Ebstein Anomaly

Tricuspid Valve

Both the origin of the tricuspid valve from the atrioventricular (AV) ring and its chordal attachments within the right ventricle (RV) are malpositioned, and the leaflets are malformed. The leaflets are either enlarged or reduced in size and are frequently dysplastic (thickened and distorted). These deformities vary widely in severity ( Table 42-1 ). In the mildest forms, the valve is functionally near normal ; in the fully developed syndrome, function is severely compromised. Displacement of the origin of the leaflets from the AV ring is reasonably constant. The septal leaflet appears always to be affected, the posterior leaflet nearly always, and the anterior leaflet seldom ( Fig. 42-1 ). As noted by Anderson and colleagues, when both the septal and posterior leaflets are displaced, the point of maximum displacement is usually at the commissure between them. Thus, the functional tricuspid anulus is rotated apically and anteriorly ( Fig. 42-2 ). In the few cases in which the anterior leaflet is displaced, the commissural area between it and the septal leaflet, attached to the right trigone at the point of penetration of the bundle of His, remains in normal position (see Fig. 42-1 ). In many patients, the apparent displacement is due to adherence of the base of the leaflet to the RV wall (see Table 42-1 and Fig. 42-1 ). Adherence of leaflet tissue to the underlying myocardium is thought to represent a failure of delamination during development. This failure effectively moves the hinge points of the septal and posterior leaflets (the functional anulus) into the ventricular cavity. When adherence is incomplete, there is a potential or obvious pocket beneath the leaflet.

The septal or posterior leaflet may be partially absent, in which case the belly of the leaflet is small or absent (see Fig. 42-1 ). The posterior leaflet is more often elongated than reduced in size (see Table 42-1 ), due in part to lack of a commissure between the posterior and anterior cusps. This was the case in 8 of 15 hearts examined at autopsy at GLH. The septal–posterior leaflet commissure may also occasionally be absent. Leaflet enlargement and elongation are characteristic of the anterior leaflet, which has been described as sail-like. The leaflet is usually diffusely thickened or ridged and occasionally consists partly of muscle. All the leaflets are frequently dysplastic, and isolated accessory leaflets may occur.

Distal leaflet attachments are variable and usually abnormal. Displaced and dysplastic posterior and septal leaflets frequently have multiple short chordae connecting to multiple small papillary muscles (see Fig. 42-1 ). The sail-like anterior leaflet may also have multiple short chordae arising around most of its free edge, binding it relatively closely to the septum and occasionally to the free wall, or the leaflet edge may be directly adherent to the anterior papillary muscle and moderator band or the posterior edge of the septal band. Presence of a free anterior leaflet is an important morphologic detail, because it greatly increases the likelihood of a successful repair. Leaflet fenestrations are common, with the opening typically guarded by a single papillary muscle, which gives rise to chords that attach to the periphery of the fenestration.

If the entire free margin of the leaflets is adherent and imperforate, one variety of tricuspid atresia is produced (see Chapter 41 ). When the adherence is partial, the large anterior leaflet produces a variable degree of stenosis between the portion of ventricle proximal to it (atrialized ventricle) and that distal to it (functional or ventricularized ventricle), because blood can pass only between openings that remain between the leaflet margin and ventricular wall (or through the commissures when these are present) ( Fig. 42-3 ). Stiffness of the anterior leaflet contributes to stenosis.

Although important stenosis is uncommon, most Ebstein valves are regurgitant, often severely so ( Fig. 42-4 ). This is contributed to by marked dilatation of the true tricuspid anulus and the RV, as by well as by morphologic abnormalities of the tricuspid valve.

The functional tricuspid orifice is determined by the hinge points of the valve leaflets, which rotate around the aortic root. The resultant functional valve orifice resides at the junction of the inlet and apical trabecular portions of the RV. We emphasize Anderson's focus on this rotational understanding of Ebstein anomaly to differentiate it from tricuspid valve dysplasia, which is often mistaken for Ebstein anomaly.

Right Ventricle

Rotational displacement of the valve divides the RV into proximal (atrialized) and distal (ventricularized) portions. The proximal portion lies between the true tricuspid anulus and the valve attachment and comprises a variable portion of the posterior and inferior (diaphragmatic) aspects of the ventricular cavity (see Figs. 42-3 and 42-4 ). The right coronary artery denotes location of the true tricuspid anulus.

