Multimodal Assessment and Intramodal Comparison of Imaging Techniques for Pediatric Pulmonary Vein Stenosis with Pulmonary Hypertension.

Pulmonary vein stenosis (PVS) is a rare, serious, and progressive disease in the pediatric population. Evaluation is complex and involves multimodality imaging. Diagnosis is important as early treatment to prevent progressive pulmonary hypertension and right ventricular dysfunction is essential. Adult studies have shown good correlation between various imaging modalities; however, there are limited data in children. This is a single-center retrospective pilot study to determine the reliability of measurement of pulmonary vein stenosis and pulmonary hypertension across different imaging modalities-computed tomography angiography (CTA), echocardiography (echo), lung perfusion scan (LPS), and cardiac catheterization (cath). PVS was defined as > 2 mmHg by echo and cath and/or 50% reduction in diameter by CTA. Patients had to have an echo, CTA and cath performed within a 1-month timeframe of one another to be included in the study, with LPS data included if testing was completed at initial evaluation. Fifteen total patients were enrolled; 87% were categorized as primary PVS; a condition not directly related to direct injury or prior surgical intervention. Twenty-seven total stenotic pulmonary veins were identified (mean 1.8, range 1-4). CTA had a slightly better agreement with cath than echo in identifying PVS in different vein locations except in the LLPV. Additionally, echo and CTA had excellent sensitivity (91%) and specificity (100%) compared to cath for diagnosis of PH. We conclude that non-invasive imaging of echo and CTA has an acceptable correlation to cardiac catheterization for screening and initial evaluation of PVS and PH, as directly related to PVS, in pediatrics.

Actigraphy methodology in the Kids Mod PAH trial: Physical activity as a functional endpoint in pediatric clinical trials.

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants' physical activity with a research-grade, wrist-worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity - a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

Kids Mod PAH trial: A multicenter trial comparing mono- versus duo-therapy for initial treatment of pediatric pulmonary hypertension.

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network.

The Use of Virtual Reality Learning on Transition Education in Adolescents with Congenital Heart Disease.

Improvement in congenital heart disease (CHD) outcomes has created a growing population of adolescents and young adults with unique health needs that require thoughtful transition planning and eventual transfer of care to an adult provider. Often, poor health literacy and limited resources can lead to interrupted care, which places them at risk for adverse health-related consequences. In 2019, the Wisconsin Adult Congenital Heart Disease transition program partnered with Stanford Virtual Heart (SVH), a virtual reality (VR) platform, to allow young adult patients to learn about their CHD in a clinic-based setting. We completed a single-center pilot study to evaluate these patients' experience and perceptions to using VR during their transition education. At an initial transition visit, we used an immediate post-VR experience survey, scored using Likert scales of 1-5 (1 = strongly disagree, 5 = strongly agree). Twenty-two patients (13 males) between the ages of 16 and 19 participated. Lesions included pulmonary stenosis, Tetralogy of Fallot, atrial and ventricular septal defect, coarctation, aortic stenosis, hypoplastic left heart syndrome, and patent ductus arteriosus. Likert averages were 4.7 for finding VR helped with understanding their heart lesion, 4.6 for finding VR helped with understanding their heart surgery, 4.7 for enjoying the VR heart simulation, and 4.6 for finding that it was a good use of time. This study demonstrates that adolescents enjoyed using SVH and found it helpful. Clinical implementation shows promise as a plausible adjunct tool for transition education.

Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience.

Introduction: Phosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH). Methods and materials: This is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation. Results: Over the study period, 154 children with a median age of 1.0 (range 0.0-6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients. Conclusion: Tadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.

Examination of Adverse Reactions After COVID-19 Vaccination Among Patients With a History of Multisystem Inflammatory Syndrome in Children.

