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Journal of the American Society of... May 2022The mechanisms and prognostic importance of left ventricular (LV) dysfunction in neonatal Ebstein's anomaly (EA) and tricuspid valve dysplasia (TVD) are not well...
BACKGROUND
The mechanisms and prognostic importance of left ventricular (LV) dysfunction in neonatal Ebstein's anomaly (EA) and tricuspid valve dysplasia (TVD) are not well understood. The authors recently demonstrated reduced cardiac output and dyssynchrony to be common in fetal EA/TVD and therefore hypothesized that LV dysfunction may be associated with worse outcomes in neonatal EA/TVD.
METHODS
A multicenter retrospective case-control study was conducted among neonatal patients with EA/TVD (n = 32) and a healthy control cohort (n = 17) encountered from 2004 to 2019. The left ventricle was assessed in the first 48 hours after birth using two-dimensional, Doppler-derived, six-segment global and segmental longitudinal strain and circumferential strain (CS) and dyssynchrony indices (the SD of time-to-peak strain and a novel global dyssynchrony index [DI], calculated as [peak segmental average - peak global average]/peak segmental average).
RESULTS
Neonates with EA/TVD demonstrated reduced combined cardiac index (4.2 ± 1.5 L/min/m vs 6.5 ± 2.2 L/min/m in control subjects, P < .001), impaired LV CS (-15.4 ± 6.9 vs -26.2 ± 5.8, P < .001), and increased circumferential dyssynchrony (CS DI 0.20 ± 0.16 vs 0.09 ± 0.04 [P = .019]; SD of time-to-peak CS 63 ± 25 vs 40 ± 15 [P = .003]). Transplantation-free survival occurred in 20 of 32 patients (63%) at 6 months. Increased CS DI and absence of pulmonary valve flow (PVF) were most predictive of mortality; CS DI > 0.2 was associated with 25% survival in subjects without PVF, whereas all patients with CS DI < 0.1 survived.
CONCLUSIONS
In neonates with EA/TVD and absence of PVF, there is abnormal LV deformation and compromised cardiac output in association with increased dyssynchrony. Increased CS DI is associated with increased risk for mortality in EA/TVD with no forward PVF.
Topics: Case-Control Studies; Ebstein Anomaly; Heart Defects, Congenital; Heart Valve Diseases; Humans; Infant, Newborn; Retrospective Studies; Tricuspid Valve; Ventricular Dysfunction, Left
PubMed: 35093556
DOI: 10.1016/j.echo.2022.01.010 -
Heart Rhythm Jul 2020
Topics: Arrhythmias, Cardiac; Ebstein Anomaly; Heart; Humans
PubMed: 32380287
DOI: 10.1016/j.hrthm.2020.04.038 -
HGG Advances Oct 2023Ebstein's anomaly is a rare congenital heart disease characterized by tricuspid valve downward displacement and is associated with additional cardiac phenotypes such as...
Ebstein's anomaly is a rare congenital heart disease characterized by tricuspid valve downward displacement and is associated with additional cardiac phenotypes such as left ventricle non-compaction. The genetic basis of Ebstein's anomaly has yet to be fully elucidated, although several genes (e.g., , , , and ) may contribute to Ebstein's anomaly. Here, in two Ebstein's anomaly families (a three-generation family and a trio), we identified independent heterozygous nonsense variants in laminin subunit 3 (), cosegregated with phenotypes in families with reduced penetrance. Furthermore, knocking out in mice revealed that haploinsufficiency of led to Ebstein's malformation of the tricuspid valve and an abnormal basement membrane structure. In conclusion, we identified a novel gene-disease association of implicated in Ebstein's anomaly, and the findings extended our understanding of the role of the extracellular matrix in Ebstein's anomaly etiology.
Topics: Animals; Mice; Ebstein Anomaly; Extracellular Matrix; Extracellular Matrix Proteins; Laminin; Tricuspid Valve
PubMed: 37635785
DOI: 10.1016/j.xhgg.2023.100227 -
Seminars in Cardiothoracic and Vascular... Mar 2016Ebstein'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... (Review)
Review
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.
