Epidemiology studies on effects of lithium salts in pregnancy are confounded by the inability to control for other potentially teratogenic factors.

INTRODUCTION: In bipolar women who took lithium during pregnancy, several epidemiology studies have reported small increases in a rare fetal cardiac defect termed Ebstein's anomaly. METHODS: Behavioral, environmental, and lifestyle-associated risk factors associated with bipolar disorder and health insurance status were determined from an Internet search. The search was conducted from October 1, 2023, through October 14, 2023. The search terms employed included the following: bipolar, bipolar disorder, mood disorders, pregnancy, congenital heart defects, Ebstein's anomaly, diabetes, hypertension, Medicaid, Medicaid patients, alcohol use, cigarette smoking, marijuana, cocaine, methamphetamine, narcotics, nutrition, diet, obesity, body mass index, environment, environmental exposures, poverty, socioeconomic status, divorce, unemployment, and income. No quotes, special fields, truncations, etc., were used in the searches. No filters of any kind were used in the searches. RESULTS: Women who remain on lithium in the United States throughout their pregnancy are likely to be experiencing mania symptoms and/or suicidal ideation refractory to other drugs. Pregnant women administered the highest doses of lithium salts would be expected to have been insufficiently responsive to lower doses. Any small increases in the retrospectively determined risk of fetal cardiac anomalies in bipolar women taking lithium salts cannot be disentangled from potential developmental effects resulting from very high rates of cigarette smoking, poor diet, alcohol abuse, ingestion of illegal drugs like cocaine or opioids, marijuana smoking, obesity, and poverty. CONCLUSIONS: The small risks in fetal cardiac abnormalities reported in the epidemiology literature do not establish a causal association for lithium salts and Ebstein's anomaly.

Significantly elevated hepatic extracellular volume in adult patients with a Fontan circulation and its correlation with impaired functional capacity.

Fontan-associated liver disease is a major concern in patients who have undergone the procedure. Regular imaging of the liver is currently recommended for Fontan patients, but not other congenital heart diseases. The extracellular volume (ECV) of the liver obtained during CMR scanning and studies can show the high liver ECV in Fontan patients. However, the correlation between the liver ECV and the functional capacity of Fontan patients has not yet been reported. This study aimed to compare the liver ECV between Fontan patients and other congenital heart diseases with significant pulmonic regurgitation (PR) or tricuspid regurgitation (TR), and to evaluate the correlation between the liver ECV in adult Fontan patients and their functional capacity as well as clinical characteristics. Retrospective analysis of cardiovascular magnetic resonance imaging from patients with history of Fontan surgery between 2017 and 2021 were conducted. The clinical characteristics and liver ECV were evaluated and compared between patients and control group. Functional capacity was evaluated using a 6-min walk distance (6MWD). The correlation between the liver ECV and functional capacity was analyzed. 35 patients were enrolled in the study, including 13 Fontan patients, 12 Ebstein's anomaly or repaired tetralogy of Fallot (rTOF) patients with significant PR or TR, and 10 patients for the control group. The liver ECV were significantly higher in Fontan patients compared with Ebstein's anomaly/rTOF and the control group (41.% in Fontan group, 33.9% in Ebstein's anomaly/rTOF, and 31.7% in control group with p = 0.01 and 0.0008 in Fontan vs. Ebstein's anomaly/rTOF and Fontan vs. control group, respectively). In Fontan patients, there was a significant correlation between the liver ECV and the liver blood biochemistry with r = 0.879, p = 0.01 for AST/ALT ratio and r = 0.65, p = 0.005 for AST. The liver ECV was inversely correlated with the six-minute walk distance (r = -0.55, p = 0.02). The liver ECV in patients who had undergone Fontan operation showed a significantly elevated and has significantly inversed correlation with their functional capacity. These findings indicated that the liver ECV may be a potentialmarker for adverse clinical outcomes. However, due to small size population, further prospective study with larger number of patients may validate this findings.

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.

Improved Tricuspid Valve Function, Preload Recruitment and Ventricular Efficiency During Submaximal Exercise in Patients with Unoperated Ebstein's Anomaly: An MRI Study.

