DESCRIPTION 
- Ebstein anomaly (EA) is a congenital abnormality of the tricuspid valve with inferior displacement of the septal and/or posterior tricuspid leaflets from the atrioventricular ring (>8 mm/m2 body surface area), leading to partitioning of the RV into "atrialized" and functional RV components.
- Tricuspid leaflets typically dysplastic and tethered to the RV endocardium. The anterior leaflet may be normal or enlarged and "sail-like."
- Tricuspid regurgitation (TR), right atrial enlargement, and right-to-left shunting through an interatrial communication are characteristic, with impaired RV compliance and systemic cyanosis common. Pulmonary stenosis may be present. Tricuspid stenosis occurs rarely.
- Atrial arrhythmias are common, due to associated pre-excitation/Wolff-Parkinson-White (WPW) syndrome and/or right atrial enlargement.
- Clinical presentation of EA is extremely variable:
- Severe malformations presenting prenatally with intrauterine death
- Severe perinatal cyanosis while pulmonary vascular resistance is high
- Exercise intolerance, cyanosis, arrhythmias and/or CHF presenting during childhood
- Cardiac arrhythmias in adults
- Mild TR in virtually asymptomatic adults
EPIDEMIOLOGY
Rare congenital heart lesion, occurs equally in male and female patients.
Incidence
5/100,000 live births
Prevalence
~0.5% of all cases of congenital heart disease
RISK FACTORS
Association with maternal lithium therapy:
- Among women receiving lithium during the 1st trimester of pregnancy: Low (0.05–0.1%), but 5:1 relative risk of EA compared with those women who did not receive lithium.
Genetics
- Most cases occur sporadically.
- Incidence of congenital heart disease in the offspring of women with EA reported as 6%. Risk of a fetus having EA <1%.
- No genetic basis for most cases elucidated to date.
GENERAL PREVENTION
See above regarding maternal lithium exposure and risk of EA.
PATHOPHYSIOLOGY
Large RA with atrialized RV inflow and significant tricuspid insufficiency. Most often is associated with right-to-left shunting across a patent foramen ovale (PFO) or ASD and decreased RV filling. The small and sometimes dysfunctional RV, with or without pulmonary stenosis, also contributes to symptoms of low cardiac output.
ETIOLOGY
The etiology has not been established in most cases of EA.
COMMONLY ASSOCIATED CONDITIONS
- Interatrial communication (secundum atrial septal defect or PFO) present in ~90% of cases
- Pulmonary stenosis and pulmonary atresia can be seen. This may be due to decreased antegrade flow through the RV during early fetal development. With low RV cardiac output and PDA "pseudo-pulmonary atresia" may be noted (no forward blood flow over normal pulmonary valve). VSD occurs rarely.
- Diastolic and/or systolic RV dysfunction. A decrease in the absolute number of RV muscle fibers has been observed.
- LV systolic and diastolic dysfunction may occur. In part, may be related to diastolic bowing of the interventricular septum. LV hypertrophy, fibrosis, and dysplasia have been reported.
- Pre-excitation/Wolff-Parkinson-White (WPW) syndrome is seen in ~20% of patients. AV nodal re-entrant tachycardia and atrial flutter/fibrillation can also be seen.
- Ebstein-like anomaly of the left-sided tricuspid valve may occur in association with congenitally corrected transposition (l-transposition) of the great arteries transposition.
Outline
Signs and symptoms:
- Extreme variability in tricuspid valve morphology influences the clinical presentation.
- Presentation of EA also affected by the degree of TR, the presence of an interatrial communication, the degree of RV or LV dysfunction, and the presence of arrhythmias.
- May be dissociation between the severity of valve dysplasia, the degree of TR, and the severity of symptoms
History
- Fetal diagnosis can almost always be made by fetal ECG, especially when significant TR is present:
- RA enlargement, often massive when there is severe TR
- Lungs may be hypoplastic due to massive cardiomegaly
- CHF with pericardial effusion, ascites, and hydrops fetalis may occur, with high rate of intrauterine demise in these severe cases
- Uncommonly, a fetus with EA may be diagnosed after an arrhythmia is noted (usually atrial flutter or supraventricular tachycardia)
- Cases diagnosed in the neonatal period most often are associated with severe TR and right-to-left shunting across an interatrial communication, leading to significant systemic cyanosis and/or heart failure. RV outflow obstruction may or may not be present.
- Older children and adults may present with increasing cyanosis, dyspnea, or exercise intolerance, and/or arrhythmias. Asymptomatic patients may also be diagnosed solely by an abnormal cardiac exam leading to a CXR and ECG.
Physical Exam
- Neonatal:
- Murmur may or may not be audible
- Evidence of RV dysfunction: Elevated venous pressure, hepatomegaly, and ascites.
- Elevated pulmonary vascular resistance (PVR) during the immediate postnatal period can accentuate the severity of cyanosis, with increased right-to-left interatrial shunting and decreased antegrade flow through the RV to the pulmonary artery.
- Low volume of antegrade flow may make it extremely difficult to differentiate functional pulmonary atresia from true valvar pulmonary atresia. Inhaled nitric oxide has been used to differentiate these conditions.
- If supported through the 1st few days of life as PVR falls, the degree of cyanosis typically improves in the patient and may remain clinically stable for months to years. However, if true pulmonary atresia is present, the patient’s condition will continue to deteriorate.
- Less-symptomatic infants: Mild cyanosis, heart murmur, and/or atrial arrhythmias
- Older children and adults:
- Mild to moderate cyanosis with clubbing common.
