Cardiac EmbryologyCardiac Embryologyfor Imagersfor Imagers

byby

John PartridgeJohn Partridge

► This is an imager’s guide to the formation of the heart. I have tried 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 to slim the topic down to those aspects that I have found useful in my interest in the imaging of congenital heart disease.my interest in the imaging of congenital heart disease.

► Many of the illustrations are from Leon Gerlis, my collaborator in Many of the illustrations are from Leon Gerlis, my collaborator in the cardiac section of “A Textbook of Radiology”, the copyright of the cardiac section of “A Textbook of Radiology”, the copyright of which has been released. Others have come to me in various ways which has been released. Others have come to me in various ways over the years and their provenance is uncertain. If you recognise over the years and their provenance is uncertain. If you recognise any, do let me know so I can acknowledge them.any, do let me know so I can acknowledge them.

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 cardiactissue become hollowed out toform a pair of endothelial tubes, which soon fuse to form the primitive cardiac tube. Paired veins from the trunk (thecardinal system), liver, yolk sacand placenta enter the heart tube from below and a series of arterial arches emerge from the upper end.

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, butlet 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.

The primitive cardiac tube has five zones:

the arterial trunk

the bulbus cordis ) } some would call these two togetherthe ventricle ) the primitive ventricle, with inlet

and outlet portions

the atrium

and the sinus venosus

The cardiac tube grows at a greaterlongitudinal rate then the rest of theembryo, causing it to fold. As it does thisit falls to the right. This is known asd-looping. It may fall to the left in anl-loop: this will lead to a malformed heart.

Below are chick embryo dissections showingthe two types of loop.

normal d-loop l-loop

•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 willresult 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?

This is an actual looped heartNote that the ventricular mass isnow in line with the atria

This is a cutaway showingthe beginnings of the ventricularseptum. The ventricles will developas outpouchings from this position,in the direction of the arrows.

so that we go from this

to this. Rather crude graphicsbut I hope you get the point

let us call the top of the septumthe “septal crest”

Now look at the area whichwas the lumen of the original tube,here.

It now forms a communication between the ventricles: persistence ofit will result in the commonestof ventricular septal defects, theperimembraneous VSD

this figure is rather simplistic but might help

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 upas a spiral, but this is achieved bydifferential growth.

The septation extends upwards fromthe valves to end just beyondthe 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 pulmonaryarteries from anterior to posterior, no matter whatother cardiac abnormality is present. We will not discussaortic branching problems here, we must concentrate on theventricles and how the great vessels connect to them.

Because of the looping, the septating arterial trunk will be dragged to theright , and twisted as well.As a result the ascending aortacomes to lie to the right of thepulmonary 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 todrag it to the left but still leave the PA over the rightventricle. (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.)

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

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:

See how close the outlet is to the inlet. If the gapbetween them fails to growwith the rest of the heart, inthe fully formed heart the twowill be in continuity.

The next stage is the most difficult to describe or illustrate,I hope I can make it reasonablyclear.

right

anterior

aortapulmonary artery

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 smalland fibroses (dotted line). These processes pin the aortic valve to the rim of the developing mitral valveas everything around them expands.

As a result, the aorta arises from theleft ventricle while the pulmonaryartery 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, andconnected to the correct ventricle.

RPA = right pulmonary arteryLPA = left pulmonary arteryAPS = aortopulmonary (truncal) septumRVO = RV outflowLVO = LV outflow

And so now you can compare the flow scheme on the left with the more lifelike imageon the right

Now we have described how the ventricles position themselves and the greatvessels spiral down to cross the circulation before the truncal septum fuses with thesuperior 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 willmeet 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.

Viewing the mature anatomy form the atrial side, the two atrioventricular valveshave 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.

pulmonary

aortic

tricuspid mitral

This pattern of connections between the annuli of the four cardiac valves constitutes the

fibrous “skeleton” of theheart, here viewed fromthe front. This is a usefulimage to carry in your head,as much of ventricular anatomycan be “dressed” on to thisframework.

Note that the commissures of theaortic and pulmonary valvesreflect their common origin withone commissure of each still inline with its old partner. Thecoronary artery origins will alwaysbe from the sinuses adjacent tothe common commissure, even incongenital abnormalities of aorticposition and/or connection.

Opposite the dividing atrioventricularvalve, the posterior walls of the atriaare beginning to lateralise. The symmetrical systemic venous systembiases its growth to the right andmany of its left sided structuresdisappear or involute. Thus the systemic veins drain to the right side.

A septum is developing down themiddle of the atrium, probably in asimilar way to the ventricular septumin that it is a ridge left behind as theatrial walls grow away from it.

The to the left of the septum, the primarypulmonary vein grows and seeks outthe primitive pulmonary venous complex.As growth proceeds, the primary vein is absorbed into the atrial wallas showed here, to achieve the adultform of separate left and right lung drainage.

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 toform the ostium secundum, which is closed by the later-developing septum secundum.

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.

Here is someone else’s interpretation

Actually, I subscribe to the feeling that the septumprimum does not actually fenestrate, but that it and the septum secundum form eccentrically overlapping flanges.

In any event, where the two cross in the middleis the oval fossa if they overlap completely, or is asecundum 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 primum

septum secundum

LA

RAAo

And to finish, a word on the AV valves. Looking backon this image from a few slides ago, you may havenoticed 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 valveresulting in a portion that is interventricular (MSV) and one that is between the LV and theright atrium (MSA). You will meet this anatomy again in echocardiography and in yourunderstanding of the atrioventricular septal defects (“canal” defects). It allows thewedging 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 congenitalmalformations on the underlying embryological fault: feel free to give it a try.

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 whydouble outlet RV is common and double outlet LV is very rare? Similarly double inlet LVis common, double inlet RV rare? And why a VSD so commonly accompanies problems of connection of the ventricles to the great vessels.