Pediatric Ebstein Anomaly


Background

Ebstein anomaly of the tricuspid valve is a congenital defect characterized by downward displacement of the insertion of septal and posterior leaflets. Such displacement leads to tricuspid regurgitation secondary to lack of coaptation of the leaflets. As a consequence of downward displacement of leaflet insertion, a portion of the right ventricle (RV) is included on the right atrial side ("atrialized portion of the RV"). The severity of  the clinical presentation depends on the degree of displacement of the leaflets and the associated cardiac defects.

The lesion was first described in 1866 by Wilhelm Ebstein and first referred to as Ebstein disease in 1927. In addition to the downward displacement of the insertion of tricuspid valve leaflets, there may also be (i) redundancy of the normally-inserted anterior leaflet of the tricuspid valve and (ii) abnormal attachment of the tricuspid valve chordae to the RV wall, causing obstruction to the RV outflow tract.

Associated cardiac defects include (i) atrial septal defect (ASD) or patent foramen ovale (PFO), which is present in 90% of the patients; (ii) pulmonary stenosis or atresia, which is present in 20%-25% of the patients; and (iii) an accessory conduction pathway similar to that of Wolf-Parkinson-White syndrome (20%).

Patients with congenitally-corrected transposition of the great arteries (L-TGA) have the tricuspid valve on the left-side of the heart. This type of Ebstein anomaly noted in such a left-sided tricuspid valve is called an Ebsteinoid anomaly.

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 patient education resources, see Heart Health Center, as well as Palpitations (Causes, During Pregnancy, Symptoms, Treatment).

Pathophysiology

Hemodynamic status in patients with Ebstein anomaly depends on the severity of the lesion. Those with mild leaflet displacement and mild valvar regurgitation may be asymptomatic for many years, whereas severe leaflet displacement with severe tricuspid valve regurgitation results in severe dilatation of the right atrium—even as a fetus. The size of the functional right ventricular (RV) (excluding the atrialized portion of RV) may be too small to generate adequate RV systolic pressure (by a combination of its small functional size and severe tricuspid regurgitation). Such severe cases present in newborns. Cyanosis occurs owing to three mechanisms: Right-to-left shunting at the atrial septal defect or patent foramen ovale, decreased pulmonary blood flow as a result of either functional or anatomic pulmonary valve stenosis/atresia and high pulmonary vascular resistance noted as neonatal transitional circulation. In such circumstances, the newborn will be dependent on the patent ductus arteriosus to maintain pulmonary blood flow at least until the pulmonary vascular resistance decreases in the newborn. Congestive heart failure may also develop secondary to a small functional RV and reduced RV compliance. Neonatal presentation of Ebstein anomaly needs careful management and has a worse prognosis than presentation at an older age.

Patients with moderate leaflet displacement present with transient cyanosis as newborns, which improves with a gradual decrease in pulmonary vascular resistance. These patients may be followed clinically for elective repair later when they're older.

Additional problems in these patients include an association with paroxysmal supraventricular tachycardia (SVT), which occurs in 25%-50% of patients. Many of these patients with SVT have Wolff-Parkinson-White (WPW) syndrome.

In short, patients with Ebstein anomaly are at risk not only for tricuspid regurgitation and RV enlargement but also for RV and left ventricular (LV) dysfunction and dyssynchrony. [12LV dysfunction and dyssynchrony are associated with heart failure and disease severity parameters that can be assessed with cardiac magnetic resonance imaging (CMRI) tracking (CMR-FT). [12]

Epidemiology

Ebstein anomaly accounts for 0.3%-0.6% of all congenital heart diseases. Most cases are sporadic, but familial cases have occurred. [345Maternal lithium and benzodiazepine exposures have been implicated as a cause of this disease. No specific gene defect has been consistently identified in association with Ebstein anomaly, although more recently, a missense mutation in FLNA (filamin A), an actin-binding protein located at Xq28, has been identified. [4]

A higher occurrence of Ebstein anomaly is reported in the offspring of women with Ebstein anomaly (6%) than for men with this disease (0.6%). [6]

Prognosis

Prognosis depends on the severity of the anomaly. However, individuals with Ebstein anomaly have a significantly increased risk for sudden death, with multivariate key clinical predictors of sudden death including previous ventricular tachycardia, heart failure, tricuspid valve surgery, pulmonic stenosis, and hemoglobin level above 15 g/dL. [7]

