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Three-dimensional echocardiography (3DE) evaluation of right ventricular (RV) volumes and ejection fraction (EF) is increasingly used for clinical serial assessments and management in children. This study aims to generate sex-specific reference values and z-score equations for RV volumetric parameters, independent of age and body size indices, derived from multiple populations across North America.We prospectively recruited 455 healthy children (ages 0 to 18 years) from 5 centres. 3DE of the RV were acquired using various vendors with analyses performed offline using vendor-independent software. 3DE datasets with all walls of the RV endocardium visible were included. We reported data on RV EF, and generated z scores for end-systolic volumes (ESV), end-diastolic volumes (EDV) and stroke volume (SV). Differences between the sexes were explored.Of 455 3DE datasets, 312 (68%) met imaging criteria for analysis. Median age was 10.1 years (interquartile ratio [IQR]: 5.6, 14.0) with 17% being younger than 3 years of age. The mean and standard deviation for RV EDV, ESV, and SV for male and female patients were reported. We provided a downloadable z-score calculator with height and weight as independent variables to facilitate clinical utility. Although statistically significant differences between male and female RVEF was present (female 52.9 ± 3.9% vs male 51.6 ± 3.5%, P = 0.006), after adjusting for age, height, and weight, the magnitude of difference was clinically insignificant.Sex-specific reference values for pediatric RV volumes and EF, and z-score equations were derived from children 3DE datasets across 5 centres in North America.

Background The Long-ter M O U tcomes after the Multisystem Inflammatory S yndrome I n C hildren (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods This multicenter observational cohort study will enroll at least 600 patients Conclusion The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

ObjectivesThe purpose of this study was to examine how the treatment and severity of multisystem inflammatory syndrome in children (MIS-C) has changed over more than two years of the COVID-19 pandemic in the United States.MethodsElectronic health record data were retrieved from the PEDSnet network as part of the NIH Researching COVID to Enhance Recovery (RECOVER) Initiative. The study included data for children ages 0 to 20 years hospitalized for MIS-C from March 1, 2020 through July 20, 2022. Descriptive statistics for MIS-C treatments and laboratory results were computed for three time periods of interest: March 1, 2020 – May 31, 2021 (pre-Delta); June 1 – December 31, 2021 (primarily Delta); January 1 – July 20, 2022 (primarily Omicron). Standardized differences measured the effect size of the difference between Omicron and pre-Omicron cohorts.ResultsThe study included 946 children with a diagnosis of MIS-C. The largest differences in the Omicron period compared to prior years were decreases in the percentage of children with abnormal troponin (effect size = 0.40), abnormal lymphocytes (effect size = 0.33), and intensive care unit (ICU) visits (effect size = 0.34). There were small decreases in the Omicron period for the majority of treatments and abnormal laboratory measurements examined, including infliximab, anticoagulants, furosemide, aspirin, IVIG without steroids, echocardiograms, mechanical ventilation, platelets, ferritin, and sodium.ConclusionsThis study provides the first evidence that the severity of MIS-C declined in the first half of the year 2022 relative to prior years of the COVID-19 pandemic in the United States.Article SummaryUsing electronic health record data for 946 children, we found evidence that the severity of MIS-C declined during the first half of the year 2022.What’s Known on This SubjectThe clinical management of multisystem inflammatory syndrome in children (MIS-C) has commonly included intravenous immune globulin, steroids, and non-steroidal anti-inflammatory agents. Many children with MIS-C have required intravenous fluids, inotropes and vasopressors, and in some cases, mechanical ventilation.What This Study AddsRecent decreases in the percentage of children with MIS-C that have abnormal troponin, abnormal lymphocytes, or intensive care unit visits provide evidence that the severity of MIS-C has declined in the first half of the year 2022.

Using electronic health record data combined with primary chart review, we identified 7 children across 8 pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) who were managed as outpatients. These findings should prompt a discussion about modifying the case definition to allow for such a possibility.

Purpose of review The purpose of this review is to summarize what is known about multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection. Recent findings The timing of presentation and features of diagnosis are described. Cardiac involvement is common and is the focus of this review. Arrhythmias, heart block, acute heart failure, shock, cardiac dysfunction, and coronary dilation have all been reported. Therapies used to treat children with this hyperinflammation syndrome include supportive care and agents that modulate the immune system. Therapies commonly described include intravenous immunoglobulin, steroids, and cytokine-directed agents, particularly tumor necrosis factor-alpha blockade and interleukin receptor blockade. The threshold for diagnosing coronary involvement in MIS-C is coronary artery dimensions indexed to body surface that exceed the normative values (Z score >2). Those hospitalized with MIS-C are evaluated by electrocardiogram and echocardiogram; outpatient assessment by a cardiologist is indicated prior to sports clearance. Summary The prognosis of treated MIS-C patients is good. Future work is needed to understand the scope of cardiac involvement associated with acute COVID-19 and MIS-C in children and to define the optimal therapeutic targets for these distinct entities.

