AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Normal closure of the ventricular septum occurs through 3 concurrent embryologic mechanisms that help to close the membranous portion of the septum: (1) downward growth of the conotruncal ridges forming the outlet septum, (2) growth of the endocardial cushions forming the inlet septum, and (3) growth of the muscular septum forming the apical and mid-muscular portions of the septum.

Ventricular septal defect (VSD) occurs when any portion of the ventricular septum does not close after the seventh week of gestation. These defects are single or multiple. VSD occurs in any portion of the interventricular septum including the membranous, muscular, inlet, or outlet septum, or a combination of locations.

Precise etiology of any delay in closure is unknown. Defects in the inlet septum may occur due to incomplete fusion of the right endocardial cushion with the muscular septum. Outlet VSD may occur because of failure of fusion of the conal septum. Muscular defects may occur because of lack of merging of the walls of the trabecular septum or excessive resorption of muscular tissue during ventricular growth and remodeling. Membranous VSD occurs because of failure of fusion of the endocardial cushions, the conotruncal ridges, and the muscular septum.

VSDs are typically classified according to the location of the defect in 1 of the 4 ventricular components: the inlet septum, trabecular septum, outlet/infundibular septum, or membranous septum.

Classification

Inlet VSD

• Located posterior and inferior to the membranous septum, immediately beneath the septal leaflet of the tricuspid valve.
• This form comprises 5-10% of VSDs.

Trabecular (muscular) VSD

• This VSD is most often located near the cardiac apex.
• Also, it occurs centrally or along the margin of the septum and free wall (anterior VSD).
• This form is the second most common type of VSD, occurring in 5-20% of most series.
• Muscular VSD is also known as Swiss cheese VSD.
• Frequently, spontaneous closure of muscular VSD occursin the first 2 years of life, the majority by 6 months.

Outlet VSD

• This type is located in the right ventricle (RV) infundibulum, beneath the pulmonary valve.
• It comprises 5-7% of diagnosed VSD.
• Higher incidence occurs in Asian populations (25-30%).
• Acquired aortic regurgitation may occur due to prolapse of the right coronary leaflet into a subpulmonary defect.

Membranous VSD

• This form is located in the left ventricle (LV) outflow tract, beneath the aortic valve.
• It is the most common VSD subtype, occurring in 75-80% of cases.
• Defects may extend into adjacent portions of the ventricular septum.
• It also is called perimembranous VSD or aneurysm of membranous septum.
• The defect may be partially or completely occluded by the septal leaflet of the tricuspid valve.

Pathophysiology

The hemodynamic significance of VSD primarily is determined by 2 factors: size of the defect and state of the pulmonary vascular resistance (PVR), including right ventricular outflow obstruction.

In small-to-moderate VSDs, left-to-right shunting primarily is limited by the size of the defect. In large VSDs, without right ventricular outflow obstruction, left-to-right shunting is determined by the relative degree of pulmonary and systemic vascular resistance.

Because PVR is high at birth and does not reach its nadir until age 6-8 weeks, significant left-to-right shunting with development of congestive heart failure (CHF) often is delayed until the second or third month of life. Additional cardiac lesions that increase left-to-right shunting (eg, atrial septal defect, patent ductus arteriosus) may predispose patients to earlier development of CHF. Noncardiac abnormalities, including prematurity, infection, anemia, or other congenital anomalies also may predispose infants to significant symptoms of heart failure.

Additional congenital heart lesions (eg, RV outflow tract obstruction, pulmonary valve stenosis, pulmonary venous obstruction, persistent elevation of pulmonary vascular resistance, mitral stenosis) can restrict shunting, even leading to right-to-left trans-VSD flow, depending on the ultimate resistance balance between the systemic and the total right-sided resistances.

Frequency

United States

VSD is the most common congenital heart defect in the first 3 decades of life, with an incidence between 1.5-3.5 cases for every 1000 liveborn term infants. VSD is more common in premature infants, with an incidence of 4.5-7.0 cases for every 1000 liveborn infants. Clinically significant VSD requiring medical or surgical management accounts for only 15% of such defects (0.35-0.50 cases for every 1000 livebirths). When viewing congenital heart disease in total, solitary VSD cases account for 20% of congenital heart disease. Muscular VSD is the second most common type, accounting for up to 20% of VSD identified in most surgical or autopsy series.

