Chapter 420 Acyanotic Congenital Heart Disease

The Left-to-Right Shunt Lesions

420.1 Atrial Septal Defect

Atrial septal defects (ASDs) can occur in any portion of the atrial septum (secundum, primum, or sinus venosus), depending on which embryonic septal structure has failed to develop normally (Chapter 414). Less commonly, the atrial septum may be nearly absent, with the creation of a functional single atrium. Isolated secundum ASDs account for ≈7% of congenital heart defects. The majority of cases of ASD are sporadic; autosomal dominant inheritance does occur as part of the Holt-Oram syndrome (hypoplastic or absent radii, 1st-degree heart block, ASD) or in families with secundum ASD and heart block.

An isolated valve-incompetent patent foramen ovale (PFO) is a common echocardiographic finding during infancy. It is usually of no hemodynamic significance and is not considered an ASD; a PFO may play an important role if other structural heart defects are present. If another cardiac anomaly is causing increased right atrial pressure (pulmonary stenosis or atresia, tricuspid valve abnormalities, right ventricular dysfunction), venous blood may shunt across the PFO into the left atrium with resultant cyanosis. Because of the anatomic structure of the PFO, left-to-right shunting is unusual outside the immediate newborn period. In the presence of a large volume load or a hypertensive left atrium (secondary to mitral stenosis), the foramen ovale may be sufficiently dilated to result in a significant atrial left-to-right shunt. A valve-competent but probe-patent foramen ovale may be present in 15-30% of adults. An isolated PFO does not require surgical treatment, although it may be a risk for paradoxical (right to left) systemic embolization. Device closure of these defects has been considered in young adults with a history of thromboembolic stroke.

Bibliography

Beda RD, Gill EAJr. Patent foramen ovale: does it play a role in the pathophysiology of migraine headache? Cardiol Clin. 2005;23:91-96.

Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest. 1999;104:1567-1573.

Jategaonkar S, Scholtz W, Schmidt H, et al. Percutaneous closure of atrial septal defects: echocardiographic and functional results in patients older than 60 years. Circ Cardiovasc Interv. 2009;2:85-89.

Kharouf R, Luxenberg DM, Khalid O, et al. Atrial septal defect: spectrum of care. Pediatr Cardiol. 2008;29:271-280.

Masura J, Gavora P, Podnar T. Long-term outcome of transcatheter secundum-type atrial septal defect closure using Amplatzer septal occluders. J Am Coll Cardiol. 2005;45:505-507.

Radzik D, Davignon A, van Doesburg N, et al. Predictive factors for spontaneous closure of atrial septal defects diagnosed in the first 3 months of life. J Am Coll Cardiol. 1993;22:851-853.

Riggs T, Sharp SE, Batton D, et al. Spontaneous closure of atrial septal defects in premature vs full term neonates. Pediatr Cardiol. 2000;21:129-134.

Swartz EN. Is transcatheter device occlusion as good as open heart surgery for closure of atrial septal defects? Arch Dis Child. 2004;89:687-688.

Yew G, Wilson NJ. Transcatheter atrial septal defect closure with the Amplatzer septal occluder: five-year follow-up. Catheter Cardiovasc Interv. 2005;64:193-196.

420.2 Ostium Secundum Defect

Daniel Bernstein

An ostium secundum defect in the region of the fossa ovalis is the most common form of ASD and is associated with structurally normal atrioventricular (AV) valves. Mitral valve prolapse has been described in association with this defect but is rarely an important clinical consideration. Secundum ASDs may be single or multiple (fenestrated atrial septum), and openings ≥2 cm in diameter are common in symptomatic older children. Large defects may extend inferiorly toward the inferior vena cava and ostium of the coronary sinus, superiorly toward the superior vena cava, or posteriorly. Females outnumber males 3 : 1 in incidence. Partial anomalous pulmonary venous return, most commonly of the right upper pulmonary vein, may be an associated lesion.