The proximal portion is atrialized in about one fourth of hearts in which the posterior and septal leaflets are severely displaced ( Fig. 42-5 ). This atrialized portion of ventricular wall is dilated. Uncommonly, it is so thin as to seem aneurysmal, in which case it is largely fibrous tissue, and the endocardium is smooth. When very thin, it moves paradoxically during ventricular systole and may also expand during atrial systole. Its electrical potentials are ventricular, but its pressure pulse has an atrial contour. More commonly, the wall of the atrialized portion is thicker than this and contains variable amounts of muscle.

The functional ventricularized portion of the RV lies distal (downstream) to the displaced valve and is therefore smaller than the normal RV. However, this feature is modified by RV dilatation, which is an almost constant finding. The functional portion consists of the infundibulum (conus), trabeculated apex, and that portion of the ventricle beneath the large anterior cusp (anterolateral recess) ( Figs. 42-6 and 42-7 ).

Ebstein anomaly is more than a valve abnormality, in that the RV has an underlying myopathy. The dilated functional ventricle is usually thinner walled than normal and contains fewer muscle fibers. Anderson and Lie suggested there may be a congenital paucity of myocardial cells in the RV, such that dilatation of both portions of the ventricle is part of the developmental anomaly rather than entirely its hemodynamic consequence.

In 1988, Carpentier proposed a classification system based on size of the functional RV and adequacy of the anterior leaflet for repair :

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  Type A: volume of true RV is adequate.

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  Type B: a large atrialized component of RV is present, and anterior leaflet of tricuspid valve moves freely.

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  Type C: movement of anterior leaflet is severely restricted and may cause obstruction of RV outflow tract.

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  Type D: RV is nearly completely atrialized, except for a small infundibular component.

Right Atrium

The right atrium is enormously dilated in advanced cases. There is usually an interatrial communication (60% of autopsy specimens, 42% at catheterization, and 21 of 22 surgical cases in Watson's collective review), most commonly a patent foramen ovale, although an atrial septal defect (ASD) of any type may be present. Interatrial communication was present in 94% of patients at operation in the series reported by Danielson and colleagues. Rarely, an ostium primum AV septal defect coexists.

The bundle of His and AV node lie in their usual locations, although the right bundle and node may be compressed by thickened endocardium (a possible explanation of the frequent right bundle branch block pattern in the electrocardiogram). WPW syndrome is present in about 14% of persons with Ebstein anomaly.

Left Ventricle

Monibi and colleagues and Ng and colleagues report that abnormal left ventricular contraction and contour and mitral valve prolapse are frequently present. Marked dilatation of the RV produces leftward septal shift and compression and posterior displacement of the left ventricle. Daliento and colleagues studied nine autopsied hearts and found the ventricular septum normal in six and thin in three, which could account for the exaggerated leftward diastolic movement observed by angiography in 24 of 26 patients. Severe leftward displacement produced a “banana” appearance of the left ventricle. Regional left ventricular wall motion abnormality was observed in 67% of patients. In a Mayo Clinic experience of over 500 surgical patients with Ebstein anomaly, 9% had moderate or severe LV dysfunction. When mitral valve prolapse is present, the valve is frequently nodular and thickened. A Mayo Clinic study of 106 patients identified left ventricular abnormalities in 39%, of whom 18% had left ventricular dysplasia resembling noncompaction.

Lungs

In severe Ebstein anomaly associated with fetal and neonatal distress or death, both lungs are usually hypoplastic but otherwise normal. The hypoplasia is secondary to gross cardiomegaly from severe tricuspid regurgitation.

Associated Anomalies

An ASD is present in 80% to 95% of patients with Ebstein anomaly. Pulmonary atresia or stenosis may be present in up to one third of autopsied hearts (see Chapter 39, Chapter 40 ). Others include ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, transposition of the great arteries, coarctation of the aorta, and congenital mitral stenosis.

In congenitally corrected transposition with atrial situs solitus, the tricuspid valve lies within a left-sided, systemic, morphologically right ventricle. Although 30% of these left-sided valves are regurgitant, this is frequently due to Ebstein anomaly. This Ebstein anomaly differs from the usual right-sided form in that dilatation of the AV ring and separation of the morphologic RV into atrialized and ventricularized portions are uncommon. The anterior leaflet is also less prominent and may be cleft (see Chapter 55 ).

