Endocardial Cushion Defect: Symptoms, Types, Causes and Treatment

Endocardial cushion defect (ECD), also known as atrioventricular septal defect (AVSD), is a complex congenital heart anomaly that affects the walls (septa) separating the heart chambers and the valves controlling blood flow between them. While ECD can range from mild to severe, it often leads to significant clinical symptoms and requires specialized care. This article offers a comprehensive guide to the symptoms, types, causes, and treatments of endocardial cushion defects, synthesizing evidence from key scientific sources.

Symptoms of Endocardial Cushion Defect

Endocardial cushion defects present with a spectrum of symptoms, often depending on the severity and type of the defect. Early identification of these symptoms is crucial for prompt intervention and optimal outcomes.

Symptom	Description	Typical Onset	Source(s)
Heart Murmur	Abnormal heart sounds due to turbulent flow	Infancy	13 14 16
Heart Failure Signs	Rapid breathing, poor feeding, sweating	Early infancy	13 16
Frequent Infections	Especially respiratory	Early childhood	13 16
Poor Growth	Failure to thrive, delayed milestones	Infancy/childhood	14 16
Arrhythmias	Irregular heartbeats (can be transient)	Post-treatment or later	14 16

Table 1: Key Symptoms

Understanding the Symptoms

Endocardial cushion defects often manifest early in life, particularly in infancy. The symptoms vary based on the anatomical form and associated cardiac anomalies.

Heart Murmurs and Abnormal Heart Sounds

A characteristic heart murmur is often the first clue. This sound results from abnormal blood flow across the defective septa and valves. In many cases, physicians notice this murmur during a routine exam, prompting further investigation 13 14 16.

Signs of Heart Failure

Infants with significant defects may develop heart failure early, showing symptoms such as:

• Rapid or labored breathing
• Poor feeding and sweating during feeding
• Irritability and lethargy

These signs occur because the heart struggles to pump blood efficiently due to the abnormal connections between chambers, leading to volume overload and pulmonary congestion 13 16.

Frequent Respiratory Infections

Because ECD increases blood flow to the lungs, children are more prone to respiratory infections, including pneumonia and bronchitis. These infections can be recurrent and severe 13 16.

Poor Growth and Failure to Thrive

Growth delay is a common symptom due to chronic heart failure and increased metabolic demand. Infants and children may not gain weight or reach developmental milestones at the expected rate 14 16.

Arrhythmias

After surgical repair, some patients experience heart rhythm disturbances (arrhythmias). These are usually transient, but in rare cases may require intervention, such as pacemaker placement 14 16.

Types of Endocardial Cushion Defect

Endocardial cushion defects exist on a spectrum, with different anatomical and clinical presentations. Understanding these types helps guide diagnosis and management.

Type	Defining Features	Severity	Source(s)
Complete AV Canal	Single AV valve, primum ASD, inlet VSD	Severe	6 8 16
Partial (Incomplete)	Primum ASD, cleft mitral valve, separate AV valves	Moderate	6 8 14
Intermediate (Transitional)	Features between complete and partial defects	Variable	8
Associated Anomalies	Cor triatriatum, supravalvular mitral ring, PDA, others	Variable/complex	3 6 16

Table 2: Types of Endocardial Cushion Defect

Breaking Down the Types

Complete Atrioventricular (AV) Canal Defect

The most severe form, complete AV canal defect, features a large hole in the center of the heart involving both the atrial and ventricular septa and a single, common AV valve 6 8 16. This allows blood to mix freely between all four chambers, leading to severe symptoms early in life.

• Features:
  • Ostium primum atrial septal defect (ASD)
  • Inlet ventricular septal defect (VSD)
  • Common AV valve bridging both ventricles

Partial (Incomplete) AV Canal Defect

The partial form, also known as ostium primum defect, involves a hole in the lower part of the atrial septum and a cleft (split) in the anterior leaflet of the mitral valve, but with two separate AV valves 6 8 14.

• Features:
  • Primum ASD
  • Cleft mitral valve (often leading to regurgitation)
  • Intact ventricular septum

Intermediate (Transitional) Forms

Intermediate forms exist between the complete and partial types. These may have a primum ASD, a small VSD, and variable valve morphology 8.

Associated Anomalies

Endocardial cushion defects frequently occur with other heart anomalies, such as:

• Cor triatriatum: Subdivision of the left atrium 3
• Supravalvular mitral ring
• Patent ductus arteriosus (PDA)
• Tetralogy of Fallot, parachute mitral valve 3 16

These associations can complicate both the symptoms and the surgical approach.

Causes of Endocardial Cushion Defect

The development of endocardial cushion defects is rooted in cardiac embryology, influenced by both genetic and environmental factors. Recent research has shed light on specific molecular pathways involved.

