Ebstein anomaly

it will help to conceptualize the basic of Ebstein's anomaly.

1. Ebstein’s Anomaly Dr. Porimal Kumar Das Phase-B Resident Paediatric Cardiology, BSMMU Date:10/12/2020

2. Ebstein’s Anomaly Ebstein’s anomaly of the tricuspid valve is a congenital malformation, in which there is downward (apical) displacement of insertion of septal and posterior leaflets.

3. History: This anomaly was first described by Wilhelm Ebstein in 1866 in an autopsy of a 19-year-old laborer who had cyanosis and dyspnea since early childhood.’ The very first reported case in a live patient was in 1949 by Tourniaire . Wilhelm Ebstein German physician

4. Epidemiolo g y Ebstein’s anomaly occurs in 0.3-0.7% of all congenital heart diseases 1 in 20,000 live births Equal male: female occurrence Mortality in children presenting in the neonatal period is 30-50% Mortality at all ages is 12.5%

5. 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.

6. 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

7. Associated defects Commonly associated with: ASD or PFO (90%) VSD, AV canal defect Pulmonary stenosis/atresia (20-25 %) PDA TOF DORV Right sided aortic arch, COA, TGA Mitral valve prolapse and stenosis Wolff-Parkinson-White Syndromes: Down, Marfan , Noonan

8. Tricuspid Valve Anatomy

9. 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

10. 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. S p A

11. The septal leaflet is in immediate proximity of the membranous ventricular septum The anterior leaflet is attached to the anterolateral margin of the annulus and is often voluminous and sail-like in Ebstein’s anomaly.

12. 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.

13. 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

14. DE F INITION 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

15. Pathology There are several anatomic components of Ebstein anomaly, namely: 1. Displacement of the septal and posterior leaflets towards apex of the right ventricle (RV). 2. Anterior leaflet is usually attached at the annular level and is large and sail-like with multiple attachments to ventricular wall. 3. The portion of RV that is proximal to the level of the displaced septal and posterior leaflets is called the ‘ atrialized RV’ and is usually thin and dysplastic

16. Pathology 4. RV cavity beyond the attachment of the septal and posterior leaflets is the ‘functional RV’ and is smaller, lacks inlet portion and has a small trabecular portion. 5. Infundibular portion of RV is sometimes obstructed by redundant anterior leaflet or its chordal attachments.

17. Pathophysiology Hemodynamic abnormalities depends on severity of the lesion D egree of displacement of the tricuspid valve D egree of tricuspid regurgitation. Mild Ebstein T ricuspid valve function close to normal.

18. Moderate to severe forms with each atrial contraction, the blood is propelled into the atrialized RV. With ventricular contraction that follows, the blood is forced back into the right atrium. (More pronounced in tricuspid regurgitation. ) With the next atrial contraction, this blood is forced back into the atrialized RV. This back and forth blood flow causes right atrial dilatation and increases right atrial pressure; right to left shunt across ASD/ PFO a rterial desaturation and pulmonary oligemia .

19. In severe case, absence of flow from ineffective RV cause physiological pulmonary atresia. All the systemic venous return must pass from right to left across PFO or ASD. thus causing severe cyanosis and acidosis.

20. Clinical Presentation May present at any age Fetal life: Diagnosed incidentally by echocardiography. Neonatal life and infancy: Cyanosis and severe heart failure SVT Improve as pulmonary vascular resistance decreases. Adult life: Fatigue, exertional dyspnea, cyanosis, heart failure, and palpitations arrhythmias are common.

21. Physical examination Cyanosis - Varying degrees of cyanosis at various times in life and transient worsening with arrhythmias . Clubbing Precordial asymmetry Usually left parasternal prominence and occasionally right parasternal prominence.

22. JVP – The jugular pulse is normal except for a prominent C wave that coincides with mobility of the anterior tricuspid leaflet. An attenuated X descent and a systolic venous V wave of tricuspid regurgitation rarely appear despite severe regurgitant flow because of ; the damping effect of the commodious right atrium the thin-walled toneless atrialized right ventricle tricuspid regurgitation is low-pressure and hypokinetic

23. Arterial pulses Usually normal Diminished volume Heart sounds First heart sound widely split with loud tricuspid component ( THE SAIL SOUND ) Mitral component - soft (long PR interval) Second heart sound widely split

24. Additional heart sounds and murmurs Third and fourth heart sounds C ommonly present .(QUADRUPLE RHYTHM) Summation of third and fourth heart sounds, especially with prolonged PR interval, can mimic an early diastolic murmur The systolic murmur of tricuspid regurgitation Medium frequency and decrescendo in nature (grade2/6 or 3/6). At the lower left parasternal area and sometimes at the apex .