BACKGROUND: Adolescents and adults with native Ebstein's anomaly (EA) are at the benign part of the Ebstein spectrum, having survived infancy without surgery. In this population, surgical indication and timing remain objects of controversy and depend, among other factors, on exercise capacity. PURPOSE: To better understand the pathophysiology of exercise adaptation in native EA. STUDY TYPE: Retrospective. POPULATION: Ten patients with unoperated EA (age range 18-61 years) and 13 healthy subjects as controls. FIELD STRENGTH/SEQUENCE: Balanced steady-state free precession cine and phase contrast flow sequences at 1.5 T. ASSESSMENT: We measured volumes and flows at rest and during submaximal exercise. Hemodynamic parameters including stroke volume (SV), cardiac index (CI), ejection fraction (EF), and tricuspid regurgitation (TR) were calculated. STATISTICAL TESTS: We used nonparametric Mann-Whitney U-test and Wilcoxon signed-rank test. A P-value of <0.05 was considered statistically significant. RESULTS: Rest CI and SV were significantly higher in controls; rest heart rate (HR) was similar in the two groups (median 71 bpm by patients and 65 bpm by controls, P = 0.448). During exercise, CI increased significantly in both groups: from 2.40 to 3.35 L/min/m2 in the patient group and from 3.60 to 4.20 L/min/m2 in controls; HR increased significantly in both groups. SV increased significantly in the patient group, whereas it remained stable in controls (P = 0.5284). Patients' median TR decreased significantly: median 42% at rest and 30% during exercise; concomitantly, left ventricular (LV) preload increased significantly (+3% indexed LV end-diastolic volume) as did LVEF (median 59% at rest vs. 65% during exercise). DATA CONCLUSION: During submaximal exercise, patients with mild to moderate EA improved their cardiovascular system's total efficiency by increasing CI; this was obtained by an increase in HR and by the recruitment of volume, as shown by an increased LV end-diastolic volume and SV, with simultaneous decrease in TR. This was different from healthy subjects in which CI increased only due to HR increase. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

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.

Neonatal Ebstein anomaly national outcomes from 2000 to 2018 using the National Inpatient Sample.

BACKGROUND: The prevalence, morbidity, and mortality associated with Ebstein anomaly (EA) remains poorly characterized in neonates. EA is a rare form of congenital heart disease (CHD) with significant heterogeneity. OBJECTIVE: To determine the recent, 2000-2018, prevalence, mortality, outcomes, and healthcare utilization of infants admitted at ≤28 days of life with EA in comparison to other critical congenital heart defects (CCHD) in the United States using a national data set. METHODS: The National Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project (HCUP) was queried for infants admitted for any reason at ≤28 days of life with a diagnosis of EA between 2000 and 2018 using ICD-9 and 10 codes in the United States. Patient characteristics, morbidity, mortality, and healthcare utilization were evaluated for EA and compared with other CCHD. RESULTS: From 2000 to 2018 a total of 68,312,952 neonatal admissions were identified, of them 4,398 neonates with isolated EA were identified, representing 7 per 100,000 neonatal admissions and 2.2% of CCHD admissions (4,398/197,881). The number of new EA cases ranged from 138 to 375 per year. In-hospital mortality was 12.3% and surgical repair occurred in 4.2% for infants with EA. There were 470 deaths without surgical repair which is 86.6% of the mortality. Arrhythmias were diagnosed in 10.6% and ECMO was used for 2.6% of neonates with EA. CONCLUSION: EA is a rare form of CHD. The prevalence has remained stable over the 19 years whereas other congenital heart defects have had an increase. The mortality in neonates with EA was significantly higher than in pooled CCHD; the burden of mortality occurred in the neonates without surgical intervention.

Electocardiographic features in Ebstein's disease.

