A 32-year-old woman presented for evaluation of decreasing exercise tolerance and a loud heart murmur. On physical examination, she had a fixed split second heart sound with a normal pulmonary component. She had a holosystolic murmur at the mid-left sternal border that did not radiate and increased with inspiration. An electrocardiogram (ECG) and echocardiogram were performed. ECG demonstrated right atrial enlargement and a right bundle branch block. Echocardiogram showed apical displacement of the septal and posterior leaflets of her tricuspid valve resulting in severe tricuspid regurgitation. Her clinical findings were consistent with Ebstein’s anomaly. Further testing included a functional vo₂ exercise stress test. With exercise, she was found to have significant oxygen desaturation to the mid-80s on room air. A subsequent transesophageal echocardiogram showed a patent foramen ovale (PFO) with bidirectional shunting, severe tricuspid regurgitation, and an apically displaced septal leaflet of the tricuspid valve consistent with Ebstein’s anomaly. Because of her significant hypoxia with exercise, she underwent a catheter-based closure of her PFO. A repeat exercise study following PFO closure showed normal oxygen saturations with exercise and improved exercise capacity. She was followed with serial imaging that continued to demonstrate the severe tricuspid regurgitation and gradual worsening in her functional capacity. She developed atrial flutter with rapid ventricular rate for which she needed to be cardioverted. She was managed with antiarrhythmic medications and has had no further arrhythmia recurrences. She finally underwent surgical management in the form of a tricuspid valve replacement with a bioprosthetic valve and plication of the atrialized ventricle. The patient had an uneventful postoperative recovery with significant improvement in her functional capacity.

CASE EXPLANATION

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  This case highlights several important concepts for the long-term complications and management of adult patients with Ebstein’s anomaly of the tricuspid valve.

  
  
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  These include the concerns for atrial arrhythmias, atrial level shunting secondary to an interatrial communication, severity of tricuspid regurgitation, and declining functional capacity.

  
  
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  Ebstein’s anomaly is a rare congenital heart disorder (1/200,000 live births), accounting for about 0.3% to 0.7% of all cases of congenital heart disease (CHD), however this case highlights that Ebstein’s anomaly can present later in life since patients can have a wide spectrum of symptoms that may prevent the underlying pathology from being discovered until adulthood.

  
  
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  Such patients require regular long-term cardiac follow-up with an adult congenital cardiologist to prevent long-term cardiac complications.

EPIDEMIOLOGY

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  Ebstein’s anomaly is a rare congenital heart disease that consists of apical displacement of the septal leaflet of the tricuspid valve and atrialization of the right ventricle. The estimated risk of Ebstein’s anomaly in the general population is 1 in 200,000 live births, with males and females being at equal risk.¹

  
  
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  Lithium use during pregnancy has been considered a risk factor for developing Ebstein in the fetus, although the classic case series of “Lithium babies” reported by Weinstein and Goldfield in 1975 showed an extremely high incidence of congenital heart disease in general, not limited to just Ebstein’s anomaly.²

  
  
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  The severity of the disease encompasses a wide spectrum of symptoms such that it may not be discovered until adulthood. The prognosis is extremely variable and can range from severe hydrops fetalis and fetal demise to simply an isolated murmur in an otherwise asymptomatic patient.

  
  
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  Severe and often fatal cases occur in newborns with severe cardiomegaly and heart failure. These cases are often diagnosed prenatally on fetal echocardiography. Patients diagnosed in the neonatal period tend to have more severe disease and present with cyanosis whereas older children tend to present with a heart murmur. Adults present most frequently with atrial arrhythmias.³

  
  
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  If unrepaired, about 25% of affected children die in the first 10 years of life, and over 70% will die before age 30.

ETIOLOGY AND PATHOPHYSIOLOGY

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  The primary abnormality in Ebstein’s anomaly occurs during embryonic development of the cardiovascular system; there is a failure of delamination of the posterior and septal leaflets of the tricuspid valve from the myocardium of the right ventricle resulting in the displacement of the attachment of the septal leaflet of the tricuspid valve into the body of the right ventricle, causing a large portion of the right ventricle to become “atrialized.”

