Effects of hemodynamic alterations and oxygen saturation on cerebral perfusion in congenital heart disease.

BACKGROUND: Patients with severe congenital heart disease (CHD) are at risk for neurodevelopmental impairment. An abnormal cerebral blood supply caused by the altered cardiac physiology may limit optimal brain development. The aim of this study was to evaluate the effect of a systemic-to-pulmonary shunt, aortic arch obstruction and arterial oxygen saturation on cerebral perfusion in patients with severe CHD. METHODS: Patients with severe CHD requiring cardiac surgery within the first six weeks of life, who underwent pre- and/or postoperative brain magnetic resonance imaging (MRI), and healthy controls with one postnatal scan were included. Cerebral perfusion in deep and cortical gray matter was assessed by pseudocontinuous arterial spin labeling MRI. RESULTS: We included 59 CHD and 23 healthy control scans. The presence of a systemic-to-pulmonary shunt was associated with decreased perfusion in cortical (p = 0.003), but not in deep gray matter (p = 0.031). No evidence for an effect of aortic arch obstruction and arterial oxygen saturation on cerebral perfusion was found. After adjusting for hemodynamic and oxygen saturation parameters, deep (p = 0.018) and cortical (p = 0.012) gray matter perfusion was increased in patients with CHD compared to controls. CONCLUSION: We detected regional differences in compensation to the cerebral steal effect in patients with severe CHD. IMPACT: Patients with severe congenital heart disease (CHD) have altered postnatal brain hemodynamics. A systemic-to-pulmonary shunt was associated with decreased perfusion in cortical gray matter but preserved perfusion in deep gray matter, pointing towards regional differences in compensation to the cerebral steal effect. No effects of aortic arch obstruction and arterial oxygenation on cerebral perfusion were seen. Cerebral perfusion was increased in patients with CHD compared to healthy controls after adjusting for hemodynamic alterations and oxygen saturation. To improve neuroprotection and neurodevelopmental outcomes, it is important to increase our understanding of the factors influencing cerebral perfusion in neonates with severe CHD.

Postnatal cerebral hemodynamics in infants with severe congenital heart disease: a scoping review.

Patients with severe congenital heart disease (CHD) are at risk for impaired neurodevelopment. Cerebral blood supply may be diminished by congenital anomalies of cardiovascular anatomy and myocardial function. The aim of this scoping review was to summarize the current knowledge on cerebral hemodynamics in infants with severe CHD. A scoping review was performed. Five databases were searched for articles published from 01/1990 to 02/2022 containing information on cerebral hemodynamics assessed by neuroimaging methods in patients with severe CHD within their first year of life. A total of 1488 publications were identified, of which 26 were included. Half of the studies used Doppler ultrasound, and half used magnetic resonance imaging techniques. Studies focused on preoperative findings of cerebral hemodynamics, effects of surgical and conservative interventions, as well as on associations between cerebral hemodynamics and brain morphology or neurodevelopment. Cerebral perfusion was most severely affected in patients with single ventricle and other cyanotic disease. Neuroimaging methods provide a large variety of information on cerebral hemodynamics. Nevertheless, small and heterogeneous cohorts complicate this field of research. Further studies are needed to improve our understanding of the link between CHD and altered cerebral hemodynamics to optimize neuroprotection strategies. IMPACT: Postnatal cerebral hemodynamics are altered in infants with congenital heart disease (CHD) as compared to healthy controls, especially in most severe types such as single ventricle or other cyanotic CHD. Associations of these alterations with brain volume and maturation reveal their clinical relevance. Research in this area is limited due to the rarity and heterogeneity of diagnoses. Furthermore, longitudinal studies have rarely been conducted. Further effort is needed to better understand the deviation from physiological cerebral perfusion and its consequences in patients with CHD to optimize neuroprotection strategies.

Morbidity and mortality in premature or low birth weight patients with congenital heart disease in three European pediatric heart centers between 2016 and 2020.

Background: The treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group. Methods: A retrospective cohort study was conducted of preterm [<37 weeks gestational age (GA)] and/or LBW neonates (<2,500 g) born with a diagnosis of CHD, which requires invasive cardiac intervention (surgery or catheter) within their first year of life. Patients born between 2016 and 2020 and treated in three European pediatric heart centers were included. Results: A total of 308 neonates (51% male) with CHD were included. Of those, 237 (77%) were born preterm, 259 (84%) were LBW, and 188 (61%) were both. The median GA was 35.4 weeks (interquartile range 33.3-36.9) and the mean birth weight was 2,016 ± 580 g. CHD was categorized as simple (12%), moderate (64%), or severe (24%). The overall complication rate was 45% and was highest in patients with severe CHD (p = 0.002). One-year mortality (19%) was associated with severe CHD, low relative birth weight in patients with genetic diagnoses, and low GA at birth, whereas GA at birth significantly impacted survival only after 3 months of life. Conclusions: The high morbidity and mortality in preterm and LBW neonates with CHD reflect their complexity and consequent limited treatment feasibility.