INTRODUCTION: Ebstein's disease (ED) is a rare and heterogeneous congenital heart disease affecting the tricuspid valve and the right ventricle. Few studies have analyzed the electrocardiographic features of this disease. AIM: To describe the electrocardiographic features observed in Ebstein's disease. METHODS: We conducted a retrospective descriptive study that enrolled 26 patients followed for ED. RESULTS: The mean age of discovery of the ME was 103.5±99 months [0-31 years]. The diagnosis of ME is most often made between 5 and 10 years. We noted right atrial hypertrophy in 11 patients (42%), right ventricular hypertrophy in half of the patients. Right axial deviation was noted in 11 patients (42%). Eight patients (30%) had wide QRS≥ 120 ms. Seven of these 8 patients (27%) had a fragmented QRS appearance. A right bandle block was noted in 22 patients (84%), it was a complete block in 7 cases (27%). A preexcitation was found in 6 patients (23%). The localization of accessory pathway was right postero-septal in all cases. Rhythmic disorders were noted in 9 patients (34%). It was a junctional tachycardia in 3 patients (11%), atrial flutter in 4 patients (15%) and atrial fibrillation in 2 patients (7%). A second degree atriventricular block was observed in one patient, it was Mobitz I type. Two cases of postoperative rhythm disturbances were recorded: paroxysmal atrial fibrillation and junctional tachycardia related to Wolf Parkinson White (WPW) syndrome. CONCLUSION: Surface ECG in the ED is often pathological with prevalence of rhythm disturbances related to WPW syndrome.

Mortality burden in patients born with Ebstein's anomaly: a 40-year nationwide cohort study.

AIMS: Survival rates for unoperated patients with Ebstein's anomaly (EA) are unknown. We estimated overall long-term mortality in operated and unoperated EA patients, compared with the general population in Sweden. METHODS AND RESULTS: Using national medical registries, Swedish individuals born 1970-93 and diagnosed with EA between 1970 and 2011 were included. The hazard ratio for overall mortality for EA patients (n = 216) vs. the matched comparison cohort (n = 2160) was 43.7 [95% confidence interval (CI): 24.8-82.5]. Mortality risk for EA patients (vs. controls) decreased as birth period progressed, with hazard ratios declining from 63.6 (95% CI: 26.3-191.8) for those born in the 1970s to 34.4 (95% CI: 15.8-83.1) for those born in the 1980s and 20.2 (95% CI: 1.6-632.5) for those born at the beginning of 1990s. The overall mortality hazard ratios for unoperated and operated patients with EA (vs. controls) were 30.2 (95% CI: 13.8-73.3) and 63.7 (95% CI: 28.1-172.5), respectively. The risk of mortality among unoperated EA patients (vs. controls) declined with progressing birth period, with hazard ratios declining from 58.4 (95% CI: 15.1-415.2) in the 1970s to 22.9 (95% CI: 8.0-75.3) in the 1980s and 10.2 (95% CI: 0.3-395.9) in the 1990s. CONCLUSION: Overall all-cause mortality for patients with EA declined dramatically from 64 times to 20 times that of controls without EA, from the 1970s to the early 1990s. Unoperated patients with EA had better survival than did operated patients, possibly reflecting the higher severity of disease or more severe associated cardiac defects in patients undergoing surgery.

An ontology-based classification of Ebstein's anomaly and its implications in clinical adverse outcomes.

BACKGROUND: Ebstein's anomaly (EA) is a rare congenital heart disease with significantly phenotypic heterogeneity, accompanied with multiple associated phenotypes. The classification of cases with EA based on a standardized vocabulary of phenotypic abnormalities from Human Phenotype Ontology (HPO) and its association with adverse clinical outcomes has yet to be investigated. METHODS: We developed a deep phenotyping algorithm for Chinese electronic medical records (EMRs) from the Fuwai Hospital to ascertain EA cases. EA-associated phenotypes were standardized according to HPO annotation, and an unsupervised hierarchical cluster analysis was used to classify EA cases according to their phenotypic similarities. A survival analysis was conducted to study the association of the HPO-based cluster with survival or adverse clinical outcomes. RESULTS: The ascertained EA cases were annotated to have a single or multiple HPO terms. Three distinct clusters with different combinations of HPO term in these cases were identified. The HPO-based classification of EA cases was not significantly associated with survival or adverse clinical outcomes at a mid-term follow-up. CONCLUSIONS: Our study provided an important implication for studying the classification of congenital heart disease using HPO-based annotation. A long time follow-up will enable to confirm its association with adverse clinical outcomes.

Epidemiological, clinical, and echocardiographic features, and outcome of dogs with Ebstein's anomaly: 32 cases (2002-2016).

