Continuing Education Activity

Pulmonary atresia with ventricular septal defect is a rare congenital anomaly that can have poor prognostic outcomes. Although similar to the tetralogy of Fallot, it has several anatomic variations. It is a serious anomaly affecting the development of the pulmonary trunk and the membranous portion of the interventricular septum. To avoid the high morbidity and mortality associated with this condition, it must be promptly diagnosed and treated. Various surgical strategies can be employed to treat this complex anomaly. Surgical intervention is depending on the patient's anatomy and development. This activity reviews the evaluation and treatment of pulmonary atresia with interventricular septal defect and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Identify the etiology of pulmonary atresia with ventricular septal defect medical conditions and associated emergencies.

• Assess the diagnostic evaluation of pulmonary atresia with ventricular septal defect.

• Evaluate the management options available for pulmonary atresia with ventricular septal defect.

• Collaborate among patients, caregivers, and a multidisciplinary team to establish the best corrective action for patients with pulmonary atresia with ventricular septal defect. 

Introduction

Pulmonary atresia with ventricular septal defect (PAVSD) is 1 of the cyanotic congenital heart diseases. It occurs due to underdevelopment or maldevelopment of the right ventricular outflow tract and atresia of the pulmonary valve and trunk. It also involves overriding the aorta and a large ventricular septal defect.[1] Previously, it was termed truncus arteriosus type IV. Whether it is a different entity or a severe form of tetralogy of Fallot (TOF) is still controversial, but there is no denying the occurrence of PAVSD. The spectrum of this defect varies in presentation and severity, largely depending on the degree of pulmonary atresia and the development of collaterals. Patients with a pulmonary circulation dependent on the arterial duct and with conjoined pulmonary arteries may become cyanotic when the duct closes. In such cases, if they have not been diagnosed prenatally, these patients may require prostaglandin treatment. On the other hand, patients with major aortopulmonary collateral arteries (MAPCAs) are usually asymptomatic at birth since the collateral arteries provide sufficient pulmonary blood flow.

Many authorities prefer to call this entity TOF with pulmonary atresia and MAPCAs. This is because the term "pulmonary atresia with VSD" can entail a plethora of variable congenital defects, including these: double-inlet left ventricle, transposition of the great arteries (congenitally corrected or not corrected), atrial heterotaxy, and atrioventricular atresia. Nevertheless, only the lungs of patients with conventional Fallot anatomy complicated by pulmonary atresia receive blood exclusively through congenital systemic-to-pulmonary arteries.[2] Luckily, TOF overlaps significantly with PAVSD and may even be managed as such, decreasing ambiguity about the treatment. For this topic, we consider PAVSD a separate entity from classical TOF. 

Etiology

The etiology of PAVSD is not completely elucidated yet, but there is a noteworthy connection with genetic syndromes. One research reported a 45% incidence of PAVSD in children with DiGeorge syndrome (22q11 deletion); DiGeorge syndrome is associated with lack of a thymus, which may be evidenced during surgical correction.[8] VATER (VACTERL association) and Alagille syndrome are also implicated in PAVSD; Alagille syndrome associated with PAVSD carries a grave prognosis.[3] 

Several risk factors have been linked with PAVSD:

• History of congenital heart diseases in either parent.
• History of intake of teratogenic drugs by the mother during gestation.
• Smoking during or before pregnancy.
• Poorly controlled diabetes.
• Pregnancy at an older age.

These risk factors are not specific to PAVSD and are also found frequently in other congenital anomalies.

Epidemiology

The incidence of congenital heart diseases is decreasing yearly due to the avoidance of known teratogens and risk factors through patient education and counseling. The incidence of pulmonary atresia is also decreasing. The prevalence of pulmonary atresia from 1999 to 2000 was 12.1% of all congenital heart diseases, which gradually decreased to 9.6% in 2008.[4]

Pathophysiology

In PAVSD, the degree of pulmonary artery involvement steers the clinical picture and the treatment options. Presentations include an isolated valvular atresia or proximal pulmonary trunk involvement. The right and left pulmonary arteries may or may not communicate, and the intrapericardial pulmonary arteries are often very diminutive (1 to 3 mm).[8] Major aortopulmonary collateral arteries (MAPCA) usually supply the lung parenchyma. These MAPCAs may arise from the thoracic or abdominal aorta, subclavian arteries, internal mammary arteries, intercostal arteries, or other less common locations. The systemic-to-pulmonary anastomoses in MAPCAs are classified into extrapulmonary, hilar, lobar, and segmental. MAPCAs are usually aberrant and stenosed at either end. In other instances, patent ductus arteriosus (PDA) may also contribute to supplying pulmonary circulation.

