Ebstein Anomaly

Ebstein anomaly is a congenital malformation of the heart that is characterized by apical displacement of the septal and posterior tricuspid valve leaflets, leading to atrialization of the right ventricle with a variable degree of malformation and displacement of the anterior leaflet.

Wilhelm Ebstein first described a patient with cardiac defects typical of Ebstein anomaly in 1866. In 1927, Alfred Arnstein suggested the name Ebstein's anomaly for these defects. In 1937, Yates and Shapiro described the first case of the anomaly with associated radiographic and electrocardiographic data.

The embryological development of tricuspid valve leaflets and chordae involves undermining of the right ventricular free wall. This process continues to the level of the atrioventricular (AV) junction. In Ebstein anomaly, this process of undermining is incomplete and falls short of reaching the level of the AV junction. In addition, the apical portions of the valve tissue, which normally undergo resorption, fail to resorb completely. This results in distortion and displacement of the tricuspid valve leaflets, and a part of the right ventricle becomes atrialized. In one study involving 50 hearts with the anomaly, the entire right ventricle was found to be morphologically abnormal.[1]

Ebstein anomaly is commonly associated with other congenital, structural, or conduction system disease, including intracardiac shunts, valvular lesions, and accessory conduction pathways (eg, Wolff-Parkinson-White [WPW] syndrome).

The hemodynamic consequences of Ebstein anomaly result from displaced and malformed tricuspid leaflets and atrialization of the right ventricle. The leaflet anomaly leads to tricuspid regurgitation. The severity of regurgitation depends on the extent of leaflet displacement, ranging from mild regurgitation with minimally displaced tricuspid leaflets to severe regurgitation with extreme displacement.

The atrialized portion of the right ventricle, although anatomically part of the right atrium, contracts and relaxes with the right ventricle. This discordant contraction leads to stagnation of blood in the right atrium. During ventricular systole, the atrialized part of the right ventricle contracts with the rest of the right ventricle, which causes a backward flow of blood into the right atrium, accentuating the effects of tricuspid regurgitation.

Ebstein anomaly is a congenital disease of often uncertain cause.

Environmental factors implicated in etiology include the following maternal factors[2] :

• Maternal ingestion of lithium in first trimester of pregnancy

• Maternal benzodiazepine use

• Maternal exposure to varnishing substances

• Maternal history of previous fetal loss

The risk of having Ebstein anomaly is higher in white persons than in other races.

Ebstein anomaly probably accounts for 0.5% of cases of congenital heart diseases. Its true prevalence is unknown because mild forms frequently are undiagnosed. With the wide application of echocardiography, more cases are being diagnosed.

Race-, sex-, and age-related demographics

Ebstein anomaly is more common in children of white females. However, no specific sex predominance exists.

Ebstein anomaly can present at various stages of life, as follows:

• Fetal life: Ebstein anomaly is usually diagnosed incidentally by echocardiography.

• Neonatal life and infancy: Ebstein anomaly presents with cyanosis and/or severe heart failure; typically, symptoms present in infancy improve as pulmonary vascular resistance decreases.

• Adult life: Ebstein anomaly presents with fatigue, exertional dyspnea, cyanosis, tricuspid regurgitation and/or right heart failure, and palpitations; arrhythmias are common.

Prognosis depends on the severity of the disease and treatment options available. Pregnancy in women with Ebstein anomaly seems to be well tolerated with adequate supervision.[3, 4]

Poor prognostic signs include the following:

• Male sex

• Earlier age at presentation[5]

• Cardiothoracic ratio of more than 0.65 on chest radiographs

• Septal leaflet attachment ratio (ie, ratio of distance between AV ring and distal attachment of septal leaflet to length of septal leaflet) of more than 0.45

• Increasing ratio of combined area of right atrium and atrialized right ventricle to that of the functional right ventricle—grade 1, which is less than 0.5, to grade 4, which is more than 1.5 (increase in the relative risk of 2.7 for each increment in the grade)

• New York Heart Association (NYHA) class: This has been linked with mortality rate in some studies[6]

Morbidity/mortality

The natural course of the disease varies according to the severity of tricuspid valve displacement. Patients presenting in infancy generally have severe disease and unfavorable prognosis.[7, 8]

The mean age of presentation is in the middle teenage years. According to older observational data, approximately 5% of these patients survive beyond age 50 years. The oldest recorded patient lived to age 85 years.