Pathophysiology

The degree of left-to-right shunting is dependent on the size of the defect, the relative compliance of the right and left ventricles, and the relative vascular resistance in the pulmonary and systemic circulations. In large defects, a considerable shunt of oxygenated blood flows from the left to the right atrium (Fig. 420-1). This blood is added to the usual venous return to the right atrium and is pumped by the right ventricle to the lungs. With large defects, the ratio of pulmonary to systemic blood flow (Qp : Qs) is usually between 2 : 1 and 4 : 1. The paucity of symptoms in infants with ASDs is related to the structure of the right ventricle in early life when its muscular wall is thick and less compliant, thus limiting the left-to-right shunt. As the infant becomes older and pulmonary vascular resistance drops, the right ventricular wall becomes thinner and the left-to-right shunt across the ASD increases. The increased blood flow through the right side of the heart results in enlargement of the right atrium and ventricle and dilatation of the pulmonary artery. The left atrium may also be enlarged, but the left ventricle and aorta are normal in size. Despite the large pulmonary blood flow, pulmonary arterial pressure is usually normal because of the absence of a high-pressure communication between the pulmonary and systemic circulations. Pulmonary vascular resistance remains low throughout childhood, although it may begin to increase in adulthood and may eventually result in reversal of the shunt and clinical cyanosis.

Figure 420-1 Physiology of atrial septal defect (ASD). Circled numbers represent oxygen saturation values. The numbers next to the arrows represent volumes of blood flow (in L/min/m²). This illustration shows a hypothetical patient with a pulmonary-to-systemic blood flow ratio (Qp : Qs) of 2 : 1. Desaturated blood enters the right atrium from the vena cavae at a volume of 3 L/min/m² and mixes with an additional 3 L of fully saturated blood shunting left to right across the ASD; the result is an increase in oxygen saturation in the right atrium. Six liters of blood flows through the tricuspid valve and causes a mid-diastolic flow rumble. Oxygen saturation may be slightly higher in the right ventricle because of incomplete mixing at the atrial level. The full 6 L flows across the right ventricular outflow tract and causes a systolic ejection flow murmur. Six liters returns to the left atrium, with 3 L shunting left to right across the defect and 3 L crossing the mitral valve to be ejected by the left ventricle into the ascending aorta (normal cardiac output).

Clinical Manifestations

A child with an ostium secundum ASD is most often asymptomatic; the lesion is often discovered inadvertently during physical examination. Even an extremely large secundum ASD rarely produces clinically evident heart failure in childhood. However, on closer evaluation, in younger children, subtle failure to thrive may be present; in older children, varying degrees of exercise intolerance may be noted. Often, the degree of limitation may go unnoticed by the family until after surgical repair, when the child’s growth or activity level increases markedly.

The physical findings of an ASD are usually characteristic but fairly subtle and require careful examination of the heart, with special attention to the heart sounds. Examination of the chest may reveal a mild left precordial bulge. A right ventricular systolic lift may be palpable at the left sternal border. Sometimes a pulmonic ejection click can be heard. In most patients with an ASD, the characteristic finding is that the 2nd heart sound is widely split and fixed in its splitting during all phases of respiration. Normally, the duration of right ventricular ejection varies with respiration, with inspiration increasing right ventricular volume and delaying closure of the pulmonary valve. With an ASD, right ventricular diastolic volume is constantly increased and the ejection time is prolonged throughout all phases of respiration. A systolic ejection murmur is heard; it is medium pitched, without harsh qualities, seldom accompanied by a thrill, and best heard at the left middle and upper sternal border. It is produced by the increased flow across the right ventricular outflow tract into the pulmonary artery, not by low-pressure flow across the ASD. A short, rumbling mid-diastolic murmur produced by the increased volume of blood flow across the tricuspid valve is often audible at the lower left sternal border. This finding, which may be subtle and is heard best with the bell of the stethoscope, usually indicates a Qp : Qs ratio of at least 2 : 1.

