Molecular Pathways and Animal Models of Ebstein's Anomaly.

Ebstein's anomaly is a congenital malformation of the tricuspid valve characterized by abnormal attachment of the valve leaflets, resulting in varying degrees of valve dysfunction. The anatomic hallmarks of this entity are the downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Additional intracardiac malformations are common. From an embryological point of view, the cavity of the future right atrium does not have a direct orifice connected to the developing right ventricle. This chapter provides an overview of current insight into how this connection is formed and how malformations of the tricuspid valve arise from dysregulation of molecular and morphological events involved in this process. Furthermore, mouse models that show features of Ebstein's anomaly and the naturally occurring model of canine tricuspid valve malformation are described and compared to the human model. Although Ebstein's anomaly remains one of the least understood cardiac malformations to date, the studies summarized here provide, in aggregate, evidence for monogenic and oligogenic factors driving pathogenesis.

Effect of concomitant atrial septal defect on left ventricular function in adult patients with unrepaired Ebstein's anomaly: a cardiovascular magnetic resonance imaging study.

BACKGROUND: Due to the heterogeneity of anatomic anomalies in Ebstein's anomaly (EA), particularly in the subset of patients with atrial septal defect (ASD), hemodynamic changes, which ultimately cause left ventricular (LV) deterioration remain unclear. The current study aimed to investigate the effect of concomitant ASD on LV function using cardiovascular magnetic resonance (CMR) imaging in patients with EA. METHODS: This study included 31 EA patients with ASD, 76 EA patients without ASD, 35 patients with simple ASD and 40 healthy controls. Left/right ventricular (RV, the RV was defined as a summation of the functional RV and atrialized RV in EA patients) volumes and functional parameters, LV strain parameters, and echocardiogram indices were compared among the four groups. Associations between variables were evaluated via Spearman or Pearson correlation analyses. The association between risk factors and LV ejection fraction (EF) was determined via multivariate linear regression analysis. RESULTS: Both EA patients and ASD patients had a higher RV/LV end-diastolic volume (RVEDV/LVEDV) as well as lower LV and RV ejection fractions (LVEF/RVEF) compared to healthy controls (all p < 0.05). Moreover, the EA patients with ASD had a significantly higher RVEDV/LVEDV and a lower LVEF and RVEF than those without ASD (all p < 0.05). Multivariate linear regression analysis revealed that the presence of ASD was independently associated with LVEF (ß = - 0.337, p < 0.001). The RVEDV/LVEDV index was associated with LVEF (r = - 0.361, p < 0.001). Furthermore, the LV longitudinal peak diastolic strain rate (PDSR) was lower in EA patients with ASD than those without ASD, patients with simple ASD, and healthy controls (p < 0.05). CONCLUSION: Concomitant ASD is an important risk factor of LV dysfunction in patients with EA, and diastolic dysfunction is likely the predominate mechanism related to LV dysfunction.

Altered contractility, Ca2+ transients, and cell morphology seen in a patient-specific iPSC-CM model of Ebstein's anomaly with left ventricular noncompaction.

Patients with two congenital heart diseases (CHDs), Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The genetic etiology and pathogenesis of combined EA/LVNC remain largely unknown. We investigated a familial EA/LVNC case associated with a variant (p.R237C) in the gene encoding Kelch-like protein 26 (KLHL26) by differentiating induced pluripotent stem cells (iPSCs) generated from affected and unaffected family members into cardiomyocytes (iPSC-CMs) and assessing iPSC-CM morphology, function, gene expression, and protein abundance. Compared with unaffected iPSC-CMs, CMs containing the KLHL26 (p.R237C) variant exhibited aberrant morphology including distended endo(sarco)plasmic reticulum (ER/SR) and dysmorphic mitochondria and aberrant function that included decreased contractions per minute, altered calcium transients, and increased proliferation. Pathway enrichment analyses based on RNASeq data indicated that the "structural constituent of muscle" pathway was suppressed, whereas the "ER lumen" pathway was activated. Taken together, these findings suggest that iPSC-CMs containing this KLHL26 (p.R237C) variant develop dysregulated ER/SR, calcium signaling, contractility, and proliferation.NEW & NOTEWORTHY We demonstrate here that iPSCs derived from patients with Ebstein's anomaly and left ventricular noncompaction, when differentiated into cardiomyocytes, display significant structural and functional changes that offer insight into disease pathogenesis, including altered ER/SR and mitochondrial morphology, contractility, and calcium signaling.

