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1 Case series of newborn with Ebstein’s Anomaly : presentation and outcome
Made Suadnyani Pasek, Eka Gunawijaya, Ni Putu Veny Kartika Yantie
Department of Child Health, School of Medicine, Udayana University/Sanglah Hospital, Denpasar [email protected]
Abstract
Ebstein’s anomaly is one of a rare malformation that responsible for less than 1% of all congenital heart anomalies in newborn. Characterized by varying degrees of downward displacement of the tricuspid valve leaflets into the cavity of the right ventricle. Fetal and neonatal presentation in Ebstein’s anomaly are predicted to have a poor overall prognosis. This study was conducted to investigate the presentation and outcome of patients with ebstein’s anomaly of newborn. Three cases were identified as Ebstein’s anomaly. The first and second case were diagnosed with Ebstein’s anomaly type C, the third case was diagnosed as Ebstein’s anomaly type B. One of three cases underwent fetal echocardiography. The newborn presented cyanosis immediately after birth, cardiomegaly, and from echocardiography revealed atrialized right ventricle, tricuspid regurgitation.
All patients got misoprostol. On follow up, the first case was doing well, second case died on 3 days of life. Third case revealed ABO incompatibility and suspect down syndrome died on 5 days of life.
Typical presentation of Ebstein's anomaly in newborn is cyanotic newborn with cardiomegaly on x- ray, associated with a worse prognosis.
Keywords: Ebstein’s anomaly; neonate; presentation; outcome; case series
Abstrak
Ebstein’s anomali adalah malformasi yang berhubungan dengan kurang dari 1% dari semua anomaly pada penyakit jantung bawaan. Anomali ini ditandai dengan berbagai tingkat perubahan letak katup katup trikuspid ke dalam rongga ventrikel kanan. Presentasi janin dan neonatal pada Ebstein’s anomali diprediksi memiliki prognosis yang buruk. Penelitian ini dilakukan untuk mengetahui manifestasi klinis dan laboratorium serta luaran pasien dengan Ebstein’s anomali pada bayi baru lahir. Tiga kasus diidentifikasi sebagai Ebstein’s anomali. Kasus pertama dan kedua didiagnosis dengan anomali tipe Ebstein C, kasus ketiga didiagnosis Ebstein’s anomali tipe B. Satu dari tiga kasus menjalani fetal echocardiography. Manifestasi klinis yang paling sering terjadi adalah sianosis segera setelah lahir. Pemeriksaan rontgen thorak didapatkan kardiomegali, dan dari ekokardiografi terdapat atrialized dari ventrikel kanan, trikuspid regurgitasi. Semua pasien mendapat misoprostol. Saat pemantauan, kasus pertama masih bertahan hidup, kasus kedua meninggal pada 3 hari kehidupan. Inkompatibilitas ABO dan suspek sindrom down ditemukan pada kasus ketiga, meninggal pada 5 hari kehidupan. Manifestasi khas dari Ebstein’s anomali pada bayi baru lahir adalah sianosis dengan kardiomegaly pada x-ray serta berhubungan dengan prognosis yang buruk.
Kata kunci: anomali Ebstein; neonatus; gejala klinis; luaran; seri kasus
INTRODUCTION
Ebstein’s anomaly is a malformation that rarely occurred. It is characterized by malformations and low deployment of septal and posterior leaflets of the tricuspid valve, showing an area of atrialized
2 right ventricle.1 The typical presentation of Ebstein’s anomaly in the newborn is cyanotic newborn with cardiomegaly to x-ray.2 Early detection of newborn with congenital heart disease makes it possible to consider to the option of termination of pregnancy considering the effect of the anomaly.
Specificity and sensitivity of fetal scanning for cardiac abnormalities were found to be 98 and 42%, respectively. The positive predictive value of fetal scanning was 90% and the negative predictive value 93%.2,3 Early presentation is associated with other cardiac lesions, usually pulmonary stenosis or atresia.
