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.

Prevalence of adverse events in pronated intubated adult COVID-19 patients: A systematic review with meta-analysis.

AIM: To present the pooled estimated prevalence of adverse events in pronated intubated adult COVID-19 patients. DESIGN: A systematic review and meta-analysis. DATA SOURCES: This study used the Cochrane Library, CINAHL, Embase, LILACS, Livivo, PubMed, Scopus, and Web of Science databases as data sources. METHODS: The studies were meta-analysed using JAMOVI 1.6.15 software. A random-effects model was used to identify the global prevalence of adverse events, confidence intervals and the heterogeneity data. Risk of bias was assessed using the Joanna Briggs Institute tool, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of the 7904 studies identified, 169 were included for full reading, and 10 were included in the review. The most prevalent adverse events were pressure injuries (59%), haemodynamic instability (23%), death (17%) and device loss or traction (9%). CONCLUSION: The most prevalent adverse events in mechanically ventilated pronated patients with COVID-19 are pressure injuries, presence of haemodynamic instability, death and device loss or traction. IMPLICATIONS FOR THE PATIENT CARE: The evidence identified in this review can help improve the quality and safety of patient care by helping to design care protocols to avoid the development of adverse events that can cause permanent sequelae in these patients. IMPACT: This systematic review addressed the adverse events related to prone position in intubated adult COVID-19 patients. We identified that the most prevalent adverse events in these patients were pressure injuries, haemodynamic instability, device loss or traction and death. The results of this review may influence the clinical practice of nurses who work in intensive care units and, consequently, the nursing care provided not only to COVID-19 patients but for all intubated patients due to other reasons in intensive care units. REPORTING METHOD: This systematic review adhered to the PRISMA reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: As this is a systematic review, we analysed data from primary studies conducted by many researchers. Thus, there was no patient or public contribution in this review.

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.

Racial and Socioeconomic Equity of Tecovirimat Treatment during the 2022 Mpox Emergency, New York, New York, USA.

We assessed tecovirimat treatment equity for 3,740 mpox patients in New York, New York, USA, during the 2022 mpox emergency; 32.4% received tecovirimat. Treatment rates by race/ethnicity were 38.8% (White), 31.3% (Black/African American), 31.0% (Hispanic/Latino), and 30.1% (Asian/Pacific Islander/other). Future public health emergency responses must prioritize institutional and structural racism mitigation.

Medical cardioversion of atrial fibrillation and flutter with class IC antiarrhythmic drugs in young patients with and without congenital heart disease.

INTRODUCTION: The use of flecainide and propafenone for medical cardioversion of atrial fibrillation (AF) and atrial flutter/intra-atrial reentrant tachycardia (IART) is well-described in adults without congenital heart disease (CHD). Data are sparse regarding their use for the same purpose in adults with CHD and in adolescent patients with anatomically normal hearts and we sought to describe the use of class IC drugs in this population and identify factors associated with decreased likelihood of success. METHODS: Single center retrospective cohort study of patients who received oral flecainide or propafenone for medical cardioversion of AF or IART from 2000 to 2022. The unit of analysis was each episode of AF/IART. We performed a time-to-sinus rhythm analysis using a Cox proportional hazards model clustering on the patient to identify factors associated with increased likelihood of success. RESULTS: We identified 45 episodes involving 41 patients. As only episodes of AF were successfully cardioverted with medical therapy, episodes of IART were excluded from our analyses. Use of flecainide was the only factor associated with increased likelihood of success. There was a statistically insignificant trend toward decreased likelihood of success in patients with CHD. CONCLUSIONS: Flecainide was more effective than propafenone. We did not detect a difference in rate of conversion to sinus rhythm between patients with and without CHD and were likely underpowered to do so, however, there was a trend toward decreased likelihood of success in patients with CHD. That said, medical therapy was effective in >50% of patients with CHD with AF.

Foveal Hypoplasia in CRB1-Related Retinopathies.

