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Objectives:To define the frequency and characteristics of acute neurologic complications in children hospitalised with infective endocarditis and to identify risk factors for neurologic complications.Study Design:Retrospective cohort study of children aged 0–18 years hospitalised at a tertiary children’s hospital from 1 January, 2008 to 31 December, 2017 with infective endocarditis.Results:Sixty-eight children met Duke criteria for infective endocarditis (43 definite and 25 possible). Twenty-three (34%) had identified neurologic complications, including intracranial haemorrhage (25%, 17/68) and ischaemic stroke (25%, 17/68). Neurologic symptoms began a median of 4.5 days after infective endocarditis symptom onset (interquartile range 1, 25 days), though five children were asymptomatic and diagnosed on screening neuroimaging only. Overall, only 56% (38/68) underwent neuroimaging during acute hospitalisation, so additional asymptomatic neurologic complications may have been missed. Children with identified neurologic complications compared to those without were older (48 versus 22% ≥ 13 years old, p = 0.031), more often had definite rather than possible infective endocarditis (96 versus 47%, p < 0.001), mobile vegetations >10mm (30 versus 11%, p = 0.048), and vegetations with the potential for systemic embolisation (65 versus 29%, p = 0.004). Six children died (9%), all of whom had neurologic complications.Conclusions:Neurologic complications of infective endocarditis were common (34%) and associated with mortality. The true frequency of neurologic complications was likely higher because asymptomatic cases may have been missed without screening neuroimaging. Moving forward, we advocate that all children with infective endocarditis have neurologic consultation, examination, and screening neuroimaging. Additional prospective studies are needed to determine whether early identification of neurologic abnormalities may direct management and ultimately reduce neurologic morbidity and overall mortality.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. Methods: We retrospectively collected data on patients Results: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1–20.3; interquartile range [IQR], 14.5–17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0–22; IQR, 1–3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0–10; IQR, 2–3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50–15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25–1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction Conclusions: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons

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.

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was “indicated.” Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2–25% for RL 5, and 0–5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Infants with staged surgical palliation for congenital heart disease are at high-risk for interstage morbidity and mortality; home monitoring programs have mitigated these risks. In 2019, we instituted telemedicine (TM) in our established Infant Single Ventricle Monitoring Program. All consecutive patients discharged following neonatal operation/intervention were monitored until subsequent stage 2 surgical palliation. We offered TM (synchronous video) visits as part of regularly scheduled follow-up, replacing at least one in-person primary care visit with a TM cardiologist visit. We tracked emergency department (ED) visits, hospitalizations, how TM identified clinical concerns, and whether use of TM prevented unnecessary ED visits or expedited in-person assessment. We assessed caregiver and clinician satisfaction. Between 8/2019 and 5/2020, we conducted 60 TM visits for 29 patients. Of 31 eligible patients, 2 families (6.9%) declined. Median monitoring time was 199 days (range 75-264) and median number of TM visits/patient was 2 (range 1-5). In 6 visits (10%), significant clinical findings were identified which avoided an ED visit. Five TM visits led to expedited outpatient assessments, of which 1 patient required hospitalization. There were no missed events or deaths. Median ED visits/patient/month were significantly lower compared to the same calendar period of the prior year (0.0 (0-2.5) vs. 0.4 (0-3.7), p = 0.0004). Caregivers and clinicians expressed high levels of satisfaction with TM. TM for this high-risk population is feasible and effective in identifying clinical concerns and preventing unnecessary ED visits. TM was particularly effective during the COVID-19 pandemic, allowing for easy adaptation of care to ensure patient safety in this fragile cohort.

Key Points sC5b9 plasma levels are elevated in children with SARS-CoV-2 infection, even if they have minimal symptoms of COVID-19. A high proportion of children with SARS-CoV-2 infection met clinical criteria for TMA., Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patients with acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized children with SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C., Visual Abstract

