Endocardial Heart Tube:
The primordium (first indication) of the heart & blood vessels in the fetus is around day 16 of pregnancy, in the form of the angiogenic cell clusters present infront & on either side of the brain plate.
The angiogenic cell clusters on both sides develop & attain lumens to form two endocardial heart tubes.
The two endocardial heart tubes fuse to form: The single endocardial heart tube.
Further Development of the Endocardial Heart Tube:
Three constrictions appear in the single endocardial heart tube dividing it into four parts:
- The sinus venosus.
- The primitive atrium.
- The primitive ventricle.
- The bulbus cordis, which is formed of a proximal part called the conus cordis and a distal part called the truncus arteriosus.
Primitive & Dorsal Aortas:
The first arteries to appear in the embryo are the right & left primitive aortas, each one developing as a continuation of the corresponding heart tube. They lie ventral to the foregut, and curve dorsally to continue as the right & left dorsal aortas.
As the two heart tubes fuse to form a single endocardial heart tube, the two primitive aortas fuse to from the aortic sac.
The truncus arteriosus is continuous with the aortic sac. The aortic sac then gives branches (aortic arches) to the pharyngeal arches.
The heart tube then bends on itself to form the cardiac loop.
The bulbus cordis divides into: the conus cordis and the truncus arteriosus.
Heart tube; developing within the pericardial cavity (blue): Note the veins converging on the caudal end of the heart and the arteries leaving the cranial end.
Formation of the cardiac loop: The developing atrium is initially located caudally, but gradually moves cranially. The next chamber, the ventricle, moves more caudally. Blood leaving the ventricle enters the truncus arteriosus before leaving the heart into the arterial system.
The Sinus Venosus:
The sinus venosus is formed of: A small median part and two horns.
The sinus venosus receives all the veins of the body.
Each horn receives:
- A vitelline vein: from the yolk sac,
- An umbilical vein: from the placenta,
- A common cardinal vein: from the body of the embryo: Each one receiving:
- An anterior cardinal vein &
- A posterior cardinal vein.
Schematic showing the sinus venosus and its tributaries: The sinus venosus drains into the primitive atrium (PA). The bulbus cordis (BC) and the truncus arteriosus (TA) are also shown.
Fate of the sinus venosus:
Schematic showing the back of the heart; superior vena cava, inferior vena cava and coronary sinus are illustrated, as well as the four pulmonary veins entering into the left atrium. You can also recognize the two pulmonary arteries and the aortic arch.
The opening of the sinus venosus into the primitive atrium is guarded by two valves: the right & left venous valves.
The upper edges of these valves fuse to form the septum spurium.
Fate of the venous valves:
The superior and inferior pulmonary veins in each lung in the fetus unite to form a common vein: These two common veins then unite to form a single vein which opens into LA.
Later on in development; the single vein and the two common veins are absorbed into LA to form its posterior smooth part.
The primitive atrium & primitive ventricle are joined via a narrow canal called: the atrioventricular (AV) canal. This is, later on, divided into the right & left AV canals.
The right AV canal is then absorbed into the RA, and the left AV canal is absorbed into the LA.
Formation of the atria:
The inter-atrial septum first develops as the septum primum, which descends downwards from the roof of the primitive atrium to divide it into two cavities: RA & LA.
At the same time, the AV canal between the primitive atrium & ventricle is being divided into the right & left AV canals by the septum intermedium.
The opening between the septum primum & septum intermedium is called: the ostium primum.
When the septum primum descends enough to unite with the septum intermedium, the ostium primum is closed.
At the same time: The upper part of the septum primum ruptures to maintain a communication between RA & LA, which is essential for fetal circulation. This communication is called: the ostium secondum.
(Note that the ostium secondum is present in the septum primum).
Another septum called: the septum secondum develops to the right of the septum primum & descends from the roof of the atrium downwards until it overlaps over the upper edge of the septum primum (or the lower rim of the ostium secondum), without fusing with it, thus keeping the inter-atrial communication, which is now called: the foramen ovale, allowing the passage of blood from RA to LA.
Thus finally the inter-atrial septum in utero is formed of two overlapping septa: the septum primum lower down & the septum secondum higher up. The communication in-between is the foramen ovale, which has a valve-like mechanism created by the septal overlap, allowing passage of blood from RA to LA that normally occurs during fetal life.
After birth, the foramen ovale closes to form the fossa ovalis.
Pathological types of ASD:
- Ostium secondum (OS) or fossa ovalis ASD: Constitutes 75 % of cases & occurs at the site of fossa ovalis.
