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This presentation will introduce development of the heart from its earliest origins through to the end of the embryonic period. The main morphological changes in the human heart will be shown in the context of the normal human timeline of development.
This presentation will introduce development of the heart from its earliest origins through to the end of the embryonic period. The main morphological changes in the human heart will be shown in the context of the normal human timeline of development.


Ultrasound scans that occur at the end of the first trimester should show a heart that has completed all aspects of septation. Differing from adult circulation will be present within the heart the atrial shunt (foramen oval) and just outside the heart the pulmonary-aortic arch shunt (ductus arteriosus).
Ultrasound scans that occur at the end of the first trimester should show a heart that has completed all aspects of septation. Differing from adult circulation will be present within the heart the atrial shunt (foramen ovale, or historically ''foramen Botalli'') and just outside the heart the pulmonary-aortic arch shunt (ductus arteriosus).





Revision as of 09:37, 8 October 2012

Introduction

Dr Mark Hill

Fetal ECHO Meeting 5th-8th October 2012 ROYAL PRINCE ALFRED HOSPITAL, SYDNEY, AUSTRALIA

This presentation will introduce development of the heart from its earliest origins through to the end of the embryonic period. The main morphological changes in the human heart will be shown in the context of the normal human timeline of development.

Ultrasound scans that occur at the end of the first trimester should show a heart that has completed all aspects of septation. Differing from adult circulation will be present within the heart the atrial shunt (foramen ovale, or historically foramen Botalli) and just outside the heart the pulmonary-aortic arch shunt (ductus arteriosus).


Note - Internet connection issues during the meeting presentation limited the movies and animations that could be shown. Please take the opportunity now in your own time to look at the various animations on this page that help your understanding of cardiac development.


Please feel free to provide the author Feedback, as I continue to improve the content even after the conference!


Developmental Timings

  • Clinical timings refer to Gestational Age (GA) from the last day of the Last Menstrual Period (LMP).
  • Embryonic timings refer to Ovulation age (OA) from day 14 of the cycle when fertilization occurs.

Other Cardiovascular Pages

Teach yourself about heart development with these online tutorials designed at different 3 levels.

Cardiac Embryology     Begin Basic     Begin Intermediate     Begin Advanced  


The pages below are more detailed descriptions of cardiovascular development, most outside the scope of this presentation. Probably the most relevant page is Abnormalities.


Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Human Embryo Development

Human development timeline graph 01.jpg

Weeks shown are ovulation age (OA) for gestational age (GA) add 2 weeks.

Carnegie Stages: 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | About Stages | Timeline

Human Carnegie stage 1-23.jpg

Heart Embryonic Timeline

Advanced Heart Development Timeline GA.jpg

Weeks shown above are for clinical Gestational Age (GA). Ages shown below are Ovulation Age (OA), subtract 2 weeks from GA. If the linked Advanced pages below are too difficult, try starting with the Basic or Intermediate level descriptions of the same events.


Begin Advanced Heart Fields Heart Tubes Cardiac Looping Cardiac Septation Outflow Tract Valve Development Cardiac Conduction Cardiac Abnormalities Molecular Development


Cardiovascular Movies

These simple cartoons show, almost in developmental sequence, aspects of cardiac development. Each linked page is supported by simple descriptions of events shown in the movie.

Week3 folding icon.jpg
 ‎‎Week 3
Page | Play
Week3 folding icon.jpg
 ‎‎Week 3
Page | Play
Heart1 looping icon.jpg
 ‎‎Heart Looping
Page | Play
Heart1 realign icon.jpg
 ‎‎Heart Realign
Page | Play
Heart1 atrium icon.jpg
 ‎‎Atrial Septation
Page | Play
Heart1 ventricle icon.jpg
 ‎‎Outflow Septation
Page | Play

Heart Field

Gastrulation
Mesoderm 001 icon.jpg
 ‎‎Week 3 Mesoderm
Page | Play

Week 5 (GA)

Stage7-sem2.jpg

Carnegie_stage_7

Early Heart Tube (Dorsal).jpg

Dorsal view of 18 day embryo

Early Heart Tube (Lateral).jpg

Lateral view of 18 day embryo

Heart fields 001 icon.jpg
 ‎‎Heart Fields
Page | Play
Week3 folding icon.jpg
 ‎‎Week 3
Page | Play
  • The heart primordium arises predominantly from the primary heart field in splanchnic mesoderm forming in the cardiogenic region of the trilaminar embryo.
  • The cardiogenic region can be thought of as bilateral fields that merge cranially to form a horseshoe-shaped field.
  • During the third week (PO) of development (approximately day 18) angioblastic cords develop in this cardiogenic mesoderm and canalise to form bilateral endocardial heart tubes.
  • The secondary heart field has been described as pharyngeal mesenchyme that contributes myocardium and smooth muscle to the arterial pole.

