Your Family Physician

Introduction

Background

Congenital heart defects are common in children, with an incidence of approximately 8 cases per 1000 live births. These defects cause an array of problems in the primary care of children. An understanding of human embryology is essential for diagnosing these abnormalities and in planning long-term treatment.

Pathophysiology

Cardiac tissues are first detectable on the 18th or 19th day of fetal life. Cardiac development continues for the next several weeks. The atrial septum begins to form during the fourth week of gestation and is complete by the end of 5 weeks' gestation.

Classic model of cardiac development

According to the classic model of cardiac development, the process begins when a thin crescent-shaped membrane (septum primum) begins to form along the dorsal and cranial walls of the atrium. The space between the septum primum and the endocardial cushions (ostium primum) becomes progressively smaller as the septum primum grows toward the endocardial cushions. Before the ostium primum completely closes, small perforations develop in the anterosuperior wall of septum primum and ultimately coalesce to form a second interatrial communication, the ostium secundum. Meanwhile, the leading edge of the septum primum fuses with the endocardial cushions, and the ostium primum disappears.

Near the end of 5 weeks' gestation, the second phase of the process begins when a second crescent-shaped membrane (septum secundum) begins to form within the atrium to the right of the first septum. This membrane also begins to grow toward the endocardial cushions, covering the ostium secundum. However, the septum secundum remains incomplete. The foramen ovale is the opening remaining after the septum secundum completely forms.

The final phase of the process begins when the upper portion of the septum secundum proceeds to degenerate and finally disappears. The fully formed atria now have 2 overlapping but incomplete septae. The upper portion of the septum secundum covers the ostium secundum and creates a one-way valve allowing right-to-left shunting of blood in the fetus.

Van Praagh and Corsini model of cardiac development

Van Praagh and Corsini proposed another model of cardiac development.¹ According to their model, the septum primum (also known as the flap valve of the foramen ovale) grows from the portion of the left venous valve of the sinus venosus that is furthest left. As it extends from the most dorsal aspect of the atrium, the septum primum begins to meet the septum secundum, which is an invagination of the most rostral portion of the primitive atrium. The marginal edges of the septum primum eventually meet the left aspect of the septum secundum.

During embryonic and fetal life, the central portion of the septum primum billows into the left atrium due to the normal right to left shunting at the atrial level. After birth, the remainder of the septum primum adheres to the left aspect of the septum secundum.

Recent identification of an anomaly called deviated superior attachments of septum primum provides evidence in favor of the Van Praagh and Corsini model. Additional detailed morphologic analysis of murine cardiac development is needed to determine which model is correct.

Types of atrial septal defects

Four basic types of atrial septal defects (ASDs) are known. Patients who simultaneously have the first 3 types of ASD, as described below, are said to have common atrium.

The first type is an ostium secundum defect. The most common yet least serious type of ASD is an ostium secundum defect. This defect occurs in the area of the fossa ovalis and presumably results from excessive fenestration or resorption of septum primum, underdevelopment of septum secundum, or some combination of the 2 conditions.

In approximately one half of patients with left atrioventricular (AV) valve underdevelopment (ie, hypoplastic left heart syndrome or Shone complex), the superior attachments of the flap valve of the foramen ovale lie on the left atrial roof, well to the left of the septum secundum. Weinberg et al (1986) called this anomaly "(leftward and posterior) deviation of the superior attachments of septum primum."² This deviation is observed extremely rarely in patients with a normal-sized left AV valve. Of importance, the classic model does not explain its existence well. This type can be regarded as a variation of an ostium secundum defect, although it is most rigorously designated as a malalignment-type ASD.

A second variant of the ostium secundum defect is its association with an aneurysm of the atrial septum. This is thought to be due to redundancy of the valve of the fossa ovalis. It may be associated with mitral valve prolapse or atrial arrhythmias (see Media files 1-3).

The second type is an ostium primum defect. This ASD presumably results from failure of the endocardial cushions to close the ostium primum. Because endocardial cushions also form the mitral and tricuspid valves, ostium primum defects are virtually always associated with a cleft in the anterior mitral valve leaflet (see Media files 4-6).

The third type is a sinus venosus defect. This ASD is found in the posterior aspect of the septum near the superior vena cava (where it may coexist with partial anomalous pulmonary venous connection of the right upper pulmonary vein) or the inferior vena cava (where it may coexist with partial anomalous pulmonary venous defect of the right lower pulmonary vein) (see Media file 7).

