We define an atrial septal defect (ASD) as a deficiency of any size in the atrial septum (Fig. 64-1). Although briefly mentioned in this chapter, we will not include among ASDs the patent foramen ovale (PFO); this flap-valve is bordered superiorly by the upper limbic tissue and inferiorly by the valve of the fossa ovalis, which opens only in specific circumstances, as during coughing or the Valsalva maneuver. The ostium primum (OP) defect is part of the spectrum of atrioventricular septal defects (AVSDs) and is discussed in detail in Chapter 66.

A partial anomalous pulmonary venous connection (PAPVC) is a condition presenting with variable anatomic patterns in which some but not all pulmonary venous flow lacks drainage into the left atrium (LA). This condition, characterized therefore by one or more pulmonary veins functionally draining into the right atrium (RA), may or may not be associated with an ASD. Similar considerations apply to scimitar syndrome (SS).

In this chapter, we will discuss clinical and surgical aspects that pertain to these malformations (ASD, PAPVC, and SS) and, eventually, briefly focus on current nonsurgical alternatives for ASD closure.

Following the successes of surgical closed heart procedures in the 1940s, surgeons focused their attention, mainly because of its relative simplicity, on the correction of ASDs.

This pathologic condition was described as a “perforating channel in the atrial septum” by Leonardo da Vinci in 1513,¹ but it was only in the mid-1930s that the first antemortem diagnosis was made by Roesler, in his report on 62 cases of ASD found at autopsy.² It was only between the late 1940s and early 1950s that, with the introduction of cardiac catheterization, a definite diagnosis became possible.

On account of the brief temporal mismatch between the possibility of safely diagnosing the condition during life and the feasibility of treating it surgically, three eras in the surgical treatment of the ASD can be identified: the closed-heart era, the semi-open era, and the open-heart era.

Murray was the first surgeon to report, in 1948, the closure of an ASD in a 12-year-old boy, using the external suturing technique.³ The patient survived, but success was subtotal owing to a residual shunt, later discovered on cardiac catheterization. In the early 1950s, various closed methods were investigated, including the intussusception technique of Santy,⁴ the invagination technique of Swan,⁵ the digital palpation closed technique proposed by Bailey,⁶ and the Sondergaard circumclusion technique.⁷ All these attempts led to unacceptable mortality and a high incidence of morbidity such as atrial distortion, coronary sinus (CoS) stenosis, and the persistence of significant residual defects.

In 1953, Robert Gross utilized a semi-open technique that entailed the introduction of a cone within the atrium, allowing for closure of the defect without direct vision in the depth of a blood-filled well.⁸ The cone was sutured to the atrial wall, and an atriotomy could be performed under hydrostatic pressure averting the possibility of air embolization. John Kirklin reported a series of 29 patients corrected with this technique at Mayo Clinic without operative mortality.⁹

The experiments of a short period of inflow occlusion under surface hypothermia gave way to the era of open-heart correction. Inspired by the laboratory work of Wilfred Bigelow, John Lewis at the University of Minnesota first reported successful closure of an ASD under direct vision in a 5-year-old girl.¹⁰ Shortly thereafter, closure was accomplished with cross-circulation by C. Walton Lillehei.

With the construction of the first heart-lung machine, John Gibbon ushered the current era of open-heart surgery in the treatment of ASDs.¹¹

In 1858, Peacock described for the first time the anatomic findings of a sinus venosus defect (SVD) in a 6-year-old girl who died of scarlet fever.¹² After initial approaches to PAPVC with palliative and closed techniques, Kirklin and colleagues first reported successful outcomes with open correction of various types of PAPVC.¹³