Background Since April 2020, there have been numerous reports of children presenting with systemic inflammation, often in critical condition, and with evidence of recent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to COVID-19, and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation. Methods We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries. Results Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation. Every respondent reported use of intravenous immunoglobulin (IVIG), including 53% administering IVIG in all patients. Steroids were most often used for patients with severe clinical presentation or lack of response to IVIG, and only a minority used steroids in all patients (14%). ASA was frequently used among respondents (91%), including anti-inflammatory and/or anti-platelet dosing. Respondents reported use of prophylactic anticoagulation, especially in patients at higher risk for venous thromboembolism, and therapeutic anticoagulation, particularly for patients with giant coronary artery aneurysms. Conclusions There is variation in management of MIS-C patients with suboptimal evidence to assess superiority of the various treatments; evidence-based gaps in knowledge should be addressed through worldwide collaboration to optimize treatment strategies., There is a delayed and often critical presentation of a multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Cardiac manifestations can include ventricular dysfunction and/or coronary artery dilation. We surveyed the management approaches of the membership of the International Kawasaki Disease Registry. Management often includes immunomodulatory therapies and thromboprophylaxis with variation in indications across institutions.

Despite progress in pharmacotherapy in pediatric pulmonary hypertension, real-world patterns of directed pulmonary hypertension therapy have not been studied in the current era. A retrospective observational study of children (≤18 years) with pulmonary hypertension was performed using data from the MarketScan® Commercial and Medicaid claims databases. Associations between etiology of pulmonary hypertension and pharmaceutical regimen were evaluated, as were the associations between subject social and geographic characteristics (insurance-type, race, and/or census region) and regimen. Annualized costs of single- and multi-class regimens were calculated. In total, 873 subjects were studied, of which 94% received phosphodiesterase-5 inhibitors, 31% endothelin receptor antagonist, 9% prostacyclin analogs, and 7% calcium channel blockers. Monotherapy was used in 72% of subjects. Phosphodiesterase-5 inhibitors monotherapy was the most common regimen (93%). Subjects with idiopathic pulmonary hypertension, congenital heart disease, and unclassified pulmonary hypertension receive more than one agent and were more likely to receive both endothelin receptor antagonist and prostacyclin analogs than other forms of pulmonary hypertension. Compared to recipients of public insurance, subjects with commercial insurance were more likely to receive more intense therapy ( p = 0.003), which was confirmed in multivariable analysis (OR: 1.4, p = 0.03). Receipt of commercial insurance was also associated with increased annual costs across all subjects ( p

Introduction: Home monitoring in the interstage (IS) period has resulted in a significant decline in mortality in infants with hypoplastic left heart syndrome (HLHS). We hypothesize that this may in part be attributed to an increase in IS readmissions preventing out-of-hospital adverse events. We sought to examine the impact of our Infant Single Ventricle Monitoring Program (ISVMP) on the frequency and severity of unanticipated IS readmissions and to identify risk factors for readmission. Methods: This retrospective single-center cohort study compared infants with HLHS enrolled in ISVMP to historical controls. Readmission rate was defined as the number of unanticipated readmissions per interstage days. Severe readmission was defined by mortality, extracorporeal support, cardiopulmonary resuscitation, mechanical ventilation, or initiation of vasoactive medication. The relationship between ISVMP and number of interstage readmissions was modeled using inverse probability weighted (IPW) Poisson regression. The effect of ISVMP on the probability of severe readmission was modeled using IPW logistic regression. Multivariable Poisson regression models were used to identify risk factors for readmission. Results: We compared 198 ISVMP infants from 12/2010 to 12/2019 to 128 historical controls from 1/2007 to 11/2010. Readmissions were more frequent in the ISVMP group vs. controls (median 1.09 vs. 0.68 readmissions/100 days, p < 0.0001) with more than double the rate of readmissions in ISVMP infants (adjusted IRR 2.13; 95% CI 1.61-2.82; p < 0.0001). Despite a greater readmission rate, ISVMP infants were less likely to have severe readmissions (adjusted OR 0.25; 95% CI 0.11-0.60; p = 0.018). Independent risk factors for readmission were residing closer to our center, younger gestational age, postnatal diagnosis, genetic syndrome, and discharge with exclusive enteral tube feeds. Conclusions: In this single-center study, ISVMP infants had more frequent but less severe unanticipated readmissions. These findings suggest that the prevention of IS morbidity and mortality may have resulted in greater resource utilization. Future efforts should focus on strategies to decrease unanticipated readmissions without increasing adverse events.

