Assessment of Left Ventricular Myocardial Fibrosis in Adult Patients With Ebstein Anomaly: A Retrospective Cohort Study Based on Cardiac Magnetic Resonance and Histopathological Samples.

BACKGROUND: The association between Ebstein anomaly and myocardial fibrosis, particularly in the left ventricle, has been controversial. We aimed to assess the prevalence of replacement fibrosis with a focus on the left ventricle (LV) using cardiac magnetic resonance (CMR), make a histopathological association between LV fibrosis and CMR findings, and explore whether LV fibrosis is an independent risk factor for cardiovascular disease mortality using a derived risk score. METHODS: We performed a 12-year (2009-2021) retrospective cohort of adult patients with Ebstein anomaly who underwent CMR. The CMR evaluation included a comprehensive assessment of myocardial fibrosis by late gadolinium enhancement (LGE). Four postmortem samples were obtained from our cohort and stained using Masson trichrome to characterize LV fibrosis. We used Cox-regression analysis to identify and derive a prediction score that associated LV fibrosis with cardiovascular disease mortality. RESULTS: We included 57 adults with Ebstein anomaly (52% men; median age, 29.52 [interquartile range, 21.24-39.17] years), of whom 12 died during follow-up. LGE prevalence by CMR was observed in 52.6% in any chamber; LV-LGE in 29.8%. Histopathological findings revealed a mid-wall pattern with predominantly interstitial fibrosis and minimal replacement fibrosis. LV-LGE was associated with increased risk of cardiovascular disease mortality (hazard ratio, 6.02 [95% CI, 1.22-19.91]) attributable to lateral and mid-wall LV segment involvement. Our mortality score achieved an overall good prediction capacity (R2, 0.435; C statistic, 0.93; Dxy, 0.86). CONCLUSIONS: There is a high prevalence of LV fibrosis replacement in adults with Ebstein anomaly, characterized by specific CMR and histological patterns. Furthermore, LV-LGE fibrosis is an independent predictor of cardiovascular disease mortality, which could be integrated into risk assessment in clinical management.

Ebstein's anomaly: epidemiological analysis and presentation of different prenatal management.

OBJECTIVES: To present the crucial role of echocardiographic examination in perinatal care and analyze influence of prenatal treatment for neonatal outcome. Furthermore, the attempt to answer the question if there was any relationship between the occurrence of fetal Ebstein's anomaly and environmental risk factors in polish population. METHODS: Forty-five prenatal diagnoses of Ebstein's anomaly were compiled over the 21-year period (1998‒2018) form our single unit. The analysis included the assessment of maternal parameters (age, past obstetric history, and place of residence) and fetal parameters (sex, gestational age, anatomy, the fetal cardiovascular condition assessed by the CVPS, associated extracardiac anomalies or malformations, prenatal treatment, delivery and follow-up). RESULTS: The average age of gravida was 29.5 years (± 5.2 years) and gravidae <35 years of age accounted for 80% . There were 43 singleton pregnancies and 2 cases of multiple pregnancy. Ebstein's anomaly was mostly (averagely) diagnosed at 28th week of gestation. Forty-three fetuses had normal karyotypes and two had trisomy 21. Cardiomegaly was present in 91% (41) of fetuses. The average heart area to chest area ratio was 0.56 (± 0.12). In 21 cases, there was only fetal monitoring - echocardiographic examinations and postnatal mortality was 44.4%. In 5 cases, transplacental digoxin treatment was administered and mortality was: 40%. In another 5 cases, only steroid therapy was applied and postnatal mortality was 100%. Steroids and transplacental digoxin treatment were administered in 11 cases and mortality was 63.6%. In 3 last cases transplacental digoxin treatment, steroids and maternal hyperoxygenation therapy were given and mortality was 0%. Cesarean section rate was 49%. Moreover, due to Ebstein's anomaly regional peak of occurrence benzopyrene was deliberated as environmental risk factor. CONCLUSIONS: Fetal Ebstein's anomaly occurred in our population in healthy young women, expecting their first child and malformation was not related to fetus gender, nor to maternal health condition. Our data can be a new signal for the development of novel treatment strategies in therapy in fetuses with Ebstein's anomaly.

Quantitative Assessment of Left Ventricular Dysfunction in Fetal Ebstein's Anomaly and Tricuspid Valve Dysplasia.

