Double Outlet Right Ventricle Research Articles

Relationship between diagnosis of conus arteriosus malformation and genetic diagnosis results in fetal cardiac axis abnormalities by echocardiography during middle pregnancy

ObjectiveTo explore the clinical value of echocardiography in detecting fetal cardiac axis abnormalities during middle pregnancy for diagnosing conus arteriosus malformation, and to compare and analyze the genetic diagnosis results, in order to provide evidence for clinical diagnosis and intervention.MethodsFour hundred twenty-one fetuses with conus arteriosus malformation from January 2020 to October 2023 were included as the conus arteriosus malformation group, and 917 healthy fetuses (all single fetuses) matched at the same gestational age were selected as the healthy group.ResultsThere was no significant difference in gestational weeks between two groups (P > 0.05). The age of pregnant women in conus arteriosus malformation group was lower compared to healthy group (P < 0.05), and the fetal cardiac axis in conus arteriosus malformation group was significantly higher compared to healthy group (P < 0.05). Among the fetuses with conus arteriosus malformation, tetralogy of Fallot (TOF), transposition of the great arteries (TGA) and double outlet right ventricle (DORV) had the highest proportions, accounting for 38.00%, 18.29% and 17.58%, respectively. Among all types of conus arteriosus malformations, atresia pulmonary valve syndrome associated with TOF, persistent truncus arteriosus and DORV exhibited higher proportions of fetal cardiac axis abnormalities, at 75.00%, 36.84% and 27.03%, respectively, while TGA and interrupted aortic arch associated with B-type interruption had lower proportions of fetal cardiac axis abnormalities, at 2.60% and 4.55%, respectively. Genetic testing was conducted on 73 cases (17.34%) of fetuses with conus arteriosus malformation in this study. Among them, fetal cardiac axis abnormalities were considered positive for genetic results due to factors such as aneuploidy, copy number abnormalities, and single-gene pathogenicity. A total of 31 cases tested positive for genetic anomalies, with a positive rate of approximately 42.47%.ConclusionIn the middle pregnancy, the fetal cardiac axis in cases of conus arteriosus malformation was significantly higher than in normal fetuses. Moreover, there were variations in fetal cardiac axis among different types of conus arteriosus malformations, and these differences were notably associated with genetic diagnostic results.

A VERY COMPLEX CASE OF DORV TYPE FALLOT: A CASE REPORT

Abstract Double outlet right ventricle (DORV) is a rare CHD characterized by ventriculoarterial connection in which both great arteries arise entirely or predominantly from the right ventricle. Its prevalence is 0.9% of all CHDs. Several chromosomal abnormalities have been associated with DORV, including trisomy 13, trisomy 18, and chromosome 22q11 deletion. Hearts with DORV are an extremely heterogeneous group showing various morphological features, connections, and relationships at each level of the cardiac segments and intersegmental junctions. As a consequence, the clinical manifestations and required surgical procedures for patients with DORV are variable. The anatomical spectrum is higly variable: it can be associated with ventricular septal defect, transposition of the great arteries (TGA) and functional single ventricle. We report the case of an infant with prenatal diagnosis of CHD and finding partial duplication of the short arm of the X chromosome. Pregnant woman at 22 weeks comes to the outpatient clinic to perform follow–up ultrasound. At that site finding of CHD which was later confirmed at birth and therefore prostaglandin therapy was started. Echocardiogram showed a wide DIV from malalignment with antero–cephalic deviation of the conal septum with significant aortic destroposition configuring picture of double outlet right ventricle. It also presents a complex right efflux obstruction already at subvalvular pulmonary departure. The pulmonary valve presented dysplastic, with en dome motion, hypoplastic. Pulmonary perfusion appears to be provided predominantly by the Botallo‘s duct originating from the isthmic region of the aorta and leading with a long and tortuous course to the pulmonary confluence near the left pulmnary artery with high velocity flow. The remaining findings are normal. Therefore, in view of the clinical picture, he was subjected to palliative surgery of right systemic–pulmonary shunt between the brachiocephalic trunk and right pulmonary artery (modified Blalock–Taussing surgery) in 3.5mm PTFE and ligation of Botallo‘s duct. At subsequent follow–up, the systemic–pulmonary shunt appeared pervious with regular flow. Wide DIV from anterior malalignment with aorta cavalier to DIV. Severe stenosis at complex pulmonary outflow with max gradient up to 124mmHg with dynamic and valvular component. For the subsequent course of treatment, the patient will be discussed collegially.