BACKGROUND The ability of transesophageal three-dimensional echocardiography (3DE) to aid in pacemaker lead extraction has not yet been evaluated. 3DE provides real-time evaluation of intracardiac anatomy and the location of pacemaker leads in greater detail than either fluoroscopy or -two-dimensional echocardiography (2DE), aiding in the extraction of such leads, which can be potentially dangerous. We sought to investigate the feasibility and utility of 3DE to visualize intracardiac anatomy and pacemaker leads, and to assist in lead extraction procedures. METHODS We utilized 3DE in nine encounters for eight different patients, to visualize intracardiac anatomy and leads before, during, and after extraction to evaluate the feasibility and utility to aid in the procedure and evaluate for potential sequelae. RESULTS 3DE was able to identify pertinent intracardiac anatomy and leads in all cases. 3DE detected procedural complications or altered management in five of nine encounters (five of eight patients); this included detection of an avulsed papillary muscle, tricuspid valve leaflet damage, and cast/thrombus after lead removal, as well as adjustment of excess lead slack to avoid future valve damage, or risk stratification of lead removal. CONCLUSION 3DE is feasible and adds utility to lead extraction cases by visualizing intracardiac anatomy and leads beyond fluoroscopy or 2DE, providing real-time information during extraction, and identifying potential complications.

Right ventricular (RV) function is a major contributor to the outcome of pulmonary arterial hypertension (PAH). Adult studies demonstrated that regional and global changes in RV deformation are prognostic in PAH using 3-dimensional echocardiography (3DE). However, regional and global dynamic changes in RV mechanics have not been described in pediatric PAH. We compared 3DE RV regional and global deformation between pediatric patients who had associated PAH with congenital heart disease (APAH-CHD), pediatric patients who had idiopathic PAH (IPAH), and normal controls, and evaluated the clinical outcomes.A total of 48 controls, 47 patients with APAH-CHD, and 45 patients with IPAH were evaluated. 3DE RV sequences were analyzed and post-processed to extract global and regional deformation (circumferential, longitudinal, and area strain). Statistical analyses compared the sub-groups on the basis of global and regional deformation, and outcome analysis was performed.Patients with PAH had significantl8y different global and regional deformation (p0.001) compared with controls. Patients with APAH-CHD and and those with IPAH significantly differed in global circumferential strain (p0.010), area strain (inlet septum, p = 0.041), and circumferential strain at the inlet septum (p0.019), apex free wall (p0.004), and inlet free wall (p0.004). Circumferential strain at the inlet free wall and circumferential, longitudinal, and area strain at the apex free wall were predictors of adverse events.RV regional and global strain differ between controls and pediatric patients with PAH. RV apical free-wall area strain provides insight into the mechanism of RV dysfunction in pediatric patients with PAH, with regional strain emerging as outcome predictors, suggesting that this novel measure may be considered as a future measure of RV function.

Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology.To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD.This multicenter cohort study included consecutive, unselected patients with KD who were diagnosed between January 1, 2018, and December 31, 2020 (multicenter cohort with 28 pediatric centers), and a detailed analysis of patients with KD who were diagnosed between January 1, 2002, and November 15, 2021 (Rady Children's Hospital San Diego [RCHSD]).For the multicenter cohort, the date of fever onset for each patient with KD was collected. For RCHSD, detailed demographic and clinical data as well as publicly available, anonymized mobile phone data and median household income by census block group were collected. The study hypothesis was that public health measures undertaken during the pandemic would reduce exposure to the airborne trigger(s) of KD and that communities with high shelter-in-place compliance would experience the greatest decrease in KD incidence.A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]; P = .02), male children (21 vs 47.6 [10.0]; P = .01), and Asian children (4 vs 11.8 [4.4]; P = .046). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; P = .04; enlarged lymph node: 21% vs 32%; P = .09; periungual desquamation: 47% vs 58%; P = .16). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates.In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).

Coronavirus disease 2019 (COVID-19) resulted in a global pandemic and has overwhelmed health care systems worldwide. In this scientific statement, we describe the epidemiology, pathophysiology, clinical presentations, treatment, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome in children and young adults with a focus on cardiovascular manifestations and complications. We review current knowledge about the health consequences of this illness in children and young adults with congenital and acquired heart disease, the public health burden and health disparities of this infection in these populations, and vaccine-associated myocarditis.

Treatment of Kawasaki disease (KD) with intravenous immunoglobulin (IVIG) administered within the initial 10 days of fever onset decreases the risk of coronary artery aneurysms (CAAs) from ∼ 25% to less than 5%. However, patients with IVIG resistance, young infants, men, highly inflamed patients, and/or those with coronary changes at diagnosis remain at high risk for CAA. High-risk patients may benefit from acute, adjunctive antiinflammatory treatment in addition to IVIG. Optimal therapy remains unknown. This article reviews the acute pharmacologic management of patients with KD, focusing on adjunctive primary therapy options and treatment of patients with IVIG resistance.

