Ventricular septal defects

Definition & Classification

Ventricular septal defects (VSDs) are openings in the ventricular septum that vary in size, location, and number. A VSD is considered a post-tricuspid shunt (other post-tricuspid shunts include: patent ductus arteriosus, aortopulmonary window, truncus arteriosus, aorto-pulmonary collaterals, etc.). Ventricular Septal Defects (VSDs) are common congenital heart defects, accounting for approximately 30% of all shunts (1% of live births). A VSD is a "hole" or communication between the left and right ventricles of the heart. Unlike atrial septal defects (ASDs), VSDs primarily affect the pulmonary vasculature during systole with pressure and volume transmission. The shunt's flow is a function of the PVR and SVR resistances. In the presence of a VSD, blood will flow from the left ventricle into the right ventricle and then into the pulmonary arteries. This increased blood flow to the lungs leads to an increased venous return through the pulmonary veins, subsequently causing dilatation of the left heart chambers. This is in contrast to ASDs, which typically cause right heart chamber dilatation and is a flow lesion (not a pressure lesion). The severity of this volumetric overload on the left side can be mitigated if a large atrial septal defect (ASD) is also present, as it can de-stress the left ventricle.

VSDs may be isolated or multiple and can be categorized based on their anatomical position within the septum:

1. Inlet VSD

• Located posteriorly, beneath the crux of the heart.

• The typical offset between the tricuspid valve (TV) and mitral valve (MV) is absent, as they attach at the same level due to the lack of septal tissue.

• Often associated with atrioventricular septal defects (AVSDs), requiring careful evaluation for a primum ASD.

• If both a primum ASD and VSD are present with two separate AV valves, the defect may be classified as a transitional AVSD. In such cases, the VSD often appears small.

• If no primum ASD is present, the defect may be termed an "AV canal type" or simply "inlet VSD."

• Given its potential relationship with AVSDs, careful assessment for a cleft mitral valve is warranted.

2. Muscular VSD

• Located in the trabecular/muscular septum.

• These are the most common small, isolated VSDs seen in otherwise healthy neonates.

• If the defect is larger than tiny, multiple muscular VSDs should be considered.

3. Outlet VSDs

• Membranous (Perimembranous) VSD:

  • Located between the tricuspid valve and aorta.

  • Smaller defects may be associated with secondary complications, such as:

    • Double-chambered right ventricle (DCRV).

    • Subaortic membrane formation.

    • Aortic valve herniation into the VSD, leading to aortic regurgitation.

  • A membranous VSD is a type of outlet VSD.

• Doubly Committed Subarterial VSD (Supracristal VSD)

  • Located beneath both the aortic valve and pulmonary valve.

  • Typically small but often associated with aortic valve herniation into the VSD, which can lead to aortic regurgitation.

  • Also referred to as supracristal VSD (Van Praagh terminology).

• Other Outlet VSDs

  • Located between membranous VSDs and supracristal VSDs.

  • Terminology varies, with some referring to them as "infracristal VSDs".

Physiological Impact of VSDs

A ventricular-level shunt may impose:

1. Pressure overload to the right heart

2. Volume overload to the left heart

3. Both pressure and volume overload

4. Neither, in cases of restrictive VSDs

• Non-Restrictive VSDs:

  • If the VSD size is equal to or larger than the aortic valve annulus, there is no pressure gradient across the defect.

  • The RV pressure equals the LV pressure, indicating a non-restrictive shunt.

• Restrictive VSDs:

  • If a small VSD is present but has a low pressure gradient, alternative causes of RV pressure elevation should be considered, such as:

    • Right ventricular outflow tract (RVOT) obstruction.

    • Pulmonary hypertension (PH).

  • The term "restrictive VSD" typically refers to pressure-restrictive, though a VSD may still impose a significant volume load.

• Right Ventricular (RV) Pressure Overload

  • Leads to right ventricular hypertrophy (RVH) and possibly RV dysfunction.

  • If chronic, Eisenmenger syndrome may develop, with severe pulmonary hypertension and eventual right-to-left shunting through the VSD.

