EBSTEIN ANOMALY

Review on ebstein anomaly including clinical features,diagnosis & management

1. Dr Awadhesh Kumar Sharma Ebstein’s Anomaly

2. Sequence of presentation Work up Treatment Anatomy Embryology Clinical Features

3. Tricuspid Valve Anatomy

4. TV annulus The tricuspid valve is the most apically (or caudally) placed valve with the largest orifice among the four valves. The tricuspid annulus is oval-shaped and when dilated becomes more circular. 20% larger than MV annulus . Normal TV annulus= 3.0 3.5 cm

5. Leaflets The tricuspid valve has three distinct leaflets described as septal , anterior, and posterior. The septal and the anterior leaflets are larger. The posterior leaflet is smaller and appears to be of lesser functional significance since it may be imbricated without impairment of valve function.

6. Leaflets The septal leaflet is in immediate proximity of the membranous ventricular septum, and its extension provides a basis for spontaneous closure of the perimembranous ventricular septal defect. The anterior leaflet is attached to the anterolateral margin of the annulus and is often voluminous and sail-like in Ebstein’s anomaly.

7. Papillary Muscles & Chordae There are three sets of small papillary muscles, each set being composed of up to three muscles. The chordae tendinae arising from each set are inserted into two adjacent leaflets. The anterior set chordae insert into half of the septal and half of the anterior leaflets. The medial and posterior sets are similarly related to adjacent valve leaflets.

8. Transthoracic Views

9. Transesophageal Views

10. Embryologic aspect The leaflets and tensile apparatus of the atrio ventricular valves seem to be formed by a process of delamination of the inner layers of the inlet zone of the ventricles. Delamination of the right ventricular free wall, continues to the level of AV junction. In EA, delamination of these leaflets may have failed to occur due to an incompletely understood mechanism Process of delamination is incomplete and falls short of reaching the level of the AV junction. The apical portions of the valve tissue fail to resorb completely. Distortion and displacement of the tricuspid valve leaflets, and a part of the right ventricle becomes atrialized .

11. DEFINITION Congenital defect Origins of septal or posterior leaflets, or both, are displaced downward into RV Leaflets are variably deformed Atrialization of right ventricle Anterior leaflet is enlarged and sail-like

12. Pathologic anatomy of TV Origin of TV from AV ring & its chordal attachments are malpositioned Leaflets are malformed, dysplastic (thickened & distorted), enlarged or reduced in size Septal leaflet always affected, posterior leaflet nearly always, and anterior leaflet seldom Septal & posterior leaflets displaced , maximal displacement is usually at the commissure

13. Top, Normal tricuspid valve with anterior, posterior, and septal leaflets in 1 plane . Middle , Tricuspid valve in right sided Ebstein’s anomaly showing displacement of posterior and septal leaflets; maximal displacement is at the crux of the posterior and septal leaflets. Bottom , Tricuspid valve in left-sided Ebstein’s anomaly; the displacement of leaflets is similar to that in the right-sided anomaly . From Anderson et al.16 Used with permission of the Mayo Foundation for Medical Education and Research .

14. Pathologic anatomy of RV Proximal Atrialized in one fourth of hearts\dilated When thin moves paradoxically during systole Electrical potentials are ventricular, but pressure pulse is atrial contoured Distal Smaller than normal RV RV dilatation Functional portion is infundibulum, trabeculated apex, portion beneath anterior cusp Thinner walled with fewer muscles

15. Severe Ebstein’s malformation of tricuspid valve (4-chamber view) showing marked downward displacement of shelf-like posterior leaflet with attachment to underlying free wall by numerous muscular stumps (arrows ), markedly dilated atrialized portion of right ventricle (ARV), small functional portion of right ventricle (RV), leftward bowing of ventricular septum, and marked dilatation of right atrium (RA). LA indicates left atrium; LV , left ventricle

16. Epidemiology Ebstein’s anomaly occurs in 0.3-0.8% of all congenital heart diseases 1 in 20,000-50,000 live births Equal male: female occurrence Mortality in children presenting in the neonatal period is 30-50% Mortality at all ages is 12.5% Arch Anat Physiol 1866:238–254.

