Outlet Septum Research Articles

The Surgical Significance of Phenotypic Variability in the Setting of Tetralogy of Fallot.

The phenotypic feature of tetralogy of Fallot is anterocephalad deviation of the muscular outlet septum, or its fibrous remnant, relative to the septoparietal trabeculation, coupled with hypertrophy of septoparietal trabeculations. Although this feature permits recognition of the entity, no two cases are identical. Once diagnosed, treatment is surgical. The results of surgical treatment have improved remarkably over recent decades. The results are now sufficiently excellent, including those in the developing world, that attention is now directed toward avoidance of morbidity, while still seeking, of course to minimize any fatalities due to surgical intervention. It is perhaps surprising that attention thus far has not been directed on the potential significance of phenotypic variation relative to either mortality or morbidity subsequent to surgical correction. The only study we have found specifically addressing this variability focused on the extent of aortic override, and associated malformations, but made no mention of variability in the right ventricular margins of the interventricular communication, nor the substrates for subpulmonary obstruction. In this review, therefore, we assessed the potential significance of known morphological variability to the outcomes of surgical intervention in over 1,000 individuals undergoing correction by the same surgeon in a center of excellence in a developing country. We sought to assess whether the variations were associated with an increased risk of postoperative death, or problems of rhythm. In our hands, double outlet ventriculoarterial connection was associated with increased risk of death, while the presence of a juxta-arterial defect with perimembranous extension was associated with rhythm problems.

Revisiting the anatomy of the right ventricle in the light of knowledge of its development.

Controversies continue regarding several aspects of the anatomy of the morphologically right ventricle. There is disagreement as to whether the ventricle should be assessed in bipartite or tripartite fashion, and the number of leaflets to be found in the tricuspid valve. In particular, there is no agreement as to whether a muscular outlet septum is present in the normally constructed heart, nor how many septal components are to be found during normal development. Resolving these issues is of potential significance to those investigating and treating children with congenitally malformed hearts. With all these issues in mind, we have revisited our own experience in investigating the development and morphology of the normal right ventricle. To assess development, we have examined a large number of datasets, prepared by both standard and episcopic microscopy, from human and murine embryos. In terms of gross anatomy, we have compared dissections of normal autopsied hearts with virtual dissections of datasets prepared using computed tomography. Our developmental and postnatal studies, taken together, confirm that the ventricle is best assessed in tripartite fashion, with the three parts representing its inlet, apical trabecular, and outlet components. The ventricular septum, however, has only muscular and membranous components. The muscular part incorporates a small component derived from the muscularised fused proximal outflow cushions, but this part cannot be distinguished from the much larger part that is incorporated within the free-standing muscular infundibular sleeve. We confirm that the tricuspid valve itself has three components, which are located inferiorly, septally, and antero-superiorly.

Mutations in genes related to myocyte contraction and ventricular septum development in non-syndromic tetralogy of Fallot.

Eighty percent of patients with a diagnosis of tetralogy of Fallot (TOF) do not have a known genetic etiology or syndrome. We sought to identify key molecular pathways and biological processes that are enriched in non-syndromic TOF, the most common form of cyanotic congenital heart disease, rather than single driver genes to elucidate the pathogenesis of this disease. We undertook exome sequencing of 362 probands with non-syndromic TOF and their parents within the Pediatric Cardiac Genomics Consortium (PCGC). We identified rare (minor allele frequency <1 × 10-4), de novo variants to ascertain pathways and processes affected in this population to better understand TOF pathogenesis. Pathways and biological processes enriched in the PCGC TOF cohort were compared to 317 controls without heart defects (and their parents) from the Simons Foundation Autism Research Initiative (SFARI). A total of 120 variants in 117 genes were identified as most likely to be deleterious, with CHD7, CLUH, UNC13C, and WASHC5 identified in two probands each. Gene ontology analyses of these variants using multiple bioinformatic tools demonstrated significant enrichment in processes including cell cycle progression, chromatin remodeling, myocyte contraction and calcium transport, and development of the ventricular septum and ventricle. There was also a significant enrichment of target genes of SOX9, which is critical in second heart field development and whose loss results in membranous ventricular septal defects related to disruption of the proximal outlet septum. None of these processes was significantly enriched in the SFARI control cohort. Innate molecular defects in cardiac progenitor cells and genes related to their viability and contractile function appear central to non-syndromic TOF pathogenesis. Future research utilizing our results is likely to have significant implications in stratification of TOF patients and delivery of personalized clinical care.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

ISUOG Practice Guidelines (updated): fetal cardiac screening.