Idiopathic pulmonary arterial hypertension (PAH) is a severe disease associated with a 20% 5-year mortality, often due to right heart failure. Recent studies suggest that compensatory changes in right atrial (RA) function may precede other clinical and echocardiographic evidence of right ventricular dysfunction. No prior prospective study has evaluated the role of RA emptying pattern as a prognostic marker of adverse clinical events in pediatric PAH.To demonstrate whether RA fractional emptying indices will prospectively predict risk of adverse clinical outcomes in pediatric PAH patients.Single-center, prospective cohort analysis of 41 patients with idiopathic or heritable PAH and 1:1 age and sex-matched controls with normal echo and electrocardiogram. Right atrial area (RAA) was measured just prior to tricuspid valve opening (RAAmax), at electrical p wave (RAAp), and just after tricuspid valve closing (RAAmin). Right atrial conduit fraction percent (RA cF%) was defined as the percentage of total RAA change happening prior to the electrical p wave = (RAAmax - RAAp)/(RAAmax - RAAmin) ∗ 100. Clinical worsening was analyzed with a predefined composite adverse event outcome.RA measurements were technically feasible in all study participants. The PAH patients (median age 11.9 years) had decreased RA cF% compared with controls (P .0001), and PAH subjects with lower RA cF% demonstrated higher right ventricular systolic (R = -0.49, P = .019) and end-diastolic (R = -0.52, P = .012) pressure than those with higher RA cF%. Sixteen subjects had a clinical event. Right atrial cF% (hazard ratio = 0.09; P .001) was highly prognostic for risk of adverse clinical event with area under the curve = 0.90 on receiver operating characteristic curve analysis (median 3.2-year follow-up).Right atrial conduit phase emptying is significantly altered in pediatric PAH. Within the PAH population, decreased RA cF% was prognostic for risk of clinical worsening. The combination of accuracy and ease of measurement could make RA cF% a clinically useful, noninvasive biomarker of early right heart failure and risk of disease progression in pediatric PAH.

Multisystem inflammatory syndrome in children (MIS-C) is a novel disease that was identified during the COVID-19 pandemic and is characterised by systemic inflammation following SARS-CoV-2 infection. Early detection of MIS-C is a challenge given its clinical similarities to Kawasaki disease and other acute febrile childhood illnesses. We aimed to develop and validate an artificial intelligence algorithm that can distinguish among MIS-C, Kawasaki disease, and other similar febrile illnesses and aid in the diagnosis of patients in the emergency department and acute care setting.In this retrospective model development and validation study, we developed a deep-learning algorithm called KIDMATCH (Kawasaki Disease vs Multisystem Inflammatory Syndrome in Children) using patient age, the five classic clinical Kawasaki disease signs, and 17 laboratory measurements. All features were prospectively collected at the time of initial evaluation from patients diagnosed with Kawasaki disease or other febrile illness between Jan 1, 2009, and Dec 31, 2019, at Rady Children's Hospital in San Diego (CA, USA). For patients with MIS-C, the same data were collected from patients between May 7, 2020, and July 20, 2021, at Rady Children's Hospital, Connecticut Children's Medical Center in Hartford (CT, USA), and Children's Hospital Los Angeles (CA, USA). We trained a two-stage model consisting of feedforward neural networks to distinguish between patients with MIS-C and those without and then those with Kawasaki disease and other febrile illnesses. After internally validating the algorithm using stratified tenfold cross-validation, we incorporated a conformal prediction framework to tag patients with erroneous data or distribution shifts. We finally externally validated KIDMATCH on patients with MIS-C enrolled between April 22, 2020, and July 21, 2021, from Boston Children's Hospital (MA, USA), Children's National Hospital (Washington, DC, USA), and the CHARMS Study Group consortium of 14 US hospitals.1517 patients diagnosed at Rady Children's Hospital between Jan 1, 2009, and June 7, 2021, with MIS-C (n=69), Kawasaki disease (n=775), or other febrile illnesses (n=673) were identified for internal validation, with an additional 16 patients with MIS-C included from Connecticut Children's Medical Center and 50 from Children's Hospital Los Angeles between May 7, 2020, and July 20, 2021. KIDMATCH achieved a median area under the receiver operating characteristic curve during internal validation of 98·8% (IQR 98·0-99·3) in the first stage and 96·0% (95·6-97·2) in the second stage. We externally validated KIDMATCH on 175 patients with MIS-C from Boston Children's Hospital (n=50), Children's National Hospital (n=42), and the CHARMS Study Group consortium of 14 US hospitals (n=83). External validation of KIDMATCH on patients with MIS-C correctly classified 76 of 81 patients (94% accuracy, two rejected by conformal prediction) from 14 hospitals in the CHARMS Study Group consortium, 47 of 49 patients (96% accuracy, one rejected by conformal prediction) from Boston Children's Hospital, and 36 of 40 patients (90% accuracy, two rejected by conformal prediction) from Children's National Hospital.KIDMATCH has the potential to aid front-line clinicians to distinguish between MIS-C, Kawasaki disease, and other similar febrile illnesses to allow prompt treatment and prevent severe complications.US Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Heart, Lung, and Blood Institute, US Patient-Centered Outcomes Research Institute, US National Library of Medicine, the McCance Foundation, and the Gordon and Marilyn Macklin Foundation.

