Definition and Morphology
Ebstein anomaly (EA) is a rare malformation of the tricuspid valve (TV) and right ventricle (RV). The anatomic and pathophysiologic characteristics are variable and lead to a wide spectrum of clinical scenarios. The clinical presentation in adults differs from that of children, particularly neonates and infants. Adult patients may present with an established diagnosis under medical management following surgical repair, or may have their initial presentation with diagnosis in adulthood.
Anatomic Features
Classic anatomic characteristics include (1) failure of delamination of the TV leaflets from the underlying RV myocardium; (2) apical (downward) displacement of the functional tricuspid annular hinge points (septal > posterior > anterior); (3) dilation of the “atrialized” portion of the RV with variable degrees of hypertrophy and thinning of the wall; (4) anterior leaflet fenestrations, redundancy, and tethering; and (5) right atrioventricular (AV) junction (true tricuspid annulus) dilation. TV regurgitation is common and stenosis is rare.
Anatomic variation within characteristic anatomic features is common. More severe forms of EA result in a posterior and downward displacement of the hinge point of the posterior and septal leaflets in a spiral fashion below the true annulus. The anterior tricuspid leaflet is commonly large and classically sail-like and often displaced into the RV outflow tract, whereas the functional posterior and septal leaflets are usually small, dysplastic, and are either tethered by short chordae and papillary muscles or are attached to the underlying myocardium by muscular bands. Chordae may be few to absent, and leaflet fenestrations are common. The atrialized portion of the RV is characteristically thinned and dilated without ventricular trabeculation. Dilation persists throughout the entire right ventricular free wall, including the infundibulum. Patent foramen ovale (PFO) and/or atrial septal defects (ASDs) are common (75% to 95%) with mostly right-to-left shunting secondary to elevated right atrial pressure and tricuspid regurgitation producing rest- or exercise-induced cyanosis and/or paradoxic embolus. Other associated cardiac defects may include mitral valve prolapse, left ventricular noncompaction, pulmonary artery hypoplasia, and pulmonary stenosis. An Ebstein variant is also commonly seen in association with congenitally corrected transposition of the great arteries. In addition, 10% to 45% of patients have accessory mediated pathways, often multiple, and approximately 10% have AV nodal reentrant tachycardia.
Genetics and Epidemiology
The incidence of EA is approximately 1 per 200,000 live births and accounts for less than 1% of all cases of congenital heart disease with no gender difference. The genetic causes of EA have not been thoroughly established. Mutation of transcription factor NKX2.5, 10p13-p14 deletion, 1p34.3-p36.11 deletion, and MYH7 mutations have been described.
Although initial studies suggested a 400 times relative risk for EA in maternal lithium use, subsequent studies reported a relative risk of 1.2 to 7.7 for any congenital heart disease in association with maternal lithium use.
Early Presentation
Patient presentation in EA is quite varied; the diagnosis may be established in utero, infancy, childhood, or well into adulthood. Age of presentation and symptomatology depend on the anatomic and functional severity of EA, the presence of associated anomalies such as pulmonary stenosis and septal defects, and arrhythmia burden. Improved fetal screening and newborn oxygen screening have improved rates of early diagnosis.
Arrhythmia, including atrial fibrillation, flutter, or ectopic atrial tachycardia, is the most common presenting symptom in adults, occurring in approximately 40% of patients. Exercise intolerance, exertional dyspnea or fatigue, and right heart failure (although less so) are also common. Cyanosis and paradoxic embolization is possible in patients with right-to-left flow across an ASD or PFO, placing these patients at risk for cerebrovascular accidents and systemic abscesses. Some asymptomatic adults with EA present with incidental cardiomegaly on chest X-ray (CXR).
Outpatient Assessment
Cardiac examination often reveals a soft parasternal heave without a thrill. Jugular venous distension is not common because of the high degree of compliance of the right atrium (RA). Cardiac auscultation may demonstrate a systolic murmur of tricuspid regurgitation; the intensity of the murmur is dependent on the RV function and tricuspid regurgitation severity. The regurgitant murmur may be inaudible with advanced RV dysfunction or free tricuspid regurgitation because of a lack of tricuspid leaflet coaptation. Rarely, a low-intensity presystolic murmur may be heard as a result of anatomic or functional tricuspid stenosis. Wide splitting of both the first and second heart sounds is typical and atrial and ventricular filling sounds are relatively common. Summation of these gallop sounds may result from prolongation of AV conduction. Lower extremity edema is common with advanced heart failure. Digital clubbing is possible in patients with cyanosis.
