Abstract Aim: In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics in the ascending aorta. Methods: In total, 30 patients after atrioventricular septal defect correction (age 27.6 ± 12.8 years) and 28 healthy volunteers (age 24.8 ± 13.7 years) underwent 4D flow cardiovascular magnetic resonance. Left ventricular ejection fraction and mean and peak wall shear stress calculated at ascending aortic peak systole were obtained from cardiovascular magnetic resonance. Left ventricular outflow tract data including velocity and diameter were obtained from echocardiography. Results: Patients showed a higher mean (911 ± 173 versus 703 ± 154 mPa, p = 0.001) and peak ascending aortic wall shear stress (1264 ± 302 versus 1009 ± 240 mPa, p = 0.001) compared to healthy volunteers. Increased blood flow velocities over the left ventricular outflow tract (1.49 ± 0.30 m/s versus 1.22 ± 0.20 m/s, p < 0.001) correlated well with mean and peak ascending aortic wall shear stress (r = 0.67, p < 0.001 and r = 0.77, p < 0.001). Conclusion: After atrioventricular septal defect correction, increased wall shear stress was observed, which correlated to velocities over the left ventricular outflow tract. These findings imply that altered outflow tract geometry contributes to changed aortic haemodynamics.

PURPOSE:To evaluate the inflow pattern and flow quantification in patients with functional univentricular heart after Fontan's operation using 4D flow magnetic resonance imaging (MRI) with streamline visualization when compared with the conventional 2D flow approach.METHOD:Seven patients with functional univentricular heart after Fontan's operation and twenty-three healthy controls underwent 4D flow MRI. In two orthogonal two-chamber planes, streamline visualization was applied, and inflow angles with peak inflow velocity (PIV) were measured. Transatrioventricular flow quantification was assessed using conventional 2D multiplanar reformation (MPR) and 4D MPR tracking the annulus and perpendicular to the streamline inflow at PIV, and they were validated with net forward aortic flow.RESULTS:Inflow angles at PIV in the patient group demonstrated wide variation of angles and directions when compared with the control group (P < .01). The use of 4D flow MRI with streamlines visualization in quantification of the transatrioventricular flow had smaller limits of agreement (2.2 ± 4.1 mL; 95% limit of agreement -5.9-10.3 mL) when compared with the static plane assessment from 2DFlow MRI (-2.2 ± 18.5 mL; 95% limit of agreement agreement -38.5-34.1 mL). Stronger correlation was present in the 4D flow between the aortic and trans-atrioventricular flow (R2 correlation in 4D flow: 0.893; in 2D flow: 0.786).CONCLUSIONS:Streamline visualization in 4D flow MRI confirmed variable atrioventricular inflow directions in patients with functional univentricular heart with previous Fontan's procedure. 4D flow aided generation of measurement planes according to the blood flood dynamics and has proven to be more accurate than the fixed plane 2D flow measurements when calculating flow quantifications.

BACKGROUND:Congenital heart disease is present in 44-56% of fetuses with Down syndrome (DS). There are, however, signs that hearts in DS without apparent structural heart defects also differ from those in the normal population. We aimed to compare the atrioventricular (AV) septum and valves in 3 groups: DS without AV septal defect (DS no-AVSD), DS with AVSD (DS AVSD) and control hearts.METHODS:The ventricular septum, membranous septum and AV valves were examined and measured in histological sections of 15 DS no-AVSD, 8 DS AVSD and 34 control hearts. In addition, the ventricular septum length was measured on ultrasound images of fetal (6 DS AVSD, 9 controls) and infant (10 DS no-AVSD, 10 DS AVSD, 10 controls) hearts.RESULTS:The membranous septum was 3 times larger in DS no-AVSD fetuses compared to control fetuses, and valve dysplasia was frequently (64%) observed. The ventricular septum was shorter in patients with DS both with and without AVSD, as compared to the control group.CONCLUSION:DS no-AVSD hearts are not normal as they have a larger membranous septum, shorter ventricular septum and dysplasia of the AV valves as compared to control hearts.

