OVERVIEW: What every practitioner needs to know
Are you sure your patient has a ventricular septal defect? What are the typical findings for this disease?
The most common symptoms associated with large ventricular septal defects are caused by increased pulmonary blood flow, which then leads to congestive heart failure. These symptoms include tachypnea, respiratory distress, frequent respiratory infections, feeding intolerance, and failure to thrive.
Most ventricular septal defects present with a murmur which usually extends throughout all of systole. The intensity of the murmur is almost always related to the size of the defect. The smaller the defect, the bigger the pressure gradient across the defect and the louder the murmur. The small and very restrictive defects are often associated with a systolic thrill. The murmur associated with tiny ventricular septal defects may occasionally not extend throughout all of systole. In contrast, big defects usually have little or no pressure difference between the left and right ventricles, making the holosystolic murmur softer or even absent. A diastolic murmur (rumble) may be heard from increased blood flow across the mitral valve in larger ventricular septal defects due to significantly increased pulmonary blood flow.
What physiologic factors determine how a patient with a ventricular septal defect presents?
A ventricular septal defect is a direct communication between the left and right ventricles. The direction and amount of flow across the defect are determined by several factors: 1) the difference in pressure between the ventricles, 2) the difference in resistance between the pulmonary and systemic vascular beds, and 3) the size of the defect.
The pulmonary vascular resistance is high in the fetus, whose lungs are filled with fluid. Although there is a sudden drop in the pulmonary vascular resistance with the first breath in the immediate neonatal period, the pulmonary vascular resistance may still be elevated in the first few days of life with a gradual drop to adult levels by around 3 to 6 months of age. Hence, the relatively small difference between the systemic and pulmonary vascular resistance will result in little if any left-to-right shunting across the defect in the first few hours of life, and the murmur may not be prominent or audible.
As the pulmonary vascular resistance drops, pulmonary blood flow increases. This results in increased pulmonary venous return to the left atrium and ventricle, and the added volume load to the left ventricle eventually results in dilation of the left atrial and left ventricular chambers.
The right ventricular and pulmonary pressures will decrease in patients with small or moderate-sized defects, leading to a bigger pressure difference between the left and right ventricles; this, in turn, results in a more prominent murmur. If the defect is large, the pressures in the right and left ventricles remain equal (the right ventricular and pulmonary pressures remain high), and the drop in pulmonary vascular resistance will result in increased pulmonary blood flow. These patients may not present with a murmur due to the absent or low pressure gradient across the defect. Instead, the increased pulmonary blood flow results in pulmonary edema which, in turn, causes tachypnea and respiratory distress, particularly during feeding.
Occasionally, the flow across the defect is directed from the right to the left ventricle, and the right-to-left shunt results in cyanosis. In this setting, the right ventricular pressure is higher than the left ventricular pressure. This may be secondary to significant obstruction along the right ventricular or pulmonary outflow tract at the subvalvar, valvar, or supravalvar level or along the branch pulmonary arteries.
One example of right-to-left flow across a ventricular septal defect in association with right ventricular outflow tract obstruction is tetralogy of Fallot. Severely elevated pulmonary vascular resistance can also cause right-to-left shunting at the ventricular septal defect; etiologies for this include primary or secondary pulmonary vascular obstructive disease (Eisenmenger syndrome), pulmonary vein stenosis, or mitral stenosis.
What are the anatomic variations of ventricular septal defects?
Ventricular septal defects are classified according to their location within the ventricular septum, although multiple classification systems, each with their own characteristic terminology, have evolved over the years. In most of these, four distinct categories of ventricular septal defects have been identified. The two most common types are membranous and muscular ventricular septal defects, and the other less common types include doubly-committed subarterial and inlet ventricular septal defects.
Membranous ventricular septal defects are located at and around the membranous septum below the aortic valve and behind the septal leaflet of the tricuspid valve (Figure 1). In fact, there is frequently accessory tricuspid valve tissue which partially covers membranous ventricular septal defects, and many of these defects close spontaneously because of further development of the overlying tricuspid valve tissue with adherence to the defect margins until there is no longer any interventricular shunting. The atrioventricular conduction pathway is almost always located along the posteroinferior margin of the defect.