Importance: Data are limited regarding adverse reactions after COVID-19 vaccination in patients with a history of multisystem inflammatory syndrome in children (MIS-C). The lack of vaccine safety data in this unique population may cause hesitancy and concern for many families and health care professionals. Objective: To describe adverse reactions following COVID-19 vaccination in patients with a history of MIS-C. Design, Setting, and Participants: In this multicenter cross-sectional study including 22 North American centers participating in a National Heart, Lung, and Blood Institute, National Institutes of Health-sponsored study, Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MUSIC), patients with a prior diagnosis of MIS-C who were eligible for COVID-19 vaccination (age ≥5 years; ≥90 days after MIS-C diagnosis) were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions. Exposures: COVID-19 vaccination after MIS-C diagnosis. Main Outcomes and Measures: The main outcome was adverse reactions following COVID-19 vaccination. Comparisons were made using the Wilcoxon rank sum test for continuous variables and the χ2 or Fisher exact test for categorical variables. Results: Of 385 vaccine-eligible patients who were surveyed, 185 (48.1%) received at least 1 vaccine dose; 136 of the vaccinated patients (73.5%) were male, and the median age was 12.2 years (IQR, 9.5-14.7 years). Among vaccinated patients, 1 (0.5%) identified as American Indian/Alaska Native, non-Hispanic; 9 (4.9%) as Asian, non-Hispanic; 45 (24.3%) as Black, non-Hispanic; 59 (31.9%) as Hispanic or Latino; 53 (28.6%) as White, non-Hispanic; 2 (1.1%) as multiracial, non-Hispanic; and 2 (1.1%) as other, non-Hispanic; 14 (7.6%) had unknown or undeclared race and ethnicity. The median time from MIS-C diagnosis to first vaccine dose was 9.0 months (IQR, 5.1-11.9 months); 31 patients (16.8%) received 1 dose, 142 (76.8%) received 2 doses, and 12 (6.5%) received 3 doses. Almost all patients received the BNT162b2 vaccine (347 of 351 vaccine doses [98.9%]). Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness (62 patients [33.5%]) and/or fatigue (32 [17.3%]). In 32 patients (17.3%), adverse reactions were treated with medications, most commonly acetaminophen (21 patients [11.4%]) or ibuprofen (11 [5.9%]). Four patients (2.2%) sought medical evaluation, but none required testing or hospitalization. There were no patients with any serious adverse events, including myocarditis or recurrence of MIS-C. Conclusions and Relevance: In this cross-sectional study of patients with a history of MIS-C, no serious adverse events were reported after COVID-19 vaccination. These findings suggest that the safety profile of COVID-19 vaccination administered at least 90 days following MIS-C diagnosis appears to be similar to that in the general population.

A multimedia paediatric cardiology assessment tool for medical students and general paediatric trainees: development and validation.

BACKGROUND: Understanding how cardiovascular structure and physiology guide management is critically important in paediatric cardiology. However, few validated educational tools are available to assess trainee knowledge. To address this deficit, paediatric cardiologists and fellows from four institutions collaborated to develop a multimedia assessment tool for use with medical students and paediatric residents. This tool was developed in support of a novel 3-dimensional virtual reality curriculum created by our group. METHODS: Educational domains were identified, and questions were iteratively developed by a group of clinicians from multiple centres to assess understanding of key concepts. To evaluate content validity, content experts completed the assessment and reviewed items, rating item relevance to educational domains using a 4-point Likert scale. An item-level content validity index was calculated for each question, and a scale-level content validity index was calculated for the assessment tool, with scores of ≥0.78 and ≥0.90, respectively, representing excellent content validity. RESULTS: The mean content expert assessment score was 92% (range 88-97%). Two questions yielded ≤50% correct content expert answers. The item-level content validity index for 29 out of 32 questions was ≥0.78, and the scale-level content validity index was 0.92. Qualitative feedback included suggestions for future improvement. Questions with ≤50% content expert agreement and item-level content validity index scores <0.78 were removed, yielding a 27-question assessment tool. CONCLUSIONS: We describe a multi-centre effort to create and validate a multimedia assessment tool which may be implemented within paediatric trainee cardiology curricula. Future efforts may focus on content refinement and expansion to include additional educational domains.