First trimester sonography is a widely used technique to examine the foetus early in pregnancy. The desire to recognise complex anatomy already in early developmental stages stresses the need for a thorough knowledge of basic developmental processes as well as recognition of cardiac compartments based on their morphology. In this paper, we describe the possibilities and limitations of sonographic assessment of the foetal heart between 10 and 14 weeks of gestation and correlate this to morphology. Examples of the most commonly detected congenital anomalies are atrioventricular septal defects, transposition of the great arteries, and hypoplastic left heart, which are shown in this paper. 65 Echocardiography in the first-trimester heart

Background In patients with an atrioventricular septal defect (AVSD), the left ventricular outflow tract (LVOT) and the ascending aorta (AAo) are located more anteriorly due to the position of the common AV valve. This may alter proximal aortic flow, and we hypothesize that this can result in impaired LV systolic function and AAo wall degeneration. We aimed to quantify differences in AAo wall shear stress (WSS), distensibility (Dist), aortic arch pulse wave velocity (PWV) and LV ejection fraction (EF) in these patients versus healthy controls using cardiovascular magnetic resonance (CMR) and four dimensional (4D) flow MRI.

PurposeTo evaluate viscous energy loss and the association with three‐dimensional (3D) vortex ring formation in left ventricular (LV) blood flow during diastolic filling.Theory and MethodsThirty healthy volunteers were compared with 32 patients with corrected atrioventricular septal defect as unnatural mitral valve morphology and inflow are common in these patients. 4DFlow MRI was acquired from which 3D vortex ring formation was identified in LV blood flow at peak early (E)‐filling and late (A)‐filling and characterized by its presence/absence, orientation, and position from the lateral wall. Viscous energy loss was computed over E‐filling, A‐filling, and complete diastole using the Navier‐Stokes energy equations.ResultsCompared with healthy volunteers, viscous energy loss was significantly elevated in patients with disturbed vortex ring formation as characterized by a significantly inclined orientation and/or position closer to the lateral wall. Highest viscous energy loss was found in patients without a ring‐shaped vortex during E‐filling (on average more than double compared with patients with ring‐shape vortex, P < 0.003). Altered A‐filling vortex ring formation was associated with significant increase in total viscous energy loss over diastole even in the presence of normal E‐filling vortex ring.ConclusionAltered vortex ring formation during LV filling is associated with increased viscous energy loss. Magn Reson Med 77:794–805, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Atrioventricular septal defect (AVSD) covers a spectrum of heart anomalies with a common atrioventricular connection and has an incidence of 4-5.3 per 10.000 live births. About half of the AVSDs occur in patient with Down syndrome. This review provides a bench to bedside overview of AVSD. Developmental aspects, nomenclature, anatomy, and classification of AVSD are discussed. Furthermore an overview of genetic and maternal risk factors for AVSD is provided, and available literature on (fetal) diagnosis, surgical techniques and follow-up is presented. Special attention is given to differences in developmental, anatomical and prognostic factors of AVSD between non-syndromic and Down syndrome patients.

Background Patients after atrioventricular septal defect (AVSD) repair may present abnormalities in valve morphology and subsequently develop altered left ventricular (LV) inflow patterns [1]. This may lead to energy loss and affect the kinetic energy in the LV. We aimed to quantify diastolic viscous energy loss and kinetic energy in the LV and to evaluate their association in AVSDrepaired patients compared to healthy controls using 4D Flow MRI.

