Revised by Jose Sierra from an article of 2001-06-27

Angela Appendino Capelanes, MD*, Alicia Martin-Hirsel, MD, RDMS^&, Cheryl Turner, RDMS, BS^#, Philippe Jeanty, MD, PhD^#

*Centro de Atendimento Materno-Fetal, Aracatuba Sao Paulo, Brazil; ^&Nashville, TN, ^#Nashville, TN

Synonyms: None.

Definition: It is a congenital heart anomaly in which the tricuspid valve has dysplasic leaflets with altered structure and/or position^,.

Every normal tricuspid leaflet consists of a peripheral zone to which the chordae tendineae inserts, a basal zone of atrioventricular attachment, and a free zone between these two. The anterior leaflet is the largest of the three. The septal leaflet is mainly attached to the atrioventricular septal wall and to the posterior leaflet to the free posterior wall of the right ventricle. In Ebstein"s anomaly the anterior valve is redundant, has a normal position, and is sometimes deformed and/or fenestrated. The septal and posterior valves can be in a normal location or more commonly with their attachments below the atrioventricular junction, to the septal ventricular wall the former and to the posterior ventricular wall the later. In either case they are firmly adhered to their insertion site, and in most cases, covering the papillary muscles and chordae tendineae. As a result, the tricuspid leaflets do not attach normally to the annulus, and the valve orifice is displaced downward into the right ventricle. This produces a deformed and dysfunctional tricuspid valve. Early presentation is usually due to associated cardiac lesions, mainly pulmonary stenosis or atresia1^,,[iv],,.

The degree of abnormality will be responsible for the findings, outcome and prognosis of the affected individuals. The most common finding varies according to each age group3:

• Abnormal routine prenatal scan for fetuses (86%)
• Cyanosis for neonates (74%)
• Heart failure for infants (43%)
• Incidental murmur for children (63%)
• Supraventricular paroxistic arrhythmias for adolescents and adults (42%).

Case report: A G3P2A0 patient had an ultrasound at 18 weeks, which demonstrated a right hydronephrosis. A follow-up examination at 32 weeks and a subsequent examination by a pediatric cardiologist, demonstrated findings consistent with Ebstein"s anomaly:

• Lower displacement of tricuspid valve which appeared competent but with mild insufficiency
• No associated cardiac enlargement
• No evidence of cardiovascular decompensation
• Possible ventricular septal defect.

Umbilical artery, ductus venosus, and umbilical vein flows were within normal limits. No other cardiac anomalies were noted.

The mother had no intercurrent illnesses and did not use of over- the-counter medications or drugs during the pregnancy. An amniocentesis was suggested due to two known anomalies (hydronephrosis and Ebstein's anomaly) but the patient declined the procedure. Follow-up examination did not reveal decompensation. The baby was born at term and is doing fine and will be scheduled for surgery.

History: In 1864, the Polish Wilhelm Ebstein made the first description of this anomaly based in clinical data and necropsy information. In 1937, Yater and Shapire reported the first case of Ebstein's anomaly with radiological and electrocardiographic data. In 1950, Engle concluded that clinical diagnosis was possible. The first description of Ebstein anomaly in America was done by William George MacCallum (1874-1944), professor of pathology at Johns Hopkins Hospital, in 1890 . Currently, ultrasonographic criteria are important elements for the prenatal detection of this congenital cardiac anomaly1^,3^,[vii].

Incidence: .5:10.000 live births3^,.

Prevalence: The reported prevalence is .3-.5% among congenital heart defects. Ebstein's anomaly represents approximately 45-60% of all tricuspid valve disease3^{,[ix],,,[xii]}.

Sex ratio: F1:M13^,8

Etiology: It is considered a sporadic event. However, familial recurrence has been documented. There are two reported sisters, born to consanguineous parents, who were diagnosed prenatally with severe Ebstein's anomaly. Exogenous female sexual hormones[xiii], lithium[xiv]^{,[xv],[xvi],[xvii]} and maternal rubella have been associated with Ebstein's anomaly[xviii]^{,[xix],[xx],[xxi]}. Older literature reports, indicate a teratogenic potential of high doses of lithium, and a 400-fold increase in the occurrence of Ebstein's anomaly in association to its exposure in utero3^,[xxii]. However, in patients with bipolar disorder, the benefits of lithium far out weight the small risk of Ebstein's anomaly[xxiii].

