Emmeline E. Calkoen

Vortex flow during early and late left ventricular filling in normal subjects: Quantitative characterization using retrospectively-gated 4D flow cardiovascular magnetic resonance and three-dimensional vortex core analysis

BackgroundLV diastolic vortex formation has been suggested to critically contribute to efficient blood pumping function, while altered vortex formation has been associated with LV pathologies. Therefore, quantitative characterization of vortex flow might provide a novel objective tool for evaluating LV function. The objectives of this study were 1) assess feasibility of vortex flow analysis during both early and late diastolic filling in vivo in normal subjects using 4D Flow cardiovascular magnetic resonance (CMR) with retrospective cardiac gating and 3D vortex core analysis 2) establish normal quantitative parameters characterizing 3D LV vortex flow during both early and late ventricular filling in normal subjects.MethodsWith full ethical approval, twenty-four healthy volunteers (mean age: 20±10 years) underwent whole-heart 4D Flow CMR. The Lambda2-method was used to extract 3D LV vortex ring cores from the blood flow velocity field during early (E) and late (A) diastolic filling. The 3D location of the center of vortex ring core was characterized using cylindrical cardiac coordinates (Circumferential, Longitudinal (L), Radial (R)). Comparison between E and A filling was done with a paired T-test. The orientation of the vortex ring core was measured and the ring shape was quantified by the circularity index (CI). Finally, the Spearman’s correlation between the shapes of mitral inflow pattern and formed vortex ring cores was tested.ResultsDistinct E- and A-vortex ring cores were observed with centers of A-vortex rings significantly closer to the mitral valve annulus (E-vortex L=0.19±0.04 versus A-vortex L=0.15±0.05; p=0.0001), closer to the ventricle’s long-axis (E-vortex: R=0.27±0.07, A-vortex: R=0.20±0.09, p=0.048) and more elliptical in shape (E-vortex: CI=0.79±0.09, A-vortex: CI=0.57±0.06; <0.001) compared to E-vortex. The circumferential location and orientation relative to LV long-axis for both E- and A-vortex ring cores were similar. Good to strong correlation was found between vortex shape and mitral inflow shape through both the annulus (r=0.66) and leaflet tips (r=0.83).ConclusionsQuantitative characterization and comparison of 3D vortex rings in LV inflow during both early and late diastolic phases is feasible in normal subjects using retrospectively-gated 4D Flow CMR, with distinct differences between early and late diastolic vortex rings.

Characterization and improved quantification of left ventricular inflow using streamline visualization with 4DFlow MRI in healthy controls and patients after atrioventricular septal defect correction

To evaluate trans‐left atrioventricular valve (LAVV) blood flow and optimize left ventricular inflow quantification in healthy controls and patients after atrioventricular septal defect (AVSD) correction.

Atrioventricular septal defect: From embryonic development to long-term follow-up

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.

Assessment of viscous energy loss and the association with three-dimensional vortex ring formation in left ventricular inflow: In vivo evaluation using four-dimensional flow MRI.

To evaluate viscous energy loss and the association with three‐dimensional (3D) vortex ring formation in left ventricular (LV) blood flow during diastolic filling.

Disturbed Intracardiac Flow Organization After Atrioventricular Septal Defect Correction as Assessed With 4D Flow Magnetic Resonance Imaging and Quantitative Particle Tracing.

ObjectivesFour-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. MethodsA 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. ResultsPatients 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. ConclusionMulticomponent 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.

Echocardiographic assessment of embryonic and fetal mouse heart development: a focus on haemodynamics and morphology.

Background. Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. Methods. A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n = 105). Results. Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. Conclusion. High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts.

Comparative Evaluation of Flow Quantification across the Atrioventricular Valve in Patients with Functional Univentricular Heart after Fontan's Surgery and Healthy Controls: Measurement by 4D Flow Magnetic Resonance Imaging and Streamline Visualization

PURPOSE To evaluate the inflow pattern and flow quantification in patients with functional univentricular heart after Fontans 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 Fontans 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 Fontans 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.

How Normal Is a 'Normal' Heart in Fetuses and Infants with Down Syndrome?

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.

Three dimensional right ventricular diastolic vortex rings: characterization and comparison with left ventricular diastolic vortex rings from 4D flow MRI

Background Efficient right ventricular (RV) pumping function requires optimal blood flow dynamics. In the left ventricle (LV), diastolic vortex ring formation distal to the mitral valve (MV) has been reported to be an important mechanism for such blood flow optimization. Earlier work based on computational fluid dynamic s( CFD) simulations using simplified RV geometry modeling have reported vortex ring formation in the RV during the early filling phase and its breakdown at the late diastolic phase. However, neither those CFD studies have characterized vortex rings nor have they been confirmed by 4D flow MRI. The purpose of this study was to investigate and characterize the formation of vortex rings during diastolic filling in the RV and to compare them with those of LV in healthy volunteers.

Abnormal sinoatrial node development resulting from disturbed vascular endothelial growth factor signaling.

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.