AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Raymond T Fedderly, MD, Assistant Professor, Department of Pediatric Cardiology, Children's Hospital of Wisconsin, Medical College of Wisconsin
Raymond T Fedderly is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, and American Medical Association
Editors: Charles Berul, MD, Associate Professor of Pediatrics, Harvard Medical School; Senior Associate, Department of Cardiology, Children's Hospital of Boston; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; John W Moore, MD, MPH, Professor of Clinical Pediatrics, Division of Pediatric Cardiology, Mattel Children's Hospital of University of California at Los Angeles; Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Department of Pediatrics, Baylor College of Medicine
Author and Editor Disclosure
Synonyms and related keywords:
Ebstein anomaly, Ebstein's anomaly, Ebstein anomaly of tricuspid valve, Ebstein's anomaly of tricuspid valve, Ebstein disease, Ebstein's disease, congenital heart defect, heart, tricuspid valve
Background
Ebstein anomaly of the tricuspid valve is a congenital heart lesion that involves abnormal attachments of the tricuspid valve leaflets to the annulus of the tricuspid valve. Marked variability exists in the degree of displacement of the septal and posterior leaflets into the cavity of the right ventricle. This may result in a right ventricle that is divided into an atrialized portion above the valve leaflets and a muscular portion below the valve leaflets. An atrial septal defect (ASD) or patent foramen ovale (PFO) is present in 90% of the patients; pulmonary stenosis or atresia is present in 20-25% of the patients. The lesion was first described in 1866 by Wilhelm Ebstein and first referred to as Ebstein's disease in 1927.
Pathophysiology
Hemodynamic consequences of this lesion are directly related to the severity of the leaflet displacement and the resultant tricuspid valve regurgitation. In the case of mild displacement and mild valvar regurgitation, the patient may be asymptomatic for many years. If, however, the leaflet displacement and valvar regurgitation are severe, pulmonary blood flow is decreased, the right atrium becomes dilated, blood is shunted right to left across an ASD or PFO, and the patient may become cyanotic. Congestive heart failure may also develop secondary to a small functional right ventricle and decreased right ventricular compliance. Additional problems in these patients include an association with paroxysmal supraventricular tachycardia (SVT), which occurs in 25-50% of patients, and 5-10% of these patients have Wolff-Parkinson-White (WPW) syndrome.
Frequency
United States
Incidence of Ebstein anomaly of the tricuspid valve is approximately 1:20,000 live births, accounting for less than 1% of all congenital heart defects.
Mortality/Morbidity
Intrauterine mortality of this lesion is as high as 85%. Mortality after birth is associated with significant cyanosis. Newborns with cyanosis have a mortality rate of up to 70% compared to 15% for newborns without cyanosis. Death is related to low cardiac output, postoperative complications, and sudden death. Actuarial survival among liveborn patients has been reported to be 67% at 1 year and 59% at 10 years.
Race
In the Baltimore Washington Infant Study (BWIS), 41 of 47 infants (87%) were white and 6 of 47 (13%) were black.
Sex
Males and females are affected equally.
Age
Severity of the leaflet displacement and the degree of associated right ventricular outflow tract obstruction determine age at presentation. In the BWIS, 81% of the patients were diagnosed during their first week of life, 6% were diagnosed when aged 1-4 weeks, 11% were diagnosed when aged 5-25 weeks, and 2% were diagnosed when older than 25 weeks. In contrast to the BWIS, a study from India in 1994 by Jaiswal et al showed age at presentation ranging from 3 months to 51 years, with a mean of 19.5 years.
History
For the purpose of clinical presentation, the patients are separated into the age groups used in a study by Celermajer et al.
- Fetus
- Abnormal fetal scan, 86%
- Arrhythmia, 5%
- Neonate (aged 0-1 mo)
- Cyanosis, 74%
- Heart failure with poor feeding and failure to thrive, 10%
- Incidental heart murmur, 9%
- Infant (aged 2 mo to 2 y)
- Cyanosis, 35%
- Heart failure with poor feeding and failure to thrive, 43%
- Incidental heart murmur, 13%
- Child (aged 3-10 y)
- Cyanosis, 14%
- Heart failure with poor growth and decreased exercise tolerance, 8%
- Arrhythmia with complaints of palpitations, 12%
- Incidental heart murmur, 66%
- Adolescent (aged 11-18 y)
- Cyanosis, 13%
- Heart failure with dyspnea on exertion and decreased exercise tolerance, 13%
- Arrhythmia with complaints of palpitations, 40%
- Incidental heart murmur, 33%
- Adult (aged >18 y)
- Cyanosis, 4%
- Heart failure with dyspnea on exertion and decreased exercise tolerance, 26%
- Arrhythmia with complaints of palpitations, 43%
- Incidental heart murmur, 13%
- Chest pain, 20%
- Syncope, 6%
Physical
The physical examination of these patients is variable based on the age of the patient and the degree of tricuspid valve regurgitation and right ventricular outflow tract obstruction.