• Left Ventricular (LV) Volume Overload

  • The LV, not the RV, experiences volume overload because the VSD shunt occurs predominantly in systole, directing blood into the RV and pulmonary circulation.

  • This results in increased LV end-diastolic volume (LVEDV), often leading to:

    • Hyperdynamic LV function.

    • LV dilation over time.

    • If prolonged, LV dysfunction may develop.

  • LV end-diastolic dimension (LVEDd) serves as an important marker of volume load and shunt impact.

• Impact on LV Afterload

  • A large VSD reduces LV afterload because the LV ejects blood into both the systemic and pulmonary circulations.

  • Since pulmonary vascular resistance (PVR) is lower than systemic vascular resistance (SVR), the combined resistance is lower than SVR alone.

  • This must be considered when evaluating LV function, as contractility may appear normal despite actual LV dysfunction.

  • A small subset of patients experience significant LV dysfunction postoperatively, due to sudden afterload and preload changes following VSD closure.

• Quantification of Shunt Flow (QP/QS Ratio): The importance of a shunt is quantified using the QP/QS ratio, which is the ratio of pulmonary blood flow (QP) to systemic blood flow (QS). This ratio is calculated using differentials of oxygen saturation. The formula for QP/QS is: (Saturation in the Aorta - Saturation in the Vena Cava) / (Saturation in the Pulmonary Veins - Saturation in the Pulmonary Artery).

• If there is no mixed blood cardiopathy, cardiac catheterization is required to obtain the exact pulmonary artery saturation value.

• In mixed blood cardiopathies, QP/QS can be calculated directly from the aortic saturation, which is considered equal to the pulmonary artery saturation.

• Oxygen extraction is generally 30%. Therefore, the numerator (Aortic Saturation - Vena Cava Saturation) is typically 30.

• Pulmonary vein saturation is assumed to be 100%.

• Vascular Resistances and Eisenmenger Syndrome: Normally, pulmonary vascular resistances are high antenatally, drop significantly in the first month of life, and then remain low. Pulmonary blood flow is minimal prenatally, increases as resistances drop, and then stabilizes. Pressures are high antenatally, decrease postnatally, and then gradually decline during childhood. With a VSD, resistances initially drop postnatally, but sustained high pulmonary blood flow (QP/QS > 1) can cause pulmonary vascular resistances to progressively increase and become fixed. This dangerous condition is known as Eisenmenger syndrome. When this occurs, pulmonary blood flow decreases, and the QP/QS ratio falls below 1. Clinically, patients initially improve but then become cyanotic ("blue"). Pressures, initially high due to the shunt, can become fixed pulmonary hypertension due to increased vascular resistance.

• Clinically, significant VSDs will present with

  • Feeding difficulties

  • Weight stagnation due to high energy consumption (they use about 130% more energy than a normal baby), failure to thrive. 

  • Polypnea (rapid breathing)

  • Sweating during bottle feeding - diaphoresis

• Auscultation Findings:

  • Holosystolic murmur in the fourth intercostal space on the left

  • A loud S2 (second heart sound)

  • A diastolic rumble

  • If pulmonary hypertension is present, a loud S2 may also be heard.

Echocardiographic Assessment of Ventricular Septal Defects (VSDs)

1. Define Anatomical Site, Type, and Size

• Best Echocardiographic Windows:

  • Inlet VSD: Best visualized in the apical four-chamber (A4C) view, with posterior angulation to include both atrioventricular (AV) valves.

  • Muscular VSD: Can be seen in any view containing the septum; small defects may require color Doppler for visualization.

  • Membranous (Perimembranous) VSD: Visible in parasternal long-axis (PSLA) view, but best localized in parasternal short-axis (PSSA) view when both the aortic valve (AoV) and tricuspid valve (TV) are present.

  • Other Outlet VSDs: Seen in PSLA view, but best defined in PSSA view when aortic valve, tricuspid valve, and pulmonary valve (PV) are included.

• Size Classification (Relative to Aortic Valve Annulus Diameter):

  • Small: < ½ annular diameter.