INTRODUCTION/OBJECTIVES: Ebstein's anomaly (EA) is a congenital heart disease characterized by apical displacement of the tricuspid valve leaflets in the right ventricle. The objective of this retrospective study was to investigate the signalment, clinical features, echocardiographic findings, and outcome of dogs with EA. ANIMALS, MATERIALS AND METHODS: Medical records of 40 dogs with EA were reviewed. Echocardiographic variables used to assess EA severity in human pediatrics were also evaluated (e.g. displacement index, Celermajer index, Carpentier class, and apex-mitral annulus:apex-tricuspid annulus distance ratio). RESULTS: Labrador retriever was the most commonly recruited breed (24 of the 40 dogs, 60%). Eight of the 40 dogs with EA had hemodynamically compromising concurrent heart (n = 7) or respiratory diseases (n = 1). A right apical systolic heart murmur (median grade = 5/6) was detected in the remaining 32 dogs, without any other clinical sign related to EA in 19 of the 32 dogs (59%). Median (interquartile range) values of the displacement index and Celermajer index were 17.4 mm/m2 (12.0-21.9) and 100% (50-130), respectively. Median time to all-cause death was 74 months, and 72% dogs (95% confidence interval, 50-86%) had not succumbed to cardiac death (CD) 160 months after diagnosis. Univariate analyses showed that the time from diagnosis to CD was associated with the presence of clinical signs, ascites, severe right atrial dilation, palpable thrill, and a Celermajer index ≥100%. DISCUSSION: Right atrial enlargement is significantly associated with decreased survival time of dogs with EA although most may live for years and may not die from CD. CONCLUSIONS: These results support medium to long-term survival for most dogs with EA.

Cerebrovascular accidents in Ebstein's anomaly.

INTRODUCTION: Mechanisms and risk factors for cerebrovascular accidents (CVAs) in Ebstein's anomaly (EA) are not well understood; hence, we aimed to clarify these in a large cohort of EA patients. METHODS: Patients with a confirmed diagnosis of EA were retrospectively reviewed. Baseline characteristics were compared between patients with and without a prior history of CVA using logistic regression modeling. Cox regression analysis was used to identify predictors of CVA following initial evaluation. CVA incidence from birth and following tricuspid valve surgery were estimated using the Kaplan-Meier method. RESULTS: Nine hundred sixty-eight patients (median age 21.1 years, 41.5% male) were included, in which, 87 patients (9.0%) had a history of CVA (54 strokes, 33 transient ischemic attacks; 5 associated with brain abscesses) prior to their initial evaluation. The odds of atrial septal defect/patent foramen ovale (odds ratio [OR] 4.91; 95% CI 2.60-21.22; p = .0002) and migraines/headaches (OR 2.38; 95% CI 1.40-4.04; p = .0013) but not atrial arrhythmias (OR 0.75; 95% CI 0.44-1.30; p = .31) were significantly higher among patients with prior CVA following multivariable adjustment. Seventeen patients experienced CVA following initial evaluation; no examined variables including atrial arrhythmias (HR 2.38; 0.91-6.19; p = .076) were predictive of CVA risk. The 10-year, 50-year, and 70-year incidences of CVA were 1.4%, 15.9%, and 23.5%, respectively, with paradoxical embolism heavily implicated. CONCLUSION: Patients with EA are at substantive risk for CVA. Histories of migraines/headaches and interatrial shunts should prompt concern for paradoxical embolic CVAs. This has significant implications for all patients with atrial-level shunting.

Potential risk factors for Ebstein anomaly, National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: Ebstein anomaly is a rare congenital heart defect (CHD) that, when severe, requires corrective surgery or other catheter-based intervention in the first year of life. Due to its rarity, risk factors for Ebstein anomaly remain largely unknown. Using national data, we examined 18 potential risk factors for Ebstein anomaly. METHODS: Using 1997-2011 data from the National Birth Defects Prevention Study, a population-based case-control study, we calculated crude and adjusted odds ratios and 95% confidence intervals for paternal age, maternal socio-demographics, reproductive history, and modifiable risk factors, and infant characteristics reported by mothers of 135 Ebstein anomaly cases and 11,829 controls. RESULTS: Mothers of Ebstein anomaly cases had 4.1 (95% confidence interval: 1.8, 9.5) times the odds of reporting a family history of CHD compared with mothers of controls. Ebstein anomaly was associated with maternal second-hand cigarette smoke exposure at home (odds ratio = 2.2 [95% confidence interval: 1.1, 4.4]), but not maternal cigarette smoking (odds ratio = 1.3 [95% confidence interval: 0.8, 2.1]). Odds were elevated, but the 95% confidence interval included 1.0, for maternal marijuana use (odds ratio = 1.8 [95% confidence interval: 0.9, 3.8]) and paternal age ≥40 years at delivery (odds ratio = 1.9 [95% confidence interval: 1.0, 3.5]). CONCLUSIONS: Maternal exposure to second-hand cigarette smoke at home and a family history of CHD were associated with elevated odds of Ebstein anomaly. Genetic analyses could clarify the potential heritability of Ebstein anomaly.

