Ebstein’s Anomaly With Tricuspid Regurgitation

Ebstein’s anomaly of the tricuspid valve and right ventricle with tricuspid regurgitation was the single largest group in this study, although it comprised only 25 of 78 cases (32%) ( Table 13.2 ). This is what most people mean when they speak of “typical” Ebstein’s anomaly, even though this subset constituted only slightly less than one-third of all of our cases.

Gender: males, 10; females, 13; and unknown, 2. The male/female ratio in this subset was 0.77/1.

Age at death ( n = 24): mean, 6.26 years ± 7.48 years; range, 0 to 20 years; and median, 1.67 years. There were 3 abortus, who were regarded as having a postnatal life = 0. The foregoing data refer only to ages at postnatal death.

Language note: Abortus is a fourth declension, masculine Latin noun: abortus, -ūs, meaning a miscarriage. Consequently, the correct plural of abortus is abortūs , or simply abortus (without the macron).

The foregoing concerns only the ages at death; that is, there were no cardiac transplants, leading to living patients, in this group.

Important associated findings: Clinically and surgically important findings that were associated with these 25 postmortem cases of Ebstein’s anomaly of the tricuspid valve and right ventricle with tricuspid regurgitation are summarized in Table 13.3 .

A secundum type of atrial septal defect was the most common associated malformation (13 cases, 52%, Table 13.3 ), as in Ebstein’s original patient ( Fig. 13.1A ) and as in Case 1 of our series ( Fig. 13.7A ).

Ebstein’s anomaly with pulmonary valvar stenosis, tricuspid regurgitation, secundum atrial septal defect, large right-to-left shunt at the atrial level, and cyanosis since birth. The patient was an 11-year-old boy who received a classical Glenn anastomosis (right superior vena cava–to–right pulmonary artery) in 1962. The operation was complicated by bradycardia, cardiac dilatation, ventricular fibrillation, and intraoperative death. These are the cardiac photos that were taken at the time of autopsy. (A) The opened right atrium (RA) and atrialized right ventricle (the right ventricular inflow tract), viewed from above. The large secundum type of atrial septal defect (D) measured 22 × 12 mm. The anterior leaflet of the tricuspid valve (A) is deep and curtain-like, and its origin is from the right atrioventricular junction (not downwardly displaced). The septal leaflet of the tricuspid valve (B) is hypoplastic and downwardly displaced. The posterior leaflet (C) is markedly downwardly displaced beneath the right atrioventricular junction (AVJ). The inferior vena cava (E) is also seen. Note that the tricuspid leaflets do not coapt, explaining the tricuspid regurgitation. (The right lateral atrioventricular junction has not been cut through.) (B) The ventricularized right ventricle (below the tricuspid valve) and the right ventricular outflow tract. A is the stenotic unopened pulmonary annulus. The septal band (B) and the moderator band are strikingly thin and attenuated. The posterior leaflet of the tricuspid valve (C) is markedly downwardly displaced, close to the right ventricular apex; some of the chordae tendineae of the posterior leaflet are seen, but the interchordal spaces are filled with fibrous leaflet-like tissue. Note how very thin the right ventricular free wall (RVFW) is, even of the ventricularized right ventricle; this is a Uhl’s disease–like feature, often seen with Ebstein’s anomaly of the tricuspid valve and right ventricle. The right atrium (F) is markedly hypertrophied and enlarged. E is the ascending aorta.

Partial absence of the tricuspid valve leaflets was one of the second most common associated anomalies (6 patients, 24%, Table 13.3 ). The septal leaflet of the tricuspid valve may be partially absent ( Fig. 13.1A ) or totally absent; and the posterior leaflet of the tricuspid valve can be deficient or absent, particularly adjacent to the septal surface of the atrialized right ventricle.

This deficiency or absence of the septal and posterior leaflets of the tricuspid valve is associated with downward displacement of these tricuspid leaflets, or leaflet remnants, toward the septal and moderator bands, and away from or beneath the right atrial–right ventricular junction. Downward displacement and leaflet deficiency or absence of the septal and posterior leaflets of the tricuspid valve are integral parts of Ebstein’s anomaly.

Indeed, if the origins of the septal and posterior leaflets of the tricuspid valve are not downwardly displaced below the right atrioventricular junction, that is, if there is no atrialized right ventricle, then we do not make the diagnosis of Ebstein’s anomaly. An Ebstein’s-like anomaly may be present, but not typical Ebstein’s malformation.

Deficiency or absence of the septal and posterior leaflets of the tricuspid valve in typical Ebstein’s malformation often means that the deep curtain-like anterior leaflet has no leaflet against which it can coapt, resulting, as noted heretofore, in tricuspid regurgitation.

Although the origin of the anterior leaflet of the tricuspid valve typically is not downwardly displaced beneath the right atrioventricular junction, this leaflet is very abnormal in other respects: it is deep, curtain-like, myxomatous, and with reduction of interchordal spaces. The anterior papillary musculature is much smaller than normal. The insertion of the anterior leaflet can be broad, right into the right ventricular free wall ( Figs. 13.2 and 13.3 ).

The normal origin of the anterior tricuspid leaflet and the very low origins of the septal and posterior leaflets means that the atrialized right ventricle is bizarrely asymmetrical: high laterally and low medially. Consequently, the annulus of the tricuspid leaflets in Ebstein’s anomaly is much larger than normal and is at very different levels, which often predisposes to tricuspid regurgitation. So, too, does functional hypoplasia or absence of the septal and posterior leaflets.

The heart of an 8-month-old girl with typical Ebstein’s malformation is shown in Fig. 13.2 . Note the small secundum atrial septal defect or stretched patent foramen ovale ( Figs. 13.2A and 13.7A ); the downward displacement of the septal leaflet of the tricuspid valve ( Fig. 13.2A ); the atrialized right ventricle between the downwardly displaced septal leaflet below and the atrioventricular junction above ( Fig. 13.2A ); the smooth septal surface of the atrialized right ventricle—smooth because it is covered by no trabeculated right ventricular septal surface myocardium above the downwardly displaced septal leaflet of the tricuspid valve ( Fig. 13.2A ); and the very deep curtain-like anterior leaflet of the tricuspid valve ( Fig. 13.2A ).

The malformation of the anterior leaflet of the tricuspid valve is also functionally important. This large and deep anterior leaflet appears to insert directly into the right ventricular free wall ( Figs. 13.2A , 13.4 , and 13.7 ). Why? Because there are few or no interchordal spaces. Consequently, the chordae tendineae are not apparent. They are not free, readily visible structures. Although present, they are abnormally surrounded by leaflet tissue and hence at first glance appear to be absent. The surrounded chordae tendineae are thus disguised as leaflet tissue; but the chordae are revealed by careful inspection and by transillumination.

The right ventricular free wall papillary muscles are very small, numerous, and spread out. The papillary musculature is thus diffuse, instead of being normally concentrated to form the anterior papillary muscle of the right ventricle.

The lack of free chordae tendineae of the anterior (and posterior) leaflets of the tricuspid valve means that in Ebstein’s anomaly, the parietal leaflet of the tricuspid valve (i.e., the anterior and the posterior leaflets) are tethered to the right ventricular parietal or free wall. The failure of formation of interchordal spaces explains why the chordae tendineae of the anterior and the posterior leaflets seem to be so short.

The “free” margin of the anterior and posterior tricuspid leaflets may be attached to the right ventricular free wall ( Fig. 13.2A ); that is, there really may be no free leaflet margins. Or, the free margins of the anterior and posterior leaflets may be much too close to the right ventricular free wall—tethered to the right ventricular free wall, but not fused with it.

Both situations are functional disasters. The fused or tethered free margins of the anterior and posterior leaflets cannot move normally toward and coapt with the septal leaflet (if functionally present) of the tricuspid valve.

Thus, the downward displacement of the deficient or absent septal and posterior leaflets, and the tethering or fusion of what normally should be the free margin of the anterior leaflet of the tricuspid valve combine to result in tricuspid regurgitation that is often severe in typical Ebstein’s anomaly. Hence, all three leaflets (septal, posterior, and anterior) can be involved in the production of tricuspid regurgitation.

As mentioned heretofore, it should be reiterated that the origin of the anterior tricuspid leaflet is from the right atrioventricular junction; that is, the origin of the anterior leaflet of the tricuspid valve in Ebstein’s’ anomaly is not downwardly displaced in typical cases. But this, too, results in another geometric problem in typical Ebstein’s malformation. The origin of the tricuspid valve, that is, the tricuspid “ring,” is at very different levels, and is both deformed and enlarged. The origin of the anterior leaflet laterally is at the normal height, that is, at the right atrioventricular junction. But as one goes posteriorly, the origin of the posterior leaflet often dips down well below the right atrioventricular junction; or part of the posterior leaflet can be absent (the origin can be broken, or cease to exist, at this point). When one reaches the ventricular septum medially, the origin of the septal leaflet is often displaced markedly downward to the level of the septal and moderator bands, or the septal leaflet can be partially or totally absent ( Fig. 13.1A ).

Thus, the tricuspid valve in typical Ebstein’s malformation is seated very abnormally into the right ventricle: Normally high laterally (anterior leaflet); very low or absent medially (septal leaflet); with the high and low levels of leaflet origin being joined posteriorly (posterior leaflet).

The abnormal locations of the origins of the septal and posterior leaflets of the tricuspid valve in Ebstein’s anomaly indicate where the right ventricular sinus myocardium is (or is not).

Explanation: How far down is the septal leaflet of the tricuspid valve in Ebstein’s anomaly? The septal leaflet is displaced down to where the right ventricular myocardium has formed. In severe cases, the septal leaflet is displaced all the way down to where the infundibulum begins, that is, down to the septal and moderator bands (that are proximal infundibular structures).

When there is partial absence of septal leaflet or posterior leaflet tissue, this means that both the right ventricular myocardium and the tricuspid leaflet tissue have focally failed to form. This closely interrelated developmental process involves the so-called delamination of the tricuspid leaflet tissue, and immediately below that the laying down of right ventricular sinus myocardium septally and posteroinferiorly. ^, The downwardly displaced septal and posterior tricuspid leaflet tissue in Ebstein’s anomaly is an eye-catching marker of the failure of ascent of these tricuspid leaflets and of the related failure of right ventricular myocardial morphogenesis above these unascended tricuspid leaflets.

Sudden arrhythmic death was also relatively frequent in this subset: 5 of 25 patients (20%, Table 13.3 ). As mentioned above, this is what happened to Ebstein’s patient: sudden, unexpected arrhythmic death.

Ebstein’s anomaly is a well-known and important cause of electrocardiographic and electrophysiologic abnormalities, including right ventricular conduction delay, P-R interval prolongation, and Wolff-Parkinson-White (WPW) syndrome (in 10% to 25% of patients). Arrhythmias with Ebstein’s malformation are common, increase with age, and include supraventricular tachycardia, atrial flutter, and atrial fibrillation. ^, When present, accessory conducting pathways are usually single (62%). Such accessory pathways can be located in the right atrioventricular free wall, or they can be right septal in 34%, or atrioventricular nodal, or multiple in 29%.

Ebstein’s anomaly is an important cause not only of supraventricular tachyarrhythmias, but also of sudden, unexpected, arrhythmic death presumably related to ventricular tachycardia progressing to ventricular fibrillation (20%, Table 13.3 ).

The lack of a normally formed, fibrous, right atrioventricular junction that normally insulates and separates the right atrium from the ventricles—except at the penetrating atrioventricular bundle of His—is thought to provide an anatomic substrate that is vulnerable to ventricular preexcitation (WPW syndrome) and to catastrophic ventricular tachyarrhythmias. Hence, sudden unexpected arrhythmic death is an important part of the natural history of Ebstein’s malformation of the tricuspid valve, right atrioventricular junction, and right ventricular sinus.

Ventricular septal defect was also a frequent abnormality associated with Ebstein’s anomaly with tricuspid regurgitation: 6 of 25 patients (24%, Table 13.3 ) ( Fig. 13.2B ). High conoventricular ventricular septal defects (between the conal septum above and the ventricular septum below) were slightly more common (5) than muscular ventricular septal defects (3) ( Table 13.3 ) that were often midmuscular—between the smooth nontrabeculated left ventricular septal surface superiorly and the finely trabeculated more apical left ventricular septal surface inferiorly.

Heart failure was a prominent clinical feature in 6 of these patients (24%) ( Table 13.3 ). The mean age at death of these patients in which heart failure was reported was 6.96 years ± 8.24 years, ranging from 14 hours to 17 4 12 years. The median age at death was 4 2 12 years.

We regard the median age at death, as opposed to the mean age at death, as more accurately indicative of the true situation. The mean age at death was skewed to an older age by the presence of two teenagers in this series (16 2 12 years and 17 4 12 years). Thus, Ebstein’s anomaly with tricuspid regurgitation and congestive heart failure is a serious situation, accurately reflected by the young median age at death (4 2 12 years).

One of our youngest patients with congestive heart failure was a 2-day-old female infant who presented with hydrops fetalis. She had congestive heart failure both prenatally and postnatally. Autopsy (in 1992) revealed ascites and bilateral pleural effusions. Her Ebstein’s anomaly was characterized by a deep, curtain-like anterior leaflet with reduction of interchordal spaces, marked downward displacement of the origin of the septal leaflet (maximal downward displacement = 17 mm), and functional absence of the septal and posterior leaflets. The pulmonary leaflets were thickened and myxomatous, and had a blood cyst. Tricuspid regurgitation was very marked. Right atrial hypertrophy and enlargement were severe and a relatively large ostium secundum type of atrial septal defect (7 mm in diameter) coexisted. A prominent Eustachian valve of the inferior vena cava was also noted and was thought to be of no functional significance.

Thus, heart failure was even more important as an immediate cause of death (24%) than were arrhythmias (20%) ( Table 13.3 ).

Cyanosis was reported in 7 of these 25 patients (28%, Table 13.3 ). This finding was eye-catching because one does not ordinarily think of Ebstein’s anomaly as a form of cyanotic congenital heart disease; and usually it was not (72%, Table 13.3 ).

The ages at death of these patients with Ebstein’s malformation, tricuspid regurgitation, and cyanosis were older than in the previous group with congestive heart failure. In the 7 patients with cyanosis, the ages at death were as follows: mean, 9.88 years ± 6.84 years; range, 4 months to 17 8 12 years; and median 11 years.

Why were these patients with Ebstein’s anomaly and tricuspid regurgitation cyanotic? ( Table 13.3 .) There appeared to be four different groups:

• 1.
  

  Isolated Ebstein’s anomaly, as in Case 6 ( Fig. 13.3A and B ). This 8 3 12 -year-old girl was found at autopsy to have marked cardiomegaly. Her heart weighed 322 grams, compared with normal controls for the age of 160 grams (2.01/1, or 101% greater than normal). Cyanosis had appeared at 4½ years of age because of right-to-left shunting through an ostium secundum atrial septal defect (a 10 × 3 mm defect). Congestive heart failure appeared at 6 years of age. The patient died at 8 3 12 years of age during cardiac catheterization (in 1951) from a ventricular tachyarrhythmia.

Thus, typical isolated Ebstein’s anomaly ( Fig. 13.8 ) can develop cyanosis when/if right-to-left shunting occurs at the atrial level through a secundum atrial septal defect or a stretched patent foramen ovale. This phenomenon also occurred in our Case 24 (2 of 7 patients, 29%).

• 2.
  

  Ebstein’s anomaly with pulmonary stenosis , as in our Case 1 ( Fig. 13.7 ). This 11-year-old boy with Ebstein’s malformation, tricuspid regurgitation, a secundum atrial septal defect, supravalvar pulmonary stenosis, and supravalvar aortic stenosis was cyanotic at birth. He developed intraoperative ventricular fibrillation leading to death in 1962. Chronic cyanosis was associated with marked clubbing (digital osteoarthropathy). Cyanosis at birth was thought to be due to the coexistence of congenital pulmonary stenosis, most marked at the top of the pulmonary sinuses of Valsalva, hence often called “supravalvar” pulmonary stenosis. This is really a form of pulmonary valvar stenosis, the tops of the pulmonary sinuses of Valsalva being part of the pulmonary valve (the so-called “annulus” or “ring,” as opposed to the leaflets).

  
  
• 3.
  

  Ebstein’s anomaly with Uhl’s disease , that is, parchment right ventricle that is marked and widespread, often involving the anterior and the diaphragmatic portions of the right ventricular free wall, as in our Cases 47 and 75 ( Table 13.3 ).

This is the waxed-heart specimen of a 25-year-old man with Ebstein’s anomaly and tricuspid regurgitation (our Case 19). Through the window that has been cut in the right ventricular free wall (RV), one can see the deep curtain-like anterior leaflet (AL) of the tricuspid valve—typical of Ebstein’s anomaly. The free margin of the anterior leaflet is not thickened or rolled, consistent with normal leaflet function. There are almost no interchordal spaces, because they are filled by leaflet-like fibrous tissue. Note how very thin the right ventricular free wall is. Despite this Uhl’s disease–like component of this patient’s Ebstein’s anomaly, he had no hemodynamic problems. Instead, his problems were electrophysiologic: Wolff-Parkinson-White (WPW) syndrome, with a history of many episodes of paroxysmal atrial tachycardia and atrial flutter, for which he was treated with quinidine (in 1974). His WPW syndrome was complicated by ventricular fibrillation, leading to death. He was thought to have no tricuspid regurgitation or stenosis. He had isolation of the left atrial appendage: the cavity within the left atrial appendage did not communication with the main left atrial cavity. To our knowledge, isolation of the left atrial appendage is of no functional significance. MPA, Main pulmonary artery; RA, right atrium.

Case 47 was a 1 8 12 -year-old boy with Ebstein’s and severe tricuspid regurgitation. The right ventricular free wall was almost paper thin (2 mm). A secundum atrial septal defect measured 7 × 4 mm. In addition to Uhl’s disease, this boy also had “supravalvar” pulmonary stenosis; the top of the pulmonary sinuses of Valsalva had an internal diameter of 9 mm, while the bottom of the pulmonary sinuses of Valsalva had an internal diameter of 12 mm. Right-to-left atrial shunting resulted in cyanosis and clubbing.

Case 75 was a 14 1 12 -year-old girl who also had marked and widespread Uhl’s disease. Her secundum atrial septal defect was small and her pulmonary valve leaflets and annulus were mildly hypoplastic, but not otherwise malformed. Right atrial hypertrophy and enlargement were moderately marked. Left atrial hypertrophy and enlargement were mild to moderate.

Left ventricular hypertrophy was very marked, so much so that this young woman had a form of hypertrophic cardiomyopathy of the left ventricle, but without asymmetric septal hypertrophy and without idiopathic hypertrophic subaortic stenosis. Given that this teenager had widespread Uhl’s disease of the right ventricle, she had a functionally single left ventricle, which may explain her marked concentric left ventricular hypertrophy (hypothesis). It is also noteworthy that patients with Ebstein’s anomaly can have significant biventricular pathology .

At 9 9 12 years of age, the patient underwent a classical Glenn anastomosis between the right superior vena cava and the right pulmonary artery. This anastomosis remained large and unobstructed.

After dancing, she suffered syncope because of documented ventricular fibrillation leading to death (in 1979). Subpleural venous lakes were found at autopsy in the right lung. Such pulmonary venous “lakes” are associated with systemic venous blood flow that goes directly to the lungs, bypassing the liver. Lack of hepatic venous blood flow to the lungs may lead to the formation of pulmonary venous lakes, perhaps because of the lack of a still mysterious “hepatic factor.” Systemic venous blood going directly to the lungs (as in Glenn shunts or Fontan operations) also is nonpulsatile, which also may predispose to pulmonary venous lakes. Such lakes are not fully understood at the present time.

This case illustrates that typical Ebstein’s with Uhl’s disease is compatible with life into the teenage years. Note how thin the right ventricular free wall can be in patients with Ebstein’s anomaly even when we did not make the diagnosis of Uhl’s disease ( Fig. 13.7 ). This is the heart of a 25-year-old man (Case 19) who died in 1974. He had WPW syndrome, with a history of many episodes of paroxysmal atrial tachycardia with atrial flutter. Treatment with quinidine was followed by ventricular fibrillation and death. Despite the thinness of his right ventricular free wall, his problems were electrophysiologic, not hemodynamic.

• 4.
  

  Ebstein’s anomaly with cyanotic congenital heart disease ( Table 13.3 ) was illustrated by Case 43, a 4-month-old boy with tetralogy of Fallot ( Fig. 13.9 ), and by Case 45, a 16 2 12 -year-old young woman with D-transposition of the great arteries ( Fig. 13.10 ).

  
  

  
  

  
  

  

  
  

  
  

  This is the heart of Case 43, a 4-month-old boy with Ebstein’s malformation of the tricuspid valve (TV) and tricuspid regurgitation, with pentalogy of Fallot {S,D,S} and multiple congenital anomalies. (A) The opened right atrium (RA) and right ventricular inflow tract (RV). (B) The stenotic right ventricular outflow tract (RVOT). (C) The opened left ventricle (LV) and the ventricular septal defect (VSD). This patient with Ebstein’s anomaly and tetralogy of Fallot had a large (10 × 4 mm) secundum atrial septal defect (hence pentalogy of Fallot), a persistent left superior vena cava to the coronary sinus to the right atrium, a thick bicuspid pulmonary valve (PV) 4 mm in diameter, congenital absence of the left kidney, bilateral undescended testes, absence of the distal portion of the vas deferens, lissencephaly (familial), subnormal brain weight (350/510 grams) and thrombosis of an end-to-end left Blalock-Taussig anastomosis (in 1961), which led to death 2 days postoperatively. These photos were taken at the time of autopsy.

