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Severe forms of pulmonary embolism (PE) in children are rare but cause significant morbidity and mortality. In this article, we review the pathophysiology of severe (high- and intermediate-risk) PE and suggest novel pediatric-specific risk stratifications and an acute treatment algorithm to expedite emergent decision making. We define pediatric high-risk PE as causing cardiopulmonary arrest, sustained hypotension or normotension with signs or symptoms of shock. Rapid primary reperfusion should be pursued with either surgical embolectomy or systemic thrombolysis in conjunction with a heparin infusion and supportive care as appropriate. We define pediatric intermediate-risk PE as those without systemic hypotension nor compensated shock but with evidence of right ventricular strain by imaging and/or myocardial necrosis by elevated cardiac troponin levels. The decision to pursue primary reperfusion in this group is complex and should be reserved for patients with more severe disease; anticoagulation alone may also be appropriate in some cases. If primary reperfusion is pursued, catheter-based therapies may be beneficial. In summary, acute management of severe PE in children may include systemic thrombolysis, surgical embolectomy, catheter-based therapies or anticoagulation alone, and may depend on patient and institutional factors. Pediatric emergency and intensive care physicians should be familiar with the risks and benefits of each therapy in order to expedite care. PE Response Teams may also have added benefit in streamlining care during these critical events.

Background: Cardiac manifestations in multisystem inflammatory syndrome in children (MIS-C) occur in ∼80% of patients. Left ventricular (LV) systolic dysfunction is the most frequent cardiac finding. Methods: In this single-centre, retrospective cohort study, we report on detailed assessment of LV function in MIS-C patients using strain and strain rate analysis. We compare those with normal peak systolic strain z-scores (both longitudinal and circumferential strain) to those with abnormal peak systolic strain z-scores (decreased circumferential and/or longitudinal strain). Results: Among 25 patients, 14 (56%) were male, 20 (80%) were Black or Hispanic, 13 (52%) were overweight/obese, and the median age was 11.4 years (interquartile range: 7.5 to 16). Median ejection fraction (EF) was 55.2% (interquartile range: 48.3% to 58%), with the abnormal strain patients having a lower EF (P < 0.01). Demographics were similar between groups. The abnormal strain patients had more organ systems involved and were more likely to require inotropic support. In a comparison of MIS-C patients with normal EF (n = 15) to controls, MIS-C patients had lower peak systolic strain as well as lower early diastolic strain rates. In patients with initially depressed function, EF normalized in 8 of 10 (80%), but 4 of 11 (36%) patients had persistently abnormal systolic strain after discharge. Conclusions: LV systolic dysfunction is common in the acute phase of MIS-C, and detection may be improved with strain imaging. Longitudinal cardiac follow-up is imperative, as some patients may be at risk for persistent LV dysfunction. Résumé: Contexte: Des manifestations cardiaques sont observées chez environ 80 % des patients atteints du syndrome inflammatoire multisystémique de l'enfant (SIM-E). La dysfonction systolique ventriculaire gauche est le problème cardiaque observé le plus fréquemment. Méthodologie: Dans cette étude de cohorte rétrospective et unicentrique, nous rapportons les résultats d'une évaluation détaillée de la fonction ventriculaire gauche chez des patients atteints du SIM-E sous l'angle de l'étude des contraintes et des taux de contrainte. Nous comparons les patients dont les écarts z des pics de contrainte systolique sont normaux (contraintes tant longitudinales que circonférentielles) et ceux dont les écarts z des pics de contrainte systolique sont anormaux (réduction de la contrainte circonférentielle ou longitudinale). Résultats: Sur 25 patients, 14 (56 %) étaient de sexe masculin, 20 (80 %) étaient noirs ou hispaniques, 13 (52 %) étaient en surpoids ou obèses, et l'âge médian était de 11,4 ans (intervalle interquartile : de 7,5 à 16). La fraction d'éjection (FE) médiane était de 55,2 % (intervalle interquartile : de 48,3 % à 58 %), et était moins élevée chez les patients présentant une contrainte anormale (p < 0,01). Les caractéristiques démographiques étaient comparables dans tous les groupes. Les patients chez lesquels la contrainte était anormale présentaient un plus grand nombre d'organes atteints et étaient plus susceptibles de nécessiter un soutien inotrope. Comparativement au groupe témoin, les patients SIM-E ayant une FE normale (n = 15) présentaient un pic de contrainte systolique moins élevé et des taux de contrainte diastolique précoce plus faibles. Chez les patients dont la fonction était déprimée à l'origine, la FE s'est normalisée chez huit patients sur 10 (80 %), mais quatre sur 11 (36 %) présentaient une contrainte systolique persistant après leur sortie de l'hôpital. Conclusions: La dysfonction systolique ventriculaire gauche est fréquente dans la phase aiguë du SIM-E, et son repérage pourrait être amélioré par l'imagerie permettant de visualiser les contraintes. Un suivi cardiaque longitudinal est impératif, car certains patients peuvent être à risque de souffrir d'une dysfonction ventriculaire gauche persistante.

BACKGROUND The size of the Fontan population with end-stage heart failure is growing. In this population, heart transplantation has been the only option. This study sought to investigate the efficacy of ventricular assist device (VAD) support in Fontan patients. METHODS We conducted a retrospective study of Fontan patients in the Advanced Cardiac Therapies Improving Outcomes Network. We evaluated patient characteristics, and the clinical and physiologic outcomes after VAD implantation. RESULTS We identified 45 Fontan patients implanted with VAD. The average age of patients was 10 years (interquartile range: 4.5–18) and 30% were female. The majority had a morphologic right ventricle (69%), moderate or greater ventricular dysfunction (83%), and moderate or greater atrioventricular valve regurgitation (65%). The majority of implants were as a bridge to transplantation (76%), and the majority of patients were Interagency Registry for Mechanically Assisted Circulatory Support Profile 2 (56%). The most commonly employed device was the Medtronic HeartWare HVAD (56%). A total of 13 patients were discharged on device support, and 67% of patients experienced adverse events, the most common of which were neurologic (25%). At 1 year after device implantation, the rate of transplantation was 69.5%, 9.2% of patients continued to be VAD supported, and 21.3% of patients had died. Hemodynamically, VAD was effective in decreasing both Fontan and ventricular end-diastolic pressures in some individuals. CONCLUSIONS VAD is effective in supporting patients with end-stage Fontan failure awaiting heart transplantation. Future research should focus on identifying clinical and physiologic characteristics predictive of a favorable response to VAD support.

BACKGROUND The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 ( n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease , and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin . Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events , including major bleeding, were reduced in the PSS group. CONCLUSIONS The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Pediatric heart failure is a complex, heterogenous syndrome that occurs relatively rarely in children, but carries a high burden of morbidity and mortality. This article reflects on the current state of medical therapy for both acute and chronic pediatric heart failure, based on expert consensus guidelines, and the extrapolation of data from trials performed in adults. For the management of acute heart failure specifically, we rely on an initial assessment of the perfusion and volume status of a patient, to guide medical therapy. This paradigm was adapted from adult studies that demonstrated increased morbidity and mortality in heart failure patients whose hemodynamics or examination findings were consistent with a PCWP >18 mmHg and a CI ≤2.2 L/min/m(2). The cornerstone of treatment in the acute setting therefore relies on achieving a euvolemic state with adequate cardiac output. In the chronic setting, patients are typically maintained on a regimen of an angiotensin converting enzyme inhibitor, a beta-blocker, and spironolactone. For those with refractory heart failure, intravenous milrinone therapy has become a mainstay of bridging children to cardiac transplantation. The pediatric-specific data driving these clinical practices are limited and often times, conflicting. The future of pediatric heart failure depends on collaboration, quality improvement, and a commitment to pediatric-specific indications for new medical and device therapies.