Prognostic value of echocardiographic parameters in pediatric patients with Ebstein's anomaly.

BACKGROUND: Accurate risk stratification of patients with Ebstein's anomaly (EA) is crucial. Aim of the study was to assess the prognostic value of echocardiography, including 2D speckle tracking (STE) derived myocardial deformation indices, for predicting outcome in pediatric and young adult unrepaired EA patients. METHODS: Fifty consecutive EA patients (1 day-18 years, 52% males) underwent echocardiography and were followed for a mean follow-up of 60 ±â€¯41 months for clinical outcome (ventricular tachyarrhythmia, heart failure, need for surgery and/or death). Clinical and instrumental features of EA patients with stable disease were compared with those of EA patients with progressive disease. RESULTS: Twenty-four (48%) EA patients had progressive disease. A more severe grade of tricuspid valve (TV) displacement [59.7 mm/m2 (IQR 27.5-83) vs 28.4 mm/m2 (IQR 17.5-47); p = 0.002], a lower functional right ventricle (RV) fractional area change (FAC) (29.2 ±â€¯7.7% vs 36.7 ±â€¯9.6%; p = 0.004), a higher Celermajer index [0.8 (IQR 0.7-0.98) vs 0.55 (IQR 0.4-0.7); p = 0.000], a lower functional RV-longitudinal strain (-10.2 ±â€¯6.2% vs -16.2 ±â€¯7.3%; p = 0.003) and a lower right atrium peak systolic strain (RA-PALS) (25.2 ±â€¯13.5% vs 36.3 ±â€¯12.5%; p = 0.004) were detected in progressive disease group compared to stable one, respectively. Functional RV-FAC and RA-PALS were independent predictors of progressive disease at multivariate analysis. CONCLUSION: Our study demonstrated for the first time the prognostic role of RV-FAC and RA-PALS in a long-term follow-up of EA young patients. A complete echocardiographic evaluation should be regular part in the evaluation and risk-stratification of EA children.

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.

Identification of clinically relevant phenotypes in patients with Ebstein anomaly.

BACKGROUND: Ebstein anomaly (EA) is a heterogeneous congenital heart defect (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities, resulting in a wide range of clinical outcomes. HYPOTHESIS: Phenotypic characterization of EA patients has the potential to identify variables that influence prognosis and subgroups with distinct contributing factors. METHODS: A comprehensive cross-sectional phenotypic characterization of 147 EA patients from one of the main referral institutions for CHD in Colombia was carried out. The most prevalent comorbidities and distinct subgroups within the patient cohort were identified through cluster analysis. RESULTS: The most prevalent cardiac comorbidities identified were atrial septal defect (61%), Wolff-Parkinson-White syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%). Cluster analysis showed that patients can be classified into 2 distinct subgroups with defined phenotypes that determine disease severity and survival. Patients in cluster 1 represented a particularly homogeneous subgroup with a milder spectrum of disease, including only patients with WPW and/or supraventricular tachycardia (SVT). Cluster 2 included patients with more diverse cardiovascular comorbidities. CONCLUSIONS: This study represents one of the largest phenotypic characterizations of EA patients reported. The data show that EA is a heterogeneous disease, very frequently associated with cardiovascular and noncardiovascular comorbidities. Patients with WPW and SVT represent a homogeneous subgroup that presents with a less severe spectrum of disease and better survival when adequately managed. This should be considered when searching for genetic causes of EA and in the clinical setting.

