Interatrial Communications

Pentalogy of Fallot

Pentalogy of Fallot means tetralogy of Fallot (TOF) with a secundum type of ASD. Pentalogy means that five anomalies are present ( pente , five, Greek), the four anomalies of the tetralogy of Fallot (pulmonary outflow tract obstruction [stenosis or atresia], subaortic VSD, overriding aorta, and right ventricular hypertrophy) plus an ASD II. Although found in the older literature, this diagnosis is not routinely used today.

How common is an ostium secundum type of ASD found in association with TOF? In an effort to answer this question, we did a study of 100 randomly selected postmortem cases from the 1980s and 1990s. An ostium secundum type of ASD was found in 35 of these 100 cases (35%). The ASD was so large as to be regarded as resulting in common atrium in 5 of these 35 patients. Thus, a very large defect (common atrium) occurred in 14% of ASD II and in 5% of the series of tetralogy patients as a whole.

To summarize, pentalogy of Fallot occurred in approximately one-third of our autopsied cases of TOF (35%).

Common Atrium

Common atrium means, as the name indicates, that a very large ASD is present—so large that the atria are in common, that is, essentially undivided. Thus, the atrial septum is largely or totally absent.

There are two main anatomic types of common atrium:

• 1.

  with a divided AV canal (see Figs. 9.4 to 9.6 ), that is, with a separate mitral and tricuspid valve, the anterior leaflet of the mitral valve often being cleft, as in the Ellis-van Creveld syndrome (chrondoectodermal dysplasia, i.e., achondroplasia with defective development of skin, hair, and teeth; polydactyly; and defect cardiac septation in about 50%, autosomal recessive inheritance); and

• 2.

  with a common AV canal, that is, with a common AV valve and an AV septal defect (see Chapter 11 ). Dr. Jesse Edwards calls this type of common atrium “the forgotten type of common AV canal,” in which there is an AV septal defect that typically is confluent with a large secundum type of ASD due to marked deficiency or absence of the components of the atrial septum. Thus, there are confluent secundum atrial and AV septal defects, resulting in a huge deficiency of cardiac septation.

Are there any other syndromes in which interatrial communications are characteristic? Yes. The heterotaxy syndrome with congenital asplenia, polysplenia, and right-sided but otherwise normally formed spleen spring to mind. Analysis of 95 postmortem cases of asplenia and 68 postmortem cases of polysplenia revealed the following findings ( Table 9.3 ):

• A PFO or an intact atrial septum was much more common in the polysplenia syndrome (22%) than in the asplenia syndrome (2%) ( p < .001) (see Table 9.3 ).

• An ASD II was somewhat more frequent with polysplenia (31%) than with asplenia (20%), but this difference was not statistically significant (see Table 9.3 ).

• An ASD I (incompletely common AV canal) was commoner with asplenia (23%) than with polysplenia (10%) ( p < .05) (see Table 9.3 ).

• Common atrium was much more frequent with asplenia (72%) than with polysplenia (32%) ( p < .001) (see Table 9.3 ).

• Overall, visceral heterotaxy with asplenia had an interatrial communication more often (97.89%) than did visceral heterotaxy with polysplenia (77.94%) ( p < .001) (see Table 9.3 ).

What about visceral heterotaxy with a normally formed but right-sided spleen? As discussed in Chapter 29 , we know too little about this least frequent heterotaxy syndrome to make any statistically supported conclusions (n = 5). The data are as follows: PFO, 1 case (20%); ASD II, 1 case (20%); and common atrium, 3 cases (60%).

Aneurysm of Septum Primum

When tricuspid atresia is associated with a PFO or a restrictive ostium secundum type of ASD, the septum primum can form a prominent aneurysm that bulges into the LA ( Fig. 9.12 ). The aneurysm of the septum primum can form a supramitral stenosing membrane, or the aneurysm can prolapse downward into the mitral canal and into the left ventricular inlet (see Fig. 9.12 ), resulting in a rare form of congenital supramitral or intramitral stenosis. The septum primum appears to bulge progressively more markedly into the LA, below the ostium secundum, that is, below the superior concave rim of septum primum that delimits the so-called ostium secundum inferiorly. In advanced cases (see Fig. 9.12 ), the septum primum resembles a suspended bird’s nest—like the nest of an oriole—that is, dangling from the anterior and posterior attachments of the septum primum to the left side of the superior limbic band of the septum. These attachments are called the anterior and posterior horns of the septum primum (see Fig. 9.12 ). The concavity of the septum primum aneurysm faces the RA and receives the thrust of right atrial systole into the concavity of the obstructive septum primum. The right atrial blood then appears to swirl upward, over the superior narrowed rim of the septum primum into the LA and then downward around the bulging convexity of the septum primum, through the obstructed mitral canal, and into the left ventricle (LV).