Abstract 14923: A Special Type Aortic Left Ventricular Tunnel With Bicuspid Aortic Valve: A Case Report

Introduction: Aortic-left ventricular tunnel (ALVT) is an extremely rare congenital cardiac lesion that is an abnormal passage connecting the ascending aorta to the left ventricle. ALVT can be diagnosed by the use of real-time two-dimensional and continuous-wave Doppler echocardiography. Case presentation: A two-year and seven-month-old boy with recently diagnosed influenza presented to the hospital because of severe tachypnea and fatigue after running. Physical examination revealed a grade 3/6 systolic and diastolic murmur at the second and third left intercostal space. Transthoracic echocardiography (GE E95 with a 5-MHz scanning head) demonstrated that the aortic valve was a bicuspid aortic valve (BAV) with mild-moderate insufficiency during diastole, the peak systolic velocity (PSV) and gradient of aortic valve were 1.9m/s and 14mmHg, respectively; The aortic sinotubular junction (ASJ) was stenotic, the PSV and gradient of ASJ were 2.7m/s and 29mmHg, respectively; A tubular-like structure originated in the outlet septum beneath the right coronary cusp and terminated in the ascending aorta superior to the right coronary aortic sinus (Fig. A, B), CDFI and continuous-wave Doppler showed unobstructed to-and-fro (systolic and diastolic) flow in the tunnel with a high-velocity color signal that aliased during systole (Fig. C-E). Clinical considerations for congenital heart disease: ALVT combines BAV with aortic insufficiency and supravalvar aortic stenosis. The patient was referred for possible surgical correction. Discussion: In this patient, the type of ALVT does not belong to any one of Hovaguimian’s classifications. Two-dimensional echocardiography can display the tunnel-like structure of ALVT in real-time, and CDFI can identify that two-stage bidirectional shunted blood flow, systolic ventricular ejection occurs through both the tunnel and the semilunar valve, and the diastolic flow reverses from the aorta to ventricle via ALVT.

Non-invasive identification of slow conducting anatomical isthmuses in patients with tetralogy of Fallot by 3D late gadolinium enhancement cardiovascular magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background Patients with repaired tetralogy of Fallot (rTOF) remain at risk of sudden cardiac death due to reentrant sustained monomorphic ventricular tachycardia (SMVT). Slow conducting anatomical isthmuses (SCAI), in particular SCAI3 at the outlet septum, bordered by the pulmonary annulus and the ventricular septal defect patch, are the dominant substrate for SMVT. Electroanatomical mapping (EAM) is the invasive gold standard to identify SCAIs, and transection of SCAI by catheter ablation has been correlated with favorable long-term outcome. Non-invasive identification of SCAI for risk stratification and treatment planning is needed but has not been established yet. Three-dimensional (3D) late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) facilitates accurate visualization of morphologically complex hearts with high-spatial resolution. Objective The study thought to determine whether 3D LGE-CMR can identify SCAIs. Methods Consecutive patients with rTOF who underwent right ventricular (RV) EAM and 3D LGE-CMR were included. LGE-CMR-derived 3D RV reconstructions were created (ADAS-3D) and merged with 3D RV EAM data. Mapping points were superimposed on the CMR-derived 3D reconstruction allowing for direct comparison of EAM data and local signal intensity (SI). The optimal SI cut-off to identify low bipolar voltage (LBV, BV&amp;lt;1.76mV) was determined by receiver operating characteristic carve. An abnormal AI on LGE-CMR was defined as AI with continuous SI above the obtained cut-off connecting AI borders. Results Forty-eight rTOF patients (34±16 years, 58% male) were included. At EAM, 21 patients had normal AI, and 20 and 7 had a SCAI (&amp;lt;0.5m/s) or blocked AI, which was AI3 in all. Patients with SCAI showed low BV of AI3 (median 0.7 [range 0.25-2.59] mV). In 11 patients, 14 SMVTs could be induced, all related to SCAI3. A total of 9240 points were analyzed, showing a significant correlation between BV and SI (R=0.4, P&amp;lt;0.001). The optimal SI cut-off to identify LBV was 42% of the maximal SI (MSI) (AUC 0.80; sensitivity, 74%; specificity, 78%). Using this cut-off of MSI, a SCAI or blocked AI3 could be correctly identified by LGE-CMR in all 27 patients, and a normal AI3 could be correctly confirmed by LGE-CMR in 14/21 patients with normal EAM findings (Figure). The sensitivity and specificity of 3D LGE-CMR for identifying SCAI or blocked AI3 were 100% and 67%, respectively. Of note, among patients with normal EAM findings, those with abnormal AI3 on LGE-CMR had significantly lower BV of AI3 than those with normal AI3 on LGE-CMR (2.06 [Range, 1.62-2.60] vs. 3.53 [2.22-5.67] mV, P&amp;lt;0.01). Conclusion 3D LGE-CMR can identify SCAI with 100% sensitivity and may identify diseased AI3 even before critical conduction delay occurs. This technique may allow for non-invasive risk stratification of VT and can refine patient selection for invasive EAM.

