB, eds. Development of Cardiovascular System: Molecules to Organisms. Cambridge, UK, New York, NY, USA, Cambridge University Press. 1997; 101–14.
DeRuiter, MC, Poelmann, RE, VanderPlas-de Vries, I, et al. The development of the myocardium and endocardium in mouse embryos. Fusion of two heart tubes? Anat Embryol 1992;185:461–73.Google Scholar
Buckingham, M, Meilhac, S, Zaffran, S. Building the mammalian heart from two sources of myocardial cells. Nat Rev Genet 2005;6:826–35.Google Scholar
Cai, CL, Liang, X, Shi, Y, et al. Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. Dev Cell 2003;5:877–89.Google Scholar
de la Cruz, M, Sanchez-Gomez, C, Palomino, MA. The primitive cardiac regions in the straight tube heart (Stage 9-) and their anatomical expression in the mature heart: an experimental study in the chick heart. J Anat 1989;165:121–31.Google Scholar
Kirby, ML, Gale, TF, Stewart, DE. Neural crest cells contribute to normal aorticopulmonary septation. Science 1983;220:1059–61.Google Scholar
Bockman, DE, Redmond, ME, Kirby, ML. Altered development of pharyngeal arch vessels after neural crest ablation. Ann N Y Acad Sci 1990;588:296–304.Google Scholar
Bergwerff, M, Verberne, ME, DeRuiter, MC, et al. Neural crest cell contribution to the developing circulatory system. Implications for vascular morphology? Circ Res 1998;82:221–31.Google Scholar
Farrell, MJ, Burch, JL, Wallis, K, et al. FGF-8 in the ventral pharynx alters development of myocardial calcium transients after neural crest ablation. J Clin Invest 2001;107:1509–17.Google Scholar
Lindsay, EA, Vitelli, F, Su, H, et al. Tbx1 haploinsufficieny in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 2001;410:97–101.Google Scholar
Poelmann, RE, Mikawa, T, Gittenberger-de Groot, AC. Neural crest cells in outflow tract septation of the embryonic chicken heart: differentiation and apoptosis. Dev Dyn 1998;212:373–84.Google Scholar
Poelmann, RE, Jongbloed, MRM, Molin, DGM, et al. The neural crest is contiguous with the cardiac conduction system in the mouse embryo: a role in induction? Anat Embr 2004;208:389–93.Google Scholar
Gurjarpadhye, A, Hewett, KW, Justus, C, et al. Cardiac neural crest ablation inhibits compaction and electrical function of conduction system bundles. Am J Physiol Heart Circ Physiol 2007;292:H1291–300.Google Scholar
Bax, NA, Bleyl, SB, Gallini, R, et al. Cardiac malformations in Pdgfrα mutant embryos are associated with increased expression of WT1 and Nkx2.5 in the second heart field. Dev Dyn 2010;239:2307–17.Google Scholar
Kruithof, BP, van Wijk, B, Somi, S, et al. BMP and FGF regulate the differentiation of multipotential pericardial mesoderm into the myocardial or epicardial lineage. Dev Biol 2006;295:507–22.Google Scholar
Perez-Pomares, JM, Phelps, A, Sedmerova, M, et al. Experimental studies on the spatiotemporal expression of WT1 and RALDH2 in the embryonic avian heart: a model for the regulation of myocardial and valvuloseptal development by epicardially derived cells (EPDCs). Dev Biol 2002;247:307–26.Google Scholar
Gittenberger-de Groot, AC, Vrancken Peeters, M-PFM, Mentink, MMT, et al. Epicardium-derived cells contribute a novel population to the myocardial wall and the atrioventricular cushions. Circ Res 1998;82:1043–52.Google Scholar
Lie-Venema, H, van den Akker, NMS, Bax, NAM, et al. Origin, fate, and function of epicardium-derived cells (EPCDs) in normal and abnormal cardiac development. Scientific World Journal 2007;7:1777–98.Google Scholar
Poelmann, RE, Gittenberger-de Groot, AC, Mentink, MMT, et al. Development of the cardiac coronary vascular endothelium, studied with antiendothelial antibodies, in chicken-quail chimeras. Circ Res 1993;73:559–68.Google Scholar
Winter, EM, Gittenberger-de Groot AC. Cardiovascular development: towards biomedical applicability: epicardium-derived cells in cardiogenesis and cardiac regeneration. Cell Mol Life Sci. 2007;64:692–703.Google Scholar
Red-Horse, K, Ueno, H, Weissman, IL, et al. Coronary arteries form by developmental reprogramming of venous cells. Nature 2010;464:549–53.Google Scholar