A rare combination of Ebstein's anomaly with left ventricular outflow tract obstruction.

We describe a rare case of Ebstein's anomaly (EA) combined with left ventricular outflow tract obstruction in a 54-year-old man that was accurately identified by echocardiography, cardiac magnetic resonance imaging (CMR). The imaging result was ultimately validated by surgery. We emphasize the clinical importance of using echocardiography and CMR together to provide a thorough, noninvasive explanation of these results.

Cardiac remodeling after tricuspid valve repair in Ebstein's anomaly: a magnetic resonance study.

OBJECTIVES: We aimed to evaluate immediate and midterm cardiac remodeling after surgery by cardiac magnetic resonance (CMR) in Ebstein's anomaly (EA), and also to investigate preoperative predictors of right ventricular (RV) normalization. METHODS: We retrospectively analyzed CMR parameters of the whole heart in adult patients with EA before surgery, at discharge and follow-up. RESULTS: A total of 26 patients were included and performed CMR at 7 days (interquartile range, 3-13 days) before surgery. Immediate postoperative CMR was finished at discharge (median: 8 [7-9] days; n = 18) and follow-up CMR at 187 days (interquartile range, 167-356 days; n = 17). RV and right atrial (RA) volumes promptly decreased immediately after surgery and at follow-up (all p < 0.05). RV ejection fraction decreased significantly at discharge (p < 0.05) but recovered at follow-up (p = 0.18). However, RV global longitudinal strain and RA reservoir strain were significantly impaired immediately and midterm after surgery (all p < 0.05). Indexed left ventricular (LV) end-diastolic volume, stroke volume, as well as global longitudinal strain increased from preoperative to follow-up (all p < 0.05). Patients who achieved normalization of RV volumes after surgery had smaller severity index and RV and RA volumes and higher LV ejection fraction and RA reservoir strain at baseline than patients without RV normalization (all p < 0.05). CONCLUSIONS: Reverse biventricular remodeling took place in EA after tricuspid valve surgery. Tricuspid valve reconstruction should be performed before deterioration of RV volume overload and LV function to achieve reverse RV remodeling. Key Points • After removing the volume load of tricuspid regurgitation in Ebstein's anomaly, reverse remodeling was detected by CMR in both left and right heart at midterm follow-up. • Tricuspid valve reconstruction should be performed before deterioration of RV volume overload and LV function to achieve reverse RV remodeling.

Inadvertent irreversible closure of arterial duct following therapeutic use of transplacental indomethacin in a fetus with severe Ebstein's anomaly and circular shunt.

We report on a fetal case of Ebstein's anomaly with severe tricuspid regurgitation, functional pulmonary atresia and progressive circular shunting (CS) across a widely patent ductus arteriosus (DA) and regurgitant pulmonary valve, contributing to significant systemic hypoperfusion. To mitigate the extent of CS and allow the pregnancy to continue, maternal non-steroidal anti-inflammatory drug (NSAID) therapy with indomethacin was started at 33 + 5 weeks to induce DA constriction. Rather than achieving the desired narrowing of the DA, the treatment led to its complete closure and only minimal antegrade flow across the pulmonary valve. While closure of the DA resulted in the anticipated improvement in fetal hemodynamics, at birth, the child was at risk of severe hypoxemia and its consequences due to the lack of adequate pulmonary perfusion. Reduction and eventual discontinuation of the NSAID treatment did not result in DA reopening. Our experience illustrates the risk of unintended irreversible DA closure when NSAIDs are used to treat CS. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Histological examination of the potential arrhythmic substrates in the setting of Ebstein's malformation.