PE-565-03 NON-INVASIVE IDENTIFICATION OF SLOW CONDUCTING ANATOMICAL ISTHMUSES IN PATIENTS WITH TETRALOGY OF FALLOT BY 3-DIMENSIONAL LATE GADOLINIUM ENHANCEMENT CARDIOVASCULAR MAGNETIC RESONANCE IMAGING

Patients with repaired tetralogy of Fallot (rTOF) remain at risk of sudden cardiac death due to sustained monomorphic ventricular tachycardia (SMVT). The majority of SMVTs are related to slow conducting anatomical isthmuses (SCAI) in particular to SCAI3 at the outlet septum, bordered by the pulmonary annulus and the ventricular septal defect patch. Electroanatomical mapping (EAM) is the invasive gold standard to identify SCAIs; non-invasive characterization of AIs has not been established.

The particular anatomy of ventricular septal defect in patients with Down syndrome and complete atrioventricular septal defect: An echocardiographic study

Complete atrioventricular septal defect (CAVSD) is associated with Down syndrome (DS) in almost half of cases, and is due in this setting to an abnormal development of the vestibular spine, derived from the posterior second heart field (SHF). Clinical studies have shown that Tetralogy of Fallot (TF), an outflow tract defect involving the anterior SHF, is more frequent in CAVSD patients with DS. We therefore decided to look for an outlet extension of the VSD in DS and non-DS. We reviewed retrospectively all 208 consecutive patients hospitalized in our unit with the diagnosis of CAVSD between 01/01/2017 and 09/12/2019. All echocardiographic examinations were screened by 2 pediatric cardiologists (ZB/LH). We excluded 46 patients whose VSD anatomical type could not be determined. We used the classification as agreed upon by ICD-11 to determine the VSD anatomical type in the 162 patients included. Among the cohort, 101/162 had DS (62.7%). An outlet extension of the VSD, with anterior malalignment of the outlet septum, was found in 88/101 (87.1%) DS vs. 4/61 (6.5%) non-DS ( P < 0.0001). Associated TF was found in 12 DS vs. 1 in non-DS ( P = ns). Ventricles were balanced in 126 patients, 23 had a hypoplastic left ventricle (LV), 13 had a hypoplastic right ventricle (RV). There was no significant difference regarding balanced or not ventricles between DS and non-DS. However, the hypoplastic ventricle was always the LV in non-DS, and was the RV in 62% of DS ( P = 0.006). This echocardiographic study describes for the first time that outlet extension of the VSD is the rule in CAVSD with DS and that hypoplastic RV occurs only in DS. This seems to confirm the involvement of the two parts of the second heart field in the morphogenesis of CAVSD in DS patients. The presence of a malaligned outlet septum in a fetus with CAVSD should raise awareness of the high risk of associated DS.

Double outlet of both ventricles: morphological, echocardiographic and surgical considerations.

