EBSTEINS ANOMALY
Ebstein's Anomaly
Ebstein's anomaly represents a cyanotic (poor circulation of oxygenated blood to the body’s cells, leading to a bluish tinge to the skin and mucous membranes) congenital (present at birth) heart defect in which the tricuspid valve on the right side of the heart is displaced inferiorly toward the right ventricular apex. Typically, the septal and posterior tricuspid leaflets are adhered to the myocardium due to failure of the underlying inner layer to detach during embryologic development.1 Additionally, there is tethering, redundancy, or fenestration of the anterior leaflet, resembling a sail and thus restricting its capacity for leaflet coaptation (where the leaflet tips come together in unison), worsening the degree of tricuspid regurgitation.2 Severe deformity of this leaflet may also cause displacement of valvular tissue into the right ventricular outflow tract (also known as the infundibulum), resulting in obstruction of the right side of the heart and into the pulmonary trunk. These findings result in essentially three chambers or sections within the right side of the heart: a true right atrium, an atrialized right ventricle (in which there is ventricular-type tissue and morphology, but proximal to the tricuspid valve which may have varying degrees of thinning or hypertrophy), and a small right ventricle. The most common leaflet of the tricuspid valve to exhibit significant compromise in this condition is the anterior leaflet.3 These findings can be remembered as the three D's of Ebstein's anomaly: apically displaced tricuspid valve that is dysplastic (abnormally developed) with a dysfunctional right ventricle.4 Right ventricular function may be so impaired that there is essentially a state of "functional" pulmonary atresia (an absence of a developed valve, thus involving a pulmonary valve that, although present, is basically not functional).5 A schematic representation of this condition can be seen at www.mayoclinic.org/ebsteins-anomaly/enlargeimage1189.html.
Causes:
The cause of Ebstein's anomaly involves the embryological malformation of the tricuspid valve leaflets in such a way so that there is incomplete alignment of the leaflets at the level of the atrioventricular (AV) junction.3 There are a variety of heterogenous (derived from two different sources) genetic and non-genetic factors associated with this condition.1 There is an increased incidence within twins or in those with a family history of congenital heart defects. There has been some evidence to suggest that maternal benzodiazepine or lithium carbonate therapy (such as would be used to manage anxiety or bipolar disorders, respectively) can lead to Ebstein’s anomaly in rare cases. Additionally, portions of the valve tissue that occur at the apical aspects (deeper towards the ventricular tip) fail to resorb during cardiac development.
As this condition involves improper development of the tricuspid valve and the right heart, there are a myriad of potential concomitant complications. Eighty percent of individuals with this condition have an intra-atrial communication (atrial septal defect or patent foramen ovale; the latter of which involves failure of the normal conduit from the right atrium to the left atrium while in utero). This results in shunting of deoxygenated blood from the right side of the heart to the left atrium, contributing to systemic hypoxemia and the presence of cyanosis.6 There are many other anomalies that are commonly associated with Ebstein's, including pulmonary valve stenosis (impaired ability of the valve to open adequately), ventricular septal defects (holes between the two ventricles as a result of failure of tissue planes to unite during fetal development), patent ductus arteriosus (failure of the tube that connects the aorta and pulmonary artery that allows for bypassing of blood from the collapsed lungs while in utero), and mitral valve prolapse (condition in which part of one or both of the mitral valve leaflets project into the left atrium during ventricular systole).7 Approximately 25% of individuals have Wolff-Parkinson-White (WPW) syndrome, an electrophysiologic condition in which there is the presence of an extra accessory pathway of conducting tissue that allows for transmission of electrical impulses between the atria and the ventricles in an uncoordinated and uncontrolled manner.8 There is also the potential for left-sided ventricular and valvular problems, noted in as many as 18% of cases evaluated in one study, giving rise to the term "bilateral Ebstein's malformation".9 The most common of these abnormalities of the left side of the heart is ventricular non-compaction, in which there is the presence of systolic and diastolic dysfunction, including impairments in myocardial wall motion.