Complications

Complications of Ebstein anomaly include the following:

• Congestive heart failure

• Sudden cardiac death

• Bacterial endocarditis

• Brain abscess

• Paradoxical embolism

• Transient ischemic attacks

• Stroke

Patients can have a variety of symptoms related to the anatomical abnormalities of Ebstein anomaly and their hemodynamic effects or associated structural and conduction system disease.

Cyanosis is fairly common and frequently due to right-to-left shunt at the atrial level and/or severe heart failure. It is transient in neonatal life, with recurrence in adult life; it may appear for the first time in adult life. The transient appearance/worsening of cyanosis in adult life is due to paroxysmal arrhythmias; once apparent, the cyanosis progressively worsens.

Fatigue and dyspnea are due to poor cardiac output secondary to right ventricular failure and decreased left ventricular ejection fraction.

Palpitations and sudden cardiac death may occur due to paroxysmal supraventricular tachycardia (SVT) or Wolff-Parkinson-White (WPW) syndrome in as many as one third of patients. Fatal ventricular arrhythmias may also occur due to the presence of accessory pathways.

Symptoms of right heart failure include ankle edema and ascites.

Other less common presenting symptoms include the following:

• Brain abscess due to right-to-left shunt

• Bacterial endocarditis

• Paradoxical embolism, stroke, and transient ischemic attacks

Physical findings, like the symptoms, span a spectrum from subtle to dramatic.

Cyanosis and clubbing may occur. Varying degrees of cyanosis occur at various times in life; there is transient worsening with concurrent arrhythmias.

Precordial asymmetry is usually with left parasternal prominence and, occasionally, right parasternal prominence. An absent left parasternal (ie, right ventricular) lift is an important negative sign.

Jugular venous pulse may be normal owing to a large, thin-walled right atrium, which can absorb the volume and pressure transmitted from the right ventricle through an incompetent tricuspid valve. Large a and v waves appear late in the course of the disease, with development of right heart failure.

Arterial pulses are usually normal. Diminished volume occurs late in the course of the disease due to severe right heart failure and decreased left ventricular stroke volume.

The first heart sound is widely split with a loud tricuspid component secondary to delayed closure of the elongated anterior tricuspid leaflet, which has an increased excursion, often producing a "sail" sound. The mitral component may be soft or absent in the presence of prolonged PR interval. The second heart sound usually is normal but may be widely split when the pulmonary component is delayed due to right bundle-branch block (RBBB).

Additional heart sounds and murmurs may be present, as follows:

• Third and fourth heart sounds are commonly present, even in the absence of congestive heart failure (CHF). The summation of the third and fourth heart sounds, especially with a prolonged PR interval, can mimic an early diastolic murmur.

• The holosystolic murmur of tricuspid regurgitation is heard maximally at the lower left parasternal area and sometimes at the apex owing to the displaced location of the tricuspid valve; murmur intensity and duration increase during inspiration.

Chest radiography

Chest radiographs may reveal the following in patients with Ebstein anomaly:

• Normal findings

• Cardiomegaly

• Small aortic root and main pulmonary artery shadow

• Decreased pulmonary vasculature

• Large right atrium

Echocardiography

Echocardiogram is the criterion standard for diagnosis.

M-mode echocardiography

• Paradoxical septal motion

• Dilated right ventricle

• Delayed closure of tricuspid valve leaflets more than 65 milliseconds after mitral valve closure

Two-dimensional echocardiography

• Apical displacement of the septal leaflet of tricuspid leaflet of greater than 8 mm/m2: Most specific sign

• Abnormalities in morphology and septal attachment of the septal and anterior tricuspid leaflets

• Eccentric leaflet coaptation

• Dilated right atrium

• Dilated right ventricle with decreased contractile performance

• Various left heart structural abnormalities (described recently in up to 39% of patients with Ebstein abnormality)

