Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis

INTRODUCTION — Ventricular septal defects (VSDs) are among the most common congenital heart lesions. VSDs occur in isolation or in combination with other congenital heart disease defects, such as atrioventricular canal, tetralogy of Fallot, and, occasionally, D-transposition of the great arteries. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects" and "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis" and "D-transposition of the great arteries (D-TGA): Anatomy, clinical features, and diagnosis".)

The anatomy, pathophysiology, natural history, clinical features, and evaluation of isolated VSDs in children will be reviewed here. The echocardiographic evaluation and management of VSDs are discussed separately. (See "Echocardiographic evaluation of ventricular septal defects" and "Management of isolated ventricular septal defects (VSDs) in infants and children".)

PREVALENCE — The prevalence of VSDs is approximately 4 per 1000 live births [1,2]. Thus, VSDs are among the most common congenital heart lesions, second only to bicuspid aortic valve (which as an isolated lesion, is rarely diagnosed in infancy). (See "Identifying newborns with critical congenital heart disease", section on 'Prevalence'.)

ANATOMY — There are three main anatomic components of the interventricular septum (figure 1 and figure 2) [3]. VSDs may occur at various locations in any of the three components (figure 3):

●The septum of the atrioventricular (AV) canal (component 1)

●The muscular septum (component 2)

●The parietal band or distal conal septum (component 3)

Embryologically, closure of the interventricular foramen is dependent upon three processes:

●Projections into the AV canal from the right-sided endocardial cushions (component 1)

●Continued growth of connective tissue on the crest of the muscular septum (component 2)

●Downward growth of ridges dividing the conus (component 3)

The particular location of the defect has no bearing on the volume of the intracardiac shunt, the size of which impacts the clinical manifestations. However, location of the VSD is important in terms of the frequency of involvement of the semilunar valves or AV valvar attachments, and the likelihood of spontaneous closure [4-6]. (See 'Pathophysiology' below.)

In addition, the relationship of the defect to the AV conduction pathway is an important aspect of surgical repair. (See "Management of isolated ventricular septal defects (VSDs) in infants and children", section on 'Closure interventions'.)

●Membranous defects — Membranous VSDs lie just beneath the aortic valve and behind the septal leaflet of the tricuspid valve. Because multiple factors are involved in embryologic closure of the region encompassing the membranous septum, this region is the most common site for clinically significant VSDs (component 3 with extension to component 2) (figure 1). Defects in this region are referred to as membranous defects, and also are called perimembranous, conoventricular, or subaortic VSDs.

Often these defects extend into the inlet or muscular septum, and can undergo partial or complete closure by apposition of the septal leaflet of the tricuspid valve, forming a tricuspid valve "pouch" or "aneurysm of the ventricular septum" [7-10]. Less commonly, they can be closed by prolapse of an aortic cusp into the defect [11]. Occasionally, these defects can be associated with left ventricular outflow tract obstruction and coarctation of the aorta. Because the bundle of His lies in a subendocardial position and courses along the posterior-inferior margin of the defect, heart block is a potential surgical complication [12].

●Muscular defects — Muscular defects can be located along the right ventricular free wall-septal junction (marginal muscular defects), in the central muscular septum, or in the apical septum (component 2) (figure 1). Small muscular defects are even more common in very premature infants. Muscular defects often close spontaneously [13]. In particular, central muscular VSDs are more likely to close spontaneously and earlier than other muscular types of VSDs [14].

Multiple muscular defects, referred to as "Swiss cheese" septum, have the same net functional effect as a single large defect [15]. Apical defects may be covered by thick trabeculations of the right ventricle, making visualization difficult during right-sided surgical repair [4]. (See 'Pathophysiology' below.)

●Malalignment defects — Malalignment VSDs result from anterior or posterior malalignment of the conal septum (component 3). Although the anatomic location may be similar to that of membranous defects, malalignment VSDs are in a separate category of VSDs. Anterior malalignment defects are part of the anatomic complex in tetralogy of Fallot (TOF), whereas posterior malalignment defects cause various degrees of left ventricular outflow tract obstruction.

