Definition and Morphology
Definitions
Atrioventricular septal defects (AVSDs) encompass a spectrum of cardiac anomalies. The hallmark feature is a five-leaflet atrioventricular (AV) valve with a common AV annulus that guards a common AV orifice, or separate left and right AV valve orifices ( Fig. 31.1 ).
Synonyms for AVSD include atrioventricular canal defect and endocardial cushion defect .
Morphology
International Pediatric and Congenital Cardiac Code Classification
The International Pediatric and Congenital Cardiac Code (IPCCC) has classified AVSDs into four main groups: (1) complete, (2) partial, (3) intermediate/transitional, and (4) AVSDs with ventricular imbalance ( Fig. 31.2 ).
Complete AVSDs include defects in which an ostium primum atrial septal defect coexists with a nonrestrictive inlet ventricular septal defect in the context of a common AV valve (ie, with a common AV valve annulus with a single AV valve orifice). The common AV valve has two bridging leaflets (superior and an inferior) that override the ventricular septum, a left lateral (mural) leaflet, a right anterosuperior mural, and a right inferior mural leaflet. Shunting occurs at the atrial and ventricular levels. Most AVSDs are complete (56% to 75%).
Approximately 80% of these complete defects are isolated defects, that is, without other associated cardiovascular anomalies. Of these isolated defects, up to 60% are associated with chromosomal abnormalities, the most frequent of which is Down syndrome. Down syndrome accounts for 84% of those with chromosomal abnormalities. The remaining 17% have other karyotype abnormalities including trisomy 18, trisomy 13, Turner syndrome, Klinefelter syndrome, and various deletions and unbalanced translocations.
Partial AVSDs can have an isolated atrial-level shunt or an isolated ventricular-level shunt. The former is more common and is also referred to as an ostium primum atrial septal defect (ASD). The anatomic features include bridging leaflets that attach to the ventricular septum, leaving only an interatrial and no interventricular connection. The attachment of the bridging leaflets to the ventricular septum also serves to create two valvular orifices despite there being a single valve annulus. Less commonly, isolated ventricular-level shunts can occur, which are effectively an inlet ventricular communication (ventricular septal defect [VSD]). In these cases, partially fused bridging leaflets attach to the atrial septum leaving only a ventricular-level but no atrial-level shunting.
Intermediate AVSDs include the spectrum of defects that comprise primum ASD in association with a restrictive VSD, commonly a result of chordal attachments to the septal crest. They are distinguished from complete AVSDs in that there are two valvular orifices rather than one, and the presence of a restrictive ventricular defect. The two separate AV valve orifices, as with partial AVSDs, are a result of fusion of the bridging leaflets by a “tongue” of tissue that divides the common valve. A single annulus remains. These defects have also been called transitional AVSDs .
The IPCCC classification groups intermediate and transitional AVSDs in the same category and names them intermediate (transitional) AVSDs.
AVSDs with ventricular imbalance arise when there is unequal commitment of the common AV valve to both ventricles resulting in hypoplasia of one of the ventricles. This may occur with any of the previously mentioned AVSDs where there exists a primum atrial defect.
Congenital Gerbode defects are left ventricular–to–right atrial shunts, and may occur through a defect in the atrioventricular septum that permits a direct left ventricle (LV) to right atrium (RA) shunt. Alternatively, the shunt may be through a perimembranous VSD and associated perforation in the septal leaflet of the tricuspid valve, that is, indirect. Although not classically considered part of the AVSD, Gerbode defects by definition represent a defect in the atrioventricular septum ( Fig. 31.3 ).
Rastelli Classification
Complete AVSDs may also be classified by the so-called Rastelli classification (three types). The classification is largely based on the anatomy of the superior bridging leaflet ( Fig. 31.4 ).
Type A (most common of Types A to C): The superior bridging leaflet is almost entirely contained within the left ventricle. It has chordal attachments to the crest of the ventricular septum. The right ventricular medial papillary muscle arises in relatively normal fashion from the interventricular septum.
Type B: The superior bridging leaflet extends farther into the right ventricle. The leaflet is attached to an anomalous right ventricle (RV) papillary muscle that arises from the trabecular septomarginalis.
Type C (often seen in association with other cardiac defects): The free-floating superior bridging leaflet extends even farther out into the right ventricle and is attached to an anterior papillary muscle.
Ventricular shunting increases progressively from Types A to C. Although the Rastelli classification was originally designed to predict surgical outcomes, its use is becoming increasingly obsolete because no consistent correlation exists between the Rastelli classification and surgical outcomes.