Cardiac arrhythmias, notably Wolff-Parkinson-White syndrome, are known to represent a major issue in patients with Ebstein's malformation of the tricuspid valve. Abnormal conducting circuits, however, can also be produced by pathways extending either from the atrioventricular node or the ventricular components of the atrioventricular conduction axis, direct to the crest of the muscular ventricular septum. We hoped to provide further information on the potential presence of such pathways by investigations of six autopsied examples of Ebstein's malformation. All were studied by histological sectioning on the full extent of the atrioventricular conduction axis, with limited sectioning of the right atrioventricular junction supporting the inferior and antero-superior leaflets of the deformed tricuspid valve. We used the criteria established by Aschoff (Verhandlungen der Deutschen Gesellschaft für Pathologie, 14, 1910, 3) and Mönckeberg (Verhandlungen der Deutschen Gesellschaft für Pathologie, 14, 1910, 64) over a century ago to define abnormal connections across the atrioventricular junctions, as these definitions retain their validity for the identification of gross myocardial connections across the insulating tissues of the atrioventricular junctions. In one specimen, we found two discrete accessory myocardial connections across the parietal right atrioventricular junction. In all of the hearts, we found so-called nodoventricular connections, and in one heart we also observed a well-formed connection originating from the penetrating atrioventricular bundle. In addition to accessory myocardial connections across the parietal right atrioventricular junction, therefore, our histological findings demonstrate a potential role for direct connections between the atrioventricular conduction axis and the ventricular myocardium in the setting of Ebstein's malformation.

Novel KLHL26 variant associated with a familial case of Ebstein's anomaly and left ventricular noncompaction.

BACKGROUND: Ebstein's anomaly (EA) is a rare congenital heart disease of the tricuspid valve and right ventricle. Patients with EA often manifest with left ventricular noncompaction (LVNC), a cardiomyopathy. Despite implication of cardiac sarcomere genes in some cases, very little is understood regarding the genetic etiology of EA/LVNC. Our study describes a multigenerational family with at least 10 of 17 members affected by EA/LVNC. METHODS: We performed echocardiography on all family members and conducted exome sequencing of six individuals. After identifying candidate variants using two different bioinformatic strategies, we confirmed segregation with phenotype using Sanger sequencing. We investigated structural implications of candidate variants using protein prediction models. RESULTS: Exome sequencing analysis of four affected and two unaffected members identified a novel, rare, and damaging coding variant in the Kelch-like family member 26 (KLHL26) gene located on chromosome 19 at position 237 of the protein (GRCh37). This variant region was confirmed by Sanger sequencing in the remaining family members. KLHL26 (c.709C > T p.R237C) segregates only with EA/LVNC-affected individuals (FBAT p < .05). Investigating structural implications of the candidate variant using protein prediction models suggested that the KLHL26 variant disrupts electrostatic interactions when binding to part of the ubiquitin proteasome, specifically Cullin3 (CUL3), a component of E3 ubiquitin ligase. CONCLUSION: In this familial case of EA/LVNC, we have identified a candidate gene variant, KLHL26 (p.R237C), which may have an important role in ubiquitin-mediated protein degradation during cardiac development.

Examination of pathologic features of the right atrioventricular groove in hearts with Ebstein anomaly and correlation with arrhythmias.

BACKGROUND: Catheter ablation of accessory pathways (APs) in patients with Ebstein anomaly (EA) has a higher recurrence rate than in subjects with normal hearts. Anatomic features could account for suboptimal ablation outcomes. OBJECTIVE: The purpose of this study was to examine the right atrioventricular (AV) groove in autopsy hearts with EA, correlate with clinical data, and identify features relevant for catheter ablation. METHODS: Thirty-three specimens with EA from our Cardiac Registry were examined. The right AV groove was inspected for gross anatomic features. Limited microscopy was performed on selected specimens. Premortem clinical data were correlated with anatomic findings. RESULTS: A prominent ridge along the right AV groove was seen in 15 of 33 specimens (45%). Ten specimens had a clinical history of AP (AP+). The extent of ventricular atrialization did not differ between AP+ and AP- groups (64 ± 63 mm/m2 vs 76 ± 42 mm/m2; P = .61), nor did the presence of visible macroscopic AV tissue connections (45% vs 51%; P = .68). The single item that differed was the presence of an AV groove ridge itself, which was significantly more common in the AP+ group (70% vs 21%; P = .03). Microscopy of ridge tissue revealed a muscular bundle in 1 AP+ specimen penetrating deep into the fibrous AV annulus that was suggestive of an AP, although complete muscular continuity was not verified in the limited sections available for examination. CONCLUSION: A prominent ridge along the inferior right AV groove is a common feature in EA and correlates with clinical history of AP. It presents a potential obstacle to catheter ablation and may contribute to recurrence rate.