Virtual reality curriculum increases paediatric residents' knowledge of CHDs.

OBJECTIVES: Virtual reality has emerged as a unique educational modality for medical trainees. However, incorporation of virtual reality curricula into formal training programmes has been limited. We describe a multi-centre effort to develop, implement, and evaluate the efficacy of a virtual reality curriculum for residents participating in paediatric cardiology rotations. METHODS: A virtual reality software program ("The Stanford Virtual Heart") was utilised. Users are placed "inside the heart" and explore non-traditional views of cardiac anatomy. Modules for six common congenital heart lesions were developed, including narrative scripts. A prospective case-control study was performed involving three large paediatric residency programmes. From July 2018 to June 2019, trainees participating in an outpatient cardiology rotation completed a 27-question, validated assessment tool. From July 2019 to February 2020, trainees completed the virtual reality curriculum and assessment tool during their cardiology rotation. Qualitative feedback on the virtual reality experience was also gathered. Intervention and control group performances were compared using univariate analyses. RESULTS: There were 80 trainees in the control group and 52 in the intervention group. Trainees in the intervention group achieved higher scores on the assessment (20.4 ± 2.9 versus 18.8 ± 3.8 out of 27 questions answered correctly, p = 0.01). Further analysis showed significant improvement in the intervention group for questions specifically testing visuospatial concepts. In total, 100% of users recommended integration of the programme into the residency curriculum. CONCLUSIONS: Virtual reality is an effective and well-received adjunct to clinical curricula for residents participating in paediatric cardiology rotations. Our results support continued virtual reality use and expansion to include other trainees.

Assessing growth of infants with chylothorax receiving fortified skimmed human breast milk.

LEARNING OUTCOME: To learn how skimmed human milk (SHM) can be used in infants with chylothorax to support adequate weight gain and nutrition while receiving human milk. BACKGROUND: Traditional nutrition management for chylothorax is to limit long-chain triglycerides (LCTs) and provide a diet high in medium-chain triglycerides (MCTs). Transition from human milk to formula has been required to provide the ratio of MCT to LCT required to stop the accumulation of chyle. Although SHM may provide the right fat content for a baby with chylothorax, previous studies have shown slow growth in infants receiving SHM. OBJECTIVE: To demonstrate that infants receiving SHM fortified with high-MCT infant formula will have age appropriate growth without re-accumulation of chyle. DESIGN/METHODS: Between 2017 and 2019, term infants with the diagnosis of chylothorax who were previously receiving human milk and transitioned to fortified SHM were monitored for growth and reaccumulation of chyle. RESULTS: The six infants who were prescribed fortified SHM with high-MCT infant formula using standardized recipes did not show reaccumulation of chyle and showed positive weight gain in five of the six study patients. The infants gained a mean weight of 30.5 g/day (±19.5), and their weight z scores improved by a mean of +0.29 (±0.33). CONCLUSIONS: Fortified SHM is a safe treatment option that can provide adequate nutrition for the infant with chylothorax to gain weight appropriately for age.

Clinical Variables Associated with Pre-Fontan Aortopulmonary Collateral Burden.

