Clinical manifestations and diagnosis of ventricular septal defect in adults

INTRODUCTION — Ventricular septal defect (VSD) is one of the most common congenital heart defects (second only to bicuspid aortic valve) at birth, but accounts for only 10 percent of congenital heart defects in adults because many close spontaneously [1,2].

VSDs are of various sizes and locations, can be single or multiple, and may occur as isolated lesions or along with more complex congenital heart lesions [3]. VSDs may be complicated by pulmonary hypertension, aortic or tricuspid valve regurgitation, which may impact their clinical presentation, and natural history. The focus of this topic is the clinical manifestation and diagnosis of isolated congenital VSDs in adults. VSDs in combination with more complex defects (eg, tetralogy of Fallot) are discussed separately. (See "D-transposition of the great arteries (D-TGA): Anatomy, clinical features, and diagnosis" and "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)

A VSD can also occur as an acquired condition as a complication after acute myocardial infarction, following surgical or transcatheter aortic valve replacement, as a complication of septal myectomy for hypertrophic cardiomyopathy, or by erosion from a strut of a mitral valve bioprosthesis, as discussed separately [4]. (See "Acute myocardial infarction: Mechanical complications", section on 'Rupture of the interventricular septum' and "Transcatheter aortic valve implantation: Complications", section on 'Ventricular perforation' and "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.)

The natural history, complications, management, and prognosis of VSDs in adults are discussed separately. (See "Management and prognosis of congenital ventricular septal defect in adults".)

ETIOLOGY OF CONGENITAL VSD — Heterogeneous genetic and environmental factors contribute to congenital VSDs, and for most congenital VSDs the cause is unknown. About 5 percent of patients with VSDs have chromosomal abnormalities including trisomy 13, 18, and 21 syndromes [5]. DNA sequence variants within the GATA4, GATA6, CITED2, NKX2-5, HAND1, TBX2, and TBX18 genes may also be involved in VSD genesis [6-10]. The discovery of SMAD3, a key intracellular messenger regulating TGF beta signaling, may explain the ascending aorta enlargement (particularly at the sinus of Valsalva) seen in some patients with VSD [11].

ANATOMIC TYPES — The ventricular septum is a nonplanar, three-dimensional partition of the ventricles with five components: the membranous, muscular (also known as trabecular), infundibular, inlet, and atrioventricular (AV) segments (figure 1 and figure 2). VSDs result from deficient growth or failure of fusion of these components and vary in size from tiny apertures to very large defects with virtual absence of the septum [12]. In 2000, the Society for Thoracic Surgery (STS) and the European Association for Cardiothoracic Surgery (EACTS) established a unified reporting system for congenital heart disease, including VSD [13]. They classified VSD into four types: Type 1 defects involve the infundibular septum, type 2 defects involve the membranous septum, type 3 defects involve the inlet septum, and type 4 defects involve the muscular septum (figure 3).

●Infundibular VSD (type 1, also referred to as supracristal, subarterial, subpulmonary, conal, or doubly-committed juxta-arterial VSD) results from deficiency in the septum above and anterior to the crista supraventricularis, beneath the aortic and pulmonary valves (figure 2 and image 1 and movie 1 and movie 2). The resultant loss of support of the right and/or left aortic valve cusp causes cusp prolapse into the VSD, leading to aortic regurgitation that could be progressive [14], and occasionally aortic sinus dilation [15,16]. Infundibular VSDs are common in Asian individuals, accounting for one-third of VSDs. They occur less frequently in White individuals (6 percent of VSDs) [17,18].

●A membranous VSD (type 2, also known as perimembranous or conoventricular) results from deficiency of the membranous septum and is the most common type of VSD in adults (80 percent of VSDs in the United States) (figure 2 and image 2 and movie 3). This defect is inferior to the crista supraventricularis and borders the septal leaflet of the tricuspid valve. The defect may extend into the muscular septum and is then referred to as a perimembranous (or paramembranous) VSD.

●Inlet VSD (type 3, also known as AV canal type) results from deficiency of the inlet septum, located beneath both mitral and tricuspid valves (image 3). Despite proximity to those valves, this type of defect is not associated with mitral or tricuspid regurgitation unless associated with atrioventricular septal defect; these defects are typically large and often associated with Down syndrome. (See "Clinical manifestations and diagnosis of atrioventricular (AV) canal defects".)

●Muscular VSDs (type 4), which account for 5 to 20 percent of VSDs in adults, are bordered only by muscle within the trabecular septum, away from the cardiac valves. Muscular defects can be small or large, single or multiple, and occasionally oblique with multiple exits resembling Swiss cheese.

