Lars Grosse-Wortmann

Reduced Fetal Cerebral Oxygen Consumption is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease

Background— Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation. Methods and Results— We measured fetal brain size, oxygen saturation, and blood flow in the major vessels of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal hemodynamic parameters were calculated from a combination of magnetic resonance imaging flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (P<0.001) and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (P<0.001), whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (P=0.08) and 32% reduction cerebral VO2 in CHD fetuses (P<0.001), which were associated with a 13% reduction in fetal brain volume (P<0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral VO2 (r=0.37, P=0.004). Conclusions— This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.

Aortopulmonary collaterals after bidirectional cavopulmonary connection or Fontan completion: quantification with MRI.

Background—Aortopulmonary collaterals (APCs) have been associated with increased morbidity after the Fontan operation. We aimed to quantify APC flow after bidirectional cavopulmonary connections and Fontan completions, using phase-contrast MRI, and to identify risk factors for the development of APCs. Methods and Results—APC blood flow was quantifiable in 24 of 36 retrospectively analyzed MRI studies. Sixteen studies were performed after the bidirectional cavopulmonary connections (group A) and 8 after the Fontan operation (group B). APC blood flow was calculated by subtracting the blood flow volume through the pulmonary arteries from that through the pulmonary veins. The ratio of pulmonary to systemic blood flow (Qp/Qs) was 0.93±0.26 in group A and 1.27±0.16 in group B. APC flow was 1.42 (0.58 to 3.83) L/min/m2 and 0.82 (0.50 to 1.81) L/min/m2 in groups A and B, respectively. The mean inaccuracies corresponded to 7.9±14.5% and 7.1±13.6% of ascending aortic flow in groups A and B, respectively. Qp/Qs was negatively correlated with a younger age at the time of the bidirectional cavopulmonary connections operation (r=0.62, P=0.01) and positively correlated with the age at the time of the Fontan completion (r=0.81, P=0.01). Patients with a previous right-sided modified Blalock-Taussig shunt had more collateral flow to the right lung than those without. Conclusions—APC blood flow can be noninvasively measured in bidirectional cavopulmonary connections and Fontan patients, using MRI in the majority of patients and results in a significant left-to-right shunt.

Hybrid Versus Norwood Strategies for Single-Ventricle Palliation

Background— Hybrid and Norwood strategies differ substantially in terms of stage II palliative procedures. We sought to compare these strategies with an emphasis on survival and reintervention after stage II and subsequent Fontan completion. Methods and Results— Of 110 neonates with functionally single-ventricle physiology who underwent stage I palliation between 2004 and 2010, 75 (69%) infants (Norwood, n=43; hybrid, n=32) who subsequently underwent stage II palliation were studied. Survival and reintervention rates after stage II palliation, anatomic and physiologic variables at pre-Fontan assessment, and Fontan outcomes were compared between the groups. Predictors for reintervention were analyzed. Freedom from death/transplant after stage II palliation was equivalent between the groups (Norwood, 80.4% versus hybrid, 85.6% at 3 years, P=0.66). Hybrid patients had a higher pulmonary artery (PA) reintervention rate (P=0.003) and lower Nakata index at pre-Fontan evaluation (P=0.015). Aortic arch and atrioventricular valve reinterventions were not different between the groups. Ventricular end-diastolic pressure, mean PA pressure, and ventricular function were equivalent at pre-Fontan assessment. There were no deaths after Fontan completion in either group (Norwood, n=25, hybrid, n=14). Conclusions— Survival after stage II palliation and subsequent Fontan completion is equivalent between the groups. The hybrid group had a higher PA reintervention rate and smaller PA size. Both strategies achieved adequate physiology for Fontan completion. Evolution of the hybrid strategy requires refinement to provide optimal PA growth.

Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI)

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Echocardiographic Assessment of Right Ventricular Volumes after Surgical Repair of Tetralogy of Fallot: Clinical Validation of a New Echocardiographic Method

BACKGROUND Assessment of right ventricular (RV) volumes and function is important in patients after tetralogy of Fallot (TOF) repair. Currently, cardiac magnetic resonance imaging (MRI) is considered the clinical reference method for RV volume and function measurements. Three-dimensional (3D) knowledge-based reconstruction derived from two-dimensional echocardiographic imaging with magnetic tracking is a novel approach to RV volumetrics. The aim of this study was to assess the feasibility and reliability of this novel echocardiographic technique in patients after TOF repair. The accuracy of the method was assessed by comparison with measurements obtained by cardiac MRI. METHODS Thirty patients (mean age, 13.7 ± 2.8 years) after TOF repair, referred for cardiac MRI, were included. Immediately after MRI, echocardiographic image acquisition was performed using a standard ultrasound scanner linked to a Ventripoint Medical Systems unit. Echocardiographic and MRI measurements were performed offline. Parameters analyzed were end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction. Intraobserver, interobserver, and intertechnique variability was assessed using Pearsons correlation analysis, coefficients of variation, and Bland-Altman analysis. RESULTS Echocardiographic two-dimensionally based 3D reconstruction was highly feasible, with low intraobserver and interobserver variability for EDV and slightly higher variability for ESV and ejection fraction. The 3D reconstruction values for EDV, ESV, and ejection fraction were correlated highly with MRI values, with low coefficients of variation. The agreement between both methods was high. Three-dimensional reconstruction slightly underestimated RV volumes, by 2.5% for EDV and 4.6% for ESV compared with MRI volumes. CONCLUSIONS In patients after TOF repair, echocardiographic 3D reconstruction is highly feasible, with good reproducibility for measurements of RV EDV. There is good agreement with MRI measurements, with a small underestimation of RV volumes. The use of this method in clinical practice warrants further investigation.

Echocardiographic assessment of right ventricular volumes: a comparison of different techniques in children after surgical repair of tetralogy of Fallot

AIMS Different echocardiographic techniques are available for assessing right ventricular (RV) volumes but their clinical validity has not been well established. We compared the feasibility, reproducibility and accuracy of three different echocardiographic techniques for measuring RV volumes and ejection fraction (EF) in children after tetralogy of Fallot (TOF) repair. METHODS AND RESULTS Seventy patients (age 14.2 ± 7.3 years) were studied using three-dimensional (3D) volume acquisition analysis (Tomtec, Germany), 2D echo with knowledge-based 3D reconstruction (3DR) (Ventripoint, USA) and the four-chamber area (4C area) methods. Parameters analysed were RV end-diastolic volume (EDV), end-systolic volume and EF. Magnetic resonance imaging (MRI) data were available in 41 patients. Intra- and inter-observer as well as inter-technique variability was assessed using Pearsons correlation analysis (R), coefficient of variance, and Bland-Altman analysis. Feasibility was good for all echo techniques (91% for the 3D, 98% for the 3DR, and 100% for the 4C area method). Intra- and inter-observer variability was low for both 3DR and the 3D echo, while more variability was observed for the 4C method. Compared with MRI volumes, 3DR and 3D underestimated EDV by 6.6 ± 10 and 18.2 ± 17.8 mL, respectively, (P < 0.001), while the 4C area method overestimated the EDV by 9.6 ± 33 mL, not significant due to a wide range. CONCLUSION Current echocardiographic techniques to assess RV volumes are highly feasible and reproducible in paediatric post-operative TOF patients. When compared with MRI measurements, 3DR was the most accurate technique but requires extra equipment that is not readily available.

Exercise induces biventricular mechanical dyssynchrony in children with repaired tetralogy of Fallot