A 20–YEAR FOLLOW–UP OF SUCCESSFUL SURGICAL MANAGEMENT OF DOUBLE–OUTLET RIGHT VENTRICLE WITH PULMONARY STENOSIS: A CASE REPORT

Abstract A 25–year–old man, suffering from worsening exertional dyspnea for 4 months, was referred to our Cardiology Unit. The patient was previously diagnosed with a late diagnosis of double outlet right ventricle (DORV), as well as pulmonary stenosis, VSD, and right–sided aortic arch for which he underwent a first surgical procedure around the age of 2 involving an intersternal anastomosis through a left lateral thoracotomy approach. A second intervention took place 2 years later for a radical correction of the anomaly through a median sternotomy. The patient had sporadic follow–up since then. A baseline ECG was performed, showing evidence of sinus rhythm, normal AV with a bifid P wave in lead II, slight RAD, incomplete RBBB, and asymmetric negative T waves from V1 to V3 and in aVL, and biphasic T waves in V4–V5. We performed an echocardiogram which showed: a dilated RA, a normal–sized LA, an apparently intact interatrial septum without evident shunts; a normal sized LV; EF 60%; a moderately dilated, hypertrophic and hypertrabeculated RV; FAC 33%; normal aortic flow; a minimal MR; a massive residual pulmonary insufficiency; a moderate TR; a dilatated pulmonary trunk; a normal–sized and collapsible IVC upon inspiration; PAPs of 70 mmHg; no pericardial effusion. A maximal exercise stress test appeared to be normal throughout. However, due to the severe pulmonary hypertension he was referred to our PH centre. While these patients are commonly affected by residual early or late left ventricular outflow tract obstruction, fortunately our patient was not. DORV is a relatively common congenital heart defect characterized by an abnormal connection between the ventricles and arteries, in which both the aorta and the pulmonary trunk are connected completely or predominantly to the right ventricle. The anatomical spectrum of this anomaly is quite large, and it can be associated with the presence of a VSD that often extends towards one or both of the arterial valves, allowing the flow of blood from the left ventricle to the aorta. An accurate diagnosis through echocardiography or CMR is essential in order to guide the surgical repair and the appropriate therapeutic approach for individuals affected by this anomaly. A successful surgical correction of DORV is essential, but it is important to be aware of the potential complications of post–operative PH (especially in patients with preoperative PH), which necessitates close surveillance and appropriate therapeutic management.

Recent advances in multimodal imaging in tetralogy of fallot and double outlet right ventricle.

In the ever-evolving field of medical imaging, this review highlights significant advancements in preoperative and postoperative imaging for Tetralogy of Fallot (TOF) and double outlet right ventricle (DORV) over the past 18 months. This review showcases innovations in echocardiography such as 3D speckle tracking echocardiography (3DSTE) for assessing right ventricle-pulmonary artery coupling (RVPAC) and Doppler velocity reconstruction (DoVeR) for intracardiac flow fields evaluation. Furthermore, advances in assessment of cardiovascular anatomy using computed tomography (CT) improve the integration of imaging in ablation procedures. Additionally, the inclusion of cardiac magnetic resonance (CMR) parameters as risk score predictors for morbidity, and mortality and for timing of pulmonary valve replacement (PVR) indicates its significance in clinical management. The utilization of 4D flow techniques for postoperative hemodynamic assessment promises new insights into pressure mapping. Lastly, emerging technologies such as 3D printing and 3D virtual reality are expected to improve image quality and surgical confidence in preoperative planning. Developments in multimodality imaging in TOF and DORV are poised to shape the future of clinical practice in this field.

Navigating the spectrum of double-outlet right ventricle presentations: Outcomes from a contemporary cohort based on subtypes.