17. Associated defects Commonly associated with: ASD or PFO (90%) VSD, AV canal defect Pulmonary stenosis / atresia (20-25%) Wolff-Parkinson-White Syndromes: Down, Marfan , Noonan sumner RG, Jacoby WJ Jr , Tucker DH. Ebstein’s anomaly associated with Car- diomyopathy and Pulmonary Hypertension. Circulation 1964;30:578–587 .

18. Etiology Congenital disease of often uncertain cause. Environmental factors Maternal ingestion of lithium in first trimester Maternal benzodiazepine use Maternal exposure to varnishing substances Maternal history of previous fetal loss Risk is higher in whites than in other races.

19. Genetic factors Rare cases of cardiac transcription factor NKX2.5 mutations , 10p13-p14 deletion, and 1p34.3-p36.11 deletion have been described in the anomaly . Recently, Postma et al. reported the results of a mutational analysis in a cohort of 141 unrelated probands with Ebstein anomaly. Eight were found to have a mutation in the gene MYH7 and six of the eight patients also had left ventricular noncompaction . This may warrant genetic testing and family evaluation in this subset emanuel R, O’Brien K, Ng R. Ebstein’s anomaly: genetic study of 26 fami -lies. Br Heart J 1976;38:5–7.

20. Origin 1866 A.D. Hypothesis on single autopsy specimen He even did not see the patient, when later was alive Word used in 1927 A.D.

21. A pencil sketch of Wilhelm Ebstein published in the Festschrift celebrating Ebstein’s 70th birthday. Published by permission of the Mayo Clinic Proceedings, where it was published by Mann RJ, Lie JT. The life story of Wilhelm Ebstein (1836–1912) and his almost overlooked description of a congenital heart disease. Mayo Clin Proc 1979;54197–204.

22. Clinical presentation

23. Presentation at various stages of life Fetal life: Diagnosed incidentally by echocardiography. Neonatal life and infancy: Cyanosis and/or severe heart failure Improve as pulmonary vascular resistance decreases. Adult life: Fatigue , exertional dyspnea, cyanosis, tricuspid regurgitation and/or right heart failure, and palpitations; arrhythmias are common.

24. Neonatal presentation Congestive heart failure Due to TR and RV dysfunction Cyanosis Decreased pulmonary blood flow due to R  L shunt through ASD or PFO Increased pulmonary vascular resistance in the neonatal period compounds this problem Murmur

25. Later presentation Cyanosis Due to R  L shunt at atrial level Fatigue and dyspnea Secondary to RV failure and decreased LV ejection fraction Palpitations and sudden cardiac death Incidental murmur Paradoxical embolism

26. Cyanosis Fairly common Right-to-left shunt at the atrial level and/or severe heart failure Transient in neonatal life with recurrence in adult life May appear for the first time in adult life Transient appearance/worsening of cyanosis in adult life due to paroxysmal arrhythmias Once apparent, progressively worsens

27. Fatigue and dyspnea Poor cardiac output secondary to right ventricular failure and decreased left ventricular ejection fraction. Palpitations and sudden cardiac death SVT in as many as one third of patients Fatal ventricular arrhythmias accessory pathways

28. Arrhythmias Due to right atrial enlargement and high prevalence of accessory pathways 30-50% have evidence of WPW secondary to the atrialized RV tissue Mapping and ablation are difficult Atrial dilation disrupts anatomic landmarks Accessory pathways are often multiple

29. Electrophysiologic studies 25-30 % have accessory pathways 5-25 % have evidence of preexcitation on the surface ECG. Right-sided pathways are more common. Fifty percent of the patients have multiple pathways. Guide ablative therapy.