Mortality/Morbidity

• Morbidity and mortality are influenced by the number and size of VSDs, the degree of left-to-right shunting, presence of associated congenital heart defects, presence of associated noncardiac defects and syndromes, and age at repair of VSD.
• Muscular and membranous VSDs may spontaneously decrease in size and eventually close. Small muscular VSDs have the greatest likelihood of spontaneous closure, with closure rates approaching 80-90% by age 2 years. Muscular defects in these patients decrease in size due to growth of the ventricular myocardium, which fills in the defect. A recent study utilizing fetal echocardiography showed that 33% of all defects closed in utero, 44% of defects closed spontaneously within the first postnatal year, and 23% of defects did not close
• Membranous VSD also may close during infancy or childhood, with up to 50% closure rates in some series. Patients with a small VSD have an excellent prognosis. Many small defects decrease in size or spontaneously close.Continued follow-up care is warranted until documented VSD closure occurs. Since a small risk of bacterial endocarditis exists with these defects, continue subacute bacterial endocarditis (SBE) prophylaxis until closure of VSD occurs.
• Small membranous VSDs may lead to development of aortic insufficiency. For patients with moderate-sized VSD, defects may allow the development of large left-to-right shunting in the first few months of life as pulmonary vascular resistance falls. Failure of medical management with persistent evidence of congestive heart failure (CHF) is the primary indication for surgical closure of moderate-sized defects. Fewer than 25% of moderate-sized defects will require surgical closure.
• For patients with large VSDs, surgical repair is indicated at any time during the first year of life if the infant fails to grow appropriately despite optimal medical management. Surgical risk and mortality for patients with large VSDs is higher in the first 2 months of life (10-20%) than after age 6 months (1-2%), although these figures currently are decreasing. Elective surgical closure of large VSDs should be planned within the first year of life to prevent development of irreversible pulmonary vascular obstructive disease (ie, Eisenmenger syndrome).

Race

• Inheritance patterns of different VSDs vary considerably by race.
• Defects located in a subpulmonary position, such as supracristal defect, are more common in the Asian population.
• Muscular VSD has no known racial predilection.

Sex

VSD is slightly more common in females than in males.

Age

• Large muscular VSD may not present until 6-8 weeks of age, when decreased pulmonary vascular resistance allows significant left-to-right shunting and clinical signs and symptoms of CHF.
• Most muscular VSDs present clinically in the neonatal period. Typically, these defects, especially the smaller defects, are not suspected at birth and may not be identified by auscultation until pulmonary vascular resistance begins to fall in the first few days to weeks of life.
• The VSD may manifest soon after birth if it is associated with significant additional congenital heart lesions or if it occurs with an associated chromosomal anomaly or syndrome.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Murmur
• • Most patients with small muscular ventricular septal defects (VSDs) are asymptomatic and come to medical attention due to the discovery of a systolic murmur.
  • Most murmurs have a delayed presentation in the newborn period, occurring in the first few days to weeks of age.
  • At birth, PVR is high which maintains an elevated RV pressure equal to LV pressure. As the PVR falls, the developing pressure gradient from LV to the RV allows high-velocity left-to-right shunting across the muscular VSD producing the typical holosystolic murmur.
• Progression of symptoms
• • Patients with an isolated large muscular VSD typically are asymptomatic in the immediate newborn period.
  • As PVR falls, the degree of left-to-right shunting is proportional to the size of the defect and the relative degree of PVR.
  • CHF signs include inadequate weight gain and growth along with recurrent lower respiratory tract infections in patients with large VSD without evidence of CHF but with elevated pulmonary artery pressure (greater than 50% systemic pressure) or greater than a ratio of 2:1.
  • The larger the VSD and the lower the PVR, the greater is the degree of left-to-right shunting.
  • Typically, infants with large VSDs present with signs and symptoms of CHF at age 6-8 weeks or later as PVR continues to fall and the degree of left-to-right shunting increases. Signs and symptoms include poor feeding, decreased weight gain, tachypnea, tachycardia, sweating (especially after feeding), and lethargy.
• Chromosomal anomalies
• • VSD is the most common congenital heart lesion (20-30%) in infants with chromosomal anomalies or syndromes.
  • Defects may be discovered in the first days of life due to additional diagnostic evaluation to exclude multiple congenital defects.

Physical

Typical physical examination findings are influenced to a significant degree by the size of the VSD and the degree of left-to-right shunting.