Objectives:To make practical and evidence-based recommendations on improving understanding of bleeding and thrombosis with pediatric extracorporeal life support and to make recommendations for research directions.Data Sources:Evaluation of literature and consensus conferences of pediatric critical c

Introduction: Infants with staged surgical palliation for congenital heart disease are at high-risk for interstage morbidity and mortality. We have previously described the mediated risk for this patient population through close home monitoring. Given high rates of intercurrent illness, geographic and sociodemographic disparities in access to care, and significant family stressors, we instituted a telecardiology (TC) program in 2019. Methods: All consecutive patients discharged home were monitored from neonatal operation or intervention to subsequent surgical palliation. All had home scales and pulse oximeters. TC visits (TCVs) were held monthly, and increased to bimonthly during the COVID-19 pandemic. TCVs were launched through the electronic medical record (EMR) through a mobile device, with a full-version EMR available for access to full records and efficient documentation. We tracked how TCVs identified clinical concerns, prevented unnecessary emergency room visits (ERV) and expedited in-person assessment. Results: Between 8/2019-5/2020, we conducted 60 TCV for 29 patients (16 had stage 1 palliation, 6 with aortopulmonary shunt or stent and 7 with biventricular physiology with shunt or stents. Initial median weight was 3.4 kg (range 2.3-5.4 kg). Median monitoring time was 199 days (75-264). Median visits per patient were 2 (1-5 V) with average length per visit of 20 minutes. Most scheduled visits were completed (90%); 5% declined, and 5% canceled. Parents reported satisfaction for 97% of visits. In 6 visits (10%) significant clinical findings were identified which avoided ERV or hospital admissions, 4 TCVs (7%) visits led to expedited outpatient assessments, 1 required hospitalization. There were no missed events nor deaths. Additional issues identified included changes to medication (23%), feedings (15%) and equipment malfunction (5%). Frequency of EDV decreased from median 0.4 (0-3.7) V/patient/month the prior year to 0 (0-2.5), p=0.0004]. Conclusions: TC in these high-risk patients is feasible and effective to identify clinical concerns, no missed events and decrease in ERV per patient. TC was particularly effective during the COVID-19 pandemic allowing for easy adaptation of care to ensure patient safety in this fragile cohort.

Background Centers from Europe and United States have reported an exceedingly high number of children with a severe inflammatory syndrome in the setting of COVID-19, which has been termed multisystem inflammatory syndrome in children (MIS-C). Objectives This study aimed to analyze echocardiographic manifestations in MIS-C. Methods We retrospectively reviewed 28 MIS-C, 20 healthy controls and 20 classic Kawasaki disease (KD) patients. We reviewed echocardiographic parameters in acute phase of MIS-C and KD groups, and during subacute period in MIS-C group (interval: 5.2 ± 3 days). Results Only 1 case in MIS-C (4%) manifested coronary artery dilatation (z score=3.15) in acute phase, showing resolution during early follow up. Left ventricular (LV) systolic and diastolic function measured by deformation parameters, were worse in MIS-C compared to KD. Moreover, MIS-C patients with myocardial injury (+) were more affected than myocardial injury (-) MIS-C with respect to all functional parameters. The strongest parameters to predict myocardial injury in MIS-C were global longitudinal strain (GLS), global circumferential strain (GCS), peak left atrial strain (LAS) and peak longitudinal strain of right ventricular free wall (RVFWLS) (Odds ratio: 1.45 (1.08-1.95), 1.39 (1.04-1.88), 0.84 (0.73-0.96), 1.59 (1.09-2.34) respectively). The preserved LVEF group in MIS-C showed diastolic dysfunction. During subacute period, LVEF returned to normal (median: from 54% to 64%, p Conclusions Unlike classic KD, coronary arteries may be spared in early MIS-C, however, myocardial injury is common. Even preserved EF patients showed subtle changes in myocardial deformation, suggesting subclinical myocardial injury. During an abbreviated follow-up, there was good recovery of systolic function but persistence of diastolic dysfunction and no coronary aneurysms. Condensed abstract Multisystem inflammatory syndrome in children (MIS-C) is an illness that resembles Kawasaki Disease (KD) or toxic shock, reported in children with a recent history of COVID-19 infection. This study analyzed echocardiographic manifestations of this illness. In our cohort of 28 MIS-C patients, left ventricular systolic and diastolic function were worse than in classic KD. These functional parameters correlated with biomarkers of myocardial injury. However, coronary arteries were typically spared. The strongest predictors of myocardial injury were global longitudinal strain, right ventricular strain, and left atrial strain. During subacute period, there was good recovery of systolic function, but diastolic dysfunction persisted.

