Babies born growth restricted are at an increased risk of both poor short‐and long‐term outcomes. Current interventions to improve fetal growth are ineffective and do not lower the lifetime risk of ...poor health status. Maternal resveratrol (RSV) treatment increases uterine artery blood flow, fetal oxygenation, and fetal weight. However, studies suggest that diets high in polyphenols such as RSV may impair fetal hemodynamics. We aimed to characterize the effect of RSV on fetal hemodynamics to further assess its safety as an intervention strategy. Pregnant ewes underwent magnetic resonance imaging (MRI) scans to measure blood flow and oxygenation within the fetal circulation using phase contrast‐MRI and T2 oximetry. Blood flow and oxygenation measures were performed in a basal state and then repeated while the fetus was exposed to RSV. Fetal blood pressure and heart rate were not different between states. RSV did not impact fetal oxygen delivery (DO2) or consumption (VO2). Blood flow and oxygen delivery throughout the major vessels of the fetal circulation were not different between basal and RSV states. As such, acute exposure of the fetus to RSV does not directly impact fetal hemodynamics. This strengthens the rationale for the use of RSV as an intervention strategy against fetal growth restriction.
Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the ...intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low‐resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way. Preterm Yucatan miniature piglets are similar in size to extremely preterm human infants and share similar umbilical cord anatomy, raising the possibility to serve as a good model to investigate the AP. To characterize fetal cardiovascular physiology, the carotid artery (n = 24) was cannulated in utero and umbilical vein (UV) and umbilical artery were sampled. Fetal UV flow was measured by MRI (n = 16). Piglets were delivered at 98 ± 4 days gestation (term = 115 days), cannulated, and supported on the AP (n = 12) for 684 ± 228 min (range 195–3077 min). UV flow was subphysiologic (p = .002), while heart rate was elevated on the AP compared with in utero controls (p = .0007). We observed an inverse relationship between heart rate and UV flow (r2 = .4527; p < .001) with progressive right ventricular enlargement that was associated with reduced contractility and ultimately hydrops and circulatory collapse. We attribute this to excessive afterload imposed by supraphysiologic circuit resistance and augmented sympathetic activity. We conclude that short‐term support of the preterm piglet on the AP is feasible, although we have not been able to attain normal fetal physiology. In the future, we propose to investigate the feasibility of an AP circuit that incorporates a centrifugal pump in our miniature pig model.
The artificial placenta (AP) as an extrauterine environment to preserve fetal physiology and to promote fetal maturation forms a promising concept to reduce morbidity and mortality in the extremely premature. We have achieved successful transition of fetal minipigs on the AP but have encountered heart failure and fetal demise within several hours of support. Our experience highlights modes of failure and ways to improve AP technology to advance this approach to clinical application.
Magnetic Resonance Imaging (MRI) is well‐suited for imaging peripheral blood flow due to its non‐invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess ...physiological changes in chronic diseases, there are currently no MRI‐based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric‐adolescent population using phase contrast MRI, and to present test‐retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC‐MRI of the femoral artery at rest and following a 5 × 30 s of in‐magnet exercise. To evaluate test‐retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest‐peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest‐peak ICC = 0.87, p = 0.003) between‐visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV’s) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest‐peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non‐invasive phase contrast MRI. The MRI‐based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test‐retest reliability both at rest and immediately post‐exercise.
Magnetic Resonance Imaging (MRI) is well‐suited for imaging peripheral blood flow due to its non‐invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI‐based data quantifying arterial flow in pediatric populations during exercise. Our objective was to document femoral arterial blood flow at rest and following exercise in a pediatric population using phase contrast MRI, and to present test‐retest reliability data for this method.
Recent large-scale sequencing efforts have shed light on the genetic contribution to the etiology of congenital heart defects (CHD); however, the relative impact of genetics on clinical outcomes ...remains less understood. Outcomes analyses using genetics are complicated by the intrinsic severity of the CHD lesion and interactions with conditionally dependent clinical variables.
Bayesian Networks were applied to describe the intertwined relationships between clinical variables, demography, and genetics in a cohort of children with single ventricle CHD.
As isolated variables, a damaging genetic variant in a gene related to abnormal heart morphology and prolonged ventilator support following stage I palliative surgery increase the probability of having a low Mental Developmental Index (MDI) score at 14 months of age by 1.9- and 5.8-fold, respectively. However, in combination, these variables act synergistically to further increase the probability of a low MDI score by 10-fold. The absence of a damaging variant in a known syndromic CHD gene and a shorter post-operative ventilator support increase the probability of a normal MDI score 1.7- and 2.4-fold, respectively, but in combination increase the probability of a good outcome by 59-fold.