The intrapulmonary arterial structure mainly relies on the size and flow of PDA. In the absence of PDA or with too many aberrant MAPCAs, the intrapulmonary arteries may not be developed properly, leading to pulmonary hypertension. The associated VSD is usually membranous in origin. Other defects, such as atrial septal defects, are not uncommon, but their association with PAVSD is not yet well understood. Pulmonary atresia leads to right ventricular outflow tract obstruction and increased resistance against the right ventricular contraction, eventually leading to right ventricular hypertrophy. At the same time, the left ventricle is usually spared. Coronary artery anomalies are not a common occurrence in PAVSD, but coronary fistulas may rarely be present.[5][6]

Pulmonary atresia and the resulting right ventricular outflow tract obstruction are responsible for right-to-left shunts in PAVSD. A critical balance between systemic and pulmonary vascular resistance is necessary for normal perfusion. A sudden decrease in systemic vascular resistance can lead to cyanotic spells similar to the ones described in the Tetralogy of Fallot. Conversely, some children may present with signs and symptoms of pulmonary overcirculation and congestive heart failure.[8]

The overriding position of the aorta has a compensatory role by receiving the blood from both the ventricles and delivering it to the systemic and pulmonary circulation via the patent ductus arteriosus. Patency of ductus arteriosus is crucial in the initial survival of these patients. In mild to moderate cases where the pulmonary vasculature and valve are mildly atretic, the right ventricle may be able to pump adequate blood in the native pulmonary circuit for oxygenation. PDA, in these cases, may spontaneously collapse before presentation.

About 75% of neonates have the standard anatomy described above; however, certain features have been described that may indicate a deviation from conventional management. These features include 1) PDA to 1 lung with MAPCAs to the other lung, 2) hemi-truncus to 1 lung with MAPCAs to the other lung, and 3) dual supply to the lung from MAPCAs and the pulmonary arterial tree.[7] Patients in the latter category of dual supply with all 18 lung segments receiving pulmonary artery blood flow may be candidates for a neonatal aortopulmonary window, allowing the pulmonary arteries to grow and avoid the need for MAPCA surgery, although some of these patients may require treatment for pulmonary artery stenoses.[8] 

History and Physical

Although evident in fetal ultrasound at 18 to 22 weeks gestation, many cases may go unrecognized where the mother refuses prenatal care or does not have access to the appropriate maternal healthcare resources. In these situations, the case may be first recognized on physical examination, usually at birth. The clinical presentation of the PAVSD is highly variable depending on the degree of pulmonary atresia and MAPCAs. Most neonates present with cyanosis and cardiac murmur.[9]  Other common symptoms include the following:

• Central cyanosis may present as bluish discoloration of the face, particularly around the mouth and lips. In severe cases, it may be seen in peripheral limbs as well.
• Increased respiratory rate or shortness of breath due to poor blood oxygenation. It may not be evident at rest and only at exertion during crying or breastfeeding.
• Easy fatigability may present as a weak cry, tone loss, and poor breast latching.
• Failure to thrive.
• Difficulty feeding.

The physical exam may reveal central cyanosis, a holosystolic murmur at the left sternal border that may radiate to the back or axilla, a single accentuated second heart sound S2, a machine-like continuous murmur of PDA best heard at the upper precordium or the interscapular region on the back, a weak grip, a low weight for age, and lethargy.[6] Peripheral edema, clubbing, and worsening cyanosis may indicate congestive heart failure (CHF), especially if presenting late in life. A small number of neonates/infants present with CHF early in life. They have large MAPCAs with excessive pulmonary blood flow, sometimes requiring mechanical ventilation. These patients require early complete repair, and outcomes are generally favorable because they often have well-developed pulmonary vasculature.[8]

Evaluation

The following investigations are a part of the comprehensive evaluation of PAVSD patients:

