Rush Center for Congenital
and Structural Heart Disease

Definition

 

   

 

Incidence

 

The most common congenital heart disease at one week of age and throughout the first three decades of life. 50% of all patients with congenital heart disease have ventricular septal defects. 0.3-0.5/1000 Live births have significant left ventricular septal defects requiring management. Premature infants have a much higher incidence (ten times as high as full term babies).  

 

 

Embryology

 

Ventricular septation is a complex process involving different septal structures from various origins and positioned at various planes [3, 27, 28, 31].  These structures eventually meet to complete the separation of the right and left ventricles.

Muscular interventricular septum:  During the fifth week, around day 30, a muscular fold extending from the anterior wall of the ventricles to the floor appear at the middle of the ventricle near the apex and grows towards the AV valves with a concave ridge.  Most of the initial growth is achieved by growth of the two ventricles on each side of the ventricular septum.  In addition trabeculations from the inlet region coalesce to form a septum which grows into the ventricular cavity at slightly different plane than the primary septum, this is the inlet interventricular septum, which is at the same plane of that of the atrial septum.  The point of contact between these two septa will cause the edge of the primary septum to protrude slightly into the right ventricular cavity forming the trabecular septomarginalis.  The fusion of these two septa forms the bulk of the muscular interventricular septum.  This septum will then become in contact with the outflow septum. 

The interventricular foramen, which is bordered by the concave upper ridge of the muscular interventricular septum and the fused AV canal endocardial tissue, closes at the end of week 7.  This is achieved by growth of three structures: the right and left bulbar ridges and the posterior endocardial cushion tissue.  This will close the interventricular foramen and connect the ventricular septum to the outflow septum, thus connecting the right ventricle to the pulmonary trunk and the left ventricle to the aortic trunk.

Outflow tract septum:  The cardiac outflow tract include the ventricular outflow tract and the aortopulmonary septum.  There has been much debate regarding this process, the following is a summary of various theories.

Kramer (1942) suggested that there are three embryological areas, the conus, the truncus and the pulmonary arterial segments.  Each segment develop two opposing ridges of endocardial tissue, the opposing pair of ridges and those from various segments meet to form the septum separating the two outflow tracts and the aortopulmonary trunks.  The aortopulmonary septum is formed by ridges separating the fourth (future aortic arch) and the sixth (future pulmonary arteries) aortic arches.  The truncus ridges are formed at the area where the semilunar valves are destined to be formed, therefore forming the septum between the ascending aorta and the main pulmonary artery.  The conus ridges form just below the semilunar valves and from the septation between the right and left ventricular outflow tracts.

Van Mierop (1979), agreed that there are three pairs of ridges forming in the aortopulmonary, truncus and conus regions, however, he stated that the pairs of ridges fuse independently and later on fuse with each other to complete the septation.  His theory indicate that the truncus ridges form  first, and as they fuse they form a truncal septum which then fuses with the aortopulmonary septum which is formed by invagination of the dorsal wall of the aortic sac between the fourth and the sixth aortic arch arteries. 

Asami(1980),  followed Van Mieropís theory, however, he stated that these ridge fuse in the opposite direction of what Van Mierop has indicated, i.e. from the outflow tract to the aortopulmonary region.

Pexieder(1978, 1984) and Orts Llorca et al (1982), stated that there are only tow septa, a conotruncal (or bulbar) and an aortopulmonary septum.

Bartlings et al (1989), introduced a new theory.  They stated that the septation process of the ventricular outflow tracts, pulmonary and aortic valves and the great vessels is mostly caused by a single septation complex, which they termed aortopulmonary septum.  This septation complex develops at the junction of the muscular ventricular outflow tract with the aortopulmonary vessel.  This junction has a saddle shape, i.e. not in one plane which would allow the right ventricular outflow tract to be long with a short main pulmonary artery, while the left ventricular outflow tract become short with a long ascending aorta.   The ventricular outflow septation is formed by condensed mesenchyme, embedded in the endocardial cushion tissue just proximal to the level of the aorto-pulmonary valves.  The condensed mesenchyme will come in close contact with the outflow tract myocardium, from the area just above the bulboventricular fold, and participate in the septation of the outflow tract by providing an analogue to muscle tissue.  Myocardium in contact with the mesenchymal arch grow rapidly and form the bulk of the outflow septum and is continuous with the primary fold on the parietal  wall of the right ventricle and the myocardium on the right side of the primary septum.

