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.

Ebstein's anomaly during pregnancy: experience from a tertiary care centre - a case series and review of literature.

Pregnancy complicated with uncorrected Ebstein's anomaly is uncommon and may pose a serious threat to maternal and foetal life in the clinical setting of altered hemodynamics of pregnancy. Data of eight pregnancies in four women with Ebstein's anomaly who delivered in a tertiary care institute was analysed. Among the four women, one had associated atrial septal defect, one had pulmonary hypertension and three had right bundle branch block. There were two miscarriages and six successful pregnancies resulting in live births. Three of the pregnancies were delivered by caesarean section. There was one pregnancy complicated by severe preeclampsia, no preterm births or maternal cardiac complications. There was one neonate with congenital ostium secundum atrial septal defect. All patients were managed by a multidisciplinary team involving Obstetrician, Cardiologist, Anaesthesiologist and Neonatologist.IMPACT STATEMENTWhat is already known on this subject? Ebstein's anomaly is a rare congenital anomaly with apical displacement of the septal tricuspid leaflet in association with leaflet dysplasia. It may cause varied presentation in pregnancy depending on the severity of the lesion.What do the results of this study add? Ebstein's anomaly may become symptomatic for the first-time during pregnancy. Patients with NYHA class II symptoms and no cyanosis generally tolerate pregnancy well. Miscarriages and intrauterine growth restriction may occur in the presence of this condition. Vaginal delivery is advised and caesarean is done only for obstetric indications.What are the implications of these findings for clinical practise and/or future research? The management of pregnancy with uncorrected Ebstein's anomaly is highly challenging especially in a low resource setting and requires tertiary centre care. Multidisciplinary team involvement can help to improve the outcomes in such pregnancies.

Visualization of tricuspid valve annulus for implantation of His bundle pacing in patients with symptomatic bradycardia.

BACKGROUND: His bundle pacing (HBP) is a physiological pacing modality, but HBP implantation remains a challenge. OBJECTIVE: This study explored the feasibility of using visualization of the tricuspid valve annulus (TVA) to locate the site for HBP. METHODS: During the lead placement in eight patients with symptomatic bradycardia, the TVA and tricuspid septal leaflet was revealed by contrast injection in the right ventricle under the fluoroscopic right anterior oblique view, and the target site for HBP was identified near the intersection of the tricuspid septal leaflet and the interventricular septum. On the basis of the imaging marker, the pacing lead was placed for HBP at either the atrial (aHBP) or ventricular side (vHBP). RESULTS: During the implantation, the pacing lead placement was attempted for aHBP in two patients, vHBP in five patients, and first for aHBP then vHBP in one patient. The aHBP was selective and had a capture threshold of 1.6 ± 0.5 V@ 1.0ms and R-wave amplitude of 1.2 ± 0.4 mV. Ventricular-side His bundle capture was selective in four patients and nonselective in two patients. The vHBP capture threshold was 0.8 ± 0.4 V@ 1.0ms (P < .05 vs aHBP) and R-wave amplitude was 4.1 ± 1.5 mV (P < .05 vs aHBP). At the final pacing programming of 3.0 V@ 1.0ms, vHBP was nonselective in all six patients and aHBP remained selective in two patients. Pacing parameters remained stable at 3 months. CONCLUSION: The location of the TVA and tricuspid septal leaflet revealed by right ventriculography can be used as a landmark to identify the HBP site.

A Systemic Mapping Approach for Right and Left Parahisian Ventricular Arrhythmias Ablation.

Background: Catheter ablation for parahisian ventricular arrhythmias (PHVA) is technically challenging and associated with increased risks of atrioventricular block (AVB). We developed a systemic mapping approach to improve the efficacy and safety of PHVA ablation. Methods: Forty-three patients (29 males; average age 65.8 ± 10.5 years) with PHVAs were enrolled. A systemic mapping approach comprising differential electrocardiogram, sequential mapping, and ablation beneath/above the septal leaflet of the tricuspid valve (SLTV) and at the neighboring/contralateral regions (the aortic root and sub-aortic valve region) was applied for PHVA. The effectiveness and safety of this approach was evaluated at 1 year's follow-up. Results: Sequential ablation beneath the SLTV (B-SLTV) succeeded in 24 (66.7 %) of 36 with right PHVA and ablation above the SLTV succeeded in 6 of the remaining 12 with failed B-SLTV ablation. Target-His bundle (HB) distance > 4.5 mm significantly predicted successful right PHVA ablation (OR 1.703; 95% CI 1.084-2.676, P = 0.02). "Seeming" right PHVA by electrocardiogram in 4 and apparent left PHVA in 3 was successfully ablated at the sub-aortic parahisian region. At 1 year's follow-up, 27 (75%) of 36 patients with right PHVA and 6 (85.7%) of 7 patients with left PHVA were free of PHVA recurrence off anti-arrhythmic drugs. The total success rate was 76.7% by using the systemic mapping approach for PHVA. One patient with A-SLTV ablation underwent pacemaker implantation due to complete AVB. Conclusions: The systemic mapping approach was effective and safe for treating PHVA. The target-HB distance was a significant predictor for right PHVA ablation.