Impact of postoperative necrotizing enterocolitis after neonatal cardiac surgery on neurodevelopmental outcome at 1 year of age.

Objectives: We analyzed the impact of postoperative necrotizing enterocolitis (NEC) after cardiac surgery in neonatal age on neurodevelopmental (ND) outcome at 1 year of age. Methods: Using data from the Swiss Neurodevelopmental Outcome Registry for Children with Congenital Heart Disease (ORCHID), we analyzed perioperative variables including postoperative NEC (Bell's stage ≥2) and 1-year ND outcome (Bayley III). Results: The included patients (n = 101) had congenital heart disease (CHD), categorized as follows: 77 underwent biventricular repair for CHD with two functional chambers, 22 underwent staged palliation until the Fontan procedure for CHD with single ventricle physiology (n = 22), or 4 underwent single ventricle palliation or biventricular repair for borderline CHD (n = 4). Neonatal cardiopulmonary bypass (CBP) surgery was performed at a median age (IQR) of 8 (6) days. NEC occurred in 16 patients. Intensive care unit (ICU) length of stay (LOS) and the total duration of the hospitalization were longer in children with NEC than those in others (14 with vs. 8 days without NEC, p < 0.05; 49 with vs. 32 days without NEC, p < 0.05). The Bayley III scores of the analyzed patients determined at an age of 11.5 ± 1.5 months showed cognitive (CCS) (102.2 ± 15.0) and language scores (LCS) (93.8 ± 13.1) in the normal range and motor composite scores (MCS) (88.7 ± 15.9) in the low-normal range. After adjusting for socioeconomic status and CHD type, patients with NEC had lower CCS scores [ß = -11.2 (SE 5.6), p = 0.049]. Using a cumulative risk score including NEC, we found a higher risk score to be associated with both lower CCS [ß = -2.8 (SE 1.3), p = 0.030] and lower MCS [ß = -3.20 (SE 1.3), p = 0.016]. Conclusions: Postoperative NEC is associated with longer ICU and hospital LOS and contributes together with other complications to impaired ND outcome at 1 year of age. In the future, national and international patient registries may provide the opportunity to analyze large cohorts and better identify the impact of modifiable perioperative risk factors on ND outcome. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT05996211.

Characterization of dynamic patterns of human fetal to neonatal brain asymmetry with deformation-based morphometry.

Introduction: Despite established knowledge on the morphological and functional asymmetries in the human brain, the understanding of how brain asymmetry patterns change during late fetal to neonatal life remains incomplete. The goal of this study was to characterize the dynamic patterns of inter-hemispheric brain asymmetry over this critically important developmental stage using longitudinally acquired MRI scans. Methods: Super-resolution reconstructed T2-weighted MRI of 20 neurotypically developing participants were used, and for each participant fetal and neonatal MRI was acquired. To quantify brain morphological changes, deformation-based morphometry (DBM) on the longitudinal MRI scans was utilized. Two registration frameworks were evaluated and used in our study: (A) fetal to neonatal image registration and (B) registration through a mid-time template. Developmental changes of cerebral asymmetry were characterized as (A) the inter-hemispheric differences of the Jacobian determinant (JD) of fetal to neonatal morphometry change and the (B) time-dependent change of the JD capturing left-right differences at fetal or neonatal time points. Left-right and fetal-neonatal differences were statistically tested using multivariate linear models, corrected for participants' age and sex and using threshold-free cluster enhancement. Results: Fetal to neonatal morphometry changes demonstrated asymmetry in the temporal pole, and left-right asymmetry differences between fetal and neonatal timepoints revealed temporal changes in the temporal pole, likely to go from right dominant in fetal to a bilateral morphology in neonatal timepoint. Furthermore, the analysis revealed right-dominant subcortical gray matter in neonates and three clusters of increased JD values in the left hemisphere from fetal to neonatal timepoints. Discussion: While these findings provide evidence that morphological asymmetry gradually emerges during development, discrepancies between registration frameworks require careful considerations when using DBM for longitudinal data of early brain development.

Neurodevelopmental and functional outcome in hypoplastic left heart syndrome after Hybrid procedure as stage I.

