Pulmonary Atresia With Ventricular Septal Defect

Pulmonary atresia with ventricular septal defect (PA-VSD) is a cyanotic congenital heart disease characterized by underdevelopment of the right ventricular (RV) outflow tract (ie, subpulmonary infundibulum) with atresia of the pulmonary valve, a large ventricular septal defect (VSD), and overriding of the aorta. In the past, this anomaly was termed pseudotruncus or truncus arterious type 4.

Pulmonary atresia with ventricular septal defect demonstrates a wide spectrum of severity, depending on the degree of pulmonary artery development. Pathologically, pulmonary atresia with ventricular septal defect is frequently considered the most severe end of the spectrum of tetralogy of Fallot (TOF), but whether pulmonary atresia with ventricular septal defect and TOF should be treated as two distinct entities is controversial. In patients with the standard type of TOF with pulmonary atresia, pulmonary arteries are usually normal in size with normal peripheral pulmonary arborization, which is unlike pulmonary atresia with ventricular septal defect. In addition, systemic-to-pulmonary collateral vessels are not as well developed in patients with TOF with pulmonary atresia as they are in patients with pulmonary atresia with ventricular septal defect.

In pulmonary atresia with ventricular septal defect, the extent of pulmonary artery development determines the clinical presentation and the surgical options available. Pulmonary artery atresia may be local only, with involvement of the pulmonary valve and the proximal portion of the pulmonary trunk, or it may involve a longer segment. The right and left pulmonary arteries may communicate freely (ie, confluence) or may not communicate (ie, nonconfluence). Pulmonary circulation may be supplied by a patent ductus arteriosus (PDA), systemic-to-pulmonary collaterals, or plexuses of bronchial and pleural arteries.

The pathology of intrapulmonary arteries depends on the pulmonary blood flow and the patency of the ductus. If the ductus is large and supplies confluent pulmonary arteries, the blood flow and the intrapulmonary arteries of both lungs are normal. If collaterals are multiple and the ductus is congenitally absent, abnormal intrapulmonary arborization (ie, stenosis of unbranched and intrapulmonary arteries) and pulmonary hypertension are present.

Collateral arteries most commonly arise from the thoracic aorta and less commonly arise from subclavian arteries, internal mammary arteries, intercostal arteries, or the abdominal aorta. Rarely, the collateral arteries arise from coronary arteries. In 60% of patients, the collateral arteries are stenosed at the aortic end or at intrapulmonary sites, and stenosis tends to progress over time.

The ventricular septal defect may be membranous or infundibular, is usually very large, and rarely is obstructed by membranous tissue. In 50% of patients, a secundum-type atrial septal defect (ASD) or a patent foramen ovale (PFO) is also present.

The RV and, to a lesser extent, the right atrium usually are moderately to markedly hypertrophied and dilated. The left atrium and left ventricle (LV) are usually normal. The coronary arteries are usually normal, although anomalies have been observed, such as a high origin of the coronary ostia, coronary artery–to–pulmonary artery fistulae,[1] and transposition anatomy with the right coronary artery originating from the left anterior aortic sinus and transversing the right ventricular infundibulum. Other associations include tricuspid atresia or stenosis, complete atrioventricular (AV) canal, complete or corrected transposition of the great arteries, left superior vena cava, anomalies of the coronary sinus, dextrocardia, and asplenia or polysplenia syndrome.

Classification

Pulmonary atresia with ventricular septal defect is classified based on the presence or absence of native pulmonary arteries and the presence or absence of main pulmonary collateral arteries, as follows[2] :

• Type A (unifocal with confluent, good-sized pulmonary arteries): Pulmonary blood flow is provided by native pulmonary arteries. Patency of the ductus maintains the pulmonary circulation.

• Type B (multifocal, with confluent but hypoplastic pulmonary arteries supplied by major aortopulmonary collateral arteries [MAPCAs]): Pulmonary blood flow is supplied by native pulmonary arteries and by MAPCAs. The native pulmonary arteries may be supplied by either a ductus and/or MAPCAs.