The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47-0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (p = 0.014). BCVA continued to worsen over time in both groups (p < 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.

Retroflexed catheter course reduces the risk of right free wall accessory pathway recurrence.

INTRODUCTION: Accessory atrioventricular pathways (APs) may mediate atrioventricular reciprocating tachycardia and, in some cases, have the potential to conduct atrial tachycardia rapidly, which can be life threatening. While catheter ablation can be curative, ablation of right free wall APs is associated with a high rate of recurrence, likely secondary to reduced catheter stability along the right free wall atrioventricular groove. We sought to identify characteristics associated with a lower rate of recurrence and hypothesized ablation lesions placed on the ventricular side of the atrioventricular groove using a retroflexed catheter approach would decrease rates of recurrence. METHODS AND RESULTS: Retrospective chart review of patients who underwent catheter ablation of a right free wall AP from January 1, 2008 through June 1, 2021 with >2 months follow up. Cox proportional hazards regression was used to identify relationships between predictor variables and AP recurrence. We identified 95 patients who underwent ablation of 98 right free wall APs. Median age was 13.1 years and median weight at ablation was 52.3 kg. Overall, 23/98 (23%) APs recurred. Use of a retroflexed catheter course approaching the atrioventricular groove from the ventricular aspect was associated with reduced risk of AP recurrence with (univariable hazard ratio of 0.10 [95% confidence interval: 0.01-0.78]), which remained significant in multiple two variable Cox proportional hazards models. CONCLUSION: Use of a retroflexed catheter course is associated with a reduced likelihood of AP recurrence. This approach results in improved catheter stability and should be considered for ablation of right free wall APs.

Near-term pathways for decarbonizing global concrete production.

Growing urban populations and deteriorating infrastructure are driving unprecedented demands for concrete, a material for which there is no alternative that can meet its functional capacity. The production of concrete, more particularly the hydraulic cement that glues the material together, is one of the world's largest sources of greenhouse gas (GHG) emissions. While this is a well-studied source of emissions, the consequences of efficient structural design decisions on mitigating these emissions are not yet well known. Here, we show that a combination of manufacturing and engineering decisions have the potential to reduce over 76% of the GHG emissions from cement and concrete production, equivalent to 3.6 Gt CO2-eq lower emissions in 2100. The studied methods similarly result in more efficient utilization of resources by lowering cement demand by up to 65%, leading to an expected reduction in all other environmental burdens. These findings show that the flexibility within current concrete design approaches can contribute to climate mitigation without requiring heavy capital investment in alternative manufacturing methods or alternative materials.

Sotatercept analog improves cardiopulmonary remodeling and pulmonary hypertension in experimental left heart failure.

Pulmonary hypertension due to left heart disease (PH-LHD) is the most frequent manifestation of PH but lacks any approved treatment. Activin receptor type IIA-Fc fusion protein (ActRIIA-Fc) was found previously to be efficacious in experimental and human pulmonary arterial hypertension (PAH). Here we tested the hypothesis that ActRIIA-Fc improves pulmonary vascular remodeling and alleviates PH in models of PH-LHD, specifically in subtypes of heart failure with reduced ejection fraction (PH-HFrEF) and preserved ejection fraction (PH-HFpEF). Treatment with murine ActRIIA-Fc reduced cardiac remodeling and improved cardiac function in two mouse models of left heart disease without PH, confirming that this inhibitor of activin-class ligand signaling can exert cardioprotective effects in heart failure. In a mouse model of PH-HFrEF with prolonged pressure overload caused by transverse aortic constriction, ActRIIA-Fc treatment significantly reduced pulmonary vascular remodeling, pulmonary fibrosis, and pulmonary hypertension while exerting beneficial structural, functional, and histological effects on both the left and right heart. Additionally, in an obese ZSF1-SU5416 rat model of PH-HFpEF with metabolic dysregulation, therapeutic treatment with ActRIIA-Fc normalized SMAD3 overactivation in pulmonary vascular and perivascular cells, reversed pathologic pulmonary vascular and cardiac remodeling, improved pulmonary and cardiac fibrosis, alleviated PH, and produced marked functional improvements in both cardiac ventricles. Studies in vitro revealed that treatment with ActRIIA-Fc prevents an abnormal, glucose-induced, activin-mediated, migratory phenotype in human pulmonary artery smooth muscle cells, providing a mechanism by which ActRIIA-Fc could exert therapeutic effects in experimental PH-HFpEF with metabolic dysregulation. Our results demonstrate that ActRIIA-Fc broadly corrects cardiopulmonary structure and function in experimental PH-LHD, including models of PH-HFrEF and PH-HFpEF, leading to alleviation of PH under diverse pathophysiological conditions. These findings highlight the important pathogenic contributions of activin-class ligands in multiple forms of experimental PH and support ongoing clinical evaluation of human ActRIIA-Fc (sotatercept) in patients with PH-HFpEF.