●Subpulmonic (outlet) — VSDs that are superior and anterior in location within component 3 are referred to as subpulmonic or outlet defects (also called supracristal, infundibular, conal septal, or doubly committed subarterial defects) (figure 1). These defects account for approximately 5 percent of defects in North America and western Europe [16], but are more common (approximately 30 percent) in the Asian population [17]. Subpulmonic defects are located immediately beneath the valves of both arterial trunks. They commonly are associated with prolapse of the right coronary cusp of the aortic valve with or without aortic regurgitation. Outlet defects rarely close spontaneously. (See 'Aortic regurgitation' below and "Management of isolated ventricular septal defects (VSDs) in infants and children", section on 'Indications'.)

●AV canal (inlet) — AV canal or inlet defects occur posterior and superior between the annulus of the tricuspid valve and the attachments of the tricuspid valve to the right ventricular wall and septum (component 1) (figure 1). They account for approximately 5 percent of VSDs. These defects are seldom isolated, and are more commonly associated with an atrial septal defect that is part of a complete AV canal or endocardial cushion defect. They do not close spontaneously. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects".)

Inlet defects occupy the area of septum inferior to the normal conduction tissue axis. This causes inferior deviation of the AV node and bundle of His, which results in abnormal QRS axis on electrocardiogram and vulnerability to AV block, both spontaneous and surgically induced.

PATHOPHYSIOLOGY

Fetus — The presence of a VSD in utero has little effect on the normal cardiac physiology. In utero, the right ventricular output preferentially flows through the ductus arteriosus to the descending aorta to supply the abdominal viscera, lower extremities, and the placenta, with minimal flow to the high resistance pulmonary bed (figure 4). Simultaneously, left ventricular output supplies flow to the head and neck with a small percentage of flow crossing the distal aortic arch. Thus, there is minimal shunting of blood even if there is a large ventricular communication, because shunting is dependent on the relative resistance to flow during systole, which is relatively equal in utero. (See "Pathophysiology of left-to-right shunts", section on 'Fetal and transitional circulation' and "Physiologic transition from intrauterine to extrauterine life", section on 'Fetal circulation'.)

Post-delivery — Following delivery, the transition from intrauterine to extrauterine life involves the removal of the low resistance placenta from the circulation and the closure of the ductus arteriosus. In addition, there is an immediate fall in pulmonary vascular resistance (PVR), and a continued, more gradual decline that extends over weeks to months. As a result, the neonatal left ventricle (LV) contracts against high systemic vascular resistance (SVR), while the right ventricle (RV) contracts against the lower resistance pulmonary circulation. In the absence of outflow obstruction, the difference in the resistance between the two vascular beds determines the direction of the shunt across the VSD post-delivery. Since SVR is considerably higher than PVR in most patients, the direction of shunting across VSDs is typically left-to-right. The exception is patients with untreated moderate to large defects in whom PVR may be equivalent to SVR, which may result in right-to-left or bidirectional shunting. (See "Physiologic transition from intrauterine to extrauterine life", section on 'Transition at delivery' and 'Natural history' below.)

The decline in PVR during the early postnatal period usually occurs gradually over several weeks. It declines more rapidly in preterm infants. In infants with moderate or large VSDs, the decline in PVR may be delayed for several months. Other factors such as development of pulmonary edema or high altitude may also delay the rate of decline in PVR [4].

Size of defect — The physiologic effects of VSDs depend upon the size of the defect and the PVR. These variables change with time, and the clinical manifestations alter accordingly [15]. (See 'Natural history' below.)

The pathophysiology of VSDs is summarized briefly below and is discussed in detail separately. (See "Pathophysiology of left-to-right shunts", section on 'Ventricular level shunts'.)

Although there is no universally accepted definition of sizes, commonly used categorizations often used in clinical studies include:

●Anatomic definition – However, one needs to consider the size of the patient especially in the neonate:

•Small <4 mm

•Moderate 4 to 6 mm

•Large >6 mm

●Size of the intracardiac shunt determined by the ratio of pulmonary to systemic blood flow (Qp:Qs):

•Small – Qp:Qs <1.5

•Moderate – Qp:Qs 1.5 to 2.3

•Large – Qp:Qs >2.3

Small defects (also called restrictive defects) with high resistance to flow permit only a small left-to-right shunt (usually <50 percent of ventricular output or a Qp:Qs <1.5). RV pressure remains normal or only minimally elevated; pulmonary artery pressures and PVR are normal and there is little increase in ventricular stroke work.