In 1988, Dr. Carpentier and his associates proposed a classification system to differentiate the various defect morphologies of Ebstein’s anomaly.1 The type A defect involves a right ventricular volume that is deemed to be adequate. Type B defects are manifested by large atrialized segregation of the right ventricle with a freely mobile anterior tricuspid valve leaflet and a decrease in right ventricular volume. The findings associated with a type C defect include severe immobilization of the anterior valve leaflet leading to restricted blood flow through the outflow tract. The final class, type D, is characterized by almost complete atrialization of the ventricle, leaving a small infundibular tract for blood to pass on into the pulmonary circuit, thus creating the aforementioned pseudo-pulmonary atresia. Obviously, the more severe the tricuspid valvular derangement and the less defined the right ventricle, the more problematic the patient’s hemodynamic status and the more difficult the surgical correction or palliation.
Prevalence:
Within India, the prevalence of congenital heart disease is approximately 4 to 17 cases per 1,000 live births, with the incidence of Ebstein's anomaly comprising just over 1% of these cases.10 There is an equal distribution between males and females, though there appears to be an increased incidence among children of white females.3, 11 The mean age at which patients present with symptoms is in the mid-teenaged years, with neonatal or infantile presentation typically occurring with more severe pathologies and subsequent poorer prognoses.
Diagnosis:
There is a wide range of variability in clinical presentation for patients with Ebstein's anomaly based on the severity of the abnormal morphology of the tricuspid valve.6 The practitioner must consider other potential cardiovascular abnormalities that can create similar clinical presentations as Ebstein's anomaly, such as acquired tricuspid regurgitation stemming from endocarditis (infection of the heart valves leading to the formation of vegetations on the leaflets) When right heart valves develop vegetations, the most common cause is unsterile needle punctures that occur with intravenous drug abuse or improper sterile medical technique during needle or intravascular catheter insertion. A good history, physical examination, and cardiac ultrasonography are all very useful in uncovering the true pathology involved.
Typical symptoms expressed by patients may include dyspnea, atypical chest pain, and fatigue.6 The individual may also have anorexia as a result of decreased energy from cardiac failure causing venous congestion in the stomach. The initial appearance during physical examination of the patient with Ebstein's anomaly typically yields a variable degree of cyanosis (a visible bluish discoloration of the skin that is attributed to impaired tissue oxygenation) that is primarily related to the degree of right-to-left shunting across a patent foramen ovale and tricuspid regurgitation. There is commonly a right parasternal lift that is palpable due to enlargement of the right ventricle. Auscultation reveals a variety of extra heart sounds, including a widely split S1 with a louder second component (due to closure of the large deformed tricuspid anterior valve leaflet and the delay in right ventricular contraction commonly due to associated right bundle branch block), and possible S3 and S4 gallops.6 A systolic murmur of tricuspid regurgitation is usually heard along the left lower sternal border, possibly with a early diastolic snap related to the opening of the elongated anterior tricuspid leaflet. This murmur does not increase with intensity during inspiration (as is typical of most cases of this valvular leakage) due to the inability of the right ventricle to accommodate the enhanced venous return. Signs of right heart failure may also be seen including jugular venous distention (backing up of blood into the veins of the neck, hepatomegaly (liver swelling and enlargement), splenomegaly (enlargement of the spleen), ascites (fluid accumulation within the abdomen), and peripheral edema (particularly noted in the ankles and calves), all due to vascular congestion.
The electrocardiograph (ECG) in Ebstein's anomaly is not specific, but does reveal changes related to the associated right-sided abnormalities. Dilatation of the right atrium is manifested on the ECG as a tall, peaked P wave in the inferior leads and an enhanced positive component to the P wave in precordial lead V1.8 The degree by which these abnormally tall and peaked P waves are in relation to other causes of right atrial enlargement leads them to sometimes be referred to as "Himalayan P waves".2 Most patients have a right bundle branch block, with an RSR' configuration in lead V1 (commonly referred to as "rabbit ears" due to the double upward deflection of the widened QRS complex). First degree atrioventricular blocks, noted by the presence of a PR interval in excess of 0.20 seconds, is also frequently noted. Since many of these patients have WPW, one may note the presence of a delta wave (slurring of the beginning portion of the QRS complex). The presence of deep Q waves in the anterior precordial leads is another potential finding, albeit nonspecific.7 Many older patients with this condition develop atrial fibrillation due to the continued stretching of the right conduction fibers. Event or loop monitoring is commonly used to evaluate or "capture" episodes of paroxysmal atrial tachycardia, atrial fibrillation, and other supraventricular arrhythmias, as well as the complications of syncope.6
Chest radiography may demonstrate normal or reduced pulmonary vasculature along with enlargement of the pulmonary artery. There is commonly enlargement of the right atrium, with a normal left atrial and ventricular size.8 It is not uncommon for the radiograph to demonstrate massive cardiomegaly (enlargement of the heart's silhouette), especially if there is severe tricuspid valvular deformity and subsequent regurgitation, presenting with an appearance that is referred to as a "balloon-shaped" heart.11 Pulmonary vascular markings are generally reduced, owing to the decrease in blood flow through this bed of vessels.7
Echocardiography is the imaging modality of choice in patients with Ebstein's anomaly. The hallmark finding is the inferior displacement of the tricuspid valve, with elongation of the anterior leaflet with increased excursion and delays in valvular closure.12 There is also a common finding of septal leaflet displacement towards the apex of the right ventricle. The apical orientation of the tricuspid valve results in an enlarged right atrium and a small right ventricle. With the abnormal positioning of the tricuspid valvular leaflets, tricuspid regurgitation is frequently noted. The patent foramen ovale or other atrial septal defects can also be noted, along with changes in intracardiac pressure, such as increased pulmonary arterial pressure and an increase in the shunting of blood from the right side of the heart to the left side.
