TOPIC #92: CONGENITAL HEART DISEASE. LEFT-TO-RIGHT SHUNTS (arterial and ventricular septal defects, patent ductus arteriousus). RIGHT-TO-LEFT SHUNTS (tetralogy of Fallot, transposition of the great arteries). COARCTATION OF THE AORTA

Morphology of VSD?

1. Size and location of defects are variable. 2. In defects associated with significant left-to-right shunts, the right ventricle is hypertrophied and often dilated. 3.The diameter of the pulmonary artery is increased due to increased volume ejected by the right ventricle.

Clinical Features of VSD?

1. Small VSDs are asymptomatic, while larger defects cause severe left-to-right shunt. 2. Complicated by pulmonary hypertensi on and congestive heart failure. 3. Progressive pulmonary hypertension results in reversal of the shunt and cyanosis.

2 of the most important congenital heart diseases associated with Right-to-Left shunts are?

1. Tetralogy of Fallot. 2. Transposition of the great vessels.

The outlook for neonates with TGA depends on?

1. The degree of shunting. 2. The magnitude of tissue hypoxia. 3. The ability of the right ventricle to maintain systemic pressure.

Morphology of TGAs?

1. The fundamental lesion is the abnormal origin of pulmonary trunk and aortic root. 2. Right Ventricular Hypertrophy (because this chamber functions as the sytemic ventricle). 3. Left Ventricle somehow becomes atrophic. (since it only has to support the low-resistance pulmonary circulation).

How does the ventricular septum usually develops?

1. The fusion of an interventricular muscular ridge that grows upwards from the apex of the heart with a thinner membranous partition that grows downwards from the endocardial cushion. 2. The basal (Membranous) region is the last part of the septum to develop (most common site for VSD development ~90%)

Morphology of the Tetralogy of Fallot?

1. The heart is large and "boot shaped" due to right ventricular hypertrophy. 2. The proximal aorta is larger than normal with diminished pulmonary trunk. 3. The chambers of the left heart are normal in size, while the right side is characterized by thickened wall that may exceed that of the left. 4. VSD is near the membranous portion of the septum. With the aortic valve immediately over the VSD. 5. The pulmonary outflow tract is narrowed, and in few cases, the pulmonic valve may be stenotic.

What are the features of the Tetralogy of Fallot?

1. VSD. 2. Obstruction to the right ventricular outflow tract. 3. An aorta that overrides the VSD. 4. Right ventricular hypertrophy.

Frequencies of congenital cardiac Malformations?

1. Ventricular septal defect. (Most Common) 2. Atrial septal defect 3. Pulmonary stenosis. 4. Patent ductus arteriosus. 5. Tetralogy of fallot. 6. coarctation of aorta. 7. Atrioventricular septal defect. 8. Aortic stenosis. 9. Transposition of great arteries. 10. Truncus arteriosus. 11. Total anomalous pulmonary venous connection. 12. Tricuspid atresia.

What is the rationale for early intervention, either surgical or non-surgical?

Once significant pulmonary hypertension develops = the structural defects of congenital heart failure are considered irreversible.

Clinical features of ASD?

ASDs initially cause left-to-right shunts due to lower pressure of the right heart and pulmonary circulation; with time, pulmonary vasclature resistance can increase, resulting in pulmonary hypertension.

Morphology of Ostium Primum ASD?

Abnormalities of the AV valves are usually present, leaflets of the valves are cleft (anterior leaflet in the mitral valve, septal leaflet in the tricuspid valve), in severe cases ventricular septal defects occur with severe AV valves deformities Occurs at the lowest part of the atrial septum.

Morphology of Sinus Venosus ASD?

Accompanied by anomalous drainage of the pulmonary veins into the right atrium or SVC. Occurs high in the atrial septum.

How could Left-to-right shunting lead to cyanosis after prolonged shunting?

After prolonged shunting > it could produce pulmonary hypertension sufficient to yield Right-sided pressures that exceed those on the left > thus result in a reversal of blood flow through a shunt

What happens in the case of Transposition of the Great Arteries? (TGAs)

An abnormal (discordant) connection of the ventricles to their vascular outflow due to abnormal formation of truncal and aortopulmonary septa => aorta arises from the right ventricle, and the pulmonary trunk originates from the left ventricle. The atrium-to-ventricle connections are normal. (concordant)

What is a Right-to-Left shunt?

Cardiac malformations that are characterized by cyanosis at the time of birth. Occurs due to direct introduction of poorly oxygenated blood from the right side of the heart, into the arterial circulation.

What is the Ventricular Septal Defect?

Incomplete closure of the ventricular septum which allows left-to-right ventricular shunting.

Three types of ASD's are recognized?

1. Ostium Secundum ASD. (90% of cases) 2. Ostium Primum ASD. (5% of cases) 3. Sinus Venosus ASD. (5% of cases)

Clinical features of PDAs?

1. PDAs are high pressure shunts, audible as "machinery-like" murmurs. 2. large defects can lead to "Eisenmenger syndrome" with cyanosis and congestive heart failure

Define Left-to-Right Shunts?