Ventricular arrhythmias after fibroma resection: Are patients still at risk?

BACKGROUND: Ventricular fibromas frequently present with life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) in children. The long-term risk of sustained ventricular arrhythmias after surgical resection is unknown. OBJECTIVES: The aims of this study were to quantify the VT/VF risk after surgical resection and to examine the results of early (during index surgical hospitalization) and late (≥3 months after surgery) postoperative ventricular stimulation (V-stim) studies. METHODS: We performed a retrospective cohort study of all patients with ventricular fibromas who underwent surgical resection at our institution (2000-2020). The primary outcome was defined as recurrent VT/VF ≥3 months after index surgical resection. RESULTS: Forty-six patients with a median age at surgery of 2 years (range 0.3-18.9 years) formed our study cohort. Indications for surgery included cardiac arrest in 11 (24%), sustained VT in 16 (35%), premature ventricular contractions/nonsustained VT in 10 (22%), and hemodynamic abnormalities in 9 (20%). Of the 11 patients who presented with cardiac arrest, 4 underwent pre-resection implantable cardioverter-defibrillator (ICD) implantation, all of which were explanted at the time of surgery. An early postoperative V-stim study was performed in 26 (57%) patients, and all were negative for inducible VT/VF. Of the 13 late postoperative V-stim studies, 3 were positive: 2 underwent ICD implantation and 1 was initiated on amiodarone and underwent loop recorder implantation. At the time of last follow-up (median 1.5 years; range 0.3-16.5 years), 45 (98%) were free of clinical VT/VF and no patient with an ICD has received an appropriate shock. CONCLUSION: Surgical resection of ventricular fibromas significantly reduces the risk of life-threatening arrhythmias in children; however, a small number of patients remain vulnerable.

FORCE Risk Stratification Tool for Pediatric Cardiac Rehabilitation and Fitness Programs.

Risk stratification is required to set an exercise prescription for cardiac rehabilitation, but an optimal scheme for congenital heart disease (CHD) is unknown. We piloted a system based on hemodynamic rather than anatomic factors: function, oxygen level, rhythm, complex/coronary anatomy, and elevated load (FORCE). Feasibility, efficacy, and safety of the FORCE tool were evaluated. Patients < 22 years old participating in the Cardiac Fitness Program at Boston Children's Hospital between 02/2017 and 12/2021 were retrospectively analyzed. Assigned FORCE levels, anatomy, adverse events, fitness and exercise test data were collected. Of 63 attempts at FORCE classification, 62 (98%) were successfully classified while one with restrictive cardiomyopathy was not. Thirty-nine (62%) were FORCE 1, 16 (25%) were FORCE 2, and seven (11%) were FORCE 3. Almost half of FORCE 1 patients had simple or complex CHD and the majority of FORCE 2 patients had single ventricle CHD. FORCE 3 patients were more likely to have serious arrhythmias or cardiomyopathy than those in FORCE 1 or 2 (p < 0.001). Postural orthostatic tachycardia syndrome patients appeared in FORCE 1 only. No adverse events occurred over 958 total sessions. The total number of fitness sessions/participant was similar across FORCE levels. It was feasible to risk stratify patients with CHD using a clinical FORCE tool. The tool was effective in categorizing patients and simple to use. No adverse events occurred with fitness training over nearly 1000 exercise training sessions. Adding diastolic dysfunction to the original model may add utility.

