Iron Deficiency and Sleep/Wake Behaviors: A Scoping Review of Clinical Practice Guidelines-How to Overcome the Current Conundrum?

Current evidence suggests that iron deficiency (ID) plays a key role in the pathogenesis of conditions presenting with restlessness such as attention deficit hyperactivity disorder (ADHD) and restless legs syndrome (RLS). In clinical practice, ID and iron supplementation are not routinely considered in the diagnostic work-up and/or as a treatment option in such conditions. Therefore, we conducted a scoping literature review of ID guidelines. Of the 58 guidelines included, only 9 included RLS, and 3 included ADHD. Ferritin was the most frequently cited biomarker, though cutoff values varied between guidelines and depending on additional factors such as age, sex, and comorbidities. Recommendations surrounding measurable iron biomarkers and cutoff values varied between guidelines; moreover, despite capturing the role of inflammation as a concept, most guidelines often did not include recommendations for how to assess this. This lack of harmonization on the interpretation of iron and inflammation biomarkers raises questions about the applicability of current guidelines in clinical practice. Further, the majority of ID guidelines in this review did not include the ID-associated disorders, ADHD and RLS. As ID can be associated with altered movement patterns, a novel consensus is needed for investigating and interpreting iron status in the context of different clinical phenotypes.

Changes in cortical grey matter volume with Cognitive Orientation to daily Occupational Performance intervention in children with developmental coordination disorder.

Introduction: Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive-based, task-specific intervention recommended for children with developmental coordination disorder (DCD). We recently showed structural and functional brain changes after CO-OP, including increased cerebellar grey matter. This study aimed to determine whether CO-OP intervention induced changes in cortical grey matter volume in children with DCD, and if these changes were associated with improvements in motor performance and movement quality. Methods: This study is part of a randomized waitlist-control trial (ClinicalTrials.gov ID: NCT02597751). Children with DCD (N = 78) were randomized to either a treatment or waitlist group and underwent three MRIs over 6 months. The treatment group received intervention (once weekly for 10 weeks) between the first and second scan; the waitlist group received intervention between the second and third scan. Cortical grey matter volume was measured using voxel-based morphometry (VBM). Behavioral outcome measures included the Performance Quality Rating Scale (PQRS) and Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). Of the 78 children, 58 were excluded (mostly due to insufficient data quality), leaving a final N = 20 for analyses. Due to the small sample size, we combined both groups to examine treatment effects. Cortical grey matter volume differences were assessed using a repeated measures ANOVA, controlling for total intracranial volume. Regression analyses examined the relationship of grey matter volume changes to BOT-2 (motor performance) and PQRS (movement quality). Results: After CO-OP, children had significantly decreased grey matter in the right superior frontal gyrus and middle/posterior cingulate gyri. We found no significant associations of grey matter volume changes with PQRS or BOT-2 scores. Conclusion: Decreased cortical grey matter volume generally reflects greater brain maturity. Decreases in grey matter volume after CO-OP intervention were in regions associated with self-regulation and motor control, consistent with our other studies. Decreased grey matter volume may be due to focal increases in synaptic pruning, perhaps as a result of strengthening networks in the brain via the repeated learning and actions in therapy. Findings from this study add to the growing body of literature demonstrating positive neuroplastic changes in the brain after CO-OP intervention.

Cerebrovascular Reactivity Following Spinal Cord Injury.

Background: Spinal cord injuries (SCI) often result in cardiovascular issues, increasing the risk of stroke and cognitive deficits. Objectives: This study assessed cerebrovascular reactivity (CVR) using functional magnetic resonance imaging (fMRI) during a hypercapnic challenge in SCI participants compared to noninjured controls. Methods: Fourteen participants were analyzed (n = 8 with SCI [unless otherwise noted], median age = 44 years; n = 6 controls, median age = 33 years). CVR was calculated through fMRI signal changes. Results: The results showed a longer CVR component (tau) in the grey matter of SCI participants (n = 7) compared to controls (median difference = 3.0 s; p < .05). Time since injury (TSI) correlated negatively with steady-state CVR in the grey matter and brainstem of SCI participants (RS = -0.81, p = .014; RS = -0.84, p = .009, respectively). Lower steady-state CVR in the brainstem of the SCI group (n = 7) correlated with lower diastolic blood pressure (RS = 0.76, p = .046). Higher frequency of hypotensive episodes (n = 7) was linked to lower CVR outcomes in the grey matter (RS = -0.86, p = .014) and brainstem (RS = -0.89, p = .007). Conclusion: Preliminary findings suggest a difference in the dynamic CVR component, tau, between the SCI and noninjured control groups, potentially explaining the higher cerebrovascular health burden in SCI individuals. Exploratory associations indicate that longer TSI, lower diastolic blood pressure, and more hypotensive episodes may lead to poorer CVR outcomes. However, further research is necessary to establish causality and support these observations.