Background The superior cavo‐pulmonary connection was introduced at our institution in 1988 for infants undergoing surgery for hypoplastic left heart syndrome. Patients with hypoplastic left heart syndrome remain at high risk for mortality in the time period between the Norwood procedure and the superior cavo‐pulmonary connection. The primary objectives of this study were to compare interstage mortality across 4 eras and analyze factors that may impact interstage mortality. Methods and Results Patients with hypoplastic left heart syndrome who underwent the Norwood procedure, were discharged from the hospital, and were eligible for superior cavo‐pulmonary connection between January 1, 1988, and December 31, 2017, were included. The study period was divided into 4 eras based on changes in operative or medical management. Mortality rates were estimated with 95% CIs. Adjusted and unadjusted logistic regression models were used to identify risk factors for mortality. There were 1111 patients who met the inclusion criteria. Overall, interstage mortality was 120/1111 (10.8%). Interstage mortality was significantly lower in era 4 relative to era 1 (4.6% versus 13.4%; P =0.02) during the time that age at the superior cavo‐pulmonary connection was the lowest (135 days; P P =0.02) and was more routinely practiced in era 4. Conclusions During this 30‐year experience, the risk of interstage mortality decreased significantly in the most recent era. Factors that coincide with this finding include younger age at superior cavo‐pulmonary connection, introduction of an interstage monitoring program, and increased use of the right ventricle to pulmonary artery shunt.

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was "indicated." Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2-25% for RL 5, and 0-5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Objectives In-hospital complications after the Norwood operation for single ventricle heart defects account for the majority of morbidity and mortality. Inpatient care variation occurs within and across centers. This multidisciplinary quality improvement project standardized perioperative management in a large referral center. Design Quality improvement project. Setting High volume cardiac center, tertiary care children's hospital. Patients Neonates undergoing Norwood operation. Interventions The quality improvement team developed and implemented a clinical guideline (preoperative admission to 48 hr after surgery). The composite process metric, Guideline Adherence Score, contained 13 recommendations in the guideline that reflected consistent care for all patients. Measurements and main results One-hundred two consecutive neonates who underwent Norwood operation (January 1, 2013, to July 12, 2016) before guideline implementation were compared with 50 consecutive neonates after guideline implementation (July 13, 2016, to May 4, 2018). No preguideline operations met the goal Guideline Adherence Score. In the first 6 months after guideline implementation, 10 of 12 operations achieved goal Guideline Adherence Score and continued through implementation, reaching 100% for the last 10 operations. Statistical process control analysis demonstrated less variability and decreased hours of postoperative mechanical ventilation and cardiac ICU length of stay during implementation. There were no statistically significant differences in major hospital complications or in 30-day mortality. A higher percentage of patients were extubated by postoperative day 2 after guideline implementation (67% [30/47] vs 41% [41/99], respectively; p = 0.01). Of these patients, reintubation within 72 hours of extubation significantly decreased after guideline implementation (0% [0/30] vs 17% [7/41] patients, respectively; p = 0.02). Conclusions This initiative successfully implemented a standardized perioperative care guideline for neonates undergoing the Norwood operation at a large center. Positive statistical process control centerline shifts in Guideline Adherence Score, length of postoperative mechanical ventilation, and cardiac ICU length of stay were demonstrated. A higher percentage were successfully extubated by postoperative day 2. Establishment of standard processes can lead to best practices to decrease major adverse events.