When there is congenital mitral atresia or severe stenosis, the septum primum can bulge in the opposite direction, into the RA. I cannot recall having seen an aneurysm of the septum primum that produced supratricuspid or intratricuspid obstruction. For reasons unknown, very impressive aneurysms of the septum primum have been associated with tricuspid atresia, as in Fig. 9.12 , rather than with mitral atresia or the hypoplastic left heart syndrome (HLHS). Time may be the critical variable. Systemic venous obstruction may be better tolerated than pulmonary venous obstruction, allowing more time for the development of a leftward bulging aneurysm with tricuspid atresia than for a rightward bulging aneurysm with mitral atresia (speculation).

However, the ostium secundum type of ASD typically is associated with underdevelopment of the septum primum, with or without fenestrations of or within the septum primum. The septum primum typically is regurgitant, not obstructive. Prenatally, the flap valve function of the septum primum may permit significant regurgitation of blood from the left heart into the right heart, resulting in underdevelopment of the left heart, that is, HLHS without mitral or aortic obstruction, with overdevelopment of the right heart. We have seen patients treated surgically for the hypoplastic left heart syndrome, when the basic diagnosis was really ASD II with significant LA-to-RA regurgitation in utero and postnatally.

This is an important clinical lesson: An ASD II can manifest as HLHS. And the left heart is relatively hypoplastic compared with the right heart. How does one diagnostically recognize this type of HLHS? There is no stenosis or atresia at any left heart level, only hypoplasia (without dysplasia). In this type of HLHS, the basic diagnosis is ASD II with significant left-to-right regurgitation (shunting).

It is the blood of the via sinistra coming from the placenta up the IVC, past the right venous valve (Eustachian and Thebesian valves) to the right, past the left venous valve and septum primum to the left, and then about 60% of the IVC’s blood stream goes over the concave top of the septum primum into the LA ( Fig. 9.13 ).

This is the via sinistra— the left road (Latin)—of the oxygenated placental venous return that normally goes from the IVC into the left heart, and normally stays in the left heart, if the septum primum (the flap valve of the foramen ovale) is normal in form and function (essentially nonregurgitant). If the blood of the via sinistra then regurgitates out of the left heart, the result can be HLHS without mitral or aortic or other dysplasia (“pure” hypoplasia).

Hence, an important question for consideration is: Why can the septum primum be underdeveloped, and/or fenestrated, or absent? What is known about the development of the septum primum?

Embryology of Septum Primum

Where do all those fenestrations, holes, and deficiency in the growth of the septum primum come from that result in the great majority of ostium secundum ASDs (see Figs. 9.2 , 9.4 to 9.9 , and 9.11 )? Is there anything known about the development of the septum primum that may make fenestrations and deficiency of the septum primum more readily understandable?

Yes indeed, there is. We were very well impressed by the Ph.D. thesis of Mary Jessica Charles Hendrix in 1977 that appears highly relevant to this question. In an electron and light microscopic study of the development of the atrial septum in the chick and in the human embryo, Hendrix found the following:

• In the chick embryo (“full term” or hatching in 21 days), at 3 days of age a common atrium is present. The beginnings of the septum primum (called the atrial septum) are present dorsally and cephalically, but without fenestrations in the septum primum ( Fig. 9.14 ).

  

• By the 4th day of incubation, fenestrations start to appear in the septum primum of the chick embryo ( Fig. 9.15 ).

  

• By the 5th day of gestation (incubation), multiple fenestrations have appeared in the septum primum of the chick embryo ( Fig. 9.16 ). If this were the heart of a postnatal human, we would certainly make the diagnosis of an ASD II due to multiple large fenestrations in septum primum.

  

• By 7 days of incubation, multiple large fenestrations are still present in the septum primum ( Fig. 9.17 ). The right venous valve is also fenestrated, forming a rete Chiari (to the right of the septum primum, unlabeled, see Fig. 9.17 ).