​Doppler studies

• Varying degrees of tricuspid regurgitation

• Excludes associated shunts

Assessment of severity and surgical options by echocardiography

• Functional right ventricular area less than 35% of total right ventricular area or an atrialized to functional right ventricular ratio greater than 0.5 associated with unfavorable prognosis

• Functional right ventricular size

• Degree of septal leaflet displacement

• Amount of leaflet tethering

• Magnitude of leaflet deformity and dysplasia

• Aneurysmal dilatation of right ventricular outflow tract (right ventricular outflow tract-to-aortic root ratio of >2:1 on parasternal short axis view)

• Moderate-to-severe tricuspid regurgitation

Magnetic resonance imaging (MRI)

Cine MRI is currently not used routinely; it may become a useful noninvasive modality in the future. Right/Left heart volume index correlates well with heart failure markers.[9]

Twelve-lead electrocardiographic (ECG) features of patients with Ebstein anomaly include the following:

• Rhythm is usually normal sinus; intermittently, supraventricular tachycardia (SVT), paroxysmal SVT, atrial flutter, atrial fibrillation, or ventricular tachycardia may occur

• Abnormal P waves are consistent with right atrial enlargement

• PR interval is most commonly prolonged; it may be normal or short in patients with Wolff-Parkinson-White (WPW) syndrome

• QRS complex may demonstrate right bundle branch block (BBB); it may also be low voltage in many patients

Cardiac catheterization

Currently, cardiac catheterization is rarely performed for the evaluation of Ebstein anomaly. It can confirm echocardiographic findings: Cardiac catheterization can reveal right ventricular electrical activity on the intracardiac electrocardiogram (ECG) with simultaneous right atrial pressure and waveform when the catheter is withdrawn from the right ventricle, back across the tricuspid valve into the right atrium.

Electrophysiologic studies

Of patients with Ebstein anomaly, 25-30% have accessory pathways, and 5-25% have evidence of preexcitation on the surface ECG. Electrophysiologic (EP) studies in patients with tachyarrhythmias can delineate accessory conduction pathways and guide ablative therapy. Right-sided pathways are more common, and 50% of the patients have multiple pathways. Tricuspid valve surgery can hinder the transcatheter access to the right-sided accessory pathways and slow pathway in the AV node reentry; it may be reasonable to assess and treat the arrhythmias with catheter ablation, if indicated, before the surgery.

Ebstein anomaly presents with a spectrum of congenital abnormalities of the tricuspid valve and the right ventricle. The age of presentation with symptoms is variable, and a wide range of treatment options is available. Treatment of Ebstein anomaly is complex and dictated mainly by the severity of the disease itself and the effect of accompanying congenital structural and electrical abnormalities. Transfer to a cardiothoracic surgery unit if necessary.

Treatment options include medical therapy, radiofrequency ablation, and surgical therapy.

Administer antibiotic prophylaxis for infective endocarditis

Pharmacotherapy for heart failure includes the use of angiotensin-converting enzyme (ACE) inhibitors, diuretics, and digoxin.

Arrhythmia treatment includes antiarrhythmic drugs or radiofrequency ablation of the accessory pathways. Curative therapy of supraventricular tachycardia (SVT) with radiofrequency ablation is currently the treatment of choice; however, the success rate is lower than that in patients without significant structural heart disease. Factors associated with lower likelihood of success include the following:

• Accessory pathways located along the atrialized right ventricle

• Multiple accessory pathways

• Complex geometry of the pathways

• Abnormal morphology of the endocardial action potentials in this region

Consultations

Consult an electrophysiologist and cardiac surgeon for the management of patients with Ebstein anomaly.

Diet and activity

A low-sodium diet is recommended for symptomatic relief from fluid overload. Activity may be allowed as tolerated.