Objective To evaluate practice variation in pharmacologic management in the International Kawasaki Disease Registry (IKDR). Study design Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described. Results We included 1627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23 out of 30 centers, (77%) infliximab was also used; 11 of these 23 centers reported using it in 20% of patients. Nonsteroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in patients with large/giant CAAs. Statins (2.7%, all patients) were mostly used in one center and only in patients with large/giant CAAs. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their patients with large/giant CAAs. Conclusions In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

Background In shunt‐dependent, single‐ventricle patients, mortality remains high in the interstage period between discharge after neonatal surgery and stage 2 operation. We sought to evaluate the impact of our infant single‐ventricle management and monitoring program ( ISVMP ) on interstage mortality and stage 2 outcomes. Methods and Results This retrospective single‐center cohort study compared patients enrolled in ISVMP at hospital discharge with historical controls. The relationship of ISVMP to interstage mortality was determined with a bivariate probit model for the joint modeling of both groups, using an instrumental variables approach. We included 166 ISVMP participants (December 1, 2010, to June 30, 2015) and 168 controls (January 1, 2007, to November 30, 2010). The groups did not differ by anatomy, gender, race, or genetic syndrome. Mortality was lower in the ISVMP group (5.4%) versus controls (13%). An ISVMP infant compared with a historical control had an average 29% lower predicted probability of interstage death (adjusted probability: −0.29; 95% CI , −0.52 to −0.057; P =0.015). On stratified analysis, mortality was lower in the hypoplastic left heart syndrome subgroup undergoing Norwood operation (4/84 [4.8%] versus 12/90 [14%], P =0.03) but not in those with initial palliation of shunt only ( P =0.90). ISVMP participants were younger at the time of the stage 2 operation (138 versus 160 days, P Conclusions In this single‐center study, we report significantly lower interstage mortality for participants with hypoplastic left heart syndrome enrolled in ISVMP . Younger age at stage 2 operation was not associated with postoperative mortality or longer length of stay.

The anatomy and physiology of adults with congenital heart disease place them at increased risk for thrombosis. This chapter discusses the most common thromboses, namely, deep venous thrombosis, pulmonary embolism, arrhythmias and thromboembolic stroke, thrombosis associated with prosthetic valves, and special concerns of the adult with Fontan circulation. The chapter closes with a discussion of therapeutics for thrombosis prevention and management.

Commonly used pediatric anticoagulants include unfractionated heparin, low molecular weight heparin, and vitamin K antagonists. Their use in pediatrics continues to be challenging secondary to modes of administration, less predictable pharmacokinetics, and complex drug-dietary interactions. Newer agents, notably factor Xa inhibitors and direct thrombin inhibitors, may offer solutions to some of these challenges although there are potential pitfalls since these medications have not been extensively studied within the pediatric patient population to date. This article serves to review the current established anticoagulants used in pediatrics, specifically among patients with congenital and acquired heart disease, explore several new clinical trials for use of factor Xa inhibitors and direct thrombin inhibitors in pediatrics, and discuss the future role of these new agents in children with heart disease.

© 2015 Elsevier Inc. All rights reserved. Background Cardiac disease is a leading cause of stroke in children, yet limited data support the current stroke prevention and treatment recommendations. A multidisciplinary panel of clinicians was convened in February 2014 by the International Pediatric Stroke Study group to identify knowledge gaps and prioritize clinical research efforts for children with cardiac disease and stroke. Results Significant knowledge gaps exist, including a lack of data on stroke incidence, predictors, primary and secondary stroke prevention, hyperacute treatment, and outcome in children with cardiac disease. Commonly used diagnostic techniques including brain computed tomography and ultrasound have low rates of stroke detection, and diagnosis is frequently delayed. The challenges of research studies in this population include epidemiologic barriers to research such as small patient numbers, heterogeneity of cardiac disease, and coexistence of multiple risk factors. Based on stroke burden and study feasibility, studies involving mechanical circulatory support, single ventricle patients, early stroke detection strategies, and understanding secondary stroke risk factors and prevention are the highest research priorities over the next 5-10 years. The development of large-scale multicenter and multispecialty collaborative research is a critical next step. The designation of centers of expertise will assist in clinical care and research. Conclusions There is an urgent need for additional research to improve the quality of evidence in guideline recommendations for cardiogenic stroke in children. Although significant barriers to clinical research exist, multicenter and multispecialty collaboration is an important step toward advancing clinical care and research for children with cardiac disease and stroke.