- Ostium primum (OP) ASD: at the lowest part of septum primum, not separated from the atrioventricular (AV) ring by any septal tissue, i.e. its lower rim is formed by the AV ring itself.
- Coronary sinus (CS) ASD: at the site of CS opening.
- Sinus venosus (SV) ASD: which is further classified into two types according to the site of the defect:
- Superior SVASD: near to the mouth of the superior vena cava.
- Inferior SVASD: near to the mouth of the inferior vena cava.
Originally the first case of this syndrome consisted of: congenital ASD with rheumatic mitral stenosis (MS).
Currently, any combination of ASD, congenital or iatrogenic, and mitral stenosis, congenital or acquired, is referred to as Lutembacher syndrome.
Some even consider the syndrome as a combination of ASD and any mitral valve lesion, i.e. mitral stenosis, mitral regurgitation, or mixed mitral valve lesion.
This syndrome consists of:
- Cardiac abnormalities: in 75% of cases:
- ASD: usually of the secondum type.
- VSD: usually of the muscular type.
- Arrhythmia: Atrioventricular block, Atrial Fibrillation.
- Upper limb abnormalities: may be unilateral or bilateral and asymmetric and may involve the radial, carpal, and thenar bones: Aplasia, hypoplasia, fusion, or anomalous development of these bones with tri-phalangeal or absent thumbs.
Holt-Oram syndrome: short arms and small hands extended not far from the shoulders.
This complex consists of:
- Coronary sinus ASD: with left-to-right shunt.
- Absent coronary sinus.
- Persistent left superior vena cava draining into LA; i.e. right-to-left shunt.
Thus, both left-to-right and right-to-left shunts occur in this complex.
Secondary cardiac changes in patients with ASD:
Secondary cardiac pathological changes that may occur in patients with ASD, result from volume overload of the right side of the heart, and include:
- RA & RV: Gross enlargement.
- Pulmonary trunk & pulmonary arteries: Dilatation.
- Pulmonary valve: stretched leaflets.
On the other hand, there is no overloaded of the left side of the heart, thus LV & usually LA remain normal; In-spite of excess blood coming back to LA from the lungs, LA is relieved by the shunt and is not overloaded.
Late complicated cases of ASD:
In late cases of ASD; pulmonary hypertension (PHT) develops:
- Right ventricular hypertrophy (RVH) results from pressure overload.
- Pulmonary arterial (PA) atherosclerosis and in situ thrombosis may occur, as well as PA aneurysm, dissection, and even rupture.
Pathophysiology of ASD:
Why the shunt is left to right (L-R) in patients with ASD?
- Right atrium (RA) is more distensible than left atrium (LA).
- Tricuspid valve (TV) is more capacious than mitral valve (MV).
- Right ventricle (RV) is more compliant than left ventricle (LV).
- There is little pressure gradient between LA & RA; LA pressure being a little higher.
Changing magnitude of the shunt during the cardiac cycle:
- In early systole, the shunt is usually small.
- During late systole, it increases,
- It gets more in early diastole,
- and maximum in late diastole.
Pressures in cardiac chambers and great vessels:
- RV end-diastolic pressure (RVEDP): Normal.
- RV end-systolic pressure (RVESP): Mild increase.
- Pulmonary valve: excess flow may create systolic pressure gradients across the valve, usually < 10 mmHg: Rarely, gradients up to 60 mmHg were reported, due to excess blood flow alone, without pulmonary stenosis.
Pulmonary circulation usually accommodates the excess flow very well for many years.
- Severe pulmonary vascular obstructive disease (PVOD) rarely occurs before age 20 years.
- When PVOD develops, the L-R shunt decreases gradually until it is reversed & becomes right to left (R-L), i.e. Eisenmenger’s syndrome.
- Some patients have accelerated course and develop PVOD earlier; they probably have a different genetic constitution of pulmonary vasculature.
What will happen if left ventricular failure develops?
If left ventricular failure (LVF) develops in a patient with ASD, for any reason, e.g. mitral valve disease, the left atrial (LA) pressure will increase due to stagnation of blood, and the L-R shunt increases.
In the presence of ASD and mitral stenosis (MS):
- The left-to-right shunt is increased due to elevated LA pressure.
- If ASD is big, LA & RA become functionally a common chamber, with equal pressures: In such a situation, the assessment of jugular venous pressure (JVP) reflects the severity of MS.
Clinical picture in patients with ASD:
Incidence of ASD:
- At birth: ASD constitutes 10 % of all cases of congenital heart disease.
