Perimembranous Ventricular Septal Defect

Perimembranous ventricular septal defects (VSDs) are located in the left ventricle outflow tract beneath the aortic valve. They are 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 tricuspid valvular in origin), it is termed an aneurysm of the membranous septum. Such tissue serves as a mechanism of restriction or spontaneous closure. The defect may be partially or completely occluded by the septal leaflet of the tricuspid valve. (See Epidemiology, Prognosis, and Treatment.)

Normal closure of the ventricular septum occurs through multiple concurrent embryologic mechanisms that help to close the septum’s membranous portion: (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 midmuscular 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 1 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. (See Etiology.)

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 or greater than the diameter of the aortic annulus) typically have left heart dilatation and pulmonary artery hypertension with normal left ventricular systolic function. (See Workup.)

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.

Hemodynamic effects of VSD

Independent of the type of ventricular septal defect (VSD), the hemodynamic significance of the VSD is determined by two 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, right heart obstructive lesions) may predispose patients to earlier development of CHF. Noncardiac abnormalities, including prematurity, infection, anemia, and 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 shunting at the VSD, depending on the ultimate resistance balance between the systemic and the total right-sided resistances.

Complications

Complications may include the following (see Prognosis):

• CHF

• Bacterial endocarditis primarily for restrictive defects

• Eisenmenger syndrome

• Aortic valve insufficiency if there is evidence of leaflet prolapse

• Subaortic stenosis

• Double-chambered right ventricle

Patient education

Advise the patient and/or his or her parents regarding the importance of good oral hygiene. Subacute bacterial endocarditis prophylaxis for unrepaired ventricular septal defects is not recommended. Educate them concerning signs and symptoms of CHF.

For patient education information, see the Heart Health Center, as well as Congestive Heart Failure and Ventricular Septal Defect.

Perimembranous ventricular septal defects (VSDs) have a multifactorial etiology and are predominantly the result of spontaneous abnormalities in development. 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.

No significant correlation between the cause of VSDs and the age of the mother or the birth order of the child is observed.

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. However, nearly 95% of VSDs are not associated with chromosomal abnormalities. Noncardiac conditions associated with VSD include prematurity.

Regular maternal cannabis use slightly increases the incidence of VSD.[1] The use of selective serotonin reuptake inhibitors (SSRIs) during early pregnancy also slightly increases the incidence of VSD.[2]

Occurrence in the United States

Without regard to type, ventricular septal defect (VSD) is the most common congenital heart defect, with an incidence between 1.5 and 4.2 cases for every 1000 live-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.

Race-, sex-, and age-related demographics

Inheritance patterns of different VSDs vary widely by race. Perimembranous VSD has no known race predilection. Defects located in a subpulmonary position, such as supracristal defects, are more common in the Asian population. VSDs are slightly more common in females than in males.

Most restrictive 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. If the PVR does not decrease normally, then the clinical presentation may be delayed further since pulmonary overcirculation does not occur. VSDs may present soon after birth if they are associated with significant additional congenital heart lesions, or if they occur with an associated chromosomal anomaly or syndrome.

Children with small-to-moderate sized ventricular septal defects (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.

Morbidity and mortality

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 age at repair of VSD.

Perimembranous VSDs may spontaneously decrease in size and eventually close. (This often occurs with a small defect.) Closure rates as high as 50% have been reported in some series, but continued follow-up care is warranted until documented VSD closure occurs.

Although patients with a small VSD have an excellent prognosis, small perimembranous VSDs may lead to the 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 VSDs, surgical repair is indicated at any time during the neonatal period if the infant fails to grow appropriately despite optimal medical management. Elective surgical closure of large VSDs should be planned as soon as feasible, especially if a genetic syndrome is present, to prevent development of irreversible pulmonary vascular obstructive disease (ie, Eisenmenger syndrome).

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 large, isolated perimembranous VSDs are typically asymptomatic in the newborn period and no murmur is typically appreciated.

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 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.

The size of the ventricular septal defect (VSD) and the degree of left-to-right shunting significantly influence findings in a typical physical examination. The following may be found with small VSDs:

• Normal vital signs with normal weight gain

• Quiet precordium with normal apical impulse

• Normal first and second heart sounds

• Absent third heart sound

• Palpable thrill at the mid- to lower left sternal border 

• Absent diastolic murmur

A grade II-VI/VI holosystolic murmur 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, indicating a significant left ventricular ̶ to ̶ right ventricular pressure gradient. In general, smaller defects produce louder murmurs. Systolic murmurs from VSDs are usually holosystolic; they may occasionally sound crescendo or crescendo-decrescendo.