Objective The mechanisms underlying adverse electro-mechanical interaction after tetralogy of Fallot (TOF) repair remain unclear. This study investigated biventricular dyssynchrony in children with TOF and its relationship to exercise, QRS duration (QRSd) and ventricular mechanics. Methods 29 asymptomatic children (5–18 years) with repaired TOF were prospectively evaluated by MRI, cardiopulmonary exercise testing and echocardiography at rest and during bicycle exertion. Their dyssynchrony results were compared with those of 44 resting and 27 exercising, age- and sex-matched controls. An intraventricular dyssynchrony index was calculated from the SD of regional time intervals in 12 left ventricular (LV) ‘Ts LV-12SD’ and eight right ventricular (RV) ‘Ts RV-8SD’ segments. Ventricular size, volumes, ejection fractions, pulmonary regurgitant volumes and peak oxygen consumption and N-terminal BNP levels were quantified in the patients. Results Despite moderate RV dilatation (median indexed RV end-diastolic volume 145.2 ml/m2) and right bundle branch block (median QRSd 130 ms) compared with controls, children with TOF demonstrated neither RV nor LV dyssynchrony at rest (Ts RV-8SD, 37.9±10.2 vs 44.3±10.3, 95% CI −11.8 to −0.99, p=0.02; Ts LV-12SD, 38.6±16.8 vs 34.0±10.8, 95% CI −1.8 to 11.0, p=0.16). Exercise stress induced biventricular dyssynchrony in patients with TOF but not in controls (Ts RV-8SD, 59.9±34.4 vs 28.2±10.4, p<0.0001, 95% CI 17.2 to 46.3; Ts LV-12SD, 48.0±18.6 vs 31.9±10.7, 95% CI 7.9 to 24.4, p=0.002). This was unrelated to QRSd, ventricular volumes and function, or peak oxygen consumption. Conclusion Exercise induces biventricular mechanical dyssynchrony in children with TOF.

Phase-contrast magnetic resonance quantification of normal pulmonary venous return.

To assess the feasibility of phase‐contrast magnetic resonance (PCMR) in quantifying the pulmonary venous return in normal subjects.

Metric optimized gating for fetal cardiac MRI

Phase‐contrast magnetic resonance imaging can be used to complement echocardiography for the evaluation of the fetal heart. Cardiac imaging typically requires gating with peripheral hardware; however, a gating signal is not readily available in utero. No successful application of existing technologies to human fetal phase‐contrast magnetic resonance imaging has been reported to date in the literature. The purpose of this work is to develop a technique for phase‐contrast magnetic resonance imaging of the fetal heart that does not require measurement of a gating signal. Metric optimized gating involves acquiring data without gating and retrospectively determining the proper reconstruction by optimizing an image metric. The effects of incorrect gating on phase contrast images were investigated, and the time‐entropy of the series of images was found to provide a good measure of the level of corruption. The technique was validated with a pulsatile flow phantom, experiments with adult volunteers, and in vivo application in the fetal population. Images and flow curves from these measurements are presented. Additionally, numerical simulations were used to investigate the degree to which heart rate variability affects the reconstruction process. Metric optimized gating enables imaging with conventional phase‐contrast magnetic resonance imaging sequences in the absence of a gating signal, permitting flow measurements in the great vessels in utero. Magn Reson Med, 2010.

Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study

BackgroundWe present the first phase contrast (PC) cardiovascular magnetic resonance (CMR) measurements of the distribution of blood flow in twelve late gestation human fetuses. These were obtained using a retrospective gating technique known as metric optimised gating (MOG).MethodsA validation experiment was performed in five adult volunteers where conventional cardiac gating was compared with MOG. Linear regression and Bland Altman plots were used to compare MOG with the gold standard of conventional gating. Measurements using MOG were then made in twelve normal fetuses at a median gestational age of 37 weeks (range 30–39 weeks). Flow was measured in the major fetal vessels and indexed to the fetal weight.ResultsThere was good correlation between the conventional gated and MOG measurements in the adult validation experiment (R=0.96). Mean flows in ml/min/kg with standard deviations in the major fetal vessels were as follows: combined ventricular output (CVO) 540±101, main pulmonary artery (MPA) 327±68, ascending aorta (AAo) 198±38, superior vena cava (SVC) 147±46, ductus arteriosus (DA) 220±39,pulmonary blood flow (PBF) 106±59,descending aorta (DAo) 273±85, umbilical vein (UV) 160±62, foramen ovale (FO)107±54. Results expressed as mean percentages of the CVO with standard deviations were as follows: MPA 60±4, AAo37±4, SVC 28±7, DA 41±8, PBF 19±10, DAo50±12, UV 30±9, FO 21±12.ConclusionThis study demonstrates how PC CMR with MOG is a feasible technique for measuring the distribution of the normal human fetal circulation in late pregnancy. Our preliminary results are in keeping with findings from previous experimental work in fetal lambs.