In this manuscript, we review the diagnosis, causes, and management of cardiac thrombosis in children with congenital and acquired heart disease. Indications for invasive management and surgery are discussed. The differential diagnostic considerations and management of cardiac thromboses will be reviewed, including those that occur as a consequence of repair and palliation of congenital heart disease. The definition of venous thromboembolism has recently been expanded to include thromboses within both the right and left heart chambers. Direct thrombin inhibitors (DTIs) and direct oral anticoagulants (DOACs) are emerging as treatment alternatives to the heparins and vitamin K antagonists for the management of thrombosis in pediatric heart disease. Thrombosis within the heart occurs as a consequence of abnormalities and alterations in blood flow resulting in stasis and turbulence. Children with acquired and congenital heart disease carry a number of risk factors in Virchow’s triad. Thrombosis can occur throughout any part of the cardiovascular system in congenital heart disease and after surgery for repair or palliation of defects.

Inborn errors of metabolism (IEM) involving the non-oxidative pentose phosphate pathway (PPP) include the two relatively rare conditions, transketolase deficiency and transaldolase deficiency, both of which can be difficult to diagnosis given their non-specific clinical presentations. Current biochemical testing approaches require an index of suspicion to consider targeted urine polyol testing. To determine whether a broad-spectrum biochemical test could accurately identify a specific metabolic pattern defining IEMs of the non-oxidative PPP, we employed the use of clinical metabolomic profiling as an unbiased novel approach to diagnosis. Subjects with molecularly confirmed IEMs of the PPP were included in this study. Targeted quantitative analysis of polyols in urine and plasma samples was accomplished with chromatography and mass spectrometry. Semi-quantitative unbiased metabolomic analysis of urine and plasma samples was achieved by assessing small molecules via liquid chromatography and high-resolution mass spectrometry. Results from untargeted and targeted analyses were then compared and analyzed for diagnostic acuity. Two siblings with transketolase (TKT) deficiency and three unrelated individuals with transaldolase (TALDO) deficiency were identified for inclusion in the study. For both IEMs, targeted polyol testing and untargeted metabolomic testing on urine and/or plasma samples identified typical perturbations of the respective disorder. Additionally, untargeted metabolomic testing revealed elevations in other PPP metabolites not typically measured with targeted polyol testing, including ribonate, ribose, and erythronate for TKT deficiency and ribonate, erythronate, and sedoheptulose 7-phosphate in TALDO deficiency. Non-PPP alternations were also noted involving tryptophan, purine, and pyrimidine metabolism for both TKT and TALDO deficient patients. Targeted polyol testing and untargeted metabolomic testing methods were both able to identify specific biochemical patterns indicative of TKT and TALDO deficiency in both plasma and urine samples. In addition, untargeted metabolomics was able to identify novel biomarkers, thereby expanding the current knowledge of both conditions and providing further insight into potential underlying pathophysiological mechanisms. Furthermore, untargeted metabolomic testing offers the advantage of having a single effective biochemical screening test for identification of rare IEMs, like TKT and TALDO deficiencies, that may otherwise go undiagnosed due to their generally non-specific clinical presentations.

Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in pediatric patients are mild or asymptomatic. However, infants have emerged at higher risk of hospitalization and severe outcomes in pediatric coronavirus disease 2019 (COVID-19). We report a case series of 4 full-term neonates hospitalized with fever and found to have SARS-CoV-2 infection with a spectrum of illness severities. Two neonates required admission to the intensive care unit for respiratory insufficiency and end organ involvement. Half of the patients were found to have a coinfection. One neonate received antiviral therapy with remdesivir and is, to our knowledge, the youngest patient to receive this drug for COVID-19. All neonates had favorable outcomes.

BACKGROUND The HeartMate 3 ventricular assist device (VAD) is a newer centrifugal continuous-flow VAD used for bridge-to-transplant and destination therapy in adults. However, there is limited experience regarding its use in children and adults with complex congenital heart disease (CHD). METHODS The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a multicenter learning network comprised of pediatric hospitals implanting VADs in children and adults with complex CHD. We examined the outcomes of patients undergoing HeartMate 3 implantation at an ACTION center between December 2017 and September 2019. RESULTS The HeartMate 3 was implanted in 35 patients at 9 ACTION centers, with a median age of 15.7 (8.8–47.3) years, median weight of 65.7 (19.1–114.1) kg, and median body surface area (BSA) of 1.74 (0.78–2.36) m2. Of the cohort, 14 patients (40%) weighed CONCLUSIONS Use of the HeartMate 3 in ACTION centers was associated with a low incidence of mortality and adverse events. Patients as small as 19 kg (BSA 0.78 m2) were successfully implanted and supported, indicating that this device may be appropriate for older children and small adults.

OBJECTIVE: To characterize viscoelastic testing profiles of children with multisystem inflammatory syndrome in children (MIS-C). METHODS: This single-center retrospective review included 30 patients diagnosed with MIS-C from March 1 to September 1, 2020. Thromboelastography (TEG) with platelet mapping was performed in 19 (63%) patients and compared to age- and sex-matched controls prior to cardiac surgery. Relationships between TEG parameters and inflammatory markers were assessed using correlation. RESULTS: Patients with MIS-C had abnormal TEG results compared to controls, including decreased kinetic (K) time (1.1 vs. 1.7 minutes, p

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a variably penetrant disease increasingly identified in young patients. OBJECTIVES: This study sought to describe the diverse phenotype, genotype, and outcomes in pediatric and adolescent patients. METHODS: Records from 1999 to 2016 were reviewed for individuals age