Our aim in this study was to investigate the prenatal and postnatal prognosis of double outlet right ventricle (DORV) cases diagnosed prenatally by analyzing the outcomes based on the subtype. This study is a retrospective chart review. Cases diagnosed with fetal DORV by prenatal ultrasound in the maternal-fetal medicine department of our hospital between 2014 and 2022 were included. Data on maternal characteristics, fetal echocardiographic features (type of DORV), pregnancy and neonatal outcomes (termination of pregnancy [TOP], intrauterine fetal death [IUD], neonatal death [NND], death in infancy (IND), survival) were collected and analyzed. Ninety-nine cases of prenatally diagnosed cases of DORV were included. The prenatal diagnosis was right in 97% of the liveborn fetuses. The cases were classified into subtypes, including transposition of great arteries (TGA), Fallot, ventricular septal defect (VSD), remote, and heterotaxy types. The cohort consisted of 32.3% TGA type, 19.1% fallot type, 11.1% VSD type, 2% remotetype, and 35.3% heterotaxy type of DORV. An additional cardiac anomaly was observed in 87% and an extra-cardiac anomaly was observed in 54% of the cases. When we excluded the cases with heterotaxy type but without any chromosomal abnormality, additional genetic abnormalities were detected in 42% of the remaining cases. Outcome of pregnancy was livebirth in 68/99 (68.7%), IUFD in 5/99 (5.1%), and TOP in 26/99 (26.3%). Postnatal cardiac surgical repair was performed in 48 cases. Survival among livebirths was 39/68 (57.3%). Twenty-nine neonates or infants who had additional cardiac anomalies and/or genetic abnormalities died before any surgical intervention. The postoperative survival rate was 39/48 (81.2%). The prognosis in DORV depends on the anatomical subtype, the presence, and severity of associated anomalies. Survival increases in isolated cases without any additional structural or genetic anomalies.

Double outlet right ventricle - the 50% rule has always been about the conus.

There has been much variability in the definition of double outlet right ventricle (DORV) spanning the last century. Historically, emphasis has been placed on the assignment of the great arteries to the right ventricle as a definition of DORV. In this review, we aim to underscore the importance of conal muscle, rather than rules surrounding assignment of great arteries to ventricles. We will be outlining the variability in patient anatomy that results from variations in conal muscle development in DORV, which may not fit perfectly into predefined constructs. This anatomic variability directly determines physiology and surgical repair options. There is a growing appreciation of the utility of cross-sectional imaging in complex DORV, and the generation of patient-specific 3D models with virtual reality simulations for surgical planning. These models improve the prediction of candidacy for biventricular repair and allow the mapping of complex baffle pathways preoperatively. DORV is not a disease entity in itself, but rather a vast spectrum of disorders associated with maldevelopment of conal muscle and often abnormal expansion of one the great vessels. Patient-specific 3D models will be crucial for improved surgical planning and patient outcomes.

Comprehensive Multiomics Analysis of Monozygotic Twin Discordant for Double Outlet Right Ventricle

AbstractThe objective of this study was to understand and measure epigenetic changes associated with the occurrence of CHDs by utilizing the discordant monozygotic twin model. A unique set of monozygotic twins discordant for double-outlet right ventricles (DORVs) was used for this multiomics study. The cardiac and muscle tissue samples from the twins were subjected to whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and liquid chromatography-tandem mass spectrometry analysis. Sporadic DORV cases and control fetuses were used for validation. Global hypomethylation status was observed in heart tissue samples from the affected twins. Among 36,228 differentially methylated regions (DMRs), 1097 DMRs involving 1039 genes were located in promoter regions. A total of 419 genes, and lncRNA–mRNA pairs involved 30 genes, and 62 proteins were significantly differentially expressed. Multiple omics integrative analysis revealed that five genes, including BGN, COL1A1, COL3A1, FBLN5, and FLAN, and three pathways, including ECM-receptor interaction, focal adhesion and TGF-β signaling pathway, exhibited differences at all three levels. This study demonstrates a multiomics profile of discordant twins and explores the possible mechanism of DORV development. Global hypomethylation might be associated with the risk of CHDs. Specific genes and specific pathways, particularly those involving ECM–receptor interaction, focal adhesion and TGF–β signaling, might be involved in the occurrence of CHDs.

Intracardiac Three-Dimensional Image as Surgical Decision-Making Tool of Congenital Heart Disease.

