Cardiac Embryology for Imagers by John Partridge

1. Cardiac Embryologyfor ImagersbyJohn Partridge • This is an imager’s guide to the formation of the heart. I have tried to slim the topic down to those aspects that I have found useful in my interest in the imaging of congenital heart disease. • Many of the illustrations are from Leon Gerlis, my collaborator in the cardiac section of “A Textbook of Radiology”, the copyright of which has been released. Others have come to me in various ways over the years and their provenance is uncertain. If you recognise any, do let me know so I can acknowledge them.

2. The first appearance of the heart is a cardiogenic plate of mesodermal tissue at the extreme head end of the embryonic disc. Rapid development and flexion of the head cause this cardiac anlage to come to lie below the head and mouth, in front of the foregut. Two lateral extensions of cardiac tissue become hollowed out to form a pair of endothelial tubes, which soon fuse to form the primitive cardiac tube. Paired veins from the trunk (the cardinal system), liver, yolk sac and placenta enter the heart tube from below and a series of arterial arches emerge from the upper end.

3. The primitive cardiac tube has five zones: the arterial trunk the bulbus cordis ) } some would call these two together the ventricle ) the primitive ventricle, with inlet and outlet portions the atrium and the sinus venosus The arterial trunk will divide to separate the pulmonary and systemic supply. The bulbus and the ventricle will differentiate into the right and left ventricles, but let me say at once that it is not a matter of a septum growing up the middle of the primitive ventricle; the real story is rather more complicated, but an understanding of it will assist greatly in your analysis of congenital cardiac malformations.

4. The cardiac tube grows at a greater longitudinal rate then the rest of the embryo, causing it to fold. As it does this it falls to the right. This is known as d-looping. It may fall to the left in an l-loop: this will lead to a malformed heart. Below are chick embryo dissections showing the two types of loop. normal d-loop l-loop

5. The fold of the loop is principally at the junction of bulbus cordis and ventricle. Note in panel C that the two end up side by side. • Now is the time to realise that the left ventricle will develop from the ventricle, and the right ventricle will develop from the bulbus cordis. (And an l-loop will • result in ventricular inversion with the left ventricle on the right.)(for more, see “The Anatomy of Ventricular Looping….Jorg Manner Clinical Anatomy Jan 2009 21-35) • Note also that the arterial trunk is above the developing right ventricle. • Now we must ask, where does the interventricular septum come from?

6. This is an actual looped heart Note that the ventricular mass is now in line with the atria This is a cutaway showing the beginnings of the ventricular septum. The ventricles will develop as outpouchings from this position, in the direction of the arrows.

7. so that we go from this

8. to this. Rather crude graphics but I hope you get the point let us call the top of the septum the “septal crest”

9. Now look at the area which was the lumen of the original tube, here. It now forms a communication between the ventricles: persistence of it will result in the commonest of ventricular septal defects, the perimembraneous VSD this figure is rather simplistic but might help

10. Now for the arterial trunk. This structure does truly septate, but embryologically it is a simple coronal division in its embryonic straight position. It will, as we will discuss, end up as a spiral, but this is achieved by differential growth. The septation extends upwards from the valves to end just beyond the origin of the paired sixth aortic arches, where it seals off against the posterior truncal wall. As the sixth arch vessels are destined to be the branch pulmonary arteries, the posterior channel is now the main pulmonary artery. The anterior channel is the aorta. This is why the aorta always arches over the pulmonary arteries from anterior to posterior, no matter what other cardiac abnormality is present. We will not discuss aortic branching problems here, we must concentrate on the ventricles and how the great vessels connect to them.

11. Because of the looping, the septating arterial trunk will be dragged to the right , and twisted as well. As a result the ascending aorta comes to lie to the right of the pulmonary artery. Note that the looping brings the trunk close to the AV canal. The aorta is now poorly placed to attach itself to the left ventricle and some mechanism is needed to drag it to the left but still leave the PA over the right ventricle. (One might wonder why the truncal septum does not seal off anteriorly above the sixth aortic arches, and so make the anterior channel the pulmonary artery.)

12. Anyway, the relocation of the aorta to the left requires an appreciation of the modelling power of differential growth. All this is happening as the embryo is rapidly growing, even though it is only millimetres long. day 9 day 13

13. At this stage, as we saw before, the ventricular mass is centralising in front of the AV canal so that separate atria can serve each ventricle. If we take a view downwards onto the crest of the septum, looking from the atria, we see something like this: anterior See how close the outlet is to the inlet. If the gap between them fails to grow with the rest of the heart, in the fully formed heart the two will be in continuity. The next stage is the most difficult to describe or illustrate, I hope I can make it reasonably clear. right

14. A surge of growth beneath the pulmonary artery pushes it up, forward and right (black arrows). The gap between the aorta and the inlet valve remains small and fibroses (dotted line). These processes pin the aortic valve to the rim of the developing mitral valve as everything around them expands. aorta pulmonary artery As a result, the aorta arises from the left ventricle while the pulmonary artery has risen over the right ventricle. Once the gap between the truncal septum and the septal crest obliterates, the systemic and pulmonary supplies will have been separated, and connected to the correct ventricle.

