Performance and failure of right ventricle to pulmonary artery conduit in congenital heart disease.

INTRODUCTION: Surgical implantation of a right ventricle to pulmonary artery (RV-PA) conduit is an important component of congenital heart disease (CHD) surgery but with limited durability leading to re-intervention. Current single-center, retrospective, cohort study is reporting results of surgically implanted RV-PA conduits in a consecutive series of children and adults with CHD. METHODS: Patients with CHD referred for RV-PA conduits surgical implantation (October 1997 and January 2022) have been included. Primary outcome was conduit failure defined as peak gradient above 64mmHg/severe regurgitation/need for conduit-related interventions. Longitudinal echocardiographic studies were available for mixed-effect linear regression analysis. RESULTS: Two-hundred and fifty-two patients were initially included. One hundred and forty-nine patients were elegible for follow-up data collection. After a median follow-up time of 49 months the primary study endpoint occurred in 44 (29%) patients. Multivariable Cox regression model identified adult age (>18 years) at implantation and pulmonary homograft as protective factors (HR 0.11, 95% CI 0.02-0.47 and HR 0.34, 95% CI 0.16-0.74, respectively). Fever within 7 days of surgical conduit implantation was a risk factor for early (within 24 months) failure (OR 4.29, 95% CI 1.41-13.01). Longterm use of oral anticoagulant was independently associated with slower progression of peak echocardiographic gradient across conduits (mixed effect linear regression p-value 0.027). CONCLUSION: In patients with CHD, surgically implanted RV-PA conduit failure is faster in children and after non-homograft conduit implantation. Early fever after surgery is a strong risk factor for early failure. Longterm anticoagulation seems to exert a protective effect.

Clinical Course of Residual Ventricular Septal Defects After Congenital Heart Disease Repair.

The clinical course of residual ventricular septal defects after congenital heart disease repair is not completely elucidated in the medical literature. This study assessed the incidence, size, and clinical course of residual defects.This single-center retrospective study included 132 patients who survived after ventricular septal defect patch closure (n = 107) and intracardiac repair of double-outlet right ventricle (n = 16) and tetralogy of Fallot (n = 9). Residual defect was evaluated on transthoracic echocardiogram upon hospital discharge and at outpatient clinic visits.The median age at surgery was 1.2 (0.3-13.9) years. In total, 45 (34.1%) patients presented with residual defects upon hospital discharge. The residual defects were within 2 mm (n = 27), 2-3 mm (n = 15), and > 3 mm (n = 3), and the median size was 1.5 (0.5-3.8) mm. There was no late mortality during a median follow-up of 5.4 years. Among 42 residual defects measuring < 3 mm upon hospital discharge, 37 (82.2%) spontaneously closed. Further, five defects decreased in size (1.8 ± 0.6 mm upon hospital discharge vs1.2 ± 0.8 mm at the latest visits, p = 0.15). However, the size of three residual defects measuring > 3 mm upon hospital discharge increased, and two patients required re-surgery for residual defect.Significant residual defect requiring reoperation was rare. In most cases, residual defects measuring < 3 mm upon hospital discharge spontaneously closed within 5 years, and the size of the other defects decreased.

Cardiac Development and Animal Models of Congenital Heart Defects.

The major events of cardiac development, including early heart formation, chamber morphogenesis and septation, and conduction system and coronary artery development, are briefly reviewed together with a short introduction to the animal species commonly used to study heart development and model congenital heart defects (CHDs).

Cardiac Transcription Factors and Regulatory Networks.

Cardiac development is a fine-tuned process governed by complex transcriptional networks, in which transcription factors (TFs) interact with other regulatory layers. In this chapter, we introduce the core cardiac TFs including Gata, Hand, Nkx2, Mef2, Srf, and Tbx. These factors regulate each other's expression and can also act in a combinatorial manner on their downstream targets. Their disruption leads to various cardiac phenotypes in mice, and mutations in humans have been associated with congenital heart defects. In the second part of the chapter, we discuss different levels of regulation including cis-regulatory elements, chromatin structure, and microRNAs, which can interact with transcription factors, modulate their function, or are downstream targets. Finally, examples of disturbances of the cardiac regulatory network leading to congenital heart diseases in human are provided.

Human Genetics of Tetralogy of Fallot and Double-Outlet Right Ventricle.