 

 

 

 

Pathology

 

Membranous ventricular septal defect:

The membranous septum is very small, therefore ventricular septal defects usually extend into the surrounding muscle septum, this is called perimembranous ventricular septal defect. This kind of ventricular septal defect is very close to the tricuspid valve septal leaflets which may be damaged by shunting across the defect whether it is involved , or not in forming an aneurysmal pouch leading which may lead to ventricular septal defect closure. This type of ventricular septal defect is most common accounting for 75% of all ventricular septal defects. It is associated with malalignment of the outflow septum as in tetralogy of Fallot.

Muscular ventricular septal defect:

This is the second most common type of ventricular septal defects. It might be in the apical portion or mid portion, either anteriorly or posteriorly. These ventricular septal defects may be single but appear as multiple from the right ventricular side.

Outflow tract ventricular septal defect:

These affect the outflow tract septum, it has the tendency to cause aortic valve cusp damage, which may lead to aortic regurgitation, this is more common in the oriental population.

Endocardial cushion type:

This is the least common type of ventricular septal defects, is located underneath the tricuspid valve. It may be associated with superior axis deviation on electrocardiography.

 
 

 

 

Pathophysiology

 

The larger the ventricular septal defect the more pressure is transmitted to the right ventricle. Once the right ventricular pressure equalizes with the left ventricular pressure, this occurs when the defect is more than 50% of the area of the aortic root. The determining factor for amount of left-to-right shunting at that point becomes the systemic and pulmonary vascular resistances. Muscular ventricular septal defects become smaller during systole allowing less shunting. Symptoms with ventricular septal defects usually start with a QP:QS ratio of 2.5:1 or more.  

Large ventricular septal defects cause hypertension of the right ventricle, pulmonary arteries and left atrium. In case of patent ductus arteriosus and ventricular septal defect, the pulmonary arterial and right ventricular pressures will become systemic if these two defects are large enough and the amount of left-to-right shunting will depend on the systemic and pulmonary vascular resistances and not the size of the defects. In the association of a ventricular septal defect and atrial septal defect, atrial shunting will further increase the left-to-right shunting occurring at the ventricular level. However, the shunting at the atrial septal defect will not affect the RV pressure.

Aortic stenosis, aortic insufficiency, mitral stenosis and pulmonary stenosis are all factors that may influence the amount of left-to-right shunting.

Hypoxemia causing elevated pulmonary vascular resistance, as is encountered in high altitudes, will decrease left-to-right shunting.

Mitral stenosis when present with ventricular septal defect will elevate the pulmonary vascular resistance resulting in less left to right shunting, if the mitral stenosis is relieved the LA and consequently the PA pressure will drop allowing more left-to-right shunting.

 

 

Clinical Manifestations

 

Although only 15% of ventricular septal defects are large enough to require hospitalization yet this is the most common cause of hospitalization amongst congenital heart diseases. Tachypnea is typically the first presenting symptom. Dyspnea results in poor nursing and frequent rest during feedings. This will result in failure to thrive. Hepatomegaly may be present.

The murmur of VSD is due to left-to-right shunting at the ventricular level. Small ventricular septal defects are typically louder than larger ones. The murmur of a VSD is heard best at the left lower sternal border.

Right-to-left shunting at the VSD are not audible due to a small amount of pressure difference between the right and left ventricles. This is the reason why in tetralogy of Fallot a ventricular septal defect murmur is not present, but rather a harsh systolic ejection murmur due to right ventricular outflow tract obstruction.

A loud third heart sound or diastolic rumble is heard with large left-to-right shunting due to increased flow across the mitral valve. A thrill is felt in many cases, particularly beyond infancy.

 
 

 

 

ECG

 

 
The electrocardiogram is typically normal or there is LVH due to volume overload exhibited by a tall R in V5, V6 with a deep Q wave. There may also be right ventricular hypertrophy and left atrial dilatation.