The cardiac tube is formed by an inner layer of endocardium, separated from the external myocardium by an extracellular matrix, known as cardiac jelly.¹⁴ At the fifth week of embryonic life, the primary septum (septum primum) appears as a partition, of mesenchymal origin, in the dome of the common atrium. With further development, it occupies more space and, at the same time, incorporates two segments of mesenchymal origin that are also concomitantly forming: the endocardial cushions of the atrioventricular canal and the vestibular spine (spina vestibuli), which originate from the dorsal mesocardium and are situated between the endocardial cushions and the anteriorly and inferiorly located septum primum. In this early phase, the space between the septum primum and the endocardial cushions is called ostium primum. It has not yet been established whether the development of the septum primum consists in growth from the roof of the common atrium toward the inferiorly displaced endocardial cushions¹⁵ or if, as stated by Van Praagh and apparently in contrast to mainstream embryology, in an upward growth, starting from the inferior vena cava (IVC, the left wall of which is in direct continuity with the septum primum) toward the roof of the common atrium.

Before complete fusion of all mesenchymal segments of the interatrial septum, the superior part of the primary septum is reabsorbed, forming multiple fenestrations that converge into a single defect known as the ostium secundum (OS).

From the dorsal aspect of the common atrium emerges to follow an infolding of the atrial wall (septum secundum) which will be directed toward (but on the right side of) the septum primum. The plane of growth of the two septa is not identical and may thus overlap for a variable extent (Fig. 64-2). The conformation of the septum resembles that of a flap valve, in which a superoinferior plane as well as a lateral plane of growth may be identified. The development of this structure allows for half of the oxygenated placental blood to cross the interatrial communication. The septum primum becomes involved in this process, leaving vestigial remnants in the segments located in proximity of the endocardial cushions. This vestigial part, which is not overlapped by the more superior septum secundum, is the floor of the fossa ovalis. The upper edge of the flap valve does not fuse with it, but simply overlaps. With postnatal changes in heart chamber pressures, the superior edge of the fossa ovalis fuses completely (in approximately 60 percent of cases) with the lower edge of the septum secundum. Fusion is otherwise incomplete and a communication between the atria persists as a PFO.

Development of the muscular septum primum and the ventral proliferation of extracardiac mesenchyme from the dorsal mesocardium aligns the common pulmonary vein (CPV) which, once incorporated into the posterior aspect of the left-sided atrium, eventually differentiates into left and right pulmonary veins. The sinus venosus (SV) segment is that part of the atrium which, in postnatal life, will be responsible for draining systemic and coronary return as well as for the development of the smooth venous tissue between the venous ostia. The connection of the sinus with the atrial segment after the primary tube is formed is represented by the sinoatrial orifice, which, forced by the predominant development of the right-sided sinus, migrates from its midline position toward the right. The sinoatrial orifice is surrounded by venous valves on the right and left sides. Once incorporated into the dorsal aspect of the right-sided atrium, the development of the sinus segment pushes the right side of the venous valve toward a ventral line and crosses two bands that are developing perpendicular to it: the superior and the inferior limbic bands. These bands develop underneath the endocardium at the periphery of the fossa ovalis. The superior band, from the upper edge of the fossa ovalis (superior limbus of the fossa ovalis) crosses the venous valve between superior and inferior caval orifices; the inferior band (inferior limbus of the fossa ovalis), crosses the venous valve between the IVC and the CoS orifices and, eventually, forms the base of the sinus septum.

The incomplete development of the septum primum results in a defect within the fossa ovalis (Fig. 64-3). This process may be related to different mechanisms, such as incomplete overlapping of the superior limbus of the fossa ovalis (patent foramen ovale); redundancy of the foraminal valve (aneurysm of the atrial septum); partial or total breakdown of the septum primum, resulting in a single perforation of the septum primum (OS defect); or in multiple fenestrations.

As previously mentioned, after maturation of the septum primum, the infolding of the dorsal common atrial cavity positions the CPV in its definitive location behind the LA. Hence, various theories have been advanced to explain the development of PAPVC. Hartley¹⁶ suggested that the incomplete migration of the sinoatrial orifice from the midline, was the main cause of the development of a superior vena cava (SVC) medially, with displacement of the septum primum toward the septum secundum and subsequent underdevelopment of the latter. This theory would indeed account for the overriding of the SVC typically observed in the superior caval ASD but not for the high prevalence of PAPVC associated with it. An elegant echocardiographic study on SVDs from Children’s Hospital Boston has shown that the deficiency in the wall that normally separates the right pulmonary veins or SVC and the RA is the leading cause of this particular defect.¹⁷ Depending on the structures involved in this anomalous process, different subsets of ASDs (with one or more right pulmonary veins overriding the septum secundum) will occur.