• Type C (multifocal wiht nonconfluent or absent pulmonary arteries supplied by MAPCAs): Pulmonary blood flow is provided by MAPCAs. Native pulmonary arteries are absent.

Genetic factors are considered to be a contributing factor in that there is an increased risk of occurrence in siblings (2.5-3%) and in offspring of adults with tetralogy of Fallot (1.2-8.3%).[3]  Microdeletion 22q11.2 is common (facial anomalies, nasal speech, and developmental delay).[2]

Associated syndromes include VATER syndrome (ie, vertebral anomalies, anal atresia, tracheoesophageal fistula, esophageal atresia, and renal anomalies), Alagille syndrome, DiGeorge syndrome (velocardiofacial syndrome), and trisomy 21. Tracheobroncial anomalies may be seen as well.

The best estimates of the relative frequency of pulmonary atresia with ventricular septal defect are 2.5-3.4% of all congenital cardiac malformations with a prevalence of 0.07 per 1000 live births.[4, 5]

Pulmonary atresia with ventricular septal defect is slightly more prevalent in males than in females.

If pulmonary atresia with ventricular septal defect (PA-VSD) is left untreated, the prognosis is very poor.[6]  An estimated half of young patients die by age 2 years. However, with appropriate treatment and follow-up, about 65% of infants alive at age 1 year survive beyond age 10 years.[6]

Prognosis appears to be good in patients in the absence of chromosomal or syndromal anomalies.[7]  Repeat interventions because of recurrent stenoses appears to be significantly higher in infants who undergo stage repair compared sith single-stage complete repair.[7]

In a single-institution, retrospective study (2005-2016) of data from 90 children with PA-VSD (median age at diagnosis: 0.5 y; range: 0-13.8 y), of whom 88 underwent surgical intervention (complete repair, n = 32), survival at age 1 year was 95%; age 5 years, 83.7%; and age 10 years, 79.6%.[8]  At median follow-up of 5.7 years, 17 patients (18.9%) had died. The presence of associated and anomalies and nonconfluent PAs were significant mortality risks.

Complications

Possible complications of pulmonary atresia with ventricular septal defect (PA-VSD) include the following[6] :

• Congestive heart failure

• Erythrocytosis as a result of chronic hypoxia

• Infective endocarditis secondary to aberrant blood flow

• Sepsis due to either infective endocarditis or poor development of the immune system

• Brain abscess

• Delayed growth and puberty

• Arrhythmias and sudden death

Patients may require repeated surgeries for a complete repair of pulmonary atresia with ventricular septal defect (PA-VSD). Educate family members regarding congenital heart disease and how to perform cardiopulmonary resuscitation (CPR). Genetic counseling for future pregnancies is necessary.

For patient education resources, see the Heart Health Center, as well as Tetralogy of Fallot and Ventricular Septal Defect.

Children born with pulmonary atresia and ventricular septal defect (PA-VSD) may have unpredictable presentations owing to the variability of the lesion.

The age at presentation may vary depending on the amount of pulmonary blood flow. However, the great majority of patients present in the newborn period after the closure of the ductus arteriosus. Late presentation may rarely occur, and findings may include polycythemia, clubbing, cerebral embolisms, and cerebral abscesses.

The vast majority of patients present in infancy with cyanosis and hypoxia. The degree of cyanosis depends on whether the ductus is patent and how extensive the systemic collateral arteries are. Rarely, an infant with a large PDA or well-developed systemic collateral arteries may present at age 4-6 weeks with heart failure symptoms secondary to increased pulmonary blood flow. This heart failure may be very difficult to control medically. Paroxysms of dyspnea and squatting occasionally occur in older children.

Hemoptysis may occur as a result of rupture of extensive systemic-to-pulmonary collateral arteries. Important and recurrent infections can occur because of immunodeficiency, especially if associated with DiGeorge syndrome. Survival to adulthood has been described in a few patients with well-developed collateral arteries.

Growth and development are usually delayed secondary to cyanosis or congestive heart failure (CHF).