In moderate defects (moderately restrictive defects) the magnitude of the left-to-right shunt depends primarily upon the size of the defect and the pressure differential between the RV and LV. In these patients, RV pressure, PVR, and pulmonary artery pressures may remain low or be moderately elevated. As the RV pressure decreases after birth, the shunt increases, which may lead to volume overload of the left atrium and ventricle with signs and symptoms of heart failure. Pulmonary pressure usually remains normal or only mildly elevated because of the restrictive nature of the defect and the resultant large pressure gradient from LV to RV.

Large defects (equal to or greater in size than the cross-sectional diameter of the aortic root) offer little resistance to flow; they are sometimes called "unrestrictive defects." The pressure in the ventricles is equal and they function as a common pumping chamber with two outlets. The magnitude of the shunt depends upon relative pulmonary and systemic vascular resistance. As PVR declines, there is a large left-to-right shunt that generates increased pulmonary blood flow, increased pulmonary venous return, and increased volume load to the LV. This left ventricular volume overload may result in LV dilation and increased end-diastolic pressure, which in turn may cause increased left atrial pressure, pulmonary venous pressure, and progressive symptoms of heart failure. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Volume overload with preserved ventricular contractility'.)

Effects on the circulation — The effects of left-to-right shunting on the pulmonary and systemic circulation are as follows:

●Pulmonary circulation – Increased pulmonary blood flow may result in pulmonary congestion and edema which manifests most commonly as tachypnea and increased respiratory effort [4]. Over time, unrestricted increased pulmonary blood flow can result in pulmonary vascular changes and pulmonary hypertension [4]. (See "Pulmonary hypertension in children: Classification, evaluation, and diagnosis" and "Pathophysiology of left-to-right shunts", section on 'Pulmonary hypertension'.)

●Systemic circulation – In patients with significant left-to-right shunting, LV output must increase to maintain systemic blood flow at normal levels. The increase in LV output depends upon the size of the shunt. For example, a 50 percent left-to-right shunt results in a twofold increase in LV output [4].

By convention, the magnitude of left-to-right shunting is defined by the ratio of pulmonary to systemic blood flow (Qp:Qs). Thus, Qp:Qs for a 25 percent shunt is 1.33:1 [4]. As shunt volumes increase above 60 percent, small increases in shunt volume must be accompanied by dramatic increases in LV output to maintain systemic circulation at normal levels. When the LV is no longer able to maintain such increased output demands, systemic blood flow falls and high output failure ensues [4].

Other factors that increase the demand for systemic blood flow in infants and children with VSDs include fever, sympathetic stimulation, increased respiratory effort, anxiety, and anemia [4]. These may contribute to cardiac failure in patients with moderate or large defects.

As systemic output decreases, several mechanisms act to increase SVR:

•Increased alpha-adrenergic stimulation by sympathetic nerves (due to distension of the cardiac chambers and baroreflex stimulation as cardiac output is reduced and arterial pressure falls)

•Increased circulating catecholamine concentrations

•Increased angiotensin II and vasopressin concentrations

These responses may exacerbate cardiac failure, and contribute to the clinical manifestations. (See 'Clinical features' below.)

NATURAL HISTORY — The natural history of untreated VSDs is related to the size of the defect, as illustrated below. (See 'Size of defect' above.)

Small ventricular septal defect — Seventy-five percent of small defects undergo spontaneous closure within the first two years of life [4,18,19]. Defects located in the muscular septum close with the growth and hypertrophy of the surrounding muscular septum. Small membranous defects may close through apposition of the septal leaflet of the tricuspid valve secondary to negative pressure created by the jet through the defect.

Small VSDs that persist into adulthood are usually benign [20-23]. This was demonstrated in the Second Joint Study on Natural History of Congenital Heart Defects which provided comprehensive data on 242 young adults known to have a small VSD who were medically managed and followed from early childhood [20]. Spontaneous closure occurred in 13.6 percent of patients with small VSDs, but most of the patients were older than two years when admitted into the study and had passed through the time when spontaneous closure is most common. Bacterial endocarditis occurred in nine patients (12.8 per 10,000 person-years of follow-up). Most patients had excellent outcome; however, there was a small but higher than normal incidence of serious arrhythmia and sudden death.

In another study of 229 adult patients with a VSD considered too small to require surgery during childhood who were followed to a mean age of 30 years, spontaneous closure occurred in 6 percent and endocarditis in 1.4 percent; there were no deaths [21]. At last visit, 95 percent were symptom-free, left ventricular (LV) size was increased in only one, no patient had LV dysfunction, and mean exercise capacity was 92 percent of predicted.