Ebstein's Anomaly of the Tricuspid Valve: A Natural Laboratory for Re-Entrant Tachycardias.

Ebstein's anomaly of the tricuspid valve is a relatively rare form of congenital heart disease that has long been a challenge to electrophysiologists and cardiac surgeons. In addition to the hemodynamic burden of the actual valve defect, Ebstein's patients must also contend with an extraordinarily high incidence of tachyarrhythmias, most of which can be attributed to accessory atrioventricular pathways (APs) located along the posterior and septal border of the tricuspid valve where the valve leaflets are most abnormal. It is the only congenital heart defect with such a dramatic predisposition toward APs. Although it is logical to postulate a link between the anatomic deformity and the conduction abnormality, the exact nature of this link is still not fully understood and remains a fertile area for investigation that might shed light on abnormal conduction pathways in many other forms of heart disease. Furthermore, for reasons that are only now being fully appreciated, successful catheter ablation of APs in this setting is frequently more challenging than would be expected in a structurally normal heart. This review will explore the gross and microscopic anatomy of Ebstein's anomaly with attention to features that could be important to both arrhythmogenesis and ablation therapy in this unique population.

Cardiovascular magnetic resonance evidence of myocardial fibrosis and its clinical significance in adolescent and adult patients with Ebstein's anomaly.

BACKGROUND: Myocardial fibrosis is a common pathophysiological process that is related to ventricular remodeling in congenital heart disease. However, the presence, characteristics, and clinical significance of myocardial fibrosis in Ebstein's anomaly have not been fully investigated. This study aimed to evaluate myocardial fibrosis using cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and T1 mapping techniques, and to explore the significance of myocardial fibrosis in adolescent and adult patients with Ebstein's anomaly. METHODS: Forty-four consecutive patients with unrepaired Ebstein's anomaly (34.0 ± 16.2 years; 18 males), and an equal number of age- and gender-matched controls, were included. A comprehensive CMR protocol consisted of cine, LGE, and T1 mapping by modified Look-Locker inversion recovery (MOLLI) sequences were performed. Ventricular functional parameters, native T1, extracellular volume (ECV), and LGE were analyzed. Associations between myocardial fibrosis and disease severity, ventricular function, and NYHA classification were analyzed. RESULTS: LGE was found in 10 (22.7%) patients. Typical LGE in Ebstein's anomaly was located in the endocardium of the septum within the right ventricle (RV). The LV ECV of Ebstein's anomaly were significantly higher than those of the controls (30.0 ± 3.8% vs. 25.3 ± 2.3%, P < 0.001). An increased ECV was found to be independent of the existence of LGE. Positive LGE or higher ECV (≥30%) was associated with larger fRV volume, aRV volume, increased disease severity, and worse NYHA functional class. In addition, ECV was significantly correlated with the LV ejection fraction (P <  0.001). CONCLUSIONS: Both focal and diffuse myocardial fibrosis were observed in adolescent and adult patients with Ebstein's anomaly. Increased diffuse fibrosis is associated with worse LV function, increased Ebstein's severity, and worse clinical status.

Ebstein Anomaly and Sudden Childhood Death.