Finally, a CoS defect may be due to a deficiency in the remnant of the left horn of the SV, which extends along the entire length of the CoS to reach its orifice. This defect is generally found in association with persistence of a left SVC.

Advances in genetic analysis and molecular biology have striven to investigate the embryonic mechanisms of cardiac looping, chamber development, myocardial cell growth, and cardiac valve formation. At present, the origin of most of the complex genetic traits of congenital heart disease remains to be completely defined. Studies focused on chromosomal abnormalities, autosomal dominant syndromes, and genetic linkage analysis of relatives of patients presenting with minor degrees of congenital heart disease have led to the detection of only a handful of the genes responsible for the development of congenital heart malformations.

Specifically (with regard to atrial septation defects), it is known that the Holt-Oram syndrome (association of ventricular septal defect and ASD with limb abnormalities) is the product of mutation of gene TBX5 in locus 12q24. Several investigations have revealed a heterozygous mutation in gene NKX2.5 in locus 5q34 in families with ASDs and conduction abnormalities.¹⁴

The five more commonly occurring variants¹⁸ of defects of the interatrial septum are (1) OS defect and PFO, (2) OP defect, (3) CoS defect, (4) SV ASD and its association in the superior position with PAPVC, and (5) SS.

The OS defect is the most common of all types of interatrial communications (80 percent). This defect is confined within the borders of the fossa ovalis (Fig. 64-3) and its name is in fact almost a misnomer, since the OS defect is actually the final result of deficiency in the development of the septum primum. OS defects may differ in size and morphology, depending on the degree of reabsorption of the septum primum and on the deficiency of the flap valve of the fossa ovalis. The degree of its absence varies from partial deficiency to complete absence, when the inferior border of the septum primum becomes continuous with the posterior wall of the IVC. Surgeons must bear this anatomic peculiarity in mind in order to distinguish the inferior edge of the defect from the eustachian valve: misperception of this may result in inadvertent baffling of the IVC to the LA. A PFO is found in approximately 30 percent of normal hearts. In the absence of left-to-right shunt (and with LA pressure > RA pressure), the lack of closure of the natural flap valve may be considered not a true interatrial communication. Intermittent shunting across the PFO may occur spontaneously or during provoking maneuvers that increase RA pressure, such as coughing or the Valsalva maneuver.

Because of the direct continuity between the leftward aspect of the IVC wall and the septum primum, when the floor of the fossa ovalis is absent and an ASD extends toward the IVC, the inferior caval ostium overrides the defect onto the LA. This anatomic pattern (or inferior SV ASD) may occasionally promote right-to-left shunt with cyanosis. Moreover, the proximity of right pulmonary veins to the deficient posteroinferior rim of the ASD favors a functional hemianomalous pulmonary venous connection.

At the extreme of septal maldevelopment is the common atrium, which may be described as an association of several defects involving structures of different embryonic origin. The association of a complete lack of the septum primum and of the superior and inferior limbi has been classified by some authors as the common atrium. This lesion is generally found in atrial isomerism in association with a persistent left SVC draining into an unroofed CoS.