  
  

  
  

  
  

  

  
  

  
  

  This is the heart specimen of Case 45, a 16 2 12 -year-old woman with Ebstein’s anomaly, severe tricuspid regurgitation, transposition of the great arteries {S,D,D}, ventricular septal defect (conoventricular type), bicuspid pulmonary valve with pulmonary regurgitation, slit-like secundum atrial septal defect (8 × 2 mm), and enormous cardiomegaly (cardiothoracic ratio = 18/19.5 cm, or 92%). She had a long history of cyanosis and severe clubbing. One year prior to death, at 15 years of age, pedal edema and congestive heart failure appeared. Congestive heart failure progressed and she died, without surgical treatment, in 1959. (An atrial switch operation that surgeons were able to perform, i.e., the Mustard procedure, was not introduced until 1964.) (A) Opened right atrium (RA), tricuspid valve (TV), and right ventricular inflow tract (RV). The septal and posterior leaflets of the TV are displaced well below the right atrioventricular junction (AVJ). (B) Opened right ventricular outflow tract and D-transposed aorta (Ao). The nondownwardly displaced anterior leaflet (AL) and downwardly displaced septal leaflet (SL) of the TV afflicted with typical Ebstein’s anomaly is well seen. The subaortic conus arteriosus (C) separates the D-transposed aortic valve from the TV. The downwardly displaced SL of the TV separates the “atrialized” RV above the SL (to the viewer’s left) from the “ventricularized” RV below the SL (to the viewer’s right). (C) Opened mitral valve (MV), left ventricle (LV), and transposed pulmonary artery (PA). These photos were taken at the time of autopsy.

  
  

In somewhat greater detail, the patient with tetralogy of Fallot {S,D,S} also had a large secundum atrial septal defect (10 × 4 mm) and hence had pentalogy of Fallot . In addition to Ebstein’s anomaly with tricuspid regurgitation and a persistent left superior vena cava to the coronary sinus and thence to the right atrium, he also had multiple congenital anomalies: congenital absence of the left kidney; bilaterally undescended testes with absence of the distal vas deferens; and familial lissencephaly. The patient’s brain weighed less than normal for his age (370/510 grams).

The pulmonary valve had thick myxomatous leaflets (1.5 mm); this valve was bicuspid and 4 mm in internal diameter.

The tricuspid valve displayed marked downward displacement of the septal and posterior leaflets (10 mm down, Fig. 13.9 ). The septal leaflet was very small, with warty growths at its margin, and was nonfunctional (noncoapting). The anterior tricuspid leaflet was curtain-like, with a wide attachment to the right ventricular free wall, instead of a normal discrete focal attachment by chordae tendineae to a well-formed anterior papillary muscle ( Fig. 13.9 ). The right ventricular free wall was 6 mm thick; that is, Uhl’s disease was not present.

Our patient (Case 45) with Ebstein’s anomaly and severe tricuspid regurgitation who also had transposition of the great arteries (TGA) {S,D,D}, a conoventricular type of ventricular septal defect, and a bicuspid pulmonary valve with pulmonary regurgitation ( Fig. 13.10 ) was a remarkable example of the natural history of complex TGA. Briefly, she was a 16 2 12 -year-old young woman with cyanosis and severe clubbing who had enormous cardiomegaly. Her heart almost completely filled her chest, her cardiothoracic ratio being 18/19.5 cm (92%). A secundum atrial septal defect was relatively small, just a slit (2 × 8 mm). Congestive heart failure with pedal edema appeared at 15 years of age, 1 year before she died (in 1959).

To summarize, cyanosis can be present in patients with Ebstein’s anomaly and tricuspid regurgitation, 7/28 (28%), in at least four different settings:

• (1)
  

  isolated Ebstein’s malformation, 2/7 patients (29%);

  
  
• (2)
  

  Ebstein’s with pulmonary stenosis, 1/7 cases (14%);

  
  
• (3)
  

  Ebstein’s with Uhl’s disease, 2/7 patients (29%); and

  
  
• (4)
  

  Ebstein’s with cyanotic congenital heart disease, that is, tetralogy of Fallot or D-transposition of the great arteries, 2/7 patients (29%).

Biventricular pathology can be prominent in patients with Ebstein’s anomaly and tricuspid regurgitation, as in 4 of these 25 patients (16%, Table 13.3 ):

Case 75, a 14 1 12 -year-old girl with widespread Uhl’s disease of the right ventricle and marked concentric left ventricular hypertrophy, has been mentioned heretofore.

Congenital mitral stenosis with absence of interchordal spaces was found in a 15-year-old boy (Case 37). He also had subacute bacterial endocarditis with vegetations on his stenotic mitral valve. This boy had the daunting combination of severe tricuspid regurgitation (Ebstein’s anomaly), congenital mitral stenosis, a hypoplastic right ventricle, and pulmonary annular stenosis. He was treated with a Brock pulmonary valvotomy at 2 years of age, tricuspid valvuloplasty and pulmonary valvotomy at 8 years of age, and a Glenn anastomosis at 15 years of age (in 1965). He did not survive the latter procedure because of the coexistence of congenital mitral stenosis.

Familial biventricular myocardial dysplasia was found in a boy who died at 4 years of age (Case 51). In addition to Ebstein’s malformation with tricuspid regurgitation and a small-chambered and dysplastic right ventricular sinus (typical of Ebstein’s), he also had bizarre left ventricular myocardial architecture and double-orifice mitral valve . There was a small anterolateral accessory orifice and a larger posteromedial main orifice—typical of double-orifice mitral valve. There was also a large conoventricular type of ventricular septal defect.

A final rare anomaly in this patient was an aneurysm of the right horn of the sinus venosus that underlay the right ventricular sinus and that communicated with the right atrium via two nonvalved openings. (Aneurysms of the sinus venosus are considered in detail in Chapter 6 concerning systemic venous anomalies.) Although most patients with Ebstein’s malformation have what may be called “isolated” Ebstein’s anomaly, occasionally we encountered patients such as this with multiple congenital cardiovascular anomalies, who may be regarded as having non-isolated Ebstein’s malformation.

A 27-week-old aborted female fetus (Case 60) from Paris, France (Courtesy of Dr. Lucile Houyel) also had a rare form of nonisolated Ebstein’s anomaly with tricuspid regurgitation. Double-outlet right ventricle {S,D,D} was associated with the hypoplastic left heart syndrome. The fetus had mitral atresia with a tiny left ventricle, and a relatively small muscular ventricular septal defect.

It should be understood that double-outlet right ventricle (DORV) with hypoplastic left heart syndrome is a special type of DORV that typically has a unilateral conus (a subpulmonary conus, with aortic valve–tricuspid valve fibrous continuity, or a subaortic conus with pulmonary valve–tricuspid valve fibrous continuity), rather than a bilateral conus (subaortic and subpulmonary, and consequently with no semilunar valve–atrioventricular valve direct fibrous continuity), which is usually present when DORV is associated with two well-developed ventricles. (For more information about DORV, see Chapter 23 .)

Hence, in this patient, it was no surprise that there was a subpulmonary conus (only, not a bilateral conus) with aortic valve–to–tricuspid valve direct fibrous continuity. The rightward and posteroinferior aortic outflow tract was squeezed between the conal septum anteriorly and somewhat to the left and the tricuspid annulus and leaflets posteriorly and to the right. As usual, this posteroinferior outflow tract was stenotic. The tight subaortic outflow tract was associated with aortic valvar atresia. DORV with aortic valvar atresia is rare. Aortic valvar atresia almost always occurs with normally related great arteries. As is usual with aortic valvar atresia, the ascending aorta was markedly hypoplastic (1 mm in internal diameter). The unobstructed pulmonary outflow tract led to a good sized main pulmonary artery and a large patent ductus arteriosus.

The right ventricular sinus (body, or inflow tract) was underdeveloped, and the septal and posterior tricuspid leaflets were downwardly displaced, typical of Ebstein’s anomaly.

Thus, biventricular pathology was present. A persistent left superior vena cava connected with the coronary sinus and flowed in the right atrium (not an unusual finding).

However, this feature had one other rare anomaly: a diverticulum at the right atrioventricular junction that communicated with the right atrium via a circular orifice in the leftward (medial) portion of the posterior leaflet of the tricuspid valve.

Thus, the pathology associated with Ebstein’s anomaly can be biventricular, complex, and rare.

Finally, a 1-day-old female infant with Ebstein’s anomaly and severe tricuspid regurgitation (Case 64) had a hypoplastic but patent right ventricular outflow tract to the pulmonary artery. However, at the time of study, echocardiography showed that there was no antegrade blood flow from the right ventricle into the pulmonary artery. The right ventricle and right atrium were severely dilated. The ductus arteriosus was patent, and a secundum atrial septal defect was present. Moderate global left ventricular dysfunction was observed echocardiographically. This newborn girl was in low cardiac output, had metabolic acidosis, and died on the first day of life.

This patient had no detectable anatomic abnormality of the left ventricle; hence, we did not include this case as an example of biventricular abnormality. This patient’s left-sided abnormality was physiologic not anatomic. Nonetheless, we think that physiologic dysfunction can be as important as anatomic malformations. This is why Table 13.3 is titled (in part): “Important Associated Findings” (not “Important Associated Anomalies/Malformations”). In this way we were able to include important physiologic events such as sudden arrhythmic death, heart failure, and cyanosis. That said, this patient’s echocardiographic study was performed when she was moribund and dying; hence the finding of left ventricular functional abnormality is not surprising. (Not many of our patients were studied echocardiographically while they were dying; but had they been, probably a high percentage would have revealed left-sided functional abnormality, as in this patient.)

To summarize, biventricular anomalies were found in 4 of these 25 patients with Ebstein’s anomaly and tricuspid regurgitation (16%):

• 1.
  

  congenital mitral stenosis with absence of interchordal spaces plus subacute bacterial endocarditis and mitral vegetations in a 15-year-old boy (Case 37);

  
  
• 2.
  

  familial biventricular dysplasia with double-orifice mitral valve and a dysplastic left ventricle in a 4-year-old boy (Case 51);

  
  
• 3.
  

  hypoplastic left heart syndrome, that is, aortic atresia, mitral atresia, tiny left ventricle, and small muscular ventricular septal defect, in a 27-week-gestation female fetal abortus (Case 60); and

  
  
• 4.
  

  very marked left ventricular hypertrophy, resembling left ventricular hypertrophic cardiomyopathy, in a 14 1 12 -year-old girl (Case 75).

Ebstein’s Anomaly With Congenital Tricuspid Stenosis

Ebstein’s anomaly with congenital tricuspid stenosis was the second most common type of “typical” Ebstein’s malformation, being found in 11 of 78 postmortem cases (14%, Table 13.2 ).

By “typical” Ebstein’s, we mean that other major forms of congenital heart disease were not present, such as pulmonary atresia with intact ventricular septum, typical congenitally corrected transposition of the great arteries {S,L,L}, or common atrioventricular canal ( Table 13.2 ).

• 
  

  Gender: males, 5; and females, 6. The male/female ratio in this subset was 0.83/1.

  
  
• 
  

  Age at death: mean 4¾ months ± 7½ months, ranging from 2.5 days to 2 10 12 years in these 11 patients. The median age at death was 27 days.

It is noteworthy that the median age at death in Ebstein’s anomaly with tricuspid stenosis (27 days) was much younger than with tricuspid regurgitation (1 8 12 years), consistent with the view that Ebstein’s anomaly with tricuspid stenosis is a more lethal subset than is Ebstein’s anomaly with tricuspid regurgitation .

Severity of tricuspid stenosis. At autopsy, the degree of tricuspid stenosis was regarded as severe in 6 of 11 (55%) (Cases 18, 22, 39, 57, 66, and 76) and as moderate in 5 (45%) (Cases 12, 24, 25, 70, and 71). In an effort to describe what these two different degrees of severity are like, I will present several of these patients in detail.

Ebstein’s Anomaly With Tricuspid Atresia (Imperforate Ebstein’s)

There were two patients with Ebstein’s anomaly of the tricuspid valve and right ventricle who had tricuspid atresia (Cases 5 and 64), comprising 3% of this series ( Table 13.2 ). This malformation is also known as imperforate Ebstein’s anomaly, in order to indicate that it is anatomically and developmentally different from typical tricuspid atresia, although physiologically the same.

Atresia is derived from two Greek words: a, the privative prefix meaning the want or absence of; and tresis, meaning hole. Thus, atresia literally means “no hole.” Consequently, imperforate Ebstein’s and typical tricuspid atresia have no opening at the junction between the right atrium and the right ventricle and hence are functionally identical in this respect.

But what are the anatomic and the embryologic differences?

In typical tricuspid atresia, the floor of the right atrium is relatively flat ( Fig. 13.11 ). There is often a very small little dimple at the expected site of the tricuspid valve, which really is the atrioventricular portion of pars membranacea septi (the AV portion of the membranous septum). In typical tricuspid atresia, the tricuspid valve usually is absent, and the right ventricular sinus (body, or inflow tract) characteristically is small, tiny, or apparently absent, that is, unexpanded or atretic—with little or no lumen of the right ventricular sinus, body, or inflow tract.

Typical tricuspid atresia (TAt). The morphologically right atrium (RA) has been opened, revealing that the floor of the RA is smooth, flat, and muscular, with no evidence of the tricuspid valve. Often there is a little dimple or fibrous depression in the floor of the RA: the leader from the label RA is pointing right at this dimple. This slight depression used to be regarded as a remnant of the atretic tricuspid valve; but now this dimple is thought to be the atrioventricular portion of the pars membranacea septi (the membranous septum). Typical tricuspid atresia is not related to Ebstein’s anomaly. Typical tricuspid atresia is now understood to be a misnomer: the tricuspid valve is absent, not atretic (lacking an orifice). Typical tricuspid atresia is lack of a right atrioventricular communication: the RA does not open directly into either ventricle. Note also how hypertrophied the right atrial myocardium is. The atrial septum is well formed in this case. It has only recently been realized that the concept of tricuspid atresia is literally erroneous. However, the term tricuspid atresia is well entrenched and we are not trying to change it. The foregoing is written in the interests of deeper understanding. The updated concept should be absent right atrioventricular communication, not absent right atrioventricular connection —because the right atrium may physically connect with a ventricle, but without opening into it. It is absence of the communication or opening that is key. So this is what is meant by typical tricuspid atresia (so-called): absence of a right atrioventricular valvar opening.

In Ebstein’s anomaly with tricuspid atresia, the floor of the atretic right atrium is not flat. Instead, there is a blind, downwardly depressed hole—reminiscent of a hole on a golf course ( Fig. 13.12 ). The downward depression is the atrialized right ventricle. The atrialized right ventricle is blind (atretic), with no outlet, because the small opening at the anterosuperior commissure of the tricuspid valve is sealed closed (instead of having a small opening, as is typically found in Ebstein’s with severe tricuspid stenosis). Also, the interchordal spaces are occluded with leaflet-like tissue. And all three leaflets—anterior, septal, and posterior—are fused. Consequently, there is no opening through this imperforate tricuspid valve ( Fig. 13.13 ).

Right: Imperforate Ebstein’s anomaly, i.e., Ebstein’s with tricuspid atresia. The floor of the right atrium (RA) is not flat, as in typical tricuspid atresia ( Fig. 13.11 ). Instead, in atretic Ebstein’s anomaly, the floor of the RA is a blind, downwardly depressed hole—like a hole on a golf course. The anterior or parietal leaflet of the tricuspid valve originates from the right atrioventricular junction; whereas the septal and posterior leaflets of the tricuspid valve originate below the right atrioventricular junction. The blind pocket above the atretic tricuspid valve is often called the “atrialized” right ventricle (RV) because, although this blind pocket is the right ventricular inflow tract (lying below the right atrioventricular junction), the pressures are the same as they are in the RA, because the tricuspid valve is downwardly displaced. The pressures in the RV below the atretic tricuspid valve are typical of the RV; hence this subtricuspid portion of the RV is known as the “ventricularized” RV. In the atrialized RV, the intracardiac electrocardiogram is typical of the RV, even though the pressures are characteristic of the RA. This discordance between the pressures and the intracardiac electrogram in the atrialized RV is diagnostically typical of Ebstein’s anomaly. Left: straddling tricuspid valve. There is ventriculoatrial malalignment such that the ventricular septum (VS) underlies the tricuspid orifice. Consequently the tricuspid valve straddles the ventricular septum, typically through a ventricular septal defect of the atrioventricular canal type. Ventriculoatrial malalignment is not typical of Ebstein’s anomaly. Right: The ventricular septum (VS) underlies the atrial septum (AS) in an approximately normal way; whereas, with straddling tricuspid valve (Left), the VS is malaligned well to the right of the AS (when D-loop ventricles are present). LA, Left atrium; LV, left ventricle.

From Edalji Kumar A, Gilbert C, Aerichide N, Van Praagh R: Ebstein’s anomaly, Uhl’s disease and absence of tricuspid leaflets: a new spectrum. Am J Cardiol 1970;25:111-112 and Van Praagh R, Ando M, Dugan WT: Anatomic types of tricuspid atresia: clinical and developmental implications. Circulation 1971;44:II-115; with permission.

Imperforate Ebstein’s anomaly. The dilated right atrium and the downwardly displaced, atretic tricuspid valve are seen. The hepatic veins were dilated and centrilobular necrosis of the liver was present. Case 5 was a 1 10 12 -year-old girl. In addition to an imperforate Ebstein anomaly, they also had a small muscular ventricular septal defect (3 mm in diameter) and a secundum atrial septal defect (6 × 4 mm). At 3 months of age, a left Blalock-Taussig anastomosis was performed, which gradually closed. Consequently, at 1 10 12 years of age (in 1966), she had a Waterston anastomosis (between the posterior surface of the ascending aorta and the anterior surface of the right pulmonary artery). Postoperatively, massive hemorrhage developed in the right lower lobe of the lung, leading to death.

The anatomic differences between imperforate Ebstein’s and typical tricuspid atresia may be summarized as follows:

• 1.
  

  In imperforate Ebstein’s, the tricuspid valve leaflet tissue, although very abnormal, is present; whereas in typical tricuspid atresia, the tricuspid valve leaflet tissue is largely or totally absent.

  
  
• 2.
  

  In imperforate Ebstein’s, the right ventricular inflow tract (the atrialized right ventricle) is present, forming a blind depression (like a hole on a putting green of a golf course); whereas in typical tricuspid atresia, the right ventricular sinus, body, or inflow tract is largely or perhaps totally absent (it may be present, but unexpanded).

  
  
• 3.
  

  Ventriculoatrial malalignment typically is not present (or not at all prominent) in imperforate Ebstein’s, that is, the ventricular septum underlies the atrial septum ( Fig. 13.12 ); whereas with typical tricuspid atresia ( Fig. 13.14 ) and with straddling tricuspid valve ( Fig. 13.12 ), the ventricular septum underlies the tricuspid valve (in straddling tricuspid valve), or the ventricular septum underlies the expected site of the tricuspid valve (in typical tricuspid atresia) ( Fig. 13.14 ).

  
  

  
  

  
  

  

  
  

  
  

  Malalignments of the ventricular septum and the tricuspid orifice. (A) In the normal heart, the ventricular septum (VS) lies slightly to the right of the plane of the atrial septum (AS). Consequently, the atrioventricular portion of the membranous septum (pars membranacea septi, PMS ) normally separates the morphologically left ventricle (LV) from the morphologically right atrium (RA). A defect in the atrioventricular portion of the PMS results in a left ventricular–to–right atrial shunt (a Gerbode shunt). (B) With single left ventricle (LV) caused by absence of the right ventricular (RV) sinus, double-inlet LV is typical. Why? Because absence of the RV sinus results in the ventricular septal remnant being displaced to the right—toward the absent RV sinus. Consequently, the ventricular septum is markedly malaligned relative to the atria and the atrioventricular valves. With a ventricular D-loop, the VS remnant and the infundibular outlet chamber lie to the right of the tricuspid valve; hence double-inlet LV is typical of single LV with an infundibular outlet chamber. (C) If the RV sinus is not absent, but just hypoplastic, the ventricular septum can be moved somewhat further to the left than it is in (B). Consequently, the result can be double-inlet left ventricle, but with congenital tricuspid stenosis (TS) due to crowding of the tricuspid valve, resulting in tricuspid hypoplasia. (D) In typical tricuspid atresia, the ventricular septal remnant often underlies the expected site of the tricuspid orifice. This type of ventriculoatrial malalignment, in which the ventricular septal remnant appears to obstruct the potential tricuspid orifice, may be important in the morphogenesis of typical tricuspid atresia. This is the usual muscular type of typical tricuspid atresia, meaning that the floor of the right atrium—in the expected site of the tricuspid valve and orifice—displays a flat muscular appearance, often with a fibrous dimple that is thought to be fibrous membranous septal tissue. (E) The typical or classical form of tricuspid atresia occasionally can be membranous (not muscular). The floor of the right atrium displays smooth, flat, fibrous tissue that we interpret as a larger than usual membranous septal component. Typical membranous tricuspid atresia transilluminates brilliantly, can occur quite frequently with left-sided juxtaposition of the atrial appendages (for reasons unknown), and this membranous right atrial floor does not resemble tricuspid leaflet tissue. (F) Tricuspid atresia (TAt) can occur with common atrioventricular canal with a common atrioventricular valve (CAVV) and an atrioventricular septal defect. When the right ventricular sinus (RV) is quite markedly underdeveloped, the ventricular septum (VS) can be displaced far to the right relative to the plane of the atrial septum (AS). The CAVV can open entirely into the morphologically left ventricle (LV), resulting in common-inlet LV. If the right corner of the common AV valve becomes attached to the ventricular septal crest, then the right atrium cannot open directly into the small right ventricle, resulting in a form of tricuspid atresia. This is what Dr. Maurice Lev and his colleagues called the left ventricular type of common AV canal (or orifice), meaning that the common AV orifice and valve open entirely (or almost entirely) into a large LV, and little or not at all into the small RV. Hypothesis: Ventricular septal tricuspid valve malalignments appear to be an important mechanism leading to tricuspid valve anomalies. Often, the tricuspid valve appears to be the “victim,” not the “villain”; i.e., tricuspid valve anomalies often appear be secondary to ventriculoatrial malalignment. For example, variable degrees of underdevelopment of the RV sinus (hypoplasia to asplasia) may play an important role in the pathogenesis of ventricular septal–to–tricuspid valvar malalignment mentioned above. Other similar anomalies include straddling tricuspid valve ( Fig. 13.12 , Left ) and double-outlet right atrium.