The fourth type is a coronary sinus septal defect. This least common type of ASD is called an unroofed coronary sinus or coronary sinus septal defect. A portion of the roof of the coronary sinus is missing; therefore, blood can be shunted from the left atrium into the coronary sinus and subsequently into the right atrium. This type is often associated with a left superior vena cava.

Left-to-right shunting

Clinical effects of isolated ASDs are usually related to left-to-right shunting. The magnitude of shunt is related to the size of the defect in the septum, to the relative compliance of the left-sided and right-sided cardiac chambers, and indirectly related to the resistance of the pulmonary and systemic circulations. At birth, the right and left ventricles are of equal thickness and similar compliance. In the first few days to weeks after birth, the pulmonary vascular resistance (PVR) remains mildly elevated and has not reached its nadir.

As impedance to pulmonary blood flow decreases and the right ventricle becomes more compliant, blood is able to flow to the pulmonary vascular bed more easily, and the atrial level left-to-right shunt increases.

On occasion, the septal defect is small, with little left-to-right shunting. However, most defects that cause murmurs or symptoms are moderately large to large, and the size of the defect does little to limit left-to-right shunting. Approximately 15% of ostium secundum ASDs spontaneously close by age 4 years.

Frequency

United States

Research indicates that congenital heart disease (CHD) is diagnosed in 0.8% of children in the first year of life. ASD occurs in about 1 in 1500 live births, or approximately 7% of these children with CHD. About 15-30% of healthy adults have an unfused foramen ovale in which the valve functions normally but has failed to fuse. In these individuals, a cardiac catheter passed into the right atrium can pass into the left atrium through the foramen ovale (ie, probe-patent foramen ovale).

Mortality/Morbidity

In developed countries, mortality rate of ASD is low (<1%). Morbidity secondary to ASD is unusual and typically limited to 3 groups of patients, as follows:

• Perhaps 1% of infants with moderate or large (ie, nonrestrictive) ASDs but no ductus arteriosus have tachypnea and failure to thrive. In these individuals, the pulmonary artery pressure, when measured during catheterization or Doppler echocardiography, is at or near systemic level. Attempts to exclude mitral or left ventricular diastolic abnormalities as a cause of these hemodynamics must be undertaken; however, these attempts frequently yield equivocal data.
• Patients in whom ASDs go unrecognized until late childhood may develop arrhythmias (eg, atrial fibrillation) or pulmonary hypertension. ASDs that initially appear in middle-aged or elderly adults can indicate congestive heart failure (CHF).
• Patients with ASDs may have an embolic stroke as the initial presentation.

Sex

The female-to-male ratio is approximately 2:1.

Age

ASD, a congenital abnormality, is present at birth. However, in most cases, a murmur is not audible until the child is a few months old. Symptoms usually do not occur in individuals with ASD until late childhood, adolescence, or adulthood.

• Secundum type (ie, ostium secundum), sinus venosus, and unroofed coronary sinus defects are sometimes not diagnosed until the third decade of life.
• Ostium primum ASDs are usually diagnosed in the first few years of life because of mitral regurgitation murmur or an abnormal ECG.
• A common atrium (ie, a combination of sinus venosus, ostium secundum, and ostium primum defects) is usually diagnosed in the first few years of life because systemic venous blood and pulmonary venous blood often partially mix before entering each ventricle; this condition manifests as cyanosis. In addition, a common atrium may be associated with complex CHD, and patients may present relatively early because of other intracardiac abnormalities.

Clinical

History

• Infants and young children with atrial septal defects (ASDs) are typically asymptomatic.
• Most ASDs are diagnosed after a suspicious murmur is detected during a routine health-maintenance examination.
• Even in symptomatic children with ASDs, clinical manifestations are often subtle and nonspecific. Some children with ASDs have poor weight gain, they remain somewhat small, and they may have exertional dyspnea or frequent upper respiratory tract infections.
• Relatively severe symptoms, such as arrhythmia, pulmonary artery hypertension, and pulmonary vascular obstructive disease (PVOD), are rare in children with ASDs. Some infants and young children with large defects may present with symptoms of congestive heart failure (CHF), especially if they have an associated lesion (eg, patent ductus arteriosus) or lung disease (eg, bronchopulmonary dysplasia and/or chronic lung disease).