Problems in neonate with ebstein’s anomaly are inadequate pulmonary blood flow due to severe tricuspid regurgitation and increase of pulmonary vascular resistance and functional pulmonary atresia, right ventricle dysfunction, inadequate left ventricular filling due to septal bowing. Arrhythmia can occur due to mechanical stimulation of the atrialized right ventricle.4 No standardized treatment protocol for these infants has been published in the literature. Each patient’s therapy is adapted according to the severity and degree of functional obstruction of the outlet of the right ventricle. The infusion of prostaglandins and nitric oxide can be advantageous in more severe patients.5 Surgical operation is done in the existance of right heart dilation and progressive impairment of ventricular functional 4,5,6
Mortality is approximately 50% of cases in the sequence of natural history, and about 30%
of patients in this age group.2,3,7 One study showed that patients with ebstein’s anomaly that had been operated demonstrated a much lower operative mortality. The research also revealed that 5- year survival rate is higher (5 year survival rate 80% vs. 66,1%) in those with bidirectional Glenn 1
CASE REPORT
During August 2016 – September 2017 there were 3 cases of newborn with Ebstein’s anomaly in our center. Prenatal, natal, and post natal history was described in Table 1. Immediately after birth, the newborn presented cyanosis and low oxygen saturation. Typical murmur for tricuspid regurgitation and cardiomegaly were noted. In all cases echocardiography revealed atrialized atrium and tricuspid regurgitation with different grade. Presentation cases of Ebstein’s anomaly cases details showed in Table 2.
Case 1
Patient was born in Sanglah Hospital. The laboratory investigation showed within normal limit at the time the baby was born. At second day of hospitalization patient became lethargy and there were temperature instability and worsen of septic marker. Patient then assessed early onset of neonatal sepsis. Patients was given first line of antibiotics, misoprostol was continued given at 20
3 mcg every 6 hours. Evaluation at 5th days of hospitalization showed no temperature instability, septic marker evaluation revealed improvement. At sixth days of hospitalization, patients was discharge against medical advice since the patient did not have insurance. On follow up patients is 17 months old and still alive.
Case 2
Patient was born in Sanglah Hospital. The treatment was administration of misoprostol 15 mcg every 4-6 hours. Blood gas analysis on second day of admission revealed metabolic acidosis with PH 7,30, PCO2 35,1 mmHg, PO2 59,50 mmHg, HCO3- 16,80 mmol/L, BEecf -9,6 mmol/L. Patient was intubated at second day of hospitalization for the need of mechanic ventilation due to frekuent desaturation and bradicardy. Patient was died on the 3rd day of hospitalization.
Case 3
Third case was reffered from Klungkung General Hospital. The baby was admitted to Sanglah Hospital due to chieft complaint yelowish of the body. Yellowish was complained since the baby was 2 days old. Clinically the baby looked lethargy, did not feed well. The laboratory investigation supported infection process. Patients was assessed as early onset of neonatal sepsis, ABO incompatibility, suspect down syndrome. The treatment were admisnitration of antibiotic, misoprostol 20 mcg every 6 hours. On second day of admission patient got worse. The analysis of blood gas revealed metabolic acidosis with PH 7,23, PO2 33,80, PCO2 50,6, HCO3 20,60. Patient was then intubated and given ventilator support, misoprostol was given 20 mcg/kg every 4 hours, fototherapy was continued. Death occurred on 5th days of age.
Table 1. Presentation of prenatal, natal, postnatal of Ebstein’s anomaly cases
Presentation Case 1 Case 2 Case 3
Prenatal
Fetal scanning No Yes, revealed PS and single
atrium
No
Fetal arythmia No No No
Fetal distress Yes No No
complication Gestational hypertention No No
Natal
Mode of delivery SC indication of non reassuring cardiotocography
SC indication of pulmonal stenosis and single atrium
Spontaneously
Gestational age 41 weeks 38 weeks 36 weeks
Risk of infection Greeny amnion fluid No No
Postnatal
APGAR score 7-8 8-9 8-9
4 Birth weight
(grams)
3850 2930 2210
Others problem Early onset of neonatal sepsis
No ABO incompatibility,
early onset of sepsis neonatal,
Anomaly No No suspect down syndrome,
microcephaly Abbreviation: PS (Pulmonal Stenosis); SC(Sectio Caesaria)
Table 2. Presentation of Ebstein’s anomaly cases
Presentation Case 1 Case 2 Case 3
Symptoms
age 0 days 0 days 0 days
presentation Cyanocis Cyanocis
hemodynamic instability at second day of age
Cyanosis, hemodynamic
intstability at third day of age
Physical examination SpO2 70-80%
Murmur (+) holosystolic LLSB grade IV/6
SpO2 75-80%