  
  

In typical tricuspid atresia, take a long straight needle and stick it straight down through the expected site of the atretic tricuspid valve. Then look at the ventricular part of the heart. Where did the needle come out? Typically, the point of the long straight needle emerges out of the posterior portion of the rightwardly deviated ventricular septum. This finding indicates that in typical tricuspid atresia, the posterior portion of the ventricular septum underlies the expected site of the tricuspid valve. The posterior portion of the ventricular septum is displaced to the right relative to the atrial septum.

Why? Our hypothesis is that when the right ventricular sinus (body or inflow tract) is underdeveloped, then the muscular ventricular septum is not moved normally to the left by expansile growth of the right ventricular sinus and consequently does not underlie the atrial septum, as the ventricular septum does normally, and as it does even with Ebstein’s anomaly of the tricuspid valve and right ventricle with tricuspid atresia (imperforate Ebstein’s anomaly) ( Fig. 13.12 , right). Thus, in typical tricuspid atresia there is an important rightward malalignment of the ventricular part of the heart relative to the atria that is not present in Ebstein’s anomaly with tricuspid atresia ( Fig. 13.14 ). In typical so-called tricuspid atresia, the floor of the right atrium is not only flat, it is also muscular. One does not see an atretic tricuspid valve, as one does in imperforate Ebstein’s anomaly. Instead, one sees a flat muscular right atrial floor, with little or no evidence of a tricuspid valve. Typically, the tricuspid valve is largely or totally absent, not atretic. The right ventricular sinus (inflow tract) is also largely or totally absent in so-called typical tricuspid atresia. Note again the very close relationship between the development of the right ventricular sinus and the tricuspid valve. This interrelationship is also evident in typical Ebstein’s anomaly, as noted heretofore.

Ironically, typical tricuspid atresia does not really have an atretic tricuspid valve — a tricuspid valve with no hole through it. Only imperforate Ebstein’s anomaly really has tricuspid atresia. This insight is recorded here in the interests of understanding. I do not wish to change conventional terminology.

Diagnostically, the blind atrialized right ventricle is typical of imperforate Ebstein’s anomaly, but this diagnostic finding is not seen with typical tricuspid atresia because anatomically and developmentally, these are two very different malformations (as above).

Data concerning our two patients with imperforate Ebstein’s anomaly follow:

• 
  

  Sex: both females.

  
  
• 
  

  Age at death: 1 10 12 years (Case 5) ( Fig. 13.13 ) and 2½ years (Case 64).

  
  
• 
  

  Associated malformations: secundum atrial septal defect in 1 (6 × 4 mm); ventricular septal defect in both, muscular in Case 5 (3 mm), and membranous (conoventricular, subaortic) in Case 64. The latter patient also had conspicuous endocardial thickening of the atrialized right ventricle, right atrium, and left ventricle. Cyanosis appeared at 4 months of age and was associated with frequent squatting. (Note that squatting does not occur only with tetralogy of Fallot.)

  
  
• 
  

  Management: Case 5 was treated with a left Blalock-Taussig anastomosis at 3 months of age. Subsequently, this anastomosis closed, and consequently a Waterston anastomosis (between the posterior side of the ascending aorta and the anterior side of the right pulmonary artery) was done in 1966. Postoperatively, a massive right pulmonary hemorrhage developed, leading to death.

In Case 64, a Waterston anastomosis was also performed (in 1968) and the patient died 3 weeks postoperatively.

Historical Note: It should be recalled that the Fontan procedure for the physiologic correction of tricuspid atresia was not published until 1971 ^, and was not widely utilized surgically until later in the 1970s.

The Problem of Borderline Cases

Perhaps somewhat arbitrarily, we decided not to make the diagnosis of Ebstein’s anomaly unless the septal leaflet of the tricuspid valve was downwardly displaced below the right atrioventricular junction. This is why we began this study thinking that we had 79 cases of Ebstein’s anomaly, not the 78 cases ( Table 13.2 ) that we ended up with. For example, a 32-hour-old newborn infant boy had a deep curtain-like anterior leaflet of the tricuspid valve, with extensive obliteration of the interchordal spaces. The septal leaflet of the tricuspid valve was bound down, with little functional free leaflet tissue; but the origin of the septal leaflet was not downwardly displaced . There was partial absence of tricuspid valve leaflet tissue beneath the anterosuperior commissure. Double-orifice of the tricuspid valve involved the posterior leaflet. All of the tricuspid leaflets were thick and myxomatous. Additional findings include marked pulmonary valve stenosis with a bicuspid pulmonary valve, an intact ventricular septum, and severe tricuspid regurgitation (confirmed by echocardiography and cardiac catheterization). The patient also had a history of fetal tachycardia (190 beats/min).

We concluded that this patient certainly had an Ebstein-like anomaly of the tricuspid valve; however, we did not make the diagnosis of Ebstein’s anomaly (unqualified) because Ebstein’s is generally understood to have downward displacement of the septal leaflet, and of at least part of the posterior leaflet of the tricuspid valve into the right ventricle, resulting in an atrialized right ventricle—which this patient did not have. Nonetheless, we now seek to focus attention and understanding on the arbitrary and artificial nature of classification, which is highlighted by borderline cases such as this. The abnormal septal leaflet underwent delamination and ascent up to the right atrioventricular junction.

All anomalies form a spectrum —from the most severe, to the mildest forms of disease. So that the accuracy of our diagnoses can be relied on, we have excluded borderline cases like this. But it must also be understood that such borderline cases— Ebstein-like or “Ebsteinoid” cases —do indeed exist, as is to be expected because all anomalies are parts of a spectrum of malformation.

With Tricuspid Regurgitation

Of these 12 patients, the age death was known in 11.

Age at death: mean = 11.4 ± 15.3 days; the range was 0 (stillborn) to 45 days; and the median was 5 days.

In terms of natural history, the age at death of Ebstein’s anomaly with pulmonary atresia or severe pulmonary stenosis, intact ventricular septum, and tricuspid regurgitation is much the youngest of any Ebstein’s group encountered to date. The median ages at death were as follows:

• 1.
  

  series as a whole, 10 weeks;

  
  
• 2.
  

  Ebstein’s with tricuspid regurgitation, 1 8 12 years;

  
  
• 3.
  

  Ebstein’s with tricuspid stenosis, 27 days;

  
  
• 4.
  

  Ebstein’s with tricuspid atresia (imperforate), n = 2, average = 2.16 years or 26 months; and

  
  
• 5.
  

  Ebstein’s with pulmonary atresia or very severe stenosis, intact ventricular septum, and tricuspid regurgitation, 5 days.

These data suggest that pulmonary atresia with intact ventricular septum and tricuspid regurgitation may well be one of the most lethal forms of congenital heart disease.

Sex: Of these 12 patients, the gender was known in 11: males, 9; and females, 2. The male/female ratio was 9/2 (4.5/1). This is the first time in studying Ebstein’s anomaly that we have encountered a strong gender preponderance, suggesting that perhaps this strong male preponderance may be related to pulmonary atresia with intact ventricular septum, rather than to Ebstein’s anomaly (speculation).

Of these 12 patients, 2 (Cases 35 and 52) had very severe pulmonary valvar stenosis (17%) ( Fig. 13.15 ), rather than pulmonary atresia (10 of 12, 83%). The anatomy of the Ebstein’s anomaly of the tricuspid valve with tricuspid regurgitation was similar to that in previous settings ( Fig. 13.15 ). Other findings are summarized in Table 13.5 .

Ebstein’s anomaly with severe tricuspid regurgitation in a patient who also had severe (dome) pulmonary valvar stenosis (opening 2 mm in diameter) with intact ventricular septum. This 1-hour-old girl had severe respiratory distress and cyanosis at birth. When she had been intubated, the lungs could not be inflated, and she could not breathe on her down. Autopsy revealed marked hypoplasia of both lungs, i.e., half the volume of normal control lungs. Her very early death was thought to be primarily related to pulmonary failure, not cardiac insufficiency. The pulmonary veins bilaterally were markedly hypoplastic and could be probed only with difficulty. Her congenital heart disease was also very severe. (A) The opened right atrium (RA), tricuspid valve, and right ventricle (RV). (B) The opened tricuspid valve and RV. In (A), note the marked right atrial hypertrophy and enlargement. A secundum type of atrial septal defect (ASDII), measuring 8 × 6 mm, is seen above a deficient septum primum. The septal leaflet (SL) of the tricuspid valve is downwardly displaced and deficient, with a small blood cyst located above it (closer to the RA). The anterior leaflet (AL) of the tricuspid valve originates normally from the right atrioventricular junction. (B) The anterior leaflet (AL) of the tricuspid valve, with very few well-formed interchordal spaces. Consequently, the AL appears to insert broadly, with few intervening papillary muscles, directly into the right ventricular free wall—immediately inferior to the anterior papillary muscle (APM) of the right ventricle. The septal band (SB) and the infundibular wall are hypertrophied. The very tight (2 mm internal diameter) unopened dome pulmonary valvar stenosis (PS) is seen from below. Note the very hypoplastic left lung (LL) and right lung (RL).

Ebstein’s Anomaly With Pulmonary Atresia, Intact Ventricular Septum, and Tricuspid Stenosis

Only two patients had Ebstein’s anomaly, pulmonary atresia, intact ventricular septum, and tricuspid stenosis (3%, Table 13.2 ).

Case 59 was a 14 3 12 -year-old girl at the time of her heart transplantation. The explanted heart specimen revealed severe congenital tricuspid stenosis, immediately beneath her atretic pulmonary valve. The opening in the stenotic tricuspid valve measured only 5 × 2 mm. In the right atrioventricular junctional region, there was no tricuspid valvar tissue. Tricuspid leaflet tissue was located only in an immediately subpulmonary site.

Case 74 was a 3¾-month-old girl (17 weeks). The expected main orifice of her tricuspid valve was atretic. However, she had several patent interchordal spaces on the diaphragmatic surface of the posterior leaflet ( Fig. 13.16 ) and of the anterior leaflet; hence, she had severe congenital tricuspid stenosis. The tricuspid leaflets were thick and myxomatous with a blood cyst.

This is the opened right ventricle (RV) of a 3¾-month-old (17 weeks) girl with pulmonary atresia, intact ventricular septum, and Ebstein’s anomaly (Case 74). The main tricuspid orifice was atretic. However, several interchordal spaces were patent, as can be seen by examining the tricuspid leaflets (TV) from below. Hence, this was severe congenital tricuspid stenosis. The tricuspid leaflets were also thick and myxomatous, with a blood cyst (not seen). This photo was taken at autopsy. (The ruler is in millimeters.)

The right coronary arterial ostium was absent, resulting in a “single” left coronary artery. The left anterior descending coronary artery was markedly enlarged, with three sinusoidal connections between the left anterior descending coronary artery and the right ventricular apical region ( Fig. 13.17 ). Sinusoids were also present between the right coronary artery and the right ventricular cavity on the diaphragmatic surface of the right ventricle. Widespread coronary arteriopathy was present.

This is the same patient as is shown in Fig. 13.16 (Case 74). The right coronary arterial ostium was absent, resulting in a “single” left coronary artery. This photo shows marked enlargement of the “single” left anterior descending (LAD) coronary artery. Between and below the forceps one can see the ostia of sinusoidal communications between the right ventricular apical region and the large left anterior descending coronary artery; there were 3 sinusoids connecting with the left anterior descending coronary artery. Sinusoids were also present between the right ventricular cavity and the right coronary artery on the diaphragmatic surface (not shown). Widespread coronary arteriopathy was also present: coronary mural thickening with luminal narrowing, which may be regarded as coronary artery “jet lesions” and their sequelae. The hypothesis concerning the coronary arteriopathy associated with sinusoids is as follows: Jets from a systemic or suprasystemic right ventricular cavity strike the coronary arteries, producing focal coronary arterial disease with mural thickening and luminal narrowing or occlusion. Sinusoids are typically associated with pulmonary atresia and intact ventricular septum, resulting in systemic or suprasystemic right ventricular pressures. But if Ebstein’s anomaly is also associated with pulmonary atresia and intact ventricular septum, and if enough blood can get into the right ventricular cavity to lead to systemic or suprasytemic right ventricular pressure, then right ventricular–to–coronary arterial sinusoids can be associated with Ebstein’s anomaly. However, it should be understood that coronary-cameral sinusoids typically are associated with high-grade semilunar valvar obstruction (e.g., pulmonary/aortic atresia) with intact ventricular septum and systemic/suprasystemic ventricular pressures. Hence, this is a rare and noteworthy case because sinusoids usually are not associated with Ebstein’s anomaly—we think because usually, Ebstein’s is not associated with system/suprasystemic right ventricular pressures, as it was in this case. If blood can get into the right ventricular cavity, and then has difficulty getting out, in this situation, right ventricular pressures can become systemic/suprasystemic. This is when sinusoids may occur (or persist) with Ebstein’s, as in this rare case.

Many of these features are characteristic of what has been called the venous valve syndrome. We think that this syndrome is better understood as the pulmonary atresia with intact ventricular septum syndrome. Characteristic features include not only pulmonary atresia or very severe pulmonary valvar stenosis with intact ventricular septum, but also coronary-cameral sinusoids ( Fig. 13.17 ), coronary arteriopathy with luminal narrowing or occlusion, prominent venous valve remnants (in particular a prominent Eustachian valve of the inferior vena cava), Uhl’s disease, Ebstein’s anomaly, and partial or total absence of the tricuspid valve leaflets (i.e., partially or totally unguarded tricuspid orifice). Thus, pulmonary atresia with an intact ventricular septum often involves much more than just these two features.

As we noted in 1970, there appears to be an anatomic and developmental relationship between Ebstein’s anomaly, Uhl’s disease, and absence of tricuspid valve leaflets. As will be seen later, these three anomalies also occur together in the setting of pulmonary atresia with intact ventricular septum.

This is why we have been emphasizing from the beginning of this chapter that Ebstein’s anomaly is about much more than just a tricuspid valve anomaly. There is a major right ventricular myocardial component, involving the right ventricular septal surface with the downward displacement of the septal leaflet, creating the “atrialized” right ventricle; plus involvement of the right ventricular free wall surface with the aneurysm of the right ventricular diaphragmatic surface, or, if more extensive, Uhl’s disease or parchment right ventricle involving much or most of the right ventricular free wall anteriorly.

Now, in the present group, we are seeing the association between the Ebstein’s anomaly of the tricuspid valve and pulmonary valvar atresia or extreme stenosis, with intact ventricular septum, and also prominent venous valves.

How does this all make sense anatomically and developmentally? Ebstein’s anomaly is often only a part of something larger—that may be regarded as the tricuspid and right ventricular dysplasia syndrome that can also be associated with right ventricular outflow tract pathology (pulmonary atresia or extremely stenosis) as well as right ventricular inflow tract pathology —prominent right and left venous valve remnants, Ebstein’s anomaly of the tricuspid valve, right ventricular aneurysm inferiorly, or Uhl’s disease (parchment right ventricle) globally.

The foregoing is not merely a developmental hypothesis. Instead, as we are seeing, these are the anatomic facts. These findings, of course, require a developmental explanation. My task here is to try to present the anatomic data as clearly as possible. Briefly, Ebstein’s anomaly, not rarely, is part of something larger, the Ebstein tricuspid valvar and right ventricular dysplasia syndrome. What does “not rarely” mean? In the 50 cases of Ebstein’s anomaly considered in detail thus far ( Tables 13.3 , 13.4 , and 13.5 ), there have been 6 cases of Uhl’s disease (12%), 3 patients with a prominent diaphragmatic right ventricular aneurysm (6%), and 5 cases with a prominent right venous valve remnant or Eustachian valve (10%). If one combines the case of Uhl’s disease with those having a prominent aneurysm, the prevalence of striking right ventricular free wall thinning is 9 patients (18%). This may well be an underestimate because we have only counted cases in which these findings were prominent . (Our impression is that the majority of adult patients with Ebstein’s anomaly have a diaphragmatic surface right ventricular free wall aneurysm that tends to become more and more prominent over time.)

Left-Sided Ebstein’s Anomaly

Wherever the morphologically tricuspid valve and the morphologically right ventricular sinus, body, or inflow tract (the true morphologically right ventricle, as opposed to the conus or infundibulum) are located, one would anticipate that there, Ebstein’s anomaly should also occur. Hence, one would expect to find left-sided Ebstein’s anomaly in association with discordant L-loop ventricles, as in classical congenitally physiologically corrected transposition of the great arteries {S,L,L} and as in double-outlet right ventricle {S,L,L}. As will soon be seen, these expectations are correct. However, to the best of my knowledge, we have never seen Ebstein’s anomaly with concordant L-loop ventricles, as in situs inversus totalis {I,L,I}. However, our failure to observe such a case may simply reflect the rarity of concordant L-loop ventricles. In principle, Ebstein’s anomaly “should” also occur in this situation.

Age at death or cardiac transplantation (in 12 patients, unknown in 2): mean = 6 3 12 ± 7 11 12 years; range from 0 (stillborn) to 19 2 12 years; and mean = 1 8 12 years.

Sex: males = 8; females = 4; unknown = 2. The male/female ratio was 2/1. Such a strong preponderance of one gender (males) was not found in our cases of Ebstein’s anomaly without other major associated cardiovascular anomalies, suggesting that this strong male preponderance may be related to the coexistence of discordant L-loop ventricles and/or major conotruncal malformations (such as L-transposition or double-outlet right ventricle with L-malposition of the great arteries) (hypothesis). However, the series is very small ( n = 12, in which the gender is known); hence no firm conclusion is drawn.

Findings

All 14 cases had Ebstein’s anomaly of the left-sided tricuspid valve and morphologically right ventricular sinus ( Figs. 13.18 , 13.19 , and 13.20 ). The downward displacement of the septal leaflet of the inverted (left-sided) tricuspid valve is well seen in Fig. 13.18 and in Fig. 13.20 .

This is the heart of a 4-month-old-girl (Case 44) with transposition of the great arteries {S,L,L}, a large muscular ventricular septal defect (18 × 14 mm), left-sided Ebstein’s anomaly, left-sided tricuspid regurgitation, congenital complete heart block with a heart rate of 64 beats/minute, and congestive heart failure. Sudden and unexpected cardiac arrest at 5 months of age led to death in 1961. (A) The left-sided cardiac chambers are seen from above and behind, looking down on the left atrium (LA) and the left-sided tricuspid valve, TV (L). VR indicates the location of what normally should have been the valve ring of the left-sided tricuspid valve at the left-sided atrioventricular junction. The lower dotted line (to the viewer’s left) indicates the actual origin of the left-sided septal and posterior leaflets of the left-sided tricuspid valve. The difference between these two lines indicates the downward displacement of the origins of the septal and posterior leaflets of the left-sided tricuspid valve. (B) The opened right-sided mitral valve, MV (R), the right-sided morphologically left ventricle, LV (R), and the transposed pulmonary artery (PA). The muscular ventricular septal defect is well seen. These photos were taken at the time of autopsy.

Transposition of the great arteries {S,L,L} with left-sided Ebstein’s anomaly, marked left-sided tricuspid regurgitation, and mild coarctation of the aorta in a 2-month-old boy. Cardiomegaly was marked, the heart weighing 61 grams (normal for the age =19 grams): 61/19 = 3.2/1, i.e., 221% greater than normal. This patient also had multiple congenital anomalies: bilateral hare lip, bilateral cleft palate, and Meckel’s diverticulum. (A) Opened left-sided morphologically right ventricle, RV (L), and L-transposed aorta (Ao). The posterior tricuspid leaflet was rudimentary, TV (L). (B) The opened right-sided morphologically left ventricle, LV (R), and transposed pulmonary artery (PA). The ventricular septum was intact. The atrial septum was normally formed with an obliquely probe patent foramen ovale. The ductus arteriosus was closed and the coarctation was mild (no measurement was recorded). Hence, from a physiologic standpoint, this patient’s main cardiovascular disability was left-sided Ebstein’s anomaly with severe tricuspid regurgitation (functionally tantamount to severe mitral regurgitation) that led to death at 2 months of age. These photographs were taken at the time of autopsy.

This is the heart of a 15-year-old boy with TGA {S,L,L} with two well-developed ventricles, a conoventricular type of ventricular septal defect that was partially obstructed by tricuspid valve tissue, subpulmonary stenosis produced by excessive atrioventricular valvar tissue attached to the right-sided mitral valve (fibrous subpulmonary stenosis) and left-sided Ebstein’s anomaly with moderate tricuspid regurgitation. He suffered a sudden, unexpected, probably arrhythmic death: he was feeling as well as usual; then he suddenly dropped dead after playing hockey. (A) External frontal view of the heart, typical of TGA {S,L,L}. The left-sided morphologically right ventricle (RV) is hypertrophied and enlarged. Ao, L-transposed ascending aorta; LV, morphologically left ventricle, right-sided; PA, transposed main pulmonary artery; RA, morphologically right atrium. (B) The opened left-sided left atrium (LA), tricuspid valve with Ebstein’s anomaly, and the markedly hypertrophied right ventricular inflow tract (RV). The anterior leaflet (AL) of the tricuspid valve arises normally from the atrioventricular junction, but this leaflet is deep and curtain-like, with marked reduction of the interchordal spaces. The anterior leaflet appears to insert directly into the anterior papillary muscle of the right ventricle—without apparent chordae tendineae intervening between the leaflet and the papillary muscle because most of the interchordal spaces are filled with, and occluded by fibrous valve leaflet-like tissue. The septal leaflet (SL) is markedly hypoplastic, plastered down against the right ventricular septal surface, and this leaflet appears to be nonfunctional. The septal leaflet is mostly well below the atrioventricular junction (AVJ). The posterior leaflet is vestigial and is also markedly downwardly displaced. The RV is left-sided and left-handed. These photos were taken at the time of this consultation (in 1974).