30. Complications Congestive heart failure Sudden cardiac death Bacterial endocarditis Brain abscess Paradoxical embolism Transient ischemic attacks Stroke

31. Pregnancy & Ebsteins Anomaly Pregnancy seems to be well tolerated with adequate supervision .

32. Prenatal presentation Difficult to diagnose prenatally Fetal presentation is variable: possible features include cardiomegaly , RA enlargement, tricuspid regurgitation or dysplasia, arrhythmia, or fetal hydrops Prognosis for the fetus diagnosed in utero with significant tricuspid valve disease is very poor (20% survival) Progressive right heart dilatation Cardiac failure Lung hypoplasia Pulmonary stenosis / atresia

33. Cardiothoracic area ratio at 33 (A) and 35 (B) weeks gestational age. A indicates anterior; P, posterior; R, right; and L , left. Circulation September 23, 2003

34. Prognosis & management Prenatal prognosis could be significantly influenced by the ability of foramen ovale to decompress the right atrium Arrythmia due to extreme dilatation of the RA might be a cause of sudden intrauterine death Ebstein ’ s anomaly without cardiac failure or hydrops : vaginal delivery Cesarean section

35. Physical Examination Cyanosis and clubbing - Varying degrees of cyanosis at various times in life and transient worsening with arrhythmias Precordial asymmetry Usually left parasternal prominence and occasionally right parasternal prominence Absent left parasternal ( ie , right ventricular) lift an important negative sign Jugular venous pulse May be normal Large a and v waves late in the course of the disease, with development of right heart failure

36. Physical Examination Arterial pulses Usually normal Diminished volume Heart sounds First heart sound widely split with loud tricuspid component Mitral component may be soft or absent in the presence of prolonged PR interval. Second heart sound usually is normal widely split when the pulmonary component is delayed due to RBBB.

37. Physical Examination Additional heart sounds and murmurs Third and fourth heart sounds commonly present, even in the absence of congestive heart failure (CHF). Summation of third and fourth heart sounds, especially with prolonged PR interval, can mimic an early diastolic murmur. The holosystolic murmur of tricuspid regurgitation At the lower left parasternal area and sometimes at the apex Murmur intensity and duration increase during inspiration.

38. Routine investigation protocal

39. 12-lead ECG Rhythm Usually normal sinus findings Intermittently SVT, paroxysmal SVT, atrial flutter, atrial fibrillation, ventricular tachycardia Abnormal P waves consistent with right atrial enlargement – “Himalayan P waves” PR interval Most commonly prolonged May be normal or short in patients with WPW (B) syndrome QRS complex RBBB Low voltage in many patients

40. Chest X-Ray Cardiomegaly ( Rounded or Box-like contour ) Small aortic root and main pulmonary artery shadow Decreased pulmonary vasculature Large right atrium

41. Echocardiogram Standard for diagnosis. M-mode Paradoxical septal motion Dilated right ventricle Delayed closure of tricuspid valve leaflets more than 65 milliseconds after mitral valve closure Roberson DA, Silverman NH. Ebstein’s anomaly: echocardiographic and clinical features in the fetus and neonate. J Am Coll Cardiol 1989;14:1300–1307.

42. Echocardiogram Two-dimensional Apical displacement of the septal leaflet of greater than 8 mm/m 2 – 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

43. Echocardiogram Doppler studies Varying degrees of tricuspid regurgitation Excludes associated shunts

44. Echocardiogram Assessment of severity and surgical options 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

45. Cardiac MRI CMR imaging has emerged as another tool for evaluation of Ebstein’s patients It provides quantitative measurement of right atrial and ventricular size and systolic function even in the presence of significant distortion of right ventricular anatomy. Yalonetsky S, Tobler D, Greutmann M, et al. Cardiac magnetic resonance imaging and the assessment of Ebstein anomaly in adults. Am J Cardiol 2011;107:767–773.

46. Cardiac Catheterization No longer required to make/confirm the diagnosis The most diagnostic characteristic- Typical atrial pressure & ventricular intracardiac ECG in the atrialized portion of the RV Elevated RAP R-L atrial shunting with systemic desaturation Elevated RVEDP

47. Natural history

48. Natural history It is not uncommon for Ebstein’s anomaly to be undiagnosed until adulthood. However, late diagnosis is associated with reduced survival. The mean age of diagnosis in a study of the natural history of 72 unoperated patients, was 23.9 ± 10.4 years. In this group of patients, arrhythmias were the most common clinical presentation (51%) . The estimated cumulative overall survival rates were 89%, 76%, 53%, and 41% at 1, 10, 15, and 20 years of follow-up, respectively.