Central (ie, perioral) cyanosis is usually mild at birth, but it becomes very severe with the closure of the PDA. Cyanosis may fluctuate for the first few days because the ductus arteriosus may constrict and relax intermittently. The patient may have anomalies of the face, palate, and ears as described in velocardiofacial syndrome. Peripheral pulses are usually normal in neonates and remain normal in cyanotic infants. In infants with wide-open PDAs, well-developed systemic collateral arteries, or surgically created shunts, pulses may become pronounced after 4-6 weeks because of a wide pulse pressure.

The following may be observed on auscultation:

• S1 is normal; S2 (ie, aortic valve closure) is always single and often accentuated. A grade 3/6 systolic murmur usually is audible along the lower left sternal border.

• A continuous murmur is best heard over the upper chest in the presence of a PDA.

• If systemic-to-pulmonary collateral arteries are present, continuous murmurs may be diffusely audible over the entire chest and back.

• In some patients with severe cyanosis, no murmur can be heard.

• An early diastolic murmur of aortic regurgitation may be noted.

No laboratory or blood tests are available to confirm pulmonary atresia with ventricular septal defect (PA-VSD). However, the following evaluations may be helpful:

• Pulse oximetry can assist the diagnosis of cyanosis, especially in patients with dark skin and anemia (>5 mg/dL of reduced hemoglobin is required). It is also a useful indicator of the adequacy of pulmonary blood flow.

• Patients with an oxygen saturation greater than 85%-90% usually have well-developed collateral systems; they are at risk for pulmonary overcirculation; patients with oxygen saturations less than 75% may have poorly developed pulmonary vascular and collateral systems.

• An arterial blood gas (ABG) assessment can reveal hypoxemia and hypocarbia without any significant improvement with hyperoxia, favoring a diagnosis of cyanotic congenital heart disease.

• Reactive polycythemia and coagulation defects may be evident from the results of hematologic studies.

• Because, in some cases, pulmonary atresia with ventricular septal defect is associated with DiGeorge syndrome and velocardiofacial syndrome, genetic evaluation, including a fluorescent in situ hybridization (FISH) test, may be required.

Electrocardiography

Right ventricular (RV) hypertrophy and right-axis deviation are the rule on electrocardiography findings. Right atrial hypertrophy is also is present.

In a small subgroup of patients with increased pulmonary blood flow, combined ventricular hypertrophy with left atrial enlargement may be present.

Chest radiography

Chest radiographic features may include the following:

• A boot-shaped heart (coeur en sabot) may be observed. It occurs secondary to an upturned cardiac apex caused by RV hypertrophy and concavity in the region of the main pulmonary artery, which is produced by underdevelopment of the subpulmonary infundibulum.

• The heart size is usually normal or slightly enlarged, most often with an RV configuration.

• The main pulmonary arterial shadow normally depicted on chest radiography is absent.

• The pulmonary vascular markings have a heterogeneous reticular pattern in the presence of collateral arteries from the systemic arteries.

• Approximately 50% of patients have a right aortic arch with a large aorta.

• The lung field is oligemic in patients with very small collateral arteries.

• Lung fields may be flooded if the patient has a large patent ductus arteriosus (PDA) with normally developed central pulmonary arteries or well-developed systemic collateral arteries.

Echocardiography

Findings on echocardiograms may include the following:

• Parasternal long-axis scans reveal a large aortic valve overriding a malaligned ventricular septal defect.

• Position of malalignment of the ventricular septal defect (membranous or infundibular) and a blind hypoplastic RV infundibulum is easily observed using parasternal cross-sectional echocardiography.

• Atrial septal defects (ASDs) and other muscular ventricular septal defects can be detected.

• Scans from the suprasternal notch and high parasternal windows usually can provide important information regarding the size of the proximal pulmonary arteries and the presence of confluence. These views can also help define the side of the aortic arch and assess the patency of the ductus arteriosus.

• A right-sided aortic arch is frequently defined using the suprasternal notch view.

