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 multiple 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 defects (VSDs) occur when any portion of the ventricular septum does not correctly form or if any of components do not appropriately grow together. The ventricular septum is complete by 6 weeks' gestation. VSDs are typically classified according to the location of the defect in one of the 4 ventricular components: the inlet septum, trabecular septum, outlet/infundibular septum, or membranous septum. This article specifically addresses defects in the trabecular muscular septum.

The precise etiology of muscular septal defect formation is unknown. However, the proposed mechanisms are many. Muscular defects may occur because of a lack of merging in the walls of the trabecular septum or because of excessive resorption of muscular tissue during ventricular growth and remodeling.

The precise etiology of any delay in closure is unknown. Perimembranous VSD is caused by failure of the endocardial cushions, the conotruncal ridges, and the muscular septum to fuse at a single point in space.

Perimembranous VSDs are located in the left ventricle outflow tract beneath the aortic valve. It is the most common VSD subtype in the United States, occurring in 75-80% of cases. Defects may extend into adjacent portions of the ventricular septum. When tissue forms on the right ventricular septal surface (often thought to be atrioventricular valvular in origin), it is termed an aneurysm of the membranous septum. Such tissue serves as a mechanism of spontaneous closure. The defect may be partially or completely occluded by the septal leaflet of the tricuspid valve.

Pathophysiology

Independent of the type of VSD, the hemodynamic significance is determined by 2 factors: the size of the defect and the resistance to flow out of the right ventricle, including the pulmonary vascular resistance (PVR) and anatomic right ventricular outflow obstruction.

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

Because PVR is high at birth and does not reach its nadir until age 6-8 weeks, the development of significant left-to-right shunting and pulmonary overcirculation, often termed congestive heart failure (CHF), can be 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, muscular right ventricular outflow tract obstruction, pulmonary valve stenosis, pulmonary venous obstruction, persistent elevation of PVR, mitral stenosis) can restrict shunting, possibly 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 of 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 cases for every 1000 liveborn infants. Clinically significant VSD that requires medical or surgical management accounts for only 15% of such defects (0.35-0.50 cases for every 1000 live births). When viewing congenital heart disease in total, solitary VSD cases account for 20-40% of congenital heart disease. Perimembranous VSD is the most common type, accounting for as many as 50% of VSD cases 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.

Perimembranous VSDs may spontaneously decrease in size and eventually close. Closure rates as high as 50% have been reported 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. Small perimembranous VSDs may lead to development of aortic insufficiency.

For patients with moderate-sized VSD, defects may allow the development of voluminous left-to-right shunting in the first few months of life as PVR falls. Failure of medical management with persistent evidence of CHF is the primary indication for surgical closure of moderate-sized defects. Fewer than 25% of moderate-sized defects require surgical closure.

For patients with large muscular 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 are currently 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 widely vary by race. Perimembranous VSD has no known racial predilection. Defects located in a subpulmonary position, such as supracristal defect, are more common in the Asian population.

Sex

VSDs are slightly more common in females than in males.

Age

Most perimembranous VSDs present clinically in the neonatal period secondary to a murmur. These defects, especially the smaller defects, are not typically suspected at birth and may not be identified by auscultation until PVR begins to fall in the first few days to weeks of life. Large perimembranous VSDs may not present until patients are aged 6-8 weeks, when decreased PVR allows significant left-to-right shunting and clinical signs and symptoms of CHF. VSDs may present soon after birth if associated with significant additional congenital heart lesions or if they occur 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 perimembranous ventricular septal defects (VSDs) are asymptomatic but come to medical attention because a systolic murmur is discovered.
  • Patients with isolated large perimembranous VSDs are typically asymptomatic in the newborn period.
• Progression of symptoms
• • Typically, infants with large VSDs present with signs and symptoms of pulmonary overcirculation or congestive heart failure (CHF) at age 6-8 weeks or older, as pulmonary vascular resistance (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 with feeding), and lethargy.
• Chromosomal anomalies
• • VSDs are the most common congenital heart lesion (20-30%) in infants with chromosomal anomalies or syndromes.
  • These defects may be discovered in the first days of life when additional diagnostic evaluations are performed to exclude multiple congenital defects.

Physical

Size of the VSD and degree of left-to-right shunting significantly influence findings in a typical physical examination.