Objective Objectives To describe the results of a clinical practice pathway (CPP) for the management of postcatheterization pulse loss in a children's hospital. Background Standardized approaches to the diagnosis and management of postcatheterization arterial thrombus are lacking. As a result, substantial practice variation exists. Methods Data collected prospectively for quality improvement purposes were retrospectively reviewed. Results Since initiation of the CPP, 93/1,672 (5.4%) catheterizations resulted in pulse loss at a median patient age and weight of 73 days (1 day–5.8 years) and 4.8 kg (2–14.1 kg). Arterial thrombus was documented by ultrasound (US) in 85. Of these, 66 resolved by 12 weeks of therapy, seven patients died, and four were lost to follow-up before completing treatment. Eight patients had persistent thrombus despite a full treatment course (89% success rate in those able to complete treatment). Of patients treated with unfractionated heparin as initial therapy, 46% (17/37) achieved a therapeutic partial thromboplastin time within 12 hr with 19% (67/343) of all levels therapeutic. As a result, the CPP was modified to use enoxaparin as first line agent, of which 57% (41/72) had a therapeutic anti-Xa level after the 2nd dose and 88% by the 4th dose. No bleeding complications were observed. A priori established process metrics were achieved. Conclusions A CPP utilizing early initiation of anticoagulation and US to aid diagnosis of postcatheterization arterial thrombus and response to therapy is feasible and effective. In those able to complete up to 12 weeks of treatment, resolution occurs in nearly 90%. © 2014 Wiley Periodicals, Inc.

Hypoplastic left heart syndrome is associated with a substantial interstage mortality between the Stage I neonatal Norwood operation and the Stage II bidirectional cavopulmonary anastomosis. One of the many endeavors to reduce interstage mortality has been the development of interstage home monitoring programs. We review the efficacy of interstage monitoring programs in general and in particularly at our center and conclude that interstage monitoring does make a difference. All programs, however, are not the same. Further research is needed to ascertain which facets of interstage monitoring truly impact outcomes and restructure monitoring programs as such.

Pediatric cardiology patients are at high risk of developing venous thromboembolism (VTE). Previously, our Cardiac Center had no consensus on VTE diagnosis, treatment or outpatient management. As part of a multidisciplinary initiative to optimize thrombosis management, members of the Cardiology and

Thrombosis has long been recognized as a potentially life-threatening complication in children with congenital heart disease (CHD), children with acquired heart disease, and in adults with CHD. High-risk groups include patients with shunt- dependent single ventricles (shunt thrombosis, 8%–12%; 4%

The objective of this article is to review the particular tendencies as well as specific concerns of bleeding and clotting in children with critical cardiac disease. MEDLINE and PubMed. Children with critical heart disease are at particular risk for bleeding and clotting secondary to intrinsic as well as extrinsic factors. We hope that this review will aid the clinician in managing the unique challenges of bleeding and clotting in this patient population, and serve as a springboard for much needed research in this area.

Objective Thrombotic complications are increasingly being recognized as a significant cause of morbidity and mortality in pediatric and congenital heart disease. The objective of this article is to review the medications currently available to prevent and treat such complications. Data sources Online searches were conducted using PubMed. Study selection Studies were selected for inclusion based on their scientific merit and applicability to the pediatric cardiac population. Data extraction Pertinent information from each selected study or scientific review was extracted for inclusion. Data synthesis Four classes of medications were identified as potentially beneficial in this patient group: anticoagulants, antiplatelet agents, thrombolytic agents, and novel oral anticoagulants. Data on each class of medication were synthesized into the follow sections: mechanism of action, pharmacokinetics, dosing, monitoring, reversal, considerations for use, and evidence to support. Conclusions Anticoagulants, antiplatelet agents, and thrombolytic agents are routinely used successfully in the pediatric patient with heart disease for the prevention and treatment of a wide range of thrombotic complications. Although the novel oral anticoagulants have been approved for a limited number of indications in adults, studies on the safety and efficacy of these agents in children are pending.

Hospital-acquired thrombosis (HAT) in children with congenital and acquired heart disease may be life-threatening. Children