• Echocardiography is sensitive for detection of aortopulmonary collaterals, but it is inadequate for complete delineation.

• Defining all the collateral arteries with echocardiography is difficult.

• Short-axis parasternal (see the image below) and subcostal views are used to detect coronary artery abnormalities.

• Pulmonary Atresia With Ventricular Septal Defect. Short-axis parasternal view (1) and diagram (3) in a patient with pulmonary atresia and ventricular septal defect (PA-VSD). Short-axis parasternal view (2) and diagram (4) in a patient with normal anatomy. LA = left atrium; PA = pulmonary artery; PV = pulmonary valve; RA = right atrium; RV = right ventricle; and TR = tricuspid valve.

Magnetic resonance imaging (MRI)

MRI is a less invasive technique used to help define the surgically relevant pulmonary artery anatomy, but MRIs are inadequate for defining peripheral pulmonary arterial distribution.[9]

Cardiac catheterization and angiography are essential in evaluating the size and distribution of the native pulmonary arteries and the collateral arteries. Findings may include the following:

• Right atrial pressure is normal unless tricuspid incompetence is present.

• Pressures in the right ventricles (RVs) are at a systemic level because of the nonrestricted ventricular septal defect.

• Evaluation of the native pulmonary arterial system may be difficult unless there is a ductal-dependent pulmonary circulation or a connection between a collateral vessel and the native pulmonary arterial system.

• The presence of elevated distal pressures within the collateral arteries (mean pressures greater than 20-25 mm Hg) suggests significant pulmonary vascular obstructive disease (PVOD) within the affected lung segments.

• Evaluation of the RV systolic pressure (RVSP) is important in assessing ventricular septal defect (VSD) closure in patients who have been managed with unifocalization and an RV-PA (right ventricle to pulmonary artery) conduit without VSD closure; an RVSP less than 70% systemic suggests that the VSD can be closed.

See the following angiograms.

In patients with pulmonary atresia with ventricular septal defect (PA-VSD) a ductal-dependent circulation, prostaglandin E2 is often required to keep the ductus arteriosus open in the early neonatal period until surgery can be performed. A neonate who is ill may require fluid and acidosis management, but mechanical ventilation is rarely needed.

Medical treatment with digitalis, diuretics, and other agents may be indicated in patients with congestive heart failure (CHF) resulting from increased pulmonary blood flow. Phlebotomy to relieve the adverse effects of extreme polycythemia in very hypoxic patients is rarely performed. In patients with CHF and increased work of breathing, a high-energy diet is required. Rarely, a patient may require placement of a nasogastric tube to achieve the goals of energy intake.

Consultations

The following specialists can help guide appropriate evaluation and treatment of young patients with PA-VSD[6] :

• Pediatric cardiologists
• Pediatric cardiac anesthesiologists
• Pediatric surgeons
• Geneticists

Also see guidelines from the European Society of Cardiology (ESC) (2020) for management of adults with PA-VSD.

There is extreme variation of the anatomy, which will require individualized approach for each patient who has pulmonary atresia with ventricular septal defect (PA-VSD). A lack of consensus exists regarding surgical management of adult patients owing to debate over optimal treatment.[2]

Indications

Criteria for complete surgical repair of PA-VSD are as follows:

• The native pulmonary arteries provide all or most pulmonary blood flow with oxygen saturations more than 75%.

• The native pulmonary arteries must supply at least 10 segments, the equivalent of one lung.

• If additional major collaterals are identified, test the level of arterial oxygen saturation after occlusion of the collaterals in the catheterization laboratory. If the oxygen saturation remains greater than 75%, then coil occlusion of the collaterals is carried out.

• The Nakata index is used to guide decision making for surgical repair. it is defined as the cross-sectional area (in mm2) of the left and right pulmonary arteries just before the lobar branches, divided by the total body surface area (BSA). Good candidates for complete repair are those with a Nakata index above 200 mm2/BSA.

Contraindications

Contraindications for complete surgical repair of pulmonary atresia with ventricular septal defect include (1) hypoplastic or absent central pulmonary arteries and (2) inadequate peripheral arborization of pulmonary arteries.

