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 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 be caused by incomplete fusion of the right endocardial cushion with the muscular septum. Outlet VSD may be caused by failure of fusion of the conal septum. Muscular defects may be caused by lack of merging of the walls of the trabecular septum or excessive resorption of muscular tissue during ventricular growth and remodeling. Membranous VSD is caused by failure of fusion of the endocardial cushions, the conotruncal ridges, and the muscular septum.

Classification

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.

• Inlet VSD
  • Location is 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 at the cardiac apex and 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.
  • Spontaneous closure of muscular VSD frequently occurs in the first 2 years of life, most by age 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 be caused by prolapse of (usually) the right coronary leaflet into 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. When tissue forms on the right ventricular septal surface (often thought to be AV valvular in origin) it is termed aneurysm of membranous septum. Such tissue serves as a mechanism of spontaneous closure.
  • The defect may be partially or completely occluded by septal leaflet of tricuspid valve.

Pathophysiology

• The hemodynamic significance of VSD primarily is determined by 2 factors: the size of the defect and the state of the pulmonary vascular resistance. In small-to-moderate VSDs, left-to-right shunting primarily is limited by the size of the defect. In large VSDs, left-to-right shunting is determined by the relative degree of pulmonary and systemic vascular resistance. Resistance to pulmonary outflow also can decrease left-to-right shunting.
• Because pulmonary vascular resistance (PVR) is high at birth and may not reach its nadir until the patient is aged 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 impose more left-to-right shunts (eg, atrial septal defect, patent ductus arteriosus) may predispose 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. Other factors may limit the degree of left-to-right shunt in patients with large VSDs. These may include RV outflow tract obstruction, pulmonary valve stenosis, pulmonary venous obstruction, persistent elevation of pulmonary vascular resistance, and mitral stenosis.

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 live births). 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 VSDs 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, the presence of associated congenital heart defects, the presence of associated noncardiac defects and syndromes, and the 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.
• 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 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 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 are higher in the first 2 months of life than after age 6 months (10-20% versus 1-2%), however these data are improving, especially in centers with a large surgical experience. Elective surgical closure of large VSDs should be planned within the first 6 months to 1 year of life to prevent the 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, but muscular VSD has no known racial predilection.

Sex

• VSDs are slightly more common in females than in males.

Age

• Large membranous VSDs may not present until patients are aged 6-8 weeks, when decreased pulmonary vascular resistance allows significant left-to-right shunting and clinical signs and symptoms of CHF.
• Most membranous VSDs present clinically in the neonatal period. These defects, especially the smaller defects, typically 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.
• 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
• • Patients with isolated large membranous ventricular septal defects (VSDs) typically are asymptomatic in the immediate newborn period.
  • Most patients with small membranous VSDs are asymptomatic but come to medical attention because a systolic murmur is discovered.
  • Most murmurs have a delayed presentation in the newborn period, occurring in the first few days to the first few weeks after birth.
  • At birth, PVR is high. This causes the right ventricular pressure to remain elevated and, therefore, equal to left ventricular pressure.
  • As PVR falls, the developing pressure gradient from the LV to the RV stimulates left-to-right shunting across the membranous VSD and produces a typical holosystolic murmur.
  • As PVR falls, the degree of left-to-right shunting is proportional to the size of the defect and the relative degree of PVR.
  • The larger the VSD and the lower the PVR, the greater is the degree of left-to-right shunting.
• Progression of symptoms
• • Typically, infants with large VSDs present with signs and symptoms of congestive heart failure 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 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 physical examination findings 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 III-VI/VI holosystolic murmur that radiates widely throughout the precordium is present along the left sternal border. The 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 louder murmurs. Systolic murmurs from VSDs usually are 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 prominent third heart sound that produces a gallop rhythm typically is present at the apex.
• A loud holosystolic murmur with wide precordial radiation is maximal at the left sternal border.
• 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
• • VSDs have a multifactorial etiology.
  • No correlation exists between the cause of VSDs and the age of the mother or the birth order of the child.
• Associated syndromes
• • VSDs are the most common congenital heart lesion associated with most 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