BACKGROUND: Fetal Ebstein's anomaly and tricuspid valve dysplasia (EA/TVD) are associated with high perinatal mortality relative to pulmonary atresia with intact ventricular septum (PAIVS), despite both requiring redistribution of the cardiac output (CO) to the left ventricle (LV). LV dysfunction is suspected to contribute to adverse outcomes in EA/TVD. OBJECTIVE: We sought to examine global and segmental LV function in fetal EA/TVD with comparison to normal controls and PAIVS. We hypothesized that LV dysfunction in EA/TVD is associated with abnormal LV remodeling and interventricular mechanics. METHODS: We retrospectively identified 63 cases of fetal EA/TVD (40 with retrograde ductal flow) and 22 cases of PAIVS encountered from 2004 to 2015 and compared findings to 77 controls of comparable gestational age. We measured the combined CO and global LV function using two-dimensional, Doppler-derived, deformational (six-segmental vector velocity imaging) and dyssynchrony indices (DIs; SD of time to peak), and a novel global DI. RESULTS: EA/TVD fetuses demonstrated abnormal LV global systolic function with reduced ejection fraction, fractional area change, and CO, while in PAIVS we observed a normal ejection fraction, fractional area change, and CO. PAIVS, but not EA/TVD, demonstrated increased LV sphericity, suggestive of remodeling, and associated enhanced radial function in the third trimester. In contrast, while EA/TVD fetuses had normal LV segmental longitudinal strain, there was abnormal radial segmental deformation and LV dyssynchrony with increased SD of time to peak and DI. CONCLUSIONS: Fetal EA/TVD is associated with a lack of spherical remodeling and presence of mechanical dyssynchrony, which likely contribute to reduced CO and ejection fraction. Clinical monitoring of LV function is warranted in fetal EA/TVD. Further studies incorporating quantification of LV function into prediction models for adverse outcomes are required.

[Prenatal and postnatal ultrasound assessment and clinical prognostic analysis for Ebstein anomaly].

Objective: To investigate the echocardiographic features of fetal Ebstein's anomaly (EA) and to analyze its clinical outcome and prognosis. Methods: A retrospective case-control study was conducted to analyze the echocardiographic features in fetus with EA. Thirty-five EA fetuses (EA group) and 35 normal fetuses matched for gestational age (control group) were enrolled. The main echocardiographic parameters of the two groups were collected and compared. According to the direction of blood flow in the ductus arteriosus (DA),fetuses in EA group were divided into DA reverse perfusion subgroup (n=11) and normal DA blood flow subgroup (n=24). The echocardiographic parameters and GOSE scores were compared between the two subgroups. The echocardiographic features of EA and the difference of fetal hemodynamics were summarized,and the clinical outcome of EA fetus was evaluated by GOSE score. Chi-square test Rank sum test or t test were used for comparison between groups. Results: Nineteen (54%) of the 35 patients terminated the pregnancy and 16 (46%) continued pregnancy until delivery during follow-up. Compared with the normal fetus group,the cardiothoracic ratio was significantly higher (0.47±0.11 vs. 0.34±0.01, t=6.640, P<0.01) and the transverse diameter ratio of right atrium to left atrium was significantly greater (1.42±0.38 vs. 1.08±0.11, t=5.030, P<0.01) in the EA group, and the ratio of pulmonary artery diameter to aortic diameter was significantly lower in the EA group (1.04±0.21 vs. 1.20±0.15, t=-3.770, P<0.01). Compared with the normal DA blood flow subgroup,the GOSE scores ≥ 1.5 was more frequently seen (7/11 vs. 3/24, P=0.004) and the ratio of pulmonary artery diameter to aortic diameter was significantly lower (0.91±0.18 vs. 1.24±0.20, t=-4.696, P=0.002) in the DA reverse perfusion subgroup. Six of the 16 delivery cases underwent EA corrective surgery after birth with 100% successful rate of operation. Among the 6 cases,two had preoperative GOSE score of ≥1.5 who were considered as severe cases,and four had low GOSE score of<1.5. The remaining ten cases who had not undergone the corrective surgery were followed up routinely. Conclusion: Prenatal hemodynamics of EA combined with GOSE score can more accurately evaluate the severity and prognosis of fetal EA, reduce unnecessary labor induction, and improve postpartum cure rate and clinical outcomes.

Assessment of Progressive Pathophysiology After Early Prenatal Diagnosis of the Ebstein Anomaly or Tricuspid Valve Dysplasia.

In fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD), poor hemodynamic status is associated with worse neonatal outcome. It is not known whether EA/TVD fetuses with more favorable physiology earlier in gestation progress to more severe disease in the third trimester. We evaluated if echocardiographic indexes in EA/TVD fetuses presenting <24 weeks of gestation are reliable indicators of physiologic status later in pregnancy. This multicenter, retrospective study included 51 fetuses presenting at <24 weeks of gestation with EA/TVD and serial fetal echocardiograms ≥4 weeks apart. We designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, left ventricular (LV) dysfunction, or tricuspid valve (TV) annulus Z-score >5.6. Median gestational age at diagnosis was 21 weeks (range, 18 to 24). Eighteen fetuses (35%) had no markers for poor hemodynamic status initially, whereas only 7 of these continued to have no markers of poor outcome in the third trimester. Nine of 27 fetuses (33%) with anterograde pulmonary blood flow on the first echocardiogram developed pulmonary atresia; 7 of 39 (18%) developed new pulmonary valve regurgitation. LV dysfunction was present in 2 (4%) patients at <24 weeks but in 14 (37%) later (p <0.001). The TV annulus Z-score and cardiothoracic area both increased from diagnosis to follow-up. In conclusion, progressive hemodynamic compromise was common in this cohort. Our study highlights that care must be taken in counseling before 24 weeks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring.

Non-volumetric echocardiographic indices and qualitative assessment of right ventricular systolic function in Ebstein's anomaly: comparison with CMR-derived ejection fraction in 49 patients.

AIMS: Ebstein's anomaly (EA) is often associated with right ventricular (RV) dysfunction. Data on echocardiographic quantification of RV function are, however, rare. The aim of this study was to determine how non-volumetric echocardiographic indices and qualitative assessment of global systolic RV function correlate with cardiovascular magnetic resonance (CMR)-derived RV ejection fraction (EF). METHODS AND RESULTS: We compared six echocardiographic indices and qualitative assessment of RV function with the gold standard CMR. A total of 49 unoperated patients with EA and a mean age of 32 ± 18 years were examined. Tricuspid annular plane systolic excursion, tissue Doppler myocardial velocities (peak S and IVA) and 2D strain and strain rate measures for the RV were compared with CMR-derived EF. Only 2D global longitudinal strain (2D-GLS), out of the six parameters investigated, showed a weak, although statistically significant correlation with CMR-derived RVEF (R = -0.4, P = 0.01). Using a cut-off value of -20.15, 2D-GLS sensitivity (77%) and specificity (46%) in detecting patients with a CMR-derived EF of <50% were comparable with qualitative assessment (sensitivity 77%, specificity 45%). CONCLUSION: Overall echocardiographic parameters of RV function correlate poorly with CMR-derived EF in patients with EA. Only 2D global longitudinal RV strain correlated weakly with CMR-derived RVEF. However, the sensitivity and specificity for detecting RV dysfunction using 2D strain imaging were comparable with qualitative RV functional assessment.

Echocardiographic assessment of Ebstein's anomaly.

Ebstein's anomaly is a complex congenital lesion which primarily involves the tricuspid valve. The tricuspid leaflets are tethered to varying degrees to the right ventricular free wall and the ventricular septum often resulting in significant tricuspid regurgitation and a small functioning right ventricular chamber. Although the septal leaflet originates normally at the right atrioventricular junction, the proximal portion is often completely tethered to the ventricular septum resulting in a misconception and erroneous statements in many publications that its attachment is apically displaced. Although two-dimensional echocardiography represents the primary modality for the diagnosis of this anomaly, three-dimensional echocardiography provides incremental value in characterizing the extent and severity of tethering of individual tricuspid valve leaflets. This information is useful in surgical decision making whether to repair or replace the tricuspid valve.

An atypical assessment of Ebstein's anomaly in an 86-year-old man.

We present the echocardiographic analysis of an 86-year-old man affected by Ebstein's anomaly. In the natural history of this congenital disease only 5% of patients survive beyond the fifth decade. The patient presented severe right atrial dilatation and right heart failure, and he was referred to our institution for supraventricular tachycardia.

Live/real time three-dimensional transthoracic echocardiographic assessment of Ebstein's anomaly.