• Echocardiography: The gold standard investigation module provides valuable insight into pulmonary valve atresia, overriding of the aorta, VSD, ASD, some MAPCA if present, the pressure gradient across valves, and ejection fraction.[6]
• Angiography: Cardiac catheterization is another important investigation. It can provide details of the arterial vasculature's anatomy, size, and distribution. It can assess pressures in the right ventricle and the pressure gradient across the pulmonary valve. MAPCAs can be confirmed by catheterization and selective injections of contrast into collateral vessels to provide the most accurate demonstration of pulmonary blood supply to lung segments. Central pulmonary arteries can be identified only if there is a patent arterial duct or connection to collateral. In recent years, computed tomography angiography has been used instead of angiography.[7]
• Pulse oximetry evaluates oxygen saturation, especially in dark-skinned infants where cyanosis may be missed during the physical exam. A hyperoxia test conducted at birth can easily single out infants with cyanotic heart diseases and facilitate early management.
• Arterial blood gasses.
• Baseline hemoglobin and blood cell indices.
• Genetic testing is mainly if other congenital defects are present.
• Traditional chest X-ray signs include absent pulmonary artery shadow, boot-shaped heart, cardiomegaly, or poor lung vasculature markings.
• Magnetic resonance angiography (MRA) or computed tomography angiography is important to delineate vascular anatomy before surgery to plan correction. It may reveal other MAPCAs that are difficult to see on echocardiography.[10]

Treatment / Management

Medical management: Oxygen saturation is critical and should be monitored continuously. Similarly, fluid imbalance and acidosis, if present, need to be addressed urgently. Since the neonate is usually unable to feed well, nutritional rehabilitation might also be needed. In severe cases where the pulmonary valve is completely atretic, and the pulmonary circulation is entirely dependent on ductus arteriosus, prostaglandin E1 should be considered to keep the duct open until a surgical correction occurs. Symptomatic treatment with diuretics or digoxin is indicated if the patient is going into congestive heart failure. 

Surgical management: Conventional treatment, occurring in about 75% of cases, involves discharge of the neonates from the hospital to return at 3 to 6 months of age when their organs are more developed.[7] The size of the pulmonary arteries, the presence/absence of MAPCAs, and PDA drive the surgical plan. Of these criteria, PAVSD can be divided into 2 main categories: PAVSD with ductus-dependent pulmonary blood flow and PAVSD with MAPCAs-dependent pulmonary blood flow.

• PAVSD with MAPCAs
  • PAVSD with under-developed MAPCAs:
    • Primary rehabilitation:  An initial procedure targeting small MAPCAs, aiming at improving the central PAs with either a prosthetic central shunt or the reimplantation of the main pulmonary artery on the side of the aorta, “the Melbourne shunt,” or a patching of the outflow tract.
      1. Central shunt: (Laks technique).
      2. Side reimplantation (Melbourne).
      3. Right Ventricular Outflow Tract Patching.
    • Secondary rehabilitation:
      1. Right ventricle to pulmonary artery shunt (Sano).
      2. Pulmonary artery patching.
    • Final repair: Involves repair patching of pulmonary arteries and VSD closure.
  • PAVSD with well-developed MAPCAs
    • Unifocalization: This involves reattaching MAPCAs to central pulmonary arteries.[11]
      • One follow-up study found a 95% patency rate of MAPCAs with the midline unifocalization approach by catheterization (although 20% of these had some degree of stenosis).[12] 
      • Risk factors for needing reoperation of a uni-focalized bed include the following:[7]
        • a) Unifocalization/shunt rather than complete repair
        • b) Higher initial right ventricle-to-aorta pressure ratios
        • c) Absence of central pulmonary arteries
    • VSD Closure.
• PAVSD with patent arterial duct: This type of lesion is treated like tetralogy of Fallot.
  • Staged Palliation: The surgical treatment of PAVSD with ductus-dependent pulmonary circulation is a staged approach that involves several admissions and many operations without any fixed number. The steps of correction are as follows:

1) Blood flow is established first in the pulmonary arteries by connecting it directly to the aorta through a modified Blalock-Taussig-Thomas shunt.

2) The right ventricle can also be connected to the aorta temporarily if the overriding of the aorta is insufficient (Sano shunt).

3) As the pulmonary arteries grow in size due to sustained blood supply from the aorta, the pulmonary circulation is then connected to the pulmonary artery.

4) The right ventricle is connected back to the pulmonary artery.

5) The MAPCAs are closed in the next step, usually at 6 months of age, if the respective lung segments receive enough supply through the now-developed pulmonary arteries.