Other terms for membranous ventricular septal defects include perimembranous, paramembranous, and subaortic ventricular septal defects. These defects can be associated with other cardiac malformations, such as a subaortic membrane or a double-chambered right ventricle. Occasionally, an aortic valve leaflet prolapses into the defect, resulting in progressive aortic regurgitation. Rarely, a membranous defect extends anteriorly into the outlet or conoventricular area with associated malalignment of the conal septum separating the right from the left ventricular outflow tract. These malalignment defects are usually seen in the setting of complex cardiac malformations such as tetralogy of Fallot, interrupted aortic arch with subaortic stenosis, or double outlet right ventricle.
Muscular ventricular septal defects are located in the muscular trabecular component of the ventricular septum away from the atrioventricular and semilunar valves (Figure 2). These defects are further subdivided based on their location in the muscular septum, and the most commonly used descriptors include mid, anterior, posterior, and apical muscular ventricular septal defects. Muscular defects can exist as single defects or as multiple defects (sometimes known as the “Swiss-cheese septum”). Occasionally, the interventricular pathways are complex, with a single orifice on the left ventricular side and multiple orifices on the right ventricular side. Small muscular defects can also close spontaneously as the muscular tissue surrounding the defect grows with the rest of the heart.
Doubly committed subarterial ventricular septal defects are located immediately below both the aortic and pulmonary valves and are therefore located anteriorly in the ventricular septum (Figure 3). In all of these cases, the conal septum separating the ventricular outflow tracts is deficient or absent, and aortic valve prolapse into these defects is common with consequent aortic regurgitation (Figure 4). Other terms for these defects include subpulmonary, supracristal, subarterial, infundibular, and conal ventricular septal defects. These defects rarely close spontaneously, and earlier surgery is more aggressively pursued if aortic regurgitation is present.
Inlet ventricular septal defects, the least common type, are associated with the atrioventricular valves and are therefore located posteriorly in the area of the atrioventricular canal (or atrioventricular septum) (Figure 5). These defects have also been called atrioventricular canal-type and perimembranous inlet ventricular septal defects, and they rarely close spontaneously. Although these defects can occur in isolation, they usually represent the ventricular component of complete atrioventricular canal defects.
What other disease/condition shares some of these symptoms?
Congestive heart failure can occur in the setting of: 1) pulmonary overcirculation secondary to a significant aortopulmonary shunt (such as a large patent ductus arteriosus, an aortopulmonary window, or a large arteriovenous malformation), or 2) pulmonary edema secondary to severe left ventricular dysfunction (due to a primary or secondary cardiomyopathy, anomalous origin of the left coronary artery from the pulmonary artery, or long-standing severe left ventricular outflow obstruction), or to significant obstruction to left atrial inflow or outflow (such as pulmonary vein stenosis, cor triatriatum, or mitral stenosis).
What caused this disease to develop at this time?
Ventricular septal defects are congenital heart defects, and as such are present at birth. Very rare causes of acquired ventricular septal defects are trauma to the heart or infarct to the ventricular septum leading to tissue death and rupture of the septum.
The murmurs associated with a ventricular septal defect may progressively become louder or softer, depending on the evolving pressure difference between the right and left ventricles and the amount of excess pulmonary blood flow. As the pressure gradient increases with or without an associated increase in pulmonary blood flow, the murmur becomes louder and higher in pitch.
Increasing pulmonary blood flow also determines how quickly the symptoms of congestive heart failure will develop. As the pulmonary blood flow increases with dropping pulmonary vascular resistance during the first few months of life, it becomes more likely that respiratory symptoms and feeding intolerance will ensue.
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
Patients with respiratory distress and a murmur should undergo a chest X-ray and electrocardiogram.