OBJECTIVES To compare initial treatment with intravenous immunoglobulin (IVIG) versus IVIG plus infliximab in multisystem inflammatory syndrome in children (MIS-C). METHODS Single-center retrospective cohort study of patients with MIS-C who met Centers for Disease Control and Prevention criteria and received treatment from April 2020 to February 2021. Patients were included and compared on the basis of initial therapy of either IVIG alone or IVIG plus infliximab. The primary outcome was need for additional therapy 24 hours or more after treatment initiation. RESULTS Seventy-two children with MIS-C met inclusion criteria. Additional therapy was needed in 13 of 20 (65%) who received IVIG alone and 16 of 52 (31%) who received IVIG plus infliximab (P = .01). The median (interquartile range) ICU lengths of stay were 3.3 (2.2 to 3.8) and 1.8 (1.1 to 2.1) days, respectively (P = .001). New or worsened left ventricular dysfunction developed in 4 of 20 (20%) and 2 of 52 (4%) (P = .05), and new vasoactive medication requirement developed in 3 of 20 (15%) and 2 of 52 (4%), respectively (P = .13). The median percentage changes in the C-reactive protein level at 24 hours posttreatment compared with pretreatment were 0% (−29% to 66%) and −46% (−62% to −15%) (P < .001); and at 48 hours posttreatment, −5% (−41% to 57%) and −70% (−79% to −49%) respectively (P < .001). There was no significant difference in hospital length of stay, time to fever resolution, vasoactive medication duration, or need for diuretics. CONCLUSIONS Patients with MIS-C initially treated with IVIG plus infliximab compared with those treated with IVIG alone were less likely to require additional therapy and had decreased ICU length of stay, decreased development of left ventricular dysfunction, and more rapid decline in C-reactive protein levels.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular complications include left ventricular dysfunction and coronary artery abnormalities (CAA). Little is known, however, about the interaction between LV function and CAA. We aimed to assess the hypothesis that increased coronary artery size is inversely correlated with LV function utilizing left ventricular ejection fraction (LVEF) and indices of myocardial work. Methods: Two-dimensional and speckle-tracking echocardiograms were performed in 34 MIS-C patients at admission. Biplane LVEF and coronary artery Z scores were measured, and pressure-strain loops were used to calculate indices of myocardial work: global work index (GWI), global work efficiency (GWE), global wasted work (GWW), global constructive work (GCW), and global longitudinal strain (GS). Treating coronary artery Z-scores as a continuous variable, correlation analysis was performed. Results: LVEF and left anterior descending artery (LAD) Z-scores were inversely correlated (Spearman coefficient of -0.47; P =0.005). Both GWI and GCW demonstrated an inverse relationship with increasing LAD Z-scores, but both were not statistically significant (Spearman coefficient -0.21; P =0.239 and Spearman coefficient -0.21; P= 0.235). GS also exhibited a trend of worsening (less negative scores) with increasing LAD Z-scores but was not statistically significant (Spearman coefficient 0.29; P =0.095). GWE and GWW did not correlate with any coronary artery Z-scores and left main coronary or right coronary artery Z-scores did not correlate with any markers of function. Conclusion: Increasing LAD Z-score showed a statistically significant association with decreased LVEF. Additionally, while not statistically significant, GWI, GCW, and GS all demonstrated a trend of decreased indices of myocardial work as LAD Z-score increases. In conclusion, this data suggests that patients with higher coronary artery Z-scores at admission are at increased risk of myocardial dysfunction.

Introduction: Right Ventricular (RV) dysfunction is the primary aspect of acute right ventricular failure, commonly realized in pulmonary arterial hypertensive (PAH) patients. As a standard clinical assessment for PAH, echocardiographic strain provides a mechanical measure of ventricular deformation during RV contraction. Current strain computation via 2D echo is limited in that imaging and strain are confined to a 2D plane, and thus the technique is unable to fully visualize the asymmetrical deformation of the RV. We believe 3D surface (3DS) strain, obtained from 3D echo (3DE) will overcome this limitation and more thoroughly evaluate myocardial mechanics. In this initial work, we hypothesize that end-systolic 3DS longitudinal and shear freewall strain group means computed from 3DE-cardiac data of the RV will differ between healthy and PAH patient groups. Methods: 3DS strain (longitudinal, circumferential, shear; principal strains, principal angle, and max shear) was computed on the RV freewall at end-systole with finite element analysis post-processing techniques from RV surface meshes obtained from 3DE from 10 normal children and 43 children with idiopathic PAH. Results: 3DS longitudinal and circumferential strain group means were significantly different (p Conclusions: These results suggest that 3DS strain is a promising approach to strain computation with potential to yield more mechanical knowledge of different segments of RV dysfunction. Future work should be directed in the evaluation of focused regional strain specific towards RV dysfunction and evaluate for prognosis.