• Small VSD
• • Physical examination findings and weight gain are normal.
  • The precordium is quiet with a normal apical impulse.
  • The first heart sound is normal.
  • The second heart sound is typically narrowly split. The pulmonary component may be accentuated.
  • A third heart sound is generally not present.
  • Small defects may have a palpable thrill at the middle-to-lower left sternal border.
  • A grade III-VI/VI holosystolic murmur, which widely radiates throughout the precordium, is present along the left sternal border.
  • Intensity of the murmur is directly proportional to the size of the defect, the LV-to-RV pressure gradient, and the degree of left-to-right shunting. In general, smaller defects produce the loudest murmur.
  • Systolic murmurs are usually holosystolic but may occasionally be crescendo or crescendo decrescendo.
  • No diastolic murmur is typically present unless prolapse of the aortic cusp into a subpulmonary defect exists.
• Large VSD
• • Poor growth and poor weight gain are common.
  • Signs and symptoms of CHF may be present, including tachypnea, tachycardia, sweating, and pallor.
  • Hyperdynamic precordium with or without a precordial bulge is due to underlying cardiomegaly.
  • Abnormal apical impulse with or without right ventricular tap is present; a thrill is uncommon with large VSDs.
  • A normal first heart sound and a narrowly split second heart sound with a loud pulmonary component are evident.
  • A prominent third heart sound is typically present at the apex, producing a gallop rhythm.
  • A loud holosystolic murmur is maximal at the left sternal border with wide precordial radiation.
  • A diastolic flow rumble may be present at the cardiac apex.
  • This diastolic murmur is caused by a significant left-to-right shunt (at least a 2:1 left-to-right shunt) with excessive flow across a normal-sized mitral annulus.

Causes

• Inheritance
• • VSDs have a multifactorial etiology.
  • No correlation exists with maternal age or birth order.
• Associated syndromes
• • VSD is the most common congenital heart lesion in most chromosomal anomalies and syndromes.
  • VSD is especially common in patients with trisomy 13, trisomy 18, and trisomy 21. In addition, there are numerous single gene deletion syndromes associated with VSDs.
  • The majority of VSDs (greater than 95%) are not associated with chromosomal abnormalities.
• Associated noncardiac conditions
• • Prematurity
  • Syndromes and chromosomal anomalies
• Risk factors: No known risk factors exist for the development of VSD.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No specific laboratory blood tests are indicated.

Imaging Studies

• Chest radiography
• • Small ventricular septal defects (VSDs) show normal cardiac size and normal pulmonary vascularity.
  • Large VSDs demonstrate cardiac enlargement and increased pulmonary vascular markings proportional to size of left-to-right shunt, left atrial and left ventricular enlargement, posterior displacement of left ventricular apex, and prominence of main pulmonary artery segment.
• Two-dimensional echocardiography and Doppler
• • Two-dimensional echocardiography with Doppler color flow mapping is the most reliable noninvasive modality to identify the presence, size, number, and location of the VSD.
  • Muscular VSD is readily identified from the apical 4-chamber, parasternal long axis, and parasternal short axis scan planes.
  • Small VSDs (defined as VSD dimension less than half the size of the aortic annulus diameter) usually are isolated defects with otherwise normal cardiac anatomy and function.
  • Large VSDs (defined as defect size equal to the diameter of the aortic annulus) typically have left atrial and left ventricular dilation with normal left ventricular systolic and diastolic function.
  • Dilation of the main and branch pulmonary arteries is also common.
  • Echocardiography is also useful in determining the presence of aneurysmal tissue on the right ventricular surface in closing defects, right ventricular muscle bundles, infundibular stenosis, pulmonary valve stenosis, and associated left-sided lesions, such as subaortic membrane, aortic stenosis, aortic cusp prolapse, or coarctation of the aorta.
  • Doppler echocardiography can be used to predict the intracardiac pressure gradient from LV to RV using the continuous wave Doppler tracing (modified Bernoulli equation = 4 [velocity squared] and subtracting the calculated gradient from the aortic systolic blood pressure [in the absence of aortic stenosis] ).
  • Color Doppler is useful to determine VSD location and size as well as the degree of intracardiac shunting.
  • These tests are also essential to rule out other commonly associated congenital heart lesions including atrial septal defects, patent ductus arteriosus, pulmonary valve stenosis, and complex congenital heart disease with associated VSD.
• Magnetic resonance imaging
• • Cardiac MRI is a useful adjunct in the evaluation of VSD. Black blood imaging at end-diastole reliably shows the anatomy of the ventricular septum, ventricular chambers, and great vessels. Bright blood gradient-echo dynamic images are useful for evaluating the anatomy in all segments of the cardiac cycle.
  • Flow-sensitive phase contrast imaging is the criterion standard for determining the direction and magnitude of shunting. It can alleviate the requirement for cardiac catheterization in some cases.
• Three-dimensional echocardiography
• • With the development of real-time three-dimensional echocardiography (RT3DE), this modality can be applied to the characterization of the ventricular septum.
  • RT3DE allows accurate determination of VSD size, shape, and location. The short acquisition time and acceptable reconstruction time make this technique clinically applicable.