Preoperative pulmonary vascular disease remains an important risk factor for death or right-heart failure in selected children undergoing two-ventricle repair, single-ventricle palliation, or heart transplantation. Preoperative criteria for poor outcome after operation remain unclear. The purpose of this review is to critically assess both the historic and current data and make recommendations where appropriate. An extensive literature search was undertaken in October 2009. Data were analyzed by an expert multidisciplinary team and recommendations were made by consensus. PubMed was searched in October 2009. Data were analyzed and recommendations were made by consensus of a multidisciplinary team. In patients with suspected pulmonary vascular disease anticipating a two-ventricle repair, although preoperative testing via cardiac catheterization with vasodilators is reasonable, the preoperative parameters and the precise values of these parameters that best correlate with early and late outcome remain unclear. Further investigation is warranted in selected populations, such as the growing group of children with congenital heart disease complicated by chronic lung disease of prematurity, and in the developing world where patients may be more likely to present late with advanced pulmonary vascular disease. In patients with a functional single ventricle, there is growing evidence that mean pulmonary artery pressure of >15 mm Hg may be associated with both early and late mortality after the Fontan operation. The relationship of preoperative pulmonary hemodynamics to early and late morbidity remains to be defined. There most likely is a level of preoperative pulmonary vascular disease that puts an individual patient at increased risk for death or severe cyanosis after a bidirectional cavopulmonary anastomosis. It remains unclear, however, how to best assess this risk preoperatively. The limitations in obtaining an accurate assessment of pulmonary vascular disease in the complex single ventricle are discussed. In children awaiting cardiac transplantation with elevated pulmonary vascular disease of >6 U.m and/or transpulmonary gradient of >15 mm Hg, heart transplantation is deemed feasible in most transplant centers if the administration of inotropes or vasodilators can decrease the pulmonary vascular disease to

Although pediatric cardiac critical care, as a distinct field of interest, is a relatively recent development, treating critically ill patients has always been a substantial part of clinical pediatric cardiology. In addition, even pediatric cardiologists who do not provide primary care for

Children with congenital and acquired heart disease are at risk for thrombotic events which, along with complications from thromboprophylaxis and antithrombotic therapy, are increasingly recognized as important contributors to morbidity and mortality in this heterogeneous group of patients.1 The prevalence and clinical relevance of thrombosis in these populations are influenced by developmental,2 acquired, and hemodynamic factors.3 Nevertheless, the pathophysiology, incidence, associated risk factors, and optimal strategies for prevention, detection/surveillance, and management of thrombosis in these populations have not been clearly defined by rigorous clinical investigations. The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group meeting on June 14 to 15, 2012 in Bethesda, Maryland, to explore the issues relevant to thrombosis in children with heart disease. The goals of the Working Group were to (1) review the current state of knowledge about thrombosis and incorporate additional knowledge derived from studies and guidelines relevant to adult populations, (2) identify gaps in the evidence base and prioritize opportunities for using basic and clinical research, and (3) identify common methodological issues and potential solutions to those issues for future studies in children. Given the broad topic, we purposely excluded discussion of cardiopulmonary bypass and extracorporeal membrane oxygenation, because these 2 topics are associated with unique issues and were thought to be beyond the focus of the Working Group. The Working Group consisted of experts in pediatric cardiology, hematology and neurology, adult cardiology and hematology, basic science of coagulation, imaging, clinical trial methodologies, quantitative analyses, and the dissemination and implementation of guidelines, along with representatives from the pharmaceutical industry and the Food and Drug Administration. This article represents the Working Group’s discussions on evidence gaps, challenges for this population, and recommendations for strategic research. There is insufficient evidence to guide the surveillance, prevention, and treatment of thrombosis in …

Objectives To describe the results of a clinical practice pathway (CPP) for the management of postcatheterization pulse loss in a children's hospital.Standardized approaches to the diagnosis and management of postcatheterization arterial thrombus are lacking. As a result, substantial practice variation exists.Data collected prospectively for quality improvement purposes were retrospectively reviewed.Since initiation of the CPP, 93/1,672 (5.4%) catheterizations resulted in pulse loss at a median patient age and weight of 73 days (1 day-5.8 years) and 4.8 kg (2-14.1 kg). Arterial thrombus was documented by ultrasound (US) in 85. Of these, 66 resolved by 12 weeks of therapy, seven patients died, and four were lost to follow-up before completing treatment. Eight patients had persistent thrombus despite a full treatment course (89% success rate in those able to complete treatment). Of patients treated with unfractionated heparin as initial therapy, 46% (17/37) achieved a therapeutic partial thromboplastin time within 12 hr with 19% (67/343) of all levels therapeutic. As a result, the CPP was modified to use enoxaparin as first line agent, of which 57% (41/72) had a therapeutic anti-Xa level after the 2nd dose and 88% by the 4th dose. No bleeding complications were observed. A priori established process metrics were achieved.A CPP utilizing early initiation of anticoagulation and US to aid diagnosis of postcatheterization arterial thrombus and response to therapy is feasible and effective. In those able to complete up to 12 weeks of treatment, resolution occurs in nearly 90%. © 2014 Wiley Periodicals, Inc.