Surgical care includes correction of the underlying tricuspid valve and right ventricular abnormalities, correction of any associated intracardiac defects, palliative procedures in early days of life as a bridge to more definitive surgical treatment later, and surgical treatment of associated arrhythmias. Complete repair of Ebstein anomaly in symptomatic neonates has been shown to be feasible, with good early and late survival and excellent functional status.[10] In patients aged 50 years or older with Ebstein anomaly, surgery is associated with good long-term survival and improved functional status, although long-term survival might be improved by performing surgery earlier.[11]

The trend is to perform surgery earlier rather later in the course of heart failure. Indications for surgery are generally as follows:

• New York Heart Association (NYHA) class I-II heart failure with worsening symptoms or with a cardiothoracic ratio of 0.65 or greater[12]

• NYHA class III-IV heart failure

• History of paradoxical embolism

• Significant cyanosis with arterial O2 saturation of 80% or less and/or polycythemia with hemoglobin of 16 g/dL or more

• Arrhythmias refractory to medical and radiofrequency ablation

Various approaches are available to treat structural abnormalities. Tricuspid valve repair is preferred over valve replacement, and bioprosthetic valves are preferred over mechanical prosthetic valves. The atrialized portion of the right ventricle can be resected surgically, and the markedly dilated, thin-walled right atrium can be resected. Associated septal defects may be closed.

In a study of 27 consecutive cone reconstructions to treat severe tricuspid valve (TV) regurgitation associated with Ebstein anomaly, Ibrahim and colleagues retrospectively compared the clinical characteristics, echocardiography, magnetic resonance imaging, and exercise data between preoperative baseline and follow-up. Patients showed improvements in left ventricle filling and objective exercise capacity. The investigators concluded that in patients with severe regurgitation associated with Ebstein anomaly, cone reconstruction of TV offers effective repair.[13]

Da Silva's cone repair is a technique for the surgical reconstruction of the tricuspid valve and the right ventricle in Ebstein anomaly. In one study, investigators evaluated echocardiographic studies and magnetic resonance imaging (MRI) before and after Da Silva's cone repair for Ebstein anomaly in 20 patients. They found that Da Silva's cone repair created excellent valve function; the size of the right ventricle decreased and the antegrade net stroke volume increased 6 months post-surgery.[14]

Palliative procedures include creation of atrial septal defect, closure of tricuspid valve with plication of the right atrium, and maintenance of pulmonary blood flow through aortopulmonary shunt. Palliative procedures usually are reserved for severely ill infants with otherwise dire prognosis.

Left ventricular dysfunction should not be considered a contraindication to tricuspid valve surgery. In these patients, although early mortality is greater with tricuspid valve surgery, the late results are favorable and left ventricular function seems to improve postoperatively.[3, 15]

Functional status improves after surgery.

Surgical treatments of arrhythmias include the following:

• Ablation of the accessory pathways

• Modified right atrial maze procedure for atrial arrhythmias.

• In the presence of atrial fibrillation, the addition of left atrial Cox Maze III procedure can reduce the risk of recurrent atrial fibrillation

Cardiac transplantation is appropriate in selected patients.

Outpatient follow-up is directed toward the following:

• Assessment of general symptoms (eg, fatigue, lassitude)

• Assessment for development of bacterial endocarditis with careful history and examination for signs of bacterial endocarditis, such as fever, weight loss, anorexia, night sweats, splinter hemorrhages, clubbing, Roth spots, Janeway lesions, Osler nodes, splenomegaly, and hematuria

• Assessment of signs of worsening heart failure, such as weight gain, ankle edema, and rales

• Assessment for arrhythmias by history of symptoms, such as faintness or syncope

• Periodic chest radiographs to assess for worsening cardiomegaly

• Evaluation and adjustment of medications

The European Society of Cardiology (ESC) updated their 2010 guidelines on the management of adult congenital heart disease (ACHD) in 2020.[16, 17] Recommendations on the management of Ebstein anomaly are outlined below.

Surgical repair is recommended in patients with severe tricuspid regurgitation and symptoms or objective deterioration of exercise capacity. Surgical repair should be performed by a congenital cardiac surgeon with expertise in Ebstein surgery.

If tricuspid valve surgery is indicated, atrial septal defect/patent foramen ovale closure is recommended at the time of valve repair if it is expected to be hemodynamically tolerated.

In patients with symptomatic arrhythmias or electrocardiographic (ECG) preexcitation, electrophysiology testing followed by ablation therapy, if feasible, or surgical treatment of the arrhythmias in the case of planned heart surgery is recommended.

The American College of Cardiology/American Heart Association (ACC/AHA) 2018 Guidelines for the Management of Adults with Congenital Heart Disease provides information regarding the diagnosis, workup, and treatment of patients with Ebstein anomaly.[18, 19] Recommendations for the evaluation and management of patients with Ebstein anomaly are summarized below.