• Small VSDs
• • Normal vital signs with normal weight gain
  • Quiet precordium with normal apical impulse
  • Normal first heart sound
  • Narrowly split second heart sound; occasional accentuated pulmonary component
  • Absent third heart sound
  • Palpable thrill at the mid-to-lower left sternal border (very small VSDs)
  • A Grade II-VI/VI holosystolic murmur: A Grade II-VI/VI that widely radiates throughout the precordium is present along the left sternal border. The intensity of the murmur is usually inversely 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 louder murmurs. Systolic murmurs from VSDs are usually holosystolic; they may occasionally sound crescendo or crescendo-decrescendo.
  • Absent diastolic murmur with small VSDs
• Large VSDs
• • Poor growth and weight gain occur.
  • Symptoms of CHF, including tachypnea, tachycardia, sweating, and pallor present.
  • Hyperdynamic precordium with or without precordial bulge is due to underlying cardiomegaly.
  • Abnormal apical impulse can present with or without right ventricular tap; a thrill is uncommon with large VSDs.
  • Normal first heart sound and a narrowly split second heart sound with occasional loud pulmonary component are evident
  • A loud holosystolic murmur with wide precordial radiation maximal at the left mid-sternal border.
  • A prominent third heart sound that produces a gallop rhythm typically is present at the apex.
  • A mid-diastolic flow rumble may be present at the cardiac apex. This diastolic murmur is caused by a significant (at least 2:1 ratio) left-to-right shunt with excessive flow across a normal mitral annulus.

Causes

• Inheritance
• • Perimembranous VSDs have a multifactorial etiology and are predominantly the result of spontaneous abnormalities in development.
  • No significant correlation between the cause of VSDs and the age of the mother or the birth order of the child is observed
• Associated syndromes
• • VSDs are the most common congenital heart lesion associated with chromosomal anomalies and syndromes.
  • VSDs are especially common in patients with trisomy 13, trisomy 18, and trisomy 21.
  • Nearly 95% of VSDs are not associated with chromosomal abnormalities.
• Associated noncardiac conditions
• • Prematurity
  • Syndromes and chromosomal anomalies
• Risk factors
• • Regular maternal cannabis use slightly increases the incidence of VSD.¹
  • The use of selective serotonin reuptake inhibitors (SSRIs) during early pregnancy slightly increases the incidence of VSD.²

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

• For children with small ventricular septal defects (VSDs), no specific laboratory blood tests are indicated.
• Occasionally, in the evaluation of children with symptomatic large VSD, brain natriuretic peptide (BNP) is measured as a marker of congestive heart failure (CHF) severity.
• Children who are maintained on diuretics and ACE inhibitors have their electrolyte levels periodically measured.

Imaging Studies

• Chest radiography
• • Small VSDs show normal cardiac size and normal pulmonary vascularity.
  • Large VSDs demonstrate cardiac enlargement and increased pulmonary vascular markings proportional to the 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
• • Echocardiography is the most reliable noninvasive modality to identify the presence, size, number, and location of the VSD.
  • Perimembranous VSDs are readily identified from the subcostal short and long axis planes, 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) are usually 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 function.
  • Dilation of the main and branch pulmonary arteries also is common.
  • Doppler echocardiography can be used to predict the intracardiac pressure gradient from the left ventricle to the right ventricle using the continuous wave Doppler tracing (modified Bernoulli equation = 4 [velocity squared]). If the systolic systemic pressure is known, in the absence of aortic outflow obstruction, right ventricle and pulmonary artery (in the absence of right ventricular outflow obstruction) systolic pressures can be predicted by subtracting the gradient between the ventricles from the aortic systolic blood pressure.
  • Color Doppler is useful to determine VSD location and size as well as the degree of intracardiac shunting.
  • Echocardiography is 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 an associated VSD.
• MRI
• • Cardiac MRI is a useful adjunct in the evaluation of large muscular VSDs. 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. Tiny muscular VSDs are not well seen using cardiac MRI.
  • 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 3-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.³

Other Tests

• ECG findings vary depending on the VSD size and the degree of intracardiac shunting.
• Patients with small VSDs have normal ECG findings.
• Large VSDs show left ventricular hypertrophy (LVH) (ie, volume overload), right ventricular hypertrophy (RVH) (ie, pressure overload), and left atrial enlargement.

Procedures

• Cardiac catheterization
• • Routine diagnostic cardiac catheterization is no longer required for perimembranous VSDs. Older children and adults with an unoperated large VSD usually require cardiac catheterization prior to surgical closure to assess pulmonary vascular resistance (PVR).
  • Indications for cardiac catheterization in patients with VSD include inadequate noninvasive echocardiographic assessment of size, number, or location of VSD as well as complicated associated anatomy.
  • Another indication is the requirement of 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, exclusion of associated congenital heart defects).
• Angiography: Membranous VSDs are best demonstrated in the long axial oblique orientation.

Histologic Findings

• No specific histological abnormality is present.

