Ebstein’s anomaly of the tricuspid valve

Incidence and prevalence

The reported prevalence of Ebstein’s anomaly varies between jurisdictions occurring in 1 to 1.5 per 20,000 live births, accounts for 0.3% to 1% of all cases of congenital heart disease, and represents about 40% of congenital malformations of the tricuspid valve. The Danish Registry and other European surveillance registries estimated that the relative risk of Ebstein’s anomaly increased in offspring exposed to in utero lithium carbonate, which is used to treat bipolar disorders. ^,

Anatomic considerations

Normal tricuspid leaflets consist of basal attachments to the annulus (right atrioventricular sulcus), peripheral zones into which chordae tendineae insert, and clear zones that lie between the basal attachments and the peripheral zones. The semicircular or quadrangular anterior leaflet is the largest of the three. The posterior leaflet is scalloped. The septal leaflet attaches chiefly to the ventricular septum, as the name indicates, but part of its basal attachment is to the posterior wall of the right ventricle. The septal leaflet normally exhibits a slight but distinct apical displacement of its basal attachment compared to the mitral valve—15 mm in children and 20 mm in adults. In Ebstein’s anomaly, the septal and posterior leaflets do not attach normally to the tricuspid annulus, so the valve orifice is displaced downward into the right ventricular cavity at the junction of the inlet and trabecular components of the right ventricle.

The right side of the heart, therefore, consists of three morphologic components—the right atrium proper , the inlet portion of the right ventricle that is thin-walled and functionally integrated with the right atrium, and the trabecular and outlet portion that constitute the functional right ventricle. The greater the apical displacement of the posterior and septal leaflets, the larger the atrialized right ventricle and the smaller the functional right ventricle ( Fig. 11.2 ). Downward displacement of the septal tricuspid leaflet is associated with discontinuity of the central fibrous body and the septal atrioventricular ring, creating a potential substrate for accessory pathways and preexcitation. The leaflets and tensile apparatus of the tricuspid valve are believed to be formed chiefly by delamination of the inner layers of the inlet zone of the right ventricle. When the tricuspid leaflets are displaced downward, delamination fails to occur.

Morbid anatomy encompasses a broad range of severity, ^, but certain features are relatively constant. The anterior leaflet is almost always normally attached to the atrioventricular junction. A salient anatomic feature is the level of the hinge points of the septal and posterior leaflets, which are characterized by apical displacement of their basal attachments, adherence to the underlying myocardium, and impaired movement because of short chordae tendineae and nodular fibrotic thickening (see Fig. 11.1 ). The anterior leaflet differs appreciably from the septal and posterior leaflets. The basal attachment is at the level of the atrioventricular sulcus (annulus). The large and potentially mobile anterior leaflet contains muscular strands instead of consisting entirely of a fibrous membrane as in the normal tricuspid valve. The displaced insertions of the malformed septal and posterior leaflets allow free communication between the proximal (atrialized) and distal (functional) right ventricle. Occasionally, communication between the atrialized right ventricle and the functional right ventricle is confined to slits or perforations in the anterior tricuspid leaflet, as Ebstein originally described, or the two segments are separated by a muscular partition or shelf ( Fig. 11.3 ) that restricts flow to the commissure between the anterior leaflet and the displaced septal leaflet. When the anteromedial commissure is fused, and the anterior leaflet is intact, the tricuspid orifice is imperforate.

The thin-walled atrialized right ventricle is relatively devoid of muscular tissue and is typically dilated, often aneurysmally. It expands paradoxically during ventricular systole, thus acting as a passive reservoir that decreases the volume of ejected blood. Morphometric analyses of the trabecular and infundibular portions of the functional right ventricle disclose an absolute decrease in the number of myocytes and an increase in fibrosis that are held responsible for infundibular dilation.

An ostium secundum atrial septal defect is present in over a third of hearts with Ebstein’s malformation, and a majority of the rest have a patent foramen ovale (see Figs. 11.1 and 11.2 ). Ebstein’s anomaly of an inverted tricuspid valve in congenitally corrected transposition of the great arteries is described in Chapter 6 . Other associate anomalies that have been reported include hypertrophic cardiomyopathy and aortic arch anomalies.