Aortopulmonary collaterals (APCs) develop universally, but to varying degrees, in patients with single ventricle congenital heart disease (CHD). Despite their ubiquitous presence, APCs remain poorly understood. We sought to evaluate the association between APC burden and common non-invasive clinical variables. We conducted a single center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent pre-Fontan cardiac magnetic resonance (CMR) imaging from 3/2018 to 3/2021. CMR was used to quantify APC flow, which was normalized to aortic (APC/QAo) and pulmonary vein (APC/QPV) blood flow. Univariate, multivariable, and classification and regression tree (CART) analyses were done to investigate the potential relationship between CMR-quantified APC burden and clinical variables. A total of 29 patients were included, all of whom had increased APC flow (APC/QAo: 26.9, [22.0, 39.1]%; APC/QPV: 39.4 [33.3, 46.9]%), but to varying degrees (APC/QAo: range 11.9-44.4%; APC/QPV: range 17.7-60.0%). Pulmonary artery size (Nakata index, at pre-Fontan CMR) was the only variable associated with APC flow on multivariable analysis (APC/QAo: p = 0.020, R2 = 0.19; APC/QPV: p = 0.0006, R2 = 0.36) and was the most important variable associated with APC burden identified by CART analysis (size inversely related to APC flow). APC flow is universally increased but highly variable in patients with single ventricle CHD and Glenn circulation. Small branch pulmonary artery size is a key factor associated with increased APC burden; however, the pathogenesis of APCs is likely multifactorial. Further research is needed to better understand APC pathogenesis, including predisposing and mitigating factors.

Impact of Reintervention During Stage 1 Palliation Hospitalization: A National, Multicenter Study.

BACKGROUND: Stage 1 palliation (S1P) for hypoplastic left heart syndrome remains associated with high morbidity and mortality. Previous studies on burden of reinterventions did not include patients who remain hospitalized before stage 2 palliation (S2P). This study described the rate of reintervention during S1P hospitalization and sought to determine the impact of reintervention on outcomes. METHODS: All participants enrolled in phase II of the National Pediatric Cardiology Quality Improvement Collaborative after S1P were included in this study. The primary outcome was the rate of reintervention during hospitalization after S1P and before hospital discharge or S2P. Reintervention was defined as 1 or more unplanned interventional cardiac catheterizations or surgical reoperations. RESULTS: Between March 1, 2016 and October 1, 2019, 1367 participants underwent S1P and 339 (24.8%) had a reintervention; most commonly to address the source of pulmonary blood flow. Gestational age, weight at S1P, atrioventricular septal defect, heterotaxy, preoperative pulmonary artery bands, hybrid S1P, and an additional bypass run or early extracorporeal membrane oxygenation were significantly associated with reintervention. Participants in the reintervention group experienced higher rates of nearly all postoperative complications, were less likely to be discharged before S2P (57.1% vs 86%; P < .001), and more likely to experience in-hospital mortality (17% vs 5%; P < .001). CONCLUSIONS: Unplanned reintervention during hospitalization after S1P palliation occurred in 25% of participants in a large, registry-based national cohort. Participants who underwent reintervention were more likely to remain as inpatient and were less likely to survive to S2P. Reintervention was associated with a multitude of postoperative complications that affect survival and long-term outcome.

Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry.

OBJECTIVE: To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry. STUDY DESIGN: We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome. RESULTS: Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension. CONCLUSIONS: Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.

Intranasal dexmedetomidine for transthoracic echocardiography in infants with shunt-dependent single ventricle heart disease.

OBJECTIVES: We investigated the efficacy and complication profile of intranasal dexmedetomidine for transthoracic echocardiography sedation in patients with single ventricle physiology and shunt-dependent pulmonary blood flow during the high-risk interstage period. METHODS: A single-centre, retrospective review identified interstage infants who received dexmedetomidine for echocardiography sedation. Baseline and procedural vitals were reported. Significant adverse events related to sedation were defined as an escalation in care or need for any additional/increased inotropic support to maintain pre-procedural haemodynamics. Minor adverse events were defined as changes from baseline haemodynamics that resolved without intervention. To assess whether sedation was adequate, echocardiogram reports were reviewed for completeness. RESULTS: From September to December 2020, five interstage patients (age 29-69 days) were sedated with 3 mcg/kg intranasal dexmedetomidine. The median sedation onset time and duration time was 24 minutes (range 12-43 minutes) and 60 minutes (range 33-60 minutes), respectively. Sedation was deemed adequate in all patients as complete echocardiograms were accomplished without a rescue dose. When compared to baseline, three (60%) patients had a >10% reduction in heart rate, one (20%) patient had a >10% reduction in oxygen saturations, and one (20%) patient had a >30% decrease in blood pressure. Amongst all patients, no significant complications occurred and haemodynamic changes from baseline did not result in need for intervention or interruption of study. CONCLUSIONS: Intranasal dexmedetomidine may be a reasonable option for echocardiography sedation in infants with shunt-dependent single ventricle heart disease, and further investigation is warranted to ensure efficacy and safety in an outpatient setting.