This study aimed to evaluate the anatomical reproducibility of a preoperative intracardiac 3D image (IC image) created using computed tomography, and to investigate its usefulness as a surgical decision-making tool. Between 2012 and 2022, ventricular septal defect (VSD) patients, and double outlet right ventricle (DORV) or transposition of the great arteries (TGA) with pulmonary stenosis (PS) patients who underwent cardiac surgery and had preoperative computed tomography were enrolled. SYNAPSE VINCENT® (Fujifilm) was used to create an IC image which was analyzed retrospectively. In 14 VSD patients, the diagnostic consistency rate in the Soto classification with intraoperative findings was 100% (14/14) for IC image versus 64% (9/14) for transthoracic echocardiography (P = 0.04). The defect size showed a higher correlation coefficient with IC image (0.837, P = 0.001) than with transthoracic echocardiography (0.567, P = 0.034). In 11 DORV/TGA with PS patients, the diagnostic consistency rate in the Lev classification was 100% (9/9) for IC image versus 77% (7/9) for transthoracic echocardiography (P = 0.47). The secondary interventricular foramen (SVF)/left ventricular outflow tract (LVOT) ratio by IC image was significantly smaller in the biventricular-repair group (median 0.71, IQR 0.67-1.06) than in the univentricular-repair group (median 1.79, IQR 1.53-2.42) (P = 0.006). An IC image is useful as a surgical decision-making tool for simple VSDs and complex congenital heart diseases such as DORV or TGA with pulmonary stenosis. The SVF/LVOT ratio determined from the IC image may be a useful indicator for avoiding LVOT obstruction.

Decreased clinical performance in TGA-ASO patients after RVOT re-interventions; multicenter European collaboration

Abstract Background In patients with transposition of the great arteries and an arterial switch operation (TGA-ASO) right ventricular outflow tract (RVOT) obstruction is a common complication requiring one or more RVOT reinterventions. However, data on the impact of reinterventions on clinical performance is scarce. Therefore, we aimed to assess in TGA-ASO patients the cardiopulmonary exercise capacity (CPET) and right ventricular function stratified for the number of RVOT reinterventions. Method This multicenter observational study was performed in adult (≥16 years) TGA-ASO patients from the EPOCH (European Collaboration for Prospective Outcome Research in Congenital Heart disease). All patients underwent a comprehensive clinical workup including CPET and echocardiography, including right ventriculo-arterial (VA) coupling (defined as tricuspid annular plane systolic excursion (TAPSE) / right ventricular systolic pressure (RVSP) ratio). Patients were stratified for the number of reinterventions at the RVOT, including re-interventions at the pulmonary valve, main pulmonary artery and pulmonary branches. Association between RVOT re-intervention(s) and functional parameters, including predicted (%) peak oxygen uptake (peak VO2), TAPSE, right ventricle (RV) S’ and VA coupling of the RV were analyzed with linear regression. Results A total of 449 TGA patients were included in this study, with a mean age of 25.4 ± 5.6 years and median time until ASO was 8 days [IQR 6-15]. Eleven (2.5%) patients with previous re-interventions at the left ventricular outflow tract (LVOT) or aortic arch were excluded from the analysis. Twenty-six percent of the included patients had a ventricular septal defect (VSD) and 1.6% were diagnosed with double outlet right ventricle (DORV). In the total cohort, 13% of the patients had 1 previous RVOT re-intervention, 8% had 2 RVOT re-interventions and 5% had 3 RVOT re-interventions. Patients had echocardiographic examination and 55% underwent CPET. Predicted VO2peak was significantly reduced in patients with 1 RVOT re-intervention (72%), 2 RVOT re-interventions (69%) and 3 RVOT re-interventions (71%) compared to patients without any-reintervention (77%) (p=0.0268). Right VA coupling was a significant predictor (p=0.017) for reduced hemodynamic performance in patients with 1 RVOT re-intervention (0,50), 2 RVOT re-interventions (0,51) and 3 RVOT re-interventions (0,26). Conclusion In TGA-ASO patients, RVOT reinterventions were associated with a reduced clinical performance. VA coupling of the right ventricle was the most sensitive marker for hemodynamic performance in TGA-ASO patients.

