Journal of The Indian Academy of Echocardiography & Cardiovascular Imaging

INTERESTING CASE REPORT
Year
: 2019  |  Volume : 3  |  Issue : 2  |  Page : 88--92

Prenatal diagnosis of Ebstein's anomaly: An autopsy correlation predicting poor prognosis


Saji Philip1, Shalom Elsy Philip2, Linta Thampi3, Sarasa Bharati4,  
1 Division of Pediatric and Fetal Cardiology, St. Gregorios Cardio-Vascular Centre, Parumala, Kerala, India
2 Department of Anatomy, Christian Medical College, Ludhiana, Punjab, India
3 Division of Pathology, St. Gregorios International Cancer Care Centre, Multi-specialty Hospital, Parumala, India
4 Division of Pathology, Laboratory Services, Lifeline Hospital and Frontier Mediville, Chennai, India

Correspondence Address:
Saji Philip
Fetal and Pediatric Cardiologist, St. Gregorios Cardio Vascular Centre, Parumala, Pathanamthitta - 689 626, Kerala
India

Abstract

Ebstein's anomaly (EA) is rare but not an uncommon congenital heart disease in the fetus. Fetal echocardiogram has progressed to detect many forms of congenital heart diseases, especially to assess the prognosis of EA based on their anatomy and presentation in utero causing nonimmune hydrops. Fetal echocardiographic findings of cardiomegaly, apical displacement of tricuspid valve with severe regurgitation, can confirm the diagnosis of EA in utero. Severe cardiomegaly and nonimmune hydrops further contribute poor prognosis leading to fetal demise. Identifying fetal risk factors for predicting perinatal mortality is important, including the lack of antegrade flow across the pulmonary valve and retrograde duct flow. Here, we describe fetal echocardiographic findings of a case of EA causing severe cardiomegaly, restricted growth of the lungs, and hydrops in a 26-year-old primigravida at 20 weeks of gestation. The diagnosis was further correlated with the autopsy, characterized by severe cardiomegaly, huge right atrium, apical displacement, and tethering of septal and posterior leaflet, with markedly reduced lung volumes. Autopsy findings of dilated ductus further suggestive of possible reversed ductal flow causing circular shunt in EA raising the possibility of the poor postnatal outcome, even intrauterine death, and warranted for safe termination. Poor prognostic factors in EA have also been discussed with autopsy findings.



How to cite this article:
Philip S, Philip SE, Thampi L, Bharati S. Prenatal diagnosis of Ebstein's anomaly: An autopsy correlation predicting poor prognosis.J Indian Acad Echocardiogr Cardiovasc Imaging 2019;3:88-92


How to cite this URL:
Philip S, Philip SE, Thampi L, Bharati S. Prenatal diagnosis of Ebstein's anomaly: An autopsy correlation predicting poor prognosis. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2019 [cited 2022 Jan 18 ];3:88-92
Available from: https://www.jiaecho.org/text.asp?2019/3/2/88/265749


Full Text

 Introduction



Ebstein anomaly (EA) is a rare congenital cardiac defect characterised by tethering and apical displacement of tricuspid valve (TV) leaflets, occurring in about 1-5 per 200,000 live births, as a result of failed delamination of the leaflets from the interventricular septum. This leads to an adherence of tricuspid leaflets to the underlying myocardium accounting 3-7% of congenital heart diseases in fetus.[1],[2],[3],[4],[5] Reversed ductal flow causing circular shunt in EA raising the possibility of the poor postnatal outcome, even intrauterine death especially in the presence of non-immune hydrops.[5] Fetal echocardiogram is an essential diagnostic tool for the early detection of EA and its severity. Here we describe fetal echocardiographic findings in EA, causing severe cardiomegaly, restricted growth of lungs and hydrops in a 26-year old primigravida at 20-weeks of gestation. Possible poor prognostic factors has been discussed with autopsy findings.