Defects located beneath the inferior limb of the primary septum (10 percent of all ASDs) are associated with morphologic abnormalities of the atrioventricular valves and are described in Chapter 66. Even if these are to be invariably classified as AVSD or endocardial cushion defects, the OP defect has been reported in hearts with no evidence of AVSD morphology.¹⁹

The CoS defect (Fig. 64-4) results from variable fenestrations along the common wall between the CoS and the posterior aspect of the LA. It represents an infrequent type of ASD, accounting for only 1 to 2 percent of all defects of the interatrial septum. The ostium of the CoS is invariably present in its expected position along the posteroinferior margin of the triangle of Koch (see Chapter 59). This defect is generally found in association with a number of lesions, most frequently with persistence of the left SVC: these associated lesions (with the extreme form being the total absence of the CoS wall) determine the spectrum of the “unroofed coronary sinus syndrome.” A surgical classification has been proposed that categorizes CoS defects into proximal, medial, and distal according to the site of the deficiency of the CoS wall along its length.^20–22

The superior SVD (SV ASD) is associated with PAPVC in 5 to 10 percent of cases. This malformation (also known as superior caval ASD) is located in the posterosuperior atrial septum, cranial to the superior limbic band. The most common position for the site of drainage of the anomalous pulmonary veins is at the superior atriocaval junction (Fig. 64-5). In 95 percent of cases with PAPVC, two right pulmonary veins (upper and middle lobes) are involved, but there may be three or even four pulmonary veins connected to the proximal SVC or SVC–right atrial junction. The SVC typically overrides the atrial septum and may result in right-to-left shunting across the ASD. When this defect is associated with the lack of the posterior limbus (posterior ASD), pulmonary venous drainage is somewhat anatomically unclear, although it flows functionally into the RA. When anomalous drainage of the right pulmonary veins is found with an intact posterior limbus or OS ASD, the anatomy is clear and a true PAPVC is present.

In SS (Fig. 64-6), an anomalous right pulmonary venous trunk (generally draining the entirety of the right lung) descends in a craniocaudal direction to connect to the IVC, generally above the IVC–RA junction.²³ This anomalous trunk usually descends along the right border of the pericardium. It has a crescent-like morphology (scimitar shape) and, at the level of the right hemidiaphragm, passes transversely and anteriorly to the hilum of the right lung to connect to the IVC. The radiologic appearance of this pathology is characteristic (Fig. 64-7). The interatrial septum may be intact or an OS/PFO defect may be associated to SS. SS generally occurs in association with several extracardiac malformations, such as right lung hypoplasia (invariably associated with a marked right mediastinal shift with dextrocardia), right pulmonary artery (PA) stenosis and/or hypoplasia and right lower lobe (RLL), or bronchopulmonary sequestration. Diaphragmatic anomalies occur in approximately 20 percent of cases, and consist of right lung herniation through the foramen of Bochdalek or of abnormal attachment of the hemidiaphragm. Very occasionally, a CPV trunk drains the entire right lung and descends in a craniocaudal direction to connect with the posterior LA. This peculiar arrangement shares similar radiologic findings with SS but has no clinical significance.

The magnitude of left-to-right shunting is determined by the size of the communication and relative compliance of the ventricles. As for ventricular septal defects (VSDs), the location of the ASD has very limited influence on the magnitude of the pulmonary-to-systemic flow ratio (Q_p:Q_s).

If even a relatively small subtricuspidal shunt (because of the high-pressure gradient between the ventricles) can give rise to a large left-to-right shunt, only a large ASD leads on the contrary to a large shunt. In the presence of a large ASD with an area similar to that of the mitral valve (MV), pulmonary venous return will be equally distributed between the ASD and the MV. If the ASD is restrictive, blood flow will be diverted preferentially toward the MV, and the Q_p:Q_s will rarely exceed 2:1.¹⁸

Only in cases of associated acquired and/or congenital heart defects that increase LA pressure (as in systemic hypertension, MV stenosis, coarctation of the aorta, patent ductus arteriosus and VSD) will flow across the atrial septum be increased independently of ASD area. If a large defect is present atrial pressures will equalize. In this circumstance, the respective flows across mitral and tricuspid valves will vary according to the relative compliance of the ventricles. In the early months of life, the thickness of the right ventricle (RV) exceeds the thickness of the left (LV), resulting in right-to-left shunting. After the neonatal period, the LV exceeds in thickness the RV, yielding a net left-to-right shunt. The effect of atrial-level shunting results in enlargement of the RA, RV, and PAs. The overload is usually well tolerated by the RV, and heart failure seldom develops in childhood. Occasionally, heart failure occurs in infancy, but it is very rare and is generally related to various extracardiac conditions. In cases of ASD with pulmonary hypertension (PHT—as in rare pediatric cases and in some adult patients) RV thickness will increase and compliance of the RV may be similar and/or higher than that of the LV. In these cases, a right-to-left shunt will appear with a marked degree of cyanosis and hypoxia, with clinically evident heart failure.