●A Gerbode defect or AV VSD is the least common VSD, caused by deficiency of the membranous septum separating the left ventricle (LV) from the right atrium, resulting in an LV-to-right atrial shunt. This defect has also been reported as an acquired lesion (eg, following endocarditis and valve replacement) [19-21].

The spectrum of VSD sizes, hemodynamic effects, and clinical manifestations are discussed below. (See 'Spectrum of clinical presentation' below.)

CLINICAL MANIFESTATIONS — The clinical manifestations of VSD in adults vary with the functional size and hemodynamic effects of the defect. (See 'Spectrum of clinical presentation' below.)

In addition, some adults with VSD have signs and symptoms related to associated lesions (such as aortic regurgitation) or complications (such as endocarditis, heart failure [HF], or arrhythmias). (See 'Associated cardiovascular conditions' below and 'Lesions associated with right atrial enlargement' below and "Management and prognosis of congenital ventricular septal defect in adults", section on 'Complications and their management'.)

Spectrum of clinical presentation — The spectrum of isolated residual VSDs in adults includes the following clinical and hemodynamic types [22]. The direction and severity of the shunt associated with VSD are determined by the VSD's functional size and, in the absence of right ventricular (RV) outflow obstruction, by the ratio of pulmonary to systemic vascular resistance or ventricular afterload. A small isolated VSD with left-to-right shunt is considered a simple congenital heart defect, whereas a VSD associated with one or more additional abnormalities and/or moderate or greater shunt is considered to be of moderate complexity. VSD associated with Eisenmenger syndrome is a complex congenital heart defect given the associated cyanosis, pulmonary hypertension, and multisystem involvement.

●Small restrictive VSDs are associated with small left-to-right shunts (pulmonary to systemic flow ratio [Qp:Qs] <1.5:1), and the pulmonary vascular resistance is not significantly elevated. The orifice dimension is ≤25 percent of the aortic annulus diameter. There is no LV volume overload or pulmonary hypertension (PH).

Most small isolated muscular and perimembranous VSDs close spontaneously during childhood. Adults with an isolated small restrictive VSD with small left-to-right shunt (often referred to as "maladie de Roger") generally remain asymptomatic and present with a systolic murmur, often with a palpable thrill from the VSD. There is risk of endocarditis associated with this lesion, but the magnitude of risk is low. In a minority of cases, a diastolic murmur from aortic regurgitation develops. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Clinical course' and "Auscultation of cardiac murmurs in adults", section on 'Ventricular septal defect'.)

●Moderately restrictive defects that have not completely closed are associated with moderate shunts (Qp:Qs ≥1.5:1 and <2:1). The defect typically measures >25 but <75 percent of the aortic annulus diameter and results in mild to moderate volume overload of the pulmonary arteries, left atrium, and LV. Patients with this type of lesion often have mild to moderate pulmonary arterial hypertension.

Children with moderate-sized VSDs may remain asymptomatic or develop symptoms of mild HF in childhood. HF usually resolves with medical therapy and with time as the child grows and the VSD gets smaller in absolute and/or relative terms. However, some adults have moderately restrictive defects that have not been completely closed, and these patients may develop PH and may have associated symptoms related to the LV volume overload or PH.

●Large nonrestrictive VSDs (defined as those with diameters ≥75 percent of that of the aortic annulus) lead to the following clinical scenarios (see "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Large ventricular septal defect'):

•Early large left-to-right shunt – Most infants with large VSDs have early large left-to-right shunts (Qp:Qs ≥2.1) as the pulmonary vascular resistance falls postnatally. This results in LV volume overload and HF. These VSDs are generally closed during the first year of life.

•Progressive pulmonary arterial hypertension – If a large VSD remains uncorrected, it can cause progressive PH due to longstanding unobstructed pulmonary flow with resultant pulmonary arterial obstructive disease. The volume of the left-to-right shunt will decline as pulmonary vascular resistance rises. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Large ventricular septal defect' and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

•Development of right-to-left shunt (Eisenmenger complex) – With progressive increases in pulmonary vascular resistance (and/or failure of pulmonary vascular resistance to fall normally postnatally), the RV pressure may reach systemic or suprasystemic levels, leading to reversal of the shunt so that it is directed right-to-left with resultant hypoxemia and cyanosis; this is known as Eisenmenger syndrome [23]. Eisenmenger syndrome in association with VSD is known as Eisenmenger complex; this typically presents during late childhood to early adulthood. Elevated RV and right atrial pressures cause RV hypertrophy and right atrial enlargement. (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Large ventricular septal defect' and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

●Some adults with prior VSD closure (frequently in childhood) have a residual VSD; these are often hemodynamically insignificant. Residual VSD and other post-closure sequelae are discussed separately. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Residual VSD' and "Management and prognosis of congenital ventricular septal defect in adults", section on 'Postoperative course'.)