In another study of 188 adult patients with a small VSD referred to a national cardiac center in the United Kingdom, 10 percent had spontaneous closure during 13-year follow-up (0.8 percent per year) [22]. Approximately one-half remained stable without any sequelae. Complications occurred in 25 percent, including infective endocarditis in 11 percent, progressive aortic regurgitation requiring surgery in 5 percent, and age-related symptomatic arrhythmias, primarily atrial fibrillation, in 8.5 percent. The higher rate of complications in this study compared with the previous two studies may be due to referral bias. Many of the patients in this study (27 percent) had other cardiac lesions, most commonly a bicuspid aortic valve or coarctation of the aorta.

Moderate ventricular septal defect — The natural history of moderate-size VSDs varies depending upon pulmonary arterial pressure, and the size and location of the defect. The size of the defect may diminish over time and spontaneous closure may occur, although less frequently than with small VSDs [18,24-26]. Less commonly than spontaneous closure, patients with a membranous VSD may develop acquired obstruction to right ventricle (RV) outflow (also referred to as double-chambered right ventricle) that reduces volume overload of the LV and protects the pulmonary vascular bed [25]. (See 'Right ventricular outflow obstruction' below.)

The risk of developing heart failure is dependent on the magnitude of left-to-right shunting. (See 'Right ventricular outflow obstruction' below.)

Some moderate VSDs are pressure restricted. This means RV and pulmonary artery (PA) pressures are <50 percent of systemic arterial systolic pressures. However, even with restrictive VSDs, the degree of left-to-right shunting may be enough to cause congestive symptoms. Most infants with restrictive moderate-size VSDs respond to medical therapy, and pulmonary vascular resistance (PVR) usually does not increase in these patients. As a result, surgical or catheter-based intervention is often not required. The risk of development of irreversible pulmonary vascular obstructive disease increases when RV and PA pressures are >50 percent of systemic pressures, a level which should prompt closure of the defect [4]. (See "Management of isolated ventricular septal defects (VSDs) in infants and children".)

Other children with moderate VSDs and a persistent left-to-right shunt may remain hemodynamically and clinically stable, or improve for several years despite increased left atrial and ventricular volume [4]. This observation was illustrated by a long-term follow-up study (mean time of follow-up 7.8 years) of 33 unoperated children with moderate-size, restrictive VSDs with severe LV dilation but no evidence of cardiac failure or pulmonary arterial hypertension [27]. At follow-up, these patients had a spontaneous reduction in LV dilation measured by echocardiography (decrease of mean LV end-diastolic dimension z score from 3 to 1.2) suggesting smaller LV volumes due to reduced left-to-right shunt.

Large ventricular septal defect — Large VSDs rarely close spontaneously. Infants with these defects usually develop large left-to-right shunts in the first few weeks of life, resulting in signs of pulmonary overcirculation and poor weight gain. (See 'Presentation' below.)

Unless surgery is performed in the first year of life, there is increasing likelihood that elevated PVR will become fixed, preventing successful repair. Irreversible pulmonary vascular disease develops earlier in children with trisomy 21; large VSDs in such children should be repaired by three to four months of age. (See "Down syndrome: Clinical features and diagnosis" and "Down syndrome: Management".)

In the rare case of a large VSD that persists into late childhood without intervention, the increase in PA blood flow from persistent left-to-right shunting results in the development of pulmonary vascular remodeling and histologic evidence of pulmonary arteriolar intimal and medial hypertrophy. The resulting elevated PA vascular resistance leads to RV pressure overload and RV hypertrophy. When PVR exceeds systemic vascular resistance, the ultimate reversal of flow with right-to-left shunting causes hypoxemia, a condition called Eisenmenger syndrome. It is a serious, and generally irreversible, medical problem resulting in death as early as the third decade. However, a small study suggests that there are some select adolescent and adult patients with severe pulmonary hypertension (defined by systolic PA pressure >70 percent of systemic systolic pressure) and uncorrected VSD (with or without great artery anomalies) who may benefit from a palliative procedure, such as a pulmonary arterial band to improve functional class and provide a small chance of eventual total repair [28]. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

CLINICAL FEATURES

Presentation

Prenatal presentation — Moderate to large VSDs can be detected in utero, as early as at 16 to 18 weeks gestation. They can occur in isolation or in association with other cardiac defects. Some isolated VSDs will close during gestation depending on the size and location [29]. Given the fetal physiology of equal ventricular pressure, small to moderate VSDs can be missed by fetal echocardiography. Detection of an in utero VSD or other structural cardiac abnormalities should prompt counseling regarding potential chromosomal abnormalities and perhaps the need for further evaluation. These issues are discussed in greater detail separately. (See "Congenital heart disease: Prenatal screening, diagnosis, and management".)

