Pulmonary Atresia With Ventricular Septal Defect: Symptoms, Types, Causes and Treatment

Pulmonary Atresia with Ventricular Septal Defect (PA-VSD) is a rare and complex congenital heart disease that poses significant challenges for both patients and clinicians. In this article, we break down the key features of PA-VSD—its symptoms, types, underlying causes, and modern treatment strategies—using up-to-date evidence and research. Understanding this condition is crucial for families, caregivers, and healthcare professionals aiming to improve outcomes and quality of life for those affected.

Symptoms of Pulmonary Atresia With Ventricular Septal Defect

Pulmonary Atresia with Ventricular Septal Defect typically presents in infancy or early childhood, though symptoms and severity can vary widely. Early recognition of symptoms is essential for prompt diagnosis and management, potentially improving long-term outcomes.

Symptom	Description	Timing	Source(s)
Cyanosis	Bluish discoloration due to low oxygen	Early infancy	1, 8
Heart murmur	Continuous murmur from abnormal blood flow	At birth or soon after	1
Heart failure	Rapid breathing, poor feeding, sweating	Infancy	1, 5
Exercise intolerance	Fatigue, shortness of breath with activity	Childhood/adulthood	5

Table 1: Key Symptoms

Cyanosis and Low Oxygen

One of the earliest and most noticeable symptoms of PA-VSD is cyanosis—a bluish tint to the skin, lips, and nails. This occurs because oxygen-poor blood bypasses the lungs and is circulated directly into the body due to blocked pulmonary outflow and the presence of a ventricular septal defect. Cyanosis may be evident immediately after birth or within the first days of life, depending on the amount of blood reaching the lungs through alternative pathways, like a patent ductus arteriosus (PDA) or systemic-to-pulmonary collaterals 1 8.

Heart Murmur

Many infants with PA-VSD have a characteristic continuous heart murmur. This murmur is not due to normal valve flow but results from abnormal blood movement through collaterals or a ductus arteriosus, compensating for the atretic (closed) pulmonary valve 1.

Heart Failure Symptoms

Some infants develop symptoms of heart failure, which might include:

• Rapid breathing (tachypnea)
• Difficulty feeding or poor weight gain
• Excessive sweating, especially during feeding

Heart failure is more likely if there is excessive blood flow to the lungs through large collateral vessels 1 5.

Exercise Intolerance and Arrhythmias

As children with PA-VSD grow older, they may experience fatigue, shortness of breath with exertion, and arrhythmias. Adults living with this condition, even after surgical repair, are at increased risk for heart failure and arrhythmias, which can contribute to significant morbidity and mortality 5.

Types of Pulmonary Atresia With Ventricular Septal Defect

PA-VSD is not a single anatomical defect but a spectrum of related conditions. Understanding the different types is vital, as the anatomical variations dictate the clinical approach and prognosis.

Type	Key Feature	Pulmonary Blood Flow Source	Source(s)
Type A	Native pulmonary arteries only	Native pulmonary arteries (NPA)	3
Type B	NPA + aortopulmonary collaterals	NPA & major aortopulmonary collateral arteries (MAPCAs)	3 6
Type C	Collaterals only, no NPA	MAPCAs only	3 12
Simple	Isolated PA-VSD	Variable	2 4
Complex	Associated with other heart defects	Variable	2 4

Table 2: Main Types of PA-VSD

Classification by Pulmonary Circulation

A widely accepted modern classification divides PA-VSD into three main types based on how the lungs receive blood 3:

• Type A: Blood reaches the lungs solely through normally developed native pulmonary arteries. This is the most straightforward for surgical repair.
• Type B: Both native pulmonary arteries and major aortopulmonary collateral arteries (MAPCAs) supply the lungs. This "mixed" type is more complex and often requires staged surgery.
• Type C: There are no native pulmonary arteries. Pulmonary blood flow is entirely dependent on MAPCAs, making surgical management particularly challenging 3 12.

Simple vs. Complex Types

• Simple PA-VSD: Refers to cases where only pulmonary atresia and VSD are present, without additional major heart defects. The size and anatomy of the pulmonary arteries, the aorta, and the flow patterns are key surgical considerations 2 4.
• Complex PA-VSD: Includes cases with additional anomalies, such as transposition of the great arteries, tricuspid or mitral atresia, single ventricle physiology, or abnormal heart positioning. These cases require individualized and highly specialized management 2 4.

Anatomical Variants

Other anatomical considerations include:

• The presence or absence of central (intrapericardial) pulmonary arteries 12
• The size and development of the native pulmonary arteries 13
• The number and distribution of MAPCAs 6 12

Causes of Pulmonary Atresia With Ventricular Septal Defect

PA-VSD is a congenital condition—meaning it develops before birth. While the exact causes are complex and not fully understood, recent research has shed light on several contributing factors.