Abstract 16255: Unraveling the Complex Interplay: Atrial Flutter in a Patient With Prior Double Outlet Right Ventricular Repair

Introduction: Double Outlet Right Ventricle (DORV) is a rare complex congenital heart disease (CHD) in which both the great arteries arise predominantly or entirely from the right ventricle. It is one of the rare CHD lesions with a prevalence of about 0.9%. These patients have complex anatomy, which increases their risk of recurrent arrhythmias. We present a challenging case of Atrial Flutter (AFL) in a patient with DORV. Case: A 31-year-old male with a history of DORV repair presented with palpitations and chest pain for 2 days. His heart rate (HR) was 240 bpm. EKG showed AFL with variable block [Figure 1]. Labs were unremarkable. The patient remained in AFL with HR above 120 bpm despite receiving diltiazem and adenosine. Considering his underlying complex anatomy, ablation was deferred, and the patient was cardioverted to sinus rhythm [Figure 1]. A loop monitor was placed and was started on flecainide with outpatient follow-up at a higher centre. Discussion: Infundibulotomy, removal of obstructive muscle bundles, and a patch to widen the passageway from the right ventricle to the pulmonary arteries are all steps in DORV repair. These surgeries result in scar tissue, an akinetic right ventricular outflow tract, and pulmonary valve insufficiency. Reentrant tachycardias may form due to surgical scars. In DORV patients, Atrial tachyarrhythmias have undesirable outcomes resulting in congestive heart failure, stroke, and mortality. Antiarrhythmics and cardioversion are the cornerstones of managing AFL in patients with DORV due to increased failure rates of catheter ablation. Conclusion: This case illustrates persistent atrial arrhythmias more likely due to DORV repair, resulting in cardiac remodeling. The abnormal anatomy makes localization of irritated ectopic foci and ablations ineffective and difficult.

Abstract 17273: Phenotypic Clustering of Patients With Heterotaxy Syndrome Predicts Outcomes of Mortality and Transplantation

Background: Current classifications of heterotaxy syndrome (HS) (e.g. left/right isomerism, polysplenia/asplenia) do not capture the heterogeneity of cardiac anomalies observed nor provide insight on risk stratification. We aimed to improve these classifications using cluster analysis to identify anatomic phenotypes in HS patients. Methods: Using a retrospective database of all HS patients seen at Boston Children’s Hospital from 1985-2014 (n=264), we performed principal component and cluster analyses on 47 cardiac anatomic variables and compared rates of mortality/transplantation across clusters. Results: Five clusters were identified ranging in size from 19 to 91 patients. Cluster #1 had a high prevalence of right-dominant complete atrioventricular canal defects (CAVC), double-outlet right ventricle (DORV), pulmonary stenosis/atresia (PS/PA), and total anomalous pulmonary venous connection (TAPVC); Cluster #2 of left-dominant CAVC, DORV, and TAPVC; Cluster #3 of left-sided obstructive lesions and interrupted IVC; Cluster #4 of transposition of the great arteries with PS/PA; and Cluster #5 of interrupted IVC with miscellaneous cardiac anomalies (Table). Over 80% of patients in clusters 1 and 2 underwent single ventricle palliation compared with only 16% of patients in cluster 5. Transplant-free survival was lowest in clusters 1, 2, and 3 but differed by single versus biventricular repair (Figure). Conclusions: Cluster analysis of cardiac anatomic variables identified 5 phenotypes of HS including 3 higher risk and 2 lower risk phenotypes. These findings highlight the need for improved phenotyping of HS to account for the high degree of disease heterogeneity.

Analysis of the distribution and orientation of oxygenated and non-oxygenated blood in a double outlet right ventricle

Double outlet right ventricle (DORV) is a malformation of the fetal heart in utero that affects the ventricular chambers. It usually presents with a displacement of the aorta and more than half the circumference of both arterial valves in the right ventricle. A peculiar characteristic is given by an interventricular septal defect (VSD), which allows communication between the left ventricle and the right with consequent mixing of oxygenated and non-oxygenated blood inside the cavities. A crucial question in assessing the degree of severity of functional dysfunction concerns the percentage of oxygenated blood that is ejected into the primary circulation via the aorta, a result that depends on the details of the vortex flow pattern within the two ventricular chambers. This study analyzes a complete DORV case through the use of numerical simulations that allow to identify the concentrations of oxygenated and non-oxygenated blood passing through this geometry. Results show that the VSD presents a significant impact on the fluid dynamic performance of the two ventricles. The analysis of blood concentration allowed to quantify the presence of oxygenated blood ejected into the pulmonary artery and of non-oxygenated blood into the aortic artery. The analysis of this specific case aims to demonstrate how the fluid dynamics analysis of this rare malformation, properly coupled with imaging technology, can provide information that could not be obtained otherwise and that are relevant for a careful clinical management including timely therapeutic intervention.