Paroxysmal atrial fibrillation and atrial tachycardia may originate from a focal source in one or multiple pulmonary veins. A focal origin facilitates a potential cure amendable to radiofrequency ablation. Herein we report the case of a 16 year old adolescent male with a tachycardia induced cardiomyopathy who presented with very frequent paroxysmal episodes of atrial fibrillation, atrial flutter and atrial tachycardia. The origin of the arrhythmia was mapped to the secondary branches of the left lower pulmonary vein using an octapolar micro-mapping catheter. Immediately following application of three radiofrequency lesions, angiography of the left lower pulmonary vein revealed a region of focal stenosis at the site of energy application, with delayed pulmonary venous emptying. Attempts to relieve any element of spasm using direct administration of nitroglycerin were unsuccessful. Three months later repeat catheterization revealed an unchanged region of tight anatomical stenosis. Balloon dilation of two stenotic areas resulted in dramatic relief of the obstruction and improved venous drainage. Recatheterization 6 months later revealed mild restenosis that was successfully redilated. Intracardiac ultrasound demonstrated focal constriction. Care should be exercised in attempting RF ablation in distal arborization sites of the pulmonary veins in children, because of the small caliber compared to adult subjects. Radiofrequency induced focal areas of stenosis may be amenable to balloon catheter dilation.

Children in the cardiac intensive care unit (CICU) with congenital or acquired heart disease are at risk for hematologic complications, both hemorrhage and thrombosis. The overall incidence of hematologic complications in the CICU is unknown, but risk factors and target groups have been identified where the essential physiologic balance between bleeding and clotting has been disrupted. Although the best management of life-threatening bleeding and clotting is prevention, the cardiac intensivist is often faced with managing life-threatening hematologic events involving patients from within the unit or those who present from outside. Part I of this review deals with the propensity of children with congenital and acquired heart disease to complications of both bleeding and clotting, and includes discussions of perioperative bleeding, thromboses in single-ventricle patients, clotting of Blalock-Taussig shunts and thrombotic complications of mechanical valves. Part II deals with the subject of stroke in children with heart disease. Part III reviews monitoring the effectiveness of anticoagulation and thrombolysis in the CICU. Currently available diagnostics modalities, medications and management strategies are reviewed and future directions discussed.

BACKGROUND Neonates with pulmonary atresia and intact ventricular septum (PA-IVS) are frequently born with hypoplastic right heart structures that must grow after right ventricular decompression (RVD) procedures for a complete two-ventricle physiology to be achieved. Previous authors have asserted that neonatal right heart size or morphology will predict right heart growth potential. Since 1983, our bias has favored early RVD regardless of initial right heart size. In 1986, we recognized a subset of patients with coronary artery abnormalities associated with poor outcome after RVD and have defined these patients as having a right ventricular-dependent coronary circulation (RVDCC). METHODS AND RESULTS To assess the influence of right heart size on outcome independent of the presence of RVDCC, we measured echocardiographic right ventricular (RV) dimensions in 37 neonates with adequate studies presenting between 1983 and 1990. Coronary artery anatomy was adequately assessed by angiography in 36. RV volume and tricuspid valve (TV) diameter were significantly smaller in patients with RVDCC than in those without. However, there was no statistically significant association between RV volume or TV diameter and survival among patients with or without RVDCC: Among 29 patients without RVDCC, 23 of 24 (95.8%) who achieved RVD are alive compared with 1 of 5 (20%) who did not achieve RVD (P = .001). Twenty-one of the 23 survivors have a complete two-ventricle physiology with low right atrial pressure. Among 7 patients with RVDCC, 2 patients who underwent RVD died early of left ventricular failure, whereas 4 of 5 who did not undergo RVD have survived single ventricular palliation. CONCLUSIONS Small right heart size is associated with RVDCC but is not associated with survival in PA-IVS. Patients without RVDCC have improved survival after RVD regardless of neonatal right heart size.