Tetralogy of Fallot (TOF) and double-outlet right ventricle (DORV) are conotruncal defects resulting from disturbances of the second heart field and the neural crest, which can occur as isolated malformations or as part of multiorgan syndromes. Their etiology is multifactorial and characterized by overlapping genetic causes. In this chapter, we present the different genetic alterations underlying the two diseases, which range from chromosomal abnormalities like aneuploidies and structural mutations to rare single nucleotide variations affecting distinct genes. For example, mutations in the cardiac transcription factors NKX2-5, GATA4, and HAND2 have been identified in isolated TOF cases, while mutations of TBX5 and 22q11 deletion, leading to haploinsufficiency of TBX1, cause Holt-Oram and DiGeorge syndrome, respectively. Moreover, genes involved in signaling pathways, laterality determination, and epigenetic mechanisms have also been found mutated in TOF and/or DORV patients. Finally, genome-wide association studies identified common single nucleotide polymorphisms associated with the risk for TOF.

Human Genetics of Defects of Situs.

Defects of situs are associated with complex sets of congenital heart defects in which the normal concordance of asymmetric thoracic and abdominal organs is disturbed. The cellular and molecular mechanisms underlying the formation of the embryonic left-right axis have been investigated extensively in the past decade. This has led to the identification of mutations in at least 33 different genes in humans with heterotaxy and situs defects. Those mutations affect a broad range of molecular components, from transcription factors, signaling molecules, and chromatin modifiers to ciliary proteins. A substantial overlap of these genes is observed with genes associated with other congenital heart diseases such as tetralogy of Fallot and double-outlet right ventricle, d-transposition of the great arteries, and atrioventricular septal defects. In this chapter, we present the broad genetic heterogeneity of situs defects including recent human genomics efforts.

Long-term outcomes of surgical repair for corrected transposition of the great arteries.

BACKGROUND: This study investigated the long-term outcomes of physiological and anatomical repair for corrected transposition of the great arteries and double outlet right ventricle with discordant atrioventricular connection. METHODS: This single-center retrospective study included 146 patients who underwent biventricular repair of corrected transposition of the great arteries or double outlet right ventricle with discordant atrioventricular connections from 1972 to 2023. Survival rate, freedom from reoperation, NYHA classification and incidence of systemic ventricular dysfunction in the long-term were compared between physiological repair group (PR group) and anatomical repair group (AR group). RESULTS: PR group consisted of 55 patients with median age at repair of 10.3 years. Thirty-one patients underwent conventional Rastelli procedure and 24 patients underwent atrial and/or ventricular septal defect closure. AR group consisted of 91 patients with median age at repair of 5.8 years. Seventy-two patients underwent atrial switch plus Rastelli procedure and 19 patients underwent atrial plus arterial switch operation. The 30-year survival was 63.5% in PR group and 72.3% in AR group (p=0.448). The 30-year freedom from reoperation was 71.9% in PR group and 62.2% in AR group (p=0.220). There was a significant difference in incidence of systemic ventricular dysfunction between the groups (87.5% in PR group and 35.3% in AR group: p<0.001) and long-term survivors' NYHA classification (mean NYHA class of 1.9 in PR group and 1.5 in AR group: p=0.009). CONCLUSIONS: The systemic ventricular function and general status in the long-term were significantly better in anatomical repair patients, suggesting the potential advantage of anatomical repair.

The developmental processes of ventricular septal defects with outflow tract malalignment.

Ventricular septal defects (VSD) with outflow tract (OFT) malalignment are a common group of congenital heart diseases with varying severity. The developmental process of these defects is challenging to understand due to the complex nature of cardiac morphogenesis and the difficulties in visualizing the temporal and spatial changes that occur during pathogenesis. However, recent advancements in imaging techniques, such as high-resolution episcopic microscopy, have provided valuable insights into the normal septation of ventricular chambers and OFT alignment. Building upon this knowledge, we have utilized lightsheet microscopy, another innovative imaging method, to further investigate the developmental processes that lead to abnormal formation of the ventricular septum and the malalignment of arterial roots with the ventricular chambers. Our study highlights endocardial cushion hypoplasia and insufficient rotation of the outflow tract as two interrelated central factors contributing to the pathogenesis of these defects. This finding has the potential to enhance our understanding of the etiology of congenital heart diseases and may contribute to the development of improved diagnostic and therapeutic strategies in the future.