Diagnosis

The chest roentgenogram shows varying degrees of enlargement of the right ventricle and atrium, depending on the size of the shunt. The pulmonary artery is enlarged, and pulmonary vascularity is increased. These signs vary and may not be conspicuous in mild cases. Cardiac enlargement is often best appreciated on the lateral view because the right ventricle protrudes anteriorly as its volume increases. The electrocardiogram shows volume overload of the right ventricle; the QRS axis may be normal or exhibit right axis deviation, and a minor right ventricular conduction delay (rsR′ pattern in the right precordial leads) may be present.

The echocardiogram shows findings characteristic of right ventricular volume overload, including an increased right ventricular end-diastolic dimension and flattening and abnormal motion of the ventricular septum (Fig. 420-2). A normal septum moves posteriorly during systole and anteriorly during diastole. With right ventricular overload and normal pulmonary vascular resistance, septal motion is either flattened or reversed—that is, anterior movement in systole. The location and size of the atrial defect are readily appreciated by two-dimensional scanning, with a characteristic brightening of the echo image seen at the edge of the defect (T-artifact). The shunt is confirmed by pulsed and color flow Doppler. The normal entry of all pulmonary veins into the left atrium should be confirmed.

Figure 420-2 Echocardiographic findings in a secundum atrial septal defect (ASD). A, 2-D echocardiogram (apical four-chamber view) shows a moderate-sized secundum ASD (arrow). B, Color flow Doppler imaging shows left-to-right shunting (the red color represents blood moving toward the ultrasound transducer and does not indicate the level of oxygenation of the blood). LA, left atrium; RA, right atrium; RV, right ventricle.

Patients with the classic features of a hemodynamically significant ASD on physical examination and chest radiography, in whom echocardiographic identification of an isolated secundum ASD is made, need undergo diagnostic catheterization before repair, with the exception of an older patient, in whom pulmonary vascular resistance may be a concern. If pulmonary vascular disease is suspected, cardiac catheterization confirms the presence of the defect and allows measurement of the shunt ratio and pulmonary pressure and resistance.

If catheterization is performed, the oxygen content of blood from the right atrium will be much higher than that from the superior vena cava. This feature is not specifically diagnostic because it may occur with partial anomalous pulmonary venous return to the right atrium, with a ventricular septal defect (VSD) in the presence of tricuspid insufficiency, with AV septal defects associated with left ventricular to right atrial shunts, and with aorta to right atrial communications (ruptured sinus of Valsalva aneurysm). Pressure in the right side of the heart is usually normal, but small to moderate pressure gradients (<25 mm Hg) may be measured across the right ventricular outflow tract because of functional stenosis related to excessive blood flow. In children and adolescents, the pulmonary vascular resistance is almost always normal. The shunt is variable and depends on the size of the defect, but it may be of considerable volume (as high as 20 L/min/m²). Cineangiography, performed with the catheter through the defect and in the right upper pulmonary vein, demonstrates the defect and the location of the right upper pulmonary venous drainage. Alternatively, pulmonary angiography demonstrates the defect on the levophase (return of contrast to the left side of the heart after passing through the lungs).

Complications

Secundum ASDs are usually isolated, although they may be associated with partial anomalous pulmonary venous return, pulmonary valvular stenosis, VSD, pulmonary artery branch stenosis, and persistent left superior vena cava, as well as mitral valve prolapse and insufficiency. Secundum ASDs are associated with the autosomal dominant Holt-Oram syndrome. The gene responsible for this syndrome, situated in the region 12q21-q22 of chromosome 12, is TBX5, a member of the T-box transcriptional family. A familial form of secundum ASD associated with AV conduction delay has been linked to mutations in another transcription factor, Nkx2.5. Patients with familial ASD without heart block may carry a mutation in the transcription factor GATA4, located on chromosome 8p22-23.