- In adults: it is the second most common congenital anomaly after bicuspid aortic valve.
- Female: male ratio 2:1.
Symptoms of ASD:
- Recurrent chest infection.
- Dyspnea & easy fatigue usually appear at age 20 years.
- Congestive Heart Failure (CHF):
- In the 1st year, it occurs in only 5% of patients.
- Becomes more common again in 4th & 5th decades, due to arrhythmia.
Signs of ASD:
According to the severity of the case, one or more of the following signs may occur:
- Wide fixed splitting of the second heart sound (S2).
- Sings of right ventricular hypertrophy (RVH).
- Sings of relative tricuspid stenosis (TS), due to excess blood flow across the tricuspid valve.
- Signs of relative pulmonary stenosis (PS), due to excess blood flow across the pulmonary valve.
- Signs of pulmonary hypertension (PHT).
- Signs of pulmonary regurgitation (PR).
- Signs of tricuspid regurgitation (TR).
Different forms of splitting of the second heart sound
Why wide splitting?
Excess flow to RV leads to prolonged RV ejection time and consequently marked delay of pulmonary component of second sound (P2). As the second sound (S2) is formed of the aortic component (A2) followed by the pulmonary component (P2), thus marked P2 delay results in wide splitting.
Why fixed splitting?
S2 splitting in ASD is fixed, i.e. does not change with respiration as occurs in normal people, because the changes in systemic venous return with respiration are balanced by the changes in the amount of left-to-right shunt from LA to RA.
During inspiration: the systemic venous return to RA increases, while the pulmonary venous return to LA and the left-to-right shunt decrease.
During expiration the reverse occurs: the systemic venous return to RA decreases, while the pulmonary venous return to LA and the left-to-right shunt increase.
The net result is a fixed amount of blood delivered to RV during inspiration & expiration, thus fixed splitting.
Chest x-ray in patients with ASD:
According to the magnitude of the left-to-right shunt; the chest x-ray may show:
- Enlarged central pulmonary arteries.
- Pulmonary plethora.
- Dilated right side of the heart.
Chest x-ray of a young patient with a proven ASD and resultant cardiomegaly and pulmonary hypertension with prominence of the pulmonary vasculature.
Electrocardiography (ECG) in patients with ASD:
ECG may show:
- Right ventricular hypertrophy.
- QRS axis:
- Right axis deviation in most cases of secondum ASD.
- Left axis deviation in secondum ASD associated with mitral valve prolapse (MVP).
- Left axis deviation in most cases of primum ASD.
ECG showing right axis deviation and right ventricular hypertrophy. http://pediatriccardiology.uchicago.edu/MP/CHD/ASD/ECG-ASD.jpg
Echocardiography in patients with ASD:
Trans-Thoracic Echocardiography (TTE) may show the defect, but some cases may not be seen except with Trans-Esophageal Echocardiography (TEE).
After the introduction of two-dimensional, Doppler & color Doppler echocardiography, most cases of ASD are adequately diagnosed, and well assessed by this technique, and cardiac catheterization is not usually needed.
Two-dimensional (2D) & M-mode TTE & TEE will usually show:
- The size, site & pathological type of ASD.
- Cardiac chambers size & function.
Doppler & color Doppler echocardiography:
- Helps detect the ASD, especially small defects which might not be seen with 2D echo.
- Assesses the blood flow & direction of the shunt across ASD.
Apical four-chamber view: Ostium primum ASD. Note that there is no tissue separating the defect from the atrioventricular ring. If a rim of septal tissue is separating the defect from the AV ring , it will be diagnosed as a secondum ASD.
Apical four-chamber view: Ostium primum ASD with Color Doppler signal showing the left-to-right shunt.
Cardiac catheterization is rarely needed in patients with ASD.
Cardiac catheterization findings:
- Catheter path: Passage of catheter from RA to LA, indicates the presence of either ASD or patent foramen ovale (PFO).
- O2 step-up: blood samples taken from different sites show sudden increase (step-up) in O2 saturation, from venous level to arterial level, at the site of the shunt:
- In RA: in most cases.
- May occur in SVC: in Sinus venosus ASD.
- LA pressure is equal to RA pressure in most cases.
- If LA pressure is higher than RA pressure: suspect stretched patent foramen ovale, rather than ASD.
- If RA pressure is higher than LA pressure: suspect partial anomalous pulmonary venous drainage (PAPVD) or LV-RA defect.