Workup

Chest radiography, echocardiography and electrocardiography (ECG) are recommended in the evaluation of Ebstein anomaly in adult patients.

Pulse oximetry, Doppler transesophageal echocardiography (TEE), electrophysiological studies, Holter monitoring, and coronary angiography can be useful in the diagnostic evaluation of Ebstein anomaly

Data obtained from cardiovascular magnetic resonance (CMR) can inform clinical care and surgical planning or decision-making, because CMR data correlate well with intraoperative findings. Two-dimensional and 3D TEE can better define the anatomy and function of the tricuspid valve before surgery.

Management

Anticoagulation, catheter ablation, and surgical intervention have a role in the management of adult patients with Ebstein anomaly.

A patent foramen ovale, otherwise usually considered normal, may have significant impact in Ebstein anomaly. Accessory pathways and arrhythmias are relatively common. Patient surveillance and management varies depending on age, severity of the lesion, and associated abnormalities. Treatments include medical and surgical therapy for patients with manifest symptoms as well as catheter-based structural and electrophysiological interventions when indicated.

Adults with Ebstein anomaly and ventricular preexcitation can have multiple accessory pathways and a high risk of sudden cardiac death; concealed pathways are also common. High prevalence of atrial tachyarrhythmia which, in the presence of ventricular preexcitation increase the risk of lethal ventricular arrhythmias. It may be reasonable to assess for arrhythmia substrates and proceed with catheter ablation if identified, before tricuspid valve surgery.

Early surgery, before heart failure or right ventricular (RV) systolic dysfunction ensues, results in improvement of symptoms and functional ability, and prevents or delays worsening symptoms. Surgical interruption of accessory pathways is largely reserved for patients who have failed attempts at catheter ablation.

Bidirectional cavopulmonary shunt in the adult patient is usually reserved for patients with severe RV dysfunction. Preoperative invasive hemodynamic assessment and feasibility of applying the bidirectional cavopulmonary shunt becomes more important in older patients, especially in those with long standing systemic hypertension with diastolic dysfunction and elevated pulmonary artery pressures.

Ebstein anomaly requires drug treatment for cardiovascular consequences resulting from tricuspid atrialization of the right ventricle, valvular regurgitation, and septal defects. Patients may require antibiotic prophylaxis for bacterial endocarditis. Treatment of SVT is typically by radiofrequency ablation rather than drug therapy. CHF is treated with ACE inhibitors, diuretics, and digoxin.

Class Summary

These agents promote excretion of water and electrolytes by the kidneys. They are used in treatment of hypertension, heart failure, and hepatic, renal, or pulmonary disease when salt and water retention has resulted in edema or ascites.

Furosemide (Lasix)

Increases excretion of water by interfering with chloride-binding cotransport system, which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized. Depending on response, administer at increments of 20-40 mg no sooner than 6-8 h after previous dose until desired diuresis occurs. When treating infants, titrate with 1 mg/kg/dose increments until satisfactory effect achieved.

Class Summary

These agents possess positive inotropic activity, which is mediated by inhibition of sodium-potassium adenosine triphosphatase (Na+/K+ ATPase). Also, cardiac glycosides reduce conductivity in the heart, particularly through the atrioventricular node, and therefore have a negative chronotropic effect. The cardiac glycosides have very similar pharmacological effects but differ considerably in their speed of onset and duration of action. They are used to slow the heart rate in supraventricular arrhythmias, especially atrial fibrillation, and also are administered in chronic heart failure.

Digoxin (Lanoxin, Lanoxicaps)

Cardiac glycoside with direct inotropic effects in addition to indirect effects on 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.

Class Summary

ACE inhibitors are beneficial in all stages of chronic heart failure. Dyspnea and exercise tolerance are improved. Unlike diuretics, studies demonstrate improvement of survival and reduced progression of mild or moderate heart failure to more severe stages. They have benefit in asymptomatic left ventricular dysfunction.

Enalapril (Vasotec)

Competitive inhibitor of ACE. Reduces angiotensin II levels, decreasing aldosterone secretion.