Treatment

Surgical or transcatheter device closure is advised for all symptomatic patients and also for asymptomatic patients with a Qp : Qs ratio of at least 2 : 1 or those with right ventricular enlargement. The timing for elective closure is usually after the 1st yr and before entry into school. Closure carried out at open heart surgery is associated with a mortality rate of <1%. Repair is preferred during early childhood because surgical mortality and morbidity are significantly greater in adulthood; the long-term risk of arrhythmia is also greater after ASD repair in adults. For most patients, the procedure of choice is percutaneous catheter device closure using an atrial septal occlusion device, implanted transvenously in the cardiac catheterization laboratory (Fig. 420-3). The results are excellent and patients are discharged the following day. With the latest generation of devices, the incidence of serious complications such as device erosion is 0.1% and can be decreased by identifying high-risk patients such as those with a deficient rim of septum around the device. Echocardiography can usually determine whether a patient is a good candidate for device closure. In patients with small secundum ASDs and minimal left-to-right shunts without right ventricular enlargement, the consensus is that closure is not required. It is unclear at present whether the persistence of a small ASD into adulthood increases the risk for stroke enough to warrant prophylactic closure of all these defects.

Figure 420-3 Intravascular ultrasound imaging of transcatheter occlusion of an atrial septal defect. A, A catheter (small arrow) has been advanced across the atrial defect, and the left-sided disk of the device (large arrow) has been extruded from the sheath into the left atrium (LA). B, The right atrial disk (arrow) has now been extruded into the right atrium (RA). The two halves of the device are then locked together and the catheter detached from the occluder device and removed.

Prognosis

Small- to moderate-sized ASDs detected in term infants may close spontaneously. Secundum ASDs are well tolerated during childhood, and symptoms do not usually appear until the 3rd decade or later. Pulmonary hypertension, atrial dysrhythmias, tricuspid or mitral insufficiency, and heart failure are late manifestations; these symptoms may initially appear during the increased volume load of pregnancy. Infective endocarditis is extremely rare, and antibiotic prophylaxis for isolated secundum ASDs is not recommended.

The results after surgical or device closure in children with moderate to large shunts are excellent. Symptoms disappear rapidly, and growth is frequently enhanced. Heart size decreases to normal, and the electrocardiogram shows decreased right ventricular forces. Late right heart failure and arrhythmias are less frequent in patients who have had early surgical repair, becoming more common in patients who undergo surgery after 20 yr of age. Although early and midterm results with device closure are excellent, the long-term effects are not yet known. Reports of resolution of migraine headaches in patients after device closure of ASD or PFO are intriguing, suggesting a possible thromboembolic etiology; there are also paradoxical reports of patients whose migraines began or worsened after placement of one of these devices.

420.3 Sinus Venosus Atrial Septal Defect

Daniel Bernstein

A sinus venosus ASD is situated in the upper part of the atrial septum in close relation to the entry of the superior vena cava. Often, one or more pulmonary veins (usually from the right lung) drain anomalously into the superior vena cava. The superior vena cava sometimes straddles the defect; in this case, some systemic venous blood enters the left atrium, but only rarely does it cause clinically evident cyanosis. The hemodynamic disturbance, clinical picture, electrocardiogram, and roentgenogram are similar to those seen in secundum ASD. The diagnosis can usually be made by two-dimensional echocardiography. If there are questions regarding pulmonary venous drainage, cardiac CT or MRI is usually diagnostic. Cardiac catheterization is rarely required, with the exception being in adult patients where assessment of pulmonary vascular resistance may be important. Anatomic correction generally requires the insertion of a patch to close the defect while incorporating the entry of anomalous veins into the left atrium. If the anomalous vein drains high in the superior vena cava, the vein can be left intact and the ASD closed to incorporate the mouth of the superior vena cava into the left atrium. The superior vena cava proximal to the venous entrance is then detached and anastomosed directly to the right atrium. This procedure avoids direct suturing of the pulmonary vein with less chance of future stenosis. Surgical results are generally excellent. Rarely, sinus venosus defects involve the inferior vena cava.