Atrioventricular Valves, Left Ventricle Outflow Tract Anatomy, and Other Anatomical Characteristics
Characteristic features of the AV valve: In contradistinction to normal AV valve anatomy, where the presence of an intact membranous septum facilitates relative apical displacement of the tricuspid valve with respect to the mitral valve, deficiency of the membranous septum in AVSD results in both AV valves being at the same septal insertion level. This is consistent with the notion of a common atrioventricular valve ( Fig. 31.5B ).
Figure 31.5
A, Apical four-chamber view showing the superior bridging leaflet, immediately above which is an ostium primum ASD and below which is a large inlet ventricular septal defect (VSD). The patient also has an ostium secundum ASD (ASD2). B, Subcostal four-chamber view showing IBL with a small VSD beneath. Note that both AV valves are at the same septal insertion plane (as opposed to the normal mitral and tricuspid valve, where the tricuspid valve is relatively apically displaced). Also note marked right ventricular hypertrophy. ASD, Atrial septal defect; IBL, inferior bridging leaflet; LA , left atrium; RA , right atrium; LV , left ventricle; RV , right ventricle; SBL, superior bridging leaflet.
Cleft, right and left AV valve characteristics : Among AVSDs that have separate left and right orifices, a cleft in the left AV valve is commonly observed. In truth this is a misnomer because it refers to a functional commissure, that is, a zone of apposition between the superior and inferior bridging leaflets ( Fig. 31.6 ). In contrast to isolated clefts (directed toward the aortic valve annulus), AVSD clefts are directed toward the midventricular septum.
Figure 31.6
A, Short-axis parasternal transthoracic echo view of a patient with a complete atrioventricular septal defect (AVSD) showing the trileaflet nature of the left atrioventricular valve (LAVV). Note adequate length of the mural leaflet, making LAVV stenosis after AVSD repair unlikely. B, Corresponding AVSD morphologic specimen demonstrating the mural (M), inferior (I), and superior (S) bridging leaflets. Note that the line of apposition of the inferior and superior bridging leaflets (“cleft”) in echo and morphologic specimens points more toward the ventricular septum and the right ventricle and not to the left ventricular outflow tract, which is commonly seen in true cleft mitral valves. 1, Inferior bridging leaflet; 2, superior bridging leaflet; I, inferior; M, mural; S, superior; RV , right ventricle.
(From Ho SY, Baker EJ, Rigby ML, Anderson RH. Color Atlas of Congenital Heart Disease: Morphology and Clinical Correlations . London: Mosby-Wolfe; 1995, with permission.)
The left atrioventricular valve (LAVV) in AVSD is a trileaflet valve, composed of the left halves of the superior and inferior bridging leaflets and the left mural leaflet. The right AV valve is a quadrileaflet valve, composed of the right halves of the superior and inferior bridging leaflet, and the right anterosuperior and right inferior leaflets ( Fig. 31.1C ). These valves should therefore not be referred to as mitral or tricuspid valves . A more appropriate terminology is left or right atrioventricular valve.
The characteristic “gooseneck deformity ” (elongation of the left ventricular outflow tract relative to the ventricular apex, best seen on angiography) is attributable to cranial displacement of the aortic valve and root. This occurs in a fashion sometimes described as “unsprung” from its normal location, which is wedged between the right and left atrioventricular annuli. As a consequence of this unwedging, the distance from the apex to aortic annulus is longer than that of the apex to the mitral annulus ( Figs. 31.7 and 31.8 ), providing the substrate for an elongated left ventricular outflow tract and creating the potential for subaortic stenosis. In contrast, normal hearts have approximately equal aortic annular-apical and mitral annular-apical distances.
Associated Intracardiac and Extracardiac Anomalies of Atrioventricular Septal Defects
Generally speaking, nonsyndromic AVSDs are more likely to be associated with other cardiovascular defects, as compared with syndromic AVSD, which tend to have isolated AVSDs.
- 1.
Common AV valve leaflets may be dysplastic and the valve may be functionally regurgitant or stenotic.
- 2.
Unbalanced AVSDs de facto have a predominant commitment of the common AV valve to either the right or left ventricle such that the other ventricle often becomes hypoplastic. Under these circumstances biventricular repair may not be possible, and a univentricular route with superior caval connection followed by Fontan completion may be the most appropriate treatment option ( Fig. 31.9B ).