Patients with a significant ventricular septal defect will show evidence for left atrial and left ventricular enlargement on the electrocardiogram as well as cardiomegaly, increased pulmonary vascular markings, and/or evidence for pulmonary edema on the chest X-ray. However, the diagnosis of a ventricular septal defect is made by transthoracic echocardiography, and the study can usually delineate the shape, size, and location of the defect, the direction of flow across the defect, the pressure gradient across the defect, and other associated cardiac lesions.
Would imaging studies be helpful? If so, which ones?
In patients with poor transthoracic echocardiographic windows secondary to body habitus, old surgical scars on the chest, or other associated medical conditions, alternative imaging modalities may be necessary to characterize the defect and associated cardiovascular lesions.
The most commonly used modalities are cardiac magnetic resonance imaging, cardiac computed tomography with angiography, and transesophageal echocardiography. There are obvious limitations to the use of computed tomography in children because of radiation exposure, but recent advances with the use of prospective electrocardiographic gating are reducing the associated radiation dose to more acceptable levels.
Occasionally, it is important to measure the degree of shunting and the pulmonary vascular resistance in order to formulate an appropriate management plan, particularly in older children with significant ventricular septal defects. In these instances, a cardiac catheterization is necessary to calculate the relative flow within the pulmonary and systemic vascular beds as well as the pulmonary vascular resistance.
If the patient has developed pulmonary vascular obstructive disease (Eisenmenger syndrome), catheterization can also help to determine if the increased pulmonary vascular resistance will respond to oxygen supplementation or to medications.
Confirming the diagnosis
Patients with a pathologic murmur should be evaluated with an electrocardiogram and a chest X-ray, especially if there is associated respiratory distress and/or failure to thrive. If the electrocardiogram reveals increased left-sided forces and the chest X-ray reveals cardiomegaly with or without increased pulmonary vascular markings, then a ventricular septal defect should be suspected. At this point, a transthoracic echocardiogram is necessary to make the diagnosis.
As stated previously, cardiac magnetic resonance imaging, cardiac computed tomography with angiography, and tranesophageal echocardiography may also be helpful, especially in patients with poor transthoracic echocardiographic windows.
According to the 2008 guidelines from the American College of Cardiology and the American Heart Association for the management of adults with congenital heart disease, a class IIa indication for cardiac catheterization in patients with a ventricular septal defect is inadequate information from standard noninvasive studies. In these instances, catheterization can provide quantitative data such as the degree of shunting, pulmonary arterial pressures, and pulmonary vascular resistance (level of evidence B) as well as qualitative data regarding the morphology and extent of the ventricular septal defect(s) as well as other associated lesions (level of evidence C).
If you are able to confirm that the patient has a ventricular septal defect, what treatment should be initiated?
If a patient with a small ventricular septal defect is asymptomatic, treatment is usually unnecessary. Most patients with a small ventricular septal defect lead normal lives and do not require any intervention. If the presentation occurs in the neonatal period and the defect is moderate to large in size, then the asymptomatic neonate should be observed carefully during the first 3 months of life for signs and symptoms of congestive heart failure as the pulmonary vascular resistance gradually drops to adult levels.
Infants who develop respiratory distress and failure to gain weight should be managed medically with diuretics and afterload reduction. It is especially important to optimize medical management in patients with membranous or muscular ventricular septal defects since spontaneous closure may still occur during the first ten years of life.
Occasionally, surgical intervention is necessary. Children with persistent failure to thrive and/or respiratory distress despite maximum medical management should be treated surgically. In addition, surgery is also indicated in children with moderate or large defects and who are at risk for developing pulmonary vascular obstructive disease if the pulmonary overcirculation is not addressed before two years of age. In patients with Trisomy 21 the threshold for surgery is typically lower due to the increased risk of development of pulmonary vascular obstructive disease in this population.