Heart Tube

Heart Tube Fusion.jpg

Week 5 (GA) to beginning Week 6 (GA)

Heart Tube Segments.jpg


  • The endothelium of the heart tube forms the internal endocardium.
  • The epicardium develops from mesothelial cells arising from the sinus venosus, that spread cranially over the myocardium.

Cardiac Looping

Human heart SEM1.jpg

Image day 21 to 25 (GA Week 6)

Heart Looping Sequence (SEMs).jpg

Stage10 bf3.jpg
  • First stage occurs from late in the sixth week (GA) to early in the seventh week (GA)
    • studied in chick embryos whose initial, straight heart tube is representative of that developing in humans.
  • Second stage (creating S-shape) occurs as the ventricular bend moves caudally and the distance between the outflow and inflow tracts diminishes.
    • dorsal mesocardium degenerates forming the transverse pericardial sinus (a point of communication across the pericardial coelom).
    • atrial and outflow poles converge and myocardial cells are added, forming the truncus arteriosus.
  • Final stage is the wedging of the aorta between the atrioventricular (AV) valves.
    • occurs during septation and is dependent on the retraction and rotation of the myocardium by 45°.

Left-Right Asymmetry

  • Heart is the first organ in the body to express left-right asymmetry in the form of looping.
  • Axis of the heart is established during gastrulation.
    • Left - Shh is expressed in the left side of Henson’s node in the primitive streak. Leads to expression of Nodal and Pitx2 in left sided mesoderm. Pitx2 expressed in the left side of the heart tube is then responsible for asymmetric organogenesis.
    • Right - Shh inhibited by the activation of Activin IIa receptors.


Stage11 sem8a.jpg

Stage11 sem5c.jpg

Stage12 sem1.jpg Stage13 bf6.jpg

Stage13 sem1c.jpg

Stage 11 Stage 12

Stage 12 detail

Stage 13

atrioventricular junction

Septation

Atrioventricular Canal

  • Partitioning of the primitive heart occurs between the middle of the week 6 (GA) and the end of week 7 (GA).
  • Division of the atrioventricular canal is described below while

Two endocardial cushions form on the dorsal and ventral surfaces of the AV canal. Following expansion of the cardiac jelly, epithelial to mesenchymal transformation (EMT) of the endocardial cells in the canal occurs forming the cushions. Synergistic signalling between BMP and TGFβ facilitates EMT. The cushions grow as they are invaded by mesenchymal cells from the endocardium during the fifth week, eventually fusing to create the right and left AV canals, hence partially separating the primitive atrium and ventricle.

Links: Atrioventricular Canal Septation

Atrial and Ventricular Septation


Links: Movie- Atrial and Ventricular Septation | Atrial and Ventricular Septation

Outflow Tract Septation

  • Cardiac neural crest - levels associated with somites 1 and 3 of the neural tube migrate through the pharyngeal arches to contribute to the conotruncal septum.
  • Week 7 (GA) - proliferation of pharyngeal mesenchyme in the bulbus cordis forms bulbar ridges, continuous in the truncus arteriosus. Cardiac neural crest migrates into these ridges, condensing as cellular columns to support the outflow tract septum. The ridges form a 180° spiral to create the helical aorticopulmonary septum. Myocardialisation of the ridges gives a zippering effect resulting in fusion.
  • Week 8 (GA) - fusion occurs distal to proximal direction, allowing for cleavage of the aorta and pulmonary trunk. The spiralling nature of the ridges causes the pulmonary trunk to twist around the aorta. The bulbus cordis accounts for the smooth conus arteriosus (or infundibulum) in the right ventricle and the aortic vestibule in the left ventricle.
Migration of the cardiac neural crest
Cross-sections of the outflow tract illustrating the truncal and bulbar ridges
Links: Movie - Outflow tract

Heart Week 7 and 10 (GA)

Stage 13 image 097.jpg Stage 13 image 098.jpg
G6L G7L


Valve Development

AV Canal Division (Superior View).jpg

AV Valves.jpg

Development of the mitral and tricuspid valves


  • Week 7 to 10 (GA) - sculpted from the ventricular wall valve leaflets form attached by chordae tendineae insert into small muscles attached to the ventricle wall: the papillary muscles.
    • left AV valve has anterior and posterior leaflets and is termed the bicuspid or mitral valve.
    • right AV valve has a third, small septal cusp and thus is called the tricuspid valve. These concepts are depicted on the right.
  • development of cardiac valves, particularly the process of epithelial to mesenchymal transformation (EMT)
  • expansion of endocardial cushion tissue and remodelled to form thin sheets.
    • cushion proliferation, is limited by neurofibromin acting through the inhibition of Ras signalling as well as Smad6 which interferes with TGFβ signalling.
Semilunar Valves.jpg

Development of the semilunar valves

Semilunar Cusps.jpg

Development of the semilunar cusps

Aortic and pulmonary valves (semilunar valves)

  • formed from the bulbar ridges and subendocardial valve tissue.
  • primordial semilunar valve consists of a mesenchymal core covered by endocardium.
  • mechanisms of valve remodelling may involve apoptotic pathways.