Atrio-ventricular deformation and heart failure in Ebstein's Anomaly - A cardiovascular magnetic resonance study.

PURPOSE: We aimed to quantify atrial and ventricular myocardial deformation in Ebstein's Anomaly (EA) in a case-control study with cardiovascular magnetic resonance (CMR) feature tracking and to correlate changes in cardiac performance with the severity of disease and clinical heart failure parameters. MATERIALS AND METHODS: Atrial and ventricular deformation was measured using CMR feature tracking in 30 EA and 20 healthy control subjects. Atrial performance was characterized using longitudinal strain and strain rate parameters for reservoir function, conduit function and booster pump function. Ventricular performance was characterized using RV and LV global longitudinal strain (εl) and LV circumferential and radial strain (εc and εr). Volumetric measurements for the ventricles including the Total Right/Left-Volume-Index (R/L-Volume-Index) and heart failure markers (BNP, NYHA class) were also quantified. RESULTS: EA patients showed significantly impaired right atrial performance, which correlated with heart failure markers (NYHA, BNP, R/L-Volume-Index). LA function in EA patients was also impaired with atrial contractile function correlating with NYHA class. EA patients exhibited impaired RV myocardial deformation, also with a significant correlation with heart failure markers. CONCLUSION: CMR feature tracking can be used to quantify ventricular and atrial function in a complex cardiac malformation such as EA. EA is characterized by impaired quantitative right heart atrio-ventricular deformation, which is associated with heart failure severity. While LV function remains preserved, there is also significant impairment of LA function. These quantitative performance parameters may represent early markers of cardiac deterioration of potential value in the clinical management of EA.

Sudden death in patients with Ebstein anomaly.

Aims: Ventricular dysfunction or structural alteration of either ventricle is a well-established risk factor for sudden death (SD). Ebstein anomaly (EA) can present with both right and left heart abnormalities; however, predictors of SD have not been described. We therefore sought to characterize the incidence and risk factors of SD among a large cohort of patients with EA. Methods and results: All EA patients who underwent evaluation at a high-volume institution over a 4-decade period were retrospectively reviewed. Clinical variables, cardiovascular surgical procedure(s), and cause of death were recorded. Sudden death incidence from birth and following tricuspid valve (TV) surgery were estimated using the Kaplan-Meier method. Cox regression analysis was used to identify clinical and surgical predictors of SD. The cohort comprised of 968 patients [mean age 25.3 years, 41.5% male; 79.8% severe EA, 18.6% accessory pathway, 0.74% implantable cardioverter-defibrillator (ICD) placement]. The 10-, 50-, and 70-year cumulative incidences of SD from birth were 0.8%, 8.3%, and 14.6%, respectively. Prior ventricular tachycardia [hazard ratio (HR) 6.37, P < 0.001)], heart failure (HR 5.64, P < 0.001), TV surgery (HR 5.94, P < 0.001), syncope (HR 2.03, P = 0.019), pulmonic stenosis (HR 3.42, P = 0.001), and haemoglobin > 15 g/dL (HR 2.05, P = 0.026) were multivariable predictors of SD. In a similar subgroup analysis of patients who underwent TV surgery, all of the above factors except syncope were significantly associated with post-operative SD on multivariable analysis. Conclusion: Patients with EA are at significant risk for SD. Key clinical SD predictors identified can aid in risk stratification and potentially guide primary prevention ICD implantation.

The changing epidemiology of Ebstein's anomaly and its relationship with maternal mental health conditions: a European registry-based study.

