Continuing Education Activity

Ventricular septal defects (VSDs) are the most common congenital cardiac anomaly in children and the second most common congenital abnormality in adults, second only to bicuspid aortic valves. The main mechanism of hemodynamic compromise in ventricular septal defects occurs due to abnormal communication between the right and left ventricles and shunt formation. This activity reviews the presentation and pathophysiology of ventricular septal defects and highlights the role of the interprofessional team in the management of patients with congenital heart defects.

Objectives:

• Describe the pathophysiology of ventricular septal defects.
• Review the presentation of ventricular septal defects.
• Outline the treatment options for ventricular septal defects.
• Explain the importance of improving care coordination among interprofessional team members to improve outcomes for patients with a ventricular septal defect.

Introduction

Ventricular septal defect (VSD) is the most common congenital cardiac anomaly in children and is the second most common congenital abnormality in adults, second only to a bicuspid aortic valve. An abnormal communication between the right and left ventricles and shunt formation is the main mechanism of hemodynamic compromise in VSD. While many VSDs close spontaneously, if they do not, large defects can lead to detrimental complications such as pulmonary arterial hypertension (PAH), ventricular dysfunction, and an increased risk of arrhythmias.[1][2][3] VSDs were first identified by Dalrymple in the year 1847.[4]

Etiology

VSD develops when there is a developmental abnormality or an interruption of the interventricular septum formation during the complex embryologic heart morphogenesis. VSDs are frequently isolated; however, they can occur in association with other congenital heart defects such as atrial septal defects, patent ductus arteriosus, right aortic arch, and pulmonic stenosis. They are also found in cases of aortic coarctation and sub-aortic stenosis, and they are a frequent component of complex congenital heart disease such as Tetralogy of Fallot and transposition of great arteries. Several genetic factors have been identified to cause VSDs including chromosomal, a single gene, and polygenic inheritance. A TBX5 mutation was recently discovered to cause septal defects in patients with Holt-Oram syndrome. Non-inherited risk factors have been implicated in the development of VSDs; these include maternal infection (rubella, influenza, and febrile illness), maternal diabetes mellitus, and phenylketonuria. Exposure to toxins like alcohol, marijuana, cocaine, and certain medications such as metronidazole and ibuprofen are also linked to VSDs.[5][6]

Epidemiology

Isolated VSD accounts for 37% of all congenital heart disease in children. The incidence of isolated VSD is about 0.3% of newborns. Because as many as 90% may eventually close spontaneously; the incidence is significantly lower in adults. VSDs have no gender predilection. The percentage of each type is presented in the pathophysiology section.[7]

Pathophysiology

The interventricular septum is an asymmetric curved structure due to the pressure difference in ventricular chambers. It is composed of five parts: the membranous, muscular (frequently referred to as trabecular), infundibular, atrioventricular, and the inlet.[8][9]

Failure of development or fusion of one of the above components during morphogenesis of the embryonic heart results in a VSD in the corresponding component. Different anatomic locations and histologic variations of VSDs have led to several classifications and nomenclature systems. Complexities in describing VSDs and multiple synonyms have been improved after a new unified classification was established and categorized VSDs into four major groups:

• Type 1: (infundibular, outlet) This VSD is located below the semilunar valves (aortic and pulmonary) in the outlet septum of the right ventricle above the crista supraventricularis, which is why it is sometimes also referred to as supracristal. It is the most uncommon type representing only 6% of all VSDs with the exception being in the Asian population where it accounts for approximately 30%. Aortic valve prolapse and regurgitation are common because of loss of support of the right and/or the noncoronary cusps of the aortic valve. It is unusual for these defects to close spontaneously.
• Type 2: (membranous) This VSD is, by far the most common type, accounting for 80% of all defects. It is located in the membranous septum inferior to the crista supraventricularis. It often involves the muscular septum when it is commonly known as perimembranous. The septal leaflet of the tricuspid valve sometimes forms a “pouch” that reduces the shunt and can result in spontaneous closure.
• Type 3: (inlet or atrioventricular canal) This VSD is located just inferior to the inlet valves (tricuspid and mitral) within the inlet part of the right ventricular septum. It only represents 8% of all defects. It is seen in patients with Down syndrome.
• Type 4: (muscular, trabecular) This VSD is located in the muscular septum, bordered by muscle usually in the apical, central, and outlet parts of the interventricular septum. They can be multiple, assuming a “Swiss cheese” appearance. They represent up to 20% of VSDs in infants. However, the incidence is lower in adults due to the tendency of spontaneous closure.