A 13-year-old girl is reported who died suddenly and unexpectedly in her sleep from previously undiagnosed Ebstein anomaly. At autopsy, there was dilatation of the right atrium with marked dilatation of the right auricle and apical displacement of the tricuspid valve into the right ventricular cavity with atrialization of the upper portion of the right ventricle. There were also prominent dysplastic changes in both the septal and posterior leaflets of the tricuspid valve with thickening of the valve and fusion of leaflets to the wall of the ventricle. Histology of the myocardium showed focal, minor microscopic areas of interstitial fibrosis with marked fibrous dysplasia and thickening of the tricuspid valve. Lethal arrhythmias occur in this condition because of the geographical relationship of the conduction system to the abnormal anatomical structures. As adolescents who died suddenly are often minimally symptomatic, cases will rarely present de novo to forensic autopsy.

Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation.

Left ventricular non-compaction (cardiomyopathy) (LVN(C)) is a rare hereditary cardiac condition, resulting from abnormal embryonic myocardial development. While it mostly occurs as an isolated condition, association with other cardiovascular manifestations such as Ebstein anomaly (EA) has been reported. This congenital heart defect is characterized by downward displacement of the tricuspid valve and leads to diminished ventricular size and function. In an autosomal dominant LVN(C) family consisting of five affected individuals, of which two also presented with EA and three with mitral valve insufficiency, we pursued the genetic disease cause using whole exome sequencing (WES). WES revealed a missense variant (p.Leu113Val) in TPM1 segregating with the LVN(C) phenotype. TPM1 encodes α-tropomyosin, which is involved in myocardial contraction, as well as in stabilization of non-muscle cytoskeletal actin filaments. So far, LVN(C)-EA has predominantly been linked to pathogenic variants in MYH7. However, one sporadic LVN(C)-EA case with a de novo TPM1 variant has recently been described. We here report the first LVN(C)-EA family segregating a pathogenic TPM1 variant, further establishing the association between EA predisposition and TPM1-related LVN(C). Consequently, we recommend genetic testing for both MYH7 and TPM1 in patients or families in which LVN(C)/non-compaction and EA coincide.

Familial Ebstein Anomaly: Whole Exome Sequencing Identifies Novel Phenotype Associated With FLNA.

BACKGROUND: Familial Ebstein anomaly is a rare form of congenital heart disease. We report 7 individuals among 2 generations of 1 family with Ebstein anomaly. This family was first reported in 1991 by Balaji et al in which family members were also reported to have a mild skeletal phenotype. The most likely mechanism of inheritance was concluded to be autosomal dominant. We sought to identify the genetic pathogenesis in this family using a next generation sequencing approach. METHODS AND RESULTS: Whole exome sequencing was performed in 2 cousins in this family using the Agilent SureSelect Human all Exon 51 Mb version 5 capture kit. Data were processed through an analytic in-house pipeline. Whole exome sequencing identified a missense mutation in FLNA (Filamin A), an actin-binding protein located at Xq28, mutations in which are associated with the skeletal phenotypes Frontometaphyseal dysplasia, Otopalatodigital, and Melnick-Needles syndrome, with X-linked periventricular nodular heterotopia and FG syndrome (Omim, 305450). Review of the phenotypes of those with the mutation in this family shows increased severity of the cardiac phenotype and associated skeletal features in affected males, consistent with X-linked inheritance. CONCLUSIONS: Although congenital heart disease is reported in families with mutations in FLNA, this is the first report of individuals being affected by Ebstein anomaly because of a mutation in this gene and details the concurrent skeletal phenotype observed in this family.

EBSTEIN ANOMALY IN THE TSUSHIMA LEOPARD CAT (PRIONAILURUS BENGALENSIS EUPTILURUS).

Ebstein anomaly is a rare congenital heart disease that has been described in domestic dogs, a meerkat, a pygmy goat, and a lion. An 11-mo-old Tsushima leopard cat presented to Osaka Prefecture University Veterinary Hospital for diagnosis and treatment of right-sided congestive heart failure. Echocardiography showed a dilated right atrium and ventricle with an enlarged tricuspid valve annulus and apical displacement of the tricuspid valve leaflets. The cat was diagnosed with Ebstein anomaly. To the best of our knowledge, this is the first report of this type of congenital heart disease in a Tsushima leopard cat.