Mechanisms Underlying Clinical Presentation and Natural History

Three primary pathophysiologic features predominate in patients with Ebstein anomaly:

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  RV abnormalities

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  Tricuspid valve abnormalities

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  Accessory conduction pathways (WPW syndrome)

Their severity determines secondary pathophysiologic features, clinical presentation, and natural history.

Symptoms and Signs

Breathlessness in association with cyanosis, severe cardiomegaly, and often heart failure may appear during the first week of life. However, many patients have milder symptoms and do not present until later in life. Nonetheless, objective exercise testing shows that their functional capacity is less than normal. Oxygen saturation at rest is a major predictor of exercise tolerance. Mild dyspnea and fatigue may become evident in childhood or early adult life, or more severe symptoms and signs of various types may develop. If heart failure develops, the patient becomes severely limited by breathlessness and fatigue.

Cyanosis is a common sign of Ebstein anomaly, occurring in more than half of patients and severe in about one third. It may appear at birth, but in most patients onset is in infancy or early childhood.

Palpitations caused by various types of arrhythmia are also common. Severe arrhythmic symptoms are frequent in patients of all ages and may be disabling. WPW syndrome is the best known type of arrhythmia, but less specific types of supraventricular tachycardias are more common. Numerous electrophysiologic abnormalities have been identified, which no doubt account for the frequent occurrence and persistence of arrhythmic symptoms even after operation. Symptoms are more severe when there are important associated cardiac anomalies.

A malar flush, similar to the so-called mitral facies, was noted by Ebstein's colleague and occurs in about one third of patients. It is unrelated to cyanosis or polycythemia or to cardiac output.

The left anterior chest is often prominent in association with marked cardiomegaly, and there may be a systolic thrill along the left sternal edge originating from the tricuspid valve. Characteristically, the precordium and apex remain quiet despite marked cardiomegaly. Jugular venous pressure is generally unremarkable and rarely suggests tricuspid regurgitation or stenosis, even though free tricuspid regurgitation is revealed by imaging studies. This is related to the large size and compliance of both the right atrium and atrialized RV, as well as the low RV and pulmonary artery pressure. Congestive hepatosplenomegaly is commonly observed and may lead to hepatic fibrosis.

On auscultation the most constant finding is wide splitting of the first sound with accentuation of the delayed component caused by closing (or termination of motion ) of the large anterior tricuspid leaflet. Delayed tricuspid valve closure is probably mechanical rather than related to right bundle branch block, although Crews and colleagues considered it correlated with the latter. The large anterior leaflet is also responsible for an opening snap in diastole, and there may be an atrial fourth sound. The pulmonary component of the second sound is delayed and soft (in relation to the right bundle branch block) or absent when pulmonary artery pressure is low. A pansystolic murmur maximal at the lower left sternal edge is due to tricuspid regurgitation and is heard in about one third of patients. Finally, there is usually a diastolic murmur, often low pitched and sometimes scratchy in quality, commencing with the opening snap and sometimes augmented by the fourth sound. The diastolic murmur is presumably due to movement of blood across the malformed tricuspid orifice.

Chest Radiography

In classic Ebstein anomaly, the chest radiograph shows marked cardiomegaly with a rounded or boxlike cardiac contour beneath a narrow pedicle ( Fig. 42-8 ). In the posteroanterior view the whole of the silhouette is then formed by the right atrium and RV, and because of their minimal excursion and the normal or oligemic lung fields, the silhouette has a peculiarly sharp edge. However, as with other features of the disease, there is wide variation in heart size. In a few cases, it remains normal; in most, it is only moderately enlarged.

Electrocardiography

A right bundle branch pattern together with a relatively low-amplitude R wave in right-sided chest leads and right atrial hypertrophy are characteristic of the anomaly. According to Kumar and colleagues, height of the P wave varies inversely with arterial oxygen saturation (r = .82, P < .001). In addition, the taller the P wave, the shorter the survival time ( P < .001). RV hypertrophy does not occur in uncomplicated Ebstein anomaly, and inverted T waves in leads V ₁ to V ₄ are fairly common. Using intraluminal electrode catheters, Kastor and colleagues demonstrated prolonged intra–right atrial and infranodal conduction in patients with a large right atrium and well-defined atrialized ventricle.