Subcutaneous Treprostinil Improves Surgical Candidacy for Next Stage Palliation in Single Ventricle Patients With High-Risk Hemodynamics.

Single ventricle (SV) patients with pulmonary vascular disease (SV-PVD) are considered poor surgical candidates for Glenn or Fontan palliation. Given limited options for Stage 1 (S1) and Stage 2 (S2) SV patients with SV-PVD, we report on the use of subcutaneous treprostinil (TRE) to treat SV-PVD in this population. This single-center, retrospective cohort study examined SV patients who were not candidates for subsequent surgical palliation due to SV-PVD and were treated with TRE. The primary outcome was ability to progress to the next surgical stage; secondary outcomes included changes in hemodynamics after TRE initiation. Between 3/2014 and 8/2021, 17 SV patients received TRE for SV-PVD: 11 after S1 and 6 after S2 (median PVR 4.1 [IQR 3.2-4.8] WU*m2 and 5.0 [IQR 1.5-6.1] WU*m2, respectively). Nine of 11 (82%) S1 progressed to S2, and 2 (18%) underwent heart transplant (HTx). Three of 6 (50%) S2 progressed to Fontan, 1 underwent HTx and 2 are awaiting Fontan on TRE. TRE significantly decreased PVR in S1 patients with median post-treatment PVR of 2.0 (IQR 1.5-2.6) WU*m2. TRE can allow for further surgical palliation in select pre-Fontan patients with SV-PVD, obviating the need for HTx. Improvement in PVR was significant in S1 patients and persisted beyond discontinuation of therapy for most patients.

Abnormal platelet aggregation in pediatric pulmonary hypertension.

Endogenous prostacyclin stimulates pulmonary vasodilation and inhibits platelet aggregation. For the synthetic analog treprostinil, used in the treatment of pulmonary hypertension (PH), conflicting, anecdotal evidence exists regarding its effects on clinically relevant platelet function. This study investigated whether treprostinil therapy results in inhibition of platelet aggregation in pediatric PH patients. This is a single institution, prospective, cohort study. Pediatric patients ≤18 years of age on medical therapy for PH underwent platelet function testing by light transmission aggregometry with U-46619-a stable analog of endoperoxide prostaglandin H2, exhibiting properties similar to thromboxane A2 (TXA2). Results were compared for those on continuous treprostinil therapy (TRE) versus those on other, non-prostacyclin therapies (non-TRE). Thirty-five patients were enrolled: 18 in the TRE group and 17 in the non-TRE group. There was no difference in platelet aggregation abnormalities between the two groups: 44% (n = 8) in the TRE group and 41% (n = 7) in the non-TRE group were abnormal. Furthermore, subgroup analysis showed no difference based on treprostinil dosing. This study demonstrated similar, moderately high rates of abnormal platelet aggregation in pediatric PH patients on continuous treprostinil therapy compared to those on other, non-prostacyclin therapies. The high rate of abnormal platelet aggregation in the entire cohort, however, warrants follow-up study to identify a potential inherent risk in this population.