Figure 31.9
Right ventricle/left ventricle (RV/LV) inflow angle. In the apical four-chamber view, the angle of the right-to-left ventricular inflow is measured from the crest of the ventricular septum to each atrioventricular valve hinge point. The angle is derived at the crest of the ventricular septum. A, An example of a patient with right-dominant, unbalanced atrioventricular septal defect (AVSD) with an RV/LV angle of 82 degrees. B, An example of a patient with balanced AVSD with an angle of 154 degrees.
(From Cohen MS, Jegatheeswaran A, Baffa JM, et al. Echocardiographic features defining right dominant unbalanced atrioventricular septal defect: a multi-institutional Congenital Heart Surgeons’ Society study. Circ Cardiovasc Imaging . 2013;6; 508-513.)
- 3.
Left ventricular outflow obstruction is associated with AVSDs. A large recent study involving 615 AVSD patients undergoing surgical repair noted a point prevalence and period prevalence for those older than 8.3 ± 6 years of 1.3% and 3.7%, respectively. Older data suggest a prevalence of approximately 10%. Obstruction is most commonly a result of (1) discrete subvalvular fibromuscular membranes, (2) septal hypertrophy impinging on the outflow tract, (3) accessory tissue originating from the atrioventricular valve, the chordal tissue, cystic valvular structures related to the valve, and/or (4) valvular aortic stenosis.
- 4.
Double orifice LAVV is associated with AVSDs in approximately 7% of cases. It coexists most often with partial AVSDs and is created by fibrous tissue dividing the LAVV into two orifices. Each orifice is associated with its own papillary muscle and subvalvular apparatus. The effective LAVV orifice area is smaller than usual and hence patients are predisposed to LAVV stenosis.
- 5.
Parachute LAVV. This anomaly occurs in the presence of a single or dominant papillary muscle. It affects 1% of AVSDs. These malformations may lead to stenosis of the LAVV.
- 6.
Heterotaxy syndrom es. AVSD is commonly observed in heterotaxy.
Other associated cardiac defects are summarized in Table 31.1 .
| Defect | Number | % of Total |
|---|---|---|
| Coarctation of the aorta | 48 | 21 |
| Pulmonary atresia | 28 | 12 |
| Double-outlet right ventricle | 26 | 11 |
| Hypoplastic left or right ventricle | 26 | 11 |
| Transposition of the great arteries | 24 | 10 |
| Tetralogy of Fallot | 20 | 9 |
| Anomalous venous return | 17 | 7 |
| Other | 40 | 17 |
| Total | 229 | 100 |
AVSD patients commonly have genetic defects affecting other extracardiac organs.
The urologic and nervous systems are most often involved, accounting for 21% and 16% respectively; other organ involvement also occurs.
Atrioventricular Conduction Tissue
In AVSDs, the AV node is displaced posteriorly and inferiorly compared with the normal position. AV conduction tissue penetrates only at the crux of the heart and the penetrating bundle is also displaced posteriorly. The His bundle is shorter than normal. The left bundle branch (also posteriorly displaced) gives rise to a longer than typical left anterior fascicle and shorter than typical left posterior fascicle. The right bundle branch is longer than that of normal patients. These patterns have been found to correlate with the electrocardiographic (ECG) patterns described in the following sections.
Embryology, Epidemiology, and Genetics/Maternal Exposure
Embryology
Embryologic formation of the atrial and ventricular septum occurs during the first 9 weeks of gestation. Earlier transgenic mouse model studies demonstrated that AVSD formation was dependent primarily on endocardial cushions. Recent studies, however, suggest that two other embryonic structures, called the dorsal mesenchymal protrusion (DMP) and the mesenchymal cap (MC) are also involved in cardiac separation and AV valve formation.
Endocardial cushions arise from the primary heart tube (myocardial progenitor cells formed from the splanchnic mesoderm). The primary heart tube has an inner endocardial layer and outer myocardial layer with a layer in between known as mesenchyme jelly. As cells from the endothelium migrate toward the jelly mesenchyme, endothelial mesenchymal transformation (EMT) occurs, at the end of which, four endocardial cushions are formed at the AV junction: superior, inferior, and two lateral cushions. The endocardial cushions contribute to AV valve formation. Also required for AV septation is growth of the muscular atrial septum premium toward the MC (another cushion-like structure). The MC will, in turn, fuse with the superior and inferior endocardial cushions. Finally, the MC and endocardial cushions will fuse with the DMP, a protruding structure at the base of the atrial septum also known as the vestibular spine. All three structures (endocardial cushions, MC, and DMP) contribute to the formation of the membranous septum and deficiencies in formation of each and/or fusion between them can theoretically contribute to AVSDs. It is important to note that the atrioventricular septum proper is the partition between the left ventricular outflow tract and right atrium, whereas the atrial septum divides the left and right atria and the ventricular septum divides the left and right ventricles.