Topics: Child; Child, Preschool; Ebstein Anomaly; Humans; Infant; Infant, Newborn; Intensive Care, Neonatal; Thoracic Surgery; Tricuspid Valve; Tricuspid Valve Insufficiency
PubMed: 26620137
DOI: 10.1177/1089253215616499 -
Expert Review of Cardiovascular Therapy Oct 2015Ebstein anomaly accounts for 1% of all congenital heart disease. It is a right ventricular myopathy with failure of tricuspid valve delamination and highly variable... (Review)
Review
Ebstein anomaly accounts for 1% of all congenital heart disease. It is a right ventricular myopathy with failure of tricuspid valve delamination and highly variable tricuspid valve morphology that usually results in severe regurgitation. It is the only congenital heart lesion that has a range of clinical presentations, from the severely symptomatic neonate to an asymptomatic adult. Neonatal operation has high operative mortality, whereas operation performed beyond infancy and into adulthood has low operative mortality. Late survival and quality of life for hospital survivors are excellent for the majority of patients in all age brackets. Atrial tachyarrhythmias are the most common late complication. There have been more techniques of tricuspid repair reported in the literature than any other congenital or acquired cardiac lesion. This is largely due to the infinite anatomic variability encountered with this anomaly. The cone reconstruction of Ebstein anomaly can achieve near anatomic restoration of the tricuspid valve anatomy. Early and intermediate results with these repairs are promising. Reduced right ventricular function continues to be a challenge for some patients, as is the need for reoperation for recurrent tricuspid regurgitation. The purpose of this article is to outline the current standard of care for diagnosis and treatment of Ebstein anomaly and describe innovative strategies to address poor right ventricular function and associated right-sided heart failure.
Topics: Cardiac Surgical Procedures; Ebstein Anomaly; Heart Defects, Congenital; Heart Failure; Humans; Quality of Life; Reoperation; Tricuspid Valve; Tricuspid Valve Insufficiency
PubMed: 26357983
DOI: 10.1586/14779072.2015.1087849 -
American Journal of Physiology. Heart... Jul 2023Patients with two congenital heart diseases (CHDs), Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The...
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 (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 (p.R237C) variant develop dysregulated ER/SR, calcium signaling, contractility, and proliferation. 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.
Topics: Humans; Ebstein Anomaly; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Cell Differentiation; Calcium Signaling
PubMed: 37204873
DOI: 10.1152/ajpheart.00658.2022 -
Mayo Clinic Proceedings Dec 2021To define the impact of tricuspid valve cone reconstruction (CR) on ventricular performance in Ebstein anomaly, both independently and after stem cell therapy.
OBJECTIVE
To define the impact of tricuspid valve cone reconstruction (CR) on ventricular performance in Ebstein anomaly, both independently and after stem cell therapy.
PATIENTS AND METHODS
The control group included 257 patients who had CR between June 2007 and December 2019. Ten subjects of a phase I stem cell therapy trial (May 2017 - March 2019) were compared with the controls to assess the echocardiographic impact on ventricular remodeling.
RESULTS
After CR, right ventricular (RV) size decreased and left ventricular (LV) volume increased in all patients. Apical and biplane RV fractional area change (FAC) initially decreased, but rebounded by 6 months postoperation. Short-axis FAC increased early and was maintained at 6 months post-CR in the control group. At 6 months post-CR, cell therapy patients showed a significantly larger increase in short-axis FAC (24.4% vs 29.9%, P=.003). In addition, whereas LV ejection fraction (EF) was unchanged at 6 months post-CR in controls, cell therapy patients showed a significant increase in EF relative to baseline and to controls (55.6% vs 65.0%, P=.007).
CONCLUSION
Cone reconstruction reduces tricuspid regurgitation and RV size, but is also associated with increased RV FAC and LV volume. Furthermore, injection of bone marrow-derived stem cells augmented the increase in RV FAC and was associated with improved LV EF at 6 months post-CR. This is evidence of a favorable interventricular interaction. These findings provide motivation for continued investigation into the potential benefits of stem cell therapy in Ebstein anomaly and other congenital cardiac malformations.
TRIAL REGISTRATION
clinicaltrials.gov identifier: NCT02914171.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Ebstein Anomaly; Echocardiography; Humans; Middle Aged; Plastic Surgery Procedures; Stem Cell Transplantation; Treatment Outcome; Tricuspid Valve; Ventricular Function, Right; Ventricular Remodeling; Young Adult
PubMed: 34479739
DOI: 10.1016/j.mayocp.2021.02.015 -
Brazilian Journal of Cardiovascular... 2018Ebstein's anomaly remains a relatively ignored disease. Lying in the 'No Man's land' between congenital and valve surgeons, it largely remains inadequately studied. We...
OBJECTIVE
Ebstein's anomaly remains a relatively ignored disease. Lying in the 'No Man's land' between congenital and valve surgeons, it largely remains inadequately studied. We report our short-term results of treating it as a 'one and a half ventricle heart' and propose that the true tricuspid annulus (TTA) 'Z' score be used as an objective criterion for estimation of 'functional' right ventricle (RV).
METHODS
22 consecutive patients undergoing surgery for Ebstein's anomaly were studied. Echocardiography was performed to assess the type and severity of the disease, tricuspid annular dimension and its 'Z' score. Patients were operated by a modification of the cone repair, with addition of annuloplasty, bidirectional cavopulmonary shunt (BCPS) and right reduction atrioplasty to provide a comprehensive repair. TTA 'Z' score was correlated later with postplication indexed residual RV volume.