- Dye injection may be needed:
- In LV: if mitral valve disease is suspected.
- In pulmonary veins: if PAPVD is suspected.
Other causes of O2 step up at atrial level:
- Atrioventricular septal defects (AVSD).
- Partial anomalous pulmonary venous drainage (PAPVD).
- Total anomalous pulmonary venous drainage (TAPVD).
- Left ventricular-right atrial (LV-RA) communication.
- Ventricular septal defect (VSD) with tricuspid regurgitation (TR).
Natural history of ASD:
Spontaneous closure occurs in the 1st year of life in 50% of cases.
Patients with ASD may continue asymptomatic for a long period.
Symptoms and complications increase with advancing age, including cardiomegaly with increased cardiothoracic ratio (CTR), pulmonary hypertension (PHT), congestive heart failure (CHF), and atrial fibrillation (AF).
Causes of death:
- Pulmonary embolism.
- Paradoxical systemic embolism: i.e. systemic embolism originating at the right side of the circulation.
- Infective endocarditis: Very rare.
Medical management of the patient with ASD:
Medical management includes the treatment and prevention of:
- Recurrent chest infections.
- Infective endocarditis.
Indications for closure:
- Symptomatic patients with congestive heart failure.
- Indications of closure in asymptomatic children;
- Right-sided heart dilation or evidence of RV volume overload.
- ASD with significant left-to-right shunt: i.e. Pulmonary blood flow (Qp)/ systemic blood flow (Qs) ratio >1.5).
- Closure of ASD for prevention of paradoxical emboli in older patients after a stroke, may be advised even with an insignificant left-to-right shunt (Qp/Qs<1.5).
- With severe pulmonary hypertension (pulmonary artery pressure > 2/3 systemic arterial blood pressure or pulmonary arteriolar
resistance > 2/3 systemic arteriolar resistance), closure can be recommended if pulmonary vascular obstructive disease is thought to be reversible, as proved by:
- Qp/Qs of at least 1.5, or
- Evidence of pulmonary artery reactivity when challenged with a pulmonary vasodilator (e.g., oxygen or nitric oxide), or
- Evidence on lung biopsy (rarely required) that pulmonary arterial changes are potentially reversible.
Catheter closure of ASD using the ASD occluding devices:
- Only secondum ASD can be closed by an occluding device.
- Stretched ASD diameter <41 mm (larger ASD cannot be closed by occluding devices, but only surgically).
- Sufficient distance from important structures (such as the aortic root, mitral & tricuspid valves, venae cavae, and pulmonary veins), should be present to avoid their damage, and to provide enough rim of tissue for device fixation.
- Patients with patent foramen ovale (PFO) and systemic embolism are considered for catheter occlusion if: An atherosclerotic cause of the embolism was excluded, and A right-to-left shunt was detected by contrast echo; at rest or during Valsalva provocation.
- ASD other than the secondum type.
- Large ASD with a stretched diameter > 40 mm.
- Presence of Chiari network.
- Presence of intra-cardiac thrombi.
- Partial or total anomalous pulmonary venous drainage or other cardiac disease needing surgery.
- Inability to use anti-coagulants.
- Endocarditis prophylaxis for one year.
- Heparin during the procedure, followed by oral anticoagulant:
- For 6 months: with sinus rhythm.
- Life-long: with AF.
Catheter closure is possible in about 87 % of cases of ASD, and effective in 90-96 % of treated cases, even in young children with large defects
Multiple ASD can also be treated with catheter closure.
- Mal position of the device.
- Supra-ventricular tachyarrhythmia.
- Transient LV failure.
- Embolization of the device into the aorta.
- Fracture of the device with atrial perforation.
Surgical closure of ASD:
Surgical closure is only indicated if device closure is not available or ASD anatomy is unsuitable (due to presence of any of the exclusion criteria).
Video: A schematic illustrating the left-to-right shunt through ASD. http://www.youtube.com/watch?v=e46jtin-H50
Video: Apical 4-chamber view: Secondum ASD
Video: Ostium primum ASD with tricuspid regurgitation.
Video: Ostium secondum ASD associated with muscular VSD
Video: Apical view: ASD associated with VSD
Video: Subcostal 4-chamber view: ASD, with Chiari network seen as shadows in the RA cavity (The anterior atrium).
Video: Atypical apical 4-chamber view: Atrial septal defect with Chiari network.
Video: Apical 4-chamber view: Atrial septal aneurysm http://www.youtube.com/watch?v=uSPzbzPVqWU
Video illustrating the ASD device closure.