Associated congenital heart disease with Hirschsprung's disease: a retrospective cohort study on 2,174 children.

To examine the incidence and phenotypes of congenital heart disease (CHD) in a large cohort of patients with Hirschsprung's disease (HSCR). Retrospective data review of children with HSCR between 2003 and 2020 was conducted at the Provincial Key Laboratory for Structural Birth Defects in Guangzhou, Guangdong, China. HSCR was confirmed by pathological diagnosis. CHD was defined as a gross structural abnormality of the heart or intrathoracic great vessels that is of functional significance. A total of 2,174 HSCR patients (84.7% males) were studied and 306 of them underwent echocardiography. Overall, 27 children (1.2%) had associated CHD. Among them, CHDs mostly presented as atrial and ventricular septal defects (n = 5 and 12 respectively) and patent ductus arteriosus (n = 4). Three patients (1.4‰) presented as a severe CHD including complete atrioventricular canal, congenitally corrected transposition of the great arteries and double-outlet of right ventricle. Among 14 patients carrying a chromosomal abnormality, CHD was detected in 4 infants (28.6%), all being mild forms of septal defects. Some new and severe types of CHD were found in patients with HSCR. Patients with syndromic features had higher incidence of CHD.

Double Outlet Right Ventricle with Pulmonary Atresia and Antero-Posterior Malposition of Great Arteries: Transthoracic Echocardiographic Evaluation of a rare cyanotic congenital heart disorder

Double outlet right ventricle (DORV) is a heterogeneous group of abnormal ventriculoarterial connections where, by definition, both great arteries (pulmonary artery and aorta) arise primarily from the morphologically right ventricle, This condition affects 1-1.5% of the patients with congenital heart diseases, with a frequency of 1 in each 10,000 live births. We are reporting a case of seven year old deeply cyanotic child with DORV, subaortic VSD with rare anatomic features of antero-posterior malposition of great arteries (GA) and pulmonary vavular atresia, with conspicuous absence of patent ductusarteriosus (PDA) or major aorto-pulmonary collaterals (MAPCAs), despite the presence of atretic pulmonary valve. Keywords: DORV, Pulmonary atresia, TGA, VSD, subaortic VSD, overriding of Aorta, cyanotic congenital heart defects.

A Case of Antenatal Diagnosis of Ectopia Cordis with Cardiac Disease

Ectopic cordis is a rare anomaly with incidence of 5.5 to 7.9 per one million. In this anomaly, fetal heart is displayed towards outside of the thoracic cavity partially or completely. We describe a case of antenatal diagnosis of Thoracic Ectopia Cordis (EC) with CongenitalHeartDisease (CHD) without any other extracardiac malformations. The mother was referred to our center at 18 weeks of gestation due to abnormal sonography. Fetal Echocardiographic examination showed isolated thoracic ectopia cordis with Double Outlet Right Ventricle (DORV), large inlet to outlet Ventricular Septal Defect (VSD), malposition of Aorta, Pulmonary Atresia with retrograde flow, narrow Pulmonary Artery (PA) and PA branches. Amniocentesis and sonography revealed no other anomaly or chromosomal derangement. Because the diagnosis of Ectopia cordis may be difficult in the fetal period due to multiple factors, meticulous attention should be paid for true diagnosis.

Characterization of ultrasound and postnatal pathology in fetuses with heterotaxy syndrome.