Original Article--Predictors of Persistent Functional Tricuspid Regurgitation After Transcatheter Closure of Atrial Septal Defect and its Relationship to Tricuspid Valve Remodeling.

OBJECTIVES: The aim of this study is assessment of persistent functional tricuspid regurgitation in patients with atrial septal defect before and after successful device closure and its relationship to tricuspid valve remodeling. METHODS: The current study was conducted on 60 patients referred to Tanta University Hospital Cardiology Department with the provisional diagnosis of atrial septal defect secundum type for transcatheter closure from December 2017 to December 2019. All patients were subjected to history taking, clinical examination, 12 lead electrocardiography, plain chest X-ray, full two dimension transthoracic echocardiography (for assessment of tricuspid regurgitation severity) before and at 3, 6 months after transcatheter closure. RESULTS: Tricuspid regurgitation was decreased significantly after atrial septal defect closure due to remodeling in the right side. Age, estimated systolic pulmonary artery pressure, right atrium end systolic area, right ventricular end diastolic area, tricuspid valve tenting area and height, tricuspid septal leaflet angle and tricuspid annular diameter were predictors of persistent tricuspid regurgitation after 3 and 6 months of closure. Only estimated systolic pulmonary artery pressure, tricuspid septal leaflet angle and tricuspid annular diameter were independent predictors of persistent tricuspid regurgitation after 3, and 6 months of closure. CONCLUSION: Tricuspid regurgitation significantly improved after transcatheter atrial septal defect closure despite its significance at baseline due to remodeling in right side and tricuspid valve.

Histological topography of the atrioventricular node and its extensions in relation to the cardiothoracic surgical landmarks in normal human hearts.

BACKGROUND: Atrioventricular (AV) nodal injury which results in cardiac conduction disorders is one of the potential complications of heart valve surgeries and radiofrequency catheter ablations. Understanding the topography of the AV conduction system in relation to the tricuspid and mitral valves will help in reducing these complications. METHODS: A tissue block of 3cmx4cm, which contain the AV node, bundle of His and the AV nodal extensions, was excised at the AV septal junction in 20 apparently normal human hearts. The block was divided into three equal segments through vertical incisions perpendicular to the insertion of the septal leaflet of the tricuspid valve. Each segment was processed and stained with H&E and Gomori to study the different parts of the AV conduction system. RESULTS: The lower pole of the AV node was located vertically above the tricuspid septal leaflet (TSL) in 100% (20/20) of cases and at the level of the muscular interventricular septum in 65% (13/20) of cases. The upper pole of the compact AV node was located at the level of the mitral valve leaflet (MVL) in 50% (10/20) of cases. The penetrating bundle of His was seen at the level of the TSL, while the branching bundle of His was situated 1.9±1.5 mm inferior to the TSL. The right and left posterior extensions of the AV node spanned from the MVL to 2.9±1.3 mm above the TSL. CONCLUSIONS: A rectangular area (2.5 mm × 12 mm) in the Koch's triangle was devoid of AV nodal tissue and could be labeled as a safe area with no risk of conduction defects during valve surgeries. Information on the separation of AV nodal extensions from the TSL, MVL and muscular interventricular septum may play a crucial role in guiding and improving the safety of radiofrequency ablations.

Predictors of mid-term functional tricuspid regurgitation after device closure of atrial septal defect in adults: Impact of pre-operative tricuspid valve remodeling.