  • Moderate: ½ to full annular diameter.

  • Large: > Annular diameter.

• Unusual Variant – Gerbode Defect:

  • A rare left ventricle (LV) to right atrium (RA) shunt, typically involving a membranous VSD.

2. Assess Hemodynamic Impact on Global Cardiac Function

• Left Ventricular Function:

  • Evaluate LV systolic function using fractional shortening (FS, M-mode) and biplane ejection fraction (EF, Simpson’s rule).

• Left Atrial (LA) Size:

  • LA/Ao ratio >1.6 (measured in PSSA) suggests a significant left-to-right shunt.

• Left Ventricular Size:

  • Assess LV end-diastolic dimension (LVEDd) Z-score.

  • Calculate LVED volume from EF (biplane Simpson’s rule).

• Pulmonary Artery (PA) Pressure Estimation:

  • LV-to-RV pressure gradient via Doppler measurement of VSD flow velocity (ensure optimal Doppler alignment).

  • Peak tricuspid regurgitation (TR) velocity to estimate RV and PA systolic pressures.

  • Peak pulmonary regurgitation (PR) velocity to assess mean PA pressure.

• Estimating Pressures: The Bernoulli equation (ΔP = 4v²) is used to estimate pressures and the significance of the VSD.

• The pressure difference between the left and right ventricles can be estimated as 4 times the square of the VSD jet velocity (4v²).

• In the absence of pulmonary stenosis or obstruction, pulmonary arterial pressures can be considered equal to right ventricular pressures.

• Pulmonary arterial pressure is also equivalent to aortic pressure minus 4 times the square of the VSD jet velocity (4v²).

• Pressures can also be estimated based on tricuspid insufficiency (for systolic right ventricular pressure) and pulmonary insufficiency (for mean and diastolic pulmonary artery pressures).

• When there is a large VSD, there is pressure equalization during systole on both sides of the VSD. 

3. Assess Shunt Size (Restrictive vs. Non-Restrictive VSDs)

• Qp/Qs measurement (via PW Doppler at LVOT and RVOT) is possible but has significant variability and limited clinical utility.

• More reliable indicator: LVEDd Z-score, which reflects the magnitude of volume overload.

4. Detection of Associated Lesions

• Aortic Valve Prolapse & Aortic Regurgitation (AI):

  • First sign is asymmetry in aortic valve cusps in PSLA view.

  • If suspected, zoom in to assess for AI, which will have a posteriorly directed jet if the right coronary cusp is involved.

  • Also assess in apical five-chamber view.

• Interventricular Septal Aneurysm:

  • A thin, redundant membrane often arises from the VSD margin due to incorporation of TV septal leaflet tissue.

  • May contribute to spontaneous VSD closure.

• Double-Chambered Right Ventricle (DCRV):

  • If a small membranous VSD is present, assess for RV anomalous muscle bundles.

  • Use 2D imaging of the RV cavity and walls in PSSA and subcostal views.

  • Look for anterior wall thickening and dynamic narrowing in systole.

  • Color Doppler may be less useful, as RV flow is already accelerated due to the VSD.

• Subaortic Membrane:

  • Best seen in PSLA and apical four-chamber (A4C) views.

  • Measure the gradient across the membrane using PW Doppler.

  • Assess for associated AI, which may indicate leaflet damage due to turbulent flow.

• Septal Malalignment (Conal Septum Malposition):

  • Anterior malalignment: Causes RVOT obstruction and is associated with Tetralogy of Fallot (TOF).

  • Posterior malalignment: Leads to LVOT obstruction, and is associated with subaortic stenosis, coarctation, or interrupted aortic arch.

• Arch Hypoplasia:

  • Multiple muscular VSDs may be linked to aortic arch hypoplasia in some cases.