To explore the diagnostic clues and abnormality spectrum of heterotaxy syndrome by prenatal ultrasonography and postnatal verification. The prenatal ultrasonic data of 88 heterotaxy syndrome fetuses were analyzed retrospectively as left isomerism (LI) and right isomerism (RI). Prenatal ultrasound compared with the anatomical casting of the fetal body after labor induction, and the confirmatory postnatal diagnosis after delivery. Fetal LI showed typical malformations of gastric vesicles on different sides from the heart, absence of hepatic segment of the inferior vena cava (IVC), abdominal aorta (AO) parallel with the azygos vein (AV), bilateral left bronchus, bilateral left atrial appendages, and polysplenia; intracardiac malformations of AV septal defects (AVSD), single atrium (SA), left ventricular outflow tract obstruction (LVOTO), and double-outlet right ventricle (DORV); and cardiac conduction abnormalities of sinus bradycardia and AV blockage. Fetal RI reported typical malformations of gastric vesicles on different sides from the heart, juxtaposition of the IVC with AO, anomalous pulmonary venous connection (APVC), asplenia, and bilateral right atrial appendages; intracardiac malformations of AVSD, SA, single ventricle, pulmonary atresia and stenosis, and DORV. The postnatal verification revealed 3 malformations misdiagnoses and 4 malformations missed diagnoses in LI fetuses and 10 misdiagnoses and 8 missed diagnoses in RI fetuses. The proposed five-step prenatal ultrasonography has an important diagnostic value for the identification and classification of heterotaxy syndrome. The different sides of gastric vesicles and cardiac apex are important diagnostic clues for heterotaxy syndrome, featuring disconnected or hypoplastic IVC, typical complex cardiac malformation, and atrioventricular block in fetal LI, and shown APVC, juxtaposition of IVC and AO, and intracardiac malformations such as AVSD, DORV, and LVOTO in fetal RI.

Double Outlet Right Ventricle Infective Endocarditis: A Rare Combination and a Therapeutic Challenge

Infective endocarditis involving the right side of the heart occurs rarely and often involves the tricuspid valve. The isolated pulmonary valve infective endocarditis (IPVIE) is a less common condition that occurs in specific population. The double outlet right ventricle (DORV) is an unusual congenital heart disease. The association of DORV and IPVIE darkens the prognosis. We report two cases of the association of DORV and IPVIE. The transthoracic echocardiography (TTE) is the base to the diagnosis. Right sided infective endocarditis in the lack of a guided strategy remains a therapeutic challenge.

Ventricular tachycardia substrates in young patients with repaired tetralogy of fallot

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): We acknowledge the support from the Netherlands Cardiovascular Research lnitiative: An initiative with support of the Dutch Heart Foundation and Hartekind. Background Patients with repaired tetralogy of Fallot (rTOF) have a time-dependent increase in risk of ventricular tachycardia (VT) after the age of 30 years (Y), with slow conducting anatomical isthmus (SCAI) 3, located between the pulmonary annulus and the ventricular septal defect (VSD) patch, as dominant VT substrate (1-4). However, SCAI may be already present before 30Y. Purpose To assess (1) the prevalence of SCAI, (2) the associated factors in SCAI development, and (3) the occurrence of clinical VT, in rTOF patients <30Y. Methods From a database of 146 patients with rTOF or related lesions who underwent electroanatomical mapping (EAM) and programmed electrical stimulation (PES) between 2007 and 2022 for treatment of ventricular arrhythmias (VA), risk stratification or before pulmonary valve replacement (PVR), those aged <30Y at time of procedure were selected and analysed. Results Of 146 rTOF patients, 55 (38%) were <30Y (median 16Y [IQR 14-22]); 33/55 (60%) had TOF, 9/55 (16%) TOF with double outlet right ventricle (DORV), and 13/55 (24%) complex TOF variants, including 8 patients with pulmonary atresia with VSD, 2 patients with absent pulmonary valve, and 3 with other variations. Initial intracardiac surgical repair (median age 0.8Y [IQR 0.4-1.4]) was performed via a ventriculotomy in 10/55 (18%) after palliative shunts in 16/55 (29%). An RV to pulmonary artery (RV-PA) conduit was inserted during initial or early after (<1Y) initial repair in 12/55 (22%). In 14/55 (25%) pulmonary valve replacement (PVR) was performed later in life (median age 10.1Y [IQR 2.7-14.3]). Five of 55 (9%) underwent EAM/PES after a spontaneous VA, 40/55 (73%) before PVR, and 10/55 (18%) for risk stratification. Monomorphic VT was inducible in 8/55 (15%), including 4/5 patients with spontaneous VT, and was proven related to a SCAI 3 in 7/8 (88%). In 16/55 (29%) SCAI 3 could be identified; no other SCAI (1,2,4) was present. Of note, 9/16 (56%) of patients with SCAI 3 had initial RV-PA conduit repair/early PVR, in comparison with only 3/39 (8%) of patients without SCAI. In univariable analysis complex TOF (OR 6.8 [95% CI 1.8-26.4]), ventriculotomy (OR 5.3 [95% CI 1.2-22.3]), any prior PVR (OR 4.8 [95% CI 1.4-16.7]), and initial RV-PA conduit/early PVR (OR 15.4 [95% CI 3.3-71.8]) were significantly associated with SCAI 3. In multivariable analysis initial RV-PA conduit/early PVR remained the only independent predictor of SCAI 3 (OR 13.0 [95% CI 1.2-142.4]). Conclusions A SCAI 3 is present in 29% of rTOF patients <30Y referred for EAM/PES and the dominant VT substrate for spontaneous and inducible VTs. RV-PA conduit placement during initial repair or early PVR (<1Y after repair) is associated with SCAI 3 in young rTOF. Whether the early conduit/valve placement causes scarring at the infundibulum with consecutive slow conduction and/or whether the complex variants contribute to SCAI requires additional studies.