If there is a chance that spontaneous closure can still occur (that is, if the patient has a moderate membranous or muscular ventricular septal defect), or if the patient cannot be placed on cardiopulmonary bypass support because of clinical status or other medical reasons, or if closure of the defect cannot be performed safely and adequately because of small size of the child and the complexity of the defect, then pulmonary artery banding is a good surgical palliation. This procedure limits pulmonary blood flow and protects the distal pulmonary vascular bed from developing pulmonary vascular obstructive disease, and it does not require cardiopulmonary bypass support. The band can then be removed at a later time when the defect is no longer clinically significant or when the child is able to undergo safe corrective ventricular septal defect closure. This approach has been particularly helpful in patients with Swiss-cheese type muscular ventricular septal defects, where surgical closure of all defects can be technically difficult.
If the defect is a doubly-committed subarterial or an inlet ventricular septal defect, or if the membranous or muscular ventricular septal defect is so large that there is little to no chance of spontaneous closure, or if there are multiple defects, then patch closure of the defect (or defects) with cardiopulmonary bypass support is the treatment of choice.
Patients with membranous or doubly-committed subarterial defects and progressive aortic regurgitation secondary to aortic valve prolapse should undergo surgical closure of the defect regardless of the size of the defect to prevent worsening aortic regurgitation and avoid the need for aortic valve replacement.
Lastly, patients with other associated cardiovascular lesions such as right or left ventricular outflow tract obstruction will often require a comprehensive surgical approach to correct most or all of the problems.
According to the 2008 guidelines from the American College of Cardiology and the American Heart Association for the management of adults with congenital heart disease, class I indications for surgical closure include a systemic-to-pulmonary blood flow ratio that is greater than 2 and evidence for left ventricular volume overload (level of evidence B) as well as a history of infective endocarditis (level of evidence C).
Class IIa indications include a systemic-to-pulmonary blood flow ratio that is greater than 1.5 with a pulmonary artery pressure that is less than two-thirds of the systemic pressure, a pulmonary vascular resistance that is less than two-thirds of the systemic vascular resistance, or evidence for left ventricular systolic or diastolic failure (level of evidence B).
More recently, patients with significant muscular ventricular septal defects who have survived into adulthood without intervention and some patients with postoperative residual ventricular septal defects have undergone transcatheter or perventricular (through a small chest incision) device closure in order to alleviate associated symptomatology such as dyspnea, exercise intolerance, and arrhythmia secondary to left atrial dilation. Device closure is feasible only if the defect is not in close proximity with the aortic or atrioventricular valves. This approach has also been utilized in adults with post-infarction ventricular septal defects for initial stabilization prior to delayed surgical correction.
Ventricular septal defect closure is not recommended in patients with severe irreversible pulmonary vascular obstructive disease (Eisenmenger syndrome) (level of evidence B). In these patients, medical management with pulmonary vasodilators may be appropriate.
Although patients with ventricular septal defects have been treated with endocarditis prophylaxis in the past, recent guidelines from the American Heart Association no longer include ventricular septal defects among the cardiac conditions for which endocarditis prophylaxis is a reasonable approach, unless there is right-to-left shunting across the defect, there is a residual defect after patch or device closure, or it is during the first six months after patch or device closure with successful repair of the defect.
What are the adverse effects associated with each treatment option?
Children with ventricular septal defects who are managed medically with diuretics and afterload reduction are at risk for developing renal dysfunction, particularly if they become dehydrated in the setting of fever, diarrhea, or vomiting. Hearing loss has also resulted from long-term use of loop diuretics.
In children with large ventricular septal defects and markedly increased pulmonary blood flow, the persistently elevated pulmonary vascular resistance may evolve into irreversible pulmonary vascular obstructive disease (pulmonary hypertension or Eisenmenger syndrome). This risk is especially increased in children with Down syndrome. When severe pulmonary vascular obstructive disease ensues, blood flows across the defect from the right to the left ventricle, resulting in cyanosis. In this instance, attempting to close the defect would result in decreased pulmonary blood flow, decreased pulmonary venous return, and decreased cardiac output.