Background: Patients with hypoplastic left heart syndrome (HLHS) undergoing staged palliation until Fontan procedure are at risk for impaired neurodevelopmental (ND) outcome. The Hybrid procedure with bilateral pulmonary artery banding, ductal stenting, and balloon atrioseptostomy may offer a less invasive stage I procedure compared to the Norwood stage I procedure avoiding early neonatal cardiopulmonary bypass (CPB) surgery. Despite altered fetal cerebral hemodynamics, the type of stage I procedure may be a covariate influencing ND outcome and functional outcome may also be altered due to postponing neonatal CPB surgery. Within this review, we analyzed ND outcome as well as functional outcome after Hybrid procedure as stage I procedure. Methods: The review analyzed original publications (OPs) published before March 15, 2022, identified by Cochrane, EMBASE, OVID, Scopus, and Web of science. An OP was included if short-to-long-term neurodevelopment outcome, brain development, somatic, and cardiac outcome in patients for HLHS and variants treated by Hybrid procedure were analyzed. In addition to database searches, we reviewed all references of the analyzed OP to obtain a comprehensive list of available studies. The author, year of publication, demographic characteristics of study population, study design (prospective or retrospective), study assessment, and main findings were summarized. Results: Twenty-one OPs were included with data of patients with ND outcome and functional cardiac outcome. Overall, there is an impaired mid-term ND outcome in patients with Hybrid procedure as stage I for HLHS. Only slight differences between stage I procedures (Hybrid vs. Norwood) in two comparing studies have been determined affecting right ventricular remodeling, short- and mid-term ND outcome, reduced brain growth until two years of age, sufficient quality of life, and altered hemodynamics influencing brain volumes and cerebral perfusion pattern. Conclusions: Despite some minor differences regarding the mid-term follow-up in patients with HLHS comparing Hybrid vs. Norwood procedure, its impact on ND outcome seems rather low. This may be explained by the large number of covariates as well as the small study populations and the different selection criteria for patients undergoing Hybrid or Norwood procedure as stage I.

Computer-Aided Detection of Seven Chest Pathologies on Standard Posteroanterior Chest X-Rays Compared to Radiologists Reading Dual-Energy Subtracted Radiographs.

RATIONALE AND OBJECTIVES: Retrospective performance evaluation of a computer-aided detection (CAD) system on standard posteroanterior (PA) chest radiographs (PA-CXR) in detection of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly and rib fractures compared to radiologists analyzing PA-CXR including dual-energy subtraction radiography (further termed as DESR). MATERIALS AND METHODS: PA-CXR/DESR images of 197 patients were included. All patients underwent chest CT (gold standard) within a short interval (mean 28 hours). All images were evaluated by three blinded readers for the presence of pulmonary nodules, infectious consolidation, pneumothorax, pleural effusion, aortic calcification, cardiomegaly, and rib fractures. Meanwhile PA-CXR were analyzed by a CAD software. CAD results were compared to the majority result of the three readers. Sensitivity and specificity were calculated. McNemar's test was applied to test for significant differences. Interobserver agreement was defined using Cohen's kappa (κ). RESULTS: Sensitivity of the CAD software was significantly higher (p < 0.05) for detection of infectious consolidation and pulmonary nodules (67.9% vs 26.8% and 54% vs 35.6%, respectively; p < 0.001) compared to radiologists analyzing DESR images. For the residual evaluated pathologies no statistical significant differences could be found. Overall, mean inter observer agreement between the three radiologists was moderate (k = 0.534). The best interobserver agreement could be reached for pneumothorax (k = 0.708) and pleural effusion (k = 0.699), while the worst was obtained for rib fractures (k = 0.412). CONCLUSION: The CAD system has the potential to improve the detection of infectious consolidation and pulmonary nodules on CXR images.

Cerebral desaturation during neonatal congenital heart surgery is associated with perioperative brain structure alterations but not with neurodevelopmental outcome at 1 year.

OBJECTIVES: The significance of intraoperative cerebral desaturation (CD) measured by near-infrared spectroscopy (NIRS) to predict neurological outcome after congenital heart surgery is uncertain. The goal of this study was to compare brain structure changes and neurodevelopmental outcome in patients with severe congenital heart disease with and without intraoperative CD. METHODS: Neonates requiring congenital heart surgery were enrolled in a cohort study. NIRS data from their first cardiac operation were collected. Pre- and postoperative brain magnetic resonance imaging results and Bayley-III scores at 1 year were compared between patients with and without CD, defined by 2 NIRS thresholds: regional cerebral oxygen saturation (rSO2) of 45% (45%rSO2) and rSO2 below 20% of baseline value (20%BLrSO2). RESULTS: Thirty-two patients (72% male) with d-transposition of the great arteries (n = 24, 75%) and other complex types of congenital heart diseases (n = 8, 25%) were analysed. Perioperative relative lateral ventricle volume change was increased in patients with versus without intraoperative CD (P = 0.003 for 45%rSO2, P = 0.008 for 20%BLrSO2). For 45%rSO2, the effect of CD remained significant after adjusting for age at postoperative scan, time between scans and cardiac diagnosis (P = 0.019). New intracranial lesions occurred predominantly in CD groups (6/6 patients for 45%rSO2, 5/6 patients for 20%BLrSO2). Neurodevelopmental outcome at 1 year was not associated with intraoperative CD. CONCLUSIONS: This study demonstrates the clinical relevance of NIRS monitoring during congenital heart surgery. The occurrence of intraoperative CD is associated with perioperative lateral ventricle volume change and new intracranial lesions.