  

• By 9 days of incubation, the septum primum is still so fenestrated in its mid-dorsal and dorsal portions that it resembles a coarse mesh of cords that are covered with endothelium ( Fig. 9.18 ). At this stage, the chick is 43% through its gestation.

  

• By 11 days of age, 52% of the way through gestation, the cords separating the fenestrations (foramina secunda of Hendrix) are becoming noticeably thicker, and the fenestrations are getting somewhat smaller ( Fig. 9.19 ).

  

• The septum primum at 14½ days in the chick embryo is seen in Fig. 9.20 . By 18½ days of gestation (88% of the way to “full term”) the cords have become much thicker and the fenestrations are fewer and smaller ( Fig. 9.21 ).

  
  

• By the time of hatching at 21 days gestation, the septum primum is normally essentially intact, with few or no remaining fenestrations ( Fig. 9.22 ).

  

The Pathologic Anatomic Findings in 640 Human Cases of Secundum Atrial Septal Defect

In an effort to amplify our understanding of ASD II, a large study was undertaken of the records of 640 autopsied human patients from the Cardiac Registry of Children’s Hospital Boston. All of these cardiac pathology examinations, description, and diagnoses were done by the author or by Stella Van Praagh, M.D., ably assisted over the years (1966 to 1996) by numerous excellent fellows. The heart specimens date from 1950 to 1996, inclusive. This study has not been published or presented previously.

• Sex: Of these 640 patients, the sex was known in 631 (98.59%). In consultations, the patient’s sex was sometimes not stated (in 9 of 640 cases, 1.4%). In these 631 patients with ASD II, there were 335 males (53%) and 296 females (47%), and the male-to-female ratio was 1.13:1.0. Thus, in this series of secundum ASD patients as a whole, there was a mild male preponderance.

• Age at Death: In this series of 640 patients with ASD II, 1 case was excluded because happily this patient did not die. Case number 637 (S94-2327) was a 10-year-old girl who had a Clamshell Septal Occluder Device that was explanted because of disarticulation and fracture of one right atrial arm of the device and a large right atrial thrombus associated with the right atrial umbrella. A 4-mm piece of metal was found to be sticking out of the right atrial umbrella. Also the left atrial umbrella had one unextended arm opposite the broken right atrial arm. The Clamshell device and the right atrial thrombus were removed uneventfully surgically and the secundum ASD was closed with a pericardial patch.

Of the 639 patients with secundum ASD who died, the age at death was known in 619 (97%). The mean age at death was 3.17 years. The standard deviation was ± 8.04 years. The age at death ranged from 65 years to 0 (stillbirths or fetal demises). The median age at death was 4 weeks and 5½ days, that is, 4.78 weeks, which may be rounded off to 5 weeks of age.

The median age at death (5 weeks of age) reflects much more accurately than does the mean age at death (3 years and 2.4 months of age) what really happened to these 619 patients with ASD II. The very young median age at death accurately indicates that these patients almost always had additional, more severe forms of congenital heart disease, as will be seen.

When Secundum Atrial Septal Defect II Was the Most Important Clinical Problem

• Sex: Male, 3 of 13 (23%); female, 10 (77%). The sex ratio was male-to-female = 3:10 (.3), or female-to-male = 10:3 (3.3/1.0). Hence, when ASD II was the main clinical problem, the expected female preponderance was found.

• Age at Death: Of the 12 deceased patients (the Clamshell case, patient 637, did not die), the mean age at death was 25.39 years. The standard deviation was ± 18.14 years. The range was from 0.625 years (7½ months) to 65 years. The median age at death was 24.75 years.

These statistics concerning the age at death are very much older than those found for the series as a whole (see earlier), indicating that when a secundum ASD is the patient’s main clinical problem, fatalities almost always occur in the young adult age group, not in the pediatric age range. This observation appears to explain why there are so few patients in our postmortem series in whom ASD II was the patient’s primary clinical problem. Thus, secundum ASD is a “sleeper.” It must be diagnosed accurately and treated effectively early in life, in order to avoid death in young adulthood.

• Salient Features: All 13 of these patients had isolated ASD II; that is, no other form of clinically significant congenital heart disease was present.