Background The influence of ventricular assist device (VAD) use in the care of children with end-stage heart failure is growing rapidly through increasing numbers, new devices, expanding indications, and improving outcomes. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Institutes of Health–sponsored United States database, provides a platform to understand this emerging population. Methods Between September 19, 2012, and December 31, 2017, 30 hospitals implanted 508 devices in 423 patients aged younger than 19 years. This past year was one of evolution for the database as its management was transitioned to The Society of Thoracic Surgery; therefore, this report does not include data from institutions not under contract by August 1, 2018. Results Of the 423 patients, the diagnosis was cardiomyopathy in 261 (62%), myocarditis in 48 (11%), other in 28 (7%), and congenital heart disease (CHD) in 86 (20%), with 52 of these patients having single-ventricle physiology. The two most common support strategies included left VAD in 342 (81%) and biventricular assist device in 64 (15%). Positive outcome (alive on device or bridge to transplantation/recovery) was 80% at 6 months (overall mortality of 20%). The patient cohort for implantable continuous-flow (IC) pumps (n = 197; age at implant, 13.4 ± 3.8 years; 19% Interagency Registry for Mechanically Assisted Circulatory Support [Intermacs] profile 1, 21% intubated at implant, and 12% with CHD) was significantly different from the paracorporeal continuous-flow (PC) pump cohort (n = 79; age, 3.9 ± 5.2 years; 49% Intermacs profile 1, 86% intubated at implant, and 38% with CHD) and the paracorporeal pulsatile (PP) pump cohort (n = 121; age, 3.3 ± 3.9 years; 41% Intermacs profile 1, 77% intubated at implant, and 21% with CHD). Consistent with their cohort composition, device type positive outcomes at 6 months were PC, 63%; PP, 77%; and IC, 92%. Parametric hazard modeling showed an early hazard for death was associated with Intermacs profile 1, biventricular assist device, percutaneous devices, PC devices, small-volume institutions, low age, and low weight, whereas a constant hazard was associated with intubation and liver dysfunction at time of implant. Conclusions IC VADs are the most common VAD type placed in children. The positive outcomes for the IC VADs exceed 90% at 6 months, which may represent our field’s maturation in both patient selection and timing of implantation. The PP/PC devices are currently limited to supporting our most challenging patients, those weighing less than 20 kg and those with CHD. The introduction of new devices and our communities’ commitment to shared learning and improvement will lead to more pediatric lives saved by VAD support and will also focus on improving the quality of life of children supported with VADs.

With growing number of pediatric cases of COVID-19, a unique hyper-inflammatory syndrome, linked to SARS-CoV-2 infection, has emerged in children referred to as multisystem inflammatory syndrome in children (MIS-C). This Kawasaki Disease (KD)-like illness has been described across the world. This syndrome shares features of KD, toxic shock syndrome, and macrophage activation syndrome and is associated with significantly elevated inflammatory markers. Everyday there are new data emerging improving the care of these patients. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative network designed to improve the outcomes of pediatric patients with end-stage heart failure and involves centers from across North America. The committee gathered information concerning COVID-19 anticoagulation practices at various centers and harmonized the data to formulate a set of recommendations.

Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2–6% of children requiring intensive care treatment. However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported. This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease. Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients. Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes. Elevated inflammatory markers and evidence of cytokine storm were frequently observed. A subset of these patients also presented with hypotension and shock (20–100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation. Coronary artery dilation or aneurysms have been described in 6–24%, and arrhythmias in 7–60%. Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase. Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection. Evidence is still scarce but rapidly emerging in the literature. Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time. What is Known:• Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2.What is New:• Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock.• Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias.• Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation.• Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.

Introduction: Thrombosis is a complication associated with Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), Corona Virus Disease 2019 (COVID-19). Although, abnormalities in coagulation markers have been reported in adults with COVID-19, coagulopathy in pediatric patients infected with coronavirus has not been elucidated. Hypothesis: In this study, we evaluated the coagulation profile in pediatric patients with COVID-19 using Thromboelastography (TEG). Methods: This is a retrospective study of pediatric (≤18yrs) patients with seropositive COVID-19 (N=35) regardless of symptom status. Coagulation markers including TEG were obtained from review of medical records under an IRB approved study. All TEG parameters were compared between patients with COVID-19 and age matched controls without COVID-19 (N=35). Results: Regardless of symptom status, COVID-19 patients had significantly lower R-time (5.3±2.7 min vs. 6.5±1.5 min; p=0.03 ), K-time (1.1±0.3 min vs. 1.8±1.1 min; p ) and fibrinolysis (1.7±1.7% vs. 3.2±3.6%; p=0.04 ); and significantly elevated angle (73.6±4.8 deg vs.66.7±6.2 deg; p ), maximum amplitude (68.9±6.1 mm vs. 59.5±8.7 mm; p ) and overall clot strength G (11.7±3.3 Kdynes/cm 2 vs. 7.8±2.4 Kdynes/cm 2 ; p ). Whereas the standard coagulation tests such as PT/INR, PTT, Thrombin time and Heparin levels were within the normal pediatric reference ranges. D-dimer expression was also higher (0.94 μg/ml) in COVID-19 patients compared to the normal pediatric reference range (p ). Conclusions: Abnormal expression of all TEG parameters and D-dimer is consistent with a hypercoagulable profile. TEG may be useful in reducing thrombosis-risk in patients with COVID-19 by guiding anticoagulation management.

Given the adverse event rates involving bleeding and thrombosis among children on ventricular assist devices (VADs), anticoagulant management has become a focal point for quality improvement and innovation. There may be advantages to using direct thrombin inhibitors, such as bivalirudin, though this has not been fully explored. As the percent time in therapeutic range (%TTR) for anticoagulants is classically associated with improved clinical outcomes, we evaluated the %TTR for bivalirudin among pediatric VAD recipients. Using a modification of the Rosendaal method, %TTR was calculated using activated partial thromboplastin time measurements for 11 VAD recipients in the early postoperative period (postoperative days 0-14) and for the duration of VAD support. In the initial 2 weeks after VAD implant, mean %TTR was 68.7 (±13.0). During the entire support course, the mean %TTR improved to 79.6 (±11.0). There was an era effect with improving %TTR in the latter half of the study period. We report very good %TTR for bivalirudin both in the first 2 weeks post implant and this improved over the duration of support. Because %TTR reflects the degree of safety and efficacy in chronic anticoagulation, this relatively high %TTR among a diverse, often critically ill cohort suggests that bivalirudin may be a promising agent. Although this study was underpowered to comprehensively evaluate adverse events on bivalirudin, this represents an important next step for larger scale study.

Thrombotic and bleeding complications have historically been major causes of morbidity and mortality in pediatric ventricular assist device (VAD) support. Standard anticoagulation with unfractionated heparin is fraught with problems related to its heterogeneous biochemical composition and unpredictable pharmacokinetics. We sought to describe the utilization and outcomes in children with paracorporeal VAD support who are treated with direct thrombin inhibitors (DTIs) antithrombosis therapy. Retrospective multicenter review of all pediatric patients (aged

Introduction Guidelines recommend trans-esophageal echocardiography (TEE) for patients with atrial fibrillation (AF) or atrial flutter (AFL) for > 48 hours, due to risk of intra-cardiac thrombus formation. With growing evidence that AFL in adults with structurally normal hearts has less thrombogenic potential compared to AF, and the need for TEE questioned, we compared prevalence of intra-cardiac thrombus detected by TEE in pediatric and congenital heart disease (CHD) patients presenting in AF and AFL. Methods/results Single center, cross-sectional analysis for unique first-time presentations of patients for either AF, AFL or intra-atrial reentrant tachycardia (IART) between 2000-2019. Patients were categorized by presenting arrhythmia (AF vs. AFL/IART), with exclusion of other forms of atrial tachycardia, hemodynamic instability, chronic anti-coagulation prior to TEE, and presentation for reason other than TEE examination for thrombus. A total of 201 patients had TEE with co-diagnosis of AF or AFL. Of these, 105 patients (29 AF, 76 AFL) met inclusion criteria, with no difference in age between AF (median 24.9 years; IQR 18.6-38.3 years) and AFL/IART (23.3 years; 15.4-38.4 years). The prevalence of thrombus in the entire cohort was 9.5%, with no difference between AF (13.8%) and AFL groups (7.9%), p=0.46. Patients with thrombus demonstrated no difference in age, systemic ventricular function, cardiac complexity, or CHADS2/CHA2DS2VASc score at presentation. Conclusions The risk for intra-cardiac thrombus is high in the pediatric and CHD population, with no apparent distinguishing factors to warrant a change in the recommendations for TEE, with all levels of cardiac complexity being at risk for clot. This article is protected by copyright. All rights reserved.