Background Endostatin, an angiogenic inhibitor, is associated with worse pulmonary arterial hypertension (PAH) outcomes in adults and poor lung growth in children. This study sought to assess whether endostatin is associated with disease severity and outcomes in pediatric PAH. Methods and Results Serum endostatin was measured in cross‐sectional (N=160) and longitudinal cohorts (N=64) of pediatric subjects with PAH, healthy pediatric controls and pediatric controls with congenital heart disease (CHD) (N=54, N=15), and adults with CHD associated PAH (APAH‐CHD, N=185). Outcomes, assessed by regression and Kaplan‐Meier analysis, included hemodynamics, change in endostatin over time, and transplant‐free survival. Endostatin secretion was evaluated in pulmonary artery endothelial and smooth muscle cells. Endostatin was higher in those with PAH compared with healthy controls and controls with CHD and was highest in those with APAH‐CHD. In APAH‐CHD, endostatin was associated with a shorter 6‐minute walk distance and increased mean right atrial pressure. Over time, endostatin was associated with higher pulmonary artery pressure and pulmonary vascular resistance index, right ventricular dilation, and dysfunction. Endostatin decreased with improved hemodynamics over time. Endostatin was associated with worse transplant‐free survival. Addition of endostatin to an NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) based survival analysis improved risk stratification, reclassifying subjects with adverse outcomes. Endostatin was secreted primarily by pulmonary artery endothelial cells. Conclusions Endostatin is associated with disease severity, disease improvement, and worse survival in APAH‐CHD. Endostatin with NT‐proBNP improves risk stratification, better predicting adverse outcomes. The association of elevated endostatin with shunt lesions suggests that endostatin could be driven by both pulmonary artery flow and pressure. Endostatin could be studied as a noninvasive prognostic marker, particularly in APAH‐CHD.

Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease, 10-20% of patients have recrudescent fever as a sign of persistent inflammation and require additional treatment. We aimed to compare infliximab with a second infusion of IVIG for treatment of resistant Kawasaki disease.In this multicentre comparative effectiveness trial, patients (aged 4 weeks to 17 years) with IVIG resistant Kawasaki disease and fever at least 36 h after completion of their first IVIG infusion were recruited from 30 hospitals across the USA. Patients were randomly assigned (1:1) to second IVIG (2 g/kg over 8-12 h) or intravenous infliximab (10 mg/kg over 2 h without premedication), by using a randomly permuted block randomisation design with block size of two or four. Patients with fever 24 h to 7 days following completion of first study treatment crossed over to receive the other study treatment. The primary outcome measure was resolution of fever at 24 h after initiation of study treatment with no recurrence of fever attributed to Kawasaki disease within 7 days post-discharge. Secondary outcome measures included duration of fever from enrolment, duration of hospitalisation after randomisation, and changes in markers of inflammation and coronary artery Z score. Efficacy was analysed in participants who received treatment and had available outcome values. Safety was analysed in all randomised patients who did not withdraw consent. This clinical trial is registered with ClinicalTrials.gov, NCT03065244.Between March 1, 2017, and Aug 31, 2020, 105 patients were randomly assigned to treatment and 103 were included in the intention-to-treat population (54 in the infliximab group, 49 in the second IVIG group). Two patients randomised to infliximab did not receive allocated treatment. The primary outcome was met by 40 (77%) of 52 patients in the infliximab group and 25 (51%) of 49 patients in the second IVIG infusion group (odds ratio 0·31, 95% CI 0·13-0·73, p=0·0076). 31 patients with fever beyond 24 h received crossover treatment: nine (17%) in the infliximab group received second IVIG and 22 (45%) in second IVIG group received infliximab (p=0·0024). Three patients randomly assigned to infliximab and two to second IVIG with fever beyond 24h did not receive crossover treatment. Mean fever days from enrolment was 1·5 (SD 1·4) for the infliximab group and 2·5 (2·5) for the second IVIG group (p=0·014). Mean hospital stay was 3·2 days (2·1) for the infliximab group and 4·5 days (2·5) for the second IVIG group (p0·001). There was no difference between treatment groups for markers of inflammation or coronary artery outcome. 24 (44%) of 54 patients in the infliximab group and 33 (67%) of 49 in the second IVIG group had at least one adverse event. A drop in haemoglobin concentration of at least 2g/dL was seen in 19 (33%) of 58 patients who received IVIG as either their first or second study treatment (three of whom required transfusion) and in three (7%) of 43 who received only infliximab (none required transfusion; p=0·0028). Haemolytic anaemia was the only serious adverse events deemed definitely or probably related to study treatment, and was reported in nine (15%) of 58 patients who received IVIG as either their first or second study treatment and none who received infliximab only.Infliximab is a safe, well tolerated, and effective treatment for patients with IVIG resistant Kawasaki disease, and results in shorter duration of fever, reduced need for additional therapy, less severe anaemia, and shorter hospitalisation compared with second IVIG infusion.Patient Centered Outcomes Research Institute.