BACKGROUND:Sinus node dysfunction is frequently observed in patients with congenital heart disease (CHD). Variants in the Vascular Endothelial Growth Factor-A (VEGF) pathway are associated with CHD. In Vegf(120/120) mice, over-expressing VEGF120, a reduced sinoatrial node (SAN) volume was suggested. Aim of the study is to assess the effect of VEGF over-expression on SAN development and function.METHODS:Heart rate was measured in Vegf(120/120) and wildtype (WT) embryos during high frequency ultrasound studies at embryonic day (E)12.5, 14.5 and 17.5 and by optical mapping at E12.5. Morphology was studied with several antibodies. SAN volume estimations were performed, and qualitative-PCR was used to quantify expression of genes in SAN tissues of WT and Vegf(120/120) embryos.RESULTS:Heart rate was reduced in Vegf(120/120) compared with WT embryos during embryonic echocardiography (52 ± 17 versus 125 ± 31 beats per minute (bpm) at E12.5, p<0.001; 123 ± 37 vs 160 ± 29 bmp at E14.5, p=0.024; and 177 ± 30 vs 217 ± 34 bmp, at E17.5 p=0.017) and optical mapping (81 ± 5 vs 116 ± 8 bpm at E12.5; p=0.003). The SAN of mutant embryos was smaller and more vascularized, and showed increased expression of the fast conducting gap junction protein, Connexin43.CONCLUSIONS:Over-expression of VEGF120 results in reduced heart rate and a smaller, less compact and hypervascularized SAN with increased expression of Connexin43. This indicates that VEGF is necessary for normal SAN development and function.

BackgroundVortex formation in the left ventricle (LV) is suggested to contribute to efficient blood pumping and minimization of energy loss.Patients after atrioventricular septal defect (AVSD) repair may present abnormalities in valve morphology and subsequently develop altered LV inflow patterns [1], in which normal vortex formation may be disturbed.This may lead to energy loss.We aimed to analyze the association between disturbed vortex ring formation during diastole and viscous energy loss during diastole in AVSD-corrected patients compared to healthy controls.

OBJECTIVES:During normal left ventricular (LV) filling, a vortex ring structure is formed distal to the left atrioventricular valve (LAVV). Vortex structures contribute to efficient flow organization. We aimed to investigate whether LAVV abnormality in patients with a corrected atrioventricular septal defect (AVSD) has an impact on vortex ring formation. METHODS:Whole-heart 4D flow MRI was performed in 32 patients (age: 26 ± 12 years), and 30 healthy subjects (age: 25 ± 14 years). Vortex ring cores were detected at peak early (E-peak) and peak late filling (A-peak). When present, the 3-dimensional position and orientation of the vortex ring was defined, and the circularity index was calculated. Through-plane flow over the LAVV, and the vortex formation time (VFT), were quantified to analyze the relationship of vortex flow with the inflow jet. RESULTS:Absence of a vortex ring during E-peak (healthy subjects 0%, vs patients 19%; P = .015), and A-peak (healthy subjects 10% vs patients 44%; P = .008) was more frequent in patients. In 4 patients, this was accompanied by a high VFT (5.1-7.8 vs 2.4 ± 0.6 in healthy subjects), and in another 2 patients with abnormal valve anatomy. In patients compared with controls, the vortex cores had a more-anterior and apical position, closer to the ventricular wall, with a more-elliptical shape and oblique orientation. The shape of the vortex core closely resembled the valve shape, and its orientation was related to the LV inflow direction. CONCLUSIONS:This study quantitatively shows the influence of abnormal LAVV and LV inflow on 3D vortex ring formation during LV inflow in patients with corrected AVSD, compared with healthy subjects.

Background The normal pattern of left ventricular (LV) inflow and ejection of affects the efficiency of cardiac pumping performance. Altered inflow direction due to a corrected atrioventricular septal defect (AVSD) may disturb this pattern leading to decreased efficiency. We aimed to quantitatively describe the LV blood flow pattern using 4-dimensional velocity-encoded cardiac magnetic resonance imaging (4DFlow MRI) and particle tracing in healthy volunteers and corrected AVSD patients.

Background Vortex formation in the left ventricle (LV) is suggested to contribute to efficient blood pumping and altered vortex formation is associated with diastolic dysfunction. Patients after atrioventricular septal defect (AVSD) correction present abnormalities in valve morphology and subsequently develop altered inflow patterns (Calkoen et al. JMRI 2014), which may disturb normal vortex formation. We aimed to analyze vortex ring formation in AVSD-corrected patients compared to healthy controls and to evaluate association with inflow angle.