Significance of α-Myosin Heavy Chain (MYH6) Variants in Hypoplastic Left Heart Syndrome and Related Cardiovascular Diseases.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with complex genetic inheritance. HLHS segregates with other left ventricular outflow tract (LVOT) malformations in families, and can present as either an isolated phenotype or as a feature of a larger genetic disorder. The multifactorial etiology of HLHS makes it difficult to interpret the clinical significance of genetic variants. Specific genes have been implicated in HLHS, including rare, predicted damaging MYH6 variants that are present in >10% of HLHS patients, and which have been shown to be associated with decreased transplant-free survival in our previous studies. MYH6 (α-myosin heavy chain, α-MHC) variants have been reported in HLHS and numerous other CHDs, including LVOT malformations, and may provide a genetic link to these disorders. In this paper, we outline the MYH6 variants that have been identified, discuss how bioinformatic and functional studies can inform clinical decision making, and highlight the importance of genetic testing in HLHS.

Building a dedicated pediatric pulmonary hypertension program: A consensus statement from the pediatric pulmonary hypertension network.

Pediatric pulmonary hypertension (PH) is a severe, life-threatening disease associated with diverse cardiac, pulmonary, and systemic disorders, which generally requires expertise from multiple disciplines for management. Unfortunately, expert centers are limited, often due to inadequate resources or unfamiliarity with needed components for success. The Pediatric Pulmonary Hypertension Network (PPHNet) includes expert centers in North America specifically dedicated to advancing the field of pediatric PH through research and excellent clinical care. PPHNet member sites were queried for valuable program components and these findings were discussed for consensus. Here we provide a collective overview of key elements of an optimal pediatric PH program: team composition, access to services, and commitment to education. It is our intention that this document will assist newer and/or smaller programs identify avenues and resources for growth and provide avenues for collaboration.

Factors Associated with Inability to Discharge After Stage 1 Palliation for Single Ventricle Heart Disease: An Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Database.

Patient-level characteristics associated with survival for single ventricle heart disease following initial staged palliation have been described. However, the impact of peri-operative events on hospital discharge has not been examined. To characterize patient-level characteristics and peri-operative events that were associated with inability to be discharged after Stage 1 palliation (S1P). Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Dataset including patients who underwent a S1P procedure between 2016 and 2019 (Norwood or Hybrid Stage 1 procedure). We examined patient-level characteristics and peri-operative events as possible predictors of inability to discharge after S1P. We constructed multivariate logistic regression models examining post-S1P discharge and in-hospital mortality, adjusting for covariates. 843 patients underwent a S1P and 717 (85%) patients were discharged home or remained inpatient until Stage 2 for social but not medical concerns. Moderate or greater pre-operative atrioventricular valve regurgitation (odds ratio (OR) 4.6, 95% confidence interval (CI) 1.8-12), presence of high-risk pre-operative adverse events (OR 1.5, 95%CI 1.0-2.3), peri-operative events: temporary dialysis (OR 5.4, 95%CI 1.5-18.9), cardiac catheterization or cardiac surgery (OR 2.9, 95%CI 1.8-4.6), sepsis (OR 2.7, 95%CI 1.2-6.2), junctional tachycardia (OR 2.6, 95%CI 1.0-6.3), necrotizing enterocolitis (OR 2.6, 95%CI 1.3-5.2), ECMO (OR 2.5, 95%CI 1.4-4.3), neurological injury (OR 2.1, 95%CI 1.1-4.1), and re-intubation (OR 1.8, 95%CI 1.1-2.9) were associated with inability to discharge after Stage 1. Cardiac anatomical factors, pre-operative adverse events, post-operative re-intubation, post-operative ECMO, infectious complications, and unplanned catheter or surgical re-interventions were associated with inability to discharge after S1P. These findings suggest that quality improvement efforts aimed at reducing these peri-operative events may improve Stage 1 survival and likelihood of discharge.

Cardiac Catheterization and Hemodynamics in a Multicenter Cohort of Children with Pulmonary Hypertension.

Rationale: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. Objectives: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. Methods: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014-2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. Results: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0-11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. Conclusions: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children.