25. I nvestigations ECG CXR ECHO Cardiac Catheterization Cardiac MRI

26. ECG Tall P wave and prolonged PR interval Features of RBBB WPW preexcitation SVT Deep Q wave in V1 to V4 and in inferior leads Atrial fibrillation, atrial flutter, VT,VF

27. C X R Cardiomegaly (Rounded or Box-like contour ) Decreased pulmonary vasculature The infundibulum either straightens the left cardiac border or forms a conspicuous convex shoulder. The most consistent and dramatic radiologic feature is the right atrial silhouette, which is almost always enlarged.

28. Lateral chest radiograph

29. Ech o cardiogram 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

30. Ech o cardiogram Doppler studies Varying degrees of tricuspid regurgitation RVOT obstruction Excludes intracardiac shunts

31. Echocardiogram from a patient with Ebstein’s anomaly. Color flow shows the jet of tricuspid regurgitation (TR) originating at the junction of the functional right ventricle (RV) and the atrialized right ventricle

32. Assessment of severity by Echo (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. RA area + aRV area fRV area+ LA area + LV area

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

34. Carpentier’s classification In 1988, Carpentier et al.proposed the following classification of Ebstein’s anomaly – Type A: T rue RV volume is adequate Type B: A large A RV but mobile anterior leaflet Type C: The anterior leaflet movement restricted causing RVOT obstruction Type D: Almost complete atrialization of the ventricle except for a small infundibular component.

35. TYPE A TYPE B TYPE D TYPE С

36. Cardiac MRI MRI is preferred for quantitative measurement of right atrial and RV size and systolic function. Provides complimentary information about TV anatomy . Axial imaging provides the most reliable information about atrialized RV volume. The ability to create 3D images may also provide greater delineation of disease severity.

37. Cardiac Catheterization Infant associated with critical pulmonary stenosis requiring balloon valvuloplsty To assess intracardiac and pulmonary pressure prior to surgical intervention. Selective right ventricular angiography demonstrates displaced TV leaflets, degree of tricuspid insufficiency and size and function of the RV .

38. Natural History Patient with less severe anomaly may be either asymptomatic or mildly symptomatic. Cyanosis tend to improve as the PVR falls during the newborn period. Cyanosis may appear later Hemodynamic deterioration with increasing cyanosis, CHF and LV dysfunction develop later in life. Some 18% of symptomatic newborn die in the neonatal period; 30% of patients die before the age of 10 years. Attacks of SVT with associated WPW preexcitation occur in 15-20% of all patients.

39. Management Medical management Surgical management

40. Medical management Severely cyanotic newborn: Oxygen Mechanical ventilation PGE1 infusion Inotropic agent Correction of metabolic acidosis

41. Medical management- Asymptomatic children with mild Ebstein’s anomaly Regular observation If CHF develops due to TR— F rusemide + Digoxin Varying degrees of activity restriction may be necessary. Acute episode of SVT Adenosine β blocker Radiofrequency Catheter Ablation

42. Surgical management Principles of Surgical Management for Ebstein Anomaly Complete or subtotal closure of intra-atrial communications Tricuspid valve repair or replacement Elimination of arrhythmias Selective plication of the atrialized RV Right reduction atrioplasty Repair of associated defects (VSD closure, relief of RVOT obstruction)

43. Neonatal Ebstein Most of the cases do not need surgical intervention. S evere forms with persistent cyanosis or important associated lesions will require intervention.

44. The surgical options in neonates are Tricuspid valvuloplasty —poor outcome Starnes procedure Neonatal biventricular repair Cardiac transplantation

45. Starnes procedure Fenestrated patch closure of the tricuspid valve orifice, Enlargement of the ASD, Plication of large RA ( atrialized RV), and Placement of a systemic-to pulmonary artery shunt (BT shunt) Particularly useful when there is anatomic RVOT obstruction.