Zhou, B, Ma, Q, Rajagopal, S, et al. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 2008;454:109–13.Google Scholar
Gittenberger-de Groot, AC, Winter, EM, Poelmann RE. Epicardium-derived cells (EPDCs) in development, cardiac disease and repair of ischemia. J Cell Mol Med 2010;14:1056–60.Google Scholar
Goumans, MJ, de Boer, TP, Smits, AM, et al. TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro. Stem Cell Res 2007;1:138–49.Google Scholar
Winter, EM, Van Oorschot, AA, Hogers, B, et al. A new direction for cardiac regeneration therapy: application of synergistically acting epicardium-derived cells and cardiomyocyte progenitor cells. Circ Heart Fail 2009;2:643–53.Google Scholar
van Vliet, P, Smits, AM, de Boer, TP, et al. Foetal and adult cardiomyocyte progenitor cells have different developmental potential. J Cell Mol Med 2010;14:861–70.Google Scholar
Poelmann, RE, Jongbloed, MR, Gittenberger-de Groot AC. Pitx2: a challenging teenager. Circ Res 2008;102:749–51.Google Scholar
Franco, D, Campione, M. The role of Pitx2 during cardiac development. Linking left-right signaling and congenital heart diseases. Trends Cardiovasc Med 2003;13:157–63.Google Scholar
Manasek, FJ, Monroe, RG. Early cardiac morphogenesis is independent of function. Dev Biol 1972;27:584–8.Google Scholar
Bouman, HGA, Broekhuizen, MLA, Baasten, AM, et al. Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment. Anat Rec 1995;243:101–8.Google Scholar
Blom, NA, Gittenberger-de Groot, AC, DeRuiter, MC, et al. Development of the cardiac conduction tissue in human embryos using HNK-1 antigen expression: possible relevance for understanding of abnormal atrial automaticity. Circulation 1999;99:800–6.Google Scholar
Bartelings, MM, Gittenberger-de Groot, AC. Morphogenetic considerations on congenital malformations of the outflow tract. Part 1: Common arterial trunk and tetralogy of Fallot. Int J Cardiol 1991;32:213–30.Google Scholar
Conway, SJ, Bundy, J, Chen, J, et al. Decreased neural crest stem cell expansion is responsible for the conotruncal heart defects within the splotch (Sp(2H))/Pax3 mouse mutant. Cardiovasc Res 2000;47:314–28.Google Scholar
Kirby, ML, Waldo, KL. Role of neural crest in congenital heart disease. Circulation 1990;82:332–40.Google Scholar
Bogers, AJJC, Bartelings, MM, Bökenkamp, R, et al. Common arterial trunk, uncommon coronary arterial anatomy. J Thorac Cardiovasc Surg 1993;106:1133–7.Google Scholar
Gittenberger-de Groot, AC, Bartelings, MM, Bogers, AJJC, et al. The embryology of the common arterial trunk. Progr Pediatr Cardiol 2002;15:1–8.Google Scholar
Van Den Akker, NM, Molin, DG, Peters, PP, et al. Tetralogy of fallot and alterations in vascular endothelial growth factor-A signaling and notch signaling in mouse embryos solely expressing the VEGF120 isoform. Circ Res 2007;100:842–9.Google Scholar
Molin, DGM, Roest, PA, Nordstrand, H, et al. Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats. Birth Defects Res A Clin Mol Teratol 2004;70:927–38.Google Scholar
Bartram, U, Molin, DGM, Wisse, LJ, et al. Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of looping, myocardialization, endocardial cushion differentiation, and apoptosis in TGFß2-knockout mice. Circulation 2001;103:2745–52.Google Scholar
Jenkins, SJ, Hutson, DR, Kubalak, SW. Analysis of the proepicardium-epicardium transition during the malformation of the RXRalpha-/- epicardium. Dev Dyn 2005;233:1091–101.Google Scholar
Hogers, B, DeRuiter, MC, Gittenberger-de Groot, AC, et al. Unilateral vitelline vein ligation alters intracardiac blood flow patterns and morphogenesis in the chick embryo. Circ Res 1997;80:473–81.Google Scholar
Van Loo, PF, Mahtab, EAF, Wisse, LJ, et al. Transcription factor Sp3 knockout mice display serious cardiac malformations. Mol Cell Biol 2007;27:8571–82.Google Scholar
Gittenberger-de Groot, AC, Vrancken Peeters, M-PFM, Bergwerff, M, et al. Epicardial outgrowth inhibition leads to compensatory mesothelial outflow tract collar and abnormal cardiac septation and coronary formation. Circ Res 2000;87:969–71.Google Scholar