Other Tests

• Electrocardiography
• • ECG findings are variable depending on the VSD size and the degree of intracardiac shunting.
  • Small VSD shows normal ECG.
  • Large VSD shows left ventricular hypertrophy (LVH) (ie, volume overload), right ventricular hypertrophy (RVH) (ie, pressure overload), and left atrial enlargement.

Procedures

• Cardiac catheterization
• • Indications for cardiac catheterization in patients with VSD include inadequate noninvasive assessment of size, number, or location of VSD by echocardiography.
  • Other indications include the requirement of determining additional hemodynamic data prior to medical management or surgical repair (eg, determination of pulmonary vascular resistance and its reactivity, quantitation of left-to-right shunting, and exclusion of associated congenital heart defects).
• Angiography
• • Muscular VSDs are best demonstrated in the long axial oblique orientation.
  • Anterior muscular defects are best demonstrated with right anterior oblique angulation
  • Posterior muscular defects are best visualized with the hepatoclavicular view.
  • Angiography is a useful method to identify multiple defects in the muscular septum, but these are usually well visualized by careful ultrasound examination.

Histologic Findings

No specific histologic abnormality is present. However, lung biopsy findings are sometimes used to stage degrees of pulmonary vascular obstructive disease.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Small muscular ventricular septal defects (VSDs) have a high spontaneous closure rate (80-90%) within the first 2 years of life and often require no medical or surgical management.
• Larger defects may not close but may become smaller with time.
• Medical therapy may be required with large muscular VSD due to excessive left-to-right shunting and the development of CHF. Therapy typically includes one or all of the following: diuretic, digoxin, and ACE inhibitor.
• Digoxin is an inotrope used to augment ventricular contractility. Diuretic therapy with furosemide is used to lessen volume overload. Significant potassium wasting may warrant the addition of spironolactone or potassium supplementation.
• Use of afterload reduction to improve systemic-pulmonary flow ratios may be beneficial in selected cases. ACE inhibitors also inhibit the tissue-based renin-angiotensin system, preventing deleterious remodeling. Be aware that ACE inhibitors have a potassium-sparing effect. When these are employed, spironolactone or supplemental potassium should be avoided or used judiciously.

Surgical Care

• Failure of medical management in the first 6 months of life requires surgical repair.
• Growth failure despite optimal medical therapy and maximized caloric intake is the most important evidence of failure of medical therapy.
• Catheter intervention and similar devices are currently undergoing FDA investigational trials for closure of a VSD, especially in the muscular septum.
• Muscular VSDs that may be candidates for device closure are defects that are less than 2 centimeters in size and located in the apical position of the ventricular septum.
• Inlet, outlet, and malalignment VSDs are not indicated for device closure.
• The left-to-right shunt usually is electively repaired within the first year of life.
• Surgical repair of an isolated large VSD involves closure of the muscular defect with a Gore-Tex patch.
• Patients with multiple muscular VSD may undergo pulmonary artery banding if primary repair is deemed too risky. This palliative procedure limits the degree of left-to-right shunting and allows additional time for these defects to decrease in size or undergo spontaneous closure.
• Older children and adults with an unoperated large VSD usually require cardiac catheterization prior to surgical closure to assess pulmonary vascular resistance.
• Elevated pulmonary arteriolar resistance more than 12 Wood units, which does not decrease with oxygen or selective pulmonary vasodilator therapy, may be regarded as inoperable.
• Surgical intervention in younger infants, especially those younger than 1-month of age, has increased risk of mortality (historically as high as 10-20%).
• Surgical mortality is low (1-2%) in patients older than 6 months of age with isolated large muscular VSDs.
• Techniques for VSD closure devices
• • Ventricular septal devices typically have 2 asymmetrical opposing discs (1 for the right ventricular side, and 1 for the left ventricular side), which are released during catheterization under fluoroscopic and transesophageal echocardiographic guidance to occlude the defect. Recent data suggest that closure of small muscular VSDs in patients with otherwise normal anatomy offers less short-term morbidity with similar results. However, the long-term morbidity is unknown.
  • VSD closure devices are placed within muscular VSD during cardiac catheterization.
  • Ongoing investigational trials currently are being performed to assess indications and outcomes in VSD closure with these devices.
  • Intractable CHF, despite optimal medical therapy, is the major indication for surgical closure in infants with a large VSD.
  • Recent data suggests that the ventricular septal occluder does not cause interventricular conduction disturbances in greater numbers than surgical repair.