  
  
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  The portion of the right ventricle that is “atrialized” does not contribute to right ventricular function and cardiac output. In severe cases, the nonatrialized part of the right ventricle is small and may consist of only the right ventricular outflow tract.

  
  
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  In addition to the apical displacement of the tricuspid valve, the tricuspid valve leaflets themselves tend to be abnormal. The morphology of the tricuspid valve in Ebstein’s anomaly is variable which may affect the severity of the clinical presentation. Typically, the tricuspid valve leaflets are partly attached to the fibrous tricuspid valve annulus as well as to the endocardium of the right ventricle. The anterior leaflet is the largest leaflet and is usually attached to the tricuspid valve annulus (Figure 8-1). Because of the large size of the anterior leaflet, it is often described as looking like a “sail” on echocardiography. The posterior and septal leaflets are often hypoplastic or even completely absent. These abnormalities result in varying degrees of tricuspid regurgitation.

  
  
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  Forward flow through the right heart is reduced, with right-to-left shunting across the atrial septum and/or reduced systemic cardiac output. The tricuspid regurgitation reduces the forward stroke volume of the hypoplastic right ventricle. The atrialized portion of the right ventricle balloons out during atrial systole, acting as a passive reservoir rather than participating in coordinated atrial contraction, thus hindering coordinated atriosystolic filling of the right ventricle.

  
  
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  Depending on the degree of valve displacement, the right ventricle can become dilated and/or dysfunctional. With severe right ventricular enlargement, the ventricular septum shifts leftward adversely affecting left ventricular (LV) filling and adversely affecting systemic cardiac output.

  
  
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  Results of the anatomic derangement stemming from Ebstein’s anomaly can include right ventricular dysfunction, right atrial dilation, atrial arrhythmias, and, in cases with an atrial communication, cyanosis due to right-to-left intracardiac shunting.

ANATOMIC CLASSIFICATION OF SEVERITY

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  Given the varying severity of disease and clinical presentation, several different classification systems have been proposed. One system stratifies severity into mild, moderate, or severe disease based on the degree of apical displacement of the tricuspid valve leaflets as well as the severity of tricuspid valve regurgitation and resultant dilation and dysfunction of the right-sided cardiac chambers.

  
  
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  A more detailed classification includes anatomy of the tricuspid valve leaflets along with the Carpentier classification (A, B, C, D). This classification is based on anatomic findings found at the time of surgery with the following 4 grades of severity:⁴

  
  
  
  
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    Type I—The anterior tricuspid leaflet is large and mobile but the posterior and septal leaflets are apically displaced, dysplastic, or absent. The size of the atrialized portion of the right ventricle ranges from relatively small to large.

    
    
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    Type II—The anterior, posterior, and often septal leaflets are present, but are relatively small and displaced. A large portion of the ventricular chamber is atrialized.

    
    
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    Type III—The anterior leaflet has restricted motion with a shortened, fused, and tethered chordae. Papillary muscles might insert directly into the anterior leaflet. The posterior and septal leaflets are not generally repairable due to severe displacement or dysplasia. A large portion of the right ventricle is atrialized.

    
    
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    Type IV—All 3 tricuspid valve leaflets are severely deformed. Chordae are often absent and there may be direct insertions of papillary muscles into the leading edge of the valve. The posterior leaflet is typically dysplastic or absent. There is no true septal leaflet but rather a ridge of fibrous material descending apically from the membranous septum. Severe tricuspid valve tissue displacement may actually cause tricuspid stenosis. Nearly the entire right ventricle is atrialized. These patients typically present very early on in the neonatal period.

ASSOCIATED ANATOMIC LESIONS

Associated congenital heart lesions are common in Ebstein’s anomaly. The most commonly seen lesions are the following:

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  Patent foramen ovale (PFO) or atrial septal defects (ASD) occur in about 80% of patients with Ebstein’s anomaly. An interatrial communication from a PFO or an ASD can allow right-to-left shunting, particularly during exercise, which can result in cyanosis as well as paradoxical embolism.