Cause/Mechanism	Key Details	Impact Level	Source(s)
Genetic Mutations	GATA4, SMAD4, Tbx20, Connexin45, ALK2	Major	5 9 10 11
Defective Cushion Fusion	Failure of dorsal/ventral cushion fusion	Critical	8
Environmental Factors	Maternal diabetes, Down syndrome, others	Contributory	8
Cellular Mechanisms	Impaired EMT, defective valve/septum formation	Central	5 9 10 11

Table 3: Causes and Mechanisms

The Underlying Causes

Genetic and Molecular Pathways

ECD arises primarily due to disruptions in the early formation of the heart's endocardial cushions—structures that eventually form the heart's septa and AV valves.

• GATA4 and SMAD4 Mutations: Mutations in these transcription factor genes interfere with the signaling required for normal endocardial cushion development, leading to septal and valve defects 5.
• Tbx20 and Wnt Signaling: Tbx20 regulates Wnt signaling necessary for cushion maturation and valve remodeling. Loss of Tbx20 disrupts valve elongation and septation 11.
• Connexin45: This gap junction protein is essential for cell-cell communication during early heart development. Its absence impairs the transformation of endocardial cells into cushion tissue, resulting in defects 9.
• ALK2 (BMP type I receptor): Essential for endothelial-to-mesenchymal transition (EMT), a critical process for cushion formation. ALK2 deficiency leads to failed septa and valve development 10.

Embryologic Mechanisms

During fetal development, the dorsal and ventral endocardial cushions must fuse to separate the heart’s chambers and form proper AV valves. Failure of this process results in ECD. The extent of fusion failure determines the severity and type of the defect 8.

Environmental and Chromosomal Influences

• Down Syndrome (Trisomy 21): Strongly associated with ECD due to underlying genetic predisposition 8.
• Maternal factors: Conditions such as poorly controlled diabetes during pregnancy may increase risk, though genetic factors are predominant 8.

Cellular Mechanisms

The transformation of endothelial cells into mesenchymal cells (EMT) is crucial for cushion formation. Disruptions in this transformation due to defective signaling (e.g., BMP/TGF-β pathways) can lead to acellular cushions and failed septal/valve development 5 9 10 11.

Treatment of Endocardial Cushion Defect

Modern management of ECD has evolved, with surgical intervention being the cornerstone. Advances in diagnosis, surgery, and post-operative care have significantly improved outcomes.

Treatment Approach	Application/Indication	Outcomes	Source(s)
Surgical Repair	Patch closure, valve reconstruction/replacement	Improved survival, function	13 14 16
Medical Management	Diuretics, digoxin (pre/post-op)	Symptom relief	16
Arrhythmia Management	Pacemaker (if needed)	Rhythm control	14
Reoperation	For valve failure, residual defects	Variable	14 16

Table 4: Treatment Strategies

Treatment Modalities and Outcomes

Surgical Repair: The Mainstay

• Complete Defects: Surgery involves closure of septal defects (using patches) and reconstruction of the common AV valve into two separate valves. In some cases, valve replacement may be necessary 13 16.
• Partial Defects: Patch closure of the primum ASD and repair of the mitral valve cleft are typical. The tricuspid valve is usually normal or requires minimal intervention 14.

Timing: Surgery is preferably performed early in life, sometimes even in infancy, to prevent irreversible damage to the lungs and heart 13 14 16.

Outcomes:

• Surgical mortality has decreased substantially with modern techniques.
• Most patients have excellent long-term function, though some may experience mild residual valve regurgitation.
• Accelerated growth and improved quality of life are common after repair 14 16.

Medical Management

Prior to surgery, or when surgery is delayed, medical management includes:

• Diuretics: To reduce fluid overload
• Digoxin: To support heart function These agents are usually discontinued after successful surgery 16.

Arrhythmia Surveillance and Management

Arrhythmias may occur post-operatively, particularly in the early period. While most are transient, some patients may require pacemaker implantation, especially if heart block develops 14.

Reoperation and Long-Term Follow-Up

Valve regurgitation, especially of the mitral valve, is a common long-term complication. Some patients may require reoperation or valve replacement years after initial repair. The need is closely correlated with the degree of preoperative valve dysfunction 14 15.

• Long-Term Outlook: Most survivors maintain good heart function and quality of life. Regular follow-up is essential to monitor for late complications such as arrhythmias or valve problems 14 16.

Conclusion

Endocardial cushion defect is a complex congenital heart condition with a wide spectrum of anatomical and clinical presentations. Early recognition, accurate diagnosis, and timely surgical intervention are critical for favorable outcomes. Ongoing research continues to unravel the genetic and molecular basis of these defects, promising even better management in the future.

Key takeaways:

• ECD manifests with heart murmurs, heart failure symptoms, poor growth, and recurrent infections.
• The defect exists in complete, partial, and intermediate forms, often associated with other heart anomalies.
• Genetic mutations (GATA4, SMAD4, Tbx20, Connexin45, ALK2) and failed embryonic cushion fusion are central to its development.
• Surgical repair is highly effective, though long-term monitoring for valve complications and arrhythmias remains essential.

Advances in understanding and treating endocardial cushion defects have transformed the outlook for affected children, offering hope for healthy, active lives.