In children who have undergone main pulmonary artery band placement, the band may slide distally into one or both of the branch pulmonary arteries. If only one branch pulmonary artery is preferentially protected by the band, the other branch pulmonary artery is at increased risk for developing early unilateral pulmonary vascular obstructive disease. Because the band does not grow as the rest of the heart grows, children with a main pulmonary artery band become more cyanotic with the progressive increase in the relative obstruction across the band. In addition, the band may cause anatomic distortion of the pulmonary vessel, occasionally requiring reconstructive surgery to alleviate residual obstruction along the original band site at the time of ventricular septal defect closure.
Ventricular septal defect closure should decrease pulmonary blood flow and eradicate the cause for ventricular volume overload. The immediate complications associated with surgical closure include atrioventricular block (sometimes requiring a permanent pacemaker implantation), residual ventricular septal defect, infection, and pericardial effusion. Because closure of a large defect means that the left ventricle is no longer exposed to the low resistance of the pulmonary vascular bed, the increased left ventricular afterload occasionally results in transient left ventricular systolic dysfunction.
If left ventricular systolic dysfunction has developed prior to surgical intervention, closure of the defect may not result in improvement of ventricular function. In addition, if irreversible pulmonary vascular obstructive disease has developed, the pulmonary artery pressure will not decrease with closure. If the defect is closed because of significant aortic valve prolapse, the degree of aortic regurgitation may also not decrease after closure.
As stated previously, transcatheter or perventricular device closure of a muscular ventricular septal defect must occur only in defects which are not in close proximity with the aortic or atrioventricular valves, given the potential for disrupting an adjacent valve apparatus. Careful evaluation of the defect size in multiple planes is crucial, since underestimation of defect size can result in placement of a device which is not big enough, with consequent embolization of the device. Three-dimensional echocardiography with an “en face” display of the ventricular septum from both the left and right ventricular aspects has been quite helpful in terms of more accurate assessment of the size and shape of these ventricular septal defects. Lastly, the surrounding muscular ventricular septum is often quite friable in the area of a myocardial infarction, and device closure must absolutely take this into account.
What are the possible outcomes of ventricular septal defects?
A small ventricular septal defect may not require any intervention other than periodic visits to a pediatric cardiologist.
Small to moderate defects may eventually become smaller and close spontaneously. Congenital ventricular septal defects do not grow with the heart; thus relative to the heart they become smaller with somatic growth.
If an infant with a significant ventricular septal defect develops signs and symptoms of congestive heart failure, medical management with diuretics and afterload reduction may alleviate some or all of the symptoms. Sometimes increased caloric density is required to achieve weight gain. If maximum medical management does not result in improved respiratory status and weight gain, pulmonary artery banding or surgical closure may be necessary. Pulmonary artery banding will require another surgery to take down the band and/or close the defect.
If done before the onset of left ventricular systolic dysfunction or pulmonary vascular obstructive disease, uncomplicated surgical closure of a ventricular septal defect should result in relief of symptoms with normal development of the child. If there is a small residual defect after patch closure, the patient must receive endocarditis prophylaxis with dental procedures or minor operations.
Right ventricular outflow tract obstruction (such as a double-chambered right ventricle ) or left ventricular outflow tract obstruction (such as a subaortic fibromuscular ridge) may develop after initial presentation. In these instances, comprehensive surgical correction of all the problems may be necessary.
Patients without symptoms and those who respond appropriately to medical management with good weight gain do well. As the child grows, the relative size of the defect often decreases, and, in many instances, the child can be weaned from the medication(s). If the medications cannot be discontinued without the recurrence of symptoms, then surgical or transcatheter closure should be considered, but not until the child is considerably bigger in size.
At this time, the risks associated with surgical closure of a single uncomplicated ventricular septal defect are quite low, and most of the immediate postoperative complications (such as atrioventricular block, residual ventricular septal defect, infection, and pericardial effusion) are usually transient. Occasionally additional treatment is necessary to address these complications.
The risks associated with surgical closure of a defect increases with other associated lesions, left ventricular systolic dysfunction, and pulmonary vascular obstructive disease. Although the Second Natural History Study of Congenital Heart Defects (NHS-2) published in 1993 reports a 25-year survival of 87% for all patients with ventricular septal defects, this number is better in the current era with earlier intervention and improvements in medical and surgical management of these patients.