  
  
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  Ventricular septal defect (VSD).

  
  
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  Right ventricular outflow tract obstruction, which can be due to complete absence of the pulmonary valve (pulmonary atresia), structural pulmonary valve stenosis, or “functional” pulmonary atresia.

  
  
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  Patent ductus arteriosus.

  
  
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  Coarctation of the aorta.

  
  
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  Accessory electrical pathways (Wolff-Parkinson-White [WPW] syndrome). These are seen in up to 20% of patients with Ebstein’s anomaly and are most often right-sided pathways.

DIAGNOSIS

Clinical Features

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  Clinical features of Ebstein’s anomaly are dependent on the severity of the disease, including the degree of tricuspid regurgitation, right ventricular size and function, presence or absence of intracardiac shunting, and accessory pathways.

  
  
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  Patients may be asymptomatic with just a murmur heard on examination or they may have more severe symptoms including cyanosis, arrhythmias, or heart failure, depending on the underlying anatomy. Neonates with severe tricuspid regurgitation and hypoplastic right ventricles tend to present with cyanosis and heart failure early on, whereas patients with less severe disease may not present until adulthood.

  
  
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  The most common presenting symptom in older adults is atrial arrhythmias which occur in 20% to 30% of patients.^{3, 5} Because of a strong association between Ebstein’s anomaly and right-sided accessory pathways (Wolff-Parkinson-White syndrome), it is important to obtain a screening echocardiogram in patients who present with WPW to evaluate for the presence of underlying congenital heart disease.

  
  
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  Female patients with Ebstein’s anomaly may not present with symptoms until pregnancy, primarily during the second trimester, when there is significant increase in plasma blood volume.

Physical Examination

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  Physical examination findings vary based on severity of disease. Mild cases may be clinically silent or present with an asymptomatic murmur and click, which may be mistaken for mitral valve prolapse.³ In more severe forms, patients may have prominent “V-waves” depending on the severity of the tricuspid regurgitation. They may be cyanotic if there is significant tricuspid regurgitation and intracardiac right to left shunting at the atrial level. Many patients will also have a prominent right ventricular impulse which is not displaced.

  
  
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  Heart sounds are frequently abnormal in patients with Ebstein’s anomaly of the tricuspid valve. Splitting of the first heart sound is due to apical displacement of the tricuspid valve and the tricuspid and mitral valves closing out of sync with each other. Splitting of the second heart sound occurs in patients with a right bundle branch block which is commonly seen in patients with severe right-sided chamber enlargement. There may also be prominent third and/or fourth heart sounds giving the impression of multiple heart sounds (triple or quadruple gallop). There is often a holosystolic murmur of tricuspid regurgitation which should increase in intensity with inspiration.

  
  
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  In cases of severe tricuspid regurgitation, a mid-diastolic rumble may be heard due to increased diastolic flow across the tricuspid annulus. In many cases of severe tricuspid regurgitation, the murmur may be soft or even absent due to lack of turbulence across the valve because of rapid equalization of pressures. In patients with severe tricuspid regurgitation, the liver can be enlarged and even pulsatile on palpation. Patients can rarely present with ascites and lower extremity edema.

Electrocardiogram

The electrocardiogram is usually abnormal in Ebstein’s anomaly. Typical findings include the following:

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  Right atrial hypertrophy with tall, broad (“Himalayan”) P-waves (Figure 8-2).

  
  
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  Right bundle branch block.

  
  
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  First-degree atrioventricular (AV) block.

  
  
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  Pre-excitation (Wolff-Parkinson-White pattern) is seen in about 20% of patients with Ebstein’s anomaly. The accessory pathway generally is right-sided including a predominant S-wave in the right precordium.^{6, 7}

  
  
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  Arrhythmias are common, including supraventricular tachycardia, atrial tachycardia, atrial flutter, and atrial fibrillation (Figure 8-3).