Dyspnea, exercise intolerance, and fatigue in patients with VSDs can result from progressive LV overload due to the VSD, associated significant aortic or tricuspid valve regurgitation, PH, or double-chambered RV (DCRV). (See 'Associated cardiovascular conditions' below.)

Syncope is a rare symptom in patients with VSD; it may be caused by severe PH, RV outflow obstruction caused by DCRV, large aneurysm of the membranous septum causing RV outflow obstruction, or arrhythmia. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Arrhythmias'.)

Associated cardiovascular conditions — A minority of adults with VSD have associated congenital or acquired lesions, including aortic regurgitation, tricuspid regurgitation, or sinus of Valsalva dilation. DCRV, an additional associated lesion, is discussed below (see 'Lesions associated with right atrial enlargement' below). These associated conditions affect the clinical presentation.

Aortic regurgitation — A minority of adults with VSD (prior to or following closure) have aortic regurgitation with characteristic signs and symptoms, including a diastolic murmur (see "Auscultation of cardiac murmurs in adults", section on 'Aortic regurgitation'). Aortic regurgitation occurs in association with infundibular VSD and less commonly with membranous VSD. It results from deficiency or hypoplasia of the conal septum, causing an anatomically unsupported aortic valve cusp and aortic sinus. During systole, a Venturi effect drives the right or left aortic valve cusp into the RV through the VSD, thus making the VSD smaller (figure 4). During diastole, the intraaortic pressure forces the aortic valve cusps to close, but the unsupported cusp is pushed down into the LV outflow tract away from the other aortic valve cusps, resulting in cusp prolapse, progressive aortic regurgitation, and progressive LV volume overload [24,25]. This ultimately also causes dilation of the aortic sinus (see 'Aortic sinus dilation' below). The progression of PH appears to be less common in adult patients with infundibular VSD [14].

Tricuspid regurgitation — A murmur of tricuspid regurgitation is present in a minority of adults with VSD (prior to or following closure) (see "Auscultation of cardiac murmurs in adults", section on 'Tricuspid regurgitation'). Tricuspid regurgitation associated with a membranous VSD is most commonly due to the septal tricuspid valve leaflet becoming partially adherent to the VSD. Tricuspid regurgitation may also be caused by a tricuspid valve cleft or dysplasia, or, rarely, by the VSD jet pushing the tricuspid anterior leaflet forward to open the tricuspid valve orifice [26].

Aortic sinus dilation — Aortic sinus dilation may occur in a patient with a VSD, most commonly with infundibular VSD. Rarely, rupture of the aneurysmal sinus of Valsalva occurs in this setting and causes a continuous murmur. This usually causes a large left-to-right shunt [27]. The change in a murmur to a continuous murmur and new symptoms occurring in a patient with a known VSD are the clinical clues that lead to this diagnosis. Echocardiography is helpful in the detection of aortic sinus dilation as well as ruptured sinus of Valsalva aneurysm.

Physical signs — Most VSDs can be readily identified by cardiac examination depending on their type, size, and associated hemodynamic abnormalities. The smaller the VSD, the louder the associated murmur. Small VSDs cause a loud high-frequency systolic murmur, often accompanied by a palpable thrill in the third or fourth left intercostal space [28]. The aortic closure sound may be normal or masked by the loud murmur. Although the VSD murmur is typically a holosystolic plateau-shaped murmur, it may stop well before the second sound with some muscular defects because of midsystolic obliteration of the defect [29]. (See "Auscultation of cardiac murmurs in adults", section on 'Ventricular septal defect'.)

Patients may present with a change in the murmur on physical examination caused by the associated conditions such as DCRV, PH, ruptured sinus of Valsalva, or aortic regurgitation (figure 5). Membranous VSD may close spontaneously via adherence of the septal leaflet of the tricuspid valve, which forms an aneurysm of the membranous septum; this septal aneurysm may cause a new midsystolic click and may lead to syncope when very large due to RV outflow obstruction. (See 'Associated cardiovascular conditions' above.)