Methods 12 healthy controls (age 9-53 years) and 8 patients (age 8-37 years) with a corrected atrioventricular septal defect and a mean mitral valve regurgitation of 25% (range 1937%) were included. The maximal left atrial volume (LAV) was calculated based on the biplane area-length method from a standardized 2and 4-chamber view. Whole-heart 4D Flow MRI was performed on a 3T MR scanner with free breathing, three-directional velocity encoding of 150cm/s in all directions, spatial resolution 2.3×2.3×3.0-4.2mm and 30 phases reconstructed over one cardiac cycle. At end-systole the vortical flow was assessed by manually segmenting the volume of circular flow in the left atrium based on streamline visualization in a stack of slices parallel to the 4-chamber view. 3Dparticle tracing was applied in reverse time order, using the defined volume as seeding, to trace back the seed points and quantify the number of particles originating from the left and right pulmonary veins (LPV and RPV). Results In controls mean LAV was 60±35mL and the vortex flow volume at end-systole 8±5mL. Tracing revealed a dominating contribution to the vortical volume originating from the LPV (41±14%), a smaller part from the RPV (17±12%) and a residual part of particles present inside the atrium at the start of systole (42±15%). In patients with mitral regurgitation the LAV was 76 ±21mL and a complex shape of the vortical flow with variation between subjects was observed (Figure 1). Mean vortical volume at end-systole was 5±4mL, with 13±14% contribution from LPV (difference with controls, p=0.001), 6±6% from the RPV (p=0.049) and a residual part of 81 ±14% (particles already inside the atrium at start of systole or coming from the ventricle as regurgitation) (p<0.001). Mean contribution ratio between LPV versus RPV was variable including patients with solely contribution from RPV or LPV.

OBJECTIVES:Four-dimensional (3 spatial directions and time) velocity-encoded flow magnetic resonance imaging with quantitative particle tracing analysis allows assessment of left ventricular (LV) blood flow organization. Corrected atrioventricular septal defect (AVSD) patients have an abnormal left atrioventricular valve shape. We aimed to analyze flow organization in corrected AVSD patients and healthy controls.METHODS:A total of 32 patients (age, 25 ± 14 years), 21 after partial AVSD correction and 11 after complete/intermediate AVSD correction, and 30 healthy volunteers (26 ± 12 years) underwent whole-heart four-dimensional velocity-encoded flow magnetic resonance imaging. Particle tracing in the 16-segment LV cavity model was used to quantitatively evaluate blood flow organization discriminating multiple components.RESULTS:Patients showed a smaller percentage of direct flow compared with controls (30% ± 9% vs 44% ± 11%; P < 0.001). In patients, more inflow was observed in the basal inferior segment (22% ± 11% vs controls, 17% ± 5%; P = 0.005), with less direct but more retained inflow (ie, part of inflow that is not ejected from LV in subsequent systole). In patients, more inflow reached the midventricular level (68% ± 13% vs controls, 58% ± 9%; P < 0.001), most notably as retained inflow in the lateral segments. Subsequently, in patients, more (mostly retained) inflow reached the apex (23% ± 13% vs 14% ± 7%; P < 0.001), which correlated with early peak filling velocity (r = 0.637, P < 0.001). Patients with a corrected complete or intermediate AVSD presented with less direct flow (24% ± 8% vs 33% ± 8%; P = 0.003) and more apical inflow (30% ± 14% vs 18% ± 12%; P = 0.014) compared with a corrected partial AVSD.CONCLUSION:Multicomponent particle tracing combined with 16-segment analysis quantitatively demonstrated altered LV flow organization after AVSD correction, with less direct and more retained inflow in apical and lateral LV cavity segments, which may contribute to decreased cardiac pumping efficiency.