Assessment of left ventricular deformation in patients with Ebstein's anomaly by cardiac magnetic resonance tissue tracking.

PURPOSE: The aim of this study was to clarify the feasibility of myocardial strain using cardiovascular magnetic resonance (CMR) for the evaluation of left ventricular (LV) deformation in patients with Ebstein's anomaly (EA). MATERIALS AND METHODS: We recruited 32 patients with EA and 30 controls for CMR examination and measured LV function, dimension and tissue tracking parameters (the global and regional radial, circumferential and longitudinal peak strain), together with the right ventricle (RV) dimension. LV strain parameters were compared among the controls, patients with preserved LV ejection fraction (LVEF; ≥55%), and patients with reduced LVEF (<55%). Pearson's correlation was used to evaluate relationships between tissue tracking parameters with the RVEDD/LVEDD index and LVEF. An ROC analysis was also performed to determine whether the cut-off values for PS could be used to differentiate LV dysfunction between patients with EA and controls. The intraclass correlation coefficient (ICC) was used to assess the inter- and intra-observer variability. RESULTS: The global strain parameters all decreased significantly in the EA group compared with the control group (all P<0.05). Furthermore, the global radial and circumferential peak strain (PS) were obviously even lower in the reduced LVEF group than the strain measured in preserved LVEF groups (28.64% vs. 37.39%, p<0.05; and -8.20% vs. -17.89%; p<0.05; respectively). The regional strain abnormalities in EA patients were mainly involved in basal and middle segments. The results also demonstrated a significant correlation between the ratio of the RV end-diastolic dimension to the LV end-diastolic dimension (RVEDD/LVEDD index) with the global circumferential PS (r=0.508) and the longitudinal PS (r=0.474), as well as a good correlation between radial PS and LVEF (r=0.465). The ICCs for intra- and inter-observer variability were 0.797-0.904 and 0.701-0.896. CONCLUSIONS: LV strain serves an earlier and more comprehensive measurement of LV dysfunction than LVEF in EA, which could potentially be included as a supplementary diagnostic procedure in the evaluation of EA.

Anomalía de Ebstein «like¼ en doble entrada ventricular. Una rara asociación / Ebstein's "like" anomaly ventricular double inlet. A rare association

Resumen: Introducción y objetivos: La asociación de corazones univentriculares con doble entrada y anomalía de Ebstein «like¼ de la válvula auriculoventricular común es extremadamente rara. Se describen 2 corazones con esta asociación. Métodos: Se utilizó el sistema secuencial segmentario que determina el situs auricular, los tipos y modos de conexión auriculoventricular y ventriculoarterial y las anomalías agregadas. Resultados: Ambos corazones presentaron situs solitus auricular, defecto septal auriculoventricular con foramen primum y doble entrada y doble salida con grandes arterias normalmente relacionadas en un ventrículo único. En el primero las 4 valvas auriculoventriculares estuvieron adosadas a la pared ventricular desde la unión auriculoventricular hasta el ápex con auricularización de la entrada y de la porción trabecular y presentó estenosis infundibular y valvular. En el segundo la porción proximal de la válvula auriculoventricular estuvo adosada a la pared ventricular con auricularización pequeña; en su porción distal mostró displasia con nodulaciones fibromixoides y cuerdas tendinosas pequeñas y gruesas y la arteria pulmonar estuvo dilatada. Conclusiones: Ambos corazones forman parte de la conexión auriculoventricular univentricular del sistema secuencial segmentario, cuya precisión diagnóstica muestra su eficacia. Las asociaciones de defectos congénitos en un solo corazón muestran el infinito espectro de las mismas, lo que expande nuestro conocimiento de la cardiología pediátrica.