As shown in the figure (figure 5), the cardiac examination of patients with VSD and valvular or subvalvular pulmonary stenosis depends on the severity of the latter lesion. The typical holosystolic VSD murmur may be replaced by a "diamond-shaped" (crescendodecrescendo) midsystolic murmur or simply consist of a systolic ejection component in the presence of pulmonic stenosis. Similarly, DCRV with VSD is associated with a loud midsystolic crescendo-decrescendo murmur at the left sternal border, often associated with a thrill [30]. An infundibular VSD allows blood to be shunted toward the pulmonary artery and therefore there may be a systolic ejection murmur heard maximally in the second intercostal space. (See "Auscultation of cardiac murmurs in adults", section on 'Ventricular septal defect'.)

Patients with infundibular or membranous VSDs who develop aortic regurgitation demonstrate a diastolic decrescendo murmur. When the aortic regurgitation is severe, wide pulse pressure, pistol shot femoral pulses, and collapsing pulses are often noted. A to-and-fro, systolic/diastolic murmur, best heard in the upper sternal border, and composed of a systolic VSD murmur and a separate high-frequency diastolic murmur of aortic regurgitation is also noted. This may simulate continuous murmurs such as those heard with ruptured sinus of Valsalva aneurysm or patent ductus arteriosus. However, in patients with VSD and aortic regurgitation, the systolic component stops at or before the second heart sound and does not envelop it as continuous murmurs do. The presence of long-standing severe aortic regurgitation will also cause LV enlargement. (See "Auscultation of cardiac murmurs in adults", section on 'Aortic regurgitation'.)

In patients with moderately restrictive or large VSDs, the character and timing of the systolic murmur changes with progressive PH. With PH, the murmur is early systolic, and the peak of the murmur occurs earlier.

When VSD is complicated by pulmonary vascular obstructive disease and severe PH as in Eisenmenger complex, the patients have central cyanosis and clubbed digits. The typical findings on cardiac examination in Eisenmenger complex include the following (see "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis", section on 'Clinical manifestations'):

●Absence of the typical holosystolic murmur of VSD due to equalization of RV and LV pressures with associated loss of the left-to-right shunt. Systolic murmur in the presence of Eisenmenger syndrome is typically caused by tricuspid regurgitation. There may also be a midsystolic pulmonary ejection murmur associated with severe PH and often a diastolic decrescendo murmur from pulmonic valve regurgitation (Graham Steell murmur). (See "Auscultation of cardiac murmurs in adults", section on 'Ventricular septal defect'.)

●Jugular venous pressure examination demonstrating a prominent "a" wave due to RV hypertrophy. Once the patient develops severe tricuspid regurgitation, a prominent "v" wave is also noted.

●Prominent RV impulse and palpable and loud pulmonary closure sound, which often fuses with the aortic closure sound, producing a single second heart sound. (See "Auscultation of heart sounds", section on 'Single S2'.)

●With advanced disease, signs of right HF such as edema, ascites, and hepatomegaly can occur.

Initial tests — An electrocardiogram (ECG) and a chest radiograph are commonly performed in the evaluation of patients with known or suspected VSD.

Electrocardiogram — An ECG is a component of the evaluation of patients with known or suspected VSD to serve as a baseline for follow-up comparison, although findings are generally non-specific. The majority of patients with isolated VSD, especially when small, have a normal ECG (eg, 66 percent in a medically-managed group of patients with VSD) [31]. However, various ECG abnormalities such as intraventricular conduction delay or right bundle branch block have been observed among those with larger defects. In addition, ECG signs of left atrial enlargement and LV enlargement or hypertrophy can be present with significant LV volume overload due to VSD shunt and/or aortic regurgitation.

In the presence of Eisenmenger complex, or significant RV outflow obstruction such as that caused by DCRV, the ECG reflects the elevated RV pressure with findings including right axis deviation, features of right atrial enlargement, and RV or biventricular hypertrophy. The prevalence of atrial and ventricular premature beats and arrhythmias increases as the RV pressure increases, and therefore may be incidentally noted on the ECG.

Chest radiograph — A chest radiograph is not routinely required to evaluate patients with known or suspected VSD but is appropriate to evaluate the cause of dyspnea or pulmonary hypertension. The chest radiograph in patients with uncomplicated small VSD demonstrates a normal cardiac silhouette and pulmonary vascular markings. With larger VSDs, the chest radiograph may show cardiomegaly with prominent LV contour and left atrial and pulmonary artery enlargement due to volume overload; this is directly related to the magnitude of the shunt. The chest radiograph may also show evidence of shunt vascularity. Cardiomegaly on chest radiograph suggests a significant left-to-right shunt through the VSD with a Qp:Qs >2 or the presence of significant aortic regurgitation, or both.