The main pathophysiologic mechanism of VSD is shunt creation between the right and left ventricles. The amount of blood shunted and the direction of the shunted blood determine the hemodynamic significance of the VSD. These factors are governed by the size, location of the VSD, and pulmonary vascular resistance.

While VSDs are classified according to location, they can also be classified into size. The size is described in comparison to the diameter of the aortic annulus. They are considered small if they measure less or equal to 25% of the aortic annulus diameter, medium if they measure more than 25% but less than 75%, and large if they are greater than 75% of the aortic annulus diameter.

In the setting of long-standing large left-to-right shunts, the pulmonary vascular endothelium undergoes irreversible changes resulting in persistent PAH. When the pressure in the pulmonary circulation exceeds the pressure in the systemic circulation, the shunt direction reverses and becomes a right-to-left shunt. This is known as Eisenmenger syndrome, and it occurs in 10% to 15% of patients with VSD.

History and Physical

The presentation of unrepaired VSDs is largely dependent on the presence of hemodynamically significant shunt; hence it is directly related to the size of the defect. Small VSDs only lead to the minimal left-to-right shunt without left ventricular (LV) fluid overload or PAH; they are usually asymptomatic or found incidentally on physical exam. Medium size VSDs result in a moderate LV volume overload and absent to mild PAH; they present late in childhood with mild congestive heart failure (CHF). Those with large defects develop CHF early in childhood due to the severe LV overload and severe PAH. The murmur of VSD is typically pan-systolic best heard in the left lower sternal border; it is harsh and loud in small defects but softer and less intense in large ones. Handgrips increase afterload, increasing the strength of the murmur. Infundibular defects are best heard in the pulmonic area. A diastolic decrescendo murmur and wide pulse pressure can be detected in the setting of aortic regurgitation. Increased LV flow may result in the mid-diastolic rumble in the lower left sternal border. A systolic click of a septal aneurysm can be appreciated sometimes in membranous defects. Eisenmenger syndrome manifests in cyanosis, desaturation, dyspnea, syncope, secondary erythrocytosis, and clubbing; in such cases, the typical murmur of VSD can be absent and accentuated pulmonic component of the second heart sound may be heard.

Evaluation

Color Doppler transthoracic echocardiography (TTE) is the most valuable tool for diagnosis due to its high sensitivity. Color Doppler TTE can detect up to 95% of VSDs, especially non-apical lesions larger than 5 mm; it provides morphologic information such as size, location, and the number of the defects as well as hemodynamic information such as jet size, severity, and estimation of pulmonary artery pressure. TTE is useful in detecting any associated aortic insufficiency and other associated congenital heart defects. Lastly, TTE is also helpful in evaluating the right and left ventricular chamber size and function. Limitations include operator dependence and poor acoustic window. When conventional TTE is equivocal, a trans-esophageal echo (TEE) is recommended.[10][11]

Electrocardiography (ECG) is entirely normal in half of the patients with VSD. When the ECG is abnormal, it may detect LV hypertrophy in those with large shunts. In patients with PAH, the ECG may show right bundle branch block, right axis deviation, and right ventricular (RV) hypertrophy and strain.

Chest radiography (CXR) is often normal in those with small defects. Enlarged cardiac silhouette can be observed in those with larger defects and increased LV size. RV enlargement and increased pulmonary diameter can be observed in those with PAH.

Cardiac magnetic resonance imaging (MRI) and computed tomography (CT) are useful in cases where anatomy is complex such as VSD accompanied with other congenital heart anomalies and in defects in unusual locations that are hard to visualize by conventional TTE.

Cardiac catheterization gives accurate hemodynamic information regarding the pulmonary vascular resistance and response to vasodilators; this is particularly useful in those who are being evaluated for surgical closure. It provides more details on coexisting aortic regurgitation, in multiple VSDs, and when coronary artery disease is suspected.