Murmur (+) holosystolic LLSB grade IV/6
SpO2 80-85%
Murmur (+) holosystolic LLSB IV/6
Electrocardiography Sinus rhytm, RAD, right atrium hyperthropy
Sinus rhytm, RAD, right atrium hyperthropy, RBBB (Figure 2.a)
Sinus rhytm, RAD, right atrium hyperthropy
Chest X-Ray
CTR 77% (Figure 1.a) 94%, box shape
appearance (Figure 2.b)
91%, box shape appearance (Figure 3.a)
others Oligaemic lung Oligaemic lung Oligaemic lung
Echocardiography Dyskinetic atrialized right ventricular, moderate TR, large turtous PDA, , Ebtein Anomaly type C (Figure 1.b)
Large atrialized right ventricle, severe TR, redundant TV, small turtous PDA, moderate ASD, pulmonary dysplasia
Ebstein’s anomaly type C (Figure 2.c)
Atrialized right ventricle, moderate TR, moderate PDA, large ASD, dysplasia pulmonal,
Ebstein’s anomaly type B
(Figure 3.b)
5 Abbreviation: SpO2 (Oxygen saturation); LLSB (Left Lower Sternal Border); RAD (Right Axis Deviation); RBBB (Right Bundle Branch Block); CTR (Cardiothoracic Ratio); TR (Tricuspid Regurgitation); PDA (Patent Ductus Arteriosus); TV (Tricuspid Valve); ASD (Atrial Septal Defect)
DISCUSSION
Ebstein’s anomaly is a cardiac anomaly with variable clinical conditions that is characterized by apical displacement of the septal and posterior leaflets of the tricuspid valve. The morphology of this condition leads to decrease the size of the functional ventricle. The region above the tricuspid ring displaced is described as an “atrialized” region of the right ventricle. It has thinner wall assuming similar aspect atrial anatomy, which is partly responsible for defect of ventricular filling.1 The clinical cardiologic examination, chest X-ray and electrocardiogram may be useful in the initial investigation of these patients. Performing Doppler / Echocardiography is relevant to anatomical assessment of the presence of obstructive lesions of the right heart.8,9,10
In these three cases this was evidenced characteristic image of caudal displacement of the tricuspid valve, and presence of significant dilation of the right atrium and the presence of tricuspid insufficiency. Physical examination revealed holosystolic murmur at left lower sternal border intercostae II-IV grade IV/6 supporting a tricuspid regurgitation. Electrocardiography revealed right axis deviation, enlargement of right atrium. Chest X ray of the patients showed cardiomegaly and oligaemic lung. Echocardiography of all these three case revealed arterialized right ventricle and tricuspid regurgitation.
Screening protocol based on results of measurements oxygen saturation from the right hand and foot. This is a tool that can be used to evaluate slight hypoxemia.An infant would be said to have positive screen if at ≥24 hours of life a pulse oximeter was <90% in either the right hand or either foot, both readings from the right hand and either foot were <95% on three measurements and a persistent >3% difference in the right hand and either foot measurement. Every measurement is separated by 1 hour.11 In all three cases showed low oxygen saturation at >24 hours. Ebstein’s anomaly, including atrial septal defect in 90% of patients, pulmonary stenosis and pulmonary atresia. 1 In small percentage of cases and occasionally can also occur ventricular septal defect.1,5 In second case there were moderate ASD, small turtous PDA and pulmonary dysplasia, no ventricular septal defect was found. In third case there were large ASD and dysplasia pulmonal, no ventricular septal defect was found.
Down’s syndrome is most commonly associated with cardiac defects such as a ventricular septal defect, and an endocardial cushion defect. Ebstein’s anomaly with Down’s syndrome is
6 extremely rare and only about six cases until now.10 In the third case the patient with short neck, with excess skin at the back of the neck facial profile and nose were flattened, The newborn also had small head, ears, and mouth was suspected down syndrome. Echocardiography revealed ebstein’s anomaly type C.
Neonates with Ebstein’s anomaly may present with cyanosis, cardiomegaly, typical tricuspid regurgitation murmur.5 In all cases, newborn presented with cyanosis immediately after birth. Saturation was under 85%. In the investigation of these three cases, the chest X-ray revealed an enlarged heart, oligaemic lung appearance and electrocardiography revealed with enlarged right atrium due to arterialized portion of the right ventricle.
As the pulmonary vascular resistance decreases, due to change in fetal circulation pattern, there is a tendency of improvement of clinical conditions. The first case was hemodynamically stable with misoprostol, and was maintained on 70–85% oxygen saturation at the first 5 days.
Better oxygen saturation which was 81-83% reached at 5th days at admission. Misoprostol was continued given at 20 mcg every 6 hours.