Preoperative details

The use of blood is a consideration in any patient who is to undergo a major surgical procedure. Thus, evaluation for the concomitant presence of other medical problems such as DiGeorge syndrome must be performed.[10] DiGeorge syndrome may be present in patients with conotruncal abnormalities such as pulmonary atresia with ventricular septal defect (PA-VSD). When blood is used in these patients, it should be previously irradiated to avoid problems during transfusion.

In a retrospective study, Jia et al assessed the predictive value of preoperative cardiac computed tomography angiography (CTA) for survival in patients with PA-VSD and major aortopulmonary collateral arteries (PA-VSD-MAPCAs).[11] They analyzed PA-VSD-MAPCA patients with preoperative CTA who underwent both right ventricular outflow tract reconstruction and MAPCA unifocalization (n = 24) or pulmonary artery rehabilitation (n = 28). They found that in PA-VSD-MAPCA patients, preoperational high pulmonary vein index (PVI) and native pulmonary artery presence were morphologic predictors of a significant survival advantage.[11]

In a different retrospective review (2004-2017) of data from 65 neonates and young infants, Lee et al found comparable overall survival between staged repair and primary repair, as well as less frequent postrepair reinterventions.[12]

Elhedai et al performed a systematic review and meta-analysis comparison of staged repair (n = 167) versus single-stage complete repair (n = 97) for PA-VSD comprising data from 264 patients.[13]  They found higher total mortality and a higher rate of freedom from right ventricular outflow tract reintervention in the group who underwent staged repair. The staged repair and complete repair groups had comparable operative and early postoperative mortality, postoperative ventilation duration, need for postoperative extracorporeal membrane oxygenation (ECMO) support, transcatheter reintervention, unplanned reoperation, and length of hospital stay.[13]

Staged repair

The aims of the staged approach (see the image above) in a patient with PA-VSD are to increase the flow of the native pulmonary arteries by establishing a direct continuity between the aorta or the right ventricle (RV) and the small PA, thereby stimulating its growth. This is followed by unifocalization of the collaterals in both lungs and, finally, closing the VSD and establishing RV-PA continuity.

The main advantage of staged palliation is that it breaks the entire repair into smaller and better tolerated procedures.

Increasing pulmonary blood flow can be accomplished either by performing a shunt between the aorta or one of its branches and one of the PAs, or by using a nonvalved conduit between the RV and main PA if it was of adequate size.

Direct aortopulmonary shunts (eg, Waterston shunt, Pott shunt) were used in the past, but these were subsequently found to create severe distortion, scarring, interruption of the PAs, and, on occasion, pulmonary hypertension. Thus, the use of these shunts has fallen into disfavor.

The modified Blalock-Taussig shunt is most commonly used, and it is connected from the subclavian or innominate artery to the PA (when anatomy permits). A central ascending aorta to the main PA shunt (Melbourne shunt) can also be considered in the presence of confluent hypoplastic main PAs.

The second stage involves ligation and transplantation of MAPCAs. Ligation is performed when there is a dual blood supply to the same segment of the lung from a native pulmonary artery as well as from the major aortopulmonary collateral arteries (MAPCAs). MAPCAs need to be transplanted when they are the only source of blood supply to a bronchopulmonary segment, there is no stenosis, and they are not hypertensive.[14]

Diagnostic angiography must be performed to establish the size and distribution of the MAPCAs. Using this road map, the surgeon will then establish anastomotic communications between these vessels and, often, the native PAs.

Initial unifocalization attempts are usually deferred until the patient is age 3-6 months. Early unifocalization around age 1-3 months can be performed when protective stenosis in the MAPCAs is absent and congestive heart failure symptoms continue to worsen despite maximal medical therapy. Flow can also be reduced by percutaneous coil occlusion in the cardiac catheterization laboratory.