Consultations

• Pediatric cardiologist
• Pediatric cardiothoracic surgeon

Diet

• No special diet is required.
• For patients with significant CHF, caloric supplementation often is required using fortified formula or breast milk.

Activity

• Patients with small muscular VSDs can maintain normal activity.
• Patients with moderate-to-large defects with significant symptomatology may self-limit strenuous exercise until the defect is repaired.
• Patients with repaired VSD and no residual cardiac sequelae can resume regular activity.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Diuretics are the mainstay of medical therapy in infants and children with large VSDs, large left-to-right shunts, and evidence of congestive heart failure. Many centers also employ digoxin, but some debate exists about its efficacy, especially in the infant. Hemoglobin level should be adequate. Afterload reduction, in certain situations, also may be beneficial.

Drug Category: Inotropic agents

These agents are used to augment ventricular contractility. Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic CHF. Some also may increase or decrease the heart rate (ie, positive or negative chronotropic agents), provide vasodilatation, or improve myocardial relaxation. These additional properties influence the choice of drug for specific circumstances. Digoxin is used predominantly for inotropic effect.

Drug Category: Afterload Reduction

These drugs decrease systemic afterload and, therefore, may decrease left-to-right shunting through a large VSD. Used to improve preoperative or postoperative cardiac output. They reduce systemic vascular resistance and increase systemic blood flow resulting from myocardial dysfunction and/or significant mitral valve insufficiency.

Drug Category: Diuretics

These agents relieve ventricular volume load and peripheral and pulmonary congestion. They promote excretion of water and electrolytes by the kidneys and are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Routine inpatient monitoring of infants and children with small muscular ventricular septal defect (VSD) is not necessary.
• Mild-to-moderate CHF secondary to large left-to-right shunting from a VSD may be managed in an outpatient setting.
• Hospitalization for severe CHF usually indicates the need for early surgical intervention for VSD closure.

Further Outpatient Care

• Small muscular VSDs have a high incidence of spontaneous closure.
• Serial follow-up care should be performed until spontaneous closure occurs.
• Prevention of bacterial endocarditis with antimicrobial prophylaxis is needed until the VSD closes. The guidelines for antimicrobial choice and dosage are documented by American Heart Association.
• Moderate-sized VSDs can be followed in the outpatient setting while awaiting evidence of reduction in size or spontaneous closure.
• Serial patient follow-up care is required for assessment of patient growth and ongoing evaluation of the need for elective surgical closure.
• Patients with a large VSD without significant CHF can be followed as an outpatient.
• Infants not responding to medical therapy (poor weight gain) are candidates for surgical closure of their VSD.

In/Out Patient Meds

• Digoxin is used as an inotrope to augment ventricular contractility in patients with a large VSD and evidence of CHF.
• Diuretics, such as furosemide and Aldactone, decrease volume overload in patients with large VSDs.
• Captopril or enalapril may affect afterload reduction in selected cases.

Transfer

• Transfer to a tertiary care center may be required for further diagnostic evaluation or surgical intervention in patients with large VSDs or multiple VSDs.

Deterrence/Prevention

• No specific activity exclusions exist.
• Patients with large VSDs may be limited by symptoms secondary to CHF.

Complications

• CHF
• Bacterial endocarditis
• Eisenmenger syndrome
• Aortic insufficiency
• Subaortic stenosis

Prognosis

• Children with small-to-moderate sized VSDs have an excellent prognosis.
• Infants and children with large VSDs have a good, overall prognosis.
• Optimal medical management with appropriate timing of surgical intervention in these patients leads to the best outcome.