49. Natural history Predictors of cardiac-related death on univariate analysis included: Cardiothoracic ratio of ≥ 0.65 Increasing severity of TV displacement on echocardiography New York Heart Association (NYHA) class III or IV Cyanosis Severe TR Younger age at diagnosis In a multivariate model, younger age at diagnosis, male sex, cardiothoracic ratio of ≥ 0.65, and the severity of TV leaflet displacement on echocardiography were predictors of late cardiac mortality.

50. Management Severity Assessment Guideline/Indications Medical management Surgical management Post operative functional status

51. Severity assessment

52. Celermajer Index Celermajer et al. described an echocardiographic grading score for neonates with Ebstein’s anomaly, the Great Ormond Street Echocardiography (GOSE) score, with grades 1 to 4. The ratio of the combined area of the RA and atrialized RV is compared to the functional RV and left heart. This classification is particularly helpful with neonatal Ebstein’s anomaly. Grade 1: ratio <0.5 Grade 2: ratio of 0.5 to 0.99 Grade 3: ratio of 1.0 to 1.49 Grade 4: ratio ≥ 1.5 Celermajer DS, Bull C, Till JA, et al. Ebstein’s anomaly: presentation and outcome from fetus to adult J Am Coll Cardiol 1994;23:170–176.

53. GOSE score Grade Ratio Mortality 1 <0.5 8% 2 0.5-0.99 9% 3 ( acyanotic ) 1-1.49 10% (neonatal) 45% (later) 3 (cyanotic) 1-1.49 100% 4 >1.5 100%

54. Carpentier’s classification In 1988, Carpentier et al. proposed the following classification of Ebstein’s anomaly - Type A: The volume of the true RV is adequate Type B: A large atrialized component of the RV exists, but the anterior leaflet of the TV moves freely Type C: The anterior leaflet is severely restricted in its movement and may cause significant obstruction of the RVOT Type D: Almost complete atrialization of the ventricle except for a small infundibular component.

55. EBSTEIN’S ANOMALY (Carpentier’s classification)

56. CANADIAN CARDIOVASCULAR SOCIETY CANADIAN CARDIOVASCULAR SOCIETY 2009 CONSENSUS CONFERENCE UPDATE ON THE GUIDELINES FOR THE MANAGEMENT OF ADULTS WITH CONGENITAL HEART DISEASE

57. EBSTEIN ANOMALY Class I The following situations warrant intervention: Limited exercise capacity (New York Heart Association class greater than II) (Level of Evidence: B) Increasing heart size (cardiothoracic ratio greater than 65%) (Level of Evidence: B) Important cyanosis (resting oxygen saturations < 90%) (Level of Evidence: B) Severe tricuspid regurgitation with symptoms (Level of Evidence: B) Transient ischemic attack or stroke (Level of Evidence: B) Patients who require operation for Ebstein anomaly should be operated on by congenital heart surgeons who have substantial specific experience and success with this operation. Every effort should be made to preserve the native TV. (Level of Evidence: C) Presentation at Annual CCS Meeting in Edmonton 2009

58. Neonatal Ebstein Neonatal Ebstein Poor prognosis Reported survival only 68% Indiactions for surgury - Heart failure Profound cyanosis J Clin Invest 1999;104:1567–1573 .

59. Initial management Prostaglandin infusion Placement of umbilical catheters Initiation of mechanical ventilation Minimum possible mean airway pressure Tidal volumes of 10-15 ml/kg to overcome atelectasis Management of pulmonary hypertension Diuretics for CHF

60. Management of pulmonary hypertension Nitric oxide Reduces after load of right ventricle Sedation Other pulmonary vasodilators

61. The surgical options include- (a) Biventricular repair (Knott-Craig approach) (b) Single ventricle pathway with right ventricular exclusion (Starnes’ approach) (c) Cardiac transplantation.