Tricuspid regurgitation due to a congenitally unguarded tricuspid orifice or to tricuspid valve dysplasia differs fundamentally from Ebstein’s anomaly. A congenitally unguarded tricuspid orifice is characterized by the absence of all three leaflets, or by a muscular partition or shelf that leaves the atrioventricular orifice unguarded (see Fig. 11.3 ). Congenital dysplasia of the tricuspid valve refers to nodular thickening and rolling of the edges of the leaflets without downward displacement.

Idiopathic dilation of the right atrium has been reported in children without Ebstein’s anomaly. ^, Transient tricuspid regurgitation of the newborn has no definable anatomical basis and resolves within a few weeks. Uhl’s anomaly is discussed at the end of this chapter.

Abnormalities of the left side of the heart have been reported in 39% of patients with Ebstein’s anomaly ^, and consist of derangements in left ventricular geometry, impairment of systolic and diastolic function, ^, and non-compaction. ^, Superior systolic displacement of the mitral valve (prolapse) occurs because mitral leaflets with normal areas and chordal lengths are housed in a left ventricular cavity that is geometrically altered and reduced in size. ^{, , ,} Depressed systolic function is due to a combination of abnormal shape, impaired diastolic filling, and increased fibrous content of the free wall and the ventricular septum.

Physiologic consequences

The physiologic consequences of Ebstein’s anomaly are determined by the morphologic derangement of the tricuspid leaflets, by the hemodynamic burden imposed on an inherently flawed right ventricle, by left ventricular function, and by atrial rhythm. The tricuspid orifice is typically incompetent, occasionally stenotic, and rarely imperforate. Functional impairment of the right ventricle depends on the severity of tricuspid regurgitation and on the size of the right atrium and atrialized right ventricle relative to the size of the functional right ventricle. The thin-walled atrialized right ventricle is either passive during the cardiac cycle or functions as an aneurysm that expands paradoxically during systole and therefore acts as a physiologic impediment (see earlier). Exercise intolerance has been ascribed to an inadequate increment in pulmonary blood flow and a fall in systemic arterial oxygen saturation. ^, The enlarging right atrium becomes sufficiently commodious to accommodate a large volume of regurgitant flow with little or no increase in pressure ( Fig. 11.4 ). In older patients, right ventricular filling pressure may increase, provoking a rise in right atrial pressure with the establishment of the right-to-left interatrial shunt.

Ebstein’s original case was an example of obstruction at the tricuspid orifice (see Fig. 11.1 ). He wrote, “The membrane divided the right ventricle into two halves. These halves communicated with each other in two ways: one through the oval opening which leads into the right conus arteriosus, and two through the already described multiple openings in the fenestrated membrane.” When the tricuspid orifice is stenotic or imperforate, the elevation of right atrial pressure reflects the degree of obstruction. The A wave is often giant, and a right-to-left interatrial shunt persists after the fall in neonatal pulmonary vascular resistance.

The electromechanical properties of the right atrium, atrialized right ventricle and functional right ventricle provided the first secure basis for the clinical diagnosis of Ebstein’s anomaly ( Fig. 11.5 ; see also Fig. 11.2 ). ^, The right atrium proper generates a right atrial pressure pulse and an intracavitary atrial electrogram . The functional right ventricle generates a right ventricular pressure pulse and a right ventricular intracavitary electrogram . The atrialized right ventricle generates a right ventricular intracavitary electrogram but an atrial pressure pulse (see Figs. 11.2 and 11.5 ). Mechanical stimulation of the atrialized right ventricle provokes a right ventricular electrogram and incurs the risk of triggering ventricular tachycardia. ^, Clusters of ventricular cardiomyocytes are isolated within a fibrous matrix that prevents spiral/scroll reentrant waves from anchoring. When spiral/scroll waves do not anchor, they meander erratically as polymorphic ventricular tachycardia. Accordingly, mechanical stimulation of the atrialized right ventricle does not provoke monomorphic ventricular tachycardia that depends on slow conduction, unidirectional block, or a substrate that permits reentry but instead results in polymorphic ventricular tachycardia. ^,

The geometric configuration and function of the right and left ventricles are closely coupled in Ebstein’s anomaly. Leftward displacement of the ventricular septum ( Fig. 11.6 ; see also Fig.11.2 ) reduces the volume of left ventricular diastolic filling and, accordingly, reduces the ejection fraction. Exercise provokes an increase in left ventricular ejection fraction because end-systolic volume decreases with little or no change in end-diastolic volume. The right ventricular free wall contributes feebly, if at all, to forward flow, which is materially assisted by a paradoxical motion of the ventricular septum that functions as part of the right ventricle as in Uhl’s anomaly (see later). In brief, left ventricular function is adversely affected by the diastolic position of the ventricular septum, geometric distortion of the ventricle (see Fig. 11.6 ), reduced end-diastolic volume, paradoxical motion of the ventricular septum, an increase in fibrous tissue, and a decrease in cardiomyocytes in the free wall and septum.