Treatment / Management

Approximately 85% to 90% of small isolated VSDs close spontaneously during the first year of life. Patients with small, asymptomatic VSDs with the absence of PAH have an excellent prognosis without any intervention. Otherwise, the management approach includes VSD closure. Patients with Eisenmenger syndrome are usually managed in advanced centers due to the complexity of managing such cases. Historically, surgical repair of VSDs was the only option; however, recent advances in interventional techniques make percutaneous VSD closure possible. It is no longer recommended for patients with unrepaired ventricular septal defects to be routinely prescribed antibiotic prophylaxis for infective endocarditis.[12] Endocarditis prophylaxis is mainly indicated in cyanotic congenital heart disease, prior episodes of endocarditis, and in those who have prosthetic heart valves or had repair with prosthetic material. In general, VSD closure is indicated in medium to large defects with a significant hemodynamic compromise such as those who are symptomatic and have LV dysfunction. An intervention should be also considered in cases of progressive aortic insufficiency or after an episode of endocarditis. The indications of a surgical closure according to the ACC/AHA 2008 guidelines are summarized in the following:

1. Those who suffered an episode of endocarditis.
2. When the ratio of the pulmonary blood flow to the systemic blood flow (Qp/Qs) is equal to or more than 2 plus clinical evidence of LV fluid overload.
3. In milder shunts such as those with Qp/Qs above 1.5, it is reasonable to intervene when there is evidence of LV systolic or diastolic dysfunction, or when the pulmonary artery pressure and pulmonary vascular resistance are less than two-thirds of systemic pressure and systemic vascular resistance, respectively.

Surgical repair reduces the risk for endocarditis, might improve PAH, and overall it increases survival. Without PAH, the operative mortality rate is approximately 1%. Complications include residual or recurrent VSD, valvular incompetence such as tricuspid regurgitation and aortic insufficiency, arrhythmias, LV dysfunction, and progression of PAH. The arrhythmias which accompany VSD repair include atrial fibrillation, complete heart block, and uncommonly, ventricular tachycardia. The main contraindication for surgical VSD closure is the presence of irreversible PAH; this is due to the high surgical perioperative mortality and pulmonary complications.

Percutaneous device VSD closure is reserved for those whose surgery is very risky due to severe PAH, multiple comorbidities, and those who had prior cardiothoracic surgery such as residual or recurrent VSD. Muscular VSDs are the main type amenable to this procedure, the proximity of other defects to the inlet valves makes performing this technique challenging in such cases. Despite the fact that it is still unpopular in the United States, current data shows excellent outcomes with complete closure and low mortality. The most frequent complication is complete atrioventricular block mostly related to perimembranous defects.

In conclusion, VSD is the most common congenital anomaly at birth. Small defects are expected to close spontaneously in the first year of life; however, larger defects can result in severe complications. Surgical VSD closure and device closure are the main intervention for large defects.[13][14][15]

Differential Diagnosis

• Atrioventricular septal defect
• Atrial septal defect

Prognosis

The prognosis is good for patients who have undergone VSD repair. However, they have a higher risk of arrhythmia, endocarditis, and congestive heart failure in the long run in comparison to the general population.[16]

Complications

• Eisenmenger syndrome
• Aortic insufficiency due to prolapse of the aortic valve leaflet
• Endocarditis
• Embolization

Consultations

• Cardiologist
• Cardiothoracic surgeon

Deterrence and Patient Education

Parents of patients with small VSDs should be educated that frequently, medical and surgical treatment are not needed as they will close over time. Prophylactic antibiotics to prevent endocarditis are no longer required in most cases. However, maintaining good oral hygiene should be encouraged to reduce the risk of endocarditis.[12] Adherence to medications and close follow-up with specialists is important for all patients with VSDs.

Pearls and Other Issues

The pansystolic murmur of VSD can be confused with the pansystolic murmur of mitral regurgitation. The VSD becomes louder towards the sternum, and the murmur of mitral regurgitation gets louder away from the sternum.

Enhancing Healthcare Team Outcomes

The management of VSD is best accomplished by an interprofessional team that includes a pediatrician, cardiologist, cardiac surgeon, ICU nurse, physical therapist, and social worker. Parents and patients need to be educated about the need to follow up. Some children with perimembranous VSD may develop aortic valve prolapse and require surgery. Finally, all unrepaired VSDs have the potential to increase pulmonary vascular resistance leading to Eisenmenger syndrome. At this stage, except for a heart and lung transplant, there is no other viable therapy. With a marked shortage in organs for transplantation, the majority of these patients succumb to progressive right heart failure and cyanosis. [Level 5][17][18]

Outcomes

Young children who remain asymptomatic and have a small VSD have a good outcome. However, the presence of anemia, infection, or endocarditis may trigger symptoms in these children. Outcomes in people with a large VSD are poor if the defect is not repaired. The continued left to right shunt eventually leads to the development of pulmonary hypertension and Eisenmenger syndrome. Today, in North America most infants have the VSD repaired electively within the first two years of life. The mortality is less than 1%, and most patients have a normal lifespan.[19]