The increase in pulmonary blood flow, over several years, may promote the development of PHT in adulthood. The onset of PHT is variable and, at present, it is not possible to reliably predict which patient will develop PHT and at what age. This variability may depend on the multiple factors involved in the pathogenesis of PHT: recurrent pulmonary infections with microatelectasis, progressive increase in left-to-right shunt with enlargement of the ASD, individual endothelial vascular hyperreactivity, thrombotic and thromboembolic lesions of pulmonary arteries, failure of the pulmonary vascular resistance to drop, and association with acquired heart diseases that would promote LV dysfunction (such as MV prolapse, coronary artery disease, and systemic hypertension among others).²⁴

In the presence of an interatrial communication, a potential reverse shunt at atrial level may account for paradoxical embolization in the cerebral circulation. This condition may depend on instantaneous trans-ASD gradient modifications, as well as the size, morphology, and position of the defect along the atrial septum. A large meta-analysis has indicated the presence of interatrial septal abnormalities as significantly associated to paradoxical embolism.²⁵ Furthermore, the incidence of PFO among adults suffering from cerebrovascular accidents was found to be higher than in the unaffected population. Coagulation disorders or thrombocytosis may also play a role in the pathogenesis of paradoxical embolization.

The reported incidence of isolated ASD ranges from 7 to 14 percent, with a slight female predominance. This fairly broad range is due to the inclusion criteria used in the reports over the past few decades that considered ASDs and PFOs referred to surgery as identical pathologic entities. In the setting of other congenital heart defects, their incidence ranges from 33 to 50 percent.²⁶ The wide use of echocardiography has led to the detection of ASDs of any size and at any age. Several investigators have reported the results from populations of children bearing an ASD at long-term follow-up.^27,28

The conclusions emerging from these studies may be summarized as follows:

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  ASDs less than 6 mm in diameter, detected in infancy, almost always restrict spontaneously.

  
  
• 
  

  ASDs between 6 and 8 mm in diameter, classified as hemodynamically insignificant, may restrict even after 5 years of age and not necessarily below 18 months of age, as once thought.

  
  
• 
  

  ASDs greater than 8 mm in diameter may increase in size during childhood, although a restrictive physiology is still a more common possibility.

Among all diagnosed ASDs, the reported incidence of SVDs varies between 2 and 10 percent.²⁹ This relatively high incidence may be due to diagnostic bias, the incidence of SVD being higher in studies focusing on cohorts with more “complex” ASDs.

The signs and symptoms of ASD and PAPVC are strictly related to the direction and magnitude of the shunt and with the age of the patient at detection. Q_p:Q_s is greater than 1 in predominant left-to-right shunt. When Q_p:Q_s is below 1.8:1,³⁰ clinical signs and symptoms are typically mild or absent in both pediatric and adult patients. When Q_p:Q_s exceeds 2:1, signs and symptoms often become clinically evident. In this subset of patients the classic “fixed split second heart sound” and systolic pulmonary flow murmur are typically audible. Reduced exercise capacity and a history of recurrent respiratory infections may be present in childhood as well as in adolescence. Several other conditions must be taken into consideration in the differential diagnosis, such as innocent murmur associated with a normal cardiovascular state and pulmonary valve stenosis; this is usually audible in the higher upper left sternal border, presents with an early systolic ejection sound, and, in cases of stenosis of the PA branches, is transmitted toward the back. In these conditions, however, splitting of the second heart sound is absent.