The following may be shown with large VSDs:

• Poor growth and weight gain

• Symptoms of CHF, including tachypnea, tachycardia, sweating, and pallor

• Hyperdynamic precordium with or without precordial bulge due to underlying cardiomegaly.

• Abnormal apical impulse with or without right ventricular tap; a thrill is uncommon

• Normal first heart sound and a narrowly split or single increased second heart sound

• A prominent third heart sound that produces a gallop rhythm at the apex.

• A mid-diastolic flow rumble at the cardiac apex, caused by a significant (at least 2:1 ratio) left-to-right shunt with excessive flow across a normal mitral annulus

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 angiotensin-converting enzyme (ACE) inhibitors must have their electrolyte levels periodically measured.

Electrocardiography

Electrocardiographic 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.

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 the size of left-to-right shunt, left atrial and left ventricular enlargement, posterior displacement of the left ventricular apex, and prominence of the main pulmonary artery segment.

Two-dimensional echocardiography and Doppler ultrasonography

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 or greater than 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.

Transesophageal echocardiography may also be utilized to better delineate the VSD anatomy when transthoracic imaging is suboptimal. This imaging modality is also utilized during hybrid or catheter device closure of VSDs. 

Three-dimensional echocardiography

Real-time 3-dimensional echocardiography (RT3DE) can be used to characterize 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]

Magnetic resonance imaging

Cardiac magnetic resonance imaging (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.

Cardiac catheterization

Routine diagnostic cardiac catheterization is no longer required for perimembranous ventricular septal defects (VSDs). However, older children and adults with a large VSD usually require cardiac catheterization prior to closure to assess pulmonary vascular resistance (PVR).

Indications for cardiac catheterization in patients with VSD include the requirement for additional hemodynamic data prior to medical management or surgical repair (eg, determination of PVR and its reactivity, quantitation of left-to-right shunting, exclusion of associated congenital heart defects).

Angiography

When angiography is employed, membranous VSDs are best demonstrated in the long axial oblique orientation.

Small perimembranous ventricular septal defects (VSDs) have a spontaneous closure rate of as high as 50% within the first 2 years of life and often do not require medical or surgical management.

Larger defects may 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. Treatment typically includes increased-calorie feedings, diuretics, and, sometimes, an angiotensin-converting enzyme (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 indications

Failure of medical management to alleviate symptoms in the first 6 months of life requires intervention. Growth failure despite optimal medical therapy and maximized calorie intake is the most important evidence of failure of medical therapy. Intervention in VSD is either by surgery or cardiac catheterization.[4] Very large left-to-right shunts are usually electively repaired within the first 6 months of age.

Severe CHF requiring hospitalization indicates the need for early intervention for VSD closure. Surgical closure is also required for any size of VSD with the development of aortic valve regurgitation.

Elevated pulmonary arteriolar resistance of more than 12 Wood units/m2 that does not decrease with oxygen or selective pulmonary vasodilator therapy may be regarded as inoperable.

Diet and activity

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

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.

Transfer

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

Consultations

Consultations with the following specialists may be indicated:

• Pediatric cardiologist

• Pediatric cardiothoracic surgeon, if surgery is needed

Surgical repair is the most common intervention currently performed. Surgery is indicated in patients with uncontrolled congestive heart failure symptoms, evidence of increased pulmonary vascular resistance, or the development of aortic valve insufficiency secondary to leaflet prolapse.

Gabriels et al investigated the long-term outcome of 266 patients with perimembranous VSD who were followed in the Belgian Registry on Adult Congenital Heart Disease. Of the 173 patients with isolated perimembranous VSD, 53 (31%) patients underwent VSD closure and 10 of those patients (19%) had a residual shunt. After VSD closure, complications included atrial arrhythmia, pacemaker implantation, and left ventricular outflow tract obstruction.[5]

In a retrospective study, Ou-Yang et al assessed the safety and effectiveness of symmetric and asymmetric occluders in 581 patients who underwent perventricular device closure of perimembranous ventricular septal defects without cardiopulmonary bypass under transesophageal echocardiography guidance from May 2011 to April 2016, as well as outpatient electrocardiography and transthoracic echocardiography assessments at 1, 3, 6, and 12 months, and annually thereafter. The success rate of device implantation was 92.6%. The investigators found a lower residual shunt disappearance rate and higher branch block incidence rate for the asymmetric occluders, thereby favoring more proactive conversion to surgical repair immediately when residual shunt is present intraoperatively.[6]

Surgical repair of an isolated large ventricular septal defect (VSD) involves closure of the defect with a Gore-Tex patch.