 

 

CXR

 

The chest x-ray shows cardiomegaly with increased pulmonary blood flow and Kerley B lines may seen but rare.  

 

 

Echocardiography

 

2-D and color Doppler are valuable in identifying ventricular septal defects. The number of defects can be determined by using multiple planes.

The ventricular septum is a complex curved structure.  Not all parts of the ventricular septum can be seen from a single echocardiographic view.  Most defects in the ventricular septum can bee seen from the various sub-xiphoid views.  In addition the muscular, apical and perimenbrenous defects can be seen from the parastrernal long axis.  the parasternal short axis shows apical, muscular, perimembrenous and outlet VSDs.  The apical four chamber is a good view to visualize the inlet VSDs.

In addition to seeing the VSD by 2-D, direction of blood shunting can be determined by color Doppler.  Shunting is typically left to right, unless the PVR is elevated.

The aortic valve may prolapse with or without regurgitation in perimembrenous and outlet VSDs, this should be interrogated by echocardiography.

  

 

 

 

Cardiac Catheterization

 

Cardiac catheterization may be indicated to further delineate the anatomy of the VSD although this is becoming unnecessary nowadays due to echocardiography. Cardiac catheterization is particularly important to determine the pulmonary vascular resistance in older patients. The best views to visualize the ventricular septal defect on a left ventricular angiogram are as follows:

  • Perimembranous, mid muscular and apical are best seen in the LAO views.
  • Anterior muscular and subpulmonary ventricular septal defects are best seen in the RAO views.
  • Posterior muscular and inlet ventricular septal defects are best seen in the hepatoclavicular (40 degrees LAO and 40 degrees cranial angulation).

Cardiac catheterization is occasionally performed to assess QP and QS as well as PVR.

Some VSDs such as muscular VSDs and some perimembrenous VSDs are amenable to device closure in the cardiac catheterization laboratory.  VSD closure continue to be a surgical procedure, however, as more experience is achieved with device closure, this may become the method of choice in the near future.

  

 

 

 

Treatment

 

Surgical repair of ventricular septal defects is done in infants less than six months of age only when the child is not gaining weight due to congestive heart failure. However, this is associated with a high mortality rate which is about 20% in infants less than one month of age versus 2% mortality rate in infants more than six months of age. Uncontrolled congestive heart failure leading to surgery is quite infrequent.

Pulmonary hypertension (more than 50% of systemic blood pressure) in children six months to one year of age is another indication for surgical repair.

Beyond the first year of life all ventricular septal defects with a QP:QS ratio of more than or equal to 2:1 should be surgically repaired.

In the past, devices were available for closure of the ventricular septal defect. These were used with muscular and apical ventricular septal defects but not with perimembranous ventricular septal defects or subaortic ventricular septal defects since these may cause damage to the aortic valve.

Perimembranous ventricular septal defects which constitute the majority of ventricular septal defects have a tendency to become smaller (about 50% of them do so). Therefore, it is worthwhile allowing the child to grow since these ventricular septal defects may close spontaneously. Closure of defects in most instances involve tricuspid valve tissue. However, perimembranous defects with malalignment as in the case of tetralogy of Fallot or without pulmonary stenosis typically do not close or become smaller and almost always require surgical intervention.

Muscular ventricular septal defects typically become smaller and may close spontaneously. If they are large and do not get smaller, surgical repair is typically more risky since it might involve placement of a patch from the left ventricular side which would necessitate surgical incision in the left ventricle which may cause left ventricular dysfunction as well as future arrhythmias.

Outflow tract ventricular septal defects are typically large and do not get smaller spontaneously. Therefore, they are referred for surgical closure after six months of age or earlier if there is failure to grow or if aortic insufficiency develops.

Inlet ventricular septal defects do not get smaller spontaneously and they are best closed surgically early rather than later.

Surgical Complications:

  • Residual ventricular septal defects 20%.
  • Right bundle branch block or bifisicular block 30-85% of the cases.
  • Complete AV block 5%.
  • Premature ventricular contractions 5%.
  • Subacute bacterial endocarditis 41.4/10,000 person-years follow-up. The incidence of subacute bacterial endocarditis occur equally in those who have been operated and those who have not been operated.
 