Pathogenesis: The low displacement of the posterior and septal leaflets of the tricuspid valve, between the inlet and the trabecular portion of the right ventricle, do not close well enough during systole and form an enlarged right atrial cavity with anatomic components of right ventricle: the so called "atrialized ventricle", which is functionally integrated to the right atrium. The greater the downward displacement of these leaflets, the smaller the functional right ventricle and the larger the "atrialized ventricle". The "atrialized ventricle" (which is abnormally located in the right atrium) has a fibrous thin wall that lacks enough muscle fibers, favoring aneurismatic formations that can alter the left's ventricle anatomy. As part of the right anatomic ventricle becomes functionally atrial, the right functional ventricle becomes significantly smaller and hypoplasic, with decreased contractility.

The tricuspid valve is usually incompetent and/or stenotic, but may be imperforate. When the commissures are fused and the anterior leaflet is intact (not fenestrated), the tricuspid orifice in Ebstein's anomaly becomes imperforate. This increases right to left shunting and decreases flow into the right ventricle, making it more hypoplasic. Note that in description of Ebstein's anomaly in children and adults the right ventricle is often described to be enlarged. This is probably a selection bias: we see the worst cases that do not reach the pediatric cardiologist.

The pulmonary valve is usually stenotic, and as a consequence, a hypoplasic main pulmonary artery with high pulmonary vascular resistance and elevated right ventricular systolic pressure will develop. Tricuspid incompetence is therefore augmented, and blood from the dysfunctional right ventricle will eventually go back to the enlarged and dysfunctional right atrium, increasing its pressure. High volume and pressure in this cavity will create a greater right to left shunt through the foramen ovale, with a resulting left heart size increase.

In those cases of isolated incompetent tricuspid valve, compensatory mechanisms will come into sight, at least partially and for several years, for symptom relief of those who do not die in utero. After birth, as the oxygen saturation rises, the pulmonary vascular resistance falls and the pressure of the functional right ventricle decreases. The right atrium will be more compliant (in order to accept large volumes of regurgitation), reducing its right to left shunting.

Later in the natural history, the filling pressure in the functionally inadequate right ventricle rises again, provoking a right atrial pressure rise with reestablishment of the right to left shunting through the atrial septum. This event is responsible for the cyanosis seen in the majority of cases.

Cardiac anomalies potentiate the occurrence of different arrhythmias according to the affected site and most of the patients with Ebstein's anomaly will die from heart failure or arrhythmia1^,3^,6,[xxiv],[xxv],[xxvi].

Sonographic findings:  Fetal echocardiography has proved to be a reliable technique in differentiating the variants of tricuspid valvular disease, diagnosing associated cardiac lesions and predicting subsequent outcome1^,3^,6^,10^,26^{,[xxvii],[xxviii],[xxix],[xxx],[xxxi],[xxxii]}:

• In the apical four chamber view, the typical distal displacement of the annular attachment of the tricuspid valve leaflets can be viewed. Displacement of the septal tricuspid leaflets is measured as the distance from the anatomic annulus to the distal attachment of the septal leaflet. The atrialized right ventricle is identified in the same view as the distance between the anatomic tricuspid annulus and the functional annulus. The functional right ventricle is the area distal to the displaced leaflet.
• Finding a right atrial enlargement on an early sonogram should prompt the search for tricuspid valve abnormalities with tricuspid regurgitation and the presence of pulmonary atresia or stenosis. A large elongated anterior leaflet can be seen in real time, with severe tricuspid regurgitation on Doppler examination.

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• If the fetus has a supraventricular paroxistic taquicardia it can eventually be diagnosed by ultrasound.
• Reversed ductus arteriosus shunting
• Left ventricular compression by the right heart dilatation has also been
• Increased cardiothoracic ratio. Even though increased cardiothoracic ratio and lesions of the right ventricular outflow tract contribute to the poor outcome in the cases detected prenatally, the absence of these features does not always indicate a good prognosis because progression of disease can occur with advancing gestational age.
• Rarely, hydrops can be seen, and these cases have been correlated postnatally with a small foramen ovale.
• No absolute measurement or single sonographic feature is a consistent predictive factor of prognosis.