In an analysis of 2010-2016 data from 255 neonates and 239 infants at 95 centers from the Society of Thoracic Surgeons Congenital Heart Surgery database to evaluate surgical management and outcomes of Ebstein anomaly, investigators found that there was a very high risk of symptomatic Ebstein anomaly in early infancy and these cases involved a variety of surgical interventions. [8The primary procedures most often performed in neonates were Ebstein repair (39.6%), systemic-to-pulmonary shunt (20.4%), and tricuspid valve closure (9.4%), with an overall surgical mortality of 27.4 (51.4% composite morbidity-mortality). Among infants, the most common primary procedures were superior cavopulmonary anastomosis (38.1%) and Ebstein repair (15.5%), with an overall operative mortality of 9.2% (20.1% composite morbidity-mortality). [8]

Pregnancy influences cardiac function and hemodynamics in women with Ebstein anomaly; these women should be clinically and hemodynamically monitored during their pregnancy to minimize their cardiac risk as well as to aid clinicians in choosing the appropriate delivery mode. [9 In a retrospective (1995-2015) single-center study of 17 women with Ebstein anomaly who underwent either elective cesarean section (8 women, 9 pregnancies) or vaginal delivery (9 women, 14 pregnancies), pregnancy was relatively safe. However, some women underwent elective cesarean delivery due to the development of cyanosis, arrhythmia, or significant heart failure. 

CLINICAL PRESENTATION


History

For the purpose of clinical presentation of Ebstein anomaly, the patients are separated into the age groups, as used in a study by Celermajer et al. [10]

Fetus

An abnormal fetal scan is present in about 86% of fetuses, and an arrhythmia is present in about 5%. [11]

Neonate (aged 0-1 mo)

About 74% of neonates have cyanosis, 10% have heart failure with poor feeding and failure to thrive, and 9% have an incidental heart murmur.

Infant (aged 2 mo to 2 y)

About 35% of infants have cyanosis, 43% have heart failure with poor feeding and failure to thrive, and 13% have an incidental heart murmur.

Child (aged 3-10 y)

About 14% of children have cyanosis, 8% have heart failure with poor growth and decreased exercise tolerance, 12% have an arrhythmia with complaints of palpitations, and 66% have an incidental heart murmur.

Adolescent (aged 11-18 y)

About 13% of adolescents have cyanosis, 13% have heart failure with dyspnea on exertion and decreased exercise tolerance, 40% have an arrhythmia with complaints of palpitations, and 33% have an incidental heart murmur.

Adult (aged >18 y)

About 4% of adults have cyanosis, 26% have heart failure with dyspnea on exertion and decreased exercise tolerance, 43% have an arrhythmia with complaints of palpitations, 13% have an incidental heart murmur, 20% have chest pain, and 6% have syncope.

Physical Examination

The physical examination findings in patients with Ebstein anomaly vary based on the age of the patient and the degree of tricuspid valve regurgitation and right ventricular outflow tract obstruction. Note the following:

  • 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 or fourth heart sound.

  • Tricuspid regurgitation causes a holosystolic or regurgitant systolic murmur at the left lower sternal border in the newborn and during infancy. The murmur is a shorter, systolic murmur in older children and adults due to low velocity flow from the hypokinetic, low pressure in the right ventricle.

  • A diastolic murmur may be heard secondary to increased flow through a normal-sized or stenotic tricuspid valve orifice. A systolic ejection murmur associated with right ventricular outflow tract obstruction may also 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.

  • Elevated jugular venous distention with prominent "V" wave may be present in older patients. Clubbing may be seen in a few patients who have had persistent cyanosis.

DDx

Differential Diagnoses

Workup

Imaging Studies

Chest radiography

Typical findings in severe cases of Ebstein anomaly consist of cardiomegaly and pulmonary oligemia. Right atrial enlargement accounts for most of the large size of the cardiac silhouette. Pulmonary vascular markings may be normal in some patients with minimal or no cyanosis. (See the following image.)

Chest radiograph of a newborn with severe Ebstein Chest radiograph of a newborn with severe Ebstein anomaly and patent ductus arteriosus. Most of the cardiomegaly is secondary to right atrial enlargement. The pulmonary vascular markings are normal in this newborn.

Echocardiography

Echocardiography is diagnostic in Ebstein anomaly. Typical findings include variable degrees of downward displacement of the septal and/or posterior leaflet of the tricuspid valve (see the image below), tricuspid valve regurgitation, and right atrial enlargement usually proportional to the degree of displacement of the septal leaflet. The large, sail-like anterior leaflet of the tricuspid valve is also usually noted.