BACKGROUND: Functional TR occurs in adults with congenital atrial septal defect (ASD) due to left-to-right inter-atrial shunting and enlarged right heart. The prevalence and the predictors of TR following ASD closure in adults remain unknown. Moreover, whether preoperative anatomical parameters of tricuspid valve related to TR after ASD closure is understudied. METHODS: Comprehensive transthoracic echocardiography was performed in 64 consecutive secundum ASD patients before and at 3 months after device closure. Tricuspid valve parameters [annulus diameter (TAD), tenting area, tenting height, distal tricuspid septal leaflet angle (TSLA)], right ventricular (RV) function, pulmonary arterial pressures and severity of TR were recorded. Post-closure TR was defined as PISA radius ≥ 6 mm at 3 months. RESULTS: The TR severity was reduced after ASD closure with post-closure TR in 31 patients (48%) at follow-up. TR patients had larger ventricles, more TR, greater TAD, and larger tenting area/height and TSLA but similar RV long-axis function and pulmonary pressures at baseline. Pre-closure TAD [odds ratio (OR): 6.076, p=0.032] and TSLA (OR: 1.218, p=0.001) were the independent predictors for TR. A TAD >3.5 cm and a TSLA >30° had sensitivity, specificity, and area under the curve of 97%, 76%, and 0.82 and 100%, 78%, and 0.84, respectively. Assessment of TSLA showed an incremental value over TAD for predicting TR after closure (χ(2)=21.3 vs. 9.9, p<0.001). CONCLUSION: Nearly half of adults had TR following device closure of ASD. It was related to the excessive pre-operative structural remodeling in tricuspid valve rather than changes in RV.

Assessment of functional tricuspid regurgitation using 320-detector-row multislice computed tomography: risk factor analysis for recurrent regurgitation after tricuspid annuloplasty.

OBJECTIVE: Functional tricuspid regurgitation (TR) often develops secondary to left heart disease. Tricuspid annuloplasty (TAP) is usually the treatment of choice for significant TRs, but recurrence of TR after surgery can occur. Previous studies have not clearly demonstrated the cause of the recurrent TR after TAP. By using an electrocardiogram-gated 320-detector-row multislice computed tomography (CT), we sought to delineate the morphologic cause of the incompetent tricuspid valve and identify the risk factors for recurrent TR. METHODS: From August 2010 to September 2011, 35 patients underwent preoperative CT of the tricuspid valve. The distance between each commissure, the tethering angle of each leaflet, and the tethering height were measured. TAP using a rigid annuloplasty ring was performed in 22 patients. Risk factors for recurrent TR were determined by multivariate analyses. RESULTS: End-diastolic and end-systolic tricuspid valve annular diameters (TVAD) correlated significantly with preoperative TR severity (R(2), 0.2734-0.4287; P < .05). However, compared with TVAD, tethering angles and height showed stronger correlation with preoperative TR severity (R(2): tethering angles, 0.5769-0.6810; tethering height, 0.6854). Multivariate analysis revealed that tethering height was an independent risk factor of postoperative recurrent TR (P = .0069). CONCLUSIONS: TVAD, tethering angles, and tethering height correlated significantly with preoperative TR severity. The tethering height of the tricuspid valve showed significant correlation with recurrent TR.

The Pathophysiology of the Transient Neonatal Tricuspid Regurgitation

PURPOSE: This study was carried out to evaluate the role of the septal leaflet of the tricuspid valve. The hypothesis was that the neonatal tricuspid regurgitation (TR) was related to a transient elevation of right ventricular pressure in the neonatal period, that deviated ventricular septum and pull the anchored septal leaflet of the tricuspid valve. The pulled septal leaflet created the incomplete coaptation between the tricuspid valves and the regurgitation. METHODS: We used cross-sectional echocardiography, Doppler and color Doppler echocardiography to measure the normalized ventricular curvature at end-systole, the angle of the septal leaflet of the tricuspid valve, the type of coaptation of the tricuspid valve, the direction of regurgitation and the peak flow rate of regurgitation in 114 normal newborn babies (87 with TR, 27 without TR). RESULTS: The normalized septal curvature ratio (p=.0113), the angle of the septal leaflet (p=.0023) and the corrected diameter of the tricuspid valve annulus (p=.0008) were related statistically to the presence of TR (not in the angle of the anterior septum). But in the TR group, right ventricular pressure (calculated through peak velocity of TR) had no correlation with the above variables except the grade of TR (p=.002). CONCLUSIONS: One of the pathophysiological aspects of the neonatal TR is mainly related to the septal leaflet of the tricuspid valve, but the exact pathophysiology of neonatal TR may also be combined with other factors.