 

 

 

Course and Prognosis

 

   

Spontaneous diminution in size:

Perimembranous and muscular ventricular septal defects typically get smaller. Inlet and infundibular ventricular septal defects do not get smaller. Most changes in size occur within the first six months of life.

Development of pulmonary vascular obstructive disease:

This is rarely encountered nowadays. It would occur after one year of age. If any of the

following are present then surgery is contraindicated.

  • Pulmonary vascular resistance more than 8 Wood units.
  • Pulmonary vascular resistance not responsive to pulmonary vasodilators such as oxygen or nitrous oxide.
  • No left-to-right shunting across the ventricular septal defect.
  • Predominantly right-to-left shunting across the ventricular septal defect.

Mortality is very high with pulmonary vascular obstructive disease during pregnancy and therefore should be avoided.

Aortic insufficiency, prolapse of the right and noncoronary sinuses cups are noted in some cases of infundibular and perimembranous ventricular septal defects. Closure of infundibular defects will prevent occurrence of aortic insufficiency but closure of ventricular septal defects after aortic insufficiency is noted does not necessarily halt progression of insufficiency.

Aortic valvuloplasty may or may not halt aortic insufficiency and sometimes aortic valve replacement is necessary. Incidence of subacute bacterial endocarditis is high in patients with ventricular septal defect and aortic insufficiency and occur in about 16% of such population.

Subaortic stenosis is usually a discrete membrane in the left ventricular outflow tract distal to the ventricular septal defect and rarely proximal to the defect. This is more common in patients with ventricular septal defect and coarctation of the aorta and in patients S/P main pulmonary artery band. It is a progressive lesion therefore surgery is indicated once pressure gradient is more than 30 mm Hg. This could occur after closure of defect surgically. Surgical resection is generally curative.

 

 

 

More

 

   

Ventricular Septal Defect & Associated Defects:

Ventricular septal defect associated with atrial septal defect:

7 % of all ventricular septal defects are associated with atrial septal defects, some of which are only stretched patent foramen ovales. Mortality for a pair of such lesions was higher in the past but this does not appear to be the case nowadays.

Ventricular septal defect s associated with patent ductus arteriosus:

After equalization of pressure through large ventricular septal defect or patent ductus arteriosus the amount of left-to-right shunting thereafter is dependent upon pulmonary vascular resistance and systemic vascular resistance.

Ventricular septal defects and pulmonary stenosis:

Acyanotic tetralogy of Fallot may present clinically in early infancy just like a small ventricular septal defect. Patients with ventricular septal defect and pulmonary stenosis without malalignment of the outflow septum is different from tetralogy of Fallot since they are not known to have right aortic arch.

Ventricular septal defects and double chambered right ventricle:

The proximal portion of the right ventricular outflow tract muscle bundle hypertrophy and divides the right ventricular cavity into two chambers. The ventricular septal defect opens into the infundibular or distal chamber. This may be associated with subaortic stenosis.

In patients with ventricular septal defects or mitral stenosis the pulmonary arterial pressures may be elevated because of mitral stenosis and increased pulmonary blood flow, however, their effects are not additive, i.e. elevated pulmonary vascular resistance in these cases has better prognosis than elevated pulmonary vascular resistance with ventricular septal defect alone.

 

Congenital aneurysm of the sinus of Valsalva:

These are lesions affecting the coronary sinuses. The right coronary sinus is most common and then noncoronary and left coronary sinus is the rarest. The affected coronary sinus is thin and protrudes and later on it may rupture into a cardiac chamber and in the case of left coronary sinus may also rupture into the pericardium. The right coronary sinus when ruptures it communicates the aorta or with the right ventricular outflow tract and sometimes into the right ventricular cavity in the area of the perimembranous ventricular septal defect. The noncoronary sinus usually ruptures into the right atrium and less commonly into the right ventricle and rarely into the right atrium and right ventricle together. The left coronary sinus when ruptures communicates the aorta to the left atrium with or without the connection to the pericardium. Lesions associated with congenital aneurysm of the sinus of Valsalva include ventricular septal defects, aortic valve abnormalities, pulmonary stenosis and less commonly subaortic stenosis, coarctation of the aorta, tetralogy of Fallot and atrial septal defect.