- The classic cardiac examination is marked by a gallop or quadruple rhythm caused by widely split first and second heart sounds, as well as a third heart sound or fourth heart sound.
- Tricuspid regurgitation causes a holosystolic or regurgitant systolic murmur at the left lower sternal border.
- A diastolic murmur of relative tricuspid stenosis and the systolic ejection murmur associated with right ventricular outflow tract obstruction also may be heard.
- Congestive heart failure, if present, may cause passive liver congestion, and the liver edge may be easily palpable below the right costal margin.
- Clubbing and elevated jugular venous distension may be present in older patients.
Causes
The majority of cases are sporadic, but familial cases have occurred. Maternal lithium and benzodiazepine exposures have been implicated as a cause of this disease.
Tricuspid Atresia
Other Problems to be Considered
Uhl anomaly
Arrhythmogenic right ventricular dysplasia
Imaging Studies
- Echocardiogram is the definitive test for diagnosis. Typical findings on echocardiogram include the segmental anatomy, whether there is inferior displacement of the septal and/or posterior leaflet of the tricuspid valve, large tricuspid valve annulus, dilated right atrium and right ventricle, tricuspid valve regurgitation, right ventricular outflow tract obstruction, and presence of an ASD or PFO.
- Chest radiography may be helpful in determining the size of the cardiac silhouette, which is related to the degree of tricuspid valve regurgitation. In severe cases, the cardiothoracic ratio may approach one. A dilated right atrium contributes the majority of cardiomegaly seen. In patients who are cyanotic, the pulmonary vascular markings will appear decreased.
Other Tests
- Electrocardiogram: Typical findings on the ECG are large P waves, a prolonged PR interval, right axis deviation, and a right bundle branch block. Atrial or ventricular arrhythmias, as well as a delta wave indicative of WPW syndrome, also can be seen.
- Holter monitor: Ambulatory ECG recording may be performed to evaluate the possibility of occult arrhythmias or to verify symptomatology, such as palpitations over 24 or 48 hours.
- Stress test: Exercise testing may be done both preoperatively and postoperatively to objectively evaluate exercise tolerance, oxygen consumption, systemic arterial oxygenation, and possible arrhythmia vulnerability during exercise.
Procedures
- Cardiac catheterization may be performed to evaluate both the hemodynamic and angiographic characteristics of the patient before surgical intervention. Depending on the particular patient's anatomic and physiologic findings, the echocardiogram is often sufficient, and may reduce the necessity for cardiac catheterization.
- Postcatheterization precautions include hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction from thrombosis or spasm.
- Complications may include rupture of blood vessel, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.
- Electrophysiological (EP) studies are performed in many patients suspected of having an arrhythmia secondary to paroxysmal SVT and WPW syndrome, both of which have a high incidence of occurrence. During invasive EP testing, an accessory pathway most often is identified along the abnormal tricuspid annulus. Manifest accessory pathways (WPW) and concealed pathways (unidirectional retrogradely conducting accessory pathways) account for the majority of SVT mechanistically in patients with Ebstein anomaly. The frequency of multiple accessory pathways is significantly higher in Ebstein anomaly than in the general population of patients with SVT and normal tricuspid valve anatomy.
Medical Care
Asymptomatic patients with mild tricuspid regurgitation need only outpatient clinic evaluation, which may include periodic ECG, chest x-ray (CXR), and oxygen saturation measurement. All patients with this diagnosis require lifetime prophylaxis for bacterial endocarditis. In neonates who have a severe form of this disease, an adequate atrial communication is crucial. If the patient is born with only a PFO or a restrictive ASD, a balloon atrial septostomy or urgent surgical intervention may be required. Atrial septostomy can be accomplished at the bedside with echocardiographic guidance or in the cardiac catheterization laboratory, under echocardiographic and/or fluoroscopic guidance.