Postnatal presentation — Most patients with VSD present in the neonatal period. However, the clinical presentation varies depending upon the size of the defect and may range from an isolated murmur that is detected incidentally at a health supervision visit to severe heart failure [30]. Infants with small, restrictive VSDs usually remain asymptomatic. In contrast, infants with moderate to large VSDs usually manifest signs of heart failure by three to four weeks of age [4,30].

●Small VSD – Patients with small VSDs typically present with an asymptomatic cardiac murmur (movie 1). In neonates, the murmur may be detectable at 4 to 10 days of life when pulmonary vascular resistance (PVR) declines sufficiently to permit left-to-right shunting. Symptoms are generally absent in small defects [3].

●Moderate to large VSD – Infants with moderate to large VSDs typically present by three to four weeks of life with symptoms and physical findings of heart failure, which may include [4,30]:

•Tachypnea

•Poor feeding (may appear hungry but tires easily; sweats with feeds)

•Poor weight gain (prolonged and severe failure may also affect linear growth and head circumference) [31,32]

•Tachycardia

•Hepatomegaly

•Pulmonary rales, grunting, and retractions (if heart failure is marked)

•Pallor (from peripheral vasoconstriction)

The severity of symptoms increases with the degree of left-to-right shunting.

Cardiac findings — The cardiac findings vary depending on the size of the defect, ranging from an isolated systolic murmur in patients with a small defect to findings indicative of high left ventricular (LV) output failure.

●Precordial palpation – In infants with small VSDs and a large pressure differential between the LV and right ventricle (RV), a thrill (4/6 murmur) may be palpated in the third or fourth left intercostal space at the left sternal border; if the defect is subpulmonic, the thrill is best palpated in the second or first and second left intercostal space [33]. Infants with moderate or large defects may develop a hyperdynamic precordial impulse as PVR falls during the first few weeks of life and left-to-right shunt increases. As LV output increases to compensate for the left-to-right shunt, vigorous LV contraction is reflected in a prominent apical impulse. As the heart enlarges, the cardiac apex is displaced outside the mid-clavicular line. Vigorous precordial activity and a dynamic LV impulse, particularly in the left lateral recumbent position, may indicate the development of aortic regurgitation [15]. (See 'Aortic regurgitation' below.)

●Systolic murmurs – The character and duration of the systolic murmur are helpful in evaluating the size of the defect [4].

•Small VSD – The murmur of a small defect is classically described as an intensity grade 2 to 3/6 harsh or blowing holosystolic murmur best heard at the left mid to lower sternal border (movie 1); subpulmonic defects are best heard at the left upper sternal border [4]. During spontaneous closure, the holosystolic murmur may shorten, occurring only in early systole before disappearing altogether [34]. The murmur of small muscular or perimuscular VSDs may occur only in early systole (movie 2), since the contraction of the septum during systole may close the defect.

•Moderate VSD – The murmur of moderate defects, usually evident within two to three days of birth, is holosystolic, mid-high frequency, intensity grade 2/6 or louder, and heard best in the third or fourth LICS. The quality of the murmur may change as PVR falls.

•Large VSD – In infants who have large VSDs, as right ventricular pressure approaches systemic levels, a murmur may not be present. If present, the systolic murmur is of grade 1 to 2/6 mid-frequency, often accompanied by a diastolic rumble, which is related to the increase in flow through the mitral valve. As PVR falls, the systolic murmur may increase in amplitude, although the character of the murmur typically does not change.

●Diastolic murmurs – The presence of diastolic murmurs in infants usually indicates increased left-to-right shunting.

•A diastolic rumble due to increased flow across the mitral valve may be heard at the apex in infants with moderate to large VSDs with a ratio of pulmonary to systemic blood flow (Qp:Qs) >2:1 [33,35].