With the increasing frequency of catheter-based interventions in congenital heart disease and structural heart disease, the use of fusion imaging has become a major enhancement for understanding complex anatomy and facilitating key steps in interventional procedures. Because transesophageal echocardiography and fluoroscopy are displayed in different visual perspectives, the interventional cardiologist must mentally reregister the images from the two modalities during the procedure. Echocardiography-fluoroscopy fusion (EFF) imaging displays the x-ray and ultrasound overlay images in the same visual perspective. This new technology allows for enhanced team communication, improved visual guidance, and more efficient navigation. The purpose of this review is to describe the EFF imaging technology, current uses of EFF imaging in congenital and structural heart disease, and future directions that will enhance this unique imaging technology to guide interventional procedures.

Background: An integrated assessment of the size and shape of the 4-chamber view (4-CV) and right and left ventricles (RV and LV) as well as the function of the RV and LV in fetuses with coarctation of the aorta (CoA) has not yet been conducted. Objectives: We evaluated the size and shape of the 4-CV, RV, and LV, and function of the RV and LV, to identify a profile for fetuses with CoA when compared to a control population. Methods: 50 CoA fetuses were compared to 200 controls. This was a retrospective case series comparing the 4-CV of CoA fetuses and controls. The 4-CV end-diastolic area, length, width, and sphericity index were measured to determine the configuration of the 4-CV. Speckle-tracking analysis was used to compute the RV and LV end-diastolic area, length, 24-segment sphericity index, 24-segment transverse width, and the following functional parameters: (1) fractional area change; (2) global, lateral, and septal strain; (3) basal-apical, lateral, and septal annular displacement and fractional shortening; and (4) 24-segment transverse width fractional shortening. Using 5 and 95% reference intervals, the CoA fetal measurements were classified; from these, the odds ratio was computed between the fetuses with CoA and the controls. p < 0.05 was considered significant. Results: In fetuses with CoA, the 4-CV was spherical in shape, increased in area and width, and decreased in length. Abnormal CoA sphericity indices reflected a flatter LV and a more spherical RV. The LV area, length, and width, and RV length were decreased. The transverse width of the RV was increased. RV and LV global, longitudinal, and transverse contractility were depressed. Conclusions: The results demonstrate previously unappreciated differences in the shape, size, and function of the heart in fetuses with CoA. These differences may assist examiners in identifying fetuses with CoA.

Background Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10–20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients. Objectives The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience. Methods The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5–18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm. Conclusion This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.

While the majority of this textbook addresses the use of transesophageal echocardiography (TEE) for the evaluation of pediatric patients and all patients (pediatric and adult) with congenital heart disease (CHD) primarily in the intraoperative and interventional settings, there are other areas in which TEE can play a significant role in these patients. This chapter focuses on other applications of TEE. We will discuss the most common indications for TEE in this setting, including evaluation for infective endocarditis, cardiac thrombi after CHD surgery, and prosthetic valves.

Background: Three-dimensional echocardiography (3DE) evaluation of left ventricular (LV) volume and function in pediatrics compares favorably with cardiac magnetic resonance imaging. The aim of this study was to establish from a multicenter, normal pediatric z-score values of 3DE left ventricular volumes and function. Methods: Six hundred and ninety-eight healthy children (ages 0 to 18 years) were recruited from five centers. LV 3DE was acquired from the 4-chamber view. A vendor independent software analyzed end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) using semi-automated quantification. Body surface area (BSA) based z-scores were generated. Intraobserver and interobserver variability were calculated using intraclass correlation (ICC) and repeatability coefficient (RC). Results: Z-scores were generated for ESV, EDV, and SV. The ICC for intraobserver variability for EDV, ESV, and SV were 0.99, 0.99, and 0.99 respectively. The ICC for interobserver variability for EDV, ESV, and SV were 0.98, 0.94, and 0.98 respectively. The RC for intraobserver and interobserver variability for LV EF was 4.39% (95% CI: 3.01, 5.59) and interobserver was 7.08% (95%CI: 5.51, 8.42). Conclusions: We report pediatric Z-scores for normal LV volumes using the semi-automated method from five centers, enhancing its generalizability. 3DE evaluation of LV volumes and EF in pediatric patients is highly reproducible.