Impact of right ventriculotomy on cardiac function after pulmonary valve sparing repair of tetralogy of Fallot and double outlet right ventricle with pulmonary stenosis.

OBJECTIVES: Pulmonary valve-sparing repair of tetralogy of Fallot and double outlet right ventricle with pulmonary stenosis has the advantage of reduced incidence of late pulmonary valve regurgitation and better-preserved cardiac function. However, a right ventriculotomy is sometimes necessary in order to adequately relieve subvalvular pulmonary stenosis. We aimed to compare postoperative cardiac function and patients' symptoms between pulmonary valve-sparing repair with and without right ventriculotomy. MATERIALS AND METHODS: We retrospectively collected data from electronic medical records of Ramathibodi Hospital from 1st January 2013 to 31st October 2023. Patients diagnosed with tetralogy of Fallot and double outlet right ventricle with pulmonary stenosis who underwent pulmonary valve-sparing repair were included. Patients who underwent other types of repairs and whose medical record data were significantly missing were excluded. Demographic data, operative, and postoperative details were collected and reviewed. RESULTS: There were 49 patients included in our study with 10 patients undergoing pulmonary valve-sparing repair with and the other 39 without right ventriculotomy. Before-discharge echocardiographic parameters were generally similar between both groups (tricuspid annular plane systolic excursion = 0.9 versus 0.89 cm, P = 0.737; pressure gradient across pulmonary valve across pulmonary valve = 24 versus 19 mmHg, P = 0.275; left ventricular end-systolic volume index = 17.84 versus 19.19 ml/m2, P = 0.437; left ventricular end-diastolic volume index = 63.79 versus 61.13 ml/m2, P = 0.436). Patients' symptoms were also not statistically different. There was no early and late death up to the end date of our study. CONCLUSIONS: Right ventriculotomy in pulmonary valve-sparing repair did not result in worse postoperative cardiac function and symptoms. This suggested that the previously thought-to-be hazardous incision could be strongly considered if mandated.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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% remote type, 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%). CONCLUSION: 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.

How best can we name the channels seen in the setting of deficient ventricular septation?

Surgical repair of channels between the ventricles is enhanced when the surgeon knows precisely where to place a patch, or baffle, so as to restore septal integrity. The paediatric cardiologist should provide the necessary information. Communication will be enhanced if the same words are used to account for the structures in question. Currently, however, the same term, namely "ventricular septal defect," is used to account for markedly different areas within the heart. Closure of perimembranous defects found in hearts with concordant or discordant ventriculo-arterial connections restores the integrity of the ventricular septum, at the same time separating the systemic and pulmonary blood streams. When both arterial trunks arise from the right ventricle, in contrast, the surgeon when placing a baffle so as to separate the blood streams, does not close the channel most frequently described as the "ventricular septal defect." In this review, we show that the perimembranous lesions as found in hearts with concordant or discordant ventriculo-arterial connections are the right ventricular entrances to the areas subtended beneath the hinges of the leaflets of the aortic or pulmonary valves. When both arterial trunks arise from the right ventricle, and the channel between the ventricles is directly subaortic, then the channel termed the "ventricular septal defect" is the left ventricular entrance to the comparable space subtended beneath the aortic root. We argue that recognition of these fundamental anatomical differences enhances the appreciation of the underlying morphology of the various lesions that reflect transfer, during cardiac development, of the aortic root from the morphologically right to the morphologically left ventricle.

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.

Multicentre study on late outcomes of biventricular repair of double outlet right ventricle.