We describe our experience in using live/real time three-dimensional transthoracic echocardiography (3D TTE) in the assessment of five adult patients with Ebstein's anomaly. The technique was found useful in assessing the distribution and extent of tethering of each of the three leaflets of the tricuspid valve (TV) to the underlying right ventricular walls and the ventricular septum. The characteristic bubble-like appearance resulting from bulging of the non-tethered areas of the TV leaflets was also well visualized in three dimensions and their size measured. Thus, an estimate of the nontethered or free segments of all three leaflets of the TV could be obtained using this technique. This has important implications when considering these patients for surgical repair of the TV. Visualization of all three leaflets of the TV and their extent of tethering by 3D TTE also made it easier to identify the boundaries of the functioning right ventricular chamber potentially providing a more reliable assessment of its volumes and ejection fraction. Cropping of color Doppler 3D TTE data sets provided en face viewing of the TV regurgitation vena contracta permitting accurate assessment of its shape and size. This has the potential to provide a more accurate quantitative estimation of TV regurgitation severity as compared to two-dimensional color Doppler. In conclusion, live/real time 3D TTE appears useful in supplementing two-dimensional echocardiography in more comprehensively assessing the morphologic features of Ebstein's anomaly.

Nongeometric quantitative assessment of right and left ventricular function: myocardial performance index in normal children and patients with Ebstein anomaly.

Assessment of ventricular systolic function has been based on the geometric models of ventricular shape. This study was designed to define normal values for a nongeometric myocardial performance index (MPI) in children and to evaluate the utility of MPI in congenital heart disease. The MPI measures the ratio of total time spent in isovolumic activity (isovolumic contraction time and isovolumic relaxation time) to the ejection time. The right ventricular (RV) and left ventricular (LV) MPI were measured in 152 normal children (ages 3 to 18 years) and 45 preoperative patients with Ebstein anomaly (age 1 week to 52 years). In normal children, the RV MPI was 0.32+/-0.03 and the LV MPI was 0.35+/-0.03. In the Ebstein group, both RV and LV MPI were abnormally increased compared with age-matched normal subjects (Ebstein group: RV MPI=0.49+/-0.12, LV MPI=0.42+/-0.09, P < .001). Increasing RV dysfunction was associated with progressively increasing (abnormal) values of RV MPI (P < .001). The myocardial performance index quantitatively reflects ventricular performance in patients with complex ventricular geometry (ie, Ebstein anomaly). In the absence of a geometric solution, this nongeometric index is particularly appealing for the assessment of RV or LV performance.

Assessment of right-to-left shunt flow in atrial septal defect by transesophageal color and pulsed Doppler echocardiography.

To investigate the clinical significance and problems of right-to-left (R-L) shunt flow dynamics in atrial septal defects, we performed transesophageal color and pulsed Doppler echocardiography in 30 patients with atrial septal defects of the ostium secundum type. The 30 patients consisted of 20 with a pulmonary artery systolic pressure of less than 40 mm Hg, four with a pressure of 40 to 60 mm Hg, three with a pressure of 90 mm Hg or more, two patients with pulmonic stenosis, and one patient with Ebstein's anomaly. R-L shunting was determined by the presence of a shunt flow signal across the defect during each cardiac cycle. The time of R-L shunt flow was compared with the various parameters obtained by echocardiography and cardiac catheterization. R-L shunt flow signals were detected at the following times: (1) at the onset of ventricular contraction or the closing phase of the tricuspid valve in five patients with isolated atrial septal defect. These patients showed an increase of mean right atrial pressure but had no severe pulmonary hypertension; (2) during ventricular systole in five of 26 patients with tricuspid regurgitation and one patient with Ebstein's anomaly. The tricuspid regurgitant signal was directed toward the ostium of the defect in three patients and was massive in the other patients; (3) during middiastole in three patients without pulmonary hypertension. These patients showed massive left-to-right shunt flow from end systole to early diastole; and (4) during atrial systole in three patients with severe pulmonary hypertension and two patients with pulmonic stenosis. The former, in particular, showed the aliasing signal as a high-speed shunt flow. In two of the three patients with severe pulmonary hypertension, R-L shunting continued from atrial systole to early ventricular systole and was also observed in early diastole. R-L shunt flow was detected in patients with atrial septal defects not only with pulmonary hypertension but also without pulmonary hypertension and was influenced by the right atrial pressure in the phase of tricuspid valve closing, the volume or direction of tricuspid regurgitation, rebound flow caused by massive left-to-right shunt flow, the grade of right ventricular distensibility or the complication of pulmonary hypertension, and complications with other cardiac anomalies. Thus R-L shunt flow in patients with atrial septal defects was detected easily by transesophageal color and pulsed Doppler echocardiography because of the high efficiency of this method for its detection.

Echocardiographic assessment of the right atrioventricular junction in Ebstein's malformation.

Echocardiographic evaluation of two infants with Ebstein's malformation of the tricuspid valve revealed an echogenic right atrioventricular junction that gave the impression of a divided right atrial cavity. Imaging of this junction resulted in better assessment of the components of the right heart of this malformation.