62. Biventricular Repair (Knott-Craig Approach) TV is repaired and the atrial septum is partially closed. This repair is typically a mono cusp type based on a satisfactory anterior leaflet Routine right atrial reduction is important to reduce the size of the markedly enlarged heart to allow room for the lungs. Although early mortality is high (about 25%), the intermediate outcome appears to be promising. Survival to hospital dismissal was 74% with no late mortality. Ann Thorac Surg 2002;73:1786–1793 .

63. Right Ventricular Exclusion Starnes Approach Starnes et al. pioneered the right ventricular exclusion approach, which involves: (a) fenestrated patch closure of the TV orifce , (b) enlarging the interatrial communication, (c) right atrial reduction, and (d) placing a systemic-to-pulmonary artery shunt. Particularly useful when there is anatomic RVOT obstruction. Right ventricular decompression is required as it passively fills from thebesian venous drainage, this is usually accomplished with a 4- to 5-mm punch fenestration in the TV patch starnes VA, Pitlick PT, Bernstein D, et al. Ebstein’s anomaly appear- ing in the neonate. A new surgical approach. J Thorac Cardiovasc Surg 1991;101:1082–1087.

64. Modified Starnes Repair (Total Ventricular Exclusion) Sano et al. modified the Starnes single-ventricle approach by performing a total right ventricular exclusion in which the free wall of the RV is resected and closed primarily or with a poly tetrafluoroethylene patch . This simulates a large right ventricular plication , which may improve the left ventricular filling and provide adequate decompression to the lungs and LV.

65. Cardiac Transplantation With the improved results of the biventricular and single ventricle approaches, transplantation rarely is performed in the current era. Cardiac transplantation remains an option in the most severe forms of Ebstein’s anomaly, particularly when there is significant left ventricular dysfunction.

66. Children & Adults

67. Children and Adults Medical Bacterial endocarditis prophylaxis may be required in the presence of prosthetic materials or patches that were used for the repair. In mild Ebstein’s anomaly, with nearly normal heart size, and in absence of arrhythmias, athletes can participate in all sports. However, in severe Ebstein’s anomaly, activity is restricted unless it has been optimally repaired with near normal heart size and no arrhythmias.

68. Surgery INDICATIONS FOR SURGERY Presence of symptoms, Cyanosis, Paradoxical embolization . Patients who have decreased exercise performance Progressive increase in cardiothoracic ratio Progressive right ventricular dilatation and dysfunction Onset or progression of arrhythmias Presence of class III or IV NYHA or significant symptoms

69. PRINCIPLES OF SURGERY FOR EBSTEIN’S ANOMALY The following principles are the goals of surgery: (a) Closure of any intra cardiac communications (b) TV repair or replacement (c) Ablation of arrhythmias (d) Selective plication of the atrialized RV from apex to base, (e) Reduction right atrioplasty (f) Repair of associated defects (e.g., closure VSD).

70. Tricuspid Valve Repair The goal of operation is to obtain a competent TV, preserve right ventricular contractility, and to decrease the risk of late rhythm disturbances.

71. Danielson Repair This repair technique was reported in 1979 and was based on the creation of a monocusp valve using the anterior leaflet. This consisted of - Plication of the free wall of the atrialized RV Posterior tricuspid annuloplasty Right reduction atrioplasty Danielson GK, Maloney JD, Devloo RA. Surgical repair of Ebstein’s anom-aly . Mayo Clin Proc 1979;54:185–192.

72. Modified Danielson Repair Modifications involves - Bringing the anterior papillary muscle(s) toward the ventricular septum, which facilitates coaptation of the leading edge of the anterior leaflet with the ventricular septum. Generally, an antero posterior tricuspid purse string or ringed annuloplasty is used, and atrialized right ventricular plication is performed selectively. This results in a TV repair at the level of the functional annulus, in contrast to the original repair, which brought the hinge point of the functional annulus up to the true annulus. A more recent modification includes patch augmentation of the mid-anterior leaflet with surgical delamination of attachments to the anterior and/or inferior leafets . Dearani JA, Danielson GK. Tricuspid valve repair for Ebstein’s anomaly. Oper Tech Thorac Cardiovasc Surg 2003;8:188–192.