In the presence of Eisenmenger complex, the cardiomegaly noted on a chest radiograph has an RV contour due to RV hypertrophy and is frequently accompanied by right atrial enlargement and prominent central pulmonary arteries with pruning of peripheral pulmonary vessels. (See "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis", section on 'Diagnosis and evaluation'.)

DIAGNOSIS

When to suspect VSD — A VSD should be suspected in a patient who presents with a characteristic holosystolic murmur; there are generally no associated symptoms in patients with small VSDs, while patients with moderate or large VSDs develop symptoms such as dyspnea and fatigue. For small and moderately restrictive VSDs, the murmur is typically holosystolic, as RV pressure is lower than LV pressure throughout systole. For large VSDs with increased RV and pulmonary artery pressure, the murmur is instead early systolic, and physical findings of pulmonary hypertension (PH) and RV hypertrophy are present. When ventricular pressures are equal in Eisenmenger complex, there is no murmur across the VSD; instead, there is a midsystolic murmur due to dilation of the pulmonary trunk or a holosystolic murmur related to tricuspid valve regurgitation, and S2 is markedly accentuated and single. (See 'Physical signs' above and "Auscultation of cardiac murmurs in adults", section on 'Ventricular septal defect' and "Clinical features and diagnosis of pulmonary hypertension of unclear etiology in adults", section on 'Examination'.)

VSD should also be suspected on echocardiography in the presence of unexplained LV dilation, aortic valve prolapse with aortic regurgitation, or when a double-chambered RV (DCRV) is noted.

How to diagnose and evaluate VSD — A VSD is generally identified and its hemodynamic effects are assessed by transthoracic echocardiography (TTE). Occasionally, in a patient with PH, a VSD is identified following intravenous agitated saline injection performed during a TTE with demonstration of a right-to-left shunt at the ventricular level. The VSD can be missed due to equal pressures in the right and left ventricles; thus, all patients presenting with PH should have one agitated saline injection at the time of TTE. TTE is also the key test for identifying and evaluating associated cardiovascular conditions such as aortic regurgitation, aortic sinus dilation, DCRV, and PH. (See 'Associated cardiovascular conditions' above.)

Since patients with congenital heart disease may underreport symptoms and functional limitations, we suggest exercise testing for the patient with a VSD, in the absence of severe PH, to provide an objective functional assessment. (See 'Exercise testing' below.)

Supporting data are obtained by further noninvasive imaging in selected cases. Cardiovascular magnetic resonance (CMR) imaging is indicated to assess the VSD in complex cases. Some experts also refer patients for CMR at an experienced center to assess the pulmonary to systemic flow ratio (Qp:Qs), as well as ventricular sizes and function if the hemodynamic significance of a VSD is uncertain on echocardiography (eg, there is borderline LV dilation). (See 'Cardiovascular magnetic resonance' below.)

If CMR at an experienced center is not available or contraindicated, cardiac computed tomography is a potential alternative noninvasive option. (See 'Cardiac computed tomography' below.)

However, evaluation by cardiac catheterization is generally required if the significance of the shunt is uncertain based upon echocardiography and is also indicated if there is PH. Cardiac catheterization includes assessment of Qp:Qs, pulmonary artery pressures, and pulmonary vascular resistance. (See 'Cardiac catheterization' below.)

Key tests

Echocardiogram — A comprehensive TTE examination is the single most important test needed in evaluating a patient with a VSD for hemodynamic burden, associated congenital defects, and potential long-term complications. TTE has an excellent detection rate for VSD depending on the size and location of the VSD, and the technical expertise of the examiner [24]. TTE is most sensitive for VSDs larger than 5 mm and those located in the membranous, inlet, or infundibular septum, while being least sensitive for those in the apical trabecular septum. TTE is performed during initial assessment of a VSD and on subsequent follow-up evaluation; the testing interval depends on the number, size, location, and impact of the VSDs; and the physiologic state of the patient [22]. (See "Echocardiographic evaluation of ventricular septal defects" and "Management and prognosis of congenital ventricular septal defect in adults", section on 'Approach to management'.)

Transesophageal echocardiography (TEE) is reserved for patients with suboptimal precordial TTE windows and when specific questions are not confidently answered using TTE, such as the degree of aortic valve distortion, severity of aortic regurgitation, and the presence of vegetations when endocarditis is suspected. TEE or intracardiac echocardiography are also used during interventional procedures.