- Hepatomegaly or a pulsatile liver from increased RA and systemic venous pressure may be noted in patients with only small interatrial communications.
- Peripheral edema
- Cardiac exam:
- Quiet precordium with a prominent RV impulse.
- Characteristic "gallop" rhythm with multiple extra heart sounds (due to widely split 1st and 2nd heart sounds, as well as S3 and/or S4 from abnormal ventricular filling).
- A "scratchy" systolic murmur is audible at the left mid to upper sternal border, and a low-intensity systolic regurgitant murmur (TR) may be heard along the left lower sternal border. A short, soft diastolic murmur may also be present (tricuspid inflow).
- Many previously undiagnosed adolescent and adult patients present with arrhythmias. These patients may be virtually acyanotic with relatively mild tricuspid abnormalities.
- Atrial arrhythmias common, a result of RA enlargement and/or accessory conduction pathways including WPW syndrome
- Ventricular arrhythmias occur less frequently.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
- Hemoglobin concentration: Increased proportionate to the degree of cyanosis. Serial analysis demonstrating increasing hemoglobin is consistent with increasing cyanosis.
- ECG abnormalities:
- First-degree AV block common (1/4–1/3 of patients)
- The P-wave usually enlarged (RA enlargement)
- Right bundle branch block with low voltage R’ pattern typical.
- Short PR interval and a delta wave in patients with WPW syndrome. The accessory pathway is usually right-sided or in the interventricular septum.
Imaging
- CXR shows cardiomegaly (may be massive) with increased RA size. There may be decreased pulmonary vascularity when there is marked right-to-left interatrial shunting.
- ECG: Imaging modality of choice (2-D, 3-D, and/or TEE):
- Inferior displacement of the effective tricuspid valve annulus and dysplasia of the tricuspid leaflets
- Color Doppler imaging will demonstrate TR originating from the effective valve annulus within the RV. An interatrial communication with right-to-left interatrial shunting can be visualized.
- Cardiac chamber enlargement, ventricular dysfunction, and associated lesions can be identified.
Diagnostic Procedures/Surgery
Cardiac catheterization is not necessary solely for diagnosis, and has been associated with increased risk.
- Historic: Simultaneous demonstration of atrial pressure with ventricular electrogram within atrialized portion of RV
- Generally reserved for assessment of associated lesions or preoperative evaluation of adult patients
- Can be combined with electrophysiologic testing to evaluate accessory pathways
DIFFERENTIAL DIAGNOSIS
- Depends on severity of the defect and degree of cyanosis.
- Must be differentiated from other cyanotic lesions, including tricuspid atresia and pulmonary atresia, as well as persistent pulmonary HTN of the newborn (PPHN).
- Uhl anomaly (parchment RV) should also be differentiated from EA. Uhl anomaly is an extremely rare malformation in which the RV myocardium is virtually absent and replaced by fibroelastic tissue. There is usually right-heart failure with peripheral edema and ascites. Arrhythmias may occur. Most patients do not survive childhood.
Outline
ADDITIONAL TREATMENT
General Measures
- Symptomatic cyanotic neonates without anatomic pulmonary obstruction often improve spontaneously as pulmonary vascular resistance (PVR) falls.
- Persistently critically ill patients may need urgent intervention to expedite the physiologic fall in PVR to increase antegrade flow through the RV.
SURGERY
Indications for surgical intervention not clearly established:
- In recent years, results of non-neonatal surgical repair of EA have improved significantly, with low operative morbidity and mortality and good early and medium-term results.
- Improved results have led most to conclude that any patient who has deteriorated to NYHA class III or IV despite medical management should undergo surgery.
- Technique: Reconstruction or replacement of dysplastic tricuspid valve, atrial plication, and closure of interatrial communication to eliminate right-to-left shunting. May include tricuspid annuloplasty with valve ring placement. Methods for tricuspid valve reconstruction vary. The recently described "cone reconstruction" technique is reported to be extremely effective. Tricuspid valve replacement using a porcine bioprosthetic valve is performed as an alternative to repair in certain surgical centers, particularly in adult populations.
- Surgical repair of the tricuspid valve has not been shown to alter the risk of sudden death from arrhythmias.
Outline
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Serial evaluation by physical exam, EKG, Holter monitor, ECG, and exercise testing with pulse oximetry: To evaluate for increasing cyanosis, exercise intolerance, or significant deterioration of tricuspid valve or ventricular function.
- Event recorder if there is a history of palpitations or ECG/Holter evidence of tachyarrhythmia.
Pregnancy Considerations
Pregnancy in asymptomatic women with EA is generally well tolerated. Risk of fetal miscarriage, premature delivery, and low birth weight are increased with maternal cyanosis.
PATIENT EDUCATION
- No diet restrictions.
- Usually no other restrictions for patients in NYHA class I and II. Those with nearly normal heart size and no significant dysrhythmias can participate in physical activities as tolerated according to the AHA Task Force 1 on Congenital Heart Disease.
- Patients with severe EA should be restricted from sports participation.
PROGNOSIS
- Quite variable, ranging from EA diagnosed as an incidental finding in an older adult, to high risk of fetal demise in severely symptomatic fetuses.
- Severity of tricuspid regurgitation, size of functional RV, and the function of RV and LV can influence prognosis of EA.
- Neonates with severe cyanosis and heart failure have high mortality despite attempts at intervention (medical or surgical).
- Some children with only mild cyanosis may develop arrhythmias with hemodynamic deterioration during adolescence or adulthood.
- Sudden death does occur rarely, and may not be predicted by the presence of symptoms, prior arrhythmias or pre-excitation syndrome.
Outline