46. Neonatal biventricular repair Partial closure of interatrial septum Tricuspid valve repair RA reduction

47. Cardiac transplantation Considered for the most severe cases in neonates, especially when the LV is abnormal.

48. Surgery in Children and Adults Indications Decreased exercise tolerance Cyanosis Progressive right ventricular dilatation (Cardiothoracic ratio >60%) Prior to significant right ventricular dysfunction Onset or progression of atrial arrhythmias Prior to left ventricular dysfunction

49. Surgical management in children Cone Reconstruction Tricuspid Valve Repair Danielson “ Monocusp ” Repair Carpentier Repair Tricuspid Valve Replacement Ventricularization Procedure Bidirectional Cavopulmonary Connection as an Adjunct to Tricuspid Valve Repair Atrialized Right Ventricular Plication and Right Atrial Reduction Surgical Treatment of Arrhythmias Cardiac Transplantation

50. Cone reconstruction Procedure: Separation of adherent segment of tricuspid valve from anatominal annulus and underlying RV. Cone created using released tricuspid valve tissue. Base of cone attached to AV junction Hinge point of tricuspid valve attached to AV junction. Atrialized portion of RV reduced by elliptical resection or plication.

51. Cone reconstruction M ost anatomically correct solution

52. Cone reconstruction Modified cone repair: Insertion of complete or partial annuloplasty ring. Selective application of Sebening stitch (approximation of anterior papillary muscle to ventricular septum) BDCPA (bidirectional cavopulmonary anastomosis, 1.5 ventricle physiology)

53. Cone reconstruction Contraindication: Patient age >60 years, Moderate pulmonary hypertension, Severe LV dysfunction (EF <30%), Absent septal leaflet, Heavy muscularization of the anterior leaflet, Severe tricuspid valve annular dilation with massive RV enlargement and systolic dysfunction.

54. Tricuspid valve repair Danielson monocusp repair: Creation of a monocusp valve using the anterior leaflet to coapt with the ventricular septum. Plication of atrialized RV Posterior tricuspid annuloplasty Right reduction atrioplasty .

55. Danielson procedure

56. Carpentier procedure: Detachment of anterior and septal leaflet Plication of atrialized RV Posterior tricuspid annuloplasty Reposition of leaflet and cover the orifice Placement of prosthetic ring

57. Tricuspid Valve Replacement Porcine bioprosthetic valve Mechanical valve

58. The Ventriculization Procedure 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.

59. Bidirectional Cavopulmonary Connection The BDCPA (bidirectional cavopulmonary shunt) does two important things in the setting of Ebstein’s anomaly. Reduces venous return to the enlarged, dysfunctional RV by approx. one-third. Provides sufficient preload to the LV to sustain adequate systemic perfusion when right-sided output is low.

60. BDCPA- Indications for BDCPA include: S evere RV enlargement and/or dysfunction, C ompression of the LV due to shift of the interventricular septum, M oderate tricuspid valve stenosis (mean gradient >8 mm Hg) after CR, or RA to LA pressure ratio >1.5 (an indicator of poor RV function).

61. Outcomes Short Term The severity of the valve malformation and dysfunction of both ventricles will affect outcome. Early mortality in neonates has been linked to marked RV enlargement, severe tethering of all leaflets, LV dysfunction, and pulmonary atresia. Patients with severe cardiomegaly (CT ratio >0.6) may also have lung hypoplasia. In the current era, early results in children are more favorable and operative mortality is∼3% in experienced centers.

62. Outcomes Long Term Most patients with Ebstein anomaly will need surgical intervention. Patients with Ebstein anomaly experience a high incidence of atrial tachyarrhythmias including atrial fibrillation and atrial flutter. Long-term outcomes after surgery for valve repair and replacement are excellent. Except for very ill newborns, adult survival with a good quality of life is expected for patients with Ebstein anomaly.

63. Take home points Ebstein anomaly is a RV myopathy with failure of TV delamination and highly variable TV morphology with severe regurgitation. It is the only congenital heart lesion that has a range of clinical presentation from the severely symptomatic neonate to an asymptomatic adult. Neonatal operation has high operative mortality, whereas operation performed in childhood and adulthood has low early mortality. Late survival and quality of life are excellent for the vast majority of patients in all age brackets.

64. Atrial tachyarrhythmias are the most common late complication and increase with age. The cone reconstruction can achieve nearly anatomic restorations of TV anatomy and function, and early-to- intermediate results are encouraging. Reduced RV function continues to be a challenge for some patients, as is the need for reoperation for recurrent TR. Innovative surgical and regenerative medicine strategies to address poor RV function and associated right-sided heart failure are evolving.

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