Our analyses suggest a modest genetic contribution to neurodevelopmental outcomes as isolated variables, similar to known clinical predictors. By contrast, genetic, demographic, and clinical variables interact synergistically to markedly impact clinical outcomes. These findings underscore the importance of capturing and quantifying the impact of damaging genomic variants in the context of multiple, conditionally dependent variables, such as pre- and post-operative factors, and demography.
Continuous data capture technology is becoming more common. Establishing analytic approaches for continuous data could aid in understanding the relationship between physiology and clinical outcomes. ...OBJECTIVESOur objective was to design a retrospective analysis for continuous physiologic measurements and their relationship with new brain injury over time after cardiac surgery. DESIGN SETTING AND PARTICIPANTSRetrospective cohort study in the Cardiac Critical Care Unit at the Hospital for Sick Children in patients after repair of transposition of the great arteries (TGA) or single ventricle (SV) lesions. MAIN OUTCOMES AND MEASURESContinuously acquired physiologic measurements for up to 72 hours after cardiac surgery were analyzed for association with new brain injury by MRI. Distributions of heart rate (HR), systolic blood pressure (BP), and oxygen saturation (Spo2) for SV and TGA were analyzed graphically and with descriptive statistics over postoperative time for data-driven variable selection. Mixed-effects regression analyses characterized relationships between HR, BP, and Spo2 and new brain injury over time while accounting for variation between patients, measurement heterogeneity, and missingness. RESULTSSeventy-seven patients (60 TGA; 17 SV) were included. New brain injury was seen in 26 (34%). In SV patients, with and without new brain injury, respectively, in the first 24 hours after cardiac surgery, the median (interquartile range) HR was 172.0 beats/min (bpm) (169.7-176.0 bpm) versus 159.6 bpm (145.0-167.0 bpm); systolic BP 74.8 (67.9-78.5 mm Hg) versus 68.9 mm Hg (61.6-70.9 mm Hg). Higher postoperative HR (parameter estimate, 19.4; 95% CI, 7.8-31; p = 0.003 and BP, 8.6; 1.3-15.8; p = 0.024) were associated with new brain injury in SV patients. The strength of this relationship decreased with time. CONCLUSIONS AND RELEVANCERetrospective analysis of continuous physiologic measurements can provide insight into changes in postoperative physiology over time and their relationship with new brain injury. This technique could be applied to assess relationships between physiologic data and many patient interventions or outcomes.
The ductus arteriosus (DA) functionally closes during the transition from fetal to postnatal life because of lung aeration and corresponding cardiovascular changes. The thorough and explicit ...measurement and visualization of the right and left heart output during this transition has not been previously accomplished. We combined 4D flow MRI (dynamic volumetric blood flow measurements) and T2 relaxometry (oxygen delivery quantification) in surgically instrumented newborn piglets to assess the DA. This was performed in Large White‐Landrace‐Duroc piglets (n = 34) spanning four age groups: term‐9 days, term‐3, term+1, and term+5. Subject's DA status was classified using 4D flow: closed DA, forward DA flow, reversed DA flow, and bidirectional DA flow. Over all states, vessel diameters and flows normalized to body weight increased with age (for example in the ascending aorta flow—term‐9: 126.6 ± 45.4; term+5: 260.2 ± 80.0 ml/min per kg; p = 0.0005; ascending aorta diameter—term‐9: 5.2 ± 0.8; term+5: 7.7 ± 0.4 mm; p = 0.0004). In subjects with reversed DA blood flow there was lower common carotid artery blood flow (forward: 37.5 ± 9.0; reversed: 20.0 ± 7.4 ml/min per kg; p = 0.032). Linear regression revealed that as net DA flow decreases, common carotid artery flow decreases (R2 = 0.32, p = 0.004), and left (R2 = 0.33, p = 0.003) and right (R2 = 0.34, p = 0.003) pulmonary artery flow increases. Bidirectional DA blood flow changed oxygen saturation as determined by MRI between the ascending and descending aorta (ascending aorta: 90.1% ± 8.4%; descending aorta: 75.6% ± 14.2%; p < 0.05). Expanded use of these techniques in preterm animal models will aid in providing new understandings of normal versus abnormal DA transition, as well as to test the effectiveness of related clinical interventions.
At birth, the lungs and surrounding vasculature work to functionally close the ductus arteriosus (DA). This process is delayed in preterm newborns. MRI techniques, namely 4D flow and T2 relaxometry, can be used to comprehensively assess cardiac blood flow and oxygen delivery in newborns. These approaches are demonstrated across preterm and term‐born piglets, and whole heart blood flow visualization is paired alongside flow and oxygenation quantification.