Initial outpatient evaluation is comprised of EKG, CXR, 24-hour Holter monitor, and echocardiography to thoroughly evaluate the anatomic and functional severity of EA and the presence of arrhythmias. Cardiac magnetic resonance imaging (MRI) plays a complementary role in assessment of RV size and function.
Imaging
Two-dimensional (2D) echocardiogram is the primary imaging modality used in EA ( Fig. 43.1A ).
Echocardiograms allow for detailed characterization of the TV leaflets and subvalvular apparatus; the size of functional components of the RV, the RA, and the presence of intracardiac shunts; mitral regurgitation; and left ventricular function. Apical displacement of the septal leaflet and/or posterior leaflet of the TV by ≥8 mm/m 2 body surface area is a diagnostic feature that distinguishes EA from other congenital abnormalities of the TV. Color flow and spectral Doppler imaging allows for assessment of TV regurgitation.
Echocardiographic features favorable for TV repair include a large, mobile anterior leaflet with a free leading edge. Any delamination of inferior leaflet tissue is helpful, and the more septal leaflet tissue that is present, the more likely a successful repair can be obtained. Features indicating a more difficult repair include significant leaflet tethering with adherence of the edge or body of the leaflet to the underlying endocardium and the presence of tricuspid leaflet tissue in the right ventricular outflow tract.
Significant right ventricular enlargement and dysfunction results in paradoxic motion of the intraventricular septum and rarely left ventricular outflow obstruction. Left ventricular systolic dysfunction may develop as a result of interventricular interaction.
Three-dimensional (3D) echocardiography offers information in addition to standard 2D images, including improved visualization of the TV leaflets. Three-dimensional echocardiograms also provide a more comprehensive assessment of right ventricular volumes and the ability to differentiate atrialized and functional portions of the RV.
Cardiac MRI, often performed with gadolinium, improves characterization of the right ventricular volume and function. Cardiac computed tomography (CT) may be used to assess the RV or for evaluation of coronary arteries preoperatively, but at the cost of additional radiation exposure.
The chest radiograph in mild forms of EA may be normal, whereas patients with the more severe form exhibit “globular” cardiomegaly, which is a classic indicator for the disease (see Fig. 43.1B ). This appearance is produced by enlargement of the RA and displacement of the right ventricular outflow tract outward and upward.
Electrophysiology
Electrocardiograms are often abnormal in EA as a result of inherent arrhythmias or conduction delays secondary to large right heart chambers ; see Box 43.1 .
| Rhythm | Normal sinus rhythm, ectopic atrial rhythm, supraventricular tachycardia, atrial fibrillation, intraatrial reentrant tachycardia |
| PR Interval | First-degree AV block is common. PR interval is short in Wolff-Parkinson-White Syndrome |
| QRS axis | Normal or left-axis deviation |
| QRS configuration | Low-amplitude multiphasic atypical right bundle branch block |
| Atrial enlargement | Right atrial enlargement sometimes with Himalayan p-waves |
| Ventricular hypertrophy | Diminutive RV |
| Other | Accessory pathway common |
AV , Atrioventricular; RV, right ventricle.
Approximately 25% to 65% of patients have an atrial tachycardia (atrial fibrillation, atrial flutter, or ectopic atrial tachycardia), and 10% to 45% of patients have accessory pathways such as Wolff-Parkinson-White (WPW) syndrome, and approximately 10% have AV nodal reentrant tachycardia. More than one accessory pathway is common (6% to 36%), which can increase the risk of sudden cardiac death. Ventricular arrhythmias are also described and are a likely cause of late sudden death in adults. Electrophysiologic evaluation, including the exclusion of accessory pathways, is an important part of preoperative EA evaluation.