Purpose To develop an alternative method for Vp‐assessment using high‐temporal velocity‐encoded magnetic resonance imaging (VE‐MRI). Left ventricular (LV) inflow propagation velocity (Vp) is considered a useful parameter in the complex assessment of LV diastolic function and is measured by Color M‐mode echocardiography. Materials and Methods A total of 43 patients diagnosed with ischemic heart failure (61 ± 11 years) and 22 healthy volunteers (29 ± 13 years) underwent Color M‐mode echocardiography and VE‐MRI to assess the inflow velocity through the mitral valve (mean interexamination time 14 days). Temporal resolution of VE‐MRI was 10.8–11.8 msec. Local LV inflow velocity was sampled along a 4‐cm line starting from the tip of the mitral leaflets and for consecutive sample points the point‐in‐time was assessed when local velocity exceeded 30 cm/s. From the position–time relation, Vp was calculated by both the difference quotient (Vp‐MRI‐DQ) as well as from linear regression (Vp‐MRI‐LR). Results Good correlation was found between Vp‐echo and both Vp‐MRI‐DQ ( r = 0.83, P < 0.001) and Vp‐MRI‐LR ( r = 0.84, P < 0.001). Vp‐MRI showed a significant but small underestimation as compared to Vp measured by echocardiography (Vp‐MRI‐DQ: 5.5 ± 16.2 cm/s, P = 0.008; Vp‐MRI‐LR: 9.9 ± 15.2 cm/s, P < 0.001). Applying age‐related cutoff values for Vp to identify LV impaired relaxation, kappa‐agreement with echocardiography was 0.72 ( P < 0.001) for Vp‐MRI‐DQ and 0.69 ( P < 0.001) for Vp‐MRI‐LR. Conclusion High temporal VE‐MRI represents a novel approach to assess Vp, showing good correlation with Color M‐mode echocardiography. In healthy subjects and patients with ischemic heart failure, this new method demonstrated good agreement with echocardiography to identify LV impaired relaxation. J. Magn. Reson. Imaging 2015;42:1297–1304.

Background 4DFlow MRI with retrospective valve tracking allows trans-valvular blood flow quantification. Valve tracking usually follows the anatomical annulus but does not take into account the inflow direction through the valve, which might lead to substantial errors when opening of the valve leaflets is restricted after surgery. We aimed to evaluate the added value of streamline visualization in the characterization and quantification of trans-left atrioventricular valve (LAVV) blood flow and assessment of left ventricular (LV) diastolic function in 4DFlow MRI. Methods

Background Blood entering the left ventricle (LV) through the left atrio-ventricular valve (LAVV) and exiting through the aorta is assumed to follow the most energy efficient pathway. In patients with a corrected atrio-ventricular septal defect (AVSD), this intra-cardiac blood flow pathway may be altered, due to the restricted opening of the LAVV. This might affect optimal LV function. Particle tracing in 4DFlow MRI data enables quantitative evaluation of the temporal distribution of blood particles in the LV. We aimed to compare the LV intra-cardiac blood flow pathway in corrected AVSD patients with that of healthy subjects, using 4DFlow MRI and particle tracing in the standard 16 segment model of the American Heart Association (AHA).

The primary unseptated heart tube undergoes extensive remodeling including septation at the atrial, atrioventricular, ventricular, and ventriculo-arterial level. Alignment and fusion of the septal components is required to ensure full septation of the heart. Deficiencies lead to septal defects at various levels. Addition of myocardium and mesenchymal tissues from the second heart field (SHF) to the primary heart tube, as well as a population of neural crest cells, provides the necessary cellular players. Surprisingly, the study of the molecular background of these defects does not show a great diversity of responsible transcription factors and downstream gene pathways. Epigenetic modulation and mutations high up in several transcription factor pathways (e.g. NODAL and GATA4) may lead to defects at all levels. Disturbance of modulating pathways, involving primarily the SHF-derived cell populations and the genes expressed therein, results at the arterial pole (e.g. TBX1) in a spectrum of ventricular septal defects located at the level of the outflow tract. At the venous pole (e.g. TBX5), it can explain a variety of atrial septal defects. The various defects can occur as isolated anomalies or within families. In this review developmental, morphological, genetic, as well as epigenetic aspects of septal defects are discussed.