In approximately 14% of patients, the electrocardiogram shows type B (right-sided) WPW syndrome. In any cyanotic patient with this type of preexcitation, Ebstein anomaly should be considered. Supraventricular arrhythmias occur in more than half of patients, and they may be paroxysmal and recurrent. Paroxysmal atrial tachycardia, atrial fibrillation, and nodal rhythm can all occur, as can first-degree heart block. Serious ventricular arrhythmias resulting from RV dilatation may also occur.

Echocardiography

Two-dimensional echocardiography has become definitive for diagnosis and anatomic evaluation of Ebstein anomaly ( Fig. 42-9 ). It is possible to identify Ebstein anomaly by the characteristic degree of displacement of the septal leaflet of the tricuspid valve (>8 mm · m ⁻² ) and the presence of an elongated, redundant anterior tricuspid valve leaflet. The feasibility of tricuspid repair rather than replacement can be determined with this method of imaging. A right-to-left atrial shunt and tricuspid regurgitation can be demonstrated using Doppler color flow interrogation.

Historically, M-mode echocardiography usually demonstrated delayed tricuspid valve closure and displacement of the tricuspid valve to the left. According to Giuliani and colleagues, the greater the delay in tricuspid valve closure, the more severe the disease. Wide excursion of the anterior leaflet, a decreased E-F slope, increased RV dimensions, and paradoxical septal motion can also be demonstrated.

Cardiac Catheterization and Cineangiography

Currently, cardiac catheterization and cineangiography are required only when specific hemodynamic details need to be identified, or in patients about aged 40, when the coronary tree should be examined.

In the past, cardiac catheterization showed that the mean right atrial pressure is often modestly elevated, and the pressure pulse may have either a dominant a or v wave. These correlate poorly with degree of tricuspid regurgitation or stenosis. An additional s wave preceding the v wave and interrupting the c wave is said to indicate tricuspid regurgitation. The right atrial waveform is also recorded in the atrialized portion of the RV so that the tricuspid valve is noted to be displaced well toward the left of the spine. An electrode catheter may define the position and size of the atrialized RV chamber. RV systolic pressure is normal or low, and RV end-diastolic pressure is frequently elevated, more so when there is the syndrome of chronic heart failure. It is uncommon to record an important gradient across the tricuspid valve, although Takayasu and colleagues noted this in 8 of 26 cases and considered that stenosis could still be important in its absence.

When there is an interatrial communication, the shunt through it is usually right to left in association with systemic arterial desaturation and a reduced pulmonary blood flow ( ). The right-to-left shunt can be quantified by indicator dilution. The shunt may occasionally be left to right, and the resultant increase in may be associated with heart failure. Direction of shunting is no doubt influenced by RV compliance.

In the newborn with Ebstein anomaly, a functional pulmonary outflow obstruction can occur. Thus, a normal pulmonary valve may fail to open following a right-sided injection of contrast media because of the combination of massive tricuspid regurgitation, poor RV contraction, and a high neonatal pulmonary vascular resistance with or without a large shunt at ductal level. High-quality imaging is therefore necessary to distinguish this situation from true pulmonary atresia.

Cineangiography (see Figs. 42-3 to 42-7 ) is usually diagnostic as long as there is important displacement and dysplasia of the septal or posterior leaflets. In the right anterior oblique projection, the conjoined posterior and anterior leaflets, and therefore the distal limit of the atrialized ventricle, can frequently be identified. Contrast media trapped beneath the posterior leaflet can indicate the degree of its adherence to, and level of its origin from, the diaphragmatic border of the RV, which may be notched at this point. The site of the true anulus is also visible more proximally. An injection into the functional RV enables tricuspid regurgitation to be assessed together with size and behavior of the functional ventricle. Angiography in left anterior oblique projection also permits visualization of the right-to-left shunt at atrial level, and any ventricular septal defects can be localized by left ventriculography.