What causes this disease and how frequent is it?
Aside from the bicuspid aortic valve and mitral valve prolapse, ventricular septal defects represent the most common type of congenital heart disease. Studies involving echocardiographic evaluation of all neonates in a nursery reveal an incidence of up to 2%-5%, although most of these defects close spontaneously by a year of age. As a result, published incidence rates may vary depending on which age groups are included in the study.
In a meta-analysis of the incidence of congenital heart disease published by Julien Hoffman and Samuel Kaplan in 2002, review of 43 incidence/prevalence studies reveals a mean incidence of 3.57 per 1000 live births for ventricular septal defects. A ventricular septal defect was also the most common diagnosis among over 83,000 patients referred to Children’s Hospital Boston for cardiac evaluation from 1975 to 2002, with a frequency between 9% and 14% among all the patients (Treidman JK. Methodologic issues for database development: trends. In: Keane JF, Lock, JE, Fyler DC, eds. Nadas’ pediatric cardiology. 2nd ed. Elsevier; 2006: 323-36).
In the report published in 1980 from the New England Regional Infant Care Program of 2,033 infants diagnosed with congenital heart disease from 1975 to 1977, the frequency of ventricular septal defects among all the congenital heart diseases was 18.9%.
Incidence rates do not appear to be affected by sex, maternal age, or socioeconomic status. Race also does not appear to play a big determining factor, although doubly-committed subarterial ventricular septal defects are seen more commonly in Asians than in non-Asians.
Embryologically, a ventricular septal defect is the result of failure of the normal septation which occurs between the primordial right and left ventricles from 4 to 7 weeks of gestation. Normally, the developing muscular ventricular septum forms from the fusion of the atrioventricular cushions, the muscular ridge separating the trabecular right and left ventricular chambers, and the outflow tract cushions.
The precise etiology for the disruption of normal ventricular septation is not known, although both genetic and environmental factors have been implicated in the development of ventricular septal defects.
Chromosomal abnormalities such as trisomy 21, 18, and 13 frequently present with a significant ventricular septal defect.
The gene mutation found in patients with Holt-Oram syndrome has been found to cause both the limb abnormalities and the septal defects which are the hallmarks of this autosomal dominant disease.
Children of people with a ventricular septal defect have a higher incidence of having a ventricular septal defect.
In addition, paternal use of marijuana and cocaine have both been associated with a higher occurrence of ventricular septal defects in the offspring.
How do these pathogens/genes/exposures cause the disease?
The mechanism by which chromosomal abnormalities, gene mutations, and paternal use of certain drugs are related to the development of a ventricular septal defect is not known.
Other clinical manifestations that might help with diagnosis and management
A diastolic rumble or murmur in the area of the mitral valve near the apex of the heart can result from a significant amount of left-to-right shunting across a ventricular septal defect (similar to the diastolic rumble in the area of the tricuspid valve which can occur in association with a large atrial septal defect).
The increased pulmonary blood flow results in increased pulmonary venous return to the left atrium, and the large volume of blood crossing the fixed mitral annulus then results in relative (rather than anatomic) mitral stenosis. The presence of a diastolic rumble suggests a pulmonary-to-systemic blood flow ratio that is greater than 2.
What complications might you expect from the disease or treatment of the disease?
The potential complications are outlined in the discussion of adverse effects of the treatment options.
Are additional laboratory studies available; even some that are not widely available?
There are no additional laboratory studies to help with the diagnosis.
How can ventricular septal defects be prevented?
There are no known therapies which can help in the prevention of ventricular septal defects.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has a ventricular septal defect? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has a ventricular septal defect, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of ventricular septal defects?
- What causes this disease and how frequent is it?
- How do these pathogens/genes/exposures cause the disease?
- Other clinical manifestations that might help with diagnosis and management
- What complications might you expect from the disease or treatment of the disease?
- Are additional laboratory studies available; even some that are not widely available?
- How can ventricular septal defects be prevented?