The last stage is usually performed between ages 1 to 3 years and involves closure of the VSD with or without fenestration, and establishment of continuity between the RV outflow tract and the PAs. The RV systolic pressure (RVSP) after correction should be less than 75% of that in the left ventricle.[15]

Complete repair

The objective of complete repair is to create an unrestricted continuity between the RV outflow tract and the PA tree using nonvalved or valved conduits. Subsequently, all extracardiac sources of pulmonary blood flow need to be ligated. The atrial septal defects (ASDs) and ventricular septal defects need to be closed. After correction, it is desirable to have a right ventricular pressure that is low, as close to normal as possible.

Various approaches have been devised to achieve a complete surgical repair, including the following:

• If a patient meets all the criteria for complete repair, single-stage unifocalization of pulmonary blood supply and complete intracardiac repair is the procedure of choice.

• Single-stage unifocalization and postponement of VSD closure to a second operation is an option.

• Sequential unilateral unifocalization followed by intracardiac repair is preferred in some patients.

Heart catheterization

More recently, new techniques and devices are being used to treat stenoses and insufficiency of the RV-PA) conduits and/or homografts in these patients. After complete surgical repair of the condition, patients require close follow-up and, on occasion, angioplasties and stent placement to overcome stenotic segments. In current practice, valved stents can be inserted during a heart catheterization, without the need to open the chest, in the presence of severe pulmonary valve insufficiency or stenosis. These percutaneous valves can be implanted using fluoroscopic guidance.

Heart-lung transplantation

In patients with completely atretic main, left, and right PAs, heart-lung transplantation is a viable option.

Complications of surgery include the following:

• Bronchospasm occurs after the unifocalization surgery because of tracheobronchial epithelial ischemia. This complication significantly contributes to early postoperative morbidity and mortality rates.

• Pulmonary parenchymal reperfusion injury, pulmonary hemorrhage, and phrenic nerve injury.

• Aortic regurgitation or aortic root dilation may occur.

• Restenoses of the shunts and neopulmonary arteries may occur, and subsequent interventions may be required.

Monitor patients for adequacy of repair and postoperative complications. Perform echocardiography on a regular basis, paying special attention to surgically created shunts, residual shunts, and the flow through right ventricular outflow tract conduits. Patients will require antibiotic prophylaxis for subacute bacterial endocarditis (SBE) for an indefinite period.

The European Society of Cardiology (ESC) updated their 2010 guidelines on the management of adult congenital heart disease (ACHD) in 2020.[2] Their recommendations regarding surgical intervention in and follow-up of patients with pulmonary atresia with ventricular septal defect (PA-VSD) are outlined below.

Surgical intervention

Note the following:

• Patients with unrepaired PA-VSD, or those who underwent previous palliative procedures, who survive to adulthood: Modern surgical or interventional procedures may be beneficial.
• Consider the following patients for surgery: Those with good-sized confluent PAs and those with large major aortopulmonary collateral arteries (MAPCAs) that are anatomically suitable unifocalization, who have not developed severe pulmonary vascular disease owing to protecting stenosis
• Catheter interventions may include balloon dilation/stenting of collateral vessels for pulmonary blood flow enhancement; however, patients with severe hemoptysis may need to undergo coiling of the ruptured collateral vessels.
• Patients with good-sized PAs absent a pulmonary trunk: Repair with a right ventricle (RV) to pulmonary artery (RV–PA) conduit.
• Patients with confluent but hypoplastic PAs: An arterial shunt or reconstruction of the RV outflow tract (OT) (without VSD closure) is usually needed. This may enhance PA growth and then be reviewed at a later stage for repair using a valved conduit.
• Patients with nonconfluent PAs and adequate, but not excessive, pulmonary blood flow in infancy: These patients can survive into adulthood without surgery.

Follow-up

Periodic follow-up of patients with PA-VSD is recommended at least once every year at a specialized ACHD institution. Monitor closely and evaluate and review sooner in the setting of symptoms such as dyspnea, increasing cyanosis, change in shunt murmur, heart failure, or arrhythmias.

Consider patients with segmental pulmonary arterial hypertension (PAH) for targeted PAH therapy.