Presentation during First Week of Life

Ebstein anomaly is a recognized cause of death in utero. When severe tricuspid regurgitation accompanies Ebstein anomaly at birth, the elevated newborn pulmonary vascular resistance worsens it. may be ductal dependent. The resultant severe hypoxemia (right-to-left shunting through an ASD), coupled with marked right-sided heart failure, may also be accompanied by low cardiac output if the ASD is restrictive. This is because maintenance of normal cardiac output requires shunting at the atrial level through a nonrestrictive ASD. Low cardiac output may also result from abnormal ventricular interactions caused by paradoxical septal bowing and flattening of the left ventricle. The hypoxemia may be aggravated by pulmonary dysfunction secondary to lung compression by marked cardiomegaly. Although lung hypoplasia has been suggested, pathologic studies indicate that the lungs are rarely hypoplastic in surviving newborns, but are instead compressed by the enlarged heart.

Celermajer and colleagues from Great Ormond Street identified neonates with good and poor outcomes based on a score (Celermajer Score or Great Ormond Street Ratio) derived from echocardiographic measurements of the right atrium, RV, left atrium, and left ventricle. The score is calculated from a four-chamber echocardiographic view in which the combined area of the anatomic right atrium plus atrialized RV is divided by the sum of the areas of the functional (nonatrialized) RV, left atrium, and left ventricle ( Table 42-2 ). The outlook is generally dismal for patients with Celermajer grades 3 or 4 (severe Ebstein anomaly; Fig. 42-10 ). Importantly, patients with Ebstein anomaly who survive after presentation early in life have a good chance of long-term survival.

Many studies have probably underestimated the incidence and severity of this entity in neonates. The review by Vacca and colleagues of 108 clinical or autopsy cases reported between 1866 and 1957 recorded only two patients younger than 1 month. In Watson's collective review of 505 cases, only 35 (7%) were younger than 1 year (half were younger than 1 month). In Bialostozky and colleagues’ review of 65 patients, neonates were not included. In a Mayo Clinic series, only 10 of 67 patients were diagnosed in infancy. In a Boston Children's Hospital series, 12 of their 55 patients (22%) were seen during the first week of life, and 34 (64%) were younger than 2 years. Eleven of the 34 died early. These series must have been in some way selective and therefore are not useful in assessing natural history. In contrast, Schiebler and colleagues’ earlier study from the Mayo Clinic found that 12 of 23 patients presented during the neonatal period, and of these, 5 died. Roberson and Silverman reported that among 16 consecutive patients diagnosed in utero or presenting during the first 3 days of life, 7 died before age 3 months; all had severe RV and tricuspid morphologic abnormalities. In the 40-institution administrative registry of the Pediatric Health Information System (PHIS), of 464 neonates diagnosed with Ebstein anomaly from January 2003 to January 2008, 415 with complete data, mortality during initial hospitalization among 257 (62%) managed medically was 22% (56/257; CL 19%-25%).

Presentation in Infancy

Presentation in infancy is associated with less risk of death and milder symptoms than occur with neonatal presentation ( Fig. 42-11 ), although some studies suggest an increased mortality until presentation is beyond about 6 months. Beyond this age, Watson's series indicates a prognosis similar to that of older children. He states that “whereas 72% of those under 1 year were in heart failure, 71% of the children and adolescents had little or no disability.”

Presentation in Childhood and Adult Life

Patients presenting after infancy often have mild symptoms. Prognosis is generally good, consistent with less severe RV and tricuspid valve pathophysiology. Patients presenting in adult life are often acyanotic and have a normal-sized heart. However, even these patients, who report few symptoms, have clearly definable abnormalities. Without preexcitation, nearly half have episodic supraventricular tachyarrhythmias, although these usually produce few symptoms. Exercise tolerance measured by objective testing is often reduced. The degree of tricuspid regurgitation does not correlate with symptoms, but as time passes, left ventricular dysfunction often appears as symptoms develop.

Death in this group of patients is often due to paroxysmal embolization or paradoxical supraventricular tachycardia, with heart failure appearing either much later or not at all. An atrial level communication increases the risk of paradoxical embolism, brain abscess, and sudden death.

Modes of Death

Heart failure is the mode of death in somewhat less than half of patients who die of causes related to their heart disease after the neonatal period. Sudden death, presumably caused for the most part by arrhythmias other than those associated with WPW, occurs in about 60% (CL 43%-77%) of these patients. Sudden death correlates with marked cardiomegaly, rather than with New York Heart Association (NYHA) status. Cerebral abscess and paradoxical emboli account for most of the remaining deaths, particularly in patients older than about 50 years. Infective endocarditis is rare.