To describe the morphology, echocardiographic features and surgical management of the entity appropriately described as 'double outlet of both ventricles'. Seven patients (5 males, age 0.5-7.5 months) were diagnosed to have a unique form of subarterial ventricular septal defect (VSD) and ventriculo-arterial connection, where a muscular outlet septum straddled the crest of the ventricular septum in a cruciate manner, such that both great arteries were equally committed to both ventricles. Diagnosis was established by echocardiography, with 6 patients submitted to surgical repair by means of intracardiac routing of the left ventricle to the aorta using 2 patches. Surgical repair was successful in all 6 patients in whom it was attempted. In addition, 1 patient underwent concomitant repair of aortic coarctation, and 2 had closure of multiple VSDs. We lost 1 patient to follow-up after diagnosis. Follow-up with a range from 3 months to 8 years in the remaining patients revealed all to be clinically well with satisfactory growth of both outflow tracts. We describe a series of patients with the ventriculo-arterial connection best described as 'double outlet of both ventricles'. Diagnosis is readily established by echocardiography. Good early and midterm results can be expected subsequent to surgical repair using 2 patches for interventricular septation.

Systematic Approach to Malalignment Type Ventricular Septal Defects.

Various congenital heart diseases are associated with malalignment of a part of the ventricular septum. Most commonly, the outlet septum is malaligned toward the right or left ventricle. Less commonly, the whole or a major part of the ventricular septum is malaligned in relation to the atrial septal plane. Although the pathological conditions associated with ventricular septal malalignment have been well recognized, the descriptions are often confusing and sometimes incorrect. In this pictorial essay, we introduce our systematic approach to the assessment of malalignment type ventricular septal defects with typical case examples. The systematic approach comprises description of the essential features of malalignment, including the following: (1) the malaligned part of the ventricular septum, (2) the reference structure, (3) the mechanism of malalignment, (4) the direction of malalignment, and (5) the severity of malalignment.

Muscularization of the Mesenchymal Outlet Septum during Cardiac Development.

After the formation of the linear heart tube, it becomes divided into right and left components by the process of septation. Relatively late during this process, within the developing outflow tract, the initially mesenchymal outlet septum becomes muscularized as the result of myocardialization. Myocardialization is defined as the process in which existing cardiomyocytes migrate into flanking mesenchyme. Studies using genetically modified mice, as well as experimental approaches using in vitro models, demonstrate that Wnt and TGFβ signaling play an essential role in the regulation of myocardialization. They also show the significance of the interaction between cardiomyocytes, endocardial derived cells, neural crest cells, and the extracellular matrix. Interestingly, Wnt-mediated non-canonical planar cell polarity signaling was found to be a crucial regulator of myocardialization in the outlet septum and Wnt-mediated canonical β-catenin signaling is an essential regulator of the expansion of mesenchymal cells populating the outflow tract cushions.

Polarized Light Imaging of the Myoarchitecture in Tetralogy of Fallot in the Perinatal Period.

Background: The pathognomonic feature of tetralogy of Fallot (ToF) is the antero-cephalad deviation of the outlet septum in combination with an abnormal arrangement of the septoparietal trabeculations.Aims: The aim of this article was to study perinatal hearts using Polarized Light Imaging (PLI) in order to investigate the deep alignment of cardiomyocytes that bond the different components of the ventricular outflow tracts both together and to the rest of the ventricular mass, thus furthering the classic description of ToF.Methods and Materials: 10 perinatal hearts with ToF and 10 perinatal hearts with no detectable cardiac anomalies (control) were studied using PLI. The orientation of the myocardial cells was extracted and studied at high resolution. Virtual dissections in multiple section planes were used to explore each ventricular structure.Results and Conclusions: Contrary to the specimens of the control group, for all ToF specimens studied, the deep latitudinal alignment of the cardiomyocytes bonds together the left part of the Outlet septum (OS) S to the anterior wall of the left ventricle. In addition, the right end of the muscular OS bonds directly on the right ventricular wall (RVW) superior to the attachment of the ventriculo infundibular fold (VIF). Thus, the OS is a bridge between the lateral RVW and the anterior left ventricular wall. The VIF, RVW, and OS define an “inverted U” that roofs the cone between the interventricular communication and the overriding aorta. The opening angle and the length of the branches of this “inverted U” depend however on three components: the size of the OS, the size of the VIF, and the distance between the points of insertion of the OS and VIF into the RVW. The variation of these three components accounts for a significant part of the diversity observed in the anatomical presentations of ToF in the perinatal period.