Abstract: Introduction and objectives: The association of univentricular heart with double inlet and Ebstein's "like" anomaly of the common atrioventricular valve is extremely rare. Methods: Two hearts with this association are described with the segmental sequential system which determine the atrial situs, the types of atrioventricular and ventriculoarterial connections and associated anomalies. Results: Both hearts had atrial situs solitus, and a univentricular heart with common atrioventricular valve, a foramen primum and double outlet ventricle with normal crossed great arteries. In the fiefirst heart the four leaflets of the atrioventricular valve were displaced and fused to the ventricular walls, from the atrioventricular union roward the apex with atrialization of the inlet and trabecular zones and there was stenosis in the infundibulum and in the pulmonary valve. In the second heart the proximal segment of the atrioventricular valve was displaced and fused to the ventricular whith shot atrialization and the distal segment was dysplastic with fibromixoid nodules and tendinous cords short and thick; the pulmonary artery was dilate. Conclusions: Both hearts are grouped in the atrioventricular univentricular connection in the segmental sequential system. The application of this method in the diagnosis of congenital heart disease demonstrates its usefulness. The associations of complex anomalies in these hearts show us the infinite spectrum of presentation of congenital heart disease which expands our knowledge of pediatric cardiology.

[Ebstein's "like" anomaly ventricular double inlet. A rare association]. / Anomalía de Ebstein «like¼ en doble entrada ventricular. Una rara asociación.

INTRODUCTION AND OBJECTIVES: The association of univentricular heart with double inlet and Ebstein's "like" anomaly of the common atrioventricular valve is extremely rare. METHODS: Two hearts with this association are described with the segmental sequential system which determine the atrial situs, the types of atrioventricular and ventriculoarterial connections and associated anomalies. RESULTS: Both hearts had atrial situs solitus, and a univentricular heart with common atrioventricular valve, a foramen primum and double outlet ventricle with normal crossed great arteries. In the fiefirst heart the four leaflets of the atrioventricular valve were displaced and fused to the ventricular walls, from the atrioventricular union roward the apex with atrialization of the inlet and trabecular zones and there was stenosis in the infundibulum and in the pulmonary valve. In the second heart the proximal segment of the atrioventricular valve was displaced and fused to the ventricular whith shot atrialization and the distal segment was dysplastic with fibromixoid nodules and tendinous cords short and thick; the pulmonary artery was dilate. CONCLUSIONS: Both hearts are grouped in the atrioventricular univentricular connection in the segmental sequential system. The application of this method in the diagnosis of congenital heart disease demonstrates its usefulness. The associations of complex anomalies in these hearts show us the infinite spectrum of presentation of congenital heart disease which expands our knowledge of pediatric cardiology.

Natural Course of Adult Ebstein Anomaly When Treated according to Current Recommendation.

The objectives of this study were to assess the clinical outcomes of adults with Ebstein Anomaly (EA) according to their treatment modalities. All adult EA patients diagnosed between October 1994 and October 2014 were retrospectively evaluated by medical record review. Total 60 patients were categorized into 3 groups according to their treatment strategy, i.e. non-operative treatment (Group I, n = 23), immediate operative treatment (Group II, n = 27), and delayed operative treatment (Group III, n = 10). A composite of major adverse cardiac and cerebrovascular events (MACCE) and factors associated with MACCE were assessed in each treatment group. MACCE occurred in 13.0% patients in Group I, 55.6% patients in Group II and 50% in Group III (P = 0.006). Event free survivals at 5 years were 90% in Group I, 52.7% in Group II, 50.0% in Group III (P = 0.036). Post-operatively, most patients showed improvement on clinical symptoms. However, event free survival rate was lower in patients with operation compared to those with non-operative treatment (58.7% vs. 90.9%; P = 0.007). Major arrhythmic event occurred more frequently even after surgical ablation (50.0% vs. 20.0%; P = 0.034). Re-operation was more frequent in patients underwent delayed surgery compared to those with immediate surgery (50.0% vs. 18.5%; P = 0.001). Current guideline to decide patient's treatment strategy appeared to be appropriate in adult patients with EA. However, surgical ablation for arrhythmia was not enough so that concomitant medical treatment should be considered. Therefore, attentive risk stratification and cautious decision of treatment strategy by experienced cardiac surgeon are believed to improve clinical outcome.