Congenital heart diseases causing significant hemodynamic and functional consequences require surgical repair. Understanding of the precise surgical anatomy is often challenging and can be inadequate ...or wrong. Modern high resolution imaging techniques and 3D printing technology allow 3D printing of the replicas of the patient’s heart for precise understanding of the complex anatomy, hands-on simulation of surgical and interventional procedures, and morphology teaching of the medical professionals and patients. CT or MR images obtained with ECG-gating and breath-holding or respiration navigation are best suited for 3D printing. 3D echocardiograms are not ideal but can be used for printing limited areas of interest such as cardiac valves and ventricular septum. Although the print materials still require optimization for representation of cardiovascular tissues and valves, the surgeons find the models suitable for practicing closure of the septal defects, application of the baffles within the ventricles, reconstructing the aortic arch, and arterial switch procedure. Hands-on surgical training (HOST) on models may soon become a mandatory component of congenital heart disease surgery program. 3D printing will expand its utilization with further improvement of the use of echocardiographic data and image fusion algorithm across multiple imaging modalities and development of new printing materials. Bioprinting of implants such as stents, patches and artificial valves and tissue engineering of a part of or whole heart using the patient’s own cells will open the door to a new era of personalized medicine.
In the current era, most single-ventricle heart disease (SVHD) is diagnosed prenatally by means of fetal echocardiography. Disparities exist, however, by socioeconomic status and remote location, ...which require further attention. Prenatal diagnosis affords the opportunity to counsel expectant parents regarding the life-long course of children with SVHD, including the stages of single-ventricle palliation and challenges of the Fontan circulation; to discuss pregnancy management options; and to optimise delivery planning and perinatal care. Prognosis may be refined by specific features on the fetal echocardiogram, such as ventricular morphology, total anomalous pulmonary venous return, and atrioventricular valve regurgitation. Expectant mothers should be referred for evaluation of extracardiac anomalies and/or a genetic syndrome, which also significantly affect outcome. Fetuses with SVHD should be cared for by a multidisciplinary team and ideally delivered at term at or near a cardiac surgical center. Serial echocardiograms refine the anticipated postnatal physiology to optimise transitional care, including the need for prostaglandin or urgent atrial septal intervention in fetuses with hypoplastic left heart syndrome. In selected patients, there may be a role for fetal cardiac intervention to improve mortality or achieve a biventricular circulation after birth. Together, these strategies enhance the preoperative status of the neonate. Recent advances in fetal cardiovascular magnetic resonance imaging have focused on studying the relationships between cardiovascular physiology and fetal growth and development. These novel techniques allow for the exploration of the physiologic effects of SVHD on the brain and open avenues for the investigation of neuroprotective therapies.
De nos jours, les cas de cœur univentriculaire (CU) sont pour la plupart diagnostiqués pendant la période prénatale par échocardiographie fœtale. Il existe toutefois des disparités, fondées sur le statut socio-économique et sur l’éloignement des grands centres, auxquelles il convient de porter davantage attention. Le diagnostic prénatal permet de renseigner les futurs parents sur le parcours de vie de l’enfant présentant un CU, notamment en ce qui concerne les étapes de la palliation univentriculaire et les défis que présente la circulation de Fontan. C’est aussi l’occasion de discuter des options de prise en charge de la grossesse et d’optimiser la planification de l’accouchement et les soins périnataux. Le pronostic peut être affiné en fonction de certaines caractéristiques de l’échocardiogramme fœtal, telles que la morphologie ventriculaire, le retour veineux pulmonaire anormal total et la régurgitation des valves atrioventriculaires. Les femmes enceintes doivent être dirigées vers les ressources appropriées afin que soit effectuée une évaluation visant à déceler la présence éventuelle d’anomalies extracardiaques ou d’un syndrome génétique, également susceptibles de peser lourdement sur le devenir de l’enfant. Les fœtus présentant un CU doivent être pris en charge par une équipe multidisciplinaire et, idéalement, naître à terme dans un centre de chirurgie cardiaque ou à proximité de celui-ci. Les échocardiogrammes en série affinent les données prévisionnelles sur la physiologie postnatale et permettent d’optimiser les soins de transition, y compris l’administration de prostaglandine ou une intervention visant à corriger d’urgence une communication interatriale en cas de syndrome d’hypoplasie fœtale du cœur gauche. Chez certains patients, la chi-rurgie cardiaque fœtale peut limiter la mortalité ou permettre d’obtenir une circulation biventriculaire postnatale. Toutes ces stratégies concourent à améliorer l’état préopératoire du nouveau-né. Les progrès récents dans le domaine de l’imagerie par résonance magnétique cardiovasculaire fœtale s’articulent autour de l’étude des relations entre la physiologie cardiovasculaire et le développement du fœtus. Les nouvelles techniques qui en sont issues permettent d’examiner les effets physiologiques du CU sur le cerveau et d’ouvrir des pistes de recherche en matière de traitements neuroprotecteurs.
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