Comparative utility of omnipolar and bipolar electroanatomic mapping methods to detect and localize dual nodal substrate in patients with atrioventricular nodal reentrant tachycardia.

BACKGROUND: Catheter-based slow pathway modification (SPM) for atrioventricular nodal reentrant tachycardia (AVNRT) is traditionally performed at empiric sites using anatomical landmarks and test ablation feedback within the triangle of Koch (TK). While studies have described more tailored techniques such as bipolar low voltage bridge (LVB) and wavefront collision identification, few have systematically compared the diagnostic yields of each and none have investigated whether omnipolar mapping technology provides incremental benefit. The objective of this study was to compare the utility of omnipolar and bipolar-derived qualitative and quantitative measurements in identifying and localizing dual AVN substrate in patients with versus without AVNRT. METHODS: A retrospective case-control study of consecutive patients with paroxysmal supraventricular tachycardia undergoing electrophysiology study with both omnipolar and bipolar mapping from 2022-2023. RESULTS: Thirteen AVNRT cases (median age 16.1 years, 512 TK points) were compared to nine non-AVNRT controls (median age 15.7 years, 332 TK points). Among qualitative variables, an omnipolar activation vector pivot, defined as a ≥45 degree change in activation direction within the TK, had the highest positive (81%) and negative predictive values (100%) for identifying AVNRT cases and had a median distance of 1 mm from SPM sites. Among quantitative variables, the optimal discriminatory performance for successful SPM sites was observed using bipolar voltage restricted to a peak frequency >340 Hz (c statistic 0.75). CONCLUSIONS: Omnipolar vector pivot analysis represents an automated, annotation-independent qualitative technique that is sensitive and specific for AVNRT substrate and co-localizes with successful SPM sites. Bipolar voltage quantitatively describes SP anisotropy better than omnipolar voltage, and the addition of peak frequency signal analysis further optimizes the selection of SPM sites.

Limited Relationship Between Echocardiographic Measures and Electrocardiographic Markers of Left Ventricular Size in Healthy Children.

Pediatric ECG standards have been defined without echocardiographic confirmation of normal anatomy. The Pediatric Heart Network Normal Echocardiogram Z-score Project provides a racially diverse group of healthy children with normal echocardiograms. We hypothesized that ECG and echocardiographic measures of left ventricular (LV) dimensions are sufficiently correlated in healthy children to imply a clinically meaningful relationship. This was a secondary analysis of a previously described cohort including 2170 digital ECGs. The relationship between 6 ECG measures associated with LV size were analyzed with LV Mass (LVMass-z) and left ventricular end-diastolic volume (LVEDV-z) along with 11 additional parameters. Pearson or Spearman correlations were calculated for the 78 ECG-echocardiographic pairs with regression analyses assessing the variance in ECG measures explained by variation in LV dimensions and demographic variables. ECG/echocardiographic measurement correlations were significant and concordant in 41/78 (53%), though many were significant and discordant (13/78). Of the 6 ECG parameters, 5 correlated in the clinically predicted direction for LV Mass-z and LVEDV-z. Even when statistically significant, correlations were weak (0.05-0.24). R2 was higher for demographic variables than for echocardiographic measures or body surface area in all pairs, but remained weak (R2 ≤ 0.17). In a large cohort of healthy children, there was a positive association between echocardiographic measures of LV size and ECG measures of LVH. These correlations were weak and dependent on factors other than echocardiographic or patient derived variables. Thus, our data support deemphasizing the use of solitary, traditional measurement-based ECG markers traditionally thought to be characteristic of LVH as standalone indications for further cardiac evaluation of LVH in children and adolescents.