Physical

Most children with ASDs are asymptomatic. In developed countries, the diagnosis is usually made during an evaluation of a suspicious murmur or during an evaluation of fatigue and exercise intolerance. ASDs that are not diagnosed in childhood can result in problems in adulthood.

• Upon initial evaluation, many children with ASDs appear completely healthy; however, careful physical examination often yields clues to the diagnosis.
• Patients with ASDs may have a precordial bulge, a prominent right ventricular cardiac impulse, and palpable pulmonary artery pulsations. All of these are signs of increased blood flow through the right side of the heart and pulmonary vascular bed.
• Upon auscultation of the individual with ASD, the first heart sound may be normal or split. The sound associated with closure of the tricuspid valve may be accentuated if blood flow across the pulmonic valve is increased and leads to a midsystolic pulmonary ejection murmur. This sound is best appreciated at the upper left sternal border and may be transmitted to the lung fields.
• Although the second heart sound may be normal in newborns with ASDs, it becomes widely split and fixed over time as pressures on the right side of the heart decrease. This fixed splitting occurs as the result of increased capacitance in the pulmonary vascular bed, leading to low pulmonary impedance and, therefore, a long hangout interval after the end of right ventricular systole. Fixed splitting of S2 is an important diagnostic finding in atrial-level shunting.
• A large shunt increases flow across the tricuspid valve, and the patient with ASD is likely to have a mid-diastolic rumble at the left sternal border.
• Mitral valve prolapse occurs with increased frequency in the presence of ASD and may be caused by compression of the left side of the heart secondary to enlargement of the right side.
  • In patients with mitral valve prolapse, an apical holosystolic or late systolic murmur often is heard radiating to the axilla.
  • A midsystolic click may be present, but this murmur can be difficult to detect in some patients with ASDs.
• Pulmonary vascular resistance (PVR) may increase through childhood, adolescence, and adulthood, resulting in PVOD. The rise in PVR and pulmonary artery pressure results in right ventricular hypertrophy, which, in turn, reduces right ventricular compliance and may subsequently reduce the degree of left-to-right shunting.
  • Upon physical examination, patients may have a prominent right ventricular impulse, but the previously noted diastolic tricuspid flow rumble and the systolic ejection murmur in the pulmonic area may be diminished.
  • The wide splitting of the second heart sound may narrow, and the pulmonic component of the second heart sound may become loud, with intensity equal to that of the aortic component.
• In all patients with common atrium, right-to-left shunting occurs, resulting in cyanosis, although this may be mild due to preferential streaming of blood across the respective atrioventricular (AV) valves.
• In adults with an unrecognized ASD, the left-to-right shunt may worsen if systemic arterial hypertension develops. The result may be left ventricular hypertrophy, reduced left ventricular compliance, and increased left-to-right shunt.

Causes

Although many cases of ASD are sporadic, ASD clearly has a genetic component and may be associated with genetic syndromes.

• Ostium secundum ASD is typically a part of the Holt-Oram syndrome, which is caused by mutations in the T-box transcription factor TBX5.³ This autosomal dominant disease also includes absent or hypoplastic radii and first-degree heart block.
• Ostium secundum, ostium primum ASD, or both may occur alone or with other lesions as part of other genetic syndromes, such as trisomy 21 (Down syndrome). For unknown reasons, sinus venosus defects are rare in Down syndrome, making common atrium similarly rare in this population.
• An autosomal dominant form of familial ASDs with incomplete penetrance has been detected.
  • Mutations in NKX2.5, a homeodomain-containing transcription factor, have been associated with ASDs with and without AV block.⁴ Additionally, mutations in GATA4, an important regulator of cardiac development, have been associated with ASDs.
  • Interactions between GATA4 and NKX2.5 and interactions between GATA4 and TBX5 may be the root of the cardiac defects seen with GATA4 mutations, which establishes a link among these genes.
  • Interestingly, a missense mutation in myosin heavy chain 6 (MHY6) has also been identified with an autosomal dominant form of ASD. MHY6 was previously described in late-onset hypertrophic cardiomyopathy. This gene is highly expressed in the developing atria and appears to be influenced by TBX5 and GATA4 mutations, again establishing a link between several genes.
  • The prognostic implications of the involvement of a sarcomeric protein with ASDs has yet to be fully elucidated. Further genetic analysis will likely yield other mutations and genetic links associated with familial ASDs.
• ASDs are found in children with fetal alcohol syndrome.

Source : http://emedicine.medscape.com/article/889394-overview