Exercise Testing
Exercise testing is recommended for accurate evaluation of functional status, particularly in asymptomatic patients. Many patients unknowingly adapt to their disease, limit their activity level or pace, and may deny limiting symptoms. Decreased exercise tolerance correlates with decreased forward stroke volume and decreased ability to augment heart rate with exercise. Exercise tolerance has been shown to rebound following surgical intervention.
Additional Evaluations
Diagnostic cardiac catheterization is rarely performed, but coronary angiography should be considered preoperatively in patients with suggestive symptoms or at increased risk for coronary artery disease.
Early Management
Medical management is generally recommended for asymptomatic patients and may be successful for many years. Follow-up should focus on early detection of new arrhythmias and deterioration of heart function. Exercise tolerance testing is generally advocated to determine true physical limitations in an otherwise asymptomatic patient with borderline heart function. Oxygenation monitoring should be performed during exercise testing because it may reveal exercise-dependent cyanosis.
Clinicians must maintain a high degree of suspicion for rhythm disturbances and evidence of worsening heart function or functional status. Arrhythmia and right heart dysfunction are associated with poor outcomes, so appropriate referrals for electrophysiologic studies (EPS) and surgery should not be delayed.
Late Outcome
Natural History
Late presentation of EA is not uncommon, and unoperated patients have decreased expected survival resulting from biventricular failure. Sudden cardiac death is well described and thought to be secondary to ventricular arrhythmias. The largest natural history study estimated the cumulative overall survival in unoperated adult patients with EA, with time zero at 25 years of age, as 89%, 81%, 76%, 53%, and 41% at 1, 5, 10, 15, and 20 years of follow-up, respectively. Univariate predictors of cardiac-related death included cardiothoracic ratio greater than or equal to 0.65, increasing severity of TV displacement on echocardiography, New York Heart Association class III or IV, cyanosis, severe tricuspid regurgitation, and younger age at diagnosis. Multivariate predictors of cardiac-related death included younger age at diagnosis, male gender, cardiothoracic ratio greater than or equal to 0.65, and the severity of TV leaflet displacement on echocardiography. Patients have been observed (unoperated) into their eighth decade; however this is not common.
Late Management
Most patients will require catheter-based arrhythmia procedures and cardiac surgery in their lifetimes; reoperation is not uncommon.
Electrophysiology
Catheter-based EPS and appropriate ablations are performed for all patients with EA with evidence of pre-excitation by electrocardiogram or who have a history of recurrent supraventricular tachycardia, undefined wide-complex tachycardia, or syncope. EPS is recommended in all adult patients prior to operative intervention for identification and treatment of atrial arrhythmias. If percutaneous ablation is not possible, mapping can be performed to aid intraoperative therapies.
Operative Intervention
Patients should be referred for surgical evaluation with onset of symptoms, decreased exercise capacity, cyanosis, paradoxic embolism, progressive RV enlargement or dysfunction, or when there are arrhythmias not amenable to catheter-based procedures. Indications for surgical referral are outlined in Box 43.2 .
Operation may be required in patients with EA who are symptomatic or in patients who have evidence of deteriorating functional status:
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Symptoms (fatigue most common) or deteriorating exercise capacity
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Cyanosis (oxygen saturation <90%)
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Paradoxic embolism
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Progressive cardiomegaly on chest radiograph
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Progressive RV dilation or reduction in RV systolic function
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Progression of atrial and/or ventricular arrhythmias not amenable to percutaneous intervention
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Ventricular pre-excitation not successfully treated in EPS
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Need for TV re-repair or replacement
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Symptoms, deteriorating exercise capacity, or NYHA Class III or IV
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Severe tricuspid regurgitation after repair with progressive RV dilation, reduction of RV function, or progression of arrhythmias
- •
Bioprosthetic TV dysfunction with significant mixed regurgitation and stenosis
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Bioprosthetic TV stenosis (mean gradient greater than 12-15 mm Hg)
- •
- •
Consider earlier intervention for tricuspid bioprosthetic stenosis with symptoms or decreased exercise tolerance
EA , Ebstein anomaly; EPS , electrophysiological studies; NYHA, New York Heart Association; RV , right ventricle; TV , tricuspid valve.
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