73. THE BRAZIL EXPERIENCE ( da SILVA APPROACH) The cone repair described by Dr. da Silva from Brazil when the anatomy allows, as this technique is the most anatomic of all the repair techniques described. Specially, some septal leaflet should be present, which facilitates this repair technique. The cone technique represents the most anatomic repair by completion of the delamination process of the TV, providing 360 degrees of leafet tissue around the AV junction with its hinge point at the AV groove (true annulus). Although not initially described with this technique, some do supplement the repair with a flexible anterior annuloplasty band from anteroseptal commissure to inferseptal commissure whenever possible.

74. Copyright ©2007 The American Association for Thoracic Surgery da Silva J. P. et al.; J Thorac Cardiovasc Surg 2007;133:215-223 Operative steps for Ebstein's anomaly repair

75. Relative contraindications to the cone reconstruction technique Age >50 years Moderate pulmonary hypertension Significant left ventricular dysfunction: ejection fraction <30% Complete failure of delamination of the septal and posterior leaflets with poor delamination of the anterior leaflet (<50%) Severe right ventricular enlargement Severe TV annular dilatation

76. THE VENTRICULIZATION PROCEDURE Ullmann et al. published their results with the ventriculization procedure in 2004. This is characterized by reintegration of the atrialized portion of the RV into the right ventricular cavity ( ventricularization ). This can be obtained by orthotopic transposition of the detached septal and posterior leaflets of the TV. The reimplanted septal leaflet serves as an opposing structure for coaptation of the reconstructed AV valve.

77. Tricuspid Valve Replacement Every effort should be made to repair the TV rather than replacing it, but if TV repair is not feasible, then porcine bioprosthetic valve replacement remains a good alternative. Most prefer bioprostheses to mechanical valves due to the relatively good durability and the lack of need for anticoagulation . Kiziltan HT, Theodoro DA, Warnes CA, et al. Late results of biopros-thetic tricuspid valve replacement in Ebstein’s anomaly. Ann Thorac Surg 1998;66:1539–1545.

78. One and Half Ventricle Repair The BDCPA does two important things in the setting of Ebstein’s anomaly. First, it reduces venous return to the enlarged, dysfunctional RV by approximately one-third Second, it provides sufficient preload to the LV to sustain adequate systemic perfusion when right-sided output is low. Surgens usually prefer it if the left ventricular end-diastolic pressure (LVEDP) is <12 mm Hg, the transpulmonary gradient <10 mm Hg, and the mean pulmonary arterial pressure <16 mm Hg, before considering a BDCPA. Kopf GS, Laks H, Stansel HC, et al. Thirty-year follow-up of superior vena cava-pulmonary artery (Glenn) shunts. J Thorac Cardiovasc Surg 1990;117:662–670.

79. Indications for the BDCPA include Severe RV enlargement and/or dysfunction Squashed LV (D-shaped LV) Moderate degree of TV stenosis (mean gradient >6 mm Hg) as a result of reduction in the valve orifice area after repair RA:LA pressure ratio >1.5, which indicates poor RV function. Preoperative cyanosis at rest or with exercise Chauvaud S, Fuzellier JF, Berrebi A et al. Bi-directional cavopulmonary shunt associated with ventriculo and valvuloplasty in Ebstein’s anomaly: benefits in high risk patients. Eur J Cardiothorac Surg 1998;13:514–519.

80. Heart Transplantation Heart transplantation rarely is necessary for Ebstein’s anomaly. Indication for transplantation is usually the presence of severe biventricular dysfunction (left ventricular ejection fraction <25%).

81. Arrythmia management The most common atrial tachyarrhythmias in Ebstein’s anomaly are atrial fibrillation and flutter. Most surgens used successfully the right-sided cut-and-sew lesions of Cox-maze III procedure in Ebstein’s anomaly. With the availability of newer devices such as radiofrequency or cryoablation , the procedure time for maze procedure is shortened significantly. A biatrial maze procedure, performed particularly when there is chronic atrial fibrillation, left atrial dilation, or concomitant mitral regurgitation.

82. FUNCTIONAL OUTCOME AFTER SURGERY