Infants with a single ventricle can develop systemic ventricular dysfunction (SVD) after stage 1 operation, but available information is sparse. We reviewed our patients having Norwood, Sano, or hybrid procedures to better understand this problem. We conducted a retrospective, case-controlled cohort study of 267 patients having stage1 operation, examining outcomes between stages 1 and 2 (survival and subsequent cardiac surgeries), predictor variables, and histology of hearts explanted at transplantation. SVD developed in 32 (12%) patients and resolved in 13 (41%); mean age of onset was 3.0 ± 1.63 months; median = 2.79. SVD was not associated with cardiac anatomy, type of stage 1 procedure, weight, coronary abnormality, or atrioventricular valve regurgitation. The mean age of resolution = 12.1 ± 9.6 months; median = 6.3, and resolution may have been more likely with a systemic LV than RV (p = 0.067). Outcomes for the entire SVD group were less favorable than for those without, but patients with resolution of SVD had outcomes at least as good those without SVD. Myocardial histology (n = 4) suggested chronic ischemia. The risk of SVD after stage 1, while low, may be a fundamental feature of this patient population. SVD occurs with either a systemic RV or LV, although patients with a systemic LV may be more likely to have resolution than those with an RV. We identified no predictor variables, but histologic findings suggest chronic ischemia may be involved. Given the low incidence of SVD, multi-center studies will be required to better define predictors of onset and resolution.

Purpose ACTION (Advanced Cardiac Therapies Improving Outcomes Network) is a multi-faceted quality improvement (QI) and research network with the goal of improving pediatric and congenital heart disease VAD and heart failure (HF) outcomes. This report describes ACTION initiatives. Methods ACTION includes QI, educational activities, and a data registry. Stakeholders include providers, patients and families, and industry partners. The core values of ACTION include collaboration and transparency. ACTION started in 2017, with data collection beginning in April 2018. This report utilizes ACTION data and describes selected completed and ongoing initiatives. Results The ACTION registry report is shared with sites as an interactive dashboard (refreshed monthly). A comprehensive data quality strategy includes data queries and adjudication of critical events. There are 50 US/Canadian sites in the network and 34 of the sites contribute data. There are additional international sites that participate in all activities except patient-level data collection. The registry includes 388 patients implanted with 511 devices with 51,411 device days. DCM (203) and CHD (143) are the major underlying diagnoses. EXCOR (148), HVAD (97), and HM3 (70), are the most common end devices. Survival is 91% (including ongoing support, transplant and wean). AE rates are: stroke 11%, bleeding 21%, and infection 26%. The dashboard allows intuitive examination of subgroups, e.g., stroke/bleeding rate in patients less than 10 kg/on a specific device. Initial QI projects include an initiative (ABC of stroke), that used a bundle of interventions to reduce stroke during VAD support; a discharge planning project; a telehealth support project; and a harmonization initiative to reduce burden of protocol development for sites. Additionally, a patient-facing education website about VAD/HF care is being deployed and a HF project is collecting baseline data for acute decompensated HF. ACTION data have been used to support regulatory (FDA) approval of selected devices. Conclusion ACTION, a collaborative, multi-stakeholder network, has undertaken numerous approaches to improve outcomes for children with HF and VADs. In keeping with the values of transparency and collaboration, the ACTION annual reports will be made available in their entirety in a patient-facing version, via the ACTION website.

Adults with congenital heart disease represent an expanding and unique population of patients with heart failure (HF) in whom the use of mechanical circulatory support (MCS) has not been characterized. We sought to describe overall use, patient characteristics, and outcomes of MCS in adult congenital heart disease (ACHD).All patients entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between June 23, 2006, and December 31, 2015, were included. Patients with ACHD were identified using pre-operative data and stratified by ventricular morphology. Mortality was compared between ACHD and non-ACHD patients, and multivariate analysis was performed to identify predictors of death after device implantation.Of 16,182 patients, 126 with ACHD stratified as follows: systemic morphologic left ventricle (n = 63), systemic morphologic right ventricle (n = 45), and single ventricle (n = 17). ACHD patients were younger (42 years ± 14 vs 56 years ± 13; p0.0001) and were more likely to undergo device implantation as bridge to transplant (45% vs 29%; p0.0001). A higher proportion of ACHD patients had biventricular assist device (BiVAD)/total artificial heart (TAH) support compared with non-ACHD patients (21% vs 7%; p0.0001). More ACHD patients on BiVAD/TAH support were INTERMACS profile 1 compared with patients on systemic left ventricular assist device (LVAD) support (35% vs 15%; p = 0.002). ACHD and non-ACHD patients with LVADs had similar survival; survival was worse for patients on BIVAD/TAH support. BiVAD/TAH support was the only variable independently associated with mortality (early phase hazard ratio 4.4; 95% confidence interval, 1.8-11.1; p = 0.001). For ACHD patients receiving MCS, ventricular morphology was not associated with mortality.ACHD patients with LVADs have survival similar to non-ACHD patients. Mortality is higher for patients requiring BiVAD/TAH support, potentially owing to higher INTERMACS profile. These outcomes suggest a promising role for LVAD support in ACHD patients as part of the armamentarium of therapies for advanced HF.

Background Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute–sponsored North American database, provides a platform to understand this emerging population. Methods Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs. Results Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3–10.0) years for paracorporeal continuous-flow pumps ( n = 60), 1.7 (0.4–5.3) years for paracorporeal pulsatile pumps ( n = 105), and 15.0 (11.3–16.9) years for implantable continuous-flow pumps ( n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high. Conclusions Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications.We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and6; and INRs1.5.In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR6 occurred in 3 patients (4 events); INRs ≥5 6 in 7 patients (12 events); and INR1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients.Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.

Mechanical circulatory support in the form of ventricular assist devices (VADs) in children has undergone rapid growth in the last decade. With expansion of device options available for larger children and adolescents, the field of outpatient VAD support has flourished, with many programs unprepared for the clinical, programmatic, and administrative responsibilities. From preimplantation VAD evaluation and patient education to postimplant VAD management, the VAD program, staffed with an interdisciplinary team, is essential to providing safe, effective, and sustainable care for a new technology in an exceedingly complex patient population. Herein, this paper describes the Boston Children's Hospital VAD experience over a decade and important lessons learned from developing a pediatric program focusing on a high-risk but low-volume population. We highlight the paramount role of the VAD coordinator, clinical infrastructure requirements, as well as innovation in care spanning inpatient and outpatient VAD supports at Boston Children's Hospital.