- Electrophysiological studies are performed both as a diagnostic tool to determine the cause of an arrhythmia and as a curative procedure using radiofrequency catheter ablation.
- Catheter ablation for paroxysmal SVT is highly successful in children, with a low complication and recurrence rate; however, the subset of patients with Ebstein anomaly and SVT has been shown to be more challenging to cure, likely because of the derangement in tricuspid valve alignment with the tricuspid annulus and the increased likelihood of multiple accessory pathways.
- The reported acute success rate in the Pediatric Radiofrequency Ablation Registry and other sources ranges from 75-90% and the recurrence rate is reported as high as 32%.
- As expected, there is variability in success rates, complications, and recurrence rates with complex pediatric radiofrequency catheter ablation procedures, dependent on operator and institutional experience.
- Radiofrequency ablation appears to be most successful in patients with a mild degree of tricuspid regurgitation.
Surgical Care
The surgical care of these patients is dependent on the severity of the leaflet displacement and on the degree of associated right ventricular outflow tract obstruction.
- In neonates with the most severe form of Ebstein anomaly, the functional right ventricle is hypoplastic, and the patient usually is treated best by closing the tricuspid valve and, in effect, creating a tricuspid atresia physiology (Starnes procedure). In addition, these infants require a systemic artery–to–pulmonary artery shunt.
- When the patient is aged approximately 6 months, a bidirectional Glenn procedure (superior vena cava–to–pulmonary artery anastomosis) and shunt takedown is performed.
- Fontan completion (inferior vena cava–to–pulmonary artery anastomosis) is usually performed when the patient is aged 2-4 years.
- In infants with mild-to-moderate tricuspid regurgitation and severe right ventricular outflow tract obstruction, a systemic artery–to–pulmonary artery shunt is performed in addition to an unrestrictive atrial communication being created.
- In patients with moderate-to-severe tricuspid regurgitation, the abnormal valve can be replaced with a mechanical or prosthetic valve, a surgical reconstruction, or a combination of the two.
Diet
Special dietary restrictions usually are not required. An infant with severe tricuspid regurgitation may require a high caloric density formula.
Activity
The activity restrictions of these patients depend on the severity of the leaflet displacement. If the displacement is mild and patients do not have an associated paroxysmal SVT, they should be allowed to determine their own level of activity. For patients with cyanosis, sports participation usually is restricted somewhat. An exercise stress test and other noninvasive assessments might be helpful in making this determination.
In patients who are asymptomatic, the only drug therapy normally required is prophylaxis for bacterial endocarditis. In patients with congestive heart failure, digoxin and diuretics may be required. Patients with cyanosis are at an increased risk for a paradoxical embolus and may require therapy with coumadin or aspirin. Patients who have paroxysmal SVT may require a beta-blocking or calcium channel–blocking agent or, possibly, a Vaughn-Williams class I or III antiarrhythmic agent. The choice of antiarrhythmic agent is somewhat dependent on symptom severity, tachycardia mechanism, potential medical contraindications, patient and physician preferences, and alternate therapeutic choices, such as catheter ablation. Antibiotics for endocarditis prophylaxis are required before performing procedures that may cause bacteremia. For more information, see Antibiotic Prophylactic Regimens for Endocarditis.
Drug Category: Inotropic agents
These agents increase cardiac output.
| Drug Name | Digoxin (Lanoxin) |
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| Description | Cardiac glycoside with direct inotropic effects in addition to indirect effects on the cardiovascular system. Acts directly on cardiac muscle, increasing myocardial systolic contractions. Its indirect actions result in increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure. |
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| Adult Dose | Maintenance dose: 0.125-0.25 mg PO qd |
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| Pediatric Dose | Maintenance dose:
Preterm infant: 5-7.5 mcg/kg/d PO divided bid
Term infant: 6-10 mcg/kg/d PO divided bid
1 month to 2 years: 10-15 mcg/kg/d PO divided bid
2-5 years: 7.5-10 mcg/kg/d PO divided bid
5-10 years: 5-10 mcg/kg/d PO divided bid
>10 years: 2.5-5 mcg/kg/d PO qd |
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| Contraindications | Documented hypersensitivity; severe hypokalemia; renal failure; WPW syndrome with antegrade conduction of accessory pathway; AV block; idiopathic hypertrophic subaortic stenosis or constrictive pericarditis |
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| Interactions | Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, oral amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil
Medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, oral colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Check renal function and previously prescribed medications before starting digoxin therapy; hypokalemia, hypomagnesemia, hypercalcemia, and hypermagnesemia predispose patients to digoxin toxicity |
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Drug Category: Diuretics
These agents decrease pulmonary or systemic edema.