Cardiac Conduction

  • Week 7 (GA) - SA node initially develops in the sinus venosus and then is incorporated into the RA.
  • AV node arises slightly superior to the endocardial cushions.


Cardiac Conduction System.jpg

Diagram of the adult cardiac conduction system

Embryonic Heart Rate

In a 1996 study normal successful human gestations were defined by EHR criteria at different early embryonic (34-56 days GA, from last menstrual period) developmental stages (at the earliest stages when embryo length is difficult to measure gestational sac diameters are included). [1]


  • Week 5-6 (GA) Stage 9 to 10 - 2 mm embryo (gestational sac diameter of 20 mm) EHR at least 75 beats / minute
  • Week 6 (GA) Stage 11 to 12 5 mm embryo (gestational sac diameter of 30 mm) EHR at least 100 beats / minute
  • Week 8 (GA) Stage 16 - 10 mm embryo EHR at least 120 beats / minute
  • Week 9 (GA) Stage 18 - 15 mm embryo EHR at least 130 beats / minute


Links: Week 17 (GA) Fetal Heart Rate

Fetal Heart

Beyond the scope of this current talk.

Study using 3 and 4-dimensional fetal echocardiography between 12 and 41 weeks gestational age measured outflow tract angles.[2]

  • ductal arch and thoracic aorta angle decreased with age.
  • between the ductal arch and the aortic arch angle increased with age.
  • between the left outflow tract (LOT) and right outflow tract (ROT) angle increased with age.