Radiofrequency Catheter Ablation for Pediatric Atrioventricular Nodal Reentrant Tachycardia: Impact of Age on Procedural Methods and Durable Success.

Background Catheter-based slow-pathway modification (SPM) is the treatment of choice for symptomatic atrioventricular nodal reentrant tachycardia (AVNRT). We sought to investigate the interactions between patient age and procedural outcomes in pediatric patients undergoing catheter-based SPM for AVNRT. Methods and Results A retrospective cohort study was performed, including consecutive patients undergoing acutely successful SPM for AVNRT from 2008 to 2017. Those with congenital heart disease, cardiomyopathy, and accessory pathways were excluded. Patients were stratified by age quartile at time of SPM. The primary outcome was AVNRT recurrence. A total of 512 patients underwent successful SPM for AVNRT. Age quartile 1 had 129 patients with a median age and weight of 8.9 years and 30.6 kg, respectively. Radiofrequency energy was used in 98% of cases. Follow-up was available in 447 (87%) patients with a median duration of 0.8 years (interquartile range, 0.2-2.5 years). AVNRT recurred in 22 patients. Multivariable Cox proportional hazard modeling identified atypical AVNRT (hazard ratio [HR], 5.83; 95% CI, 2.01-16.96; P=0.001), dual atrioventricular nodal only (HR, 4.09; 95% CI, 1.39-12.02; P=0.011), total radiofrequency lesions (HR, 1.06 per lesion; 95% CI, 1.01-1.12; P=0.032), and the use of a long sheath (HR, 3.52; 95% CI, 1.23-10.03; P=0.010) as predictors of AVNRT recurrence; quartile 1 patients were not at higher risk of recurrence (HR, 0.45; 95% CI, 0.10-1.97; P=0.29). Complete heart block requiring permanent pacing occurred in one quartile 2 patient at 14.9 years of age. Conclusions Pediatric AVNRT can be treated with radiofrequency-SPM with high procedural efficacy and minimal risk of complications, including heart block. Atypical AVNRT and dual atrioventricular nodal physiology without inducible tachycardia remain challenging substrates.

Sotatercept analog suppresses inflammation to reverse experimental pulmonary arterial hypertension.

Sotatercept is an activin receptor type IIA-Fc (ActRIIA-Fc) fusion protein that improves cardiopulmonary function in patients with pulmonary arterial hypertension (PAH) by selectively trapping activins and growth differentiation factors. However, the cellular and molecular mechanisms of ActRIIA-Fc action are incompletely understood. Here, we determined through genome-wide expression profiling that inflammatory and immune responses are prominently upregulated in the lungs of a Sugen-hypoxia rat model of severe angio-obliterative PAH, concordant with profiles observed in PAH patients. Therapeutic treatment with ActRIIA-Fc-but not with a vasodilator-strikingly reversed proinflammatory and proliferative gene expression profiles and normalized macrophage infiltration in diseased rodent lungs. Furthermore, ActRIIA-Fc normalized pulmonary macrophage infiltration and corrected cardiopulmonary structure and function in Bmpr2 haploinsufficient mice subjected to hypoxia, a model of heritable PAH. Three high-affinity ligands of ActRIIA-Fc each induced macrophage activation in vitro, and their combined immunoneutralization in PAH rats produced cardiopulmonary benefits comparable to those elicited by ActRIIA-Fc. Our results in complementary experimental and genetic models of PAH reveal therapeutic anti-inflammatory activities of ActRIIA-Fc that, together with its known anti-proliferative effects on vascular cell types, could underlie clinical activity of sotatercept as either monotherapy or add-on to current PAH therapies.