| Drug Name | Furosemide (Lasix) |
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| Description | Increases excretion of water by interfering with chloride-binding cotransport system, which inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. |
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| Adult Dose | 20-80 mg/d PO qd or divided tid |
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| Pediatric Dose | 0.5-1 mg/kg/dose PO q8-24h |
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| Contraindications | Documented hypersensitivity; severe hypovolemia; severe electrolyte imbalance |
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| Interactions | Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication |
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| Pregnancy | C - Safety for use during pregnancy has not been established.
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| Precautions | Carefully monitor electrolytes and volume status; may increase risk of renal stones |
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Drug Category: Prostaglandins
Neonates with severe Ebstein anomaly and insufficient or ductal dependent pulmonary blood flow require prostaglandin E1 therapy.
| Drug Name | Alprostadil (Prostaglandin E1, Prostin VR Pediatric injection) |
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| Description | Temporary maintenance of patency of ductus arteriosus in neonates with ductal-dependent congenital heart disease until surgery can be performed. The underlying conditions may present as cyanotic or acyanotic heart disease. Provides vasodilation by direct effects on vasculature and ductus arteriosus smooth muscle. |
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| Pediatric Dose | Neonates and infants: 0.05-0.1 mcg/kg/min IV; reduce to lowest effective dose; if unresponsive, dose may be slowly increased; maintenance range is typically 0.01-0.4 mcg/kg/min IV |
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| Contraindications | Documented hypersensitivity; hyaline membrane disease, respiratory distress syndrome |
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| Interactions | Caution with concomitant drugs that may lower blood pressure, decrease serum glucose, cause respiratory depression, or have proarrhythmic effects |
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| Pregnancy | X - Contraindicated in pregnancy
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| Precautions | May cause apnea (10-12%), which most often occurs in neonates <2 kg at birth and usually appears during the first hour of the infusion, monitor respiratory status throughout treatment and have ventilatory assistance immediately available; caution with bleeding tendencies; monitor for hypotension, bradycardia, and arrhythmias; prolonged infusions associated with hypocalcemia or hypoglycemia |
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Further Inpatient Care
- Neonates with severe Ebstein anomaly initially require admission to a neonatal intensive care unit (NICU) for stabilization. If pulmonary blood flow is insufficient or ductal dependent, they also require prostaglandin E1 therapy.
Further Outpatient Care
- Patients who are asymptomatic initially may develop increasing cyanosis or congestive heart failure. They require continued outpatient monitoring.
Complications
- Patients who have cyanosis have an obligatory right-to-left shunt at the atrial level through the ASD or PFO. This places them at risk for paradoxical embolus and stroke. Therapy with coumadin or aspirin may reduce the risk of embolic complications.
Prognosis
- The prognosis for patients with Ebstein anomaly varies significantly based on the severity of the leaflet displacement and the resultant tricuspid valve regurgitation.
- Actuarial survival among liveborn patients has been reported to be 67% at 1 year and 59% at 10 years.
- In those patients who require and survive tricuspid valve replacement or valvuloplasty, the 10- to 18-year survival rate is reported to be 83-92%; 92-94% were in New York Heart Association class I or II.
- Freedom from reoperation is approximately 80% at 15 years.
Patient Education
- Patient and family education is directed at communicating the importance of prophylaxis for bacterial endocarditis and identifying the signs and symptoms of potential arrhythmias and progressive congestive heart failure.
- For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Palpitations.
Special Concerns
- Pregnancy: In a study from the Mayo clinic, 44 women with Ebstein anomaly had 111 pregnancies resulting in 85 live births (76%), 19 miscarriages (17%), 7 therapeutic abortions (6%), and 2 neonatal deaths (1.8%). Premature deliveries occurred in 23 of 85 live births (30%). The mean birth weight was 2.53 kg. One infant had Ebstein anomaly; 6% of the infants had some form of congenital heart disease.
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Ebstein Anomaly excerpt Article Last Updated: May 3, 2006
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