Echocardiogram components — A thorough TTE examination is best achieved by imaging the ventricular septum and surrounding structures in multiple planes with color flow and spectral Doppler. The parasternal long-axis views allow the distinct visualization of muscular, membranous (image 2 and movie 3), and infundibular VSDs (movie 1). The latter two defects are both seen below the aortic valve and may be difficult to differentiate from each other on the long-axis image alone. On parasternal short-axis imaging, these VSD types are clearly distinguished with a membranous defect adjacent to the tricuspid valve, whereas an infundibular defect is adjacent to the pulmonary valve (figure 2). The parasternal view also enables visualization of an aneurysm of the membranous septum or sinus of Valsalva and assists in the evaluation of aortic regurgitation severity (image 1) and DCRV (image 4 and movie 4).

The apical views enable assessment of inlet, muscular, and Gerbode defects. Inlet VSDs are adjacent to the mitral and tricuspid valves (image 3) and extend into the chordal attachments of the tricuspid valve, whereas the muscular VSDs are located in the trabecular septum away from the cardiac valves (image 5). Gerbode defects are best visualized within the cardiac crux on apical four-chamber view in which color flow Doppler demonstrates an LV-to-right atrial shunt.

In addition to the accurate identification of the morphologic features of the VSD, its size, and its borders, echocardiography also provides a hemodynamic assessment of the shunt severity; identifies volume overload of the left atrium, LV, right atrium, RV, and pulmonary artery; and identifies the presence and severity of associated complications including DCRV, aortic regurgitation, PH, and aneurysm of membranous septum or sinus of Valsalva aneurysm. Finally, echocardiography provides an excellent noninvasive assessment of the degree of aortic valve distortion, prolapse, and aortic regurgitation in most patients with infundibular or membranous VSDs.

Qp:Qs is generally not calculated by echocardiography due to technical limitations. The presence of normal left atrial and LV size in an adult is suggestive of a small restrictive uncomplicated VSD with a small left-to-right shunt. On the other hand, unexplained enlargement of the left atrium, LV, and pulmonary artery in an adult is indicative of a larger VSD with significant left-to-right shunt, necessitating consideration of repair. (See "Echocardiographic evaluation of ventricular septal defects".)

Color flow Doppler, including color M mode, and spectral Doppler analysis across the VSD can determine the size, impact, severity, timing, and the direction of the shunt.

●A continuous wave Doppler velocity of ≥5 m/s across the VSD is suggestive of a small restrictive defect with a small left-to-right shunt. With a tunnel-type VSD (suggested by defect length/width >1.2), continuous wave Doppler may overestimate the interventricular pressure gradient due to pressure recovery phenomena [32].

●On the other hand, low continuous wave Doppler velocities across the VSD suggest elevated RV pressure, which may be related to the presence of valvular pulmonary stenosis, DCRV, or PH. When the RV pressure is elevated, the pressure difference between the LV and RV is reduced.

In isolated VSDs, shunting across the defect is predominantly left-to-right (in systole and diastole). However, in case of associated lesions of the right heart (eg, pulmonary stenosis), right ventricular diastolic dysfunction, or broad right bundle branch block with prolonged/delayed right ventricular systole, diastolic right-to-left shunting may occur, which can be detected by spectral Doppler recordings or by agitated saline bubble-contrast echocardiography. (See "Contrast echocardiography: Contrast agents, safety, and imaging technique", section on 'Agitated saline contrast'.)

When assessing the hemodynamic burden of a VSD and any associated lesions, it is imperative to obtain an accurate estimation of the systemic blood pressure as well as the RV and pulmonary artery pressures. All echocardiographic windows should be used to acquire noncontaminated tricuspid and pulmonic regurgitant velocity signals to enable accurate estimation of the RV and pulmonary artery diastolic pressures. Occasionally, these cannot be accurately measured by Doppler echocardiography, due to the location or direction of the VSD jet. The pulmonary regurgitation jet may help define the pulmonary artery pressure. A study found poor correlation between tricuspid regurgitant and VSD jet in pulmonary artery systolic pressure assessment using the Bernoulli equation [33]. When the Doppler echocardiography data are inconclusive or do not correlate with clinical assessment, cardiac catheterization is required to assess the pulmonary pressures and shunt flow.

Echocardiographic assessment of VSD can usually be performed accurately using two-dimensional TTE. VSDs can also be accurately visualized using 3D full volume with cropping or narrow-sector live 3D imaging protocols, irrespective of their location [34]. 3D echocardiography may also be used in the evaluation of ventricular volumes.