 Clinical Presentation



A 26-year-old primigravida, at 20 weeks of gestation was referred to us with a history of the fetal ultrasound diagnosis of congenital heart disease, cardiomegaly, effusion, and ascites for expert diagnosis. Fetal cardiac ultrasound showed severe cardiomegaly occupying 2/3rd of the chest cavity (12.2/14.4 cm 2; cardio-thoracic ratio 0.87, normal 0.53; 97.5thP(percentile) for gestational age (GA) of 20 week, massive pericardial effusion, hypoplasia of both lungs; area of the lungs was small and ascites bilaterally seen (7.5 mm) [Figure 1]a and [Figure 1]b, [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d and [Figure 3]d, and cardiac dimensions measured as, dilated right atrium 15 mm × 14 mm, 17.5 mm in autopsy (normal 9.37 mm 95.5th P) and right atrium area was 7 cm2, atrialized right ventricle 10.5 mm and right ventricle (RV) 7.8 mm, z-score 1.66 (normal 8.3 mm 97th P) [Figure 1]c. Septal tricuspid valve leaflet was apically placed, 4 mm from the mitral valve annulus (Becker's dysplasia classification [BDC] Grade III tethering valve >50% distance from the atrioventricular junction to the apex), TV annulus (7 mm/specimen 8 mm × 7 mm), severe TV regurgitation with peak velocity 148 cm/s, with right-to-left shunt through large fossa ovalis [Figure 1]d, [Figure 1]e, [Figure 1]f, ductal reversal flow, pulmonary artery 4.2 mm (normal 4.5 mm 97.5th P), no antegrade flow across the pulmonary valve, left atrium 10.2 mm (normal 8.6 mm 95.5th P), left ventricle 8.6 mm (normal 8.2 mm 95.5th P), aortic valve 4.3 mm (normal 4.2 mm 95.5 P), aorta 4.6 mm, mitral valve annulus (3.6 mm/specimen 4 mm × 5 mm), and unrestricted fossa ovalis 4–5.7 mm, were measured in routine recommended two-dimensional (2-D) echocardiographic views. Normal left aortic arch was well documented. Left side chambers, mitral valve, and interventricular septum were normal. Family members preferred for the termination in view of severe hydrops and its complication alerted. Gross morphologic findings from the fetal autopsy showed congested enlarged liver with granular surface, severe cardiomegaly with pericardial effusion, huge right atrium, normally related great arteries, dilated ductus, and mild growth restriction of the lungs with the lace-like appearance of medial border of both right and left lungs [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d and [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d. The transverse cut of right atrium superiorly showed paper thin atrial wall, dilated TV annulus and non-visibility of TV cusp [Figure 3]e. RV was opened by triangular cut through PA showed tethering of apically placed posterior leaflet [Figure 3]f. Histopathology studies of the lungs with hematoxylin and eosin stain (H and E) ×40 and × 100 magnification showed fetal lung in canalicular phase of development, corresponding to 16–24 weeks of gestation as tubule structures of varying sizes with wide lumen lined by low cuboidal and flattened cells, separated by mesenchyme invaded by capillaries and canalicular phase of development lungs [Figure 4]c and [Figure 4]d. Gross description of the liver was whole measuring 6.4 cm × 2.8 cm × 2 cm and entire surface showed closely placed multiple tiny nodularities measuring <0.2 cm. Further × 40 and × 100 of H and E stained section showed hepatocytes arranged in cords of 1–2 cell thick, separated by congested sinusoids filled with nucleated red blood corpus cells and hematopoietic cells. The portal triad showed bile ductules, hepatic arteriole, and venule. Central vein appeared congested. No features of cirrhosis, necrosis, fibrosis or interface hepatitis, or periportal infiltrates were noted. Moreover, findings were consistent with congested liver [Figure 4]a and [Figure 4]b. Many classifications are available to grade EA, but we had taken a modified version of BDC to classify EA during the morphological examination of the heart. The degree of leaflet tethering to the ventricular wall was calculated according to their extension by BDC: grade I up to 25% of the distance from the atrioventricular junction to the apex, Grade II from 25% to 50%, Grade III >50% of the distance. In this case, morphologically, Grade III EA was observed.[4] Echocardigraphic prognostic score was calculated as score ratio of the combined area of the right atrium and atrialized RV to that of functional RV in four-chamber view at end diastole as Grade 4 (1.68; ratio >1.5 prognostic score very poor and 100% mortality likely).[5]{Figure 1}{Figure 2}{Figure 3}{Figure 4}

 Discussion



A German physician Wilhelm Ebstein reported EA in 1866 in a 19-year-old laborer with severe TV regurgitation.[1],[2] EA is rare but not uncommon occurs in about 1–5 in 200,000 live births and accounts for 3%–7% of congenital heart disease in the fetus.[3] EA is the result of the failure of delamination of the TV leaflets from the interventricular septum, resulting in adherence of the leaflets to the underlying myocardium, and further characterized by downward displacement of the functional annulus, dilation of atrialized portion of RV, redundancy, fenestrations, and tethering of TV leaflet. The malformed TV is usually regurgitant, but may rarely be stenotic. This anomaly may show various ultrasonographic manifestations, thus making the prenatal diagnosis sometimes difficult, especially valves are not visible.[6] TV dysplasia, a rare congenital TV malformation, characterized by leaflet deformation, most often which is attached to the annulus level and can easily differentiate from EA. However, sometimes, identifying these two entities by fetal echo alone may be difficult.[1],[2],[3] The difference between the two groups is largely academic in terms of functional effects. Genetic bases of this congenital heart defect may be related to the mutations in myosin heavy chain NKX2.5.[7]