RESULTS
There was one (4.5%) early and no late postoperative death. There was a significant reduction in tricuspid regurgitation grading (3.40±0.65 to 1.22±0.42, P<0.001). Residual RV volume reduced to 71.96±3.8% of the expected volume and there was a significant negative correlation (rho -0.83) between TTA 'Z' score and indexed residual RV volume. During the follow-up of 20.54±7.62 months, the functional class improved from 2.59±0.7 to 1.34±0.52 (P<0.001).
CONCLUSION
In Ebstein's anomaly, a higher TTA 'Z' score correlates with a lower postplication indexed residual RV volume. Hence, a complete trileaflet repair with offloading of RV by BCPS (when the TTA 'Z' score is >2) is recommended. The short-term outcomes of our technique are promising.
Topics: Adolescent; Adult; Cardiac Valve Annuloplasty; Child; Child, Preschool; Ebstein Anomaly; Echocardiography; Female; Follow-Up Studies; Fontan Procedure; Heart Ventricles; Humans; Infant; Male; Medical Illustration; Postoperative Complications; Recovery of Function; Severity of Illness Index; Treatment Outcome; Tricuspid Valve; Young Adult
PubMed: 30184032
DOI: 10.21470/1678-9741-2018-0100 -
Chinese Medical Journal May 2024Ebstein's anomaly (EA) is a rare and complex congenital heart anomaly, and the effect of surgical treatment is not ideal. This study aims to introduce our experience in...
BACKGROUND
Ebstein's anomaly (EA) is a rare and complex congenital heart anomaly, and the effect of surgical treatment is not ideal. This study aims to introduce our experience in management strategies, surgical techniques, and operative indications for patients with Ebstein's anomaly.
METHODS
A retrospective study of 258 operations was performed in 253 patients by the same cardiac surgeon in The First Hospital of Tsinghua University between March 2004 and January 2020. 32 patients had previously received cardiac surgery in other hospitals. The clinical data including diagnosis, operative indications, techniques, pathological changes, and survival rates were collected and analyzed.
RESULTS
Anatomical correction was performed in 203 (78.7%) operations, 1½ ventricle repair in 38 (14.7%) operations, tricuspid valve repair only in four operations (1.6%), tricuspid valve replacement in ten (3.9%), total cavopulmonary connection (TCPC) in two (0.8%), and Glenn operation in one operation (0.4%). Reoperation was performed in five patients (2.0%) during hospitalization. Among them, tricuspid valve replacement was performed in one patient, 1½ ventricle repair in two patients, and tricuspid valve annulus reinforcement in two patients. Five patients died with an early mortality rate of 2.0%. Complete atrioventricular conduction block was complicated in one patient (0.4%). A total of 244 patients was followed up (four in the 253 patients lost) with a duration of 3.0-168.0 (87.6 ± 38.4) months. Cardiac function of 244 patients improved significantly with mean New York Heart Association (NYHA) functional class recovery from 3.5 to 1.1. The mean grade of tricuspid valve regurgitation improved from 3.6 to 1.5. Three late deaths (1.2%) occurred. The survival rates at five and ten years after surgery were 98.6% and 98.2%, respectively. Reoperation was performed in five patients (2.0%) during the follow-up period.
CONCLUSION
Based on our management strategies and operative principles and techniques, anatomical correction of EA is capable of achieving excellent long-term results, and low rates of TCPC, 1½ ventricle repair and valvular replacement.
Topics: Humans; Ebstein Anomaly; Retrospective Studies; Male; Female; Adult; Adolescent; Child; Young Adult; Child, Preschool; Tricuspid Valve; Infant; Middle Aged; Cardiac Surgical Procedures
PubMed: 38030389
DOI: 10.1097/CM9.0000000000002854 -
World Journal For Pediatric &... Nov 2020Ebstein anomaly has a breadth of presentations, including "typical" and "atypical," and can be confused with congenital tricuspid dysplasia. We summarize how to... (Review)
Review
Ebstein anomaly has a breadth of presentations, including "typical" and "atypical," and can be confused with congenital tricuspid dysplasia. We summarize how to differentiate within this spectrum of disease. Both typical and atypical Ebstein have an underlying failure of delamination, but atypical Ebstein does not have ≥8mm/m apical septal leaflet displacement. In congenital tricuspid dysplasia, delamination is normal, while the leaflets and subvalvar apparatus are abnormal. To summarize, the sine qua non feature of Ebstein anomaly, present in both typical and atypical, is the failure of delamination. These are distinct from congenital tricuspid valve dysplasia in which the pathology is in the leaflet itself.
Topics: Cardiac Surgical Procedures; Child; Ebstein Anomaly; Echocardiography; Humans; Tricuspid Valve
PubMed: 33164686
DOI: 10.1177/2150135120949235