1. Permit the flow of blood from the left heart to the right heart. 2. NOT associated with cyanosis as an early feature.

Clinical Features of TGAs?

1. Predominant manifestation is early cyanosis. 2. The outlook for neonates with TGA depends on: a. The degree of shunting. b.The magnitude of tissue hypoxia. c.The ability of the right ventricle to maintain systemic pressure.

Common congenital obstructions include?

1. Pulmonic valve stenosis. 2. Aortic valve stenosis. / atresia. 3. Coarctation of the aorta. 4. Subpulmonic Stenosis as in Tetralogy of Fallot.

Such reversal of flow and shunting of unoxygenated blood to the systemic circulation is called?

Eisenmenger Syndrome.

In what disorder, causing and obstruction which is associated with a shunt?

Ex: Tetralogy of Fallot causes an obstruction (Pulmonary stenosis) associated with a shunt (Right-to-Left shunt through a Ventricular Septal Defect).

Left-to-Right Shunt include? and their effect on the pulmonary circulation?

1. Atrial Septal Defects (ASD). (increase pulmonary blood volume) 2. Ventricular Septal Defects. (VSD). (increase pulmonary blood flow and resistance) 3. Patent Ductus Arteriosus. (PDA) (increase pulmonary blood flow and resistence)

What are the 2 clinical finidings associated with long-lasting cyanosis?

1. Clubbing of the fingertips (Hypertrophic Osteoarthropathy). 2. Polycythemia.

Clinical features of Right-to-Left shunts?

1. Decreased pulmonary blood flow. 2. Increased aortic volume. 3. Pulmonary stenosis protects the lungs from overload and pulmonary hypertension. (no pulmonary hypertension develops). 4. Erythrocytosis (due to a cyanotic heart). 5. Hypertrophic Osteoarthropathy. 6. Risk for infective Endocarditis, systemic emboli and brain abscesses.

Morphology of PDAs?

1. Ductus arteriosus arises from the left pulmonary artery and joins the aorta just distal to the origin of the left subclavian artery. 2. In PDAs, some of the blood flowing out of the left ventricle is directed back to the lungs => volume overload => dilation of proximal pulmonary arteries, left atrium and ventricle => pulmonary hypertension => atherosclerosis of the main pulmonary arteries and proliferative changes in distal pulmonary vessels => right heart hypertrophy and dilation.

Pathogenesis of Congenital Heart Failure?

1. In most cases (~90%) the cause of the abnormality is unknown. 2. Environmental factors - congenital rubella infection. 3. Genetic factors - familial forms of congenital heart disease, and certain chromosomal abnormalities (trisomies 13, 15, 18 & 21, and Turner syndrome). 4. Several congenital heart diseases are associated with mutations in transcription factors => TBX5 (cause the atrial and ventricular septal defects seen in Holt-Oram syndrome), NKX2.5 (associated with isolated atrial septal defects ASDs) 5. Abnormal development of neural crest cells can cause defects in the formation of the outflow tract => caused by deletions of a segment in the long arm of chromosome 22.

In response to what does the constriction of the ductus occur?

1. Increased atrial Oxygenation. 2. Decreased Pulmonary vascular resistence. 3. Declined local levels of Prostaglandin E2.

What are the 2 forms of Aortic Coarctation?

1. Infantile form: with hypoplasia of the aortic arch proximal to a PDA. 2. Adult form: In which there is a discrete ridge-like infolding of the aorta, just opposite to the ligamentum arteriosum distal to the arch vessels.

How does the atrial septum begin to develop?

1. It begins as an ingrowth of the "septum primum" from the dorsal wall of the common atrial chamber towards the developing "Endocardial Cushion". 2. A gap; termed "Ostium Primum" initially seperates the two. 3. Continous growth and fusion of the septum with the endocardial cushion ultimately obliterates the ostium primum. 4. A second opening, "Ostium Secundum, now appears in the central area of the primary septum (allowing continued flow of oxygenated blood from the right to left atria, essential for fetal life). 5. As the "Ostium Secundum" enlarges, the "Septum Secundum makes its appearance adjacent to the septum primum. 6. This Septum Secundum proliferates to form a cresent-shaped structure overlapping a space termed the "Foramen Ovale". 7. The foramen ovale on its left side is closed by a flap of tissue derived from the primary septum. 8. This flap acts as a one way valve that allows right-to-left blood flow during intrauterine life. 9. At the time of birth > Falling Pulmonary vascular resistance and rising systemic arterial pressures causes left atrial pressures to exceed those in the right atrium 10. The result is functional closure of Foramen Ovale. 11. In most individuals the foramen ovale is permanently sealed by fusion of the primary and secondary septa. 12. Abnormalities in this sequence leads to development of ASD's.

For the purpose of discussion, congenital heart diseases are subdivided into 3 groups?

1. Malformations causing a Left-to-Right Shunt. (Most common type of congenital cardiac malformations) 2. Malformations causing a Right-to-left Shunt. 3. Malformations causing Obstruction.

What happens when we have a right-to-left shunt for example and why?