Transposition of the great arteries {S,L,L} (classical physiologically “corrected” transposition) was present in 12 of 14 patients (86%), whereas DORV was found in 2 (14%). The segmental anatomy was DORV {S,L,L} in one, and DORV {S,L,D} in the other. The patient with DORV {S,L, L } indicates that the aortic valve lay to the left (levo, or L) relative to the pulmonary valve; whereas DORV {S,L, D } means that the aortic valve lay to the right (dextro or D) relative to the pulmonary valve.

In TGA { S,L, L}, DORV { S,L, L}, and DORV { S,L, D}, the S,L part of the segmental anatomy indicates that visceroatrial situs solitus {S,-,-}—the usual or normal pattern of anatomic organization—coexisted with L-loop ventricles, {S,L,-}. Hence, discordant or inappropriate L-loop ventricles were present in patients with visceroatrial situs solitus. (In visceroatrial situs solitus, D-loop ventricles “should” be present, as in the solitus normal heart, { S,D, S}.)

Many of the important findings in these 14 patients with discordant L-loop ventricles in visceroatrial situs solitus are summarized in Table 13.6 .

One of our patients with transposition of the great arteries {S,L,L} had the very rare findings of aortic valvar atresia with left-sided Uhl’s disease, left-sided Ebstein’s anomaly with extreme tricuspid regurgitation, and atresia of the right atrial ostium of the coronary sinus ( Fig. 13.21 , patient of Dr. Ghislaine Gilbert, Institut de Cardiologie de Montreal, Canada, our Case 53). Valvar aortic atresia occurs almost always with normally related great arteries, almost never with transposition of the great arteries. Uhl’s disease almost always involves the ventricle of the pulmonary or lesser circulation, almost never the ventricle of the aortic or systemic circulation. So this is a very rare and noteworthy case ( Fig. 13.21 ).

This is the heart of a patient with transposition of the great arteries {S,L,L} with aortic valvar atresia, Uhl’s disease of the left-sided morphologically right ventricle, Ebstein’s anomaly of the left-sided tricuspid valve and right ventricle, extreme left-sided tricuspid regurgitation and atresia of the right atrial ostium of the coronary sinus. (A) External frontal view of the heart and lungs. Note that the free wall of the left-sided morphologically right ventricle (RV) appears thin and wrinkled. The ascending aorta (Ao) is very hypoplastic. The morphologically left ventricle (LV) is right-sided and well developed. (B) Interior view of the left-sided left atrium (LA) opening into the very dysplastic morphologically right ventricle (left-sided). The septal and posterior leaflets of the tricuspid valve are markedly hypoplastic, i.e., functionally absent. The anterior leaflet (AL) of the tricuspid valve is deep, curtain-like, and bound-down to the right ventricular free wall (FW). Note how very thin and almost membranous much of the collapsed right ventricular free wall is. Not only is the right ventricular free wall very deficient in myocardium, but so too is the right ventricular septal surface (VS). The right ventricular septal surface appears smooth or nontrabeculated—because there is no right ventricular septal myocardium covering the left ventricular component of the interventricular septum. This is what electrophysiologists sometimes call “the barrier”: the normally invisible surface of the left ventricular component of the interventricular septum, which normally is covered by right ventricular septal myocardium (but is not in this rare case). Normally, the junction between the left ventricular and right ventricular myocardial components of the ventricular septum can only be seen histologically on transverse sections of the septum. (C) The opened right-sided right atrium, mitral valve, and morphologically left ventricle. Septum primum is deficient and is deflected into the right atrium; a secundum atrial septal defect was also present. This was a patient of Dr. Ghislaine Gilbert of the Institut de Cardiologie de Montréal (the Institute of Cardiology of Montreal), Canada, that we were privileged to study in consultation in 1976. These photographs were taken at the time of this consultation.

Tricuspid Valve Function in Ebstein’s Anomaly

Tricuspid valve function in these 78 postmortem cases of Ebstein’s malformation is summarized in Table 13.9 .

In this series as a whole, tricuspid regurgitation (67%) was much more common than tricuspid stenosis (22%) or tricuspid atresia (imperforate Ebstein’s) (8%). Essentially normal function (no significant tricuspid regurgitation or stenosis) (3%) and noteworthy tricuspid regurgitation plus tricuspid stenosis (1%) were both infrequent ( Table 13.9 ).

Tricuspid regurgitation was more common than tricuspid stenosis or tricuspid atresia, not only in the series as a whole ( Table 13.9 ), but also in each of the four major Ebstein’s subsets, except for Ebstein’s anomaly with incompletely common atrioventricular canal ( Table 13.2 ). In the latter infrequent and consequently unfamiliar Ebstein’s subset ( n = 9), only 3 patients had tricuspid regurgitation (4%), while 4 patients had tricuspid atresia (5%) and 2 had tricuspid stenosis (3%). Thus, 6 patients had tricuspid obstruction (atresia in 4 and stenosis in 2) (8%), while only 3 had tricuspid regurgitation (4%) ( Table 13.2 ). Because the numbers are so small, no conclusion is drawn.

The Ebstein subset with an incomplete form of common AV canal was also interesting in terms of associated anomalies. Congenital asplenia was present in 3 of the 6 patients with tricuspid obstruction: 2 with tricuspid atresia and 1 with tricuspid stenosis (Cases 11 and 17, and Case 21, respectively). One patient with tricuspid atresia (Case 28) had Down syndrome , and another (Case 9) had Uhl’s disease. One patient with Ebstein’s, common AV canal, and tricuspid regurgitation (Case 78) also had coexisting tetralogy of Fallot .

Types of Literature

There are many different kinds of published studies concerning Ebstein’s anomaly:

• 
  

  Pathologic anatomy. Investigations that focus importantly on the pathologic anatomy include the following references: 1, 2, 4, 8, 9, 20, 25, 28, 37, 38, 47, 55, 59, 61, 70, 75, 78, 79, 85, 86, 88, 90, 94, 101, 102, 111, 113, 114, 115, 118, 119, 126, 127, 138, 140, 141, 146, 155, 168, 175, 176, 177, 194, 197, 206.

  
  
• 
  

  Clinical profile and natural history. Studies that focus mainly on the clinical profile and natural history of prenatal and postnatal patients with Ebstein’s anomaly include the following: 12, 13, 14, 24, 30, 35, 41, 44, 46, 49, 50, 51, 54, 62, 76, 83, 87, 100, 121, 122, 125, 132, 134, 135, 137, 141, 143, 145, 147, 149, 152, 154, 158, 161, 165, 172, 175, 187, 189, 195, 211.

  
  
• 
  

  Imaging studies. Investigations that focus on diagnostic imaging studies (angiocardiography, echocardiography, magnetic resonance imaging, and other modalities) are also very important: 1, 12, 38, 40, 52, 56, 58, 60, 61, 64, 66, 67, 74, 77, 83, 91, 93, 96, 107, 108, 112, 113, 115, 116, 124, 126, 131, 132, 134, 135, 137, 140, 144, 153, 156, 157, 159, 167, 168, 200, 207.

  
  
• 
  

  Electrophysiologic studies. Investigations of arrhythmias, their anatomic basis, and their management have also been of considerable importance in patients with Ebstein’s anomaly: 15, 32, 36, 42, 43, 53, 55, 58, 68, 80, 91, 103, 114, 120, 123, 130, 145, 163, 177, 180, 182, 190, 191, 202, 204, 205, 210, 211, 216.

  
  
• 
  

  Pregnancy and delivery. The management and outcome of the pregnancy and delivery of mothers with Ebstein’s anomaly have also been studied with care: 46, 143, 152, 211.

  
  
• 
  

  Who was Wilhelm Ebstein? A few papers have told his story: 3, 5, 6.

  
  
• 
  

  Etiology. What are the basic causes of Ebstein’s anomaly? Several investigations have attempted to address this important question: 31, 41, 65, 71, 119, 120, 141, 155, 203. There appear to be genetic, familial, ^, embryologic, and teratogenic (i.e., lithium) ^, aspects to this question.

  
  
• 
  

  Cardiovascular support. The use of extracorporeal membrane oxygenation (ECMO) as a postnatal rescue technique has been advocated. Balloon pulmonary valvuloplasty has been helpful when significant pulmonary valvar stenosis coexists. The use of prolonged prostaglandin therapy (PGE) to keep the ductus arteriosus open has been advocated, until the neonatal pulmonary resistance falls sufficiently to permit adequate pulmonary blood flow (Qp) at subsystemic right heart pressures. On the other hand, it has been pointed out that limiting ductal patency can be very helpful in avoiding deleterious “circular” shunts that promote right heart failure. So the medical aspects of management can be delicate and difficult. ^{, ,}

  
  
• 
  

  Surgical management. How should patients with Ebstein’s anomaly be managed surgically?

First, perhaps not everyone with Ebstein’s anomaly requires cardiac surgery. For example, Seward and his colleagues reported Ebstein’s anomaly in an unoperated 85-year-old man, the longest known survival in the natural history of this malformation. But what happened to this man? He had tricuspid regurgitation leading to congestive heart failure and death. Despite his “great age,” he might have lived a healthier and longer life had he not had the Ebstein-related tricuspid regurgitation that led to his death. Bearing in mind that the human longevity limit is about 120 years, and 85 is no longer considered all that old.

Although patients with “mild” Ebstein’s (i.e., with little tricuspid regurgitation, no arrhythmias, and no associated malformations) may never require surgery, many do. The worst group is those who present in utero. The dilemma of these patients is presented in several studies. These are the “presurgical” patients, too young (in utero) to be helped by currently available surgical procedures. For example, in the ultrasound (two-dimensional echocardiography) study by Hornberger, Sahn, Kleinman, Copel, and Reed (1991), there were 26 fetuses, 17 with Ebstein’s (63%) and 7 with tricuspid valve dysplasia with normally attached but poorly developed leaflets (27%). Two patients had congenitally unguarded tricuspid orifice (8%). All of these patients had massive right atrial dilation (100%). Hydrops fetalis (massive congestive heart failure) was observed in 6 of 26 (23%). Atrial flutter was present in 5 (19%). Pulmonary outflow tract obstruction coexisted in 11 of 26 (42%): stenosis in 5 and atresia in 6.

The clinical course of 23 patients tells the story: death in utero, 48%, and live born but died, 35%. Hence, the prenatal plus the neonatal death rate was 83%—a devastating natural history. Significant lung hypoplasia—probably secondary to massive cardiomegaly—was found in 10 of 19 autopsied cases (53%).

It is not widely understood that Ebstein’s malformation is a much more malignant disease than are most other forms of congenital heart disease that we think of as being very bad (e.g., transposition of the great arteries), because Ebstein’s anomaly is associated with a high intrauterine death rate, whereas transposition of the great arteries is not.

This grave conclusion was also reached by McElhinney, Salvin, Colan, Thiagarajan, Crawford, Marcus, del Nido, and Tworetzky (2005). Fetal death occurred in 9 of 25 (36%). Of the prenatally diagnosed patients (excluding 8 abortions or terminations), only 7 of 25 survived beyond the neonatal period (28%); that is, the fetal plus neonatal mortality rate was 72%. Independent predictors of death (by multivariable logistic regression analysis) included the following:

• 1.
  

  a right atrial (RA) area >1; and

  
  
• 2.
  

  absence of anterograde blood flow across the pulmonary valve.

(The RA area index = the ratio of the RA area/the area of the “ventricularized” right ventricle + the area of the left atrium + the area of the left ventricle.)

These authors concluded that although outcomes in fetuses and neonates with Ebstein’s anomaly have improved, survival at the severe end of the spectrum remains poor. As a novel approach to management, McElhinney and his colleagues suggested the possibility of giving corticosteroids to ensure fetal pneumatocyte maturity, followed by elective mid–third trimester delivery and then intensive postnatal care.

Thus, at the present time, the surgeons are meeting only the “winners”—the survivors of the often devastating prenatal and neonatal periods.

So this, then, is the current surgical question: how best to treat those Ebstein patients who require (postnatal) surgery? (Prenatal surgery is, of course, the dream. But we’re not there yet.)

• 
  

  Repair. Investigators who favored repair, that is, tricuspid annuloplasty and valvuloplasty typically with plication or exclusion or the atrialized right ventricle, include the following: 27, 45, 69, 73, 87, 97, 105, 106, 110, 129, 131, 142, 144, 150, 160, 166, 169, 173, 174, 178, 180–186, 188, 190, 192, 193, 198–201, 208, 212, 213.

  
  
• 
  

  Replacement. Investigators who favored tricuspid valve replacement include the following: 26, 29, 34, 39, 48, 57, 72, 81, 82, 89, 95, 98, 99, 104, 109, 110, 117, 128, 162, 171, 179, 199.

  
  
• 
  

  Fontan. Ebstein’s anomaly with severe tricuspid stenosis has been treated with a Fontan procedure: 92, 148.

  
  
• 
  

  Creation of tricuspid atresia with central shunt. Another approach to the almost imperforate Ebstein’s anomaly has been pericardial patch closure of the tricuspid orifice and aortopulmonary central shunt (Gore-Tex conduit, 4 mm in diameter).

  
  
• 
  

  Which is the best surgical approach? As the aforementioned references indicate, there is still considerable disagreement concerning the best surgical approach to the management of Ebstein’s anomaly. I am now more than old enough to know that a cardiologist-pathologist-embryologist (like me) should never try to tell a surgeon how to do the operation. However, a few anatomic hints may be helpful.

First, read all the references, think about them, and then make up your own mind, as a surgeon. What can you do technically? What do you feel about the various options? You should like the operation that you are going to do.

I favor repair (as opposed to tricuspid valve replacement). As Carpentier and his colleagues have repeatedly emphasized (correctly, I think), the surgical operation should be tailored to the patient’s function and anatomic status. ^{, ,}

I like the posterior annular plication technique used by Hancock Friesen and her colleagues (2004). It is elegant, it is simple, and it worked well. One ends up with a bicuspid right atrioventricular valve. However, this was a small series ( n = 7) and the ages of the patients ranged from 3.6 to 63.8 years, the mean being 39 years. Hence, this was not a neonatal series, even in part. Mortality was 0 and long-term follow-up will be necessary.

The report by Chauvaud and colleagues (2006) is another excellent example of where we are surgically at the present time. In a series of 26 consecutive patients, mean age 30 ± 16 years (a postneonatal series), the surgeon mobilized the anterior tricuspid leaflet, did a longitudinal placation of the atrialized right ventricle, reduced the size of the tricuspid annulus, closed the secundum atrial septal defect or patent foramen ovale, and performed a bidirectional Glenn procedure in 54% of cases (14/26) to reduce right ventricular preload. Chauvaud et al thought that the indication for plication of the atrialized right ventricle is dyskinesis of this structure. In all cases (mortality = 0), the left ventricular ejection fraction and stroke volume index increased postoperatively.

But now let us consider the more difficult problem: neonatal Ebstein’s . For example, Reemtsen, Fagan, Wells, and Starnes (2006) published their experience with 16 neonates who all had profound heart failure. The indications for surgery were overt heart failure, cyanosis, acidosis, tricuspid regurgitation, depressed right ventricular function, and severe cardiomegaly.

The operative strategy began with an assessment of the possibility of tricuspid valve repair, with or without right ventricular outflow tract reconstruction. If the tricuspid valve was thought to be repairable, this was done ( n = 3, 19%).

If tricuspid valve repair did not seem feasible, then the tricuspid valve was oversewn with a pericardial patch; the tricuspid patch was fenestrated (in 10 of 13 patients) to decompress the right ventricle; reduction atrioplasty was performed; if extensive, the atrialized right ventricle was plicated; and a modified Blalock-Taussig shunt was established to guarantee adequate pulmonary blood flow. Heart transplantation was the initial therapeutic option in 1 patient (6%). Early (hospital) mortality was 31% (5 of 16 patients). Late deaths were 0 of 11 survivors.

In the discussion that followed Dr. Reemtsen’s presentation, Dr. Knott-Craig, who has championed the repair of Ebstein’s malformation to create a competent monocusp valve, noted that his mortality was less than 30%. (In fact it was 12.5%, 1/8.)

Then Dr. Sano, who has advocated total right ventricular exclusion for isolated congestive right ventricular failure, said that he excises the right ventricular free wall, instead of plicating it, in order to reduce the size of the right ventricle and the right atrium. He reported that immediately postoperatively, the cardiothoracic ratio was reduced to 52%; the left ventricular ejection fraction increased from 27% to 62%; and the cardiac index increased from 2.1 to 3.5. Dr. Sano’s mortality with this operative approach has been zero (early = 0; late = 0).

The foregoing are just a few of the many promising surgical studies concerning the surgical therapy of Ebstein’s anomaly. If time, strength, and space permitted, many other investigations would merit discussion. But this I must leave to the reader. I have only three general comments:

• 1.
  

  We should distinguish between studies of the surgical management of neonatal Ebstein’s anomaly, and those that deal with postneonatal Ebstein’s malformation. The difference in severity is huge.

  
  
• 2.
  

  We should be in favor of whatever works best. Although my present bias is in favor of repair rather than replacement, it must be understood that there are many examples of successful results following tricuspid valve replacement (see the above-cited references). At the present time, we simply do not know what the conclusions of the future will be. The optimal medical and surgical management of Ebstein’s anomaly is still evolving. As my old friend and teacher, Dr. Maurice Lev, used to say, “It’s a research problem.” I agree and I would like to add that we are making progress. As mentioned heretofore, I think that repair of the tricuspid valve and of the atrialized right ventricle may well ultimately be accepted as preferable to tricuspid valve replacement; but only time will tell.

  
  
• 3.
  

  Most of the references concerning Ebstein’s anomaly are presented in chronological order (from references 24 onward). This makes it readily possible to comprehend our growth in the understanding of this malformation. In-depth understanding, facilitated by a historical approach, is much better than memorizing a few rules or criteria.

Tricuspid Regurgitation With Pulmonary Atresia and Intact Ventricular Septum

It will perhaps come as no surprise that tricuspid regurgitation (TR) with pulmonary atresia (or extremely severe pulmonary valvar stenosis) and intact ventricular septum (or with one or more very small ventricular septal defects) ( Fig. 13.24 ) was the most common anatomic type of congenital TR without Ebstein’s anomaly ( Table 13.10 ). It should be recalled that Davignon, Greenwold, DuShane, and Edwards described two anatomic types of pulmonary atresia with intact ventricular septum in 1961. When the tricuspid valve was competent, allowing little or no tricuspid regurgitation, then the right ventricular cavity was small, with a very thick-walled right ventricle. However, when the tricuspid valve was regurgitant or incompetent, then the right ventricular cavity was much larger ( Fig. 13.25 ). A competent tricuspid valve permitted the right ventricle (RV) to do pressure work, but little or no flow work; hence the RV was thick-walled and small-chambered. By contrast, an incompetence or regurgitant tricuspid valve allowed the RV to do both pressure work and flow work (even though the flow was largely retrograde into the right atrium). Thus, severe tricuspid regurgitation was associated with an RV that was larger-chambered and thinner-walled. The importance of tricuspid regurgitation in association with pulmonary atresia and intact ventricular septum has been known for almost 50 years (time of writing, 2007).

• 
  

  Age at death ( n = 18):

  
  
  
  
  • 
    

    mean = 191.153 ± 280.159 days (6.37 ± 9.34 months);

    
    
  • 
    

    range = 1.25 to 850 days (1.25 days to 2.33 years); and

    
    
  • 
    

    median = 43.5 days (1.45 months).

  
  

Case 17 was 14-month-old boy with pulmonary atresia, intact ventricular septum, and massive tricuspid regurgitation. The tricuspid valve displayed thickened leaflets, fusion of chordae tendinae, and a markedly reduced number of chordae. The right atrium was hypertrophied and enlarged, with large focal areas of endocardial thickening and whitening (jet lesions). The right ventricular cavity size was considered to be moderate (neither very small, nor very large). An aberrant right subclavian artery was also present. Therapy included the injection of 10% formalin into the adventitia of the ductus arteriosus (in an effort to promote ductal patency) at 1 day of age (in 1976); surgical pulmonary valvotomy at 2 days of age using inflow occlusion; a Waterston anastomosis (ascending aorta to right pulmonary artery, side-to-side) at 3 weeks of age; and attempted repair of the atretic pulmonary valve and right ventricular outflow tract at 3½ weeks of age, leading to death 6 weeks postoperatively. View of the opened right atrium. Note that the tricuspid leaflets are bulging upward, toward the right atrium. The jet lesions on the interior of the right atrial free wall are large, but focal. Right atrial hypertrophy and enlargement are very marked. AS, Atrial septum; RAA, right atrial appendage or free wall.

Photograph taken at autopsy in 1977.