OBJECTIVES: The aim of this study was to describe the epidemiology of Ebstein's anomaly in Europe and its association with maternal health and medication exposure during pregnancy. DESIGN: We carried out a descriptive epidemiological analysis of population-based data. SETTING: We included data from 15 European Surveillance of Congenital Anomalies Congenital Anomaly Registries in 12 European countries, with a population of 5.6 million births during 1982-2011. Participants Cases included live births, fetal deaths from 20 weeks gestation, and terminations of pregnancy for fetal anomaly. Main outcome measures We estimated total prevalence per 10,000 births. Odds ratios for exposure to maternal illnesses/medications in the first trimester of pregnancy were calculated by comparing Ebstein's anomaly cases with cardiac and non-cardiac malformed controls, excluding cases with genetic syndromes and adjusting for time period and country. RESULTS: In total, 264 Ebstein's anomaly cases were recorded; 81% were live births, 2% of which were diagnosed after the 1st year of life; 54% of cases with Ebstein's anomaly or a co-existing congenital anomaly were prenatally diagnosed. Total prevalence rose over time from 0.29 (95% confidence interval (CI) 0.20-0.41) to 0.48 (95% CI 0.40-0.57) (p<0.01). In all, nine cases were exposed to maternal mental health conditions/medications (adjusted odds ratio (adjOR) 2.64, 95% CI 1.33-5.21) compared with cardiac controls. Cases were more likely to be exposed to maternal ß-thalassemia (adjOR 10.5, 95% CI 3.13-35.3, n=3) and haemorrhage in early pregnancy (adjOR 1.77, 95% CI 0.93-3.38, n=11) compared with cardiac controls. CONCLUSIONS: The increasing prevalence of Ebstein's anomaly may be related to better and earlier diagnosis. Our data suggest that Ebstein's anomaly is associated with maternal mental health problems generally rather than lithium or benzodiazepines specifically; therefore, changing or stopping medications may not be preventative. We found new associations requiring confirmation.

Clinical characteristics and outcomes in pregnant women with Ebstein anomaly at the time of delivery in the USA: 2003-2012.

BACKGROUND: Ebstein anomaly is an uncommon congenital cardiac lesion that may be associated with cyanosis, arrhythmias and right heart dysfunction. Investigation into patient characteristics and outcomes in pregnant women with Ebstein anomaly has been limited. AIMS: To characterize patient characteristics and clinical events for pregnant women with Ebstein anomaly during hospitalization for delivery in the USA; also, to determine the effect of Ebstein anomaly on maternal clinical outcomes and individual predictors of poor outcome at time of delivery. METHODS: We screened the Healthcare Cost and Utilization Project's National Inpatient Sample for hospital admissions of pregnant women for delivery (vaginal or caesarean section) in the USA from 2003-2012, and identified a cohort of 7,850,381. Clinical characteristics and maternal outcomes were identified in those with and without Ebstein anomaly. The primary outcome of interest was major adverse cardiac events (MACE), a composite of in-hospital death, acute myocardial infarction, cerebrovascular events, embolic events, cardiac complications of labour and delivery heart failure or arrhythmia. RESULTS: Our study population consisted of 82 hospitalizations of pregnant women with Ebstein anomaly and 7,850,299 without. The Ebstein cohort more frequently had ostium secundum-type atrial septal defect and/or patent foramen ovale and anomalous atrioventricular excitation (P<0.001 for both). The MACE rate was significantly higher among Ebstein patients (P<0.001). Preterm delivery, postpartum haemorrhage and caesarean delivery occurred more frequently among the Ebstein cohort (19.5% vs 7.2%, 8.5% vs 2.8% and 47.6% vs 31.1%, respectively; P≤0.001). In a multivariable analysis, anomalous atrioventricular excitation (odds ratio [OR] 21.75, 95% confidence interval [CI] 1.03-457.91) and preterm delivery (OR 11.71, 95% CI 1.39-98.89) were associated with MACE among those with Ebstein anomaly. CONCLUSIONS: Pregnant women with Ebstein anomaly are at higher risk of MACE during pregnancy and delivery. Preterm delivery occurred more frequently in women with Ebstein anomaly.

Preoperative Physiology, Imaging, and Management of Ebstein's Anomaly of the Tricuspid Valve.

Ebstein's anomaly of the tricuspid valve (TV) refers to an embryological derangement of TV formation causing tethering of the septal and posterior leaflets of the valve to the underlying myocardium and apical displacement of the effective valve annulus, resulting in significant TV insufficiency and dilation of the right heart structures. The pathological abnormalities of the valve can vary significantly, resulting in a wide range of clinical presentations. Fetal diagnosis and neonatal presentations of the disease are typically the most severe and are associated with the highest mortality rates. Patients with less-severe disease will present later in life with symptoms of right heart failure and tachyarrhythmias. Medical and surgical management strategies are driven by the age at presentation, severity of disease, and any associated cardiac abnormalities. There are an increasing number of surgical options focused on valve repair.