OBJECTIVES: The goal of this retrospective multicentre study was to present late surgical outcomes of the treatment of children with double outlet right ventricle (DORV) coming from emerging countries. METHODS: The Mécénat Chirurgie Cardiaque brings to France for surgery selected children with simple and complex congenital diseases, including DORV. The patients are operated on in 9 hospitals that specialize in paediatric cardiac surgery. Data are collected from the Mécénat Chirurgie Cardiaque comprehensive database, with a strict postoperative follow-up. The patients included only those who had biventricular repair of DORV with 2 viable ventricles. According to the classification of the Eleventh Revision of the International Classification of Diseases, DORV was defined as a congenital cardiovascular malformation in which both great arteries arise entirely or predominantly from the morphologically right ventricle. RESULTS: From January 1996 to January 2022, a total of 81 consecutive DORV biventricular repair operations were performed. There were 6 subtypes of DORV divided into 2 groups: DORV-committed ventricular septal defect (VSD): DORV-VSD (n = 25), DORV-Fallot (n = 34), DORV-transposition of the great arteries (n = 5); and DORV-non-committed (nc) VSD: DORV-ncVSD-no pulmonary stenosis (PS) (n = 7), DORV-ncVSD-PS (n = 5) and DORV-atrioventricular septal defect (AVSD)-PS (n = 5). Four Fontan patients were excluded. Three patients were lost to follow-up (3.4%). The overall perioperative mortality was 7.4% ± 2.6%, 6/81 (95% confidence interval: 2.8%-15.4%) ranging from 0% in DORV-AVSD-PS to 14% for DORV-ncVSD-no PS. The overall 10-year survival was 86%. The early mortality of DORV-ncVSD at 5.9% ± 2.4% (1/17) was similar to that of DORV-committed VSD at 7.8% ± 2.7% (5/64) (P = 0.79). There was a trend towards an optimal outcome for the arterial switch operation and the DORV-AVSD-PS repair. VSD enlargement was significantly more frequent in DORV-ncVSD at 42% (5/12) (P = 0.001). There were low numbers in the complex groups. The number of Fontan cases was noticeably low. The aorta located entirely on the right ventricle represents the fundamental anomaly and the surgical challenge of DORV. CONCLUSIONS: Overall survival at 10 years was 86%. This study shows a trend towards satisfactory early and late outcomes in BVR of simple DORV with committed VSD, compared to complex DORV with ncVSD.

Double outlet right ventricle.

This review article addresses the history, morphology, anatomy, medical management, and different surgical options for patients with double outlet right ventricle.

Exploring the Role of Modified Vascular Anatomical Molding (MVAM) in Prenatal Diagnosis Teaching and Prognosis Prediction of Fetal Complex Congenital Heart Disease (CCHD): A Preliminary Study.

Objective: The present study aimed to explore the role of modified vascular anatomical molding (MVAM) in prenatal diagnosis teaching and prognosis prediction of fetal complex congenital heart disease (CCHD). Methods: Step 1, MVAM method was used to cast the micro-blood vessels and trachea of 52 CCHD specimens. Subsequently, 52 MVAMs were analyzed and compared with the prenatal ultrasound to summarize their characteristics, misdiagnosis and MVAM's teaching role. Step 2, the surgical and follow-up data of 206 CCHD cases were retrospectively analyzed. Cases that evolved into critical illnesses or died within 1-3 years after surgery (poor prognosis) were classified into the study group (n = 77) and those with good prognosis into the control group (n = 129), which were split into the training set and the test set in the ratio 7:3 based on the time cut-off. In the training set, the prognosis of CCHD was predicted using the MVAM anatomical soft markers (distortion and narrowing of aorta/pulmonary artery, right ventricular infundibulum, etc.) and the decision curve analysis (DCA) performed. The model was validated using the test set, and a nomogram was finally established. Results: It was observed that all 52 CCHD cases were confirmed using MVAM. A total of 91 cardiac malformations were recorded, among which 41 malformations were misdiagnosed, and 29 malformations were missed by the prenatal echocardiography. The MVAM method has a good teaching/feedback effect on prenatal diagnosis. The combined model exhibited a higher predictive performance in the training- and test-set. Its high clinical net benefit was proved by DCA. Additionally, the nomogram established using the combined model received a favorable response in clinical practice. Conclusion: The research results indicated that MVAM improved the prenatal diagnosis teaching and training performance. The combined model established based on MVAM anatomical soft markers can offer a high clinical significance for prognosis prediction of CCHD.

Rare Occurrence of Double Outlet Right Ventricle and Cardiomyopathy on Dynamic Contrast-Enhanced Cardiac MRI: A Case Report.

We present a case of a middle-aged man with recent onset of vague chest pain. On dynamic contrast-enhanced cardiac magnetic resonance (CMR) imaging, he was found to have a double outlet right ventricle (DORV) and restrictive/infiltrative cardiomyopathy. These two conditions are not known associations and could be two entirely different entities.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.