Patient Education

• Advise patient and/or parents regarding bacterial endocarditis indications and prophylaxis.
• Educate them concerning signs and symptoms of CHF.
• For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Ventricular Septal Defect.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to intervene with surgical closure prior to the development of pulmonary vascular obstructive disease
• Failure to detect associated heart lesions or sequela prior to, or following, surgery (aortic insufficiency and subaortic stenosis)
• Failure to counsel or prescribe bacterial endocarditis prophylaxis

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Aleem IS, Karamlou T, Benson LN, McCrindle BW. Transcatheter device versus surgical closure of ventricular septal defects: a clinical decision analysis. Catheter Cardiovasc Interv. Apr 2006;67(4):630-6. [Medline].
• Arciniegas E, Farooki ZQ, Hakimi M, et al. Surgical closure of ventricular septal defect during the first twelve months of life. J Thorac Cardiovasc Surg. Dec 1980;80(6):921-8. [Medline].
• Axt-Fliedner R, Schwarze A, Smrcek J, et al. Isolated ventricular septal defects detected by color Doppler imaging: evolution during fetal and first year of postnatal life. Ultrasound Obstet Gynecol. Mar 2006;27(3):266-73. [Medline].
• Dammann JF, Thompson WM, Sosa O. Anatomy, physiology and natural history of simple ventricular septal defects. Am J Cardiol. 1960;5:136-66.
• Ellis JH 4th, Moodie DS, Sterba R, et al. Ventricular septal defect in the adult: natural and unnatural history. Am Heart J. Jul 1987;114(1 Pt 1):115-20. [Medline].
• Gibbin C, Touch S, Broth RE, Berghella V. Abdominal wall defects and congenital heart disease. Ultrasound Obstet Gynecol. Apr 2003;21(4):334-7. [Medline].
• Haworth SG. Pulmonary vascular disease in ventricular septal defect: structural and functional correlations in lung biopsies from 85 patients, with outcome of intracardiac repair. J Pathol. Jul 1987;152(3):157-68. [Medline].
• Hoffman JI, Rudolph AM. The natural history of ventricular septal defects in infancy. Am J Cardiol. Nov 1965;16(5):634-53. [Medline].
• Houston AB, Lim MK, Doig WB, et al. Doppler assessment of the interventricular pressure drop in patients with ventricular septal defects. Br Heart J. Jul 1988;60(1):50-6. [Medline].
• Kidd L, Driscoll DJ, Gersony WM, et al. Second natural history study of congenital heart defects. Results of treatment of patients with ventricular septal defects. Circulation. Feb 1993;87(2 Suppl):I38-51. [Medline].
• Lock JE, Block PC, McKay RG, et al. Transcatheter closure of ventricular septal defects. Circulation. Aug 1988;78(2):361-8. [Medline].
• Moller JH, Patton C, Varco RL, et al. Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960. Am J Cardiol. Dec 1 1991;68(15):1491-7. [Medline].
• Nadas AS, Fyler DC. Nadas's Pediatric Cardiology. Philadelphia: Hanley & Belfus, Inc.;1992:435-57.
• Pieroni DR, Nishimura RA, Bierman FZ, et al. Second natural history study of congenital heart defects. Ventricular septal defect: echocardiography. Circulation. Feb 1993;87(2 Suppl):I80-8. [Medline].
• Rein JG, Freed MD, Norwood WI, et al. Early and late results of closure of ventricular septal defect in infancy. Ann Thorac Surg. Jul 1977;24(1):19-27. [Medline].
• Rudolph AM. The effects of postnatal circulatory adjustments in congenital heart disease. Pediatrics. Nov 1965;36(5):763-72. [Medline].
• Sharif DS, Huhta JC, Marantz P, et al. Two-dimensional echocardiographic determination of ventricular septal defect size: correlation with autopsy. Am Heart J. Jun 1989;117(6):1333-6. [Medline].
• Soto B, Becker AE, Moulaert AJ, et al. Classification of ventricular septal defects. Br Heart J. Mar 1980;43(3):332-43. [Medline].
• van den Bosch AE, Ten Harkel DJ, McGhie JS, et al. Feasibility and accuracy of real-time 3-dimensional echocardiographic assessment of ventricular septal defects. J Am Soc Echocardiogr. Jan 2006;19(1):7-13. [Medline].

Article Last Updated: May 25, 2006