Misoprostol is a synthetic PGE1 analogue, it consists of 15-deoxy-16-hydroxy-16-methyl (PGE1). Misoprostol is usually used in obstetric and gynecological practice because of its utero- tonic and cervical priming action. Misoprostol has many advantages such as cheap, easily available, stable at room temperature, can be given orally and having few side effect. Misoprostol can be differentiate structurally from prostaglandin E because of methyl ester at C-1. Misoprostol can increase the anti-secretory potency. The effect of hydroxyl group from C-15 to C-16 and the addition of methyl group at C-16 can improve the duration of action, the safety profile of the drug and also increase oral activity of that drug. 12 In these case, to maintain ductus patency we use misoprostol because the PGE1 was not available in our centre.
If the deformity of the tricuspid valve is severe, neonatal or even intrauterine death may occur.9,13 In second case which was ebstein anomaly type C there was severe tricuspid regurgitation, death occurred at third days of admission.
With early diagnosis, however, most infants with congenital heart defect can benefit from successful surgical repair or palliation.1,2,8,9 In second case, patient was diagnosed pulmonal atresia through fetal scanning. Mode of labour selected was sectio caesaria and performed echocardiography soon after birth.
Neonates with Ebstein's anomaly have a high early mortality rate. Neonate that has been detected to have this anomay is said have poor prognosis. It is said to have 45 % intrauterine deaths and frequent terminations. Prenatal diagnosis that is available recently now allow earlier detection
7 of these malformations. Comunnication, education must be done to assist parents to make decision.
Those surviving the 1st month of life remain at high risk of late hemodynamic deterioration or sudden death. Echocardiographic grading of severity of the defect permits prognostic stratification.
The Carpentier classification divided this anomaly into 3 type which are type A, which show minimal displacement of septal leaflet attachment with small atrialized right ventricle, Type B, show there is moderate displacement of septal leaflet attachment and large atrialized right ventricle, Type C, important displacement of septal and posteroinferior leaflet attachment with nonatrialized or dyskinetic atrialized right ventricle, restrained anterior leaflet motion, and short chords, and the last is type D with tricuspid sack. The prognosis depends on severity of the anomaly, degree of tricuspid regurgitation, degree of heart failure, type of Ebstein’s anomaly, associated anatomical defects and associated arrhythmias.14 In second case patients was diagnosed before birth, diagnosed with Ebstein’s anomaly type C, there was severe tricuspid regurgitation, deterioration of hemodynamic. Patients was died at 3rd days of hospitalization. In third case there were moderate tricuspid regurgitation, pulmonal dysplasia and some others condition such as ABO incompability, suspect of down syndrome, patient was died at 3rd days of admission.
Prognostic factors for ebstein anomaly are young age at presentation (12 months). Age less than 12 month was significantly associated with death of patient with ebsteins anomaly. Estimated mortality risk among patients diagnosed before the age of 1 year was 7.9 times the risk in the group of patients diagnosed after 1 year of age. Another prognostic usch as male gender, gestational age, birth weight were not significantly associated with mortality. Celermajer index (Gose score) is used to predict mortality in Ebstein’s anomaly. Increasing severity, that is, a higher grade, was associated with a high mortality rate.7 Many studies was done to conduct predictors of a long-term outcome from fetal until adult life. Some research revealed that fetus and newborns without symptom have a significantly worse outcome than older children.15,16
Several risk factors have been associated with death and survival in Ebstein’s anomaly patient, but there were no general consensus been established. One Study revealed that organomegaly at the time of EA diagnosis was made significantly associated with death.
Mechanical ventilation used at presentation was correlated with shorter survival time of newborn with this anomay. Abormality in chest X-ray and ECG were not associated with prognostic with significant level. In the second case, patient with ebstein anomaly with small turtous PDA, and the need of mechanical ventilation was died on the 3rd day of hospitalization. The third case with dysplasia pulmonal and used ventilator support was died on the 3rd day of hospitalization.
8 The outcome of symptomatic neonates with EA is not satisfiying, out of medical or surgical management. It will need stent implantation to make stabilization of duct. Performing that supporting therapy could be a reliable and life-saving and can be a choice as an alternative to surgical palliation.14,17 The surgical procedure should be carried out taking into account the anatomy and the probability that it will be successful, since studies showed up to 47% mortality level in operated neonates. The repair of the valve in a gravely ill newborn with low right ventricular function is generally unwise, given the variability of anatomy and unpredictable results. In the third case newborn assessed as early onset neonatal sepsis, hyperbilirubinemia et causa ABO incompatibility, clinically syndrome on the face got worse by day. Since the baby was not stable, BAS and ductus stenting was not possible to be done.