Possible pathophysiology

In the context of displacement of the TV and severe TR in our case, lack of antegrade flow across the pulmonary valve leads to retrograde duct flow, which increases afterload on the RV. Meanwhile, the chronic volume overload from TR leads to RV dilatation and because TR favors the high-capacitance systemic venous circuit, the RV fails to generate adequate pressure which were found to be significantly associated with adverse outcome. Reason behind the left ventricular (LV) compression in the echo findings could be right-sided dilation and may cause ineffective LV loading and inadequate systemic cardiac output from direct compression. Meanwhile, cardiomegaly may restrict pulmonary growth and lead to deleterious cardiorespiratory interactions, particularly in the postnatal setting. Development of pulmonary valve regurgitation (PR) serves as the final insult that completes the circular shunt.

Predictors of poor outcome

Lack of antegrade flow across the pulmonary valve (PV) or retrograde duct flow seen in this case was considered as the most important markers of mortality risk. The relationship between mortality and TV annulus diameter z-score, presence of PR, and hydrops at the time of diagnosis could be more powerful hemodynamic indicator of risk and worse prognosis which were seen at our 20-week gestational echo screening. Grade III TV displacement and severe cardiomegaly with hydrops in early gestation can also predict fetal loss. The prognosis for a fetal diagnosed EA has been extremely poor in the past with a reported mortality rate as high as 81%.[8] In the fetus with severe TR may lead to cardiomegaly, hydrops, and arrhythmia, with demise rates as high as 48%.[9] In such cases, early safe termination can be advised.

Few studies focused on the lack of antegrade flow across the pulmonary valve or retrograde duct flow and low RV pressure, were found to be significantly associated with adverse outcome and most important markers of mortality risk in EA.[10] EA can be associated with aneuploidy, and chromosomal errors can be 50% with EA. Fetal demise or neonatal death was more pronounced when there was a moderate-to-severe TR, hydrops, and pericardial effusion.[7],[8] Selamet Tierney et al. designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, LV dysfunction, or TV annulus Z-score > 5.6, and presentation age <24 GA. Another study had revealed that perinatal mortality is higher if TV annulus diameter Z-score 6.8 ± 3.0, moderate TR, and jet V max >200 cm/s.[11] Arrhythmia and fetal hydrops are also possible fetal manifestations of EA.[12] In addition, 25% of patients with EA also present with Wolf-Parkinson-White preexcitation syndrome.[13] In our case, no arrhythmia observed and PR interval was normal.

Pathology of specimens

Gross description of both lobe of the liver was congested and enlarged secondary to severe heart failure. Entire surface of the liver showed closely placed multiple tiny nodularities and the cause of this unusual nodulaties yet to be answered and we had ruled out other possible differential diagnosis of nodular liver such as cirrhosis, nodular regenerative hyperplasia, hepatocellular carcinoma, necrosis, fibrosis or interface hepatitis, or periportal infiltrates were especially overlooked in the histopathology studies [Figure 3]a. Authors presume that it could be the result of massive retention of blood secondary to severe heart failure. Fetal lung in canalicular phase of development, was corresponding to 16–24 weeks of gestation; hence, the possibility of lung hypoplasia with decreased bronchoalveolar development in EA were ruled out, though the volume of lung was much less and impressed as bilateral lung hypoplasia by 2-D echocardiogram and autopsy study [Figure 1]e and [Figure 2]a, [Figure 2]b. Growth restriction of the lungs may happen by compression of dilated heart evidenced by the lace-like appearance of medial border of the lungs [Figure 2]c and [Figure 2]d. It can eventually go into lung hypoplasia as the gestational age increases yet to be studied. Transplacental digoxin therapy may be helpful to control heart failure and effusion, and subsequently can reduce the severity of hydrops. The prenatal diagnosis of EA and its severity is essential in future because the outcomes of surgical and conservative management have improved a great deal in the current era.[14]

 Conclusion



Fetal echocardiogram is an essential diagnostic tool for the early detection of EA and its severity. The histopathology studies proved that lung hypoplasia may not be a feature of EA, but severe cardiomegaly and effusion can restrict the lung growth in later gestation. Looking at the routine essential echo parameters in the diagnosis of EA such as, cardiothoracic ratio, severity of TR, TV annulus diameter z score, pulmonary valve regurgitation, ductal reversal flow, no antegrade PV flow, pericardial effusion, hydrops, and fetal arrhythmia would be helpful in predicting severity and outcome, even intrauterine death, warranted for safe termination.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgment

The authors would like to thank Dr. G Sulochana, visiting Senior Consultant Pathologist, International Centre for Cancer Research Institute, Parumala, Mannar, Kerala, for evaluating histopathology slides and for discussions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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