Ebstein’s anomaly in children and adults: multidisciplinary insights into imaging and therapy

Embriology and anatomy

Ebstein’s anomaly (EA) is a congenital valvular and ventricular dysplasia of the right-sided heart, frequently associated with left-sided heart anomalies.1 2 EA results from incomplete delamination of the tricuspid valve (TV) from the right ventricular (RV) endocardium, which occurs between the 7th and 12th week of intrauterine life.3 During this process, the innermost layer of the ventricular wall separates from the underlying tissue, forming TV leaflets and tendinous chordae. Genetics and environmental factors supposed to be involved in EA pathogenesis are provided in online supplemental material (section A, table 1).

Impaired fibrous transformation from the muscular precursor results in adherence of TV components to the RV wall, thus causing an apical displacement of the septal leaflet (SL) hinge point.1 The same pathological process may involve the posterior leaflet (PL) while less frequently the anterior leaflet (AL), due to a supposed different embryology.1 3 Leaflets may adhere to the endocardium either directly, through linear (figure 1A, C and D; online supplemental video 1) or focal attachments (online supplemental ideo 2), or indirectly, through accessory fibrous chordae or muscular stumps (figure 1C and D; Online supplemental video 1).1

Leaflets adherence to RV wall determines two key EA anatomopathological features: (1) the TV effective orifice separates from the anatomical annulus and rotates towards the right ventricular outflow tract (RVOT) of a degree which depends on the extension of the delamination defect (figure 1C and D)4; (2) the myocardial wall above the effective TV orifice is ‘atrialized’ (figure 1A, C and D), thus rendering EA a ‘RV myopathy’ beyond a valve disease.1 5

The atrialized RV (aRV) lacks of myocardial fiber concentration and presents reduced wall thickness (figure 1A, C and D). The part of RV responsible for stroke volume (SV) generation is the functional RV (fRV), which extends from the effective TV orifice to the pulmonary valve (figure 1B, C and D).1 5 The combination of aRV and fRV identifies the anatomical RV (ARV).

Multimodality imaging

The quantitative criterion for EA diagnosis is an apical displacement of the SL hinge point by at least 8 mm/m² from the anterior mitral leaflet insertion, assessed in four-chamber view1 6 (figure 1B). An absolute distance in atrioventricular valves offsetting of 15 mm in children and 20 mm in adults is also considered diagnostic.7 Multimodality imaging is pivotal not only for anatomical and functional assessment of TV and right-sided chambers but also for identifying associated lesions (online supplemental material, section B

Transthoracic echocardiography (TTE) is usually the first diagnostic tool. Second-line imaging includes transoesophageal echocardiography (TOE) and cardiovascular magnetic resonance (CMR), the former with particular usefulness in TV assessment, the latter in right-sided chamber volumes calculation and myocardial characterization. CMR is superior to TTE in the detection of PL and extra-cardiac abnormalities, while TTE reveals small septal communications more frequently.6 Echocardiography and CMR are both recommended for evaluating unoperated patients, informing on progressive disease and anatomies suitable of repair, as well as for monitoring operated patients, revealing surgical results and possible complications (figure 2).8 9

TOE is the fundamental imaging technique in the operation theatre. Cardiac computed tomography may be considered instead of CMR in cases of contraindications or major artefacts in the magnetic field, as well as before planning redo surgeries or ‘valve-in-valve’ replacements.

Over time, various classifications of EA severity had been proposed (figure 3). In patients older than 10 years, the CMR-derived total right/left-volume index showed higher association with clinical decompensation compared with Celermajer index and fRV to left ventricle (LV) ratio (figure 3), but revealed no correlation with the occurrence of major cardiovascular events (MACEs).10–12 Imaging parameters predictive of adverse outcome in EA are reported in online supplemental tables 2 and 3.

Clinical manifestations and outcome in unoperated patients

EA is a rare disease, counting 1–2.6 cases per 200 000 of live births (<1% of congenital heart disease).1 25 Clinical presentation after neonatal period has a more favourable outcome than cases diagnosed in earlier life.26 Subjects growing up to adulthood exhibit less severe anatomical abnormalities and, due to high right chambers compliance to volume overload, are usually asymptomatic for a long time.25 27 28 Mean age at diagnosis is around 14 years among children and 20–35 years in adults.25 26 New York Heart Association (NYHA) class I or II characterises the majority of adult patients at diagnosis.28 Arrhythmias are the most common clinical manifestation both in children and in adults, being a possible cause of NYHA class deterioration.25 28 Typical electrocardiographic and arrhythmic profiles of patients with EA are detailed in online supplemental material (sections C and D, respectively).

Right-to-left shunt may lead to chronic hypoxia and exertional cyanosis, while rest cyanosis is more common during infancy.26 Cerebrovascular embolic events, as assessed in around 8%–10% of cases, are attributable to either paradoxical embolization or atrial fibrillation occurrence.26 28 Endocarditis is rare and favoured by device implantation or surgery.26 29 Figure 5 illustrates distinctive EA symptoms and their physiological substrates.

Contemporary survival at 10 years from the diagnosis or at an age of 60 years old is assessed ≥80% among unoperated subjects.25 30 Causes of death are principally related to HF (40%) and arrythmias (20%).28 30 In a cohort of unoperated adults, sudden death (SD) had been reported in 23% of cases.28 Clinical and instrumental features associated with unfavourable clinical outcome are reported in online supplemental table 2.