A dusky blueness of the skin appears (cyanosis), because the pulmonary circulation is bypassed and poorly oxygenated blood enters the systemic circulation. In contrast to left-to-right shunts, which increases the pulmonary blood flow, and is not associated with cyanosis but it exposes the low pressure, low resistance pulmonary circulation to increased pressure and volume, resulting in Right Ventricular Hypertrophy and Right Ventricular Failure eventually.

What does the Tetralogy of Fallot result from?

Anterosuperior displacement of the infundibular septum, so that there is abnormal division into pulmonary trunk and aortic root.

What are congenital heart diseases?

Are abnormalities of the heart or great vessels that are present at birth, most of which arise during weeks 3-8 of gestation

What is a comple called?

Atresia

Aortic Coarctation is often (in 50% of cases) accompanied with?

Bicuspid aortic valve. In some cases Berry aneurysms occur in the circle of Willis.

What is an Aortic Coarctation?

Coaraction (narrowing/constriction) of the aorta is a relatively common structural anomaly and the most important form of obstructive congenital heart disease.

Clinical Features of Aortic Coarctation?

Depend entirely on the severity of the narrowing and patency of the ductus arteriosus. Preductal coarctation of the aorta with a PDA usually leads to manifestations: 1. Cyanosis. 2. Femoral pulses are weaker than in the Upper Extremities. Postductal Coarctation of the aorta with PDA is usually asymptomatic but could present with: 1. Hypertension in the upper extremities. (due to poor perfusion to the kidneys). 2. Weak pulses and lower blood pressure in the Lower Extremities. 3. Claudication and coldness of the lower extremities result from arterial insufficiency. 4. Notching of the ribs due to the expansion of the flow through the enlarged intercostal and internal mammary arteries.

How do shunts work?

Depending on the pressure relationships, the shunts permit the flow of blood from the left heart to the right heart or (vice versa).

What happens after birth to the Ductus Arteriosus?

Ductus arteriosus constrics and becomes ligamentum arteriosum

What happens in Patent Ductus Arteriosus? (PDAs)

During intrauterine life, ductus arteriosus allows blood flow from the pulmonary artery to the aorta => bypass the unoxygenated lungs.

When is the Ductal closure delayed?

In infants with hypoxia, resulting from respiratory distress or heart disease.

Morphology of Aortic Coarctation?

Infantile Form: 1. Tubular narrowing of the aortic segment between the left subclavian and the ductus arteriosus. 2.Right ventricle is typically Hypertrophied and dilated (because the right side of the heart muscle perfuse the body distal to the narrowing) 3. The pulmonary trunk is also dilated to accommodate the increased blood flow. Postductal (Adult) Form: 1. The aorta is sharply constricted by a ridge of tissue at or just distal to the ligamentum arteriosum. 2. The constricted segment is made up of smooth muscle and elastic fibers that are continuous with the aortic media and are lined by a thickened layer of intima. 3. The ductus arteriosus is closed. 4. Proximal to the coarctation, the aortic arch and its branch vessels are dilated and in older patients often atherosclerotic. 5. The left ventricle is Hypertrophic.

What is an Obstructive Lesion?

It is a Congenital obstruction to blood flow that occurs at the level of the heart valves, or within a great vessel.

What is a shunt?

It is an abnormal communication between chambers and blood vessels.

Who does Aortic Coarctation affect more?

Males are affected twice as much as females. Although females with Turner syndrome frequently have aortic coarctation.

A venous emboli that by passes the lungs and enters the arterial circulation due to a Right-to-Left shunt is called?

Paradoxical Emoblism.

What can be used to maintain the patency of the ductus arteriosus?

Prostaglandins E2 and maneuvers such as atrial septostomy to create ASDs that enhance oxygen saturation.

Morphology of Ostium Secundum ASD?

Right atrial and ventricular dilation, right ventricular hypertrophy, and dilation of the pulmonary artery (reflecting the effects of a chronically increased volume load on the right side of the heart due to Left-to-Right shunting)

What other developmental anomalies are present and what are they called?

Some anomalies obstruct vascular flow by narrowing the chambers, valves, or major blood vessels; These are called Obstructive Congenital Heart Diseases

What happens in Ostium Primum ASD?

The Septum primum and endocardial cushion fail to fuse; associated with other abnormalities in structures derived from the endocardial cushion (AV valves)

What happens in Ostium Secundum ASD?

The Septum secundum does not enlarge sufficiently to cover the ostium secundum

How is the severity of the Right-To-Left shunt determined by?

The amount of right ventricular outflow obstruction.

What is the functional outcome of TGAs?

The separation of the systemic and pulmonary circulations, a condition inadequate with postnatal life. Unless a shunt exists, mixing of blood and delivery of oxygenated blood to aorta occurs => patients with TGA and VSD tend to have a stable shunt.

What is the difference between VSD and ASD?

VSD closes spontaneously often during childhood.

What happens in Sinus Venosus ASD?

located near the entrance of SVC. Has been associated with frameshift mutations in the NKX2.5 Transcription factor.