Clinical Management:
As many patients with Ebstein's anomaly present with significant cyanosis, supplemental oxygenation is imperative. Severe cases of Ebstein's may be deemed as ductal dependent, in which the neonate must rely on maintenance of the ductus arteriosus in order to allow for oxygenated blood to bypass the right ventricular outflow obstruction by going from the aorta to the pulmonary arterial vasculature.11 Compounding the inherent problems with adequate oxygenation and perfusion in severe cases is the potential for underdevelopment of the lungs as a result of the in-utero enlargement of the heart mechanically compressing on the developing lung.13 If the oxygen saturation is noted to be less than 75%, infusion of prostaglandin E1 should be considered in order to prevent the physiologic closure of this shunt (which usually takes place within the first or second week of life).10 Oxygen is also beneficial in lowering the resistance within the pulmonary vasculature, thus increasing pulmonary blood flow.
In both pediatric and adult patients with right-sided heart failure due to significant tricuspid insufficiency, there may be benefit from diuresis with drugs like furosemide (Lasix). Recently, there has been some limited success using nitric oxide to reduce pulmonary afterload, thereby decreasing the work that the deficient right ventricle must overcome to propel blood to the lungs.13 Angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril and enalopril, may be of some use in reducing the amount of tricuspid regurgitation and improving the overall function of the right ventricle, although definitive evidence for this pharmacologic modality is limited and some consider these agents as speculative.7 The WPW-associated tachycardic (accelerated) arrhythmias should be managed with either amiodarone or synchronized cardioversion. Drugs that slow conduction through the atrioventricular node should be avoided as they can lead to uncontrolled conduction through the accessory pathway and lead to potentially lethal ventricular arrhythmias. These drugs can be remembered by the mnemonic ABCD: adenosine, beta-blockers, calcium-channel blockers, and digoxin. However, in the absence of an accessory pathway, digoxin has proven beneficial for decreasing the ventricular heart rate associated with atrial fibrillation as well as increasing the inotropic (ventricular myocardial squeeze) state of the small right ventricle noted in patients with Ebstein's anomaly.6 Patients should be educated to maintain a low-sodium diet to minimize the onset of right heart failure. They should also be advised to avoid any types of stimulants, including caffeine and tobacco. Infective endocarditis antibiotic prophylaxis should be instituted prior to any dental or other invasive procedure.