Epidemiology
The incidence of AVSDs is approximately 4 to 5.3/10,000 live births constituting 7% of all congenital heart defects. The male:female ratio is equal. Among 84,308 Adult Congenital Heart Disease inpatient admissions in the United States in 2007, AVSDs constituted 0.7%. )
Most AVSDs (56% to 75%) are complete. Unbalanced AVSDs comprise 6% to 10% of complete AVSDs and occur mostly in nonsyndromic patients. Recent studies show that almost half of all AVSDs occur in DS patients and conversely approximately 25% of DS patients have AVSDs. Most cases of AVSDs in DS patients are complete AVSDs. Conversely, almost two-thirds of all complete AVSDs occur in DS patients. Most cases (90%) of partial AVSDs occur in non-DS patients. Heterotaxy syndrome is commonly associated with AVSDs. Approximately 90% of right isomerism patients are expected to have complete AVSD, whereas 60% to 70% of left isomerism patients have partial AVSDs.
The National Birth Defects Prevention Study (NBDPS) noted in a retrospective study of 302 nonsyndromic AVSDs patients from 1997 to 2005 that more than 20% had extracardiac anomalies. These were most commonly gastrointestinal, genitourinary, and central nervous system disorders.
Genetics and Maternal Exposure
Although a large component of the genetic basis for congenital heart disease in DS patients is attributable to trisomy 21, there are also thought to be other genetic factors such as copy number variations (CNVs), single nucleotide polymorphisms (SNPs), and other genetic mutations. The genetic modifiers of congenital heart disease (CHD) in DS are thought to represent incomplete penetrance because only 40% to 50% of DS patients have CHD. This in contrast to cognitive impairment, which is almost always present (albeit to varying degrees) in DS patients. AV septal defects are indeed the most common CHD abnormality in DS (among 43%) followed by VSDs, ASDs, tetralogy of Fallot (TOF) (at 32%, 19%, and 6%, respectively).
Some of the non-trisomy 21 genes implicated in the development of AVSDs include CRELD1, CRELD2, GATA4, BMP4, and TBX5. CRELD1 (located on chromosome 3p25) is one of the more commonly associated genes in DS and non-DS patients. It has been associated with 6% of non-trisomy 21–related AVSD patients. GATA4 mutations (on chromosome 8p23) have been found in families with AVSDs, ASDs, VSDs, and valvular abnormalities. Transgenic mice strains have demonstrated a correlation between BMP4 expression and the presence of AVSDs. TBX5 mutations are associated with Holt-Oram syndrome (syndrome of cardiac septation defects and upper-limb skeletal abnormalities). Other genes include ALK2, CFC1, ITX2, NODAL, ZIC3, and NKX2.5.
Syndromes that can involve AVSDs include CHARGE (coloboma, heart defects, atresia of choanae, retardation of growth, genital defect, ear anomalies) syndrome, VATER (vertebral anomalies, anal atresia, tracheoesophageal fistula, renal anomalies) association, Noonan syndrome, Holt-Oram syndrome (as described previously), and Smith-Lemli-Opitz syndrome.
Studies suggest that there are ethnic predispositions to AVSD, at least among the DS population. The US National Down Syndrome Project demonstrated that DS patients of Hispanic descent had a reduced risk of AVSD (odds ratio [OR] 0.48; 95% confidence interval [CI] 0.30 to 0.77) but are at somewhat increased risk (although not statistically significant) for VSDs. Other studies suggest that DS patients of Caucasian descent are at increased risk for AVSD.
Several nongenetic, maternal risk factors have been studied. Positive correlations have been found with pregestational diabetes, gestational diabetes, obesity, and smoking. Data from the National Birth Defects Prevention Study (1997–2005) demonstrated that mothers with an active smoking history and passive smoking exposure history during the periconceptual period were at increased risk of having infants with AVSDs compared to their nonsmoking counterparts (OR 1.5; 95% CI 1.1 to 2.4 among active smokers; OR 1.4; 95% CI among those with passive smoking history).
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