Pulmonary atresia (valvar and subvalvar), intact ventricular septum, massive tricuspid regurgitation with hypertrophied and large-chambered right ventricle (RV). The anterior leaflet (AL) is quite deep, curtain-like, and bound down by its chordae tendineae and papillary muscles. The septal leaflet (SL) is dysplastic, consisting of several masses of fibrous tissue that appear to be nonfunctional. The upper two masses of fibrous tissue are downwardly displaced only minimally; however, the most inferior mass of dysplastic septal leaflet fibrous tissue is definitely downwardly displaced. Consequently, we regarded this patient as having an Ebstein variant anomaly or an Ebstein-like malformation (but not typical Ebstein’s anomaly). This is an excellent example of the large RV cavity that can be associated with pulmonary atresia, intact ventricular septum, tricuspid dysplasia, and severe congenital tricuspid regurgitation. FW, Free wall; VS, ventricular septum. (This patient was studied prior to our coming to Boston. Consequently, this case was not included in the present study. I can find no record of this patient’s gender, or age at death.)

As you can see, the mean age at death in this anatomic type of non-Ebstein tricuspid regurgitation was young (6.37 ± 9.34 months). However, the median age at death, which more truly reflects the real situation, was even younger (1.45 months). Thus, pulmonary atresia with an intact ventricular septum and non-Ebstein tricuspid regurgitation was a rapidly fatal combination of anomalies.

• 
  

  Gender: males = 10, females = 8; male/female ratio = 1.25/1.0.

  
  
• 
  

  Death related closely in time to surgery: In these 18 patients, death was closely related in time to surgical intervention in 13 (72%). In another patient (Case 17, in 1977), death occurred 6 weeks postoperatively (more than 30 days postoperatively; so we did not regard it as “hospital” death, occurring soon after surgery). An additional case (Case 50, in 1969) died from severe intractable congestive heart failure and supraventricular tachyarrhythmia related to an excessively large Waterston anastomosis (5 × 4 mm). None of these fatalities occurred following a Fontan or Fontan-like procedure.

  
  
• 
  

  Anatomic variations: One of these patients (Case 37) had multiple very small ventricular septal defects (not an anatomically intact ventricular septum). Two of these patients had extremely severe pulmonary valvar stenosis (Cases 50 and 60), not a totally atretic pulmonary valve.

Non-Ebstein Tricuspid Regurgitation With Double-Inlet Left Ventricle

Congenital tricuspid regurgitation with double-inlet left ventricle was the second most common anatomic type of tricuspid regurgitation in patients who did not have Ebstein’s anomaly: in 13 of 80 patients (16.25%) ( Table 13.10 ).

• 
  

  Age at death: ( n = 13):

  
  
  
  
  • 
    

    mean = 9.65 ± 9.66 years;

    
    
  • 
    

    range = 0 (18-week fetus) to 31 years; and

    
    
  • 
    

    median = 4.67 years (4 8 12 years).

  
  
  
  
• 
  

  Gender ( n = 12): males = 6, females = 6; male/female ratio = 1. The gender of the 18-week fetus was unknown to us.

  
  
• 
  

  Segmental anatomy ( n = 13): Four different segmental anatomic sets ^∗ (or combinations) were found:

  
  
  
  
  • 1.
    

    TGA {S,L,L} = 6 (46%) ( Fig. 13.26 );

    
    

    ∗ TGA {S,L,L} means transposition of the great arteries with the segmental situs set of situs solitus of the viscera and atria, ventricular L-loop, and L-transposition of the great arteries. TGA {S,D ,D} means TGA with solitus atria, ventricular D-loop and D-TGA. {S,D,S} denotes solitus atria, ventricular D-loop, and solitus normally related great arteries. DORV {S,L,L} indicates double-outlet right ventricle with solitus atria, ventricular L-loop, and L-malposition of the great arteries. The atrioventricular alignments were double-inlet into the morphologically left ventricle in all ( Table 13.10 ). The ventriculoarterial alignments are indicated by the segmental anatomy: L-TGA in 6, D-TGA in 3, solitus normally related great arteries in 3, and DORV with L-malposition of the great arteries in 1.

    
    

    
    

    
    

    

    
    

    
    

    The most common anatomic type of single left ventricle (LV) with an infundibular outlet chamber (Inf) and L-transposition of the great arteries. The aortic valve (Ao) is anterior and to the left of the pulmonary valve (PA). The segmental anatomy is TGA {S,L,L}. The angulation of the atrial septum (AS) 30° to the left of the anteroposterior plane (AP) is typical of solitus atria. The morphologically right atrium (RA) (not drawn) lies to the right of the AS, and the morphologically left atrium (LA) (not drawn) lies to the left of the AS. Double-inlet LV is present because the RA opens through the right-sided mitral valve (MV) into the LV, and the LA opens through the left-sided tricuspid valve (TV) also into the right-sided LV and a little bit into the left-sided and anterior infundibular outlet chamber. The ventricular septal remnant (VS) is located anteriorly and to the left relative to the AS. Why? Because the right ventricular sinus (body, or inflow tract) is absent. The VS is displaced toward the location of the absent RV sinus. Absence of the RV sinus is why the LV is regarded as single (or unpaired), even though an infundibular outlet chamber (which is not a ventricle) is also present. Displacement of the VS to the left and anteriorly is also why there is double-inlet LV. Why is the TV regurgitant? Because of its abnormal insertions, both into the large LV and also into the Inf. Although the TV opens mostly into the right-sided LV, it also opens to a small degree into the left-sided and anterior Inf; consequently the left-sided TV straddles the VS. The abnormal bicameral insertion of the straddling TV appears to be the most important factor predisposing toward tricuspid regurgitation (left-sided). Note the thickening and rolling of the tricuspid leaflet margins (depicted diagrammatically). Geometrically, the AS lies 30° to the left of the anteroposterior (AP) plane. The VS is 20° to the right of the AP plane. The semilunar valves show 40° of rotation to the left of the AP plane.

    
    

    Reproduced with permission from Van Praagh R, Ongley PA, Swan HJC: Anatomic types of single or common ventricle in man. Morphologic and geometric aspects of 60 necropsied cases. Am J Cardiol 1964;13:367.

    
    
    
    
  • 2.
    

    TGA {S,D,D} = 3 (23%);

    
    
  • 3.
    

    {S,D,S} = 3 (23%) ( Fig. 13.27 ); and

    
    

    
    

    
    

    

    
    

    
    

    Holmes hearts, without pulmonary outflow tract stenosis (A), and with pulmonary outflow tract stenosis (B). Single left ventricle (LV) with infundibular outlet chamber (Inf) and normally related great arteries was first described in 1824 by W. F. Holmes, the first Dean of Medicine at McGill University in Montreal, Canada. The right ventricular sinus (RV) is absent; hence the LV is single or unpaired. Absence of the RV inflow tract is also why there is double-inlet LV: there is no RV sinus for the tricuspid valve (TV) to open into. The ventricular septum is displaced to the right—in the direction of the absent RV inflow tract. Although the TV opens mostly into the LV because of the rightward displacement of the VS, the TV straddles the VS remnant to a small degree and opens into the infundibular outlet chamber. Tricuspid regurgitation is frequent, apparently because of the bicameral insertions of the TV associated with straddling of the TV. Tricuspid regurgitation is suggested diagrammatically by the thickening of the tricuspid leaflet margins and by the incomplete coaptation of the TV leaflets. In (B), pulmonary outflow tract stenosis is suggested by the relative smallness of the pulmonary artery (PA) compared with the aorta (Ao) and by the fact that the pulmonary valve is bicuspid. The distinctive and unusual feature of the Holmes heart is that the great arteries are normally related; single LV with infundibular outflow chamber is usually associated with abnormally related great arteries, such as transposition of the great arteries. The segmental anatomy in the Holmes heart is {S,D,S}. In (A), the anatomic geometry is as follows: The atrial septum (AS) is angulated 30° to the left of the sagittal plane (if the AS is considered to be hinged posteriorly to the sagittal plane); this angulation is normal for solitus atria. The ventricular septal remnant (VS) is displaced far to the right of the AS, and the VS is 40° to the left of the sagittal plane (if the VSD is considered for the purposes of measurement to be hinged posteriorly to the sagittal plane). The semilunar valves display 150° dextrorotation relative to the sagittal plane, which is normal (for solitus normally related great arteries). In (B), the anatomic geometry is as follows: atrial septum, 30° to the left (normal); ventricular septum, marked rightward displacement and angulated 60° to the left; and the semilunar relationships as in tetralogy of Fallot (TOF), the aortic valve 100° dextrorotation (subnormal). Even though the dextrorotation of the aortic valve is subnormal (150° is normal), nonetheless this TOF-like semilunar interrelationship is considered to be within the normal range (but at the subnormal end of the range) because there is aortic valve–to–mitral valve direct fibrous continuity (typical of normally related great arteries). MV, Mitral valve.

    
    

    Reproduced with permission from Van Praagh R, Ongley PA, Swan HJC: Anatomic types of single or common ventricle in man. Morphologic and geometric aspects of 60 necropsied cases. Am J Cardiol 1964;13:367 and from Van Praagh R, Plett JA, Van Praagh S: Single ventricle: pathology, embryology, terminology, and classification. Herz 1979;4:113.

    
    
    
    
  • 4.
    

    DORV {S,L,L} = 1 (8%).

  
  

State of the Right Ventricular Sinus

All 13 patients had double-inlet left ventricle because the RV sinus (body, or inflow tract) was either very underdeveloped ( n = 4, 31%) or absent ( n = 9, 69%). All had functionally single left ventricle because none had a physiologically adequate RV sinus (body, or inflow tract). Of these 13 patients, 9 (69%) had no anatomically demonstrable RV sinus. Hence, the RV sinus was considered to be absent, resulting in an anatomically single LV in these 9 patients. Thus, double-inlet LV indicated (1) that the atrioventricular canal was divided into two AV valves, that is, that the AV canal was not in common (undivided), and (2) that anatomically single LV (absent RV sinus) or functionally single LV (marked hypoplasia of the RV sinus) was present. From a physiologic and/or surgical standpoint, there is no practical difference between functionally and anatomically single LV. Both types of patients must be treated as having univentricular hearts (i.e., single LV), because the RV inflow tract (the main pumping portion of the RV) is functionally useless or absent.

Why was tricuspid regurgitation present in all? Typically, because the tricuspid valve was abnormally attached, opening into both the morphologically left ventricle (the LV) and into the infundibular outflow chamber (when the RV sinus was absent), or into the infundibular outlet chamber and into the diminutive RV sinus (when the latter was present). Consequently, the tricuspid valve typically straddled the ventricular septal remnant because of its bicameral insertions, resulting in tricuspid regurgitation that was right-sided relative to the mitral valve with a ventricular D-loop, or left-sided relative to the mitral valve when a ventricular L-loop was present ( Figs. 13.26 and 13.27 ).

Let us examine this important question (why TR?) on a case-by-case basis.

Case 7: An 11-year-old girl, with normal segmental anatomy, that is, {S,D,S}, had double-inlet LV because the RV sinus was extremely underdeveloped, but not absent. She had congenital mitral stenosis (supravalvar and valvar). The tricuspid valve was straddling through a ventricular septal defect of the AV canal type with biventricular insertions into the large LV and the diminutive RV. The tricuspid leaflets were thickened and rolled, typical of tricuspid regurgitation. This patient also had severe pulmonary outflow tract stenosis involving marked narrowing of the subpulmonary os infundibuli. She died 3 days following a modified Fontan procedure.

Thus, the most important factor predisposing to tricuspid regurgitation appeared to be the abnormal tensor apparatus: the straddling tricuspid valve inserting into the large LV and the diminutive RV; the tricuspid valve straddled through a VSD of the AV canal type (typical of straddling tricuspid valve). In association with marked underdevelopment of the RV sinus, there was marked ventriculoatrial malalignment, because the ventricular septal remnant was displaced in the direction of the small or absent right ventricular sinus—to the right with a ventricular D-loop, or to the left with a ventricular L-loop ( Figs. 13.26 and 13.27 ). Congenital mitral stenosis was also present. Thus, both AV valves were dysfunctional.

From a physiologic and surgical standpoint, this patient did have a functionally (if not anatomically) Holmes heart , that is, a functionally single LV (because the RV sinus was uselessly small), with an infundibular outlet chamber and normally related great arteries. The presence of double-inlet LV helpfully indicates that a functionally single LV is present.

Case 8, a 4-year-old girl with normal segmental anatomy, that is, {S,D,S} and extreme hypoplasia of the RV sinus, also had a tricuspid valve that straddled through a VSD of the AV canal type. The tricuspid valve inserted into the infundibular outlet chamber and into the large left ventricle. The tricuspid valve leaflets were thickened, consistent with tricuspid regurgitation, and mitral regurgitation was also present. Double-inlet left ventricle indicated that from the functional standpoint, a Holmes heart was present. Again, both AV valves were dysfunctional (both regurgitant). This patient died after a Fontan takedown.

Case 10, a 21-year-old man, had TGA {S,D,D} (TGA {S,D,D} indicates that transposition of the great arteries is present with situs solitus of the viscera and atria, ventricular D-loop, and D-TGA), double-inlet left ventricle, marked hypoplasia of the RV sinus, and two ventricular septal defects (of the AV canal type and of the conoventricular type). The regurgitant tricuspid valve straddled through the VSD of the AV canal type. A persistent left superior vena cava drained into the coronary sinus and opened into the right atrium. Pulmonary stenosis (valvar and subvalvar) coexisted. The patient also had Leopard syndrome. Atrial flutter-fibrillation, congestive heart failure, and left ventricular dysfunction led to terminal ventricular fibrillation. Tricuspid regurgitation was moderate in severity and was only one of this young man’s many cardiovascular problems.

Case 13, a 2 5 12 -year-old boy, had TGA {S,L,L} (TGA {S,L,L} means transposition of the great arteries with situs solitus of the viscera and atria, ventricular L-loop, and L-TGA) with double-inlet into the right-sided LV, single LV (no RV sinus found), and infundibular outlet chamber. The left-sided tricuspid valve leaflets opened into the LV free wall, without well-formed chordae tendineae or papillary muscles. This myxomatous tricuspid valve was both regurgitant and stenotic. A blood cyst of the pulmonary valve resulted in pulmonary valvar stenosis. Congestive heart failure appeared at 3 months of age.

At 22 months of age, atrial septectomy was performed, followed by a modified Fontan procedure at 2 5 12 years. A subsequent Fontan takedown was followed by intraoperative death. This patient illustrated tricuspid regurgitation and stenosis occurring together, the left-sided tricuspid valve having congenital absence of tensor apparatus (no chordae tendineae and no papillary musculature). Congenital absence of the tricuspid tensor apparatus (chordae tendineae and papillary muscles) is a rare and largely unknown anomaly.

Case 15, a 31-year-old woman, had TGA {S,L,L} with double-inlet LV, single LV with infundibular outlet chamber, moderate fibrous subvalvar pulmonary stenosis, and straddling of the left-side tricuspid valve through the bulboventricular foramen into the infundibular outlet chamber. The tricuspid valve did not obstruct the bulboventricular foramen. The left-sided tricuspid valve was basket-like and was associated with only mild tricuspid regurgitation. The Eustachian valve of the inferior vena cava was prominent. Complete heart block appeared spontaneously postnatally. Ventricular premature beats and atrial flutter—fibrillation occurred later. There was one episode of syncope. A pacemaker was inserted at 22 5 12 years. The pacemaker generator was changed at 24 8 12 years. Another pacemaker was inserted at 30 7 12 years of age. Sudden death occurred 10 months later at age 31 5 12 years of age, thought to be secondary to a ventricular tachyarrhythmia.

This patient, with the most common form of single ventricle (i.e., single LV with an infundibular outlet chamber and TGA {S,L,L}) demonstrates a situation in which ectopy was predominant and led to death. Tricuspid regurgitation (left-sided) was only mild in severity and was regarded as of relatively minor clinical importance.

Case 27, a 3 11 12 -year-old boy, had TGA {S,D,D}, double-inlet LV, single LV with infundibular outlet chamber, and thickening and rolling of the right-sided tricuspid valve indicating tricuspid regurgitation. At 1 month of age, he had banding of the main pulmonary artery. At 1 year, he had a modified right Blalock-Taussig anastomosis. By 3 11 12 years of age (in 1987), he underwent a Stansel procedure (anastomosis of the proximal main pulmonary artery to the ascending aorta to bypass developing subaortic stenosis at the bulboventricular foramen) and a modified Fontan procedure (anastomosis of the right atrium to the distal main pulmonary artery, to reestablish pulmonary arterial blood flow); he died intraoperatively.

This patient exemplifies the problem of achieving optimal pulmonary blood flow, and managing the development of subaortic stenosis in TGA {S,D,D} with single LV and double-inlet LV. Tricuspid regurgitation was present, but was not the main clinical problem.

Case 28, a 22-day-old boy, had TGA {S,L,L} with double-inlet LV, single LV and infundibular outlet chamber, and subaortic stenosis because of a restrictively small bulboventricular foramen. There was mild stenosis of the right atrial ostium of the superior vena cava. The leaflets of the left-sided tricuspid valve were thickened, nodular, regurgitant, and stenotic. The tricuspid chordae tendineae inserted directly into the left ventricular septal surface; the tricuspid valve had no papillary muscles. Death at 22 days of age occurred in 1967.

This patient illustrates the general problem of all of these patients with double-inlet LV: marked ventriculoatrial malalignment, resulting in abnormal tensor apparatus of the tricuspid valve—when the right ventricular inflow tract is diminutive or absent (absent in this patient) ( Figs. 13.26 and 13.27 ). Tricuspid regurgitation (with or without tricuspid stenosis) is a sequela of ventriculoatrial malalignment and right ventricular sinus malformation. In other words, congenital tricuspid regurgitation (with or without congenital tricuspid stenosis) is not really a primary diagnosis; instead congenital TR (with or without tricuspid stenosis) is a secondary effect of the malformations of the tricuspid tensor apparatus, the small or absent RV sinus, the very abnormal location of the ventricular septal remnant, the abnormally hypertrophied and enlarged LV, and the associated ventriculoatrial malalignment.

Case 36, a 15 7 12 -year-old boy with TGA {S,L,L}, had absence of the left-sided right ventricular sinus, single left ventricle (right-sided) with infundibular outlet chamber (left-sided), double-inlet left ventricle (right-sided), with straddling of the left-sided tricuspid valve, and tricuspid regurgitation (left-sided) with left atrial jet lesions.

This patient underwent banding of the main pulmonary artery at 18 months of age. At 4 1 12 years of age, he developed acquired complete heart block. In 1980, at 15 7 12 years of age, the patient had a Fontan type of procedure. His right-sided normally functioning mitral orifice was closed with a Dacron patch. The band of the main pulmonary artery was removed. The pulmonary valve was sutured closed. A 20 mm nonvalved conduit was placed from the right atrium to the distal main pulmonary artery. The patient died soon postoperatively.

Enthusiasm at our institution soon waned for the surgical creation of “tricuspid” atresia to facilitate a Fontan type of procedure, particularly when it involved patching closed the patient’s only normally functioning atrioventricular valve, the only postoperatively patent atrioventricular valve being malfunctional (in this case, regurgitant).

Case 58, a 4 8 12 -year-old boy, had TGA {S,D,D} with single left ventricle and infundibular outlet chamber. There was double-inlet left ventricle with tricuspid regurgitation. The tricuspid leaflets were thickened and rolled, whereas the mitral leaflets were unremarkable. The right superior vena cava was absent. A persistent left superior vena cava drained into the coronary sinus and thence into the right atrium, where a prominent Chiari’s network (remnants of the right sinoatrial valvar leaflet) was present.

Case 65 was an 18-week-old fetus with complex congenital heart disease. We examined the heart of this patient as a consultation; we do not know the gender of this fetus.

The heart displayed double-outlet right ventricle {S,L,L} with mitral atresia (right-sided), a large and functionally single left ventricle (right-sided), an almost absent right ventricular sinus (left-sided), and a secundum type of atrial septal defect. The leaflets of the left-sided tricuspid valve were myxomatous, with attachments to the left ventricular free wall (right-sided), to the ventricular septal crest, and to the right ventricular free wall (left-sided). This left-sided tricuspid valve straddled the ventricular septum and severe tricuspid regurgitation was thought to have been present in utero because of noncoaptation of the leaflets.

In order to understand this case it is necessary to know that mitral atresia rarely can be associated with a large left ventricle. Usually with mitral atresia, the left ventricle is small to tiny. Mitral atresia with a large left ventricle also is typically associated with a small (or absent) right ventricular sinus. Hence, mitral atresia with a large left ventricle is an anatomically or functionally single left ventricle (depending on whether the right ventricular sinus is absent, or very small as it was in this patient) with an infundibular outlet chamber. Both great arteries originated above the diminutive right ventricle in this patient; hence the diagnosis of DORV {S,L,L}—with mitral atresia (right-sided), tricuspid regurgitation (left-sided), large left ventricle (right-sided), diminutive right ventricle (left-sided) and straddling tricuspid valve (left-sided). To the best of our present knowledge, mitral atresia with large (or single) left ventricle was first reported by Quero in 1972.

Case 68 was a 12-year-old girl with dextrocardia, TGA {S,L,L}, single left ventricle with infundibular outlet chamber, double-inlet left ventricle, extreme mitral stenosis (right-sided) with parachute mitral valve and all chordae tendineae inserting into the anterolateral papillary muscle of the left ventricle, tricuspid regurgitation (left-sided) with marked left atrial hypertrophy, enlargement, and jet lesions. The regurgitant tricuspid valve was replaced with a Björk-Shiley valve in 1985 at another institution. Postoperatively, there was severe pulmonary outflow tract obstruction related to the tricuspid valve prosthesis. A modified Fontan procedure had also been performed.