15. And so now you can compare the flow scheme on the left with the more lifelike image on the right RPA = right pulmonary artery LPA = left pulmonary artery APS = aortopulmonary (truncal) septum RVO = RV outflow LVO = LV outflow

16. Now we have described how the ventricles position themselves and the great vessels spiral down to cross the circulation before the truncal septum fuses with the superior margin of the septal crest. Inferior to this, the posterior part of the septal crest is heading towards the AV valve, which itself is dividing into the mitral and tricuspid valves Four cushions (AVC) have developed at the A/V junction; the superior and inferior cushions will meet to divide the AV orifice (AVO) into the tricuspid and mitral valves. The inferior septal crest (VS) will aim to meet the divided valve where the cushions fuse.

17. Viewing the mature anatomy form the atrial side, the two atrioventricular valves have assumed their circular orifice shapes. The aortic valve, as we have discussed, is in continuity with the mitral annulus: the AV valves have separated slightly at the top, allowing the aortic valve to wedge between the mitral and tricuspid annuli, coming to rest very close to the tricuspid annulus. The pulmonary valve remains pushed up and forward, though still in continuity with the aortic valve.

18. This pattern of connections between the annuli of the four cardiac valves constitutes the fibrous “skeleton” of the heart, here viewed from the front. This is a useful image to carry in your head, as much of ventricular anatomy can be “dressed” on to this framework. Note that the commissures of the aortic and pulmonary valves reflect their common origin with one commissure of each still in line with its old partner. The coronary artery origins will always be from the sinuses adjacent to the common commissure, even in congenital abnormalities of aortic position and/or connection. pulmonary aortic tricuspid mitral

19. Opposite the dividing atrioventricular valve, the posterior walls of the atria are beginning to lateralise. The symmetrical systemic venous system biases its growth to the right and many of its left sided structures disappear or involute. Thus the systemic veins drain to the right side.

20. A septum is developing down the middle of the atrium, probably in a similar way to the ventricular septum in that it is a ridge left behind as the atrial walls grow away from it. The to the left of the septum, the primary pulmonary vein grows and seeks out the primitive pulmonary venous complex. As growth proceeds, the primary vein is absorbed into the atrial wall as showed here, to achieve the adult form of separate left and right lung drainage.

21. All that is left now is to cover the development of the atrial septum in more detail. This is another difficult topic, requiring some effort in all four dimensions. This diagram is a simplified two dimensional version. The septum primum grows downwards towards the developing AV valves, but “fenestrates” posteriorly to form the ostium secundum, which is closed by the later-developing septum secundum.

22. This diagram is a little more true. The septum secundum is not really a true intracavitary septum, but is a fold of atrial wall invaginating from the superior surface.

23. Here is someone else’s interpretation

24. Actually, I subscribe to the feeling that the septum primum does not actually fenestrate, but that it and the septum secundum form eccentrically overlapping flanges. In any event, where the two cross in the middle is the oval fossa if they overlap completely, or is a secundum atrial septal defect if they leave a gap. I feel this orientation of the septa explains best why on transoesophageal echo the septa around a PFO do not quite look like they should from the diagrams septum secundum LA RA Ao septum primum

25. And to finish, a word on the AV valves. Looking back on this image from a few slides ago, you may have noticed that the way the septum seals off the “VSD” space is not a simple line. The area in question becomes the membranous septum, and is offset towards the mitral valve resulting in a portion that is interventricular (MSV) and one that is between the LV and the right atrium (MSA). You will meet this anatomy again in echocardiography and in your understanding of the atrioventricular septal defects (“canal” defects). It allows the wedging of the aortic valve between the mitral and tricuspid valves described before. Well, that’s it. I do hope it has helped. On the next slide I have classified some congenital malformations on the underlying embryological fault: feel free to give it a try.

26. What if?.............. - then you get the truncal septum fails to fuse with the septal crest? - perimembraneous VSD the truncal septum is deviated to the PA side? - tetralogy of Fallot the truncal septum fails to develop? - truncus arteriosus the ventricular septum fails to reach the AV valve? - AV septal defects the arterial trunk stays over the RV but does divide? - double outlet RV the aortic valve pushes up and right instead of the pulmonary? - transposition of the great vessels the ventricles fail to centralise over the AV valve - double inlet left ventricle (commonest form of single ventricle) the loop is to the left? - ventricular inversion (RV on the left, LV on the right) and of course, combinations exist! This is just a rough summary, but I hope you get the idea. Can you see now why double outlet RV is common and double outlet LV is very rare? Similarly double inlet LV is common, double inlet RV rare? And why a VSD so commonly accompanies problems of connection of the ventricles to the great vessels.