6) VSD is repaired at the end, usually at 1 to 3 years old. The major benefit of this approach is that the whole procedure becomes more tolerable by the already feeble neonate, and breaks are available to allow for healing. In contrast to staged repair, the other approach is complete repair in 1 surgery. This procedure is only suitable for limited candidates on the low end of the severity spectrum. One high-volume center found that infants with a basal oxygen saturation higher than 85% have well-developed pulmonary vasculature amenable to single-stage intervention.[7]

Early Total Correction

In this less popular approach, preferred mostly in mild cases, surgeons usually correct the anatomy within the same admission if not the same operation. The patients are carefully picked, and risks versus benefits are critically analyzed before choosing this option. Some centers have found lower mortality and intervention rates with single-stage total correction.[11] As noted above, neonates with frank CHF symptoms may require early correction. In addition, infants with persistent PDA or hemi-truncus can develop pulmonary vascular obstructive disease, also requiring early correction.[7]

Perioperative Care

Improved outcomes have been associated with early anticoagulation to decrease thrombotic occlusion of shunts; 1 suggested dose is 10 mg/kg of aspirin (ASA). Another suggestion is improved post-surgical care with frequent clinic visits to re-dose ASA and caregiver education regarding the symptoms of shunt failure with 24-hour medical availability by phone.[13]

Cardiac Transplant

In patients with a completely atretic pulmonary system or who have failed the surgical corrective measures, a cardiac transplant can be a viable option.[6]

Differential Diagnosis

Differential diagnoses of PAVSD include the following:

• Severe tetralogy of Fallot
• Transposition of the great arteries with pulmonary stenosis
• A single ventricle with severe pulmonary stenosis 
• Tricuspid atresia
• Pulmonary atresia with intact interventricular septum
• Double-outlet right ventricle with pulmonary atresia
• Double-inlet left ventricle with pulmonary atresia
• Congenitally corrected transposition of the great arteries (L-TGA) with ventricular septal defect and pulmonary atresia[14][15] 

Prognosis

Without surgical correction, about 50% of patients die within the first 2 years of life, and 20-year survival is around 10%.[10] With proper treatment and follow-up, 65% of patients alive at 1 year can live beyond the age of 10.[9] One high-volume center estimated operative mortality at 1.5% to 8%, depending on the procedure performed.[7] 

Complications

On top of surgical and anesthesia complications in treated patients, some of the complications of PAVSD are:

• Congestive heart failure (CHF)
• Reactive erythrocytosis in response to chronic hypoxia
• Infective endocarditis due to the aberrant flow of blood
• Sepsis either due to infective endocarditis or poor immune system development
• Delayed growth and puberty
• Arrhythmias
• Sudden death

Consultations

Pediatric cardiologists, pediatric cardiac anesthesiologists, pediatric surgeons, and geneticists should be consulted for appropriate assessment and management.

Deterrence and Patient Education

Education of parents regarding congenital heart diseases is important as the prognosis is particularly poor, and the patient usually requires multiple surgeries for correction of anomalies. Parents should be educated regarding performing cardiopulmonary resuscitation in children. Genetic counseling should be provided to plan future pregnancies. Possible termination of pregnancy should be discussed as an option if presenting in the early fetal stage.

Enhancing Healthcare Team Outcomes

PAVSD is a rare disease that presents with a wide variety of clinical signs and symptoms that overlap with other congenital anomalies. Patients may initially present with vague symptoms like feeding difficulty and lethargy. A final diagnosis requires a comprehensive evaluation, with consultation from different departments like pediatric cardiology, pediatric surgery, and geneticists. History and physical exam are usually insufficient for diagnosis, and further investigations are required. PAVSD is a rare condition that requires prompt referral to pediatric cardiologists when echocardiographic or CT/MRI scans reveal cardiac defects. Radiologists play a vital role in identifying the underlying defect. Getting the pediatric surgeons involved in the plan and assessment is vital. Nutritionists are an essential part of the team to supplement patient nutritional requirements, as they often face feeding difficulties. Geneticists are also an important part of the team that provides counseling on future pregnancies. As the mainstay of treatment is surgery, preoperative and postoperative management are crucial, and anesthetists are pivotal in these delicate patients. Pharmacists are responsible for the correct dosages of medicine. A team-based approach is crucial to providing the best possible care to these patients. The outcomes of a PAVSD depend on the time of presentation and extent of severity. However, prompt consultation with interprofessional specialists is pivotal to improving patient outcomes.