"Laubry-Pezzi Syndrome" - "Syndrome de Pezzi-Laubry"

Laubry-Pezzi syndrome refers to the association between a perimembranous ventricular septal defect (VSD) and aortic regurgitation caused by prolapse of an aortic valve cusp into the defect, in the absence of infective endocarditis. Pathophysiology: In patients with a perimembranous VSD, the high-velocity left-to-right systolic shunt passes just beneath the aortic valve. This jet creates a Venturi effect, generating a low-pressure zone that draws the adjacent aortic cusp (typically the right or non-coronary) toward the defect. Over time, the valve cusp may prolapse into the VSD, resulting in progressive aortic regurgitation. Clinical Importance: Aortic regurgitation may develop even if the VSD is small or restrictive. It is usually progressive and mechanical in nature (not due to infection). The development of aortic regurgitation is a clear surgical indication, regardless of VSD size, to prevent further valvular damage and preserve long-term cardiac function. The syndrome is named after Albert Laubry and Maurice Pezzi, who first described this mechanism in the early 20th century. It underscores the risk of valvular distortion in perimembranous VSDs and the importance of timely intervention.

Hemodynamics of Ventricular Septal Defect

• • Hemodynamic Assessment of a VSD:

    • Shunt Direction: Determined by colour Doppler (e.g., left-to-right is red on Doppler).

    • Restrictiveness: A restrictive VSD implies a significant pressure gradient across it, preventing equalization of LV and RV pressures, thus protecting the pulmonary circulation from high pressure. This gradient is measured using Bernoulli's equation (ΔP = 4V²). A high gradient (e.g., >60 mmHg for an infant with 90 mmHg systemic pressure) is reassuring, suggesting no significant pulmonary hypertension.

    • Significance (QP/QS): A restrictive VSD does not always mean an insignificant shunt. High QP/QS ratios (>1.5 or 2:1) indicate hyper-flow to the lungs. This can be measured via echocardiographic flow calculations (multiplying velocity time integral by outflow tract area) or estimated by ventricular dilation (e.g., dilated LV and LA suggests a significant shunt).

  • Pitfalls in VSD Assessment: Doppler measurements must be accurately aligned with the jet, as misalignment can severely underestimate the true velocity and gradient.

  • Classification of VSDs based on Hemodynamics:

    • Restrictive VSD (Small Shunt): No clinical signs, normal ventricular size, insignificant shunt (QP/QS < 1.5:1).

    • Large Shunt VSD with Pulmonary Hypertension: LV and RV pressures are equal (P LV = P RV = P PA). Shunt is not restrictive, often leading to heart failure symptoms. Requires early surgical closure (typically before 6 months). If multiple VSDs (swiss-cheese) and apical VSDs, may require banding of the Pulmonary Artery and addressing the VSDs alter in life when some of them have closed spontaneously. 

    • VSD with Protected Pulmonary Bed: These VSDs may be large but are associated with a concomitant obstruction to RV outflow (e.g., pulmonary stenosis, subpulmonary obstruction), which protects the pulmonary arteries from excessive flow and pressure. These patients often have minimal symptoms and can undergo delayed surgery.

    • Eisenmenger Syndrome (VSD with Irreversible PH): If large shunts are left untreated for too long, they can lead to irreversible pulmonary vascular damage, increased PVR, and shunt reversal (right-to-left). This constitutes Eisenmenger syndrome.

  • The shunt occurs from left-to-right when (usual setup) pulmonary vascular resistance is lower than systemic resistance. 

    • Example Calculation: If Ao saturation=100%, Mixed venous saturation=70%, Pulmonary Venous saturation=100%, and Pulmonary arterial saturation=85% (indicating oxygen enrichment from the shunt), then Qp/Qs = (100-70)/(100-85) = 30/15 = 2/1. This means the pulmonary circulation receives twice the systemic flow. 

    • Morphological Consequences: The increased pulmonary blood flow leads to dilatation of the pulmonary arteries and their branches, as well as the structures receiving the increased venous return: pulmonary veins, left atrium, and left ventricle. The left ventricle becomes hyperkinetic to handle this increased volume load.

    • Physiological Consequences: This hyper-flow results in elevated left ventricular end-diastolic pressure, which translates to high filling pressures in the left atrium and pulmonary circulation. This manifests as respiratory symptoms like dyspnea, especially during exertion like feeding, and can lead to feeding difficulties. The increased cardiac work also contributes to poor weight gain in affected children.

