Ebstein's anomaly in an infant: Case report and literature review

 Corresponding author: Akhil Mehrotra Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Ebstein’s anomaly in an infant: Case report and literature review Akhil Mehrotra 1, *, Mohammad Shaban 2 and Faiz Illahi Siddiqui 2 1 Pediatric and Adult Cardiology, Prakash Heart Station, Nirala Nagar, Lucknow, UP, India. 2 Cardiac Technician, Prakash Heart Station, Nirala Nagar, Lucknow, UP, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 Publication history: Received on 29 January 2025; revised on 07 March 2025; accepted on 10 March 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.21.3.0268 Abstract Ebstein’s anomaly is a rare congenital heart defect characterized by apical displacement of the tricuspid valve and reduced volume of the true functional right ventricle. In its most severe form, the disease presents as right heart failure and cyanosis in the infant. Although many of these infants can be managed conservatively, surgical intervention may become necessary in the sickest of them. Surgical intervention in this subgroup can be challenging and requires meticulous appreciation of the anatomy and physiology on a case-to-case basis. Multicenter studies are required to define a uniform algorithm and approach towards these patients. Keywords: Ebstein’s Anomaly; ASD; RV Dysfunction in Ebstein’s Anomaly; Himalayan P Waves On ECG; Severe Tricuspid Regurgitation; DORV; Complete atrio-ventricular canal defect; CAVCD 1. Introduction Ebstein’s anomaly (EA) is a rare congenital cardiac defect with a prevalence of 2.4 per 10,000 live births and accounts for less than 1% of all newly diagnosed congenital disorders [1]. EA is characterized by apical displacement of the tricuspid valve and reduced volume of the true functional right ventricle [2] (Figure 1, 2). World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 260 Figure 1 Diagrammatic illustration. Illustration of a heart with Ebstein's anomaly. The right atrium (RA) is dilated and so is the tricuspid annulus. The septal tricuspid leaflet is apically displaced, and there is a fibromuscular ridge instead (arrow). The coronary sinus (CS) ostium is dilated, and the AV node (AVN) is irregular, and its body can reach the upper border of the CS ostium. ASD, atrial septal defect; aRV, atrialised RV; LA, left atrium; LV, left ventricle; RV, right ventricle Figure 2 Pathologic specimen cut in the 4-chamber plane from a patient with Ebstein anomaly. The tricuspid valve is displaced markedly inferiorly, and the right ventricular wall is extremely thin EA is not just a disorder of the tricuspid valve but also affects the right ventricle (RV) myocardium [3]. It encompasses a wide anatomical spectrum and the disorder can present itself either as cyanosis in the infant or exercise intolerance in the older adult [4, 5]. Symptomatic infants represent a distinct group of very sick patients with serious medical and surgical challenges [6]. Infants with symptomatic Ebstein's anomaly have a poor prognosis, with an expected mortality rate of 50% to 75% [7]. Previous attempts at palliative surgical treatment in this neonatal group have produced equally dismal results [7-9]. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 261 2. Classification of Ebstein anomaly There are several classification systems for Ebstein anomaly. The most commonly used are the Carpentier classification (anatomical classification) (Figure 3) and the Celermajer index or the Great Ormond Street Echocardiography (GOSE) score for neonates. These classification systems are crucial for determining the severity of the Ebstein anomaly. 2.1. Carpentier classification [4] 2.1.1. Type A: mild • Mild apical displacement of the septal and posterior tricuspid valve leaflets • Small "atrialized" ventricle • Adequate function of the functional right ventricle (frv) 2.1.2. Type B: moderate • Moderate apical displacement of the septal and posterior tricuspid valve leaflets • Abnormal attachment of the otherwise freely mobile anterior leaflet • Moderately sized "atrialized" ventricle with reduced function • Reduced volume but adequate function of the FRV 2.1.3. Type C: severe • Severe apical displacement of the septal and posterior tricuspid valve leaflets • Abnormal attachments restricting the mobility of the anterior leaflet and potentially obstructing the right ventricular outflow tract • Large "atrialized" ventricle with reduced function • Small frv 2.1.4. type D: extensive (tricuspid valve sac) • Complete non-delamination of the tricuspid valve leaflets • Multiple abnormal attachments • Almost complete "atrialization" of the right ventricle with the exception of a small insufficient infundibular component. Figure 3 Carpentier classification of Ebsteins anomalyDiagrammatic illustration. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 262 2.2. GOSE scoring system First reported by Celermajer et al [10], the Great Ormond Street Echocardiogram (GOSE) score has important prognostic value in stratifying risk of mortality (Figure 4). 2.3. Mortality prediction based on GOSE score. Figure 4 Gose Score. 2.4. Case Report An 11 month severely breathness and cyanotic female infant was referred to our cardiology OPD for comprehensive color echocardiography and opinion regarding management of cyanotic congenital heart disease. On clinical examination, the child was of average built highly irritable and continuously crying (Figure 5). There was significant central cyanosis present, which was increasing on crying. Figure 5 Facial appearance of our index patient The infant’s weight was 6.6 kg, height was 64 cm, BP was 80/60 mmHg, HR was 110/min, respiratory rate was 26/min and SPO2 was 77% at room air and 97 % on continuous oxygen. All the peripheral pulses were normally palpable without any radio-femoral delay. Cardiovascular examination revealed LVS3 and LVS4 gallop sounds over apex and multiple clicks during systole at left lower sternal edge. Systemic examination was normal. Xray chest (PA) view demonstrated severe cardiomegaly with reduced pulmonary blood flow (Figure 6). World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 263 Figure 6 X-ray chest PA view depicting severe cardiomegaly with reduced pulmonary blood flow 2.4.1. Resting ECG exhibited the following features (Figure 7): • Himalayan P waves in L1, L2, AVF, V3-V6 • QRS axis of + 120°. • Sinus tachycardia which ventricular rate of 132/min. Figure 7 Resting ECG exhibited Himalayan P waves in leads L1, L2, AVF, V3-V6, QRS axis of +120°, and sinus tachycardia with ventricular rate of 132/min; Black arrows pointing towards Himalayan P waves 2.5. Transthoracic Echocardiography All echocardiography evaluations were performed by the author, using My Lab X7 4D XStrain echocardiography machine, Esaote, Italy. The images were acquired using a pediatric probe equipped with harmonic variable frequency electronic single crystal array transducer while the subject was lying in supine and left lateral decubitus positions. Conventional M-mode, two-dimensional, pulse wave doppler (PWD), continuous wave doppler (CWD) and sequential segmental transthoracic echocardiography was performed in the classical subcostal, parasternal long axis (LX), parasternal short axis (SX), 4-Chamber (4CH), 5-Chamber (5CH) and suprasternal views. 2.6. M-mode Echocardiography M-mode echocardiography of left and right ventricle was implemented for estimating various ventricular parameters (Table 1, Figure 8). World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 264 Table 1 Calculations of M-mode echocardiography. Measurements RV LV IVS d 5.5 mm 5.2 mm ID d 18.1 mm 20.5 mm PW d 6.4 mm 5.5 mm IVS s 5.8 mm 7.0 mm ID s 16.5 mm 12.2 mm PW s 8.6 mm 13.2 mm EF 20 % 74 % %FS 8 % 40 % EDV 9.8 ml 13.6 ml ESV 7.8 ml 3.5 ml SV 2.0 ml 10.0 ml Mass 18 g 19 g IVS, interventricular septum, ID, internal dimension; PW, posterior wall, d, diastole; s, systole; FS, fractional shortening; EDV, end-diastolic volume; ESV, end systolic volume; SV, stroke volume; EF, ejection fraction. Figure 8 M-mode echocardiography (A) M-mode RV estimations; (B) M-mode LV estimations 2.7. Summary of M-mode echocardiography mode echocardiography depicted dilated FRV with severely reduced FRV EF (20 %). On the contrary the LV showed normal dimensions and LVEF (74 %) World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 265 3. 2-Dimensional-Transthoracic Echocardiography 2Dimensional transthoracic echocardiography (TTE) was conducted in explicit detail and it demonstrated typical features of EA: • Apical displacement of the TV (Figure 9). • Apical displacement and dilation of TV annulus (Figure 9). • Septal TV leaflet (STVL) was rudimentary and adhered to the ventricular septum (Figure 9). • STVL was displaced by 27.2 mm from MV insertion (Figure 9). • Anterior TV leaflet (ATVL) was large, sail like, redundant and attached to the AV junction (Figure 9). (A) (B) Figure 9 Transthoracic echocardiography. (A) and (B) demonstrates apically displaced rudimentary septal leaflet and large, sail like and redundant anterior leaflet of TV in apical 4C view. FRV, functional right ventricle; TV, tricuspid valve; AML, anterior mitral leaflet; LV, left ventricle; mv, mitral valve. • Huge dilatation of RA (atrialized RV). The area of atrialized RV was 11.22 sqcm (Figure 10). • Dilated FRV. The area of FRV was 9.03 sqcm (Figure 