Surgical mortality is now very low (approximately 1%) in neonates and patients older than 6 months with an isolated perimembranous VSD. New surgical approaches using smaller incisions have proven effective in VSD closure.[7, 8]

Devices are being investigated (not currently FDA approved) for the transcatheter closure of perimembranous ventricular septal defects (VSDs).[9, 10, 11, 12, 13, 14] VSD closure devices typically have two 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 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 for and outcomes in VSD closure with these devices.

One report noted effective closure in children using the Amplatzer asymmetrical perimembranous occluder in 35 patients with a median age of 4.5 years.[12, 15] 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%. Two further studies concluded that the procedure is safe, but warrants further study and requires great skill in cases with small infants.[12, 16]

Complications in the study 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.[12, 15] Conduction abnormalities, primarily heart block, related to the procedure occurred in 20% of the patients. The abnormalities were permanent in all but one of these patients. In a different study of 1046 patients with perimembranous VSD who underwent percutaneous closure using a modified double-disk occluder (MDO), postprocedure complete atrioventricular block (cAVB) occurred in only 1.63% (n=17) of patients, of whom 8 received permanent pacemaker implantation. Patients older than 18 years were more likely to develop cAVB.[17] The investigators noted that lifelong follow-up with periodic electrocardiography monitoring may be necessary owing to the recurrence of cAVB.

More recent findings in retrospective studies with second-generation Amplatzer vascular occluders for closure of perimembranous VSDs reported similar results regarding the safety and efficacy of these devices.[18, 19]

Another retrospective study evaluated 51 patients younger than 1 year with VSD and reported that perventricular device closure of VSDs was safe and effective in this age population as compared with conventional surgical repair with cardiopulmonary bypass.[20] The infants underwent minimally invasive transthoracic device closure under the guidance of transesophageal echocardiography without cardiopulmonary bypass and had a short rehabilitation period and excellent cosmetic results.

Routine inpatient monitoring of infants and children with small perimembranous ventricular septal defects (VSDs) is not necessary.

Manage patients with large VSDs and no CHF on an outpatient basis but consider early surgical closure. Mild to moderate congestive heart failure (CHF) secondary to large left-to-right shunting caused by a VSD is also managed on an outpatient basis.

Small perimembranous VSDs have a more than 50% spontaneous closure rate. Perform serial follow-up care until the VSD closes.

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 increased pulmonary artery pressures, and evaluate the need for elective surgical closure.

For routine perimembranous VSDs, antibiotics for the prevention of bacterial endocarditis are no longer recommended by the American Heart Association.[21] A modest risk of endocarditis is still observed; thus, the importance of vigilant oral hygiene should be reinforced. For patients who underwent postsurgical VSD closure utilizing a gortex patch or other material, subacute bacterial endocarditis (SBE) precautions are recommended for 6 months post closure.

Diuretics are now the mainstay of medical therapy for infants and children with large ventricular septal defects (VSDs), large left-to-right shunts, and symptoms of 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.

As previously mentioned, be aware that ACE inhibitors have a potassium-sparing effect; when these are used, spironolactone or supplemental potassium should be avoided or judiciously used.

Class Summary

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

Furosemide (Lasix)

Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule.

Spironolactone (Aldactone)

Spironolactone is used for the management of edema resulting from excessive aldosterone excretion. It competes with aldosterone for receptor sites in the distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

Class Summary

These drugs decrease systemic afterload and may decrease left-to-right shunting through a large ventricular septal defect (VSD). They are used to improve preoperative or postoperative cardiac output, reducing systemic vascular resistance and increasing systemic blood flow resulting from myocardial dysfunction.

Enalapril (Vasotec)

Enalapril is a competitive inhibitor of ACE; it reduces angiotensin II levels, decreasing aldosterone secretion.

Captopril

Captopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

Class Summary

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.

Digoxin (Lanoxin)

Digoxin is a cardiac glycoside with direct inotropic effects; it also has indirect effects on the cardiovascular system. Digoxin inhibits sodium- and potassium-activated adenosine triphosphatase (NaK-ATPase), which causes intracellular calcium in the sarcoplasmic reticulum of cardiac cells to increase.