Nakajima, Y, Morishima, M, Nakazawa, M, et al. Inhibition of outflow cushion mesenchyme formation in retinoic acid-induced complete transposition of the great arteries. Cardiovasc Res 1996;31:E77–85.Google Scholar
Blom, NA, Ottenkamp, J, Jongeneel, TH, et al. Morphogenetic differences of secundum atrial septal defects. Pediatr Cardiol 2005;26:338–43.Google Scholar
Benson, DW, Silberbach, GM, Kavanaugh-McHugh, A, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest 1999;104:1567–73.Google Scholar
Moskowitz, IP, Kim, JB, Moore, ML, et al. A molecular pathway including Id2, Tbx5, and Nkx2–5 required for cardiac conduction system development. Cell 2007;129:1365–76.Google Scholar
Blaschke, RJ, Hahurij, ND, Kuijper, S, et al. Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development. Circulation 2007;115:1830–38.Google Scholar
Barlow, GM, Chen, X-N, Lyons, GE, et al. Down syndrome congenital heart disease: a narrowed region and a candidate gene. Genet Med 2001;3:91–101.Google Scholar
Blom, NA, Ottenkamp, J, Wenink, AG, et al. Deficiency of the vestibular spine in atrioventricular septal defects in human fetuses with down syndrome. Am J Cardiol 2003;91:180–4.Google Scholar
Mahtab, EAF, Wijffels, MCEF, van den Akker, NMS, et al. Cardiac malformations and myocardial abnormalities in podoplanin knockout mouse embryos: correlation with abnormal epicardial development. Dev Dyn 2008;237:847–57.Google Scholar
Hinton, RB Jr, Martin, LJ, Tabangin, ME, et al. Hypoplastic left heart syndrome is heritable. J Am Coll Cardiol 2007;50:1590–5.Google Scholar
Wenink, ACG, Gittenberger-de Groot, AC, et al. Developmental considerations of mitral valve anomalies. Int J Cardiol 1986;11:85–98.Google Scholar
Elzenga, N, Gittenberger-de Groot, AC. Coarctation and related aortic arch anomalies in hypoplastic left heart syndrome. Int J Cardiol 1985;8:379–89.Google Scholar
Sedmera, D, Pexieder, T, Rychterova, V, et al. Remodeling of chick embryonic ventricular myoarchitecture under experimentally changed loading conditions. Anat Rec 1999;254:238–52.Google Scholar
Bartram, U, Bartelings, MM, Kramer, HH, et al. Congenital polyvalvular disease: a review. Pediatr Cardiol 2001;22:93–101.Google Scholar
Garg, V, Muth, AN, Ransom, JF, et al. Mutations in NOTCH1 cause aortic valve disease. Nature 2005;437:270–4.Google Scholar
Fernandez, B, Duran, AC, Fernandez-Gallego, T, et al. Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities. J Am Coll Cardiol 2009;54:2312–18.Google Scholar
Gittenberger-de Groot, AC, Tennstedt, C, Chaoui, R, et al. Ventriculo coronary arterial communications (VCAC) and myocardial sinusoids in hearts with pulmonary atresia with intact ventricular septum: two different diseases. Progr Pediatr Cardiol 2001;13:157–64.Google Scholar
Chaoui, R, Tennstedt, C, Göldner, B, et al. Prenatal diagnosis of ventriculo-coronary communications in a second-trimester fetus using transvaginal and transabdominal color Doppler sonography. Ultrasound ObstetGynecol 1997;9:194–7.Google Scholar
Oosthoek, PW, Wenink, ACG, Macedo, AJ, et al. The parachute-like asymmetric mitral valve and its two papillary muscles. J Thorac Cardiovasc Surg 1997;114:9–15.Google Scholar
Wu, B, Wang, Y, Lui, W, et al. Nfatc1 coordinates valve endocardial cell lineage development required for heart valve formation. Circ Res 2011;109:183–92.Google Scholar
Lie-Venema, H, Eralp, I, Markwald, RR, et al. Periostin expression by epicardium-derived cells (EPDCs) is involved in the development of the atrioventricular valves and fibrous heart skeleton. Differentiation 2008;76:809–19.Google Scholar
Haissaguerre, M, Jais, P, Shah, DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659–66.Google Scholar
Jongbloed, MR, Mahtab, EAF, Blom, NA, et al. Development of the cardiac conduction system and the possible relation to predilection sites of arrhythmogenesis. Scientific World Journal 2008;8:239–69.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×