Endocardial biventricular pacing for chronic heart failure patients: Effect on transmural dispersion of repolarization.

Background and AimConventional epicardial cardiac resynchronization therapy (CRT) can cause fatal arrhythmia associated with increased transmural dispersion of repolarization (TDR). It is unknown whether endocardial biventricular pacing in various locations will decrease TDR and hence the occurrence of fatal arrhythmia. This study aimed to find out the most effective location of endocardial biventricular pacing resulting in the shortest homogenous TDR.MethodsA before‐and‐after study on adult chronic heart failure (CHF) patients undergoing endocardial biventricular pacing in several defined locations. The changes in TDR from baseline were compared among various pacing locations.ResultsFourteen subjects were included with age ranged 36‐74 years old, of which 10 were males. Location revealed the highest post biventricular pacing TDR (113.4 (SD 13.8) ms) was the outlet septum of right ventricle in combination with lateral wall of left ventricle (RVOTseptum‐LVlateral) while the lowest one (106.1 (SD 11.6) ms) was of the right ventricular apex and posterolateral left ventricle (RVapex‐LVposterolateral). Two CRT locations resulted in the most homogenous TDR, that is the right ventricular apex ‐ left ventricular lateral wall (RVapex‐LVlateral, mean difference −9.43; 95% CI (−19.72;0.87) ms, P = 0.07) and right ventricular apex ‐ left ventricle posterolateral wall (RVapex‐LVposterolateral, mean difference −6.85; 95% CI (−13.93;0.22) ms, P = 0.056).ConclusionEndocardial biventricular pacing on right ventricular apex and left ventricular lateral/posterolateral walls results in the most homogenous TDR.

Ventricular septal defect associated with aortic valve prolapse: An echocardiographicstudy

Ventricular septal defects (VSD) can be associated with aortic valve prolapse (AVP) with or without regurgitation. Aortic valve prolapse may be due to both lack of leaflet support and Venturi's phenomenon. There is a great diversity in the literature about the anatomic type of the VSDs associated with AVP. The objective of the study was then to assess the anatomy of the VSD on echocardiography. From 2009 to 2017, 51 consecutive patients with VSD complicated by AVP were admitted for surgery. We screened retrospectively all preoperative echocardiographies in double-blind test. We analyzed the anatomic type of the VSD according to ICD-11 classification and looked for outlet septum malalignment, the nature of the prolapsed aortic leaflet, the severity of aortic regurgitation and other complications. The VSD was central perimembranous (pm) in 23 patients (45%), outlet with malalignment in 21 (41%) and outlet juxta-arterial in 7 (13.7%). We found a significant difference between the initial diagnosis and the final one after reviewing echography in double-blind test: among the 23 VSD initially described as central pm, eleven were reclassified as outlet VSD, and one outlet VSD was reclassified as central pm ( P < 0.001). Aortic valve prolapse involved the right aortic cusp in 98% of patients. Aortic regurgitation was severe in 2 patients, moderate in 5, mild in 24 and trivial or absent in 20. Outlet VSDs were significantly more often associated with aortic regurgitation ( P = 0.036). Subaortic membrane was found in 8 patients (15.6%), 6 with outlet and 2 with central pm VSD ( P < 0.001). Right ventricular obstruction was found in 8 patients (15.6%). Aortic valve prolapse complicates indifferently central pm and outlet VSD. However, aortic insufficiency is more frequent in outlet VSD. The accurate echocardiographic diagnosis of the anatomic type of the VSD is difficult and multiple views are necessary.

Tetralogy of Fallot: morphological variations and implications for surgical repair.