Case 70 was a 9-month-old girl with a Holmes heart. She had a single left ventricle with double-inlet left ventricle, an infundibular outlet chamber, normally related great arteries, normal segmental anatomy—{S,D,S}, tricuspid regurgitation, and subaortic stenosis (related to abnormal insertion of the septal leaflet of the tricuspid valve). The anterior papillary muscle was absent from the infundibular outlet chamber. The superior commissure of the tricuspid valve inserted abnormally into the conal septum.

Case 71 was a 19-year-old woman with TGA {S,L,L}, a single left ventricle with infundibular outlet chamber, double-inlet left ventricle, straddling of both atrioventricular valves with tricuspid regurgitation (left-sided) and mitral regurgitation (right-sided). Both AV valves inserted into the single left ventricle and into the infundibular outlet chamber. Both AV valves had thickening and rolling of the leaflet free margins. There was mild to moderate subaortic stenosis caused by narrowing of the bulboventricular foramen, with a fibrous rim of endocardial sclerosis surrounding the bulboventricular foramen. Subpulmonary stenosis was also present because the pulmonary outflow tract passed between the medial leaflets of both AV valves as they entered the left ventricle. Hence, this 19-year-old woman had the devastating combination of regurgitation of both atrioventricular valves and stenosis of both great arterial outflow tracts.

Non-Ebstein Regurgitation Associated With Hypoplastic Left Heart Syndrome

Although the two most common anatomic types of non-Ebstein tricuspid regurgitation are, on reflection, not too surprising (pulmonary atresia with intact ventricular septum in 22.5%, and double-inlet left ventricle in 16.25%, Table 13.10 ), the third most common anatomic type—with hypoplastic left heart syndrome in 15% ( Table 13.10 )—is not as intuitively obvious. One wonders, why may the hypoplastic left heart syndrome have tricuspid regurgitation? This is the question that we must now explore. To avoid vague generalizations let’s examine these patients case by case.

Case 34 was an 8-month-old girl with double-outlet right ventricle {S,D,D} with a subpulmonary conus and aortic valve–tricuspid valve fibrous continuity, mitral atresia, a subaortic conoventricular type of ventricular septal defect, subaortic stenosis between the conal septum anterosuperiorly and the tricuspid valve posteroinferiorly. There was tricuspid regurgitation with thickened and myxomatous tricuspid leaflets. The aortic valve was bicuspid (bicommissural) because of absence of the right coronary–left coronary commissure, the aortic isthmus was hypoplastic, and the ductus arteriosus was patent. At 12 days of age, the main pulmonary artery was banded, the patent ductus arteriosus was ligated, and the hypoplastic aortic isthmus was amplified with a subclavian flap angioplasty. Congestive heart failure postoperatively was associated with ineffective main pulmonary artery banding. Consequently, at 1½ months of age (in 1983) the main pulmonary artery was rebanded and an atrial septectomy was performed. Sudden unexpected death occurred at home at 8 months of age. The immediate cause of death was thought probably to have been a ventricular arrhythmia.

Why did this patient have congenital, non-Ebstein, tricuspid regurgitation? We think that the answer may involve two factors: (1) the thick and myxomatous tricuspid valve leaflets; and (2) the coexistence of double-outlet right ventricle with aortic outflow tract stenosis, plus main pulmonary artery banding.

Again, it is noteworthy that this patient had a specific type of DORV associated with hypoplastic left heart syndrome , that is, DORV with a subpulmonary conus (only)—a unilateral (not a bilateral) conus, with aortic-tricuspid fibrous continuity, and aortic outflow tract stenosis between the conal septum anterosuperiorly and the tricuspid valve posteroinferiorly, with a somewhat hypoplastic and bicuspid aortic valve and a hypoplastic (low-flow) aortic isthmus.

Some of the problems associated with DORV plus hypoplastic left heart syndrome are illustrated by this case: an abnormal and myxomatous tricuspid valve and double-outlet right ventricle with obstruction of both great arterial outflow tracts (congenital aortic outflow tract narrowing, and banding of the main pulmonary artery).

Case 46 was a 1 8 12 -year-old boy with mitral atresia {S,D,S}. Tricuspid regurgitation was observed both echocardiographically and angiocardiographically. A Norwood procedure was performed at 21 days of age (in 1986). The postoperative course was characterized by otitis media and upper respiratory tract infections. The clinical picture of congestive heart failure appeared. The modified Blalock-Taussig anastomosis was thought to be excessive. At autopsy, the tricuspid valve appeared to be morphologically unremarkable.

How should we interpret this case? Certainly the tricuspid regurgitation, although well documented, did not appear to be the patient’s only hemodynamic problem. This may well be the type of patient that may have done better with a Sano shunt from the right ventricular infundibulum to the pulmonary artery bifurcation, rather than having a modified Blalock-Taussig shunt as in the original Norwood procedure.

This case also reminds one that the tricuspid valve is not designed to occlude an approximately circular systemic atrioventricular orifice. This task is well performed by the deep anterior leaflet of an uncleft mitral valve. The tricuspid valve is designed to occlude the elliptical pulmonary atrioventricular orifice, not the nearly circular systemic atrioventricular orifice; and the tricuspid valve is normally cleft (between the anterior and the septal tricuspid leaflets). So, when the tricuspid valve is required to serve as the systemic atrioventricular valve it is not surprising that it may prove to be regurgitant. The papillary muscles of the tricuspid valve also are not the large, well-balanced pair that the mitral valve normally has. The right ventricle has only one radiation of the conduction system: the right bundle branch is the superior radiation. The right ventricle normally does not have an inferior radiation of the conduction system, whereas the left ventricle normally does. The right ventricle normally is supplied mainly by only one coronary artery branch (the right coronary artery), whereas the left ventricle is normally supplied mainly by two coronary artery branches (the anterior descending and the circumflex branches).

Hence, there are a lot of anatomic reasons why the tricuspid valve and its tensor apparatus and ventricle may not perform as well as the mitral valve and its tensor apparatus and ventricle.

Nonetheless, it is still sobering to see that significant tricuspid regurgitation can and does occur through a morphologically normal tricuspid valve in the setting of typical hypoplastic left heart syndrome (as in this case of mitral atresia).

Case 48 was a 36-day-old black boy with aortic valvar atresia, mitral atresia, intact ventricular septum, a restrictive patent foramen ovale, and normal segmental anatomy, that is, {S,D,S}. At 14 days of age the patient underwent a Norwood procedure (in 1985). The postoperative course was characterized by supraventricular tachycardia, and mild coarctation of the aorta was noted at the distal end of the aortic arch reconstruction. Mild to moderate tricuspid regurgitation was observed both by angiography and by echocardiography. At autopsy, tricuspid regurgitation was thought to have been significant because the tricuspid leaflets were unable to coapt completely. Right ventricular hypertrophy and enlargement were very marked, as were right atrial hypertrophy and enlargement.

Thus, in this 36-day-old post-Norwood patient, significant tricuspid regurgitation was confirmed at autopsy because of incomplete tricuspid leaflet coaptation associated with very marked right ventricular hypertrophy and enlargement. This case again illustrates that the tricuspid valve is not designed to occlude the approximately circular systemic atrioventricular orifice that is associated with mitral and aortic valvar atresia.

Case 49 was at autopsy a 1 1 12 -year-old-boy with aortic valve atresia {S,D,S} and intact ventricular septum. There was also fibrous subaortic stenosis produced by adherence of the anterior mitral leaflet to the left ventricular septal surface. A Norwood procedure was performed at 5 days of age (in 1985). Postoperatively, a residual coarctation was found at the distal end of the aortic arch reconstruction with a gradient of 70 mm Hg. Attempted balloon dilation of the coarctation site was ineffective. Sudden unexpected death occurred 12¾ months postoperatively. Autopsy revealed partial obstruction of the modified right Blalock-Taussig shunt. Thickening and rolling of the anterior tricuspid leaflet was also found, consistent with tricuspid regurgitation. However, tricuspid regurgitation was not regarded as the patient’s most important disability. Instead, the coarctation of the aorta and the partially obstructed Blalock-Taussig shunt were thought to be the patient’s main hemodynamic problems.

This patient illustrates the important point that tricuspid regurgitation is not necessarily the patient’s most important hemodynamic problem; instead, tricuspid regurgitation may be only part of the hemodynamic handicap—and not necessarily the most important part. Hemodynamic problems are often multiple.

Case 51 was a 3½-year-old girl with aortic valve atresia, extreme mitral stenosis, intact ventricular septum, and {S,D,S} segmental anatomy who underwent a Norwood procedure in 1985 at 3½ days of age and who died intraoperatively. Autopsy revealed precoronary stenosis, that is, kinking of the neoaortic root such that the coronary ostia were nonpatulous. Echocardiography preoperatively had shown moderate tricuspid regurgitation, but at autopsy the tricuspid valve appeared morphologically normal. This case again illustrates that in hypoplastic left heart syndrome, tricuspid regurgitation can occur through an anatomically normal tricuspid valve.

Case 53 was a 43-day-old boy with aortic valvar atresia, mitral atresia, and {S,D,S} segmental anatomy who had tricuspid regurgitation with marked hypoplasia of the right ventricular papillary muscles, and very abnormal chordae tendineae. The chordae were reduced in number and were long and redundant. Thus, tricuspid regurgitation in this patient was related to very abnormal tricuspid tensor apparatus (papillary muscles and chordae tendineae).

This patient illustrates how difficult it is to generalize about the tricuspid regurgitation that may be associated with hypoplastic left heart syndrome. The tricuspid valve can be morphologically unremarkable (as above), or very abnormal (as in this patient).

This patient with hypoplastic left heart syndrome had additional cardiovascular abnormalities. There was atresia of the right atrial ostium of the coronary sinus. A small persistent left superior vena cava was confluent with the coronary sinus. Because the right atrial ostium of the coronary sinus was atretic, we thought that the blood flow in the coronary sinus may well have been retrograde—into the small left superior vena cava.

This patient died in 1984. One wonders, was there trisomy 18, or some other trisomy? We don’t know the answers to these questions. (One may assume that if we do not mention an abnormal finding, either it was not present, or we do not know. All relevant findings of which we are aware are included here.)

Case 57 was a stillborn male fetus. (The intrauterine demise was natural, not induced by abortion.) This fetus had DORV {S,D,D}, that is, double-outlet right ventricle with solitus viscera and atria, D-loop ventricles, and D-malposition of the great arteries. The infundibulum was subpulmonary, with aortic valve-to-tricuspid valve direct fibrous continuity.

It should be recalled at this point that DORV with a unilateral (as opposed to bilateral) conus, either a subpulmonary infundibulum with aortic-tricuspid fibrous continuity or a subaortic conus with pulmonary-tricuspid fibrous continuity, is typical of DORV with hypoplastic left heart syndrome. So, one should be wondering at this point, What kind of hypoplastic left heart syndrome did this fetus have?

Septum primum was redundant and spinnaker-like, reducing the via sinistra into left atrium which was small. The mitral valve was hypoplastic and was abnormally attached both to the left ventricular septal surface and to the left ventricular free wall. Hypoplasia of the left ventricle was marked.

There was a patent foramen ovale, as was suggested above. Tricuspid regurgitation was severe. The anterior tricuspid valve was deep and curtain-like, tethered to the right ventricular free wall, and this leaflet was nonfunctional. The septal leaflet of the tricuspid valve was not downwardly displaced. Hence, Ebstein’s malformation of the tricuspid valve was considered not to be present. The pulmonary valve was bicuspid (bicommissural). This fetus also had a small ventricular septal defect of the conoventricular type (between the conal septum above and the ventricular septum and septal band below).

Thus, this fetus died in utero because of the combination of hypoplastic left heart syndrome with severe tricuspid regurgitation through a dysplastic tricuspid valve with a tethered and nonfunctional anterior leaflet.

Case 62 was a 19-month-old boy whose hypoplastic left heart syndrome consisted of marked congenital mitral stenosis (thickening of leaflet tissue, with a small anterolateral papillary muscle, but not parachute mitral valve, and not Shone syndrome), mild valvar aortic stenosis with a hypoplastic and bicuspid (bicommissural) aortic valve, and preductal coarctation of the aorta. This patient also had pulmonary artery hypertension, severe congenital tricuspid regurgitation (with thickening, rolling, and redundancy of the anterior and septal leaflet), massive right ventricular hypertrophy and enlargement, and marked right atrial hypertrophy and enlargement. This patient, who died in 1992, had polyvalvar disease (mitral, aortic, and tricuspid). His karyotype is unknown; hence we cannot establish or exclude the possibility of a trisomy.

Case 72 was a 12-year-old boy with DORV {S,L,L}, that is, double-outlet right ventricle with situs solitus of the viscera and atria, a discordant ventricular L-loop, and L-malposition of the great arteries. His hypoplastic left heart syndrome consisted of membranous right-sided mitral atresia, very marked hypoplasia of the right-sided left ventricle (the left ventricular cavity was 1 to 2 peas in size, with endocardial fibroelastosis), with an intact ventricular septum. The patent foramen ovale was restrictive. Left-sided tricuspid regurgitation was marked, with thickening and rolling of all leaflet free margins. Congenital absence of pulmonary valve leaflets was associated with marked pulmonary outflow tract stenosis (3 to 4 mm in diameter). This patient had a functionally single right ventricle (because the diminutive left ventricle was functionally useless).

This patient, who died in 1978, illustrates that severe congenital left-sided tricuspid regurgitation can be associated with right-sided hypoplastic left heart syndrome in discordant L-loop ventricles.

Case 75 was a 5-day-old girl with mitral atresia, aortic atresia, intact ventricular septum, and {S,D,S}. She had a truly hypoplastic left heart syndrome with a tiny left ventricle that was both small-chambered and thin-walled .

It should be understood that many patients with so-called hypoplastic left heart syndrome may in fact not have a hypoplastic left ventricle. Consider aortic valvar atresia with intact ventricular septum and a patent mitral valve. The left ventricle typically is small-chambered, but it is also thick-walled . This is the so-called peach-stone left ventricle: the left ventricle resembles a thick-walled peach from which the peach stone has been removed. When pulmonary valvar atresia is associated with an intact ventricular septum and a patent tricuspid valve, the same analogy pertains: this is a peach-stone right ventricle, resembling a thick-walled peach from which the peach stone has been removed.

In both situations, the same question remains: Is the ventricle truly hypoplastic? Yes, the cavity is small because the ventricle can do little or no flow work (assuming that the atrioventricular valve is competent). But the wall is thick, because the ventricle can do pressure work. Are such ventricles really hypoplastic? Do they weigh significantly less than normal? This question has proved difficult to answer with certainty because each ventricle makes a contribution to the ventricular septum. To get an accurate weight of the left ventricle, one would have to weigh not only the left ventricular free wall, but also the left ventricular component of the interventricular septum . It is the latter—the ventricular septal component—that has proved difficult to weigh with precision. This understanding, or mental reservation, concerning hypoplastic left heart syndrome applies to this entire section concerning congenital tricuspid regurgitation with hypoplastic left heart syndrome. Patients with mitral and aortic valvar atresia and intact ventricular septum have truly hypoplastic left ventricles (like Case 75). However, patients with aortic atresia, intact ventricular septum, and patent mitral valves may or may not in fact have truly hypoplastic left ventricles.

To summarize, there are two very different anatomic types of hypoplastic left heart syndrome: (1) those with mitral and aortic valvar atresia and intact ventricular septum with very thin left ventricular free walls; and (2) those with aortic atresia with intact ventricular septum and patent mitral valve with thick left ventricular free walls, and often with endocardial fibroelastosis. We call these patent mitral valves “hypoplastic.” Often they are as normal as they can be, but these mitral valves have to be small in order to open into these small left ventricular cavities.

So Case 75 had a truly hypoplastic left ventricle. The secundum atrial septal defect measured 5 × 8 mm. Echocardiography revealed moderate tricuspid regurgitation, confirmed at autopsy by thickened and myxomatous tricuspid leaflets. Dextrocardia was present. A ventricular malposition similar to crisscross atrioventricular relations was also found. Compared with normal, the ventricles were rotated 90°. The rotation was 90° in a counterclockwise direction as viewed from the atria, or 90° in a clockwise direction as seen from the ventricular apex. The ventricles were superoinferior with a horizontal ventricular septum, large right ventricle superiorly and small left ventricle inferiorly. The appearance of crisscross AV relations is better seen when both AV valves are patent. In typical crisscross AV relations, which this patient did not have, the ventricular malposition, as measured by the ventriculoatrial septal angle, often is greater than 90°.

Case 76 was a 17-day-old girl with membranous mitral atresia, subaortic narrowing, a bicuspid aortic valve with underdevelopment of the right coronary/left coronary commissure, tubular hypoplasia of the transverse aortic arch, preductal coarctation of the aorta, a large patent ductus arteriosus, a small secundum type of atrial septal defect consisting of multiple small restrictive foramina in septum primum, and tricuspid regurgitation with thickening and rolling of the free margins of the anterior and septal leaflets. Therapeutic interventions in 1993 included a balloon atrial septostomy and a Norwood procedure.

So, this is another patient with significant non-Ebstein tricuspid regurgitation associated with hypoplastic left heart syndrome.

Case 77 was a 1½-month-old girl with a small-chambered left ventricle, with a left ventricular free wall that was 4 to 6 mm thick. There was diffuse endocardial fibroelastosis of the left ventricular endocardium. Remarkably, the mitral valve was a normal miniature, and the aortic valve was also a normal miniature.

Consequently, we concluded that the patient had primary hypoplasia of the left ventricle with endocardial fibroelastosis; in other words, the left ventricular hypoplasia did not appear to be secondary to mitral or aortic valve pathology. In this sense, the left ventricular hypoplasia and the left ventricular endocardial fibroelastosis were both regarded as “primary,” that is, idiopathic, of cause unknown—not apparently secondary to (or associated with) mitral and/or aortic obstructive pathology, as left ventricular hypoplasia usually is.

A secundum type of atrial septal defect (6 × 2 mm) was present. Right ventricular hypertrophy and enlargement were massive. Right atrial hypertrophy and enlargement were marked. Tricuspid regurgitation was described as moderate by two-dimensional echocardiography.

Autopsy revealed thickened, myxomatous nodules of the septal leaflet of the tricuspid valve. However, the anterior and posterior leaflets were morphologically unremarkable. The papillary muscles of the right ventricle were very small. Diffuse jet lesions were present of the right atrial endocardium.

In 1993 it was decided not to perform a Norwood procedure because of the presence of significant tricuspid regurgitation. Instead, the therapeutic plan was cardiac transplantation. However, this patient died waiting for a donor heart.

Congenital Non-Ebstein Tricuspid Regurgitation Associated With Trisomies

Tricuspid regurgitation associated with trisomies and having nothing to do with Ebstein’s anomaly was found in 5 of these 80 patients (6.25%, Table 13.10 ): trisomy 18 in 3 patients ( Fig. 13.28 ), and trisomy 13 in 2.

Dysplastic tricuspid valve in trisomy 18 syndrome. The valve leaflets are thickened with gelatinous nodular formations. The chordae tendineae are thickened and shortened, and they also display focal nodules. Many of the interchordal spaces are obliterated with dysplastic fibrous tissue, and the right ventricular papillary muscles are dysplastic. Similar abnormalities are present in almost all cardiac valves in both full and partial trisomy 18 patients. RA, Right atrium; RV, right ventricle.

Reproduced with permission from Matsuoka R, Yamamoto Y, Kuroki Y, Matsui I: Phenotypic expression of the trisomic segments in partial trisomy 18. In: Van Praagh R, Takao A (eds), Etiology and Morphogenesis of Congenital Heart Disease. Futura Publishing Co, Mt Kisco, NY, 1980, p. 41.

Non-Ebstein Congenital Tricuspid Regurgitation in Marfan Syndrome

The sixth most common cause of non-Ebstein congenital tricuspid regurgitation in this series of 80 postmortem cases was Marfan syndrome: n = 4 (5%, Table 13.10 ), Cases 2, 31, 55, and 66 ( Figs. 13.29 and 13.30 ).

Infantile Marfan syndrome in a girl who died at 11 months of age from congestive heart failure in 1958. (A) Opened left atrium (LA), mitral valve, and left ventricular outflow tract (LV). (B) Opened LV outflow tract, aortic root (Ao root), and ascending aorta. (C) Opened right atrium, tricuspid valve, and right ventricular inflow tract. In (A), the thickened and redundant mitral valve leaflets herniate upward, toward the LA, creating a “hemorrhoidal” appearance when the mitral valve is viewed from above. The mitral chordae are thickened, elongated, and redundant. There is a small accessory orifice (Acc Orif) in the anterior mitral leaflet. The LA is markedly hypertrophied and enlarged, reflecting the severity of the mitral regurgitation. Even the ostia of the left pulmonary veins (LPV) and the right pulmonary veins (RPV) are enlarged. Septum primum (Sept. 1°) is redundant; all cardiac valves are redundant, and septum primum—the flap valve of the foramen ovale—is a cardiac valve antenatally. Left ventricular hypertrophy and enlargement are generalized, also involving the anterolateral and the posteromedial papillary muscles ( ALPM and PMPM ), but greater of the ALPM than of the PMPM. In (B), note the elongation and redundancy of the chordae tendineae of the mitral valve (MV). The Ao root is markedly dilated at the sinuses of Valsalva. The aortic leaflets are dilated and redundant; but note that their leaflet margins are thin and delicate (not thick and rolled), indicating that little or no aortic regurgitation had occurred. Thus, this patient died of massive congestive heart failure at 11 months of age because of marked mitral and tricuspid regurgitation, before significant aortic and pulmonary regurgitation had appeared. Mitral and tricuspid regurgitation is prominent in infantile Marfan syndrome, but is much less so in the adolescent-adult form of Marfan syndrome . In (C), the anterior leaflet (AL), the septal leaflet (SL), and the posterior leaflet (PL) of the tricuspid valve are thickened, redundant, and protrude upward into the right atrium that is markedly hypertrophied and enlarged. CT, Crista terminalis (terminal crest); SVC, superior vena cava. This patient was diagnosed as having the Marfan syndrome at birth. Her family history was negative. Weight was less than the 3rd percentile. Height was at the 50th percentile. Arachnodactyly, contractures, kyphoscoliosis, joint hyperelasticity, high-arched palate, and myopia were present. Additional associated anomalies were also found (see text, regarding Case 2).