TREATMENT

Section 6 of 10  

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

Medical Care

• Small perimembranous ventricular septal defects (VSDs) have a spontaneous closure rate as high as 50% within the first 2 years of life and often do not require medical or surgical management.
• Larger defects may not close but often become smaller with time. Medical therapy may be required with large membranous VSDs due to excessive left-to-right shunting and congestive heart failure (CHF). Therapy is directed at alleviating the symptoms of pulmonary overcirculation. Therapy typically includes increased calorie feedings, diuretics, and, sometimes, an ACE inhibitor.
• Diuretic therapy with furosemide is used to lessen volume overload. Significant potassium wasting may warrant the addition of spironolactone or potassium supplementation.
• The 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 used, spironolactone or supplemental potassium should be avoided or judiciously used.

Surgical Care

• Failure of medical management to alleviate symptoms in the first 6 months of life requires intervention.
• Growth failure despite optimal medical therapy and maximized caloric intake is the most important evidence of failure of medical therapy.
• 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.
• Very large left-to-right shunts are usually electively repaired within the first year of life.
• Intervention is either by surgery or cardiac catheterization.
• • Surgery
  • • Surgical repair is the most common intervention currently performed.
    • Surgical repair of an isolated large VSD involves closure of the defect with a Gore-Tex patch.
    • Surgical intervention in younger infants, especially those younger than 1 month, is associated with an increased risk of mortality (historically as high as 10%, although currently much lower).
    • Surgical mortality is now very low (approximately 1%) in patients older than 6 months with isolated perimembranous VSDs.
    • New surgical approaches using smaller incisions have proven effective in VSD closure.
    • Surgery is indicated in patients with progressive aortic insufficiency or greater than trivial insufficiency at the time of initial presentation.
  • Cardiac catheterization or hybrid procedures
  • • Devices are now available for closure of perimembranous VSDs.^{4, 5}.  
    • VSD closure devices typically have 2 asymmetrical opposing discs (one for the right ventricular side and one for the left ventricular side), which are released during catheterization under fluoroscopic and transesophageal echocardiographic guidance to occlude the defect. These devices can be placed percutaneously in the cardiac catheterization laboratory or in the operating room during a "hybrid procedure." These procedures are slightly more complicated than closure of muscular VSDs because of the asymmetry of the device, the proximity to the aortic valve, and the presence of conduction tissue very near the defect.
    • Hybrid procedures may involve inserting the device through a very small incision in the free wall of the right ventricle.
    • Ongoing investigational trials are currently being performed to assess indications and outcomes in VSD closure with these devices.
    • One report noted effective closure in children using the Amplatzer asymmetric perimembranous occluder in 35 patients with a median age 4.5 years.⁶ The defects were 3-8 mm in size, and the size of the occluder varied from 4-12 mm. After 2.5 years, the rate of complete closure was 91%. Complications included residual shunting that required surgical closure of the defect subsequent to the insertion of the device and persistent regurgitation across the tricuspid or aortic valve related to the occluder. Conduction abnormalities related to the procedure occurred in 20% of the patients. The abnormalities were permanent in all but one of these patients.

Consultations

• Pediatric cardiologist
• Pediatric cardiothoracic surgeon if surgery is needed

Diet

• Patients with significant CHF may require caloric supplementation with fortified formula or breast milk.

Activity

• Patients with small perimembranous VSDs have no activity restrictions.
• Patients with moderate-to-large perimembranous defects and significant symptomatology limit their own exercise activity levels until the defect is repaired.
• Patients with repaired VSDs and no residual cardiac sequelae have no activity restrictions.

MEDICATION

Section 7 of 10  

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

Diuretics are now the mainstay of medical therapy for infants and children with large ventricular septal defects (VSDs), large left-to-right shunts, and evidence of congestive heart failure (CHF). Current debate is ongoing concerning the use of digoxin. In certain situations, the addition of afterload reduction may also be beneficial. Hemoglobin levels should be normal.

Drug Category: Diuretics

These agents relieve ventricular volume load and peripheral and pulmonary congestion.

Drug Category: Afterload reducers

These drugs decrease systemic afterload and may decrease left-to-right shunting through large VSD. They are used to improve preoperative or postoperative cardiac output. They reduce systemic vascular resistance and increase systemic blood flow resulting from myocardial dysfunction.

Drug Category: Inotropic agents

These agents augment ventricular contractility. Positive inotropic agents increase the force of contraction of the myocardium and are used to treat acute and chronic CHF. Some may also 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. Cardiac glycosides are used predominantly for their inotropic effects.

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 perimembranous ventricular septal defects (VSDs) is not necessary.
• Mild-to-moderate congestive heart failure (CHF) secondary to large left-to-right shunting caused by a VSD is managed on an outpatient basis.
• Severe CHF requiring hospitalization indicates the need for early intervention for VSD closure.