Optimized preoperative planning of double outlet right ventricle patients by 3D printing and virtual reality: a pilot study.

In complex double outlet right ventricle (DORV) patients, the optimal surgical approach may be difficult to assess based on conventional 2-dimensional (2D) ultrasound (US) and computed tomography (CT) imaging. The aim of this study is to assess the added value of 3-dimensional (3D) printed and 3D virtual reality (3D-VR) models of the heart used for surgical planning in DORV patients, supplementary to the gold standard 2D imaging modalities. Five patients with different DORV subtypes and high-quality CT scans were selected retrospectively. 3D prints and 3D-VR models were created. Twelve congenital cardiac surgeons and paediatric cardiologists, from 3 different hospitals, were shown 2D-CT first, after which they assessed the 3D print and 3D-VR models in random order. After each imaging method, a questionnaire was filled in on the visibility of essential structures and the surgical plan. Spatial relationships were generally better visualized using 3D methods (3D printing/3D-VR) than in 2D. The feasibility of ventricular septum defect patch closure could be determined best using 3D-VR reconstructions (3D-VR 92%, 3D print 66% and US/CT 46%, P < 0.01). The percentage of proposed surgical plans corresponding to the performed surgical approach was 66% for plans based on US/CT, 78% for plans based on 3D printing and 80% for plans based on 3D-VR visualization. This study shows that both 3D printing and 3D-VR have additional value for cardiac surgeons and cardiologists over 2D imaging, because of better visualization of spatial relationships. As a result, the proposed surgical plans based on the 3D visualizations matched the actual performed surgery to a greater extent.

Congenital heart defects caused by FOXJ1.

FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left-right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left-right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease. Here, we report a novel truncating FOXJ1 variant (c.784_799dup; p.Glu267Glyfs*12) identified by clinical exome sequencing from a patient with isolated congenital heart defects (CHD) which included atrial and ventricular septal defects, double outlet right ventricle (DORV) and transposition of the great arteries. Functional experiments show that FOXJ1 c.784_799dup; p.Glu267Glyfs*12, unlike FOXJ1, fails to induce ectopic cilia in frog epidermis in vivo or to activate the ADGB promoter, a downstream target of FOXJ1 in cilia, in transactivation assays in vitro. Variant analysis of patients with heterotaxy or heterotaxy-related CHD indicates that pathogenic variants in FOXJ1 are an infrequent cause of heterotaxy. Finally, we characterize embryonic-stage CHD in Foxj1 loss-of-function mice, demonstrating randomized heart looping. Abnormal heart looping includes reversed looping (dextrocardia), ventral looping and no looping/single ventricle hearts. Complex CHDs revealed by histological analysis include atrioventricular septal defects, DORV, single ventricle defects as well as abnormal position of the great arteries. These results indicate that pathogenic variants in FOXJ1 can cause isolated CHD.