Lesions associated with right atrial enlargement — Right atrial enlargement is not typical for isolated VSD but is associated with a VSD in the following settings:

●Eisenmenger complex. (See 'Spectrum of clinical presentation' above and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

●Gerbode defect, which is a shunt between the LV and right atrium, resulting from either a congenital defect or as an acquired condition. (See 'Anatomic types' above.)

●DCRV, which is a form of acquired subpulmonic stenosis caused by hypertrophy of an aberrant muscle bundle that develops in the RV in the region of the membranous VSD jet flow (image 4). As its name implies, in DCRV, the RV is divided into two chambers: a proximal high-pressure chamber close to the tricuspid valve and a distal low-pressure chamber proximal to the pulmonary valve separated by the obstructive muscle bundle. This condition occurs in 3 to 10 percent of patients with membranous VSDs and protects against the development of PH [35].

●Severe tricuspid regurgitation, which most commonly occurs when the septal tricuspid valve leaflet adheres to the membranous VSD, causing distortion of the leaflet and malcoaptation.

Exercise testing — Exercise testing, preferably a cardiopulmonary exercise test, may be helpful in select patients with VSD, especially when functional limitation is suspected [22]. Adult patients with congenital heart disease exhibit a great ability to adapt to the functional limitations imposed by their congenital anomaly. Concern has been raised that this adaptability may result in a lack of reported symptoms, which in turn may delay intervention, since the presence of symptoms is a common indication for repair.

As a result, we advocate the use of exercise stress testing to objectively assess the exercise tolerance and functional aerobic capacity for patients with VSD who do not have severe PH. The inability to achieve 70 percent of expected functional aerobic capacity is felt to be abnormal.

A documented deterioration in exercise capacity over time might be an early sign of functional decline. Such a finding may be useful in defining optimal timing of intervention.

For patients with severe symptoms and those with PH who are unable to complete an exercise test, a six-minute walk test may be helpful to provide a basis for follow-up and potential therapeutic response [22].

Cardiovascular magnetic resonance — CMR imaging can provide accurate, reliable, and reproducible assessment of cardiac structure and function in congenital heart disease when performed by an expert [36]. These techniques offer certain advantages over echocardiography, since they allow for unrestricted evaluation of cardiac chambers and great arteries not compromised by air, bone, or surgical scar. Summation of disks on multiple tomographic slices during ventricular diastole and systole permits direct and accurate measurement of ventricular volume and function. Such data are helpful in determining timing of intervention or repair in adults with VSDs. However, these techniques have not been widely adopted in the evaluation of VSD, primarily because echocardiography is more widely available and provides sufficient information in most cases.

CMR may be particularly helpful for the following:

●CMR phase contrast cine techniques enable quantitation of Qp:Qs which correlates strongly with results obtained by cardiac catheterization [37,38].

●CMR enables assessment of coexisting lesions in the pulmonary artery, pulmonary veins, or aorta [3].

●CMR can identify lesions such as apical VSD not well characterized by echocardiography [39].

Cardiac computed tomography — For patients who require imaging beyond echocardiography and for whom CMR is contraindicated or unavailable, cardiac computed tomography (CCT) is an alternative noninvasive option for evaluating coexisting lesions in the pulmonary arteries, veins, or aorta, and further assessment of the VSD. Only limited data are available on the use of CCT for Qp:Qs [40]. In selected patients, coronary CT angiography is an alternative preoperative diagnostic tool for assessment of coronary artery disease or coronary artery anomalies. A disadvantage of CCT is that it exposes patients to ionizing radiation, which is of concern when serial studies are required over a lifetime. (See "Cardiac imaging with computed tomography and magnetic resonance in the adult".)

Cardiac catheterization — Given the key role of echocardiography in evaluating patients with VSDs, cardiac catheterization is a key clinical test reserved mainly for the following scenarios:

●VSD with indeterminate hemodynamic significance by noninvasive measures, since cardiac catheterization is helpful in determining the Qp:Qs and pulmonary artery pressures.

●VSD associated with DCRV or valvular pulmonary stenosis in which shunt size and/or RV outflow tract gradient and pulmonary artery pressure are incompletely delineated by noninvasive measures.

●VSD with PH to measure pulmonary artery pressure, cardiac index, pulmonary and systemic vascular resistance and the response to oxygen, vasodilators, and nitrous oxide in order to assess the operability of the patient and/or potential benefit of alternative treatment options, such as pulmonary hypertension therapies. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Indications for VSD closure'.)