•A high-frequency decrescendo murmur beginning with the first component of the second heart sound and best heard at the mid to lower sternal border suggests the development of aortic regurgitation secondary to prolapse of an aortic cusp through either a perimembranous or a subpulmonic defect. Patients with such murmurs usually require early surgery. (See 'Aortic regurgitation' below and "Management of isolated ventricular septal defects (VSDs) in infants and children".)

•An early diastolic decrescendo murmur at the mid-left sternal border in patients with elevated pulmonary artery pressures suggests pulmonary regurgitation. Patients with such murmurs should be evaluated for elevated PVR. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

●Second heart sound – The intensity and degree of splitting of the second heart sound provide useful information about the size of the defect and the elevation of PVR, although these features may be difficult to appreciate [4]. The second heart sound may be obscured by a holosystolic murmur and splitting also may be difficult to appreciate when the heart rate is increased.

•A loud second sound at the left upper sternal border (movie 3) indicates elevated pulmonary arterial pressure, suggesting that the defect is large.

•A well-split second sound suggests that PVR is not markedly increased, whereas a narrow or single accentuated sound indicates that PVR is elevated.

•Exaggerated splitting, reflecting an increase in right ventricular volume and prolonged systole, may be detected in infants with moderate to large defects and PVR less than systemic vascular resistance.

Initial tests — Most patients will undergo initial testing that includes electrocardiogram (ECG). In addition, chest radiography may be performed if the patient presents with symptoms of heart failure. However, the diagnosis is generally confirmed by echocardiography. (See 'Diagnosis' below.)

Electrocardiogram — The ECG findings, which represent the effects of increased volume and pressure loads on the left and right ventricles, are nonspecific and vary with the size of the VSD [4]:

●In patients with small VSDs, the ECG is typically normal.

●In patients with moderate or large left-to-right shunting, the ECG may demonstrate LV hypertrophy (LVH) manifested as increased voltage in V5 and V6, or leads II, III, and aVF (waveform 1). LVH occurs because of the increased LV workload imposed by excessive blood volume returning to the left heart.

●In patients with elevated RV pressure, the ECG demonstrates RV hypertrophy (RVH), often manifested by tall R waves in leads V4R and V1, or upright T waves in these leads beyond the first 24 hours of life, in addition to LVH.

●In patients with a PVR elevation sufficient to minimize or even reverse the direction of the shunt, the ECG may demonstrate evidence of right atrial enlargement (narrow P wave with increased amplitude) in addition to RVH (waveform 2); LVH is no longer present.

●Patients who have undergone surgical closure may develop right bundle branch block (complete or incomplete).

Patients with findings consistent with marked RVH require further evaluation to determine the cause. Possibilities include elevated PVR, pulmonary stenosis, or double-chambered RV, and management varies accordingly.

Chest radiograph — If a chest radiograph is obtained, findings vary depending upon the size of the left-to-right shunt and the state of the pulmonary vascular bed.

●In small defects, the radiograph is usually normal.

●In moderate to large defects with increased left-to-right shunts, the pulmonary vascular markings are increased, and the left atrium, LV, and pulmonary artery may be enlarged.

●As PVR increases, RV enlargement becomes more prominent and the LV decreases in size; anterior bulging of the lower sternum may be present.

DIAGNOSIS — The diagnosis of VSD is confirmed with echocardiography. Two-dimensional with Doppler echocardiography is usually sufficient to make the diagnosis, identify the location of the defect, and estimate the size of the shunt. Although experienced pediatric cardiologists are often able to make the diagnosis clinically based on the characteristic cardiac features of a blowing holosystolic murmur, most choose to obtain an echocardiogram to confirm the diagnosis, identify the location of the defect(s) and any associated lesions, and estimate the size of the shunt.

Color flow Doppler is invaluable for detecting smaller muscular defects (image 1 and movie 4). Membranous defects can be seen in the parasternal long axis echocardiographic view just below the aortic valve (image 2 and movie 5). A detailed discussion on the use of echocardiography in assessing VSDs is presented separately. (See "Echocardiographic evaluation of ventricular septal defects".)

Cardiac catheterization, once commonly performed in the evaluation of infants with VSD, is now rarely utilized. In some clinical situations, a catheterization may help assess the need for closure (ie, to precisely measure Qp:Qs) or plan perioperative management (ie, to measure pulmonary vascular resistance and assess responsiveness to vasodilators) [4].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of VSD includes other acyanotic congenital heart defects that present with a systolic murmur, such as tricuspid regurgitation or mitral regurgitation. Echocardiography distinguishes VSD from these other congenital cardiac conditions. (See "Approach to the infant or child with a cardiac murmur".)