Conclusion
Ebstein’s anomaly is a malformation characterized by malformations and low deployment of septal and posterior leaflets of the tricuspid valve, showing an area of atrialized right ventricle. This case illustrates the typical presentation newborn with ebstein’s anomaly were cyanocis and cardiomegaly. Ebstein anomaly is almost uniformly fatal in severely symptomatic neonates. Fetal and neonatal presentation in Ebstein's anomaly is predicted to have a poor overall prognosis.
References
1. Yuan SM. Ebstein’s Anomaly: genetics, clinical manifestations, and management. Pediatr- neonatol 2017;58:211-15.
2. Digilio MC, Silvestri LM, Dallapiccola B, Marino B. Genetics of ebstein anomaly. In:
Giamberti A, Chessa M, editors. The Tricuspid valve in congenital heart disease. 1st ed.
Italia: Springer; 2014. p. 25-30.
3. Paranon S, Acar P. Ebstein’s Anomaly of the tricuspid valve: from fetus to adult. Heart 2008;94:237-43.
4. Schwartz MC, Glatz AC, Gillespie MJ. Valvular insufficiency and heart failure. In: Jefferies JL, Chang AC, Rossano JW, Shaddy RE, Towbin JA, editors. Heart failure in the child and young adult: from bench to bedside. 1st ed. United States: Academic Press; 2017. p. 297-306.
5. Nakanishi K, Kawasaki S, Takahashi K, Smimizu T, Amano A. Successful treatment of a rare case of neonatal Ebstein Anomaly in a very low-birth-weight premature neonate. J Card Surg 2014;20:1-3.
9 6. Pinasco GC, Rocha RF, Lougon MH, Fiorio LM, Santos LS, Cola E, et all. Ebstein’s
anomaly: a case report. Int Arch Med 2016;9:1-5.
7. Shetty RK, Vivek G,Nayak K,Pai UM. Fetal ebstein's anomaly. BMJ case rep 2012;8:1-3.
8. Park MK. The Pediatric Cardiology Handbook. 4th ed. Philadelphia: Elsevier;2010.
9. Yun WS. Congenital heart disease in the newborn requiring early intervention. Korean J Pediatr 2011;54:183–91.
10. Upadhyay S, Law S, Kholdwala D. A newborn with cardiomegaly. J Emerg Trauma Shock 2010;3:298-301.
11. Engel M, Kochilas L. Pulse oximetry screening: a review of diagnosing critical congenital heart disease in newborns. Med Devices 2016; 9: 199–203.
12. Tang OS, Danielsson G. Misoprostol:pharmacokinetic profiles, effects on the uterus and side- effects. International Journal of Gynecology and Obstetrics. 2007;99:S160-7.
13. Livia K, Rhona ME, Sumayah E, Marry EJ, Gideon JD, Jan LS, Tammo D, Chris LK, Ton F, William AH. Ebstein’s Anomaly: factors associated with death in childhood and adolescence:
a multi-centre, long-term study . European Heart Journal 2008;28:2661–6.
14. Ya-Fei Z, Xian-Ling Z, En-Fa Z, Hong-Wei L. Diagnostic value of fetal echocardiography for congenital heart disease A Systematic review and meta-analysis. Medicine 2015;94:1-11.
15. Bove EL, Hirsch JC, Ohye RG, Devaney EJ. How I Manage Neonatal Ebstein’s Anomaly.
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2009;12:63-5.
16. Giuseppe S, Gianpiero G, Maria TP, Marianna C, Carola L, Maria GR, Giuseppe C, RaffaeleC. Transcatheter ductal stenting in critical neonatal Ebstein’s anomaly. J Cardiovasc Med 2008;9:419–422.
17. Hazelzet T, David N. Ebstein’s anomaly and tricuspid valve dysplasia: prognosis after diagnosis in utero. Pediatr Cardiol 2012;33:1391-6.
10 Figure 1.a. X ray of 1st case showed cardiomegaly with cardiothoracic ratio 77%, oligaemic lung
Figure 1.b. Echocardiography of 1st case, showed displacement of tricuspid valve leaflet
11 Figure 2.a. Electrocardiography of 2nd showed RAD, right atrium hypertrophy and RBBB
Figure 2.b. Chest X ray of 2nd case, cardiomegaly with CTR 94%, oligaemic lung
Figure 2.c. Echocardiography of 2nd case showed large atrialized right ventricle, redundant tricuspid valve
12
Figure 3.a. Chest X ray of 3rd caseshowed cardiomegaly with CTR 91%, oligaemic lung
Figure 3.b. Echocardiography of 3rd case right atrium enlargement, atrialized right ventricle