Purpose Establishing and maintaining target anticoagulation (AC) levels is perceived as a way to mitigate the risk of bleeding and thrombotic complications in pediatric ventricular assist device (VAD) support. To better understand potential reasons of having monitoring labs outside institutionally-set goal ranges, we surveyed centers to understand perceived barriers. Methods As part of the Advanced Cardiac Therapies Improving Outcomes Network (ACTION), a 37-center collaborative, we surveyed participating VAD centers across North America. The survey was comprised of multiple choice questions addressing reasons for out of range coagulation labs. Specifically, asking centers to rate the frequency of occurrences; low, happens rarely, medium, happens often, high, happens almost daily and not applicable, meaning this barrier does not exists. We then weighted the average responses. Results Of the 49 responses received from the pediatric VAD-ACTION centers that responded to a 4-question multiple choice survey, the most commonly reported barrier was contamination of lab samples by sampling from a line infusing an anticoagulant through it in over 65% of respondents. This was followed by multiple providers involved in managing AC and micro-managing lab results as the second and third chosen as barriers reported in just under 50%. Interestingly, lack of documentation and obscure guidelines were not perceived as frequent causes of out of range values. Conclusion While achieving and maintaining stable anticoagulation is the goal of therapy, understanding perceived obstacles is vital to targeted intervention. Targeted interventions to decrease the most common barriers, such as contaminated labs, will guide future ACTION quality improvement initiatives.

Apixaban is well studied in adults; paediatric data are extremely limited. We describe 3 children (age 2–6 years, weight 13–17 kg) with congenital heart disease who developed intracardiac thrombosis, and in whom typical treatments had failed (in 1) or were considered impractical (in 2). All were treated with apixaban 2.5 mg orally twice daily with complete (in 2) or partial (in 1) thrombus resolution and no clinical bleeding events.

Background Enoxaparin is a commonly used anticoagulant for treatment of thrombosis in pediatric patients. Its use in pediatric cardiac patients has not been well described. We sought to examine the utilization trends, dosing, and safety of enoxaparin in pediatric cardiac patients. Methods Retrospective study of pediatric cardiac patients treated with enoxaparin from 2011 to 2018. Starting and final doses of enoxaparin, number of dose adjustments, and time to therapeutic anti-factor Xa level were compared between age groups utilizing the Kruskal Wallis test with the Dunn test for pairwise comparisons. Results Seventy-one patients were treated with 77 courses of enoxaparin. Most enoxaparin courses were started on patients aged >12 months (40%) and for arterial thrombosis (22 patients, 29%). The most common cardiac diagnosis was hypoplastic left heart syndrome (12 patients, 17%). The mean final dose of enoxaparin was significantly different when comparing patients 0–3-month, 3–12 month, and >12 months (2.1 ± 0.5 mg/kg vs. 1.5 ± 0.4 mg/kg vs. 1.2 ± 1.4 mg/kg, respectively; p 12-month age group (0.4 ± 0.4 mg/kg vs. 0.4 ± 0.4 mg/kg vs. 0.1 ± 0.3 mg/kg, respectively; p 12 months (2.2 ± 1.6 vs. 1.4 ± 1.4, p = 0.02). Antiplatelet therapy was used in 74% of courses. Adverse events were rare and had no relationship to antiplatelet use. Conclusions Enoxaparin is an effective and safe anticoagulant in pediatric cardiac patients. Initial enoxaparin dosing should be increased from current recommended doses in patients between 3 and 12 months of age to achieve more timely therapeutic anticoagulation.

Purpose We sought to characterize strokes in children supported with ventricular assist devices (VADs) in the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). Methods All patients entered in the ACTION registry (4/1/2018-6/8/2020) were included. Stroke was defined by pre-specified criteria and categorized as hemorrhagic or ischemic in etiology. All strokes were adjudicated by the data coordinating center and the adjudication committee which is comprised of members from multiple sites. Results Of 270 patients in the ACTION registry, 26 patients (9.6%) experienced 28 strokes (25 ischemic and 3 hemorrhagic). Of these 26 patients, 12 (46%) were ≤1yo, 12 (46%) had congenital heart disease, 8 (26%) had preimplant ECMO use, 23 (88%) were on paracorporeal VADs and 3 (15%) had intracorporeal VADs. The median time to stroke was 17.5 days. There were 11 (39%) and 17 (60%) strokes that occurred within 7 and 30 days, respectively, and all strokes occurring ≤30 days post-implant were ischemic. On paracorporeal VADs, there were 23 ischemic (EXCOR=9, Centrimag=6, Pedimag=6, Rotaflow=2) and 2 hemorrhagic (EXCOR=1, Centrimag=1) strokes. With intracorporeal support there were 2 ischemic (HVAD=1, HM3=1) and 1 hemorrhagic (HVAD=1) strokes. The overall stroke rate was 145.4 per 10,000 patient-days. Mortality rates were significantly higher for patients who did (10/26; 38.5%) vs. those who did not (32/144; 13.1%) experience a stroke (p Conclusion Although the stroke rate in children on VADs has decreased over time, strokes still occur in 1/10 patients and are associated with significantly increased mortality. The large majority of strokes are ischemic in nature, associated with paracorporeal VADs, and occur within the first 30 days after implant. About half of the children experiencing strokes on a VAD are ≤1yo and/or have congenital heart disease. Based on these data, ACTION is focusing ongoing quality improvement projects on decreasing strokes for children on paracorporeal devices with particular attention to the early post-implant period.

Purpose Cardiac disease results in significant morbidity and mortality in patients with muscular dystrophy (MD). Single centers have described their ventricular assist device (VAD) experience in this population, however broader applicability and outcomes remain unknown. Methods We examined outcomes of all patients with MD and dilated cardiomyopathy implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers 9/2012-9/2020. Results A total of 19 VADs were implanted in 18 patients across 10 ACTION sites. The median duration of support was 252 days (range 11-1681 days). The majority of pts had dystrophinopathy (66%) and the median age at implant was 17.2 years (Table). Device strategy was bridge to transplant in 5 (27.8%), 4 of whom survived to transplant. The frequency of a positive outcome (transplanted or alive on device) at 6 months and 1 year were 89% and 84%, respectively (Figure). A single patient suffered a stroke (hemorrhagic), 2 patients developed sepsis, 1 patient developed respiratory failure requiring tracheostomy and 4 patients patient developed right heart failure (1 of whom required temporary right VAD). Conclusion In selected MD patients, VADs can serve as effective bridges to HT and chronic therapy. Right heart failure and infectious complications were relatively common, while stroke and respiratory failure were rare. Further research is needed to understand the patients who may benefit most from VAD therapy in terms of survival and quality of life and how to mitigate the risks the of the adverse events identified in the current report.