Further Outpatient Care

• Small perimembranous VSDs have a 50% spontaneous closure rate. Perform serial follow-up care until the VSD closes.
• For routine perimembranous VSDs, antibiotics for the prevention of bacterial endocarditis are no longer recommended by the American Heart Association.⁷ A modest risk of endocarditis is still observed; thus, the importance of vigilant oral hygiene should be reinforced. For more information, see Endocarditis, Bacterial.
• Perform surgical closure of any size of VSD with the development of progressive aortic valve regurgitation.
• Manage moderately-sized VSDs on an outpatient basis by monitoring for evidence of a reduction in size or a spontaneous closure. Assess patient growth and evaluate the need for elective surgical closure.
• Manage patients with large VSDs and no CHF on an outpatient basis.
• Infants who do not respond to medical therapy (eg, poor weight gain) are candidates for surgical closure.

In/Out Patient Meds

• Diuretics, such as furosemide and spironolactone, decrease volume overload in patients with large VSDs.
• Captopril or enalapril may be used to reduce afterload.
• In some centers, digoxin is used as an inotrope to augment ventricular contractility in patients with a large VSD and evidence of CHF.

Transfer

• Patients with large or multiple VSDs may be transferred to a tertiary care center for further diagnostic evaluation or surgical intervention.

Complications

• CHF
• Bacterial endocarditis
• Eisenmenger syndrome
• Aortic insufficiency
• Subaortic stenosis
• Double-chambered right ventricle

Prognosis

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

Patient Education

• Advise patient and/or parents regarding the risks of bacterial endocarditis indications and the importance of oral hygiene. Educate them concerning signs and symptoms of CHF.
• For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education articles Congestive Heart Failure and 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 surgically close the ventricular septal defect (VSD) prior to the development of pulmonary vascular obstructive disease
• Failure to detect associated heart lesions or sequelae prior to or following surgery (aortic insufficiency, subaortic stenosis)
• Failure to counsel parents and patients regarding the risk of bacterial endocarditis
• Failure to detect associated lesions
• Failure to detect chronic left ventricular dilatation

REFERENCES

Section 10 of 10

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

1. Williams LJ, Correa A, Rasmussen S. Maternal lifestyle factors and risk for ventricular septal defects. Birth Defects Res A Clin Mol Teratol. Feb 2004;70(2):59-64. [Medline].
2. Oberlander TF, Warburton W, Misri S, Riggs W, Aghajanian J, Hertzman C. Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Defects Res B Dev Reprod Toxicol. Feb 2008;83(1):68-76. [Medline].
3. Chen FL, Hsiung MC, Nanda N, Hsieh KS, Chou MC. Real time three-dimensional echocardiography in assessing ventricular septal defects: an echocardiographic-surgical correlative study. Echocardiography. Aug 2006;23(7):562-8. [Medline].
4. Fu YC, Bass J, Amin Z, et al. Transcatheter closure of perimembranous ventricular septal defects using the new Amplatzer membranous VSD occluder: results of the U.S. phase I trial. J Am Coll Cardiol. Jan 17 2006;47(2):319-25. [Medline].
5. Thanopoulos BD. Catheter closure of perimembranous/membranous ventricular septal defects using the Amplatzer occluder device. Pediatr Cardiol. Jul-Aug 2005;26(4):311-4. [Medline].
6. Fischer G, Apostolopoulou SC, Rammos S, Schneider MB, Bjornstad PG, Kramer HH. The Amplatzer Membranous VSD Occluder and the vulnerability of the atrioventricular conduction system. Cardiol Young. Oct 2007;17(5):499-504. [Medline].
7. Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation. Oct 9 2007;116(15):1736-54. [Medline].
8. 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].
9. Chessa M, Butera G, Negura D, et al. Transcatheter closure of congenital ventricular septal defects in adult: Mid-term results and complications. Int J Cardiol. Jan 28 2008;[Medline].
10. Dammann JF Jr, Thompson WM Jr, Sosa O. Anatomy, physiology and natural history of ventricular septal defects. Am J Cardiol. 1960;5:136-66.
11. 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].
12. Hoffman JI, Rudolph AM. The natural history of ventricular septal defects in infancy. Am J Cardiol. Nov 1965;16(5):634-53. [Medline].
13. 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].
14. 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].
15. McMahon CJ, Said HG, Clapp SK. Interrupted aortic arch type B in trisomy 21: repair with carotid artery interposition. Pediatr Cardiol. Jan-Feb 2003;24(1):40-2. [Medline].
16. 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].
17. Nadas AS, Fyler DC. Ventricular septal defects. In: Nadas's Pediatric Cardiology. Philadelphia, PA: Hanley & Belfus Inc; 1992:435-57.
18. 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].
19. Rudolph AM. The effects of postnatal circulatory adjustments in congenital heart disease. Pediatrics. Nov 1965;36(5):763-72. [Medline].
20. 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].
21. Soto B, Becker AE, Moulaert AJ, et al. Classification of ventricular septal defects. Br Heart J. Mar 1980;43(3):332-43. [Medline].

Article Last Updated: Nov 25, 2008