Reproduced from Geva T, Sanders SP, Diogenes M, Rockenmacher S, Van Praagh R: Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome. Am J Cardiol 1990;65:1230.

Histologic characteristics of infantile Marfan syndrome. (A) Sections from the ascending aorta at the level of the sinuses of Valsalva: Left, normal control; Right, from a 10-month-old girl with infantile Marfan syndrome (Case 55). Note the fragmentation and disarray of the elastic fibers, and the increased interfiber ground substance in the patient (×100). Inset, high-power magnification (×400) showing details of elastic fibers in infantile Marfan syndrome (right) compared with the elastic laminae in the normal control (left). Verhoeff-Van Gieson stain for elastic fibers. Ad, Adventitia; L, lumen.

Reproduced with permission from Geva T, Sanders SP, Diogenes M, Rockenmacher S, Van Praagh R: Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome. Am J Cardiol 1990;65:1230.

Case 2 was an 11-month-old girl with infantile Marfan syndrome. The right atrium was huge. Both the tricuspid valve and the mitral valve were redundant and regurgitant ( Fig. 13.29 ). Dilation of the aortic and pulmonary valves was characterized by aneurysmal dilatation of the sinuses of Valsalva of both semilunar valves ( Fig. 13.29B ). Congestive heart failure was present with dilation of all cardiac chambers. Cardiomegaly was marked; the heart weighed 80 grams (normal = 40 grams), 100% greater than normal. Marfan lung disease was also observed, with marked lobular emphysema. High origins of the coronary ostia were noted.

This patient with infantile Marfan syndrome also had numerous additional congenital anomalies: small cranium, right coronal synostosis, loose skin, poor muscle development, bilateral wrist drop, bilateral dislocation of the hips, high-arched palate, arachnodactyly, lenticular densities (but without ectopia), esphoria, delayed dentition, arthrogryposis, and osteochrondrodystrophy.

Case 31 was a 13-year-and-21-day old girl with a familial connective tissue disorder (present in one other sibling) that was considered to be Marfanoid. She had arachnodactyly, an increased lower body segment, hyperextensible joints, contractures of the toes, kyphosis, osteoporosis, and wedged dorsal vertebrae. Chronic congestive heart failure was present. Echocardiography revealed moderate tricuspid regurgitation and severe mitral regurgitation with a flail mitral valve. This cachectic young girl underwent mitral valve replacement in 1988 with a #29 St. Jude prosthesis. Postoperatively, acute aortic dissection and a massive right hemothorax resulted in death.

Case 55 was a 10-month-old boy with infantile Marfan syndrome that was characterized by marked hyperextensibility of the joints; bilateral inguinal hernias treated with herniorrphaphies; hypertrophic pyloric stenosis treated with pyloromyotomy (Ramstedt operation) at 7 weeks of age; progressive congestive heart failure that appeared at 5 months of age; severe mitral regurgitation with marked mitral valve prolapse; marked left atrial enlargement; clinical and angiocardiographic evidence of tricuspid regurgitation, with hemorrhoidal anatomic appearance of the atrial surfaces of the tricuspid valve leaflets, tricuspid valve prolapse with thickened leaflets, and elongated redundant tricuspid chordae tendineae; secundum atrial septal defect; moderate left ventricular enlargement; severe failure to thrive; pectus excavatum; arachodactyly; high-arched palate; ventricular arrhythmias at 10 months of age consisting of ventricular premature beats with bigeminy and trigeminy; contractures of the elbows, knees, and ankles; and upward eventration of the right-sided portion of the central fibrous tendon of the diaphragm.

At 10 months of age in 1978, the patient underwent mitral valve replacement with a #19 Hancock prosthesis. Cardiac arrest and death occurred on the second postoperative day.

Autopsy revealed infarction of the posterior papillary muscles of the right ventricle. Severe bilateral pulmonary emphysema with blebs was found. The aortic and pulmonary valve leaflets and sinuses of Valsalva were redundant and enlarged, but without evidence of aortic regurgitation or pulmonary regurgitation. Dilation and thinning of the walls of the ascending aorta and main pulmonary artery were also observed.

Case 66 was a 1-day-old boy with infantile Marfan syndrome. Salient features included arachnodactyly, contractures, and massive cardiomegaly. Marked regurgitation of all four cardiac valves (tricuspid, mitral, pulmonary, and aortic) led to fatal congestive heart failure. There was tricuspid valve prolapse with focal absence of tricuspid leaflet tissue in the region of the anterosuperior commissure. A large secundum atrial septal defect was caused by deficiency and fenestration of septum primum.

Congenital Non-Ebstein Tricuspid Regurgitation With Uhl’s Disease

Congenital tricuspid regurgitation with Uhl’s disease was found in 3 of these 80 postmortem-proved cases (3.75%, Table 13.10 , Cases 59, 74, and 80) ( Figs. 13.31 and 13.32 ).

Congenital tricuspid regurgitation because of congenitally unguarded tricuspid orifice, with Uhl’s disease (parchment right ventricle). This 2-week-old black boy had pulmonary atresia (valvar), intact ventricular septum, Uhl’s disease, and congenitally unguarded tricuspid orifice. (A) External frontal view of the heart. (B) Opened right atrium (RA) and right ventricle (RV). (C) Opened left ventricle (LV) and ascending aorta (Ao). In (A), the right ventricular free wall looks very thin and wrinkled; it has a “scrotal” appearance. By contrast, the right atrium appears hypertrophied and enlarged. The main pulmonary artery is small, consistent with pulmonary valvar atresia. The segmental anatomy is normal, i.e., {S,D,S}. (B) This image confirmed that the right atrium is markedly hypertrophied and enlarged. A large secundum type of atrial septal defect (ASDII) is seen because septum primum (the flap valve of the foramen ovale) is very deficient: a cobweb appearance, with multiple large fenestrations in septum primum. The tricuspid leaflets, chordae tendineae, and papillary muscles are totally absent. Thus, the right atrioventricular orifice is wide open, but totally unguarded, because all elements of the tricuspid valve (leaflets, chordae, and papillary muscles) are absent; only the orifice is present. The right ventricular septal surface below the right atrioventricular junction (AVJ) is smooth, or nontrabeculated (reminiscent of the right ventricular septal surface above the downwardly displaced septal leaflet in Ebstein’s anomaly—except here, there is no downwardly displaced septal leaflet of the tricuspid valve). The right ventricular free wall is almost paper thin, and its trabecular architecture is abnormally fine (not normally coarse); i.e., the right ventricular free wall’s trabecular architecture is dysplastic. The ventricular septal surface is intact (no ventricular septal defect), and the pulmonary outflow tract is atretic. In (C), the architecture of the mitral valve (MV), left ventricle, aortic valve, and ascending aorta is unremarkable.

Another patient, an 18-month-old white boy, with congenital tricuspid regurgitation because of congenitally unguarded tricuspid orifice and associated with Uhl’s disease, valvar pulmonary atresia, and an intact ventricular septum. In (A), the opened right atrium (RA) and right ventricle (RV) reveal almost total absence of tricuspid leaflet tissue—just a few thread-like strands are present—at or below the right atrioventricular junction (AVJ). The right atrium is markedly hypertrophied and enlarged. A secundum type of atrial septal defect (ASDII) is seen. The right ventricular free wall (RV) is extremely thin. The ventricular septum is intact, and there is no patent pulmonary outflow tract. (B) The paper-thin right ventricular free wall (RV) and the blind pulmonary outflow tract (PAt). (C) Posterior viewing showing that the very thin right ventricular free wall (RVFW) transilluminates brilliantly. VS, Ventricular septum. (D) The opened left atrium (LA), mitral valve (MV), and left ventricle (LV) are all morphologically unremarkable.

Case 59 was a 40-year-old woman with Uhl’s disease. Autopsy revealed marked thinning of the right ventricular free wall that measured approximately 1 mm in thickness. The right ventricular free wall transilluminated brilliantly, particularly the diaphragmatic surface of the right ventricular free wall. The right ventricular free wall consisted mostly of subepicardial fat. Although the tricuspid valve was structurally normal, tricuspid regurgitation had developed because of gradual right ventricular dilation secondary to Uhl’s disease. The presence of tricuspid regurgitation was confirmed anatomically by right atrial jet lesions above the septal and posterior leaflets of the tricuspid valve.

In 1967, this patient was treated surgically with tricuspid annuloplasty (plication) in an attempt to reduce her tricuspid regurgitation. She had a history of peripheral thromboembolism to the first and fifth toes of the right foot. She also had a history of severe cardiac arrhythmias, with an episode of cardiac standstill, which she survived. The clinical picture of congestive heart failure developed and she died suddenly because of ventricular fibrillation that was documented electrocardiographically.

Congenital Polyvalvar Disease With Congenital Non-Ebstein Tricuspid Regurgitation

This group of anomalies also occurred in 3 of these 80 patients (3.75%, Table 13.10 , Cases 12, 30, and 41).

Case 12 was an 11-month-old girl with a redundant tricuspid valve and mild tricuspid regurgitation (documented by two-dimensional echocardiography), a redundant mitral valve without mitral regurgitation, and a mildly redundant aortic valve with mild aortic regurgitation; thus, congenital polyvalvar disease was present. But, as will soon be seen, mild congenital tricuspid regurgitation with congenital polyvalvar disease was not the patient’s main hemodynamic problem. She had multiple congenital anomalies (karyotype unfortunately unknown) with a conoventricular paramembranous ventricular septal defect, a secundum atrial septal defect, and a moderate-sized patent ductus arteriosus. A posterior fossa subdural hematoma was diagnosed at 8 days of age in 1991. Ligation of the patent ductus arteriosus and banding of the main pulmonary artery were performed at 17 days of age. Microcephaly with developmental delay gradually became apparent.

At 5 months of age, stenosis of the left pulmonary veins was diagnosed, followed by diagnosis of stenosis of the right pulmonary veins. Thus, the clinical diagnosis was made of idiopathic stenosis of individual pulmonary veins, which at the present time remains a dreaded diagnosis with an exceedingly poor prognosis (virtually 100% fatal, despite all therapeutic efforts). Hydrocephalus appeared and increased, and was associated with premature closure of the cranial sutures.

At 6 months of age, a gastrostomy was performed. At 7 months of age, patch closure of the ventricular septal defect was performed. The main pulmonary artery band was removed, following which the band site was resected, with end-to-end anastomosis of the main pulmonary artery. Fibrous tissue was resected from the orifices of the left pulmonary veins, and the secundum atrial septal defect was closed primarily (without a patch).

At 10 months of age, pulmonary venous dilation and stenting were undertaken: A 7 mm stent was placed into the right upper lobe pulmonary vein; and dilation and stenting were also performed of the left lower lobe pulmonary vein. At 11 months of age, inexorable pulmonary distress led to death. Autopsy confirmed all of the above-mentioned findings and established that the tricuspid leaflets were redundant and thickened.

Congenital Tricuspid Regurgitation Associated With Transposition of the Great Arteries {S,D,D} and (Usually) Dysplastic Tricuspid Valve

This defect occurred in 3 of these 80 patients (3.75%, Table 13.10 , Cases 5, 11, and 21).

Case 5 was a 7-day-old girl with transposition of the great arteries {S,D,D}, that is, with situs solitus of the viscera and atria ({ S ,-,-}), D-loop ventricles ({S, D ,-}), and D-transposition ({S,D, D }). There was atrioventricular AV concordance, with the right-sided morphologically right atrium (RA) opening appropriately or concordantly into the right-sided morphologically right ventricle (RV), and the left-sided morphologically left atrium (LA) opening concordantly or appropriately into the left-sided morphologically left ventricle (LV). But there was ventriculoarterial (VA) discordance with the right-sided RV ejecting inappropriately or discordantly into the right-sided transposed aorta (Ao) and the left-sided LV ejecting discordantly or inappropriately into the left-sided transposed pulmonary artery (PA). All of the foregoing is to be expected in TGA {S,D,D}, unless specifically stated to the contrary. For example, if there is straddling of the tricuspid valve or double-inlet LV with TGA {S,D,D}, this is stated so that one immediately understands that the usual AV concordance is not present. Hence, saying that Case 5 has TGA {S,D,D}, without further qualification of the atrioventricular alignment, means that the usual segmental anatomy ({S,D,D}) and segmental alignments (AV discordance with VA discordance, and hence physiologic uncorrection of the systemic venous and the pulmonary venous circulations) are present. All of this should be immediately understood, unless qualified to the contrary.

But now here comes the interesting part. This newborn girl with TGA {S,D,D} had a hypoplastic RV. Consequently, the tricuspid annulus was also hypoplastic. Hence, the patient had one type of congenital tricuspid stenosis—because of the hypoplastic tricuspid valve and right ventricular sinus. In addition, there was a small membranous ventricular septal defect, a hypoplastic transposed aortic valve, a hypoplastic aortic arch, coarctation of the aorta, and a patent ductus arteriosus.

Surprisingly, cardiac catheterization and angiocardiography (in 1988) revealed moderately severe tricuspid regurgitation. Mystified, we reexamined this heart specimen and found that the tricuspid valve was small (i.e., hypoplastic). But otherwise it was a well-formed, undeformed tricuspid valve: a beautiful, normal miniature.

This cardiac catheterization was performed when the patient was moribund (dying). Our conclusion is that marked tricuspid regurgitation can occur through an intrinsically normal (although small) tricuspid valve, if the patient is moribund at the time of the study, and if TGA is present, that is, if the tricuspid valve is functioning as the systemic atrioventricular valve. Suffice it to say that we were surprised to learn that moderately severe tricuspid regurgitation can occur through a normal (if miniature) tricuspid valve, under the aforementioned conditions. We expected to find some anatomic anomaly of the tricuspid valve (apart from hypoplasia), but we did not. We think that this is a lesson to be remembered.

Case 11 was an 8-month-old boy with TGA {S,D,D}, intact ventricular septum, and pulmonary valvar stenosis (bicuspid, myxomatous, with a 40 to 50 mm Hg gradient). This patient had mild tricuspid regurgitation, but without right atrial jet lesions. The tricuspid valve was abnormally formed, the anterolateral papillary muscle of the right ventricle inserting directly into the tricuspid leaflet tissue, without intervening free chordae tendineae or interchordal spaces. There was mild thickening and rolling of the free margin of the anterior tricuspid leaflet. This little boy’s mild tricuspid regurgitation was thought not to be one of his main clinical problems.

He also had stenosis of the left upper lobe pulmonary vein. A balloon atrial septostomy was attempted on the first day of life (in 1974), but it failed. Consequently, a Blalock-Hanlon surgical atrial septectomy was performed on the first day of postnatal life. Postoperatively, a wound infection of the median sternotomy developed. Subsequently, a Mustard procedure was performed in this patient with TGA {S,D,D} and unrelieved valvar pulmonary stenosis (40 to 50 mm Hg gradient). Following this atrial switch operation, low cardiac output developed, leading to death 13 hours postoperatively.

Our conclusion was that this patient’s mild congenital tricuspid regurgitation related to tricuspid valvar dysplasia did not help hemodynamically, but this little boy had other more major problems. In other words, mild congenital tricuspid regurgitation was present, but was not the major problem. We now know that an atrial switch operation such as the Mustard procedure is contraindicated in a patient with TGA {S,D,D} if significant pulmonary outflow tract stenosis coexists and cannot be relieved.

Case 21 was a 9 1.5 12 -year-old boy with TGA {S,D,D}, a small to moderate-sized conoventricular type of ventricular septal defect, a bilateral conus (subaortic and subpulmonary), pulmonary stenosis (infundibular and valvar, with a bicuspid pulmonary valve), and congenital tricuspid regurgitation because of a dysplastic tricuspid valve. The tricuspid valve had an accessory right ventricular papillary muscle arising from the right ventricular free wall, with multiple fenestrations in the anterior tricuspid leaflet. Moderately marked congenital tricuspid regurgitation occurred through these multiple fenestrations, and multiple jet lesions were present of the right atrial endocardium.

This patient, who died in 1979, had additional problems. The left coronary artery originated from the right coronary ostium. The left coronary artery then ran posteriorly to the transposed main pulmonary artery and then appeared anteriorly and to the left as a preventricular branch. There was a small communication between this preventricular termination of the left coronary artery and the LV cavity. This left coronary artery–to–left ventricular communication was 2 mm in diameter and was probe patent. This left coronary artery–to–left ventricular fistula created the unusual angiocardiographic picture of “aortic” regurgitation between the right-sided D-transposed aorta and the left-sided left ventricular cavity.

A balloon atrial septostomy was performed when the patient was 2 months of age. At 3 3 12 years of age, a right Blalock-Taussig anastomosis was done to the upper lobe branch of the right pulmonary artery. When the patient was 8 9 12 years old, an anatomic repair was performed (in 1979). Intraventricular rerouting was done between the left ventricle and the D-transposed aorta via a tunnel-like patch. The ventricular septal defect was enlarged by excision of the conal septum superiorly. The pulmonary valve was closed. A 20 mm valved Hancock conduit was placed externally from the right ventricle to the distal end of the main pulmonary artery. Hence, this anatomic repair involved both intraventricular (LV-to-Ao) and extraventricular (RV-to-PA) rerouting. Left ventricular pump failure appeared 4 months postoperatively. A surgical attempt to close a residual ventricular septal defect was associated with intraoperative death.

Our conclusion was that moderately marked congenital tricuspid regurgitation was present because of a dysplastic tricuspid valve, but that this was only one part of a complex clinical and surgical management problem. Again, it is essential to understand the presence of significant congenital tricuspid regurgitation in context with everything else that was a hemodynamic problem for the patient.

Tricuspid Valve Prolapse Causing Congenital Non-Ebstein Tricuspid Regurgitation

This defect was found in 2 of these 80 patients (2.5%, Table 13.10 , Cases 22 and 25).

Case 22 was a 9¾-month-old black girl with Down syndrome. Echocardiography revealed mild to moderate tricuspid regurgitation with tricuspid valve prolapse. The anterior leaflet of the tricuspid valve had a hooded and redundant appearance. The anterior tricuspid leaflet was also deep and curtain-like, but the septal leaflet was not downwardly displaced (and hence Ebstein’s anomaly was not diagnosed). The atrioventricular canal was normally divided into mitral and tricuspid valves. The ventricular septum was intact, but the patient had a large secundum atrial septal defect (14 × 7 mm) because of deficiency of septum primum; and a patent ductus arteriosus (3 mm in internal diameter) was also present. Heart block with bradycardia appeared 4 days prior to death. Thrombus with almost completely luminal occlusion of the superior vena cava was found at the superior vena caval–right atrial junction. She had diffuse pulmonary alveolar disease that was thought probably to be caused by respiratory syncytial virus pneumonia (not virologically proved).

To summarize, diffuse syncytial pneumonia was the principal cause of death. Tricuspid valve prolapse with congenital mild to moderate tricuspid regurgitation was present, but was thought not to be a major cause of disability or death.

Case 25 was a 12-year-old boy with tetralogy of Fallot {S,D,S}, a bicuspid pulmonary valve, and tricuspid valve prolapse with mild to moderate tricuspid regurgitation. In 1962, he developed a right frontal brain abscess caused by Staphylococcus aureus that led to cerebral edema, hemorrhage, and death.

Thus, tricuspid valve prolapse and tricuspid regurgitation were present. But these problems were overshadowed clinically by the congenital heart disease (tetralogy of Fallot) and its complication (brain abscess).

Dysplastic Right Ventricle and Tricuspid Valve

These defects were present in 2 of these 80 patients (2.5%, Table 13.10 , Cases 19 and 64).

Case 19 was a 10-month-old girl with a ventricular septal defect of the atrioventricular canal type, without mitral or tricuspid valve clefts. There was dysplasia of the right ventricular sinus (body or inflow tract) with anomalous muscle bands, abnormal papillary muscles, and abnormal tricuspid chordae tendineae. All of the foregoing was associated with congenital tricuspid regurgitation. The papillary muscles of the right ventricle were short and very hypertrophied. The tricuspid chordae tendineae were also very short and thick. The leaflets of the tricuspid valve were extremely thickened with rolled edges (consistent with tricuspid regurgitation). An enlarged right ventricular cavity was associated with marked right ventricular hypertrophy. Right atrial hypertrophy and enlargement coexisted. An abnormal muscle band of the right ventricle ran from the septum to the right ventricular free wall. This anomalous right ventricular band did not resemble the moderator band; it appeared to be truly anomalous. This patient died in 1976. Ebstein’s anomaly was not present.

Our assessment was that in this case, congenital tricuspid regurgitation was exceedingly important—the most important anomaly in this patient. Note that all levels of this tricuspid valve were anomalous: the leaflets, the chordae tendineae, the papillary muscles, and the underlying right ventricular myocardium. It should be recalled that there is an important right ventricular myocardial component in the development of the tricuspid valve, as is indicated by Ebstein’s anomaly and by muscular tricuspid valve.

Case 64 was a 3-day-old boy with severe congenital tricuspid regurgitation. The tricuspid leaflets were nodular and myxomatous. There was also dysplasia of the right ventricular sinus. The septal surface of the right ventricular sinus (inflow tract) was smooth (nontrabeculated). A small muscular ventricular septal defect was present anterosuperiorly, half way between the ventricular apex and the base, at the junction of the ventricular septum and the anterior free walls of the right and left ventricles. There was also a large secundum atrial septal defect because of a deficient septum primum; and a patent ductus arteriosus was also present.