Continuous-flow (CF) ventricular assist devices (VADs) have largely replaced pulsatile-flow VADs in adult patients. However, there are few data on CF VADs among pediatric patients. In this study we aimed to describe the overall use, patients' characteristics and outcomes of CF VADs in this population.The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a national registry for U.S. Food and Drug Adminstration (FDA)-approved VADs in patients19 years of age. Patients undergoing placement of durable CF VADs between September 2012 and June 2015 were included and outcomes were compared with those of adults from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS).CF VADs were implanted in 109 patients at 35 hospitals. The median age at implantation was 15 years (2.8 to 18.9 years) and median weight was 62 kg (range 16 to 141 kg). The underlying disease was cardiomyopathy in 89 (82%) patients. The INTERMACS level at time of implant was Level 1 in 20 (19%), Level 2 in 64 (61%) and Levels 3 to 7 in 21 (20%) patients. Most were implanted as LVADs (n = 102, 94%). Median duration of support was 2.3 months (range1 day to 28 months). Serious adverse event rates were low, including neurologic dysfunction (early event rate 4.1 per 100 patient-months with 2 late events). Competing outcomes analysis at 6 months post-implant indicated 61% transplanted, 31% alive with device in place and 8% death before transplant. These outcomes compared favorably with the 3,894 adults supported with CF VADs as a bridge to transplant.CF VADs are commonly utilized in older children and adolescents, with excellent survival rates. Further study is needed to understand impact of patient and device characteristics on outcomes in pediatric patients.

The last five yr have been monumental for the pediatric heart failure community. In the US, the most notable has been the FDA approval of the first pediatric specific device (Berlin Heart EXCOR(®) ; Berlin Heart, Inc., Berlin, Germany). Subsequently, the field of heart failure has gained a great deal of knowledge regarding the nuances of MCS in children. Despite FDA approval in the US, the Berlin EXCOR(®) is only currently indicated for in-hospital use. Due to the limitations with discharge and the positive in- hospital experiences with the Berlin EXCOR(®) , there has been an increased interest in the implantation of adult durable devices into children. While many institutions have focused their intial efforts on the first phase of care within the hospital, they are now ready to tackle the challenge of how to safely transition children to the community setting.

Purpose Ventricular assist devices (VADs) increase waitlist survival, yet the risk of stroke is not trivial. There is a knowledge gap regarding the impact of these strokes on heart transplant outcomes. We sought to analyze how strokes during VAD support impact post-transplant (post-Tx) outcomes in children. Methods 520 pediatric ( Results Overall, there were 146 (28%) VAD patients with a pre-Tx stroke; 86 (59% of stroke patients) of them were transplanted at a median of 57 [17-102] days from stroke, significantly lower than the no stroke cohort (90%; p Conclusion Patients with stroke on VAD once transplanted, enjoy similar survival compared to no stroke patients. Allowing children who suffer stroke while on VAD support to have more time to recover appears to improve post-Tx outcomes.

Purpose The use of intracorporeal continuous flow (CF) ventricular assist devices- namely the Heartware™ HVAD™- has expanded dramatically in the children, with many being discharged home. We sought to evaluate the feasibility and outcomes of children discharged home with point of care (POC) INR monitors for their warfarin anticoagulation management. Methods This is a retrospective single center review of all pediatric patients, aged ≤19 years at time of implantation, who were discharged home for longer than 1 week. Efficacy of warfarin anticoagulation and outcomes were evaluated in those with home POC monitors as compared to children who went to laboratory. Results Between November 11, 2012 and January 1, 2018, a total of 12 patients, 33% female, aged median 14.5 years (range 10-18 years), weighing median 65.8kg (range 18.0-89.5 kg) were discharged home or to rehab with HeartWare as a bridge to transplantation. Underlying diagnosis included dilated cardiomyopathy in 67% (n=8), arrhythmogenic right ventricular dysplasia (ARVD) in 8% (n=1), and biventricular congenital heart disease (CHD) in 25% (n=3).Two patients were discharged to rehab before returning home. All patients were discharged with Coagucheck XS™ POC INR machines, with goal INR of 2-3 in first 3 patients (23%) and goal INR of 2.5-3.5 in later 10 patients. There were a median number of INR tests of 27 (range 1-99) at home, over the course of a median 185 days (25-625) outpatient VAD support days. Overall median time in the therapeutic range(TTR) was 62.1%(range 20.0-70.7%). There was 100% adherence to clinician recommended INR testing at home. There was 4 bridging events with low molecular weight heparin for sub-therapeutic INR. There were no pump thrombosis or other thrombotic events. There were no major bleeding or clinically relevant non major bleeding events. Epistaxis was the most common minor bleeding event that was mitigated by dose reductions and preventative strategies. All patients were bridged to transplantation with no mortality. Conclusion Use if home POC INR machines in children with intracorporeal VADs, in the outpatient setting was associated with 100% adherence to recommended testing regime. Despite low TTR, there was no major bleeding or thrombotic events.

Purpose Pulmonary arterial catheters (PAC) provide real-time hemodynamic data that has been used to tailor ICU therapies, aid in surgical decision making in adults with ADHF and in predicting right-heart failure (RHF) in adults undergoing LVAD evaluation. Approximately 1/3 of patients develop RVF after LVAD insertion. Patients who required rescue RVAD have increased mortality when compared to planned BiVAD implantation. Right ventricular stroke work index (RVSWI) has been demonstrated to predict RHF in adults. Prediction of RHF and data on use of PAC in children are limited. Methods Pediatric patients with ADHF and biventricular circulation undergoing PAC placement at Boston Children's Hospital from 2013 through 2018 were included in this retrospective cohort study. Data were collected as part of an ongoing QI project. Variables predictive of RVF in adults undergoing LVAD implantation were compared between patients with and without RHF. Pedimacs definition of RHF was used for post-VAD patients: RV dysfunction requiring inotropic support at 14 days. Results Thirteen PAC were placed in 11 patients, aged 2 to 18 years old, with biventricular circulation and ADHF. Eight patients had DCM, 2 had CHD and one RCM. Nine PAC were placed to aid in pre-VAD decision making. One to assess awake hemodynamics for transplant candidacy, and one was placed at the time of OHT. Nine PAC were placed by catheterization and 4 in the OR. Mean duration of PAC monitoring was 3.7 days (0.4 to 9.3 days). RVSWI alone was able to significantly predict post-LVAD RVF. All patients free from RVF post-LVAD implantation were discharged home before OHT, at an average or 27 +/-4 days. No patients with RVF reached discharge before transplantation. There were 2 AEs possibly related to the presence of a PAC, including one episode of hemodynamically well-tolerated EAT and one episode of slow VT. Conclusion PAC use in pediatrics is feasible with low rates of adverse events. Low pre-implantation RVSWI was associated with RHF after LVAD implantation. All patients undergoing LVAD implantation with no RHF were discharged home while every patient with RHF remained hospitalized until RVAD implantation or OHT. Arrhythmias occurred in two patients PACs. Though both were hemodynamically stable lines were removed, illustrating the opportunity for managing staff in optimum use of PACs.