Background: Right ventricular (RV) free wall longitudinal strain (FWLS) is a functional assessment in pediatric pulmonary hypertension (PH). RV FWLS analysis requires study transfer to an offline software which can hinder clinical use. Autostrain RV (AS-RV) uses an automatic recognition and speckle tracking that allows for an efficient tool in routine clinical use. We evaluated the feasibility and reproducibility of AS-RV FWLS in controls and PH patients, and compared the timing of AS-RV to the offline analysis. Methods: Two and 3-dimensional echocardiography 4-chamber RV images were obtained in 32 PH patients and 33 controls. RV FWLS was analyzed by AS-RV software on the EPIQ machines and offline by TomTec 4D RV strain software. AS-RV timing with and without RVFW adjustments were compared to TomTec. Adjusted AS-RV and TomTec RVFWLS were compared between controls and PH patients using paired T-tests, Intraclass correlation (ICC), and Bland-Altman. Results: Controls and PH patients were not statistically different in age, body surface area, or heart rate. PH patients had decreased RV FWLS than controls (-24.1 ± 5.2 vs -28.3 ± 3.6; p Conclusion: RV FWLS evaluation is feasible and reproducible using AS-RV, but frequent adjustments need to be made for data accuracy. Adjusted AS-RV can be incorporated into clinical use with less time, making quantification of RV easier in clinical practice.

Introduction: Transseptal puncture (TSP) is an essential step in percutaneous structural heart interventions, such as the MitraClip® procedure. Radiation exposure is a hazard for Interventional Cardiologists, Echocardiographers, and patients. Advancements in shielding and radiation equipment have reduced this exposure, but further reduction is desired. EchoNav® (Philips) fuses fluoroscopy and echocardiography resulting in a single multimodal image display. Prior studies demonstrated reduced time to TSP with use of EchoNav® but failed to show significant reduction in radiation. We hypothesized that increased experience using EchoNav® would further decrease TSP time and radiation dose. Methods: Single center, retrospective analysis evaluated 202 patients undergoing MitraClip® procedure pre and post-EchoNav® from 6/2010 to 12/2019: 8 pre and 194 post. We measured time to TSP and radiation exposure by Air Kerma and dose area product (DAP). For the post-EchoNav® cases, we evaluated these variables by 2-year time periods to examine change over time. Results: Comparing pre and post-EchoNav ® procedures, time to TSP was non-significantly reduced overall (40.00±14.95 to 33.63±15.92, p=0.23). However, post-EchoNav ® had a decreasing trend (48.00±28.39, 43.47±15.86, 28.45±11.94, 27.55±10.64; R 2 =0.89, p =0.009) that was significantly less than pre-EchoNav ® by the third time period (40.00±14.95 vs 28.45±11.94, p=0.05) and remained less in the fourth (40.00±14.95 vs 27.55±10.64, p=0.03). Radiation was reduced post-EchoNav ® by both DAP (264.52±150.03 to 109.00±97.68) (p=0.02) and Air Kerma (1472.92±883.50 to 582.49±485.28) (p=0.05). Significant radiation reduction occurred by the third time period for Air Kerma (1472.92±883.50 vs 494.12±413,79, p=0.03) and second time period for DAP (264.52±150.03 to 127.51±110.35, p=0.03). Conclusion: These results suggest that use of EchoNav® has a learning curve, but ultimately reduces time to TSP and radiation.

Recent studies show adverse right atrial (RA) emptying pattern is prognostic for clinical worsening events in pediatric pulmonary arterial hypertension (PAH). No study has reported changes in RA emptying over time or evaluated whether serial measurements offer further prognostic information.Prospective study of 32 children with idiopathic or heritable PAH undergoing echocardiogram at baseline and 1-year. RA conduit fraction percent (RA cF%) was measured as percentage of total diastolic RA area change prior to the electrical p wave. Clinical worsening was analyzed with a predefined composite adverse event outcome.Longitudinal subjects (median age 13.3 yr) had RA cF% 61% (IQR 32-68%) at baseline and 60% (IQR 35-73%) at 1-year (NS). 11 subjects had a qualifying event during median 21-month follow-up. Subjects with an event had 1-year RA cF% = 33% (IQR 20-40%) compared to 72% (IQR 63-75%) for those with no event (p 0.001). Event rates were lowest for subjects with both echocardiograms showing RA cF% 60% (0%), highest for subjects with neither (80%), and intermediate for those with one (38%, p = 0.003).Changes in RA cF% inform risk of adverse events in pediatric PAH. This finding supports the role of RA cF% as both a prognostic biomarker and potential treatment target.