VSD can be distinguished from noncardiac causes of respiratory distress (eg, pneumonia, bronchiolitis, or asthma) by the presence of a systolic murmur on physical examination, and by diagnostic tests including chest radiography and echocardiography. (See "Causes of acute respiratory distress in children".)

COMPLICATIONS — In addition to pulmonary vascular disease, discussed above, complications of VSDs may include the development of endocarditis, aortic regurgitation, subaortic stenosis, right ventricular (RV) outflow tract obstruction, and atrial shunting.

Endocarditis — Infective endocarditis is an uncommon complication [20,36-42]. Surgical closure reduces the risk, even in patients who have restrictive defects [43]. However, the risk of endocarditis is increased in the immediate postoperative period [44]. (See "Native valve endocarditis: Epidemiology, risk factors, and microbiology", section on 'Structural heart disease'.)

The clinical manifestations and diagnosis of infective endocarditis, and antibiotic prophylaxis to prevent endocarditis are discussed in detail separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis" and "Management of isolated ventricular septal defects (VSDs) in infants and children" and "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Aortic regurgitation — Aortic valve prolapse and regurgitation may occur in subpulmonic and membranous defects. This complication is more common in boys [45,46], with a peak onset between five and nine years of age, and seldom occurs before 2 or after 10 years of age [45-48].

Aortic regurgitation is often asymptomatic until it progresses to moderate or severe levels. Clinical features of moderate to severe aortic regurgitation include neck pulsations, diaphoresis, vigorous precordial movement (particularly in the left lateral recumbent position) [15], bounding pulses, wide pulse pressure, and early diastolic murmur (movie 6). Radiographic features include enlargement of the LV that is out of proportion to the evidence of left-to-right shunt and a prominent ascending aorta.

In membranous defects, aortic regurgitation is associated with sagging or herniation of the right coronary cusp alone or in conjunction with the noncoronary cusp [49-55]. Herniation into the RV outflow tract may cause obstruction [55,56] and herniation through the VSD may reduce the left-to-right shunt [45,57].

In subpulmonic VSDs, the aortic and pulmonary valves are in fibrous continuity with each other [58]. The aortic valve is unsupported and the right and noncoronary sinuses move into the RV outflow tract causing aortic regurgitation [45,56,57].

In patients with VSD and aortic regurgitation, the left ventricle (LV) is doubly overloaded because of both the regurgitant volume from the aorta and the increased volume returning to the left atrium from the pulmonary circulation. The natural history is usually one of gradual progression. The risk of infective endocarditis is increased [45]. (See "Native valve endocarditis: Epidemiology, risk factors, and microbiology", section on 'Structural heart disease'.)

Subaortic stenosis — Patients with membranous VSDs can occasionally develop discrete fibrous or fibromuscular subaortic stenosis [59-62]. Indications for surgical resection defined by LV outflow tract gradient vary between both clinicians and institutions. The LV outflow tract obstruction generally is progressive with potential for damage to the aortic valve. Long-term follow-up after surgical resection is necessary because recurrence is possible.

Right ventricular outflow obstruction — Patients with membranous defects may develop hypertrophy in the right ventricular infundibulum, which, over a variable period of time, may result in narrowing of the outflow tract [4,45,63]. Double-chambered RV (DCRV) results when hypertrophied bands of muscle divide the RV cavity into two chambers. DCRV may develop in patients with membranous VSD (whether or not they have undergone surgical repair) [64-69].

Obstruction to RV outflow results in increased resistance to RV ejection and decreased left-to-right shunt. Initially this process may account for improvement of cardiac failure in infants; however, with severe hypertrophy, right-to-left shunting may develop, with clinical features similar to those in tetralogy of Fallot. (See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)

Left ventricle to right atrium shunting — Some VSDs in the perimembranous region may cause effective shunting from the LV to the right atrium (RA). The mechanism may be related to incompetence of the septal leaflet of the tricuspid valve allowing blood to be directed from the LV to the RV with resultant shunt volume entering the RA. Alternatively, some VSDs may be located slightly more superior to the tricuspid valve apparatus, allowing direct LV to RA flow [70]. In either case, the effective impact of such a shunt is to produce right ventricular volume overload and elevated right atrial pressure. Patients with LV-to-RA shunts may still have spontaneous closure of their VSDs, but appear to be at increased risk for endocarditis [71].