420.4 Partial Anomalous Pulmonary Venous Return

Daniel Bernstein

One or several pulmonary veins may return anomalously to the superior or inferior vena cava, the right atrium, or the coronary sinus and produce a left-to-right shunt of oxygenated blood. Partial anomalous pulmonary venous return usually involves some or all of the veins from only one lung, more often the right one. When an associated ASD is present, it is generally of the sinus venosus type, although can be of the secundum type (Chapter 420.3). When an ASD is detected by echocardiography, one must always search for associated partial anomalous pulmonary venous return. The history, physical signs, and electrocardiographic and roentgenographic findings are indistinguishable from those of an isolated ostium secundum ASD. Occasionally, an anomalous vein draining into the inferior vena cava is visible on chest radiography as a crescentic shadow of vascular density along the right border of the cardiac silhouette (scimitar syndrome); in these cases, an ASD is not usually present, but pulmonary sequestration and anomalous arterial supply to that lobe are common findings. Total anomalous pulmonary venous return is a cyanotic lesion and is discussed in Chapter 425.7. Echocardiography generally confirms the diagnosis. MRI and CT are also useful if there is a question regarding pulmonary venous drainage or in cases of scimitar syndrome. If cardiac catheterization is performed, the presence of anomalous pulmonary veins is demonstrated by selective pulmonary arteriography and anomalous pulmonary arterial supply to the right lung is demonstrated by descending aortography.

The prognosis is excellent, similar to that for ostium secundum ASDs. When a large left-to-right shunt is present, surgical repair is performed. The associated ASD should be closed in such a way that pulmonary venous return is directed to the left atrium. A single anomalous pulmonary vein without an atrial communication may be difficult to redirect to the left atrium; if the shunt is small, it may be left unoperated.

420.5 Atrioventricular Septal Defects (Ostium Primum and Atrioventricular Canal or Endocardial Cushion Defects)

Daniel Bernstein

The abnormalities encompassed by AV septal defects are grouped together because they represent a spectrum of a basic embryologic abnormality, a deficiency of the AV septum. An ostium primum defect is situated in the lower portion of the atrial septum and overlies the mitral and tricuspid valves. In most instances, a cleft in the anterior leaflet of the mitral valve is also noted. The tricuspid valve is usually functionally normal, although some anatomic abnormality of the septal leaflet is generally present. The ventricular septum is intact.

An AV septal defect, also known as an AV canal defect or an endocardial cushion defect, consists of contiguous atrial and ventricular septal defects with markedly abnormal AV valves. The severity of the valve abnormalities varies considerably; in the complete form of AV septal defect, a single AV valve is common to both ventricles and consists of an anterior and a posterior bridging leaflet related to the ventricular septum, with a lateral leaflet in each ventricle. The lesion is common in children with Down syndrome.

Transitional varieties of these defects also occur and include ostium primum defects with clefts in the anterior mitral and septal tricuspid valve leaflets and small ventricular septal defects, and, less commonly, ostium primum defects with normal AV valves. In some patients, the atrial septum is intact, but an inlet VSD is similar to that found in the full AV septal defect. Sometimes AV septal defects are associated with varying degrees of hypoplasia of one of the ventricles, known as either left- or right-dominant AVSD. If the affected ventricular chamber is too small to establish a two ventricle circulation, then surgical palliation, aiming for an eventual Fontan procedure, is performed (Chapters 424.4 and 425.10).

Pathophysiology

The basic abnormality in patients with ostium primum defects is the combination of a left-to-right shunt across the atrial defect and mitral (or occasionally tricuspid) insufficiency. The shunt is usually moderate to large, the degree of mitral insufficiency is generally mild to moderate, and pulmonary arterial pressure is typically normal or only mildly increased. The physiology of this lesion is therefore similar to that of an ostium secundum ASD.

In complete AV septal defects, the left-to-right shunt occurs at both the atrial and ventricular levels (Fig. 420-4). Additional shunting may occur directly from the left ventricle to the right atrium because of absence of the AV septum. Pulmonary hypertension and an early tendency to increase pulmonary vascular resistance are common. AV valvular insufficiency increases the volume load on one or both ventricles. If the defect is large enough, some right-to-left shunting may also occur at both the atrial and ventricular levels and lead to mild arterial desaturation. With time, progressive pulmonary vascular disease increases the right-to-left shunt so that clinical cyanosis develops (Eisenmenger physiology, Chapter 427.2).