The history

Males and females are equally affected. ^, Familial Ebstein’s anomaly has been reported. Genetic heterogeneity and associated microdeletions and novel mutations have been reported in populations of patients with Ebstein’s anomaly. ^,

The clinical course of Ebstein’s anomaly ranges from intrauterine death to asymptomatic survival to late adulthood. ^, The most common presentations are (1) the detection of the anomaly in a routine fetal echocardiogram, (2) neonatal cyanosis, (3) heart failure in infancy, (4) murmur in childhood, and (5) arrhythmias in adolescents and adults. ^, The outlook for fetal Ebstein’s anomaly has aptly been characterized as appalling . Of neonates with Ebstein’s anomaly, 20% to 40% do not survive 1 month, and less than 50% survive to 5 years. Fetal hydrops is almost invariably fatal with rare exception. ^, Neonates not only confront high mortality but also confront a significant ongoing risk of morbidity and death. ^{, ,} Even if symptoms resolve in the first month of life, the infant may then die suddenly. Transient neonatal cyanosis that recurs a decade or more later is an uncommon but distinctive and usually benign feature of Ebstein’s anomaly. A neonatal right-to-left interatrial shunt disappears as pulmonary vascular resistance normalizes; the shunt subsequently reappears as filling pressure rises in the functionally abnormal right ventricle. Tachyarrhythmic sudden death looms as a threat regardless of the severity of the anomaly ^, and is held responsible for the decline in survival rate in the fifth decade. Wolff-Parkinson-White syndrome in otherwise normal individuals carries an estimated sudden cardiac death risk of 0.02%, but in Ebstein’s anomaly, atrial flutter or fibrillation with accelerated conduction is accompanied by a major increase in the risk of sudden death. Stimulation of the arrhythmogenic atrialized right ventricle initiates polymorphic ventricular tachycardia that promptly degenerates into ventricular fibrillation ( Fig. 11.7 ) (see earlier), and spontaneous ventricular tachycardia/fibrillation looms as a threat. The degree of cyanosis does not necessarily correspond with symptoms, but once cyanosis and symptoms and develop, disability tends to be progressive, even in patients who were relatively asymptomatic before adulthood. The onset of chronic atrial fibrillation prefigures death within 5 years.

Despite qualifications, there are legendary accounts of astonishing longevity in Ebstein’s anomaly, with survivals into the eighth and ninth decades. ^{, , , ,} Ebstein’s anomaly was discovered at necropsy in a 75-year-old man who, as a youth, had been a lumberjack working on log booms. He was reportedly asymptomatic until his fifties, when he was obliged to outrun an irate female bear. At necropsy 25 years later, his right atrium was thin-walled and greatly dilated, and the tricuspid valve was characteristically malformed. The oldest recorded patient with Ebstein’s anomaly lived to age 85 years and was devoid of cardiac symptoms until age 79 years.

The chest pain that occasionally occurs with Ebstein’s anomaly is an enigma. The pain is retrosternal, epigastric, or in the right or left anterior chest, and it is sharp, stabbing, or shooting, features that suggest serious surface origin. A fibrinous pericardium has been found at necropsy over the atrialized right ventricle (see Auscultation).

Important although less frequent manifestations result from paradoxical emboli or brain abscess. Infective endocarditis is uncommon because regurgitant flow across the malformed tricuspid valve is low velocity with low turbulence. Prophylaxis for the low risk of infective endocarditis is open to question. Pregnancy incurs the risks inherent in a functionally inadequate volume overloaded right ventricle that copes poorly with the additional hemodynamic burden of gestation. Paroxysmal atrial tachyarrhythmias are potential hazards during pregnancy especially, the rapid rates associated with accessory pathways. Cyanosis may first become manifest during pregnancy because of a rise in filling pressure in the volume overloaded right ventricle. Hypoxemia increases the risk of fetal wastage, and a right-to-left interatrial shunt incurs a puerperal risk of paradoxical embolization.