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 radiographs
• • 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
• • Echocardiography 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 also is common.
  • Doppler echocardiography can be used to predict the intracardiac pressure gradient from LV to RV (modified Bernoulli equation = 4 [velocity squared] ). If the systolic systemic pressure is known, in the absence of aortic outflow obstruction, RV and PA (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.
• 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 vary depending on the size of the VSD and the degree of intracardiac shunting.
  • A small VSD has a normal ECG result.
  • A 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 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 membranous ventricular septal defects (VSDs) have a spontaneous closure rate of up to 50% within the first 2 years of life and often need no 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 CHF.
• Digoxin is an inotrope used to augment ventricular contractility. Diuretic therapy with furosemide serves to lessen the volume of overload. Significant potassium wasting may warrant the addition of spironolactone or another potassium supplement. In selected cases, afterload reduction may be beneficial in improving systemic-pulmonary flow ratios.

Surgical Care

• Failure of medical management within 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 currently are undergoing FDA investigational trials for closure of a VSD.
• 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. Device closure is not yet considered for inlet, outlet, or malalignment VSDs.
• Although still in the evolutionary phase, multiple groups have shown that transcatheter closure of perimembranous VSD can be performed safely and effectively with the asymmetric Amplatzer occluder device in selected patients with good short- and midterm results. Transcatheter closure of a membranous VSD is technically feasible and appears safe in children over 8 kg in weight, but further clinical trials are needed to assess the long-term safety and efficacy.
• The left-to-right shunt usually is electively repaired within the first year of life.
• Patients with multiple muscular VSDs may undergo pulmonary artery banding. 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.
• Elevated pulmonary arteriolar resistance greater than 12 Wood units that 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, significantly increases mortality rates (10-20%).
• Surgical mortality is low (1-2%) in patients older than 6 months with isolated large muscular VSDs.
• Techniques for VSD closure devices
• • These devices typically have 2 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.
  • 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.

Consultations

• A pediatric cardiologist should assess the patient for pediatric cardiothoracic surgery.

Diet

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

Activity

• Patients with small membranous VSDs have no activity restrictions.
• Patients with moderate-to-large 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

Digoxin and diuretics have been the mainstay of medical therapy for infants and children with large ventricular septal defects (VSDs), large left-to-right shunts, and evidence of CHF. Current debate is ongoing concerning the use of digoxin, but most centers still use it. In certain situations, the addition of afterload reduction also may be beneficial. Hemoglobin levels should be normal.

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.

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. Used to improve preoperative or postoperative cardiac output. They reduce systemic vascular resistance and increase systemic blood flow resulting from myocardial dysfunction.

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 membranous ventricular septal defects (VSDs) is not necessary.
• Manage mild-to-moderate CHF secondary to large left-to-right shunting caused by a VSD on an outpatient basis.
• Severe CHF requiring hospitalization indicates the need for early surgical intervention for VSD closure.

Further Outpatient Care

• Small membranous VSDs have a 50% spontaneous closure rate. Perform serial follow-up care until the VSD closes.
• Prevent bacterial endocarditis with antimicrobial prophylaxis.
• 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

• Digoxin is used as an inotrope to augment ventricular contractility.
• Diuretics, such as furosemide and Aldactone, are used to decrease volume overload.
• Afterload reduction with captopril or enalapril may be effective in selected cases.
• Maintain adequate hemoglobin levels.

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

Prognosis

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

Patient Education

• Counsel parents regarding the indications and prophylaxis of bacterial endocarditis.
• Educate parents on the 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 or prescribe bacterial endocarditis prophylaxis
• Failure to detect associated lesions.
• Failure to detect chronic left ventricular dilation.

REFERENCES

Section 10 of 10

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

• 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].
• Dammann JF Jr, Thompson WM Jr, Sosa O. Anatomy, physiology and natural history of ventricular septal defects. Am J Cardiol. 1960;5:136-66.
• 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].
• 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].
• 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].
• 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. Ventricular Septal Defects. In: 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].
• 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].
• 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].

Article Last Updated: May 25, 2006