• Natural History of Left-to-Right Shunts: 

  • Eisenmenger Syndrome The natural history of a large left-to-right shunt (e.g., VSD) in congenital heart disease is a critical concept. 

    • Initial Stage: After the collapse of PVR at birth, a left-to-right shunt results in pulmonary hyper-flow, causing symptoms like dyspnea. 

    • Progressive Arterial Remodeling: If the shunt persists, the pulmonary arterioles undergo progressive muscularization and intimal remodeling. This process increases pulmonary vascular resistance, which initially can reduce the shunt volume and alleviate symptoms, giving a false impression of improvement. 

    • Irreversible Pulmonary Vascular Disease: Unfortunately, this remodeling eventually leads to irreversible pulmonary vascular disease, characterized by severe vessel muscularization and occlusive plexiform lesions. 

    • Shunt Reversal (Eisenmenger Syndrome): As pulmonary vascular resistance continues to rise, eventually becoming suprasystemic (higher than systemic resistance), the shunt direction reverses from left-to-right to right-to-left, resulting in cyanosis. This condition is known as Eisenmenger Syndrome.

    • Operability Considerations: 

      1. "Shunt closure is advised for patients with PVR < 4 WU*m2, Rp/Rs < 0.3 and discouraged for patients with PVR > 8 WU*m2, Rp/Rs > 0.5 as they approach the Eisenmenger physiology"

      2. Usual Rp/Rs is 1/20.

      3. Eisenmenger physiology is established (e.g., Rp/Rs > 1/3 or 1/5), closing the shunt is contraindicated, as it would accelerate the patient's demise by forcing the right ventricle to pump against high PVR without a relief valve. The "gray zone" of operability exists when remodeling has begun but may still be reversible. 

  • Clinical Example - Large VSD Evolution. 

    • Infant (6 months): 

      1. Aortic pressure is 90/60 (mean 70)

      2. The LA pressure is estimated at 15 mmHg. 

      3. There is no hepatomegaly (low IVC pressure).

      4. The Aortic pressure is assumed to be the same as LV pressure (unless aortic stenosis). The PA pressure is isosystemic in systole because the VSD is large so pressure between RV and LV will equalize in systole (unless there is outflow tract obstruction). The PA pressure in systole is thus 90 mmHg as well. A large VSD often presents with a systolic pulmonary artery pressure equal to systemic pressure. A dilated left ventricle indicates significant pulmonary hyper-flow (Qp > Qs) and very low PVR.

      5. The LV is dilated on echocardiography (LV end-diastolic diameter with a Z-score 3.5) due to the high pulmonary blood flow by the left to right shunt. 

      6. Qp >> Qs because the LA and LV are dilated. 

      7. If Qp/Qs = 3: the pulmonary vascular resistance: 

         1. Pulmonary Vascular Resistance: Rp = ΔP = (Mean PAP – Mean PCWP) / Qp

         2. Systemic Vascular Resistance: Rs = ΔP = (Mean Ao Pressure – Mean RAP) / Qs 

         3. Pulmonary/Systemic Resistance Ratio = Rp / Rs = (ΔPp × Qs) / (ΔPs × Qp) 

         4. Rp / Rs = (ΔPp / ΔPs) × (Qs / Qp)

            1. Here we know LA pressure is 15 and we know that Mean Aortic pressure is 70. We also know that the RA pressure is around 5 mmHg. We also mentioned that the Qs/Qp is 1/3

            2. Rp/Rs = (mPAP-15)/(70-5) x 1/3. If mPAP is around 30 mmHg, we get Rp/Rs = (30-15)/65 x 1/3 = 0.076 ~ 0.08 ~ 1/12 of Rp/Rs

    • Child (6 years): 

      1. If PVR has risen, the shunt might no longer be measurable (Qp/Qs ≈ 1)

      2. The patient has an aortic blood pressure of 110/60 (85 mean). The systolic PA pressure will also be 110 mmHg because of the large VSD equalizing pressure in systole.