Differential diagnosis:

1. Since Ebstein's anomaly may be associated with pulmonary stenosis or atresia, other problems in which isolated or associated pulmonic atresia or stenosis should be sought.
2. Other forms of congenital tricuspid regurgitation:
   • Unguarded tricuspid valve
   • Pure tricuspid valve dysplasia
   • Endocardial cushion defect should be taken into consideration.
3. Idiopathic right atrium enlargement is occasionally seen in children without Ebstein's anomaly.
4. Ebstein's anomaly with an imperforate tricuspid orifice (atresia within the right ventricle) is to be distinguished from Ebstein's anomaly with pulmonary atresia and intact ventricular septum1

• Ebstein's anomaly
• tachyarrhythmias with distention of the right atrium
• idiopathic giant atrium (a rare anomaly)
• Uhl's anomaly
• common atrium
• pulmonary atresia with regurgitant tricuspid
• pulmonary stenosis with intact interventricular septum
• premature closure of the foramen oval.

• Ebstein's anomaly
• pulmonary atresia
• severe obstructive tricuspid valve abnormalities
• severe tetralogy of Fallot
• single ventricle
• pulmonary stenosis

7.   Left axis cardiac deviation can be demonstrated in fetuses with:

·        Ebstein's anomaly

·        truncus arteriosus

·        pulmonic stenosis

·        coarctation of the aorta

·        tetralogy of Fallot[xxxiv]

8. Non-cardiac anomalies can mimic Ebstein's anomaly. The most common is a lung cyst, but cystic teratoma, pericardial cyst, or duplication of the gut can give a similar appearance.

Associated anomalies: The most consistent associations are pulmonary atresia and/or stenosis. Holt-Oram syndrome is an autosomal dominant disorder characterized by heart defects (atrial septal defect and Ebstein's anomaly) in combination with characteristic upper-limb abnormalities[xxxv]. It may also be associated with trisomy 13, 21, Turner, Cornelia de Lange and Marfan syndromes.

Prognosis: The prognosis of Ebstein's anomaly detected prenatally is poor, with mortality around 80 to 90%. Although the disease has a variable severity with some cases discovered only late in life, prenatal cases are almost uniformly fatal. Fetuses with cardiomegaly and cardiothoracic ratio > 0.6 will have lung hypoplasia as a sequel of compression by cardiac enlargement. The presence of hydrops, an obstruction of the right ventricular outflow tract, and lung hypoplasia can be considered as signs of poor prognosis[xxxvi].

Recall that after birth those cases of isolated incompetent tricuspid valve, will have some heart overload relief, at least partially and for several years, due to an oxygen saturation rise, with a decrease in peripheral vascular resistance in the pulmonary artery. This reduces the pressure of the right functional ventricle. The right atrium will also be more compliant to accept large volumes of regurgitation, reducing its right to left shunting for several months or years. Later in the natural history, the filling pressure in the functionally inadequate ventricle rises again, provoking a rise in right atrial pressure with reestablishment of the right to left shunting through the atrial septum. These mild to moderate Ebstein's anomalies will have a benign neonatal course.

The prognosis worsens when there is an associated pulmonic stenosis and/or atresia, or if there is an imperforate tricuspid valve. Fetuses that develop hydrops usually die in uteri due to an associated small foramen ovale that is inadequate for the right to left shunting.

Intermittent or persistent cyanosis occurs in 50 to 80% of the patients with Ebstein's anomaly. The acyanotic patients can be appreciably handicapped.

Patients who survive the first year, are acyanotic, and/or do not have paroxistic taquicardia will have the best prognosis. Patients with Ebstein's anomaly usually die in the second, third or forth decade of life, but natural history ranges from intrauterine or neonatal death to asymptomatic cases with normal life span.

No absolute measurement or echocardiographic feature has emerged as a consistent predictive factor of prognosis1^,3^,5^,10^,11^,24^,25^,[xxxvii].

Recurrence risk: Unknown. Most cases of Ebstein's Anomaly are sporadic, but familial occurrence has been documented2.

Management: No special treatment during pregnancy is offered. Adequate counseling is highly recommended. Labor and delivery should be undertaken under fetal and maternal surveillance. Surgical procedures may be offered according to each case, with variable results. Management of paroxistic arrhythmias will improve life quality1^,3.

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