OBJECTIVESTetralogy of Fallot is characterized by anterocephalad deviation of the outlet septum, along with abnormal septoparietal trabeculations, which lead to subpulmonary infundibular stenosis. Archives of retained hearts are an important resource for improving our understanding of congenital heart defects and their morphological variability. This study aims to define variations in aortic override, coronary arterial patterns and ventricular septal defects in tetralogy of Fallot as observed in a morphological archive, highlighting implications for surgical management.METHODSThe Birmingham Children’s Hospital archive contains 211 hearts with tetralogy of Fallot, of which 164 were analysed [69 (42.1%) unrepaired and 95 (57.9%) operated specimens]. A detailed morphological and geometric analysis was performed using a rigorous 5-layer review process.RESULTSAnomalies were observed in the orifices, origins and course of the coronary arteries: 20 hearts (13.0%) had more than 2 orifices and 3 hearts (1.9%) had a single orifice. In 7 hearts (4.3%), a coronary artery crossed the right ventricular outflow tract. The extent of aortic override ranged from 31.0% to 100% (median of 59.5%). The ventricular septal defect was most often perimembranous (139, 84.8%), but we also found muscular (14, 8.5%), atrioventricular (7, 4.3%) and doubly committed juxta-arterial (2, 1.2%) variants.CONCLUSIONSAnatomical variations are common and can impact surgical management. Anomalous coronary arteries may require a conduit rather than a transannular patch. Variability in aortic override determines the size of patch used to baffle blood to the aorta. The type of ventricular septal defect affects patch closure and the risk of postoperative conduction defects.

Ventricular septal defect associated with aortic valve prolapse: An echocardiographic study

Ventricular septal defects (VSD) can be associated with aortic valve prolapse (AVP) with or without regurgitation. Aortic valve prolapse may be due to both lack of leaflet support and Venturi's phenomenon. There is a great diversity in the literature about the anatomic type of the VSDs associated with AVP. The objective of the study was then to assess the anatomy of the VSD on echocardiography. From 2009 to 2017, 51 consecutive patients with VSD complicated by AVP were admitted for surgery. We screened retrospectively all preoperative echocardiographies in double-blind test. We analyzed the anatomic type of the VSD according to ICD-11 classification and looked for outlet septum malalignment, the nature of the prolapsed aortic leaflet, the severity of aortic regurgitation and other complications (subaortic membrane, right ventricular stenosis). The VSD was central perimembranous (pm) in 23 patients (45%), outlet with malalignment in 21 (41%) and outlet juxta-arterial in 7 (13.7%). We found a significant difference between the initial diagnosis and the final one after reviewing echography in double-blind test: among the 23VSD initially described as central pm, eleven were reclassified as outlet VSD, and one outlet VSD was reclassified as central pm ( P < 0.001). Aortic valve prolapse involved the right aortic cusp in 98% of patients. Aortic regurgitation was severe in 2 patients, moderate in 5, mild in 24 and trivial or absent in 20. Outlet VSDs were significantly more often associated with aortic regurgitation ( P = 0.036). Subaortic membrane was found in 8 patients (15.6%), 6 with outlet and 2withcentral pm VSD ( P < 0.001). Right ventricular obstruction was found in 8 patients (15.6%). Aortic valve prolapse complicates indifferently central pm and outlet VSD. However, aortic insufficiency is more frequent in outlet VSD. The accurate echocardiographic diagnosis of the anatomic type of the VSD is difficult and multiple views are necessary.

A new anatomic approach of the ventricular septal defect in the interruption of the aortic arch.

The aim of this study was to analyse the anatomy of the ventricular septal defect (VSD) in heart specimens with interruption of the aortic arch (IAA) in order to explore the hypothesis of different embryologic mechanisms for the different anatomic types of IAA. We examined 42 human heart specimens, 25 with IAA as the main disease with concordant atrioventricular and ventriculo-arterial connections and two distinct great arteries, and 17 hearts with IAA associated with other malformations [six common arterial trunk (CAT), five double-outlet right ventricle (DORV), three transposition of the great arteries (TGA), three atrioventricular septal defect (AVSD)]. The interruption was classified according to Celoria and Patton. We focused on the anatomy of the VSD viewed from the right ventricular side. There were 15 IAA type A, 27 type B, no type C. The VSD in IAA type B was always an outlet VSD, located between the two limbs of the septal band, with posterior malalignment of the outlet septum in hearts with concordant ventriculo-arterial connections, without any fibrous tricuspid-aortic continuity. In addition, the aortic arch was always completely absent. Conversely, the VSD in IAA type A could be of any type (outlet in six, muscular in four, central perimembranous in two, inlet in three) and the aortic arch was either atretic or absent. In addition, IAA type B, when found in the setting of another anomaly, was always associated with neural crest-related anomalies (CAT and DORV), whereas IAA type A was found in association with anomalies not related to the neural crest (TGA and AVSD). These results reinforce the hypothesis that different pathogenic mechanisms are responsible for the two types of IAA, and the inclusion of IAA type B in the group of neural crest defects. Conversely, IAA type A could be due to overlapping mechanisms: flow-related defect (coarctation-like) and neural crest contribution.