Other indications for cardiac catheterization include evaluation of aortic regurgitation in patients with aortic valve prolapse, determination of whether multiple VSDs are present before surgery, determination of VSD anatomy if percutaneous device closure is contemplated, and performance of preoperative coronary angiography in patients at risk for coronary artery disease [3,41]. CT of the coronary arteries has emerged as an alternative reliable preoperative diagnostic tool for assessment of coronary artery disease in selected patients.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis in a patient with a murmur suggestive of small VSD includes other causes of holosystolic murmurs (figure 5), such as mitral and tricuspid regurgitation. As noted above, since VSD may be accompanied by valve lesions such as tricuspid regurgitation, some patients may have two causes of a holosystolic murmur. At times, the systolic murmur originating from LV outflow obstruction can be harsh, simulating VSD murmur, but an LV outflow murmur is typically an ejection type and can also be distinguished from a VSD murmur by dynamic auscultation maneuvers. The early systolic or midsystolic murmur of a VSD associated with pulmonary hypertension should be distinguished from other causes of midsystolic murmurs, such as aortic or pulmonic valve stenosis. The systolic and diastolic murmurs noted in sequence in patients with VSD associated with aortic regurgitation can at times be mistaken for a continuous murmur of a patent ductus arteriosus or ruptured sinus of Valsalva aneurysm, or those caused by a large coronary artery fistula. Echocardiography (generally transthoracic) is the key test in distinguishing VSD from these other causes of murmurs. (See 'Physical signs' above and "Echocardiographic evaluation of ventricular septal defects".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Congenital heart disease in adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail 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 topics (see "Patient education: Ventricular septal defects in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Ventricular septal defects (VSDs) are classified into four anatomic types: Type 1 defects involve the infundibular septum, type 2 defects involve the membranous septum (the most common type), type 3 defects involve the inlet septum, and type 4 defects involve the muscular septum (figure 1 and figure 2). (See 'Anatomic types' above.)

●The spectrum of VSDs in adults includes the following hemodynamic and clinical types (see 'Spectrum of clinical presentation' above):

•Small restrictive VSDs with small left-to-right shunts (pulmonary to systemic flow ratio [Qp:Qs] <1.5:1); this type is generally associated with no symptoms and no pulmonary hypertension (PH).

•Moderately restrictive VSDs with moderate shunts (Qp:Qs ≥1.5:1 and <2:1) that have not undergone closure often cause mild to moderate PH, and/or left heart volume overload, which may cause symptoms.

•Large nonrestrictive unrepaired VSDs cause progressive pulmonary arterial hypertension. The left-to-right shunt declines and then reverses; the resultant right-to-left shunt causes hypoxemia and cyanosis (Eisenmenger syndrome). (See "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis", section on 'Large ventricular septal defect' and "Pulmonary hypertension with congenital heart disease: Clinical manifestations and diagnosis".)

•Some adults with prior VSD closure may have a residual VSD. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Residual VSD'.)

●A minority of adults with VSD have associated congenital or acquired lesions including aortic regurgitation, tricuspid regurgitation, double-chambered RV, or sinus of Valsalva dilation/rupture. These patients require close monitoring. (See 'Spectrum of clinical presentation' above and 'Lesions associated with right atrial enlargement' above and "Management and prognosis of congenital ventricular septal defect in adults", section on 'Approach to management'.)

●A VSD should be suspected in a patient who presents with a characteristic murmur. There are generally no associated symptoms in patients with small VSDs, while patients with moderate or large VSDs develop symptoms such as dyspnea and fatigue. (See 'When to suspect VSD' above.)

●A VSD is generally identified and its hemodynamic effects assessed by transthoracic echocardiography (TTE). TTE is also the key test for identifying and evaluating associated cardiovascular conditions such as aortic regurgitation, tricuspid regurgitation, and double-chambered RV. (See 'How to diagnose and evaluate VSD' above.)

●Cardiovascular magnetic resonance imaging (CMR) is recommended to assess VSD anatomy, impact on chamber size and function, and in some situations can be used to assess Qp:Qs. If CMR is not available or contraindicated, cardiac computed tomography is an alternative noninvasive option. (See 'How to diagnose and evaluate VSD' above and 'Cardiovascular magnetic resonance' above and 'Cardiac computed tomography' above.)

●If the results of noninvasive imaging evaluation for VSD are inconclusive or if there is evidence of moderate or severe PH, cardiac catheterization is indicated for hemodynamic evaluation, including the evaluation of PH. (See 'How to diagnose and evaluate VSD' above and 'Cardiac catheterization' above.)