      3. By cath, the PA saturation is 70%. The pulmonary venous saturation is 100%. The Aortic saturation is 100%. The he RA saturation is 70%. Mean PAP is 45 mmhg, Mean LA pressure is 10 mmHg, Mean Aortic pressure is 70 and Mean RA pressure is 5. 

         1. Qp/Qs = (Aortic Sat - RA Sat)/(PA Sat - Pulm Vein sat) = (100 - 70) / (100 - 70) = 1 of Qp/Qs

         2. Rp / Rs = (ΔPp / ΔPs) × (Qs / Qp) = (Mean PAP – Mean LA pressure)/ (Mean Ao Pressure – Mean RA Pressure) x Qs/Qp = (45 - 10) / (85 - 5) x 1 = 35/80 x 1 = 0.44 (almost 1/2). 

      4. This reveals significantly elevated pulmonary resistance, confirming inoperability if it exceeds the critical threshold (e.g., 1/3 or 1/5 of systemic resistance). 

    • Adolescent (16 years) with larve VSD: In established Eisenmenger syndrome, a right-to-left shunt is evident. 

      1. The Rp/Rs ratio will be greater than 1 by definition because the pulmonary vascular resistance is suprasystemic.

      2. Ao saturation is 85%, SVC saturation is 55 (AV difference of 30%).

      3. PA saturation is 55% because it is the same as the SVC saturation (no oxygen enrichement since the shunt is right to left). The pulmonary venous saturation is 100% if there is no V/Q mismatch at the pulmonary level. Qp/Qs = (Aortic Saturation - RA saturation)/(Pulm vein saturation - Pulm Artery saturation) = (85-55)/(100-55) , leading to a Qp/Qs ratio less than 1. Here 2/3.

      4. The patient has an aortic blood pressure of 110/60 (85 mean). The systolic PA pressure will also be 110 mmHg because of the large VSD equalizing pressure in systole.

      5. If the PA pressure is: 110/38 (mean 70). 

      6. We have already outlined shunt by the shunt direction that the Rp/Rs is > 1. 

         1. Rp / Rs = (ΔPp / ΔPs) × (Qs / Qp) = (Mean PAP – Mean LA pressure)/ (Mean Ao Pressure – Mean RA Pressure) x Qs/Qp = (70 - 10) / (85 - 5) x 3/2 = 60/80 x 3/2 = 1.13

Some may use this hemodynamics classification of VSD: 

• Type 1: Roger's Disease - A small, restrictive VSD with minimal blood flow and little hemodynamic consequence. Roger’s Disease (Maladie de Roger) A small ventricular septal defect (VSD), typically located in the membranous septum, is referred to as “maladie de Roger” in honor of Henri Louis Roger, a French pediatric cardiologist renowned for his expertise in cardiac auscultation. He first described this condition in 1879. The term “bruit de Roger” refers to the characteristic loud, harsh holosystolic murmur produced by a small VSD. Despite its size, the defect generates a high-velocity jet that often results in a prominent murmur, frequently accompanied by a palpable thrill.

• Type 2A: High-Flow VSDs without Pulmonary Arterial Hypertension (PH) - VSDs with significant blood flow but no fixed pulmonary hypertension yet.

• Type 2B: High-Flow VSDs with Iso-Systemic PH - VSDs with high blood flow and pulmonary arterial hypertension that matches systemic pressure. SVR near PVR.

• Type 3: Eisenmenger Syndrome - Characterized by high, fixed pulmonary vascular resistances. In this stage, the VSD should not be surgically closed as it acts as a "pressure relief valve" for the right ventricle.

• Type 4: VSDs with Pulmonary Protection - VSDs associated with a mid-ventricular or pulmonary stenosis that limits pulmonary over-circulation.

Restrictive muscular ventricular septal defect close to the Apex of the left ventricle. Left to right.

Peak systolic gradient is 20-23 mmHg (left to right), indicating that the sPAP is about 20 mmHg less than the systolic systemic blood pressure.

Subcostal views re-demonstrating the muscular VSD

Another Case of Muscular VSD