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Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Ventricular septal defects in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Prevalence – Ventricular septal defects (VSDs) are among the most common congenital heart lesions, with a reported prevalence of 4 per 1000 live births. (See 'Prevalence' above.)

●Anatomy – There are three main anatomic components of the interventricular septum (figure 1), and VSDs may occur at various locations in any of the three components (figure 3). Membranous VSDs are the most common type of clinically significant VSD. (See 'Anatomy' above.)

●Clinical features – The clinical presentation and natural history of isolated VSDs in children depends upon the size of the defect (see 'Clinical features' above and 'Natural history' above):

•Small VSDs most commonly come to attention when a murmur is detected, typically during a routine health care visit. The murmur is heard best at the mid to lower left sternal border and it can be either holosystolic or a blowing high pitched systolic murmur of variable length (movie 1 and movie 2).

Small VSDs rarely cause symptoms, and often close spontaneously. Spontaneous closure is heralded by shortening and ultimate disappearance of the murmur. Small VSDs that persist into adulthood typically remain benign. (See 'Small ventricular septal defect' above and 'Presentation' above.)

•Moderate VSDs with low pulmonary vascular resistance (PVR) usually present with heart failure and poor growth in infancy due to left atrial and ventricular volume overload. Cardiac examination reveals a dynamic precordium, a holosystolic murmur (with or without a thrill) at the mid to lower left sternal border (movie 1), and increased second component of the second heart sound (movie 3). The presence of a diastolic murmur at the apex indicates a ratio of pulmonary to systemic blood flow (Qp:Qs) of at least 2:1. The presence of a diastolic murmur at the mid to lower sternal border may indicate aortic or pulmonary regurgitation and warrants further evaluation. Moderate defects decrease in size with time and may close spontaneously. In the interim, patients may develop signs and symptoms of heart failure that may require treatment. (See 'Moderate ventricular septal defect' above and 'Clinical features' above and "Management of isolated ventricular septal defects (VSDs) in infants and children", section on 'Moderate to large ventricular septal defect'.)

•Large nonrestrictive VSDs with elevated PVR present in infancy with heart failure, feeding difficulties, and poor weight gain. Examination findings are similar to those in infants with moderate defects. In infants with large defects, irreversible pulmonary vascular changes may begin within 6 to 12 months and may be advanced by two to three years of age. Large defects may decrease in size, but rarely close completely. (See 'Large ventricular septal defect' above and 'Clinical features' above.)

In some infants with large VSDs, PVR remains sufficiently elevated to limit the shunt. The clinical presentation in these infants may be more subtle. If these infants are not treated, PVR progressively increases and right-to-left shunting may occur. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

●Chest radiograph and electrocardiogram (ECG) findings – Radiographic findings associated with moderate to large defects include increased pulmonary vascular markings and enlargement of the left atrium, left ventricle, and pulmonary artery. The ECG may demonstrate left atrial and ventricular enlargement (waveform 1). If right ventricular pressure is elevated, the ECG may demonstrate both right and left ventricular hypertrophy (waveform 2). (See 'Chest radiograph' above and 'Electrocardiogram' above.)

●Diagnosis – The diagnosis of VSD is confirmed with echocardiography, which can also identify the location of the defect and estimate the size of the shunt. Color flow Doppler is invaluable for detecting smaller muscular defects (image 1 and movie 4). Membranous defects can be seen in the parasternal long axis echocardiographic view just below the aortic valve (image 2 and movie 5). Use of echocardiography in assessing VSDs is discussed in greater detail separately. (See "Echocardiographic evaluation of ventricular septal defects".)

●Differential diagnosis – The differential diagnosis of VSD includes other noncyanotic congenital heart defects that present with a systolic murmur. Echocardiography distinguishes VSD from these other congenital cardiac conditions. (See 'Differential diagnosis' above.)

●Complications – Complications that can occur in patients with isolated VSDs include endocarditis, aortic regurgitation, subaortic stenosis, right ventricular obstruction, and left ventricular-to-right atrial shunting. (See 'Complications' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas Graham Jr, MD, and Kirsten Dummer, MD, who contributed to an earlier version of this topic review.