The ASD was large in 12 of 13 patients (92%) ( Fig. 9.23 ). In one case, this assessment could not be made because the ASD had been surgically closed with direct sutures. Typically, the ASD was described as large, very large, or huge, with marked deficiency of the septum primum, resulting in a common atrium or almost a common atrium.

Death occurred postoperatively in 7 of these 13 patients (54%), early in our experience. We have not seen at autopsy a patient from our institution in whom ASD II was the primary clinical problem for the past 22 years, not since 1983.

However, we had one consultation in 1992 concerning a patient from another hospital (Case 579, C92-165). This patient was a 15 3/12-year-old young woman who had a very large ASD II. At 2 3/12 years, she underwent pericardial patch closure of her atrial defect. Postoperatively, she had sick sinus syndrome. At 10 9/12 years of age she received a pacemaker. Subsequently, she developed atrial fibrillation that spontaneously converted to normal sinus rhythm. Sudden unexpected death occurred 13 years postoperatively, in what appeared to be an arrhythmic demise. This case emphasizes the great importance of avoiding injury to the sinoatrial (SA) node and the SA nodal artery during atriotomy and atrial repair. Knowing exactly where these structures are located and taking care to avoid them (see Chapter 2 ) should make it possible to avoid sick sinus syndrome and its sequelae.

Pulmonary vascular obstructive disease (PVO) was very prominent in 4 of these patients. Right-to-left atrial shunting, polycythemia, cyanosis, clubbing, systemic embolization, stroke, and brain abscess all occurred.

Right-to-left shunting at any cardiac level (atrial, ventricular, or great arterial) is the Eisenmenger reaction of Dr. Paul Wood, who developed the Wood units in which pulmonary resistance is measured. The Eisenmenger reaction (right-to-left shunting because of elevated pulmonary vascular resistance) is not to be confused with the Eisenmenger complex (large subaortic VSD, aortic overriding, and right ventricular hypertrophy, but without pulmonary outflow tract obstruction and hence distinct from TOF). Thus, late-stage ASD II typically displays the Eisenmenger reaction (but not the Eisenmenger complex).

When Atrial Septal Defect II Was an Important Part of the Patient’s Main Clinical Problem

• In 8 patients, the secundum ASD was an important part of the patient’s main clinical problem (8/640 = 1.25%), but not the whole clinical problem.

• Sex: Male, 1; females, 7; male-to-female ratio 1:7 (.14) or female-to-male ratio, 7:1 (7).

• Age at Death: Mean, 15.99 years; standard deviation, ± 17.07 years; range, 5 weeks to 53 years; and median, 13 years.

• Salient Features: All had large secundum ASD. Rheumatic heart disease had occurred in 2 of these 8 patients. One had chronic mitral regurgitation that distended the LA and enlarged the ASD II. The other had severe rheumatic mitral stenosis that had been treated (in the 1950s and 1960s) with old and recent mitral valvuloplasties. This 53-year-old woman had a large ASD II (20 mm in diameter) with a very deficient septum primum. This combination of findings—secundum ASD and mitral stenosis—is known as the Lutembacher syndrome ( pronounced lootem-baker, i.e., in the German way), despite the fact that Rene Lutembacher (1884–1968) was a French physician from Paris who described this association in 1916, which was a very busy time in Paris.

  • A second patient had mitral regurgitation , but its cause (congenital or acquired) was not definitely established.

  • Down syndrome was present in 2 of these 8 patients with large secundum ASDs.

  • Multiple congenital anomalies (intellectual disability, hypospadias, hypoplastic penis, and cryptorchidism), sepsis (perirectal pelvic abscess related to Escherichia coli and Aerobacter, esophagitis, gastroenteritis, duodenal ulcers from which Monilia were cultured, tracheobronchitis, pulmonary edema, and bronchopneumonia), and pulmonary hemorrhage occurred in 1 patient each. Congestive heart failure and PVO were prominent in 3 patients each.

So, let us assume that most experienced observers know that ASD II can be the patient’s primary clinical problem or that ASD II can be associated with other disease processes that together may constitute the patient’s main clinical problem (as earlier).

But now we must consider a great unknown: What about the more than 95% of pediatric patients that have a secundum ASD, but in whom the ASD II is clinically overshadowed by other “more serious” forms of congenital heart disease? What do these patients have? What is ASD II associated with and masked by? This is what most books and papers on secundum ASD do not mention. We shall now attempt to answer these questions.