Pediatric ECG-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling.

BACKGROUND: Artificial intelligence-enhanced ECG analysis shows promise to detect ventricular dysfunction and remodeling in adult populations. However, its application to pediatric populations remains underexplored. METHODS: A convolutional neural network was trained on paired ECG-echocardiograms (≤2 days apart) from patients ≤18 years of age without major congenital heart disease to detect human expert-classified greater than mild left ventricular (LV) dysfunction, hypertrophy, and dilation (individually and as a composite outcome). Model performance was evaluated on single ECG-echocardiogram pairs per patient at Boston Children's Hospital and externally at Mount Sinai Hospital using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC). RESULTS: The training cohort comprised 92 377 ECG-echocardiogram pairs (46 261 patients; median age, 8.2 years). Test groups included internal testing (12 631 patients; median age, 8.8 years; 4.6% composite outcomes), emergency department (2830 patients; median age, 7.7 years; 10.0% composite outcomes), and external validation (5088 patients; median age, 4.3 years; 6.1% composite outcomes) cohorts. Model performance was similar on internal test and emergency department cohorts, with model predictions of LV hypertrophy outperforming the pediatric cardiologist expert benchmark. Adding age and sex to the model added no benefit to model performance. When using quantitative outcome cutoffs, model performance was similar between internal testing (composite outcome: AUROC, 0.88, AUPRC, 0.43; LV dysfunction: AUROC, 0.92, AUPRC, 0.23; LV hypertrophy: AUROC, 0.88, AUPRC, 0.28; LV dilation: AUROC, 0.91, AUPRC, 0.47) and external validation (composite outcome: AUROC, 0.86, AUPRC, 0.39; LV dysfunction: AUROC, 0.94, AUPRC, 0.32; LV hypertrophy: AUROC, 0.84, AUPRC, 0.25; LV dilation: AUROC, 0.87, AUPRC, 0.33), with composite outcome negative predictive values of 99.0% and 99.2%, respectively. Saliency mapping highlighted ECG components that influenced model predictions (precordial QRS complexes for all outcomes; T waves for LV dysfunction). High-risk ECG features include lateral T-wave inversion (LV dysfunction), deep S waves in V1 and V2 and tall R waves in V6 (LV hypertrophy), and tall R waves in V4 through V6 (LV dilation). CONCLUSIONS: This externally validated algorithm shows promise to inexpensively screen for LV dysfunction and remodeling in children, which may facilitate improved access to care by democratizing the expertise of pediatric cardiologists.

Aortic arch shape after arch repair predicts exercise capacity: a multicentre analysis.

Aims: Coarctation of the aorta is associated with long-term morbidity including decreased exercise capacity, despite successful repair. In the absence of discrete recoarctation, the haemodynamic mechanism remains unknown. This multicentre study evaluated the relationship between aorta shape, flow, and exercise capacity in patients after arch repair, specifically through the lens of aortic size mismatch and descending aortic (DAo) flow and their association with exercise. Methods and results: Cardiac magnetic resonance, cardiopulmonary exercise test, and echocardiogram data within 1 year were analysed from 58 patients (age 28 ± 10 years, 48% male) across four centres with history of isolated arch repair. Aortic arch measurements were correlated with % predicted VO2max with subgroup analyses of those with residual arch obstruction, bicuspid aortic valve, and hypertension. Ascending aorta (AAo) to DAo diameter ratio (DAAo/DDAo) was negatively correlated with % predicted VO2max. %DAo flow positively correlated with VO2max. Sub-analyses demonstrated that the negative correlation of DAAo/DDAo with VO2max was maintained only in patients without arch obstruction and with a bicuspid aortic valve. Smaller aortic arch measurements were associated with both hypertension and exercise-induced hypertension. Conclusion: Aorta size mismatch, due to AAo dilation or small DAo, and associated decreased %DAo flow, correlated significantly with decreased exercise capacity after aortic arch repair. These correlations were stronger in patients without arch obstruction and with a bicuspid aortic valve. Aorta size mismatch and %DAo flow capture multiple mechanisms of altered haemodynamics beyond blood pressure gradient or discrete obstruction and can inform the definition of a successful repair.