Increased catheter-based interventions in congenital and structural heart disease require imaging modalities to be oriented in the same visual perspective. The use of echocardiography-fluoroscopy fusion (EFF) imaging has been developed for better characterization of complex anatomy and to facilitate key steps in interventional procedures. This review will detail the technology behind EFF, the differences between the two ultrasound fusion systems, and essential features of EFF imaging in congenital and structural heart disease interventions.

Three-dimensional echocardiography allows for presurgical planning for congenital heart disease, reduces radiation using fusion imaging in catheter interventions, and provides guidance during catheter interventions and lead placements or extractions. The purpose of this review is to detail applications of three-dimensional transesophageal echocardiography in presurgical planning of congenital heart disease, guidance of catheter interventions such as fusion imaging, and guidance in electrophysiology lead extractions or placements.

Kawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children.Circulating miRNA profiles from 84 KD patients and 29 non-KD febrile controls (7 viral and 22 bacterial infections) were evaluated. 3 ul of serum from each subject was submitted to 3 freeze/heat cycles to ensure miRNA release from microvesicles or interaction with serum proteins. miRNAs were reverse transcribed using a pool of primers specific for each miRNA. Real-time PCR reactions were performed in a 384 well plate containing sequence-specific primers and TaqMan probes in the ABI7900. '.KD patients (3.6 ± 2.2 yrs., 58% male) were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, -184, and -19a-3p (p .0001), compared to non-KD febrile controls (8.5 ± 6.1 yrs., 72% male).Circulating miRNAs can differentiate KD from infectious febrile childhood diseases, supporting their potential as a diagnostic biomarker for KD.

The Adult Congenital and Pediatric Cardiology (ACPC) Section of the American College of Cardiology sought to develop quality indicators/metrics for ambulatory pediatric cardiology practice. The objective of this study was to report the creation of metrics for patients with Kawasaki disease. Over a period of 5 months, 12 pediatric cardiologists developed 24 quality metrics based on the most relevant statements, guidelines, and research studies pertaining to Kawasaki disease. Of the 24 metrics, the 8 metrics deemed the most important, feasible, and valid were sent on to the ACPC for consideration. Seven of the 8 metrics were approved using the RAND method by an expert panel. All 7 metrics approved by the ACPC council were accepted by ACPC membership after an “open comments” process. They have been disseminated to the pediatric cardiology community for implementation by the ACPC Quality Network.

Pulmonary hypertension (PH) is a progressive disease affecting patients across the life span. The pathophysiology primarily involves the pulmonary vasculature and right ventricle (RV), but eventually affects the left ventricular (LV) function as well. Safe, accurate imaging modalities are critical for diagnosis, serial monitoring, and tailored therapy. While cardiac catheterization remains the conventional modality for establishing diagnosis and serial monitoring, noninvasive imaging has gained considerable momentum in providing accurate assessment of the entire RV-pulmonary axis. In this state-of-the-art review, we will discuss the most recent developments in echocardiography, magnetic resonance imaging, and computed tomography in PH evaluation from pediatric to adult population.

Introduction Eleven-year-old male presented with nonsustained ventricular tachycardia presented for ablation of ventricular tachycardia located on the left lateral wall that is likely associated with anterolateral papillary muscle. Although he was asymptomatic, his atria have become dilated over time thus he was scheduled for a catheter ablation. Echocardiographic-fluoroscopic fusion imaging has shown transseptal puncture using this technology is safe and required less time in crossing the atrial septum; however, fusion imaging with 3D echocardiography overlay of left ventricular papillary muscle onto fluoroscopy has not been used in ventricular tachycardia ablations. Purpose The purpose of this clinical case was to evaluate the application of this new technology of echocardiography-fluoroscopy fusion imaging to guide left ventricular tachycardia ablation. Methods Echocardiographic-fluoroscopic fusion imaging was used for transseptal puncture and a 3D echocardiographic image of the left ventricle with anterolateral papillary muscle was overlaid onto fluoroscopy (Figure 1). The radiofrequency catheter was used to ablate the left anterolateral papillary muscle. With fused imaging, the ablation catheter was seen at the left anterolateral papillary muscle, and care was taken to prevent perforation of the lateral wall of the left ventricle. Results With fusion imaging of the left anterolateral papillary muscle overlaid onto fluoroscopy, the lateral wall of the left ventricular was also delineated. The catheter was easily visualized with fusion imaging to prevent perforation of the left ventricle while radiofrequency ablation was performed (Figure 1). Discussion 3D echocardiography provides excellent soft tissue definition of the lateral wall of the left ventricle and papillary muscle while fluoroscopy provides clear visualization of the ablation catheter. The ability of fusion imaging to overlay the 3D echocardiographic images onto fluoroscopy allowed for easy visualization of the anterolateral papillary muscle while the radiofrequency ablation was performed to avoid lateral wall perforation of the left ventricle. Future studies of echocardiographic-fluoroscopic fusion imaging should evaluate the potential to reduce procedure time and improve patient outcomes. Abstract P635 Figure.