Definitive therapy for this condition involves surgical repair or replacement of the dysfunctional tricuspid valve with closure of the associated ASD.5 The most commonly used valve for replacement is a bioprosthetic valve, such as one obtained from a cadaver or manufactured using bovine or porcine tissue. Atrial closure devices can be placed via transcatheter approaches; if the atrial septal detect is too large or too numerous (resembling Swiss cheese), open heart surgery may be needed to repair this membrane. Alternatively, the Fontan procedure may be performed, in particular in severely symptomatic infants; this procedure involves connecting systemic venous drainage to the pulmonary artery in order to circumvent the inadequate right ventricle, while improving its ability to pump blood to the pulmonary vasculature.8 Surgical interventions for supraventricular tachydysrhythmias (extremely fast cardiac impulse transmission causing heart rates ranging from 180 to 260 beats per minute) arising from the associated WPW are best managed by ablation of the accessory pathway via radiofrequency ablation or cryoablation (use of focally placed cold to freeze and induce necrosis the offending tissue). The incidence of major complications in patients undergoing surgical repair of the tricuspid valve, the atrial septal defects, or the accessory pathways is remarkably low, with the primary problems arising including possible need for permanent pacemaker implantation from ablation of the AV node or the onset of non-lethal atrial dysrhythmias.14
Prognosis:
When Ebstein's anomaly is discovered during intrauterine ultrasound, postpartum mortality is high.6 After delivery, there may be transient improvement in their condition as the pulmonary vascular resistance decreases, subsequently lessening the degree of right-to-left shunting; however the condition may worsen following closure of the ductus arteriosus, therefore resulting in decreased pulmonary blood flow. Adolescents and young adults commonly present for evaluation of the associated murmur or for evaluation of supraventricular arrhythmias. The New York Heart Association (NYHA) functional class is the most important prognostic indicator for adults with this and various other cardiovascular conditions, integrating such factors as the degree of activity intolerance and symptom severity. Patients with Ebstein's are at most risk of death due to cardiac failure, paroxysmal embolization across the atrial septal defect that may result in arterial occlusion or even brain abscess, or even sudden cardiac death due to lethal ventricular arrhythmias (noted in up to 20% of Ebstein’s anomaly patients with accessory pathways).14
References and Further Reading:
A schematic representation of this condition can be seen at www.mayoclinic.org/ebsteins-anomaly/enlargeimage1189.html.
1. Attenhofer-Jost, C.H., Connolly, H.M., Dearani, J.A., Edwards, J.A., & Danielson, G.K. (2007). "Ebstein's Anomaly." Circulation: Journal of the American Heart Association, 115, 277-285.
2. Murphy, J.G. & Lloyd. M. A. (2007). Mayo Clinic Cardiology: Concise Textbook, 3rd ed. Mayo Foundation for Medical Education and Research, Rochester, MO.
3. Riza, K. (2009). "Ebstein Anomaly." Accessed on November 22, 2010 from emedicine.medscape.com.
4. Levine, G.N. (2010). Cardiology Secrets, 3rd ed. Mosby / Elsevier, Philadelphia.
5. Peacock, W.F. & Tiffany, B.R. (2006). Cardiac Emergencies. McGraw-Hill, New York, et al.
6. Brickner, M.E. (2000). "Congenital Heart Disease in Adults (Second of Two Parts)." New England Journal of Medicine, 243 (5), 334-342.
7. Wu, J.C. & Child, J.S. (2004). "Common Congenital Heart Disorders in Adults." Current Problems in Cardiology 2004, 29, 641-700.
8. Crawford, M.H., Srivathson, K., & McGlothlin, D.P. (2006). Current Consult Cardiology. Lange Medical Books / McGraw-Hill, New York, et al.
9. Attenhofer-Jost, C.H., Connolly, H.M., O'Leary, P.W., Warnes, C.A., Tajik, A.J., & Seward, J.B. (2005). "Left Heart Lesions in Patients with Ebstein Anomaly." Mayo Clinic Proceedings, 80(3), 361-368.
10. Saxena, A (2005). "Congenital Heart Disease in India: A Status Report." Indian Journal of Pediatrics, 72 (July, 2005): 595-598.
11. Karlsen, K.A. & Tani, L.Y. (2003). S.T.A.B.L.E. – Cardiac Module: Recognition and Stabilization of Neonates with Severe CHD. The S.T.A.B.L.E. Program, Park City, UT.
12. Otto, C. M. (2007). The Practice of Clinical Echocardiography, 3rd ed. Saunders / Elsevier, Philadelphia.
13. Taeusch, H.W., Ballard, R.A., & Gleason, C.A. (2005). Avery's Diseases of the Newborn, 8th ed. Elsevier, Philadelphia.
14. Radmehr, H., Salehi, M., Forouzan, S., Emami, S., Mirhoseini, S., & Sanatkarfar, M. (2006). "Repair of Ebstein Anomaly: Early and Mid-Term Results." Archives of Iranian Medicine, 9(4), 354-358.
Contributor:
Sean Marcus Hancock, RDCS (AE), RCS, RCSA, RCIS, CCT
Staff Cardiovascular Technician and Clinical Educator
Naval Hospital Bremerton, Bremerton, Washington, USA
April 2012