Tricuspid Valve Anomalies

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 ).

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 $\frac{4}{12}$ years. The median age at death was 4 $\frac{2}{12}$ 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 $\frac{2}{12}$ years and 17 $\frac{4}{12}$ 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 $\frac{2}{12}$ 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 $\frac{8}{12}$ 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 $\frac{3}{12}$ -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 $\frac{3}{12}$ 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 ).

Case 47 was a 1 $\frac{8}{12}$ -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 $\frac{1}{12}$ -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 $\frac{9}{12}$ 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 $\frac{2}{12}$ -year-old young woman with D-transposition of the great arteries ( Fig. 13.10 ).

  
  

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 $\frac{2}{12}$ -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 $\frac{1}{12}$ -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 $\frac{1}{12}$ -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 $\frac{10}{12}$ 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 $\frac{8}{12}$ 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.

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 ).

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 ).

  

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 $\frac{10}{12}$ 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 $\frac{8}{12}$ 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 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 $\frac{3}{12}$ -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.

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.

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 $\frac{3}{12}$ ± 7 $\frac{11}{12}$ years; range from 0 (stillborn) to 19 $\frac{2}{12}$ years; and mean = 1 $\frac{8}{12}$ 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 .

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 ).

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).

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 $\frac{8}{12}$ 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.

    

  • 2.

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

  • 3.

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

    

  • 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 $\frac{5}{12}$ -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 $\frac{5}{12}$ 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 $\frac{5}{12}$ years. The pacemaker generator was changed at 24 $\frac{8}{12}$ years. Another pacemaker was inserted at 30 $\frac{7}{12}$ years of age. Sudden death occurred 10 months later at age 31 $\frac{5}{12}$ 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 $\frac{11}{12}$ -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 $\frac{11}{12}$ 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 $\frac{7}{12}$ -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 $\frac{1}{12}$ years of age, he developed acquired complete heart block. In 1980, at 15 $\frac{7}{12}$ 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 $\frac{8}{12}$ -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 $\frac{8}{12}$ -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 $\frac{1}{12}$ -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.

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 ).

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 ).

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.