Abnormalities

Diagram Abnormality Epidemiology Description
VSD
Ventricular Septal Defect 25% of CHD; more frequent in males Result from growth failure of the membranous IV septum or endocardial cushions leading to a lack of closure of the IV foramen. Many VSDs are actually from defects in the outflow tract septum. 30-50% close spontaneously; large VSDs result in dyspnoea and cardiac failure in infancy.
Tetralogy of Fallot
Tetralogy of Fallot 9-14% of CHD Comprises a classic group of four defects: pulmonary stenosis, VSD, dextroposition of the aorta and right ventricle hypertrophy. An additional ASD creates a ‘pentalogy’ of Fallot. Results in cyanosis.
Transposition of the Great Vessels
Transposition of the Great Vessels 10-11% of CHD The most common form of transposition is where the aorta arises from the right ventricle while the pulmonary trunk arises from the left. This occurs either via abnormal rotation of the arterial pole or abnormal development of the outflow septum. In order for a newborn to survive prior to surgery there must be mixing of systemic and pulmonary circulations through a VSD, ASD or patent ductus arteriosus. It is the most common cause of cyanotic heart disease in newborns and is surgically corrected.
ASD
Atrial Septal Defect 6-10% of CHD; more common in females The atrial septal myocardium is derived from multiple sources making various places susceptible to defects. The most common is a patent foramen ovale. Others include an ostium secundum defect and ostium primum defect (where there is usually some defect with the AV cushions as well). Defects in the sinus venosus act as ASDs yet are really defects in the wall separating the right pulmonary veins and SVC. A common atrium results from a complete lack of atrial septation. ASDs results in cyanosis due to a right-to-left shunt.
Pulmonary Atresia
Pulmonary Stenosis
Pulmonary Atresia & Pulmonary Stenosis 10% of CHD Unequal division of trunks causes cusps to fuse to form a dome with a narrow/non-existent lumen and hence obstruction to blood flow from the right ventricle to the pulmonary artery. The most common side of stenosis/obstruction is at the pulmonary valve itself (rather than distal or proximal to the valve). Heart-lung transplantation may be the only therapy.
Patent Ductus Arteriosus
Patent Ductus Arteriosus 6-8% of CHD; 2-3 times more common in females; common in preterm newborns Failure of contraction of the muscular wall of the DA. This imposes greater pressure on the pulmonary circulation. Many will close spontaneously, however if this does not occur, surgical closure is advised to prevent the development of congestive heart failure.
Aortic Stenosis
Aortic Stenosis 7% of CHD Stenosis is caused either by a muscular obstruction below the aortic valve, obstruction at the valve itself or aortic narrowing above the valve. The most common site is at the valve itself which results from a persistence of endocardial tissue that normally degenerates. Results in LV hypertrophy and heart murmurs.
Hypoplastic Left Heart
Functional Hypoplastic Left Heart
Hypoplastic Left Heart Syndrome 4-8% of CHD The left ventricle is incapable of supporting the systemic circulation, hence the right ventricle maintains both pulmonary and systemic circulations aided by an ASD. Other defects such as stenosis or atresia of the mitral and aortic valves, anomalous pulmonary venous connections and hypoplasia of the aortic arch can be responsible for hypoplastic left heart syndrome. Infants usually die within weeks.
Coarctation of the Aorta
Coarctation of the Aorta 5-7% of CHD Aortic constriction in the region of the ductus arteriosus. It is associated with patent ductus arteriosus, VSD and aortic stenosis. Closure of the ductus arteriosus in neonates with a coarctation imposes a greater afterload on the left ventricle which can lead to congestive heart failure. Treatment aims at maintaining the ductus arteriosus via prostaglandins.
PAPVD
TAPVC
Partial/Total Anomalous Pulmonary Venous Connection <4% of CHD; more common in females In partial anomalous pulmonary venous drainage (PAPVD) a portion of the pulmonary venous blood flow returns to the right atrium. When over 50% of the veins return to the right atrium the condition is clinically significant. All types of total anomalous pulmonary venous connection (TAPVC) (those compatible with survival) are accompanied by an atrial septal defect. Pulmonary veins in TAPVC tend to open into one of the systemic veins before returning to the right atrium. The overloaded pulmonary circuit leads to cyanosis, tachypnoea and dyspnoea. Treatment is via surgical redirection.
Tricuspid Atresia
Tricuspid Atresia 1-3% of CHD Complete lack of formation of the tricuspid valve which results in an hypoplastic right ventricle. The pulmonary circulation can be maintained via a VSD, and an ASD is necessary for survival. Results in cyanosis and tachypnoea. Treatment is initially via administration of prostaglandins followed by surgery to place a shunt to maintain the pulmonary circulation.
DORV
Double Outlet Right Ventricle 1-1.5% of CHD Both large arteries arise wholly or mainly from the right ventricle. This defect is considered to be present if the aorta obtains 50% of its blood from the right ventricle. The defect arises due to absence of the secondary heart field such that myocardium is not added to the outflow tract during looping. Arrangement of the atrioventricular valves, coronary arteries and the ventriculoarterial connections as well as clinical manifestations are variable.
Interrupted Aortic Arch
Interrupted Aortic Arch Very rare An extreme form of coarctation of the aorta involving a gap in the ascending or descending thoracic aorta that results from abnormal proliferation/migration/function of neural crest cells. Different types of interrupted aortic arch are defined based on their relation to the arterial branches of the aortic arch. It is greatly associated with other defects such as a patent ductus arteriosus or VSD. It is treated with prostaglandin to maintain ductus arteriosus followed by surgery.

Magnetic Resonance Imaging

The following movies show aspects of heart development from mid-embryonic to the end of embryonic development.[3] Original image resolution of the scans ranges from 30-150 microns/pixel.

Gestational Age



Image source: The Kyoto Collection embryo MRIs are reproduced with the permission of Prof. Shige Yamada, Cecilia Lo and Kohei Shiota. This material is provided for educational purposes only and cannot be reproduced electronically or in writing without permission. MRI Atlas of Human Embryo Ref:<pubmed>20503356</pubmed>| PMC3401072


Further Online Reading

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

References

  1. <pubmed>8921130</pubmed>
  2. <pubmed>17384040</pubmed>| MC2190734 J Ultrasound Med.
  3. <pubmed>20503356</pubmed>| PMC3401072 | MRI Atlas of Human Embryo

Additional References


Online Textbooks

Search Bookshelf heart development

Reviews

<pubmed>21940548</pubmed> <pubmed>17224285</pubmed>| PMC1858673 <pubmed></pubmed>

Articles

<pubmed></pubmed> <pubmed></pubmed> <pubmed></pubmed> <pubmed>9475206</pubmed>

Search Pubmed

Search Pubmed heart development

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External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

  • Cardiovascular Ultrasound is an open access, peer-reviewed, online journal covering clinical, technological, experimental, biological, and molecular aspects of ultrasound applications in cardiovascular physiology and disease. Search - Fetal

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Cite this page: Hill, M.A. (2024, March 28) Embryology Fetal ECHO Meeting 2012. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Fetal_ECHO_Meeting_2012

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