10). (A) (B) Figure 10 (A) 4C view showing huge RA (atrialized RV) with an area of 11.23 sqcm; (B) FRV is dilated having an area of 9.03 sqcm; TV, tricuspid valve; FRV, functional right ventricle; SL, septal leaflet; LV, left ventricle; MV, mitral valve; S, septal leaflet; A, anterior leaflet World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 266 • Moderate ostium secundum ASD of size 4.5 mm with right to left shunt (Figure 11). (A) (B) Figure 11 (A) Moderate size ostium secundum ASD detected in the subcostal view; (B) Right to left shunt across ASD. ra, right atrium; rv, right ventricle; lv, left ventricle; mv, mitral valve; la, left atrium • Severe TR with a jet area of 9.67 sqcm, occupying nearly whole of RA with a TR velocity of 2.6 m/sec (Figure 12). (A) (B) Figure 12 (A) On color flow mapping, a severe TR jet with an area of 8.54 sqcm is clearly demarcated in the apical 4C view; (B) On continuous wave doppler analysis across TV valve, a TR jet with a peak velocity of 2.70 m/sec (gradient 29.2 mmHg). TR, tricuspid regurgitation; RV, right ventricle; RA, right atrium; VS, ventricular septum; LV, left ventricle 3.1. Summary of Color echocardiography On transthoracic color echocardiography, classical features of EA were displayed. According to the Carpentier’s classification our index patient was Type C, even though the FRV was dilated with severely reduced RV systolic function (FRV EF 20 %). Subsequently, the patient’s attendants were advised immediate surgical correction of EA and the infant was referred to a tertiary care pediatric cardiovascular institute. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 259-273 267 4. Discussion EA is a rare congenital cardiac abnormality involving the tricuspid valve and the right ventricle (RV) [11]. Ebstein anomalies comprise < 1% of congenital heart defects [12]. The anomaly was initially described by the pathologist Wilhelm Ebstein in 1866 after performing an autopsy on a 19-year-old cyanotic male with exertional dyspnea and palpitations who died of a sudden cardiac arrest [13]. 4.1. Associated Anomalies [2] Abnormalities commonly associated with Ebstein anomaly include: • Secundum atrial septal defect • Variable degree of RV outflow tract obstruction. • Functional or anatomical pulmonary atresia • Ventricular septal defects, tetralogy of Fallot • Transposition of the great arteries • Atrioventricular canal defects. In general, the clinical manifestations of Ebstein anomaly can range from asymptomatic to severe, depending on the degree of tricuspid valve displacement and severity of regurgitation, the effective right ventricular volume, and the associated malformations [14]. Atrial tachycardias, including atrial fibrillation, atrial flutter, or ectopic atrial tachycardia, can occur in 25% to 65% of patients with Ebstein anomaly. Additionally, 10% to 25% of patients have one or more accessory pathways, which increase the risk of protracted arrhythmias that can produce cardiac failure and sudden cardiac death [15, 16]. 4.2. Etiopathogenesis Ebstein anomaly is thought to be associated with chromosome 15q duplications during embryological cardiac development. There are also case reports suggesting a possible association of Ebstein anomaly with chromosome 11q rearrangements. Other reports indicate an association between Ebstein malformation and mutations in MYH7; MYH7 mutations are frequently associated with cardiomyopathies [17, 18]. Another known association of Ebstein anomaly is the teratogenic effect of lithium. Case-control and cohort studies of pregnant women taking lithium in the 1970s and 1980s demonstrated a risk of Ebstein anomaly in < 2% of their newborns [19]. Ebstein anomaly has also been associated with maternal exposure to benzodiazepines and varnishing materials [16, 20]. 4.3. Epidemiology Ebstein anomaly accounts for 0.3% to 0.6% of all congenital heart defects and is reported to occur in 0.2 to 0.7 per 10,000 live births [21]. Most cases of Ebstein anomaly are sporadic, with no identifiable etiology. Some studies suggest that there may be a familial inheritance, as has been observed in monozygotic twins [22]. There is a higher incidence of recurrence in the offspring of affected women (6%) than in the offspring of affected men (1%) [23]. 4.4. Pathophysiology 4.4.1. Anatomic Abnormalities The main pathophysiological abnormality of Ebstein anomaly is the failure of delamination of the tricuspid valve leaflets from the interventricular septum in utero [24]. The apical displacement mainly affects the posterior and septal leaflets, leading to the apical displacement of the tricuspid annulus and anteroapical displacement of the tricuspid orifice [3, 22] (Figure 13).