In addition, echocardiography should define the following: (i) the chordal attachments of the tricuspid valve, (ii) an atrial septal defect (ASD) or patent foramen ovale (PFO), (iii) the status of the right ventricular (RV) outflow tract and the pulmonary valve size and orifice, (iv) a patent ductus arteriosus, (v) estimation of the RV systolic pressure, and (vi) ventricular systolic function. The presence of other associated cardiac defects should be ruled out. Fetal echocardiography identifies Ebstein anomaly well and is useful in determining prognosis. (See the Prognosis Assessment by Imaging section).

Echocardiogram in an apical four-chamber view. ThiEchocardiogram in an apical four-chamber view. This image reveals downward displacement of the insertion of the septal leaflet of the tricuspid valve (arrow) in a 3-year-old boy. The child has moderate tricuspid regurgitation and has not required surgical intervention so far. aRV = atrialized portion of right ventricle, LA = left atrium, LV = left ventricle, RA = right atrium, RV = functional portion of the right ventricle.

A case of prenatally diagnosed Ebstein anomaly of the mitral valve has been described. [12 Fetal echocardiography revealed tethering of the mitral valve posterior leaflet to the lateral wall of the left ventricle (LV) with downward displacement into the LV cavity. The diagnosis was confirmed with postnatal transthoracic and transesophageal echocardiography, which showed apical displacement of the level of coaptation mitral valve into the LV cavity. [12]

Prognosis Assessment by Imaging

Celermajer index:

An echcardiography-based scoring system is useful to assess the severity and outcome of Ebstein anomaly and, therefore, aid in counseling families. In this system, the ratio of the combined area of the right atrium and the atrialized portion of the right ventricle (RV) to the combined area of  the functional portion of of the RV, left atrium (LA), and left ventricle (LV) is calculated from an apical four-chamber view of an echocardiogram. Four grades are derived, as follows [13:

  • Grade 1 (ratio < 0.5): 0% mortality
  • Grade 2 (ratio 0.5-1.0): Mortality of 10%
  • Grade 3 (ratio 1.0-1.49): Mortality of 44%
  • Grade 4 (ratio >1.5): Mortality of 100%.

This system has been used in fetal and postnatal echocardiography. [13]

Simpson-Andrews-Sharland (SAS) score for fetal echocardiography

The SAS score is calculated from a fetal echocardiogram. A value of 0, 1 or 2 is assigned for five parameters from the fetal echocardiogram, comprising the following [14:

  • Cardiothoracic ratio
  • Celemajer index
  • RV-to-LV ratio
  • Reduced/absent pulmonary blood flow
  • Retrograde ductus arteriosus flow

Other Tests

Electrocardiography (ECG)

Typical findings on the ECG are right atrial enlargement (tall, peaked P waves), a prolonged PR interval, right axis deviation, and a right bundle branch block. In the presence of Wolff-Parkinson-White syndrome (30%), a short PR interval and Delta wave are noted. Atrial arrhythmias may be seen, if present.

Holter monitoring

An 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 testing

Exercise testing may be performed both preoperatively and postoperatively to objectively evaluate exercise tolerance, oxygen consumption, systemic arterial oxygenation, and possible arrhythmia vulnerability during exercise. [15]

Procedures

Cardiac catheterization

Cardiac catheterization is not routinely needed for presurgical evaluation. Pressure traces in the right atrium and right ventricle (RV) are useful however. RV angiography either in the posteroanterior or right anterior oblique view will demonstrate downward displacement of the tricuspid leaflet(s), RV outflow tract, and pulmonary valve and arteries. Rarely, balloon atrial septostomy of a restrictive atrial septal defect or patent foramen ovale may be needed to stabilize the hemodynamic status of a newborn or infant. However, septostomy may lead to worsening cyanosis from an increased right-to-left shunting, and thus it needs to be weighed in such decision making. 

Electrophysiologic studies (EPS)

EPS are performed in many patients suspected of having an arrhythmia secondary to paroxysmal supraventricular tachycardia (SVT) and Wolff-Parkinson-White (WPW) syndrome, both of which occur at a high incidence. During invasive EPS, an accessory pathway is most often identified along the abnormal tricuspid annulus. Manifest accessory pathways (WPW) and concealed pathways (unidirectional retrograde conducting accessory pathways) account for most supraventricular tachycardias (SVTs) mechanistically in patients with Ebstein anomaly. The frequency of multiple accessory pathways is significantly higher in those with Ebstein anomaly than in the general population of patients with SVT and normal tricuspid valve anatomy.