Thus, severe non-Ebstein congenital tricuspid regurgitation was considered to be this newborn’s main hemodynamic problem.

Double-Inlet and Double-Outlet Right Ventricle (DIDO RV) With Congenital Non-Ebstein Tricuspid Regurgitation

This defect occurred in 2 patients (2.5%, Table 13.10 , Cases 24 and 69).

Case 24 was a 1-year-old boy with DORV {S,L,L}, that is, double-outlet right ventricle with situs solitus of the viscera and atria, L-loop ventricles, and L-malposition of the great arteries. The morphologically left ventricle (LV) was absent; that is, following a very careful search, no vestige of the LV was identified. Consequently, single right ventricle was present. There was a double-inlet right ventricle (DIRV) with congenital tricuspid regurgitation of the left-sided tricuspid valve and congenital mitral stenosis of the right-sided mitral valve. Thickening and rolling was present of the tricuspid leaflet margins and there were jet lesions of the left atrial endocardium, both confirming the presence of left-sided tricuspid regurgitation. Dextrocardia was present (usual for a ventricular L-loop). This patient also had pulmonary outflow tract atresia.

To summarize, this patient with complex congenital heart disease had DIDO RV {S,L,L} with single RV (L), absent LV (R), congenital TR (L) and congenital MS (R), with PAt and dextrocardia.

Therapeutic interventions in 1983 included a right-sided Blalock-Taussig anastomosis at 2 days of age, a central shunt at 9 months of age using a 4 mm Gore-Tex conduit between the ascending aorta and the left pulmonary artery, plus a Gore-Tex patch plasty of a stenosis between the left and right pulmonary artery branches and of the right Blalock-Taussig anastomotic site. Failure of the single right ventricle occurred, with right ventricular end-diastolic pressures of 23 to 30 mm Hg, leading to death at 1 year of age.

Thus, congenital non-Ebstein tricuspid regurgitation was considered to be one important hemodynamic handicap that led to the death of this patient with DIDO RV {S,L,L} and pulmonary atresia.

Case 69 was a 15-year-old girl with congenital heart disease that was similar to that of the previous patient. This teenager had a single RV (absent LV), DIRV, DORV {S,L,L}, bilateral conus (subaortic and subpulmonary), mild pulmonary stenosis with a bicuspid pulmonary valve, severe TR (L), left atrial hypertrophy and enlargement with jet lesions, and two coronary ostia originating from the left septal sinus of Valsalva of the aortic valve. The left-sided tricuspid valve had thickened and rolled margins, confirming the presence of severe left-sided TR.

Congenitally Unguarded Tricuspid Orifice

Absence or very marked underdevelopment of the tricuspid valve leaflets, but with a widely patent tricuspid orifice, was the cause of very severe congenital non-Ebstein tricuspid regurgitation in 1 case (1.25%, Table 13.10 , Case 18). This was a male fetus, 29 weeks gestational age, who was a stillborn macerated abortus weighing 2.75 lb (1247 grams). Intrauterine death was spontaneous (natural), not medically induced. Fetal echocardiography had revealed free tricuspid regurgitation, with intrauterine congestive heart failure (hydrops fetalis). Thus, congenital tricuspid regurgitation was very important as a cause of intrauterine death. The anterior leaflet of the tricuspid valve was very hypoplastic. The posterior leaflet was slightly better developed, but it too was also very hypoplastic. The septal leaflet of the tricuspid valve was virtually absent, just a minimal vestige being present. Right atrial hypertrophy and enlargement were marked. The segmental anatomy was normal, that is, {S,D,S}, and apart from the marked hypoplasia of the tricuspid leaflets, the heart was otherwise structurally normal. (Note that pulmonary valvar atresia with intact ventricular septum was not present, as it was in the previously presented cases of congenitally unguarded tricuspid orifice ( Figs. 13.31 and 13.32 ).

Multiple congenital anomalies were present: hypertelorism, microphthalmia, micrognathia, bilateral epicanthal folds, widely spaced nipples, low hairline posteriorly, posterior displacement of the anus, and talipes equinovarus (typical club foot).

This was also a case of familial congenital heart disease. An older brother had tetralogy of Fallot with pulmonary outflow tract atresia and severe tricuspid regurgitation (but with a well-formed tricuspid valve). We could find no evidence that a karyotype had been done.

Downward Displacement of the Anterior Tricuspid Leaflet With Blood Cysts of the Tricuspid Valve Leaflets

These anomalies were associated with massive tricuspid regurgitation in 1 patient (1.25%, Table 13.10 , Case 3). This patient was a 3-year-old boy who died in 1961. There was marked dilation of the right atrium that almost filled the entire thorax. The right atrium measured 12 × 9 × 9 cm (i.e., 4.7 × 3.5 × 3.5 inches). There was a pronounced bulge of the anterior chest wall because of the enormous right atrial enlargement. The heart weighed 95 grams. The tricuspid annulus was enlarged with a circumference of 14 cm (5.5 inches). The right ventricle was hypertrophied and enlarged with a thickness of 6 mm. Histology showed myocardium in all sections of the right atrium.

The conclusion following postmortem examination was that this patient had massive congenital tricuspid regurgitation because of dysplasia of the tricuspid leaflets, not idiopathic dilation of the right atrium (as had been thought clinically). In other words, the basic anomaly was thought to be at the level of the tricuspid valve leaflets, resulting in massive tricuspid regurgitation, the very marked right atrial enlargement being regarded as secondary to tricuspid regurgitation. Following autopsy, the right atrial enlargement was no longer considered to be idiopathic.

Congenital Mitral Regurgitation With Pulmonary Hypertension, Pulmonary Vascular Obstructive Disease, and Tricuspid Regurgitation

This combination of abnormalities was associated with tricuspid regurgitation in 1 of these 80 patients (1.25%, Table 13.10 , Case 4).

Case 4 was a 15 8 12 -year-old girl with congenital mitral regurgitation, ventricular septal defect, secundum atrial septal defect, pulmonary hypertension, mild valvar pulmonary stenosis, and aberrant right subclavian artery. At 10 years of age in 1960, she underwent mitral valvuloplasty for congenital mitral regurgitation (“reefing” of the annulus) and atrial septal defect closure. Pulmonary artery hypertension and severe pulmonary vascular obstructive disease (Heath and Edwards grades III and IV) were also found to be present. Left ventricular hypertrophy, right ventricular hypertrophy, tricuspid regurgitation, and right atrial enlargement were also found.

At 12 years of age, atrial fibrillation appeared that was quinidine resistant. Congestive heart failure appeared. The patient was cyanotic, dyspneic, and had a pulsatile hepatic margin 3 cm below the right atrial margin.

Cardiac catheterization at 15 5 12 years showed a ventricular septal defect with bidirectional shunt, pulmonary artery hypertension (106/24 mm Hg), pulmonary vascular obstructive disease, marked dilation of the pulmonary arteries, and tricuspid regurgitation.

At 15 8 12 years of age (in 1965), she underwent surgical ventricular septal defect closure, mitral valve replacement with a Starr-Edwards ball-valve prosthesis, and tricuspid annuloplasty. Postoperatively, she received a tracheostomy and her clinical condition deteriorated, leading to death 2 days postoperatively. Autopsy confirmed all of the foregoing findings and also revealed 6 accessory splenuli and a common mesentery, but without visceral heterotaxy. She also had talipes cavus—an abnormally high arch of the foot. Mild cardiac cirrhosis and widespread phlebosclerosis were also noted.

Thus, this patient illustrated that tricuspid regurgitation can be associated with congenital mitral regurgitation, ventricular septal defect, and secundum atrial septal defect when pulmonary hypertension progresses to pulmonary vascular obstructive disease and congestive heart failure.

Was this patient’s tricuspid regurgitation truly congenital, that is, was it present at birth? The answer to this question is not known to us. All that we can say with confidence is that this patient’s tricuspid regurgitation was based on the deleterious hemodynamic effects of her other forms of congenital heart disease (congenital mitral regurgitation, ventricular septal defect, atrial septal defect) and her acquisition of pulmonary vascular obstructive disease. Thus, her tricuspid regurgitation may have been acquired—appearing postnatally—but based on her other congenital heart disease. We simply do not know the answer to this question with certainty. So the reader may prefer to delete this case from our list of congenital non-Ebstein tricuspid regurgitation ( Table 13.10 ). However, this tricuspid regurgitation has a congenital basis in the sense that it is based on her other congenital heart disease, as above. Congenital heart disease can predispose to other abnormalities with variable times of clinical appearance.

Hypoplastic Pulmonary Arteries With Pulmonary Artery Hypertension and Congenital Tricuspid Regurgitation

This rare combination of abnormalities occurred in 1 of these 80 patients (1.25%, Table 13.10 , Case 54). This patient was a 29-day-old girl with severe pulmonary artery hypertension that was unresponsive to vasodilators. Two-dimensional echocardiography revealed tricuspid regurgitation.

Differential diagnoses included persistent pulmonary hypertension of the newborn, and primary pulmonary hypertension.

However, postmortem examination in 1984 revealed that the pulmonary intraparenchymal arteries all were markedly hypoplastic, more so than were the extraparenchymal pulmonary artery branches that accompanied the bronchi. Postmortem pulmonary arteriography showed that the branching pattern was normal, but that the arterial luminal diameters were much smaller than normal relative to the lung volume. There was also minimal background haze because the intraparenchymal arteries seen histologically were markedly hypoplastic.

Although anatomically normal, the tricuspid valve permitted significant tricuspid regurgitation (documented echocardiographically) in association with severe pulmonary artery hypertension. In turn, the pulmonary artery hypertension was caused by the marked hypoplasia of the pulmonary artery branches that was most marked within the pulmonary parenchyma. Goldstein, Rabinovitch, Van Praagh, and Reid published another very similar case in 1979. This is a rare cause of significant congenital tricuspid regurgitation associated with an anatomically normal tricuspid valve.

Classification

Edwards and colleagues ^, introduced in 1949, and later, an influential classification of tricuspid atresia ( Fig. 13.33 ). Although used less now than formerly, this classification should be understood as an aid to the comprehension of the literature on tricuspid atresia. Type I means that the great arteries are normally related, and type II indicates that transposition of the great arteries coexists. Type a means that pulmonary atresia is present, typically with no ventricular septal defect (VSD). Type b denotes that a small VSD is present, while type c denotes that a larger unrestrictive VSD coexists. See the legend to Fig. 13.33 : the meanings of subtypes a and b are different, depending on whether the great arteries are normally related or transposed. ^,

Classification of tricuspid atresia by Edwards and colleagues. ^, Upper, Tricuspid atresia with normally related great arteries, type I. Lower, Tricuspid atresia with transposition of the great arteries, type II. Upper Left, Tricuspid atresia type Ia. Tricuspid atresia is present, meaning that there is no direct communication between the right atrium (RA) and the ventricular part of the heart. All of the systemic venous blood passes from the superior and inferior venae cavae (VC) into the RA and thence across the atrial septum into the left atrium (LA) and from there across the mitral valve into the left ventricle (LV). In type Ia, because there is no ventricular septal defect (the ventricular septum is intact) and because there is pulmonary valvar atresia, all of the systemic venous blood (from the RA) and all of the pulmonary venous blood (from the LA) is ejected from the LV into the ascending aorta. Then some blood shunts from left to right through the patent ductus arteriosus into the left pulmonary artery (LPA) and the right pulmonary artery (RPA) to the lungs where it is oxygenated. Thus, in tricuspid atresia type Ia, there is no antegrade blood flow from the small right ventricle (RV) into the small pulmonary trunk (PT). Pulmonary blood flow is ductus dependent or collateral artery dependent. Upper Center, Tricuspid atresia type Ib. The great arteries are normally related (type I). But now there is a small ventricular septal defect (VSD) between the LV and the RV (type b). Because it is small, the VSD constitutes subpulmonary stenosis. A relatively small amount of blood shunts left to right across this small VSD from the LV into the RV and thence to the lungs. Hence, pulmonary blood flow is reduced. No patent ductus arteriosus is shown. Upper Right, Tricuspid atresia type Ic. The great arteries are normally related (type I). But now, a relatively large VSD is present, which does not constitute subpulmonary stenosis (type c). Consequently, pulmonary blood flow is normal, or it can be increased; whereas in tricuspid atresia types Ia and Ib, the pulmonary blood flow typically is reduced. Lower Left, Tricuspid atresia type IIa. Transposition of the great arteries is present (type II). Subpulmonary stenosis (type a) coexists; hence pulmonary blood flow is reduced. Lower Right, Tricuspid atresia type IIb. No pulmonary stenosis is present (type b). Note: The meanings of subtypes a, b, and c change, depending on whether the great arteries are normally related (type I) or transposed (type II). This may be why Edwards and his colleagues deemphasized the use of these subtypes in their later work. Some of us just misremembered. For me, tricuspid atresia type II a meant with pulmonary outflow tract atresia (Edwards et al ^, did not classify this type). For me, tricuspid atresia type II b had pulmonary outflow tract stenosis (instead of no pulmonary stenosis, as Edwards and colleagues did it, as in the lower right diagram). For me, tricuspid atresia type II c meant no pulmonary outflow tract stenosis (which should have been type II b , as above). ^, In other words, I made the mental error of assuming that subtypes a, b, and c meant the same things, no matter whether their great arteries were normally related or transposed. My error was easier to remember; but it was an error nonetheless. To minimize confusion, I would suggest that the meanings of symbols used in classification should be constants (not variables). Such meanings should not change; as in arithmetic, 2 must always mean two .

From Edwards JE, Burchell HB: Congenital tricuspid atresia: classification. Med Clin North Am 1949;33:1177–1196, with permission.

The advantages of this classification are that it allows one to express three important anatomic features with brevity and accuracy. For example, tricuspid atresia type Ib ( Fig. 13.33 ) is the most common anatomic type. This designation indicates: (1) that tricuspid atresia is present; (2) that the great arteries are normally related (type I); and that a small VSD is present (type b), constituting subpulmonary stenosis with reduced pulmonary blood flow.

What are the disadvantages of this early classification ( Fig. 13.33 ) of tricuspid atresia? Briefly, congenital heart disease with tricuspid atresia is much more complicated than can be classified using only these two variables (type of relationship between the great arteries, and the presence and size of the VSD—which helps to determine the size of the pulmonary blood flow). For example, subaortic stenosis (not just subpulmonary stenosis or atresia) can be present. The atria are not always in situs solitus. A ventricular D-loop is not always present. Other types of infundibuloarterial anatomy can be present—such as truncus arteriosus, double-outlet right ventricle, doublet-outlet left ventricle, and anatomically corrected malposition of the great arteries. This is one of the reasons why the segmental approach to diagnosis and classification is now used: (1) The segmental approach always applies accurately, no matter how complex the anatomy. (2), Also, the segmental approach is a general classification that applies to all forms of congenital heart disease, not just to a special classification that pertains to tricuspid atresia only. (See Chapter 3, Chapter 4 for more details concerning the segment-by-segment approach to the diagnosis and classification of congenital heart disease.)

Nonetheless, Edwards and Burchell’s classification of tricuspid atresia ( Fig. 13.33 ) ^, was very helpful and influential when it was introduced, because of what it could do. Its deficiencies only became apparent over time, as our knowledge and understanding increased.

Personal Note. In 1956 to 1957 (July 1 to June 30), I was an Assistant Resident in Pathology at the Children’s Medical Center (as it was then known) in Boston, in the Department of Dr. Sidney Farber, the world-famous father of chemotherapy for leukemia and lymphoma, with Dr. John M. Craig as my immediate and greatly admired supervisor. I was a 26-year-old resident in Pediatrics, doing my year of basic science. One of my autopsies was a patient with tricuspid atresia. The fascinating thing was that this patient’s anatomic type of tricuspid atresia did not fit into the then extant and widely accepted classification of tricuspid atresia ( Fig. 13.33 ). ^, If memory serves, I think my patient had tricuspid atresia with transposition of the great arteries, but with subaortic stenosis . I realized that I was looking at a previously undescribed anatomic type of tricuspid atresia.

This chance occurrence stimulated me to do a study of the pathologic anatomy of tricuspid atresia, which in turn led me in the directions of pediatric cardiology and pediatric cardiac pathology and embryology. Briefly, I became fascinated by these interrelated fields and decided to devote my professional life to them.

Perhaps I should add that I never published my study of tricuspid atresia because, when Keith, Rowe, and Vlad’s first edition of Heart Disease in Infancy and Childhood appeared in 1958, I discovered that the chapter on tricuspid atresia (that I would later learn had been written by my old friend and teacher Dr. Peter Vlad) said almost everything I wanted to say about tricuspid atresia. As Dr. John Craig told all of his pathology residents at that time, “To merit publication, a paper has to be only two things. It has to be true. And it has to be new.” I knew that my prospective paper on tricuspid atresia was true. But I also knew that it was no longer new. So this is why I did not publish my first tricuspid atresia study.

However, I owe a great debt of gratitude to my old friend and teacher, Dr. Jesse Edwards, and his classification of tricuspid atresia ( Fig. 13.33 ). ^, Trying to amplify his classification led me into my life’s work.

Classifications

Now we must endeavor to answer the question: How many anatomic types of tricuspid atresia are there? We are intentionally excluding Ebstein’s anomaly with tricuspid atresia, that is, imperforate Ebstein’s anomaly, only because we have already considered this malformation. Thus, the question should be rephrased as follows: In addition to imperforate Ebstein’s anomaly, how many other anatomic types of tricuspid atresia are there?

Table 13.11 represents our attempt to answer this question, based on an analysis of our database ( n = 94). (Cases were excluded when the data were considered not adequate for accurate analysis, as, for example, when the records were illegible.) It should be understood that other anatomic types of tricuspid atresia may well exist that we have not encountered in our database.

We are initially going to attempt to answer this question by following as closely as possible the approach of Dr. Jesse Edwards and his original classification of tricuspid atresia, ^, because it is useful and widely understood. However, it should also be appreciated that Edwards’ initial classification of tricuspid atresia ^, was not really a classification of tricuspid atresia per se . Instead, it was a classification of some of the situations in which tricuspid atresia occurs. Edwards’ classification ^, considers two questions: What is the relationship between the great arteries? And what is the status of the pulmonary outflow tract? These are clinically and surgically important variables, but they have nothing to do with the pathologic anatomy of tricuspid atresia itself.

Later, we will attempt to answer the question, How many anatomic types of tricuspid atresia per se are there? But first, let us begin with Dr. Jesse Edwards’ clinically and surgically useful approach ( Table 13.11 ).

Using the now classical Edwardian approach, ^, there are at least 11 different anatomic types of tricuspid atresia ( Table 13.11 ). A few words of explanation concerning the table may be helpful: Our anatomic types 1, 2, and 3 correspond to Edwards’ types Ia, Ib, and Ic. Our type 5 corresponds to Edwards’ type II. Most of our other anatomic types of tricuspid atresia are more recently discovered and described anomalies ( Table 13.11 ) that were not envisioned by, and not included in, earlier classifications. As mentioned earlier, there may well be other anatomic types of tricuspid atresia that we have not been privileged to see and study. So Table 13.11 should be regarded as provisional—the best we can do at the present time (September 2007), based on the data available to us.

Why did we talk about D-loop transposition of the great arteries (type 5, Table 13.11 ), rather than simply D-transposition of the great arteries? Because there were two patients with TGA {S,D,A} and one with TGA {S,D,L} (see table footnote). Thus, although D-loop ventricles were present in all, the semilunar interrelationships were those of A-TGA in two and L-TGA in one (not D-TGA) ( Table 13.11 ).

What does isolated noninversion of the great arteries mean? This anomaly (type 10, Table 13.11 ) is so rare that the meaning of the aforementioned designation may not be immediately obvious. Again, the segmental anatomy spells out the anatomy clearly (footnote): {A(I),L,S} with polysplenia, meaning situs ambiguus (A) of the viscera and atria, with basically situs inversus of the atria (I), with concordant L-loop ventricles (L), and with solitus normally related great arteries (S). Hence, only the great arteries are not inverted, whereas both the atrial and the ventricular segments are inverted; thus isolated noninversion of the great arteries is present. However, for rarities like this, we prefer the spelled-out segmental anatomic designation rather than an unfamiliar verbal term. {A(I),L,S} with polysplenia is clear—as long as one understands segmental anatomy. The segmental anatomy also indicates that there is atrioventricular concordance (between inverted atria and L-loop ventricles) and ventriculoarterial concordance (between L-loop ventricles and solitus normally related great arteries). If either concordance (AV or VA) is altered by additional anomalies, such additional malformations must also be described. In a well formulated diagnosis, when additional anomalies are not mentioned, their absence may be assumed.

Specifically what does conjoined twins mean (type 11, Table 13.11 )? Patient 30 was a 4.5-hour-old female (the youngest in this series), conjoined twin B of thoracopagus twins, with multiple congenital anomalies. She had atresia of all four cardiac valves, a unique finding to our knowledge.

Relative frequencies: What is the most common anatomic type of tricuspid atresia, and which is the rarest? Based on our 94 postmortem cases, the relative frequencies of the anatomic types of tricuspid atresia were found to be as follows ( Table 13.11 ):

• 1.
  

  The most common was tricuspid atresia {S,D,S} with pulmonary outflow tract stenosis (47%). (As expected.)

  
  
• 2.
  

  Second in frequency (and this was a surprise to us) was tricuspid atresia with D-loop transposition of the great arteries (19%) ( Fig. 13.34 ).

  
  
• 3.
  

  Third in frequency (and also a surprise) was left-sided tricuspid atresia with TGA {S,L,L} (11%) ( Fig. 13.35 ).

  
  

  
  

  
  

  

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