Purpose Elevated blood pressure (BP) is a risk factor for stroke in adult ventricular assist device (VAD) patients. There are currently no data or BP management guidelines for pediatric VAD patients. ACTION ( Advanced Cardiac Therapies Improving Outcomes Network) is the first pediatric VAD quality improvement network. The initial goal of ACTION is stroke reduction. This report describes the methods used to obtain BP and effectiveness of BP control among ACTION members. We also describe the development of a BP clinical decision support (CDS) tool to standardize BP reporting and goals. Methods The BP protocols among ACTION members were assessed. Process measures that may impact stroke rates were identified via anonymous surveys beginning June 2018. Statistical process control charts were used to assess baseline metrics. Results A total of 28 patients from 11 centers were identified with BP data. Including 12 Heartware, 10 Berlin, 2 Heartmate3, and 4 paracorporeal continuous flow (CF) devices. Height/age BP %iles were used to guide BP goal in 19 (68%) patients. Among CFVAD patients, BP measurement method (outside the perioperative period) and BP goal value varied, especially among the 11 patients (55%) with a palpable pulse (Figure 1). Patients had well controlled BP on 69% of support days (Figure 2). Conclusion The BP measurement methods and goals varied across ACTION, especially among patients on a CF-VAD with a pulse. A CDS tool has been developed to standardize BP measurement and management among ACTION members and will guide subsequent collaborative studies to assess the role of BP in stroke among pediatric VAD patients.

The field of mechanical circulatory support for children has shown tremendous growth and evolution over the last decade. This is in part due to the worldwide epidemic of heart failure in adults—a prevalence of 23million and counting [1,2] feeding the burgeoningmarket for ventricular assist device (VAD) design and development. Device design in children has been markedly more challenging due to the biotechnical demands of device miniaturization and the limited market field in children compared to adults. Based on most recent data from the International Society of Heart and Lung Transplantation, over 550 children underwent heart transplantation worldwide in 2011, of which 20% required mechanical circulatory support in the form of a VAD or total artificial heart as a bridge to transplantation [3]. This suggests a market for pediatric specific VADs in the hundreds of devices per year, as opposed to the tenfold higher demand for VADs in adults. As such, the substantial growth of pediatric VAD support can be in large part attributed to the adoption of newer generation intracorporeal continuous flow (CF) VADs designed for adults, but small enough for implantation in children and adolescents. The advent of CF VADs is an important milestone in the history of mechanical circulatory support. To fully appreciate the pivotal role of CF VAD in the progression of circulatory support for both children and adults, one must have an understanding of the predecessor devices. The last 40 years has seen 3 generations of VADs. The first generation of implantable VADs were volume displacement pulsatile flow (PF) devices, such as the HeartMate XVE® in 1998 (Thoratec Inc.; Plesanton, California, US). These devices had significant limitations secondary to its large size, need for extensive surgical dissections, poor pumpdurability andhigh thromboembolic, bleeding and infection event rate. Its large size precluded applicability to children. Appreciating the need for long

Ventricular assist device (VAD) support for children has advanced tremendously in the last 5 years. This is attributable to the adoption of newer generation intracorporeal devices, originally intended for use in adults, but small enough for children. Having access to additional VAD options has opened the door to new indications of VAD use in children beyond just bridge to transplant. Today, bridge to decision, bridge to transplant candidacy, destination therapy, and potentially bridge to recovery are all established and viable therapeutic strategies. However, as the field grows, with ever more device options and support strategies, we are faced with more decisions to reconcile. Initially the looming question was “who needs a VAD” but now we also need to address a myriad of other considerations that are a direct result of the burgeoning growth in device options and applications. In this chapter, we will address the decisions that face the pediatric heart failure cardiologist in supporting the advanced heart failure patient from VAD evaluation to implantation and beyond.

Background Adult congenital heart disease (ACHD) prevalence is increasing worldwide, with advanced heart failure (HF) as a leading cause of death. Limited data are available on durable mechanical circulatory support (MCS) in ACHD patients. Methods ACHD patients from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database were identified and propensity matched with non-ACHD patients using risk factors from the INTERMACS Seventh Annual Report. We compared these groups for the primary outcome of post-MCS mortality. We also investigated adverse event rates, functional status, and health-related quality of life. Results ACHD (n = 128) and non-ACHD (n = 512) patients were appropriately matched by baseline characteristics. ACHD patients had a longer length of stay at MCS implant (24 vs 19 days, p = 0.006) but similar rates of post-MCS adverse events and hospitalization. There were similar improvements in functional status and health related quality of life post-MCS in both groups. ACHD patients had significantly higher mortality post-MCS exclusively during the first 5 months after implant (p = 0.003) and a lower probability of receiving a transplant (p = 0.003). Risk factors for early mortality were biventricular or total artificial heart device implant and age > 50 years. Conclusions ACHD patients experience a higher early mortality after MCS but have similar adverse event rates and similar improvements in functional capacity and quality of life compared with non-ACHD patients. These data support expansion of MCS use in selected ACHD patients.

Anticoagulation with unfractionated heparin (UFH) after pediatric cardiac surgery can be monitored using either activated partial thromboplastin time (aPTT) or anti-factor Xa activity (anti-Xa). However, correlation of bleeding with either of these laboratory values has not been established. We sought to determine the correlation between bleeding events and aPTT and anti-Xa in patients who undergo anticoagulation after congenital heart surgery.We prospectively studied pediatric patients treated with UFH after cardiac surgery over an 11-month period. Bleeding events were prospectively assessed and adjudicated. The highest aPTT and corresponding anti-Xa for the 24 hours before bleeding events were collected to assess for association with bleeding. Statistical analysis was performed using generalized additive logistic regression.A total of 202 patients received UFH over 1488 patient-days. The median age at surgery was 0.4 years (interquartile range, 0.1-2.2). A total of 45 major or clinically relevant bleeding events were observed. The correlation between aPTT and anti-Xa was of moderate strength (R = 0.58; P .001). The odds of bleeding increased significantly when aPTT exceeded 150 (odds ratio, 1.71 per 10-second increase in aPTT, 95% confidence interval, 1.21-2.42; P = .003). Anti-Xa was not associated with bleeding (odds ratio, 1.11 per 0.1 IU/mL increase, 95% confidence interval, 0.89-1.29; P = .34).In heparinized pediatric patients after cardiac surgery, increased risk of bleeding is more closely associated with elevated aPTT levels than elevated anti-Xa levels. In addition to anti-Xa, monitoring of aPTT levels should be considered during titration of UFH in pediatric patients after cardiac surgery.

Background Patients undergoing surgery for congenital heart disease are at high risk for bleeding as well as thrombosis in the postoperative period. The objective of the study was to describe the design and effects of implementing a standardized unfractionated heparin anticoagulation protocol for children after congenital heart surgery. Methods We created a tiered guideline for the postoperative management of bleeding and thrombosis. In patients treated with unfractionated heparin, anti-factor Xa activity level as well as activated partial thromboplastin time were used for dose titration. Clinical outcomes, including bleeding and thrombosis events, were prospectively collected for 5 months before and after protocol implementation and adjudicated as either minor, clinically relevant nonmajor, or major. Results Among 792 surgical patients followed during the study period, a total of 203 patients (87 preimplementation, 116 postimplementation) were treated with therapeutic unfractionated heparin over a total of 1481 patient days. Of these, 28% were neonates and 35% were infants (29 days to 1 year), with a trend toward fewer neonates and lower Risk Adjustment for Congenital Heart Surgery (RACHS) scores after protocol implementation. Among 1321 time-matched pairs, activated partial thromboplastin time and antifactor Xa activity levels were poorly correlated (r2 = 0.33). Clinically relevant bleeding events, which required increased medical care, including blood transfusion, decreased after protocol implementation (4.14 vs 1.62 bleeding events per 100 patient-days; risk ratio, 0.39 [0.20-0.75]; P = .005), even after correcting for differences in age and RACHS scores (P = .006). This finding was primarily found after RACHS category 1 to 3 procedures (risk ratio, 0.27 [0.10-0.73]; P = .0099) and in noninfants (risk ratio, 0.25 [0.09-0.65]; P = .005). There were no significant differences in the incidences of major bleeding (P = .88) or any thrombosis (P = .55). Conclusions The use of a standardized anticoagulation protocol is feasible and might reduce the incidence of bleeding and thrombosis events in postcardiotomy patients.