TREATMENT AND MANAGEMENT


Medical Care

Asymptomatic patients with Ebstein anomaly who have mild tricuspid regurgitation need only outpatient clinic evaluation, which may include periodic electrocardiographic (ECG) evaluation, chest radiography, and oxygen saturation measurement. All patients with this diagnosis require lifetime prophylaxis for bacterial endocarditis.

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, these newborns also require prostaglandin E1 therapy.

In addition, it is crucial that neonates with a severe form of this disease have an adequate atrial communication. If the patient is born with only a patent foramen ovale (PFO) or a restrictive atrial septal defect (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.

Electrophysiologic 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 supraventricular tachycardia (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% to 90%, and the recurrence rate is reported to be as high as 32%. [16As expected, success rates, complications, and recurrence rates vary with complex pediatric radiofrequency catheter ablation procedures, depending on operator and institutional experience. Radiofrequency ablation appears to be most successful in patients with a mild degree of tricuspid regurgitation.

Outpatient monitoring

Patients who are asymptomatic initially may develop increasing cyanosis or congestive heart failure. They require continued outpatient monitoring.

Adult patients are best served by having their follow-up at a center with adult congenital heart disease specialists and technologists. [17]

Surgical Care

The surgical care of patients with Ebstein anomaly depends on the severity of the leaflet displacement and on the degree of the associated right ventricular (RV) outflow tract obstruction.

In neonates with the most severe form of Ebstein anomaly, the functional RV is hypoplastic, and the patient is usually best treated 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. This surgical repair is akin to single-ventricle physiology.

In infants with mild-to-moderate tricuspid regurgitation and severe RV outflow tract obstruction, a systemic artery–to–pulmonary artery shunt is performed in addition to creation of an unrestrictive atrial communication. In patients with moderate-to-severe tricuspid regurgitation, the abnormal valve can be replaced with a mechanical or prosthetic valve, surgical reconstruction, or a combination of the two. [181920 This type of surgical approach will result in two-ventricle physiology.

In some infants and children, a one and a half ventricle repair strategy may be used, in which a bidirectional Glenn operation is performed in addition to closing the atrial septal defect/patent foramen ovale (ASD/PFO) and repair of the tricuspid valve. Bidirectional Glenn operation decreases the volume load, allowing the hypoplastic RV handle venous return from inferior vena cava only. This strategy is suitable for certain select patients. [21]

Brown et al described their results from 539 patients (mean age, 24 y) who had 604 cardiac operations. [22 The first repair in 182 patients consisted of tricuspid valve repair, and 337 patients underwent tricuspid valve replacement. Late survival was 84.7% at 10 years and 71.2% at 20 years. Preoperative characteristics associated with mortality included increased hematocrit levels, an associated mitral valve repair, prior cardiac operation, and moderate-to-severe reduction in RV systolic function. [22]

Another study evaluated the outcomes of 32 patients who underwent surgery for Ebstein anomaly. [23After 16-years' follow-up, the results for early and late survival rates for patients without pulmonary atresia were 60% ± 12% versus 85% ± 10 (P = .06), respectively, and those for early and late survival rates in patients with pulmonary atresia were 60% ± 12% (9/15) versus 94.1% (16/17) (P< .05), respectively. The investigators concluded that biventricular and tricuspid valve repair of Ebstein anomaly is feasible in neonates and young infants with good results, especially those without pulmonary atresia. [23]

Diet and Activity

Diet

Special dietary restrictions are not usually required. An infant with severe tricuspid regurgitation may require a high caloric density formula.

Activity

The activity restrictions of patients with Ebstein anomaly depend on the severity of the leaflet displacement. If the displacement is mild and patients do not have an associated paroxysmal supraventricular tachycardia, they should be allowed to determine their own level of activity. For patients with cyanosis, sports participation is usually somewhat restricted. An exercise stress test and other noninvasive assessments might be helpful in making this determination

MEDICATION


Medication Summary

In patients with Ebstein anomaly 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 warfarin (Coumadin) or aspirin. Patients who have paroxysmal supraventricular tachycardia 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 somewhat depends the 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 the Medscape Drugs and Diseases topic Antibiotic Prophylactic Regimens for Endocarditis.

Inotropic agents

Class Summary

These agents increase cardiac output.

Digoxin (Lanoxin)

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.

Diuretics

Class Summary

These agents decrease pulmonary or systemic edema.

Furosemide (Lasix)

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.

Prostaglandins

Class Summary

Neonates with severe Ebstein anomaly and insufficient or ductal dependent pulmonary blood flow require prostaglandin E1 therapy.

Alprostadil (Prostaglandin E1, Prostin VR Pediatric injection)

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.

0 comments:

Post a Comment