Cause Type	Example/Explanation	Evidence	Source(s)
Genetic mutations	NDRG4 p.T256M, CNVs in PPP4C, FLT4, RICTOR	Identified in patient cohorts	7 8
Chromosomal deletions	22q11 deletion syndrome	High prevalence in PA-VSD	9
Developmental errors	Disrupted heart and vessel formation	Observed in embryology	8
Unknown/Multifactorial	Likely multiple genes + environment	Ongoing research	7 8

Table 3: Key Causes of PA-VSD

Genetic Mutations and Chromosomal Abnormalities

Recent genomic studies have identified specific genetic changes associated with PA-VSD:

• Copy Number Variants (CNVs): Rare CNVs such as deletions and duplications in genes like PPP4C, FLT4, RICTOR, and FGF22 have been found in patients with PA-VSD but not in controls, suggesting a strong genetic component 7.
• NDRG4 Mutation: A loss-of-function mutation (p.T256M) in the NDRG4 gene impairs cardiac myocyte proliferation and has been implicated in the pathogenesis of PA-VSD and similar defects 8.
• 22q11 Deletion: This chromosomal deletion, also known as DiGeorge syndrome, is found in a significant proportion of PA-VSD patients and is associated with worse surgical outcomes 9.

Developmental Disruptions

PA-VSD arises during early fetal development, when the pulmonary valve and the outflow tract from the right ventricle fail to form or open properly. This is often accompanied by a defect in the ventricular septum, allowing communication between the right and left ventricles 8. The resulting abnormal blood flow patterns can influence the development of pulmonary arteries and the formation of collateral vessels.

Multifactorial Nature

While specific mutations and deletions increase risk, many cases of PA-VSD likely result from a combination of genetic predispositions and environmental influences during pregnancy. However, in most patients, no identifiable cause is found, and the condition appears to occur sporadically 7 8.

Treatment of Pulmonary Atresia With Ventricular Septal Defect

Treating PA-VSD requires a highly individualized approach, guided by the specific anatomy and physiology of each patient. Advances in surgical techniques and perioperative care have significantly improved survival and quality of life.

Treatment	Approach/Goal	Key Considerations	Source(s)
Surgical repair	Complete repair of defects	Anatomy, size of pulmonary arteries	1 3 6 10 13
Unifocalization	Bring all collaterals together	Especially for MAPCAs type	6 10 11 12
Palliative surgery	Improve pulmonary blood flow	For patients not ready for full repair	1 6 13
Catheter-based interventions	Balloon/stent dilation	For branch or collateral stenosis	1
Medical management	Supportive care, manage heart failure	Prior to/after surgery	5 13

Table 4: Main Treatments for PA-VSD

Surgical Repair

The primary goal is to establish normal blood flow from the right ventricle to the lungs and close the ventricular septal defect. The surgical approach is determined by the patient's anatomy:

• Single-Stage Complete Repair: Preferred when possible; involves closure of the VSD and creation of a right ventricle to pulmonary artery connection, with or without the use of a conduit. More than 90% of suitable patients can achieve complete repair, with lower mortality rates in single-stage repairs 10 12.
• Staged Repair: Used for patients with complex anatomy or small pulmonary arteries. Initial surgeries may focus on improving pulmonary artery size and development, followed by complete repair at a later stage 3 6 13.

Unifocalization

For patients with MAPCAs (types B and C), unifocalization is a key strategy. This involves surgically connecting all collateral arteries supplying the lungs into a single, unified pulmonary circulation, which can then be attached to the right ventricle 6 10 11 12. Early unifocalization improves outcomes, especially when combined with simultaneous intracardiac repair 11.

Palliative Surgery

Some patients, particularly those with severely underdeveloped arteries or very complex anatomy, may not be candidates for complete repair initially. In such cases:

• Systemic-to-pulmonary artery shunt: Increases pulmonary blood flow and can promote growth of pulmonary arteries, potentially making full repair possible later 13.
• Central shunt or fenestrated septal repair: Used as temporary measures to improve oxygenation and survival 13.

Catheter-Based Interventions

Balloon or stent dilation can be used to open narrowed branches of the pulmonary arteries or collaterals, often in conjunction with surgical strategies 1.

Medical Management and Long-Term Care

Even after successful repair, lifelong follow-up is essential. Adults with PA-VSD are at risk for:

• Heart failure
• Arrhythmias
• Need for further interventions due to conduit or shunt failure

Medical management includes heart failure medications, arrhythmia control, and infection prevention. Despite advances, adult survivors continue to face high morbidity and mortality, highlighting the need for specialized adult congenital heart disease care 5 13.

Conclusion

Pulmonary Atresia with Ventricular Septal Defect is a rare but serious congenital heart disease with complex anatomy and challenging management. Here’s a summary of the main points covered:

• Symptoms: Early cyanosis, heart murmur, heart failure in infancy, and ongoing exercise intolerance or arrhythmias in older patients 1 5 8.
• Types: Classified by pulmonary blood flow sources (native arteries, collaterals, or both) and by the presence of simple or complex additional heart defects 2 3 4 6 12.
• Causes: Largely genetic, involving rare mutations and chromosomal deletions, especially 22q11, but often multifactorial 7 8 9.
• Treatment: Highly individualized, involving surgical repair, unifocalization, palliative procedures, catheter interventions, and lifelong medical care. Outcomes have improved dramatically but challenges remain, especially in adults 1 3 6 10 13.

Early diagnosis, careful anatomical assessment, and a multidisciplinary approach are essential to improving outcomes and quality of life for individuals with PA-VSD. Ongoing research into genetics and new therapies holds promise for the future.