Pediatric mechanical circulatory support (MCS) has advanced tremendously over the last decade, with momentum building in the development and implantation of durable ventricular assist devices (VADs) in smaller children with increasingly complex anatomy. Despite these advancements, VAD support for children continues to lag behind support options for adults. The most obvious disparity is the limited number of devices suitable for children for both short- and long-term support. Thus, there has been burgeoning interest in developing devices specifically tailored to suit the unique needs of children. From a design perspective, pediatric VADs differ significantly from adult devices: they are required to support a wide range of patient sizes (from newborn to adolescence), to allow for the increased circulatory demand commensurate with growth, and to accommodate the anatomic and physiological heterogeneity of congenital heart disease. Beyond the challenges of designing and developing pediatric VADs, there are multiple barriers to the clinical evaluation of these devices because of the small number of children who require this level of support. Therefore, it is considered infeasible to test device safety and effectiveness through large randomized, controlled trials like the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH),1 a large adult study. Additionally, industry is disincentivized to invest the necessary resources in the research and development of pediatric-specific medical devices with applicability to such a narrow market population.2 In the United States, the Food and Drug Administration (FDA) is tasked with the responsibility of ensuring that medical devices marketed in the United States have met the requirements establishing the safety and effectiveness for use in humans to treat a specific condition. Many pediatric-specific medical devices, including VADs, fall under the category of a humanitarian use device.3 Humanitarian use devices are devices that are used to treat or diagnose …

Purpose Pediatric Ventricular Assist Device (VAD) therapy is associated with high rates of stroke and bleeding. There have been limited efforts to date, to define and implement optimal anticoagulation (AC) strategies in this population. ACTION (Advanced Cardiac Therapies Improving Outcomes Network) is the first pediatric VAD quality improvement network, with an initial goal of stroke reduction. This report describes baseline AC data from ACTION centers, including agents used and aggregate levels of performance, to inform development of specific interventions. Methods The AC practices of ACTION centers were assessed. Data collected included VAD type, weekly data characterizing AC agents used; time to achieve desired levels; and percentage of levels within the desired range. Results Data were collected from 11 centers, with a total of 30 patients. AC data were collected from 6/1-9/1/18, while strokes were collected retrospectively for the entire VAD support interval. Devices included: HVAD (12); EXCOR (10); Heartmate 3 (3); and 5 paracorporeal continuous flow devices. There were 5 strokes (16.7%). Intravenous AC included unfractionated heparin (36%), and bivalirudin (64%). There was wide variability between patients in the time to achieve first therapeutic AC level (Figure 1), with 15 patients at goal within 20 hours, while others required up to 170 hours. Heparin levels varied widely, with the percent of labs within range falling below 50%, in 50% of the weeks reported. For bivalirudin, levels were less variable, with percent of labs within range falling below 50% in only 14% of weeks reported. Conclusion At baseline, stroke rates remain high in the ACTION centers. Intravenous AC includes both heparin and bivalirudin, with high variability in time until therapeutic levels are achieved, and with high variability in subsequent levels, particularly for heparin. These data will inform interventions designed to reduce variability in AC performance as a basis for stroke reduction.

The field of mechanical circulatory support for children has evolved dramatically over the last decade. This is in part attributable to the development of smaller ventricular assist devices (VADs) which has expanded the array of support strategies in pediatrics. Extracorporeal membrane oxygenation (ECMO) was originally the cornerstone of mechanical circulatory support for children. Its ease of implantation, wide accessibility, and applicability to all patient sizes made it the first-line choice for urgent cardiopulmonary support. However, ECMO has significant limitations related to its extracorporeal design (i.e., pump external to the body with cannula inserted either in peripheral vessels or centrally similar to cardiopulmonary bypass), its thrombogenic nature, need for aggressive anticoagulation, and secondary complications. These issues limit the duration of support to weeks, with an exponential rise in complications beyond that time. Additionally, ECMO cannulation prevents easy mobilization of patients. Many patients remain heavily sedated and ventilated for the duration of support, and as such, there is no way to engage patients in active physiotherapy or rehabilitation. The advent of pediatric VADs has changed the way we approach children on mechanical circulatory support. The first pediatric VAD to gain widespread global use was the Berlin Heart EXCOR® (Berlin Heart GmbH, Germany). This paracorporeal pulsatile-flow device can be used for right, left, or biventricular support. A variety of pump sizes are available to accommodate all sized children, infants to adolescent. The more secure central cannulation technique with externalization of the cannula through the upper abdominal wall allows patients to be woken up, extubated, fed, mobilized, reconditioned, and rehabilitated. While the Berlin Heart EXCOR® is vastly superior to ECMO in terms of survival to and after transplantation, it still has a high risk of stroke [1]. The largest multicenter prospective study on the Berlin Heart was conducted in North America for the Investigation Device Exemption (IDE) Food and Drug Administration (FDA) trial [1]. This study reported a 29% incidence of stroke despite standardized anticoagulation and antiplatelet therapy. As such, a comprehensive approach to mitigating stroke risk and improving recovery post stroke through rehabilitation has evolved from the Berlin Heart experience.

A successful VAD program requires organization, planning, and appropriate personnel to make up a core VAD team. The VAD coordinator is an integral part of the VAD team and helps to bridge the technical and medical aspects of the field. They are a necessity for successful inpatient and outpatient care of the patient supported by a VAD.

Although there are numerous smart phone applications available for patients to promote medical adherence, there are none identified in the literature specific to aid patients in advanced heart failure being supported by ventricular assist devices (VADs). By developing a smart phone application called VADKids App, we sought to improve how we communicate, relay information, and share data with our patients and other providers on our VAD team. More research is needed to determine whether the VADKids App is indeed effective in achieving these goals.

A multicenter study of the HeartWare ventricular assist device in small children Oliver Miera, MD, Richard Kirk, MD, Holger Buchholz, MD, Katharina R.L. Schmitt, MD, Christina VanderPluym, MD, Ivan M. Rebeyka, MD, Neil Wrightson, MD, Felix Berger, MD, Massimo Griselli, MD, and Jennifer Conway, MD From the Department of Congenital Heart Disease/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany; Department of Pediatric Cardiology, Freeman Hospital, Newcastle Upon Tyne, UK; Stollery Children’s Hospital, University of Alberta, Edmonton, Alberta, Canada; and the Department of Cardiology, Boston Children’s Hospital, Boston, Massachusetts, USA