Ventricular septal defect associated with aortic valve prolapse: An echocardiographic study

Objectives Ventricular septal defects (VSD) can be associated with aortic valve prolapse (AVP) with or without regurgitation. Aortic valve prolapse may be due to both lack of leaflet support and Venturi's phenomenon. There is a great diversity in the literature about the anatomic type of the VSDs associated with AVP. The objective of the study was then to assess the anatomy of the VSD on echocardiography. Methods From 2009 to 2017, 51 consecutive patients with VSD complicated by AVP were admitted for surgery. We screened retrospectively all preoperative echocardiographies in double-blind test. We analyzed the anatomic type of the VSD according to ICD-11 classification and looked for outlet septum malalignment, the nature of the prolapsed aortic leaflet, the severity of aortic regurgitation and other complications (subaortic membrane, right ventricular stenosis). Results The VSD was central perimembranous (PM) in 23 patients (45%), outlet with malalignment in 21 (41%) and outlet juxta-arterial in 7 (13.7%). We found a significant difference between the initial diagnosis and the final one after reviewing echography in double-blind test: among the 23VSD initially described as central PM, eleven were reclassified as outlet VSD, and one outlet VSD was reclassified as central PM (P Conclusion Aortic valve prolapse complicates indifferently central PM and outlet VSD. However, aortic insufficiency is more frequent in outlet VSD. The accurate echocardiographic diagnosis of the anatomic type of the VSD is difficult and multiple views are necessary.

Essential Modifiers of Double Outlet Right Ventricle: Revisit With Endocardial Surface Images and 3-Dimensional Print Models.

Hearts with double outlet right ventricle are a heterogeneous group of malformations in which a comprehensive diagnostic approach is required for tailored surgical management. This pictorial essay revisits essential modifiers of clinical and surgical importance in management of the patients with double outlet right ventricle using 3-dimensional volume-rendered endocardial surface images and 3-dimensional print models. Special emphasis is paid to the infundibular morphology, including the size and orientation of the outlet septum, relative to the margin of the ventricular septal defect, and the extent of the muscular infundibulum as an additional modifier of the distance between the ventricular septal defect margin and the arterial valve or valves.

Characterization of new bone morphogenetic protein (Bmp)‐2 regulatory alleles

Bone morphogenetic protein 2 (BMP2, HGNC:1069, GeneID: 650) is a classical morphogen; a molecule that acts at a distance and whose concentration influences cell proliferation, differentiation, and apoptosis. Key events requiring precise Bmp2 regulation include heart specification and morphogenesis and neural development. In mesenchymal cells, the concentration of BMP2 influences myogenesis, adipogenesis, chondrogenesis, and osteogenesis. Because the amount, timing, and location of BMP2 synthesis influence pattern formation and organogenesis, the mechanisms that regulate Bmp2 are crucial. A sequence within the 3'UTR of the Bmp2 mRNA termed the "ultra-conserved sequence" (UCS) has been largely unchanged since fishes and mammals diverged. Cre-lox mediated deletion of the UCS in a reporter transgene revealed that the UCS may repress Bmp2 in proepicardium, epicardium, and epicardium-derived cells (EPDC) and in tissues with known epicardial contributions (coronary vessels and valves). The UCS also repressed the transgene in the aorta, outlet septum, posterior cardiac plexus, cardiac and extra-cardiac nerves, and neural ganglia. We used homologous recombination and conditional deletion to generate three new alleles in which the Bmp2 3'UTR was altered as follows: a UCS flanked by loxP sites with or without a neomycin resistance targeting vector, or a deleted UCS. Deletion of the UCS was associated with elevated Bmp2 mRNA and BMP signaling levels, reduced fitness, and embryonic malformations.