Socioeconomic Factors Influencing Pediatric Peak Oxygen Consumption Prediction.

OBJECTIVE: To determine if socioeconomic status (SES) has a greater effect than standard demographic values on predicted peak oxygen consumption (pVO2). STUDY DESIGN: We conducted a single-institution, retrospective analysis of maximal cardiopulmonary exercise test (CPET) data from 2010 to 2020 for healthy patients age <19 years with body mass index (BMI) percentile (BMI%) between 5-95. Data were sorted by self-identified race, BMI%, and adjusted gross income (AGI); AGI served as a surrogate for SES. Mean percent predicted pVO2 (pppVO2) was compared between groups. Linear regression was used to adjust for differences. RESULTS: A total of 541 CPETs met inclusion criteria. Mean pppVO2 was 97% ± 22.6 predicted (P < .01) with 30% below criterion standard for normal (85% predicted). After excluding unknown AGI and race, 418 CPETs remained. Mean pppVO2 was lower for Blacks (n = 36) and Latinx (n = 26) compared with Whites (n = 333, P < .01). Mean pppVO2 declined as AGI decreased (P < .01). The differences in pppVO2 between racial categories remained significant when adjusted for BMI% (Black r = -7.3, P = .035; Latinx r = -15.4, P < .01). These differences both decreased in magnitude and were no longer significant when adjusted for AGI (Black r = -6.0, P = .150; Latinx r = -9.3, P = .06). CONCLUSIONS: Lower SES correlates with lower measured cardiovascular fitness and may confound data interpretation. When using normative reference ranges in clinical decision making, providers should recognize that social determinants of health may influence predicted fitness. Social inequities should be considered when assessing pediatric cardiovascular fitness.

Mejoría de la función ventricular sistólica en pacientes pediátricos y/o portadores de cardiopatías congénitas sometidos a resincronización cardíaca / Cardiac resynchronization therapy is associated with improved systolic ventricular function in pediatrics and congenital heart disease

Antecedentes: Diversas publicaciones han validado el uso terapéutico de resincronización cardíaca en adultos portadores de insuficiencia cardíaca, pero la experiencia en pacientes pediátricos y en pacientes portadores de cardiopatías congénitas es limitada. Objetivo: Determinar los resultados de resincronización cardíaca en pacientes pediátricos y/o portadores de cardiopatías congénitas.Método: Revisión retrospectiva de los antecedentes clínicos, ecocardiogramas y electrocardiogramas en 40 pacientes consecutivos con disfunción ventricular, tratados con resincronización cardíaca entre septiembre 2002 y julio 2006 en el Children's Hospital Boston.Resultados: Al momento del implante la mediana de edad fue 16,4 años (4 meses-47años). Cinco pacientes teníancorazón estructuralmente normal, 33 eran portadores de cardiopatía congénita y 2 tenían diagnóstico de miocardiopatía. Dieciocho pacientes (45 por ciento) tenían marcapaso definitivo. La mediana de seguimiento fue 1,7 años (2 meses-4 años). Cinco pacientes no usan su sistema de estimulación biventricular. La función ventricular mejoró en 30/35 pacientes (85,7 por ciento). La fracción de eyección aumentó de 31,4 a 41,5 por ciento, principalmente como consecuencia de disminución del volumen ventricular izquierdo de fin de sístole, con mínima disminución del volumen ventricular izquierdo de fin de diástole. Cinco pacientes no respondieron y no se identificaron factores predictores de los no respondedores. Análisis por intención de tratar reflejamejoría en 30/40 pacientes (75 por ciento). Conclusión: La resincronización cardíaca produce mejoría de la función ventricular en un porcentaje significativo de unapoblación seleccionada de pacientes pediátricos y/o portadores de cardiopatías congénitas, predominantemente asociada con disminución del volumen ventricular izquierdo de fin de sístole. Estos hallazgos pueden tener importante relevancia en el tratamiento a largo plazo de este grupo de pacientes.