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Despite recent data suggesting improved outcomes with bivalirudin vs heparin in pediatric Ventricular assist devices (VAD), higher costs remain a barrier. This study quantified trends in bivalirudin use and compared outcomes, resource utilization, and cost-effectiveness associated with bivalirudin vs heparin.Children age 0 to 6 year who received VAD from 2009 to 2021 were identified in Pediatric Health Information System. Bivalirudin use was evaluated using trend analysis and outcomes were compared using Fine-Gray subdistrubtion hazard ratios (SHR). Daily-level hospital costs were compared due to differences in length of stay. Cost-effectiveness was evaluated using incremental cost-effectiveness ratio (ICER).Of 691 pediatric VAD recipients (median age 1 year, IQR 0-2), 304 (44%) received bivalirudin with 90% receiving bivalirudin in 2021 (trend p-value0.01). Bivalirudin had lower hospital mortality (26% vs 32%; adjusted SHR 0.57, 95% CI 0.40-0.83) driven by lower VAD mortality (20% vs 27%; adjusted SHR 0.46, 95% CI 0.32-0.77) after adjusting for year, age, diagnosis, and center VAD volume. Post-VAD length of stay was longer for bivalirudin than heparin (median 91 vs 64 days, respectively, p0.001). Median daily-level costs were lower among bivalirudin (cost ratio 0.87, 95% CI 0.79-0.96) with higher pharmacy costs offset by lower imaging, laboratory, supply, and room/board costs. Estimated ICER for bivalirudin vs heparin was $61,192 per quality-adjusted life year gained with a range of $27,673 to $131,243.Bivalirudin use significantly increased over the past decade and is now used in 90% young pediatric VAD recipients. Bivalirudin was associated with significantly lower hospital mortality and an ICER$65,000, making it a cost-effective therapy for pediatric VAD recipients.

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 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.

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.

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.

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

Since 2012, there has been growing use of the HeartWare (Medtronic, Mounds View, MN) intracorporeal continuous flow (CF) ventricular assist device (VAD) in children, despite it not being labeled for use in pediatric patients. We sought to describe the use and outcomes of children with HeartWare VADs.We identified all patients aged19 years and young adults aged 19 to 30 years supported with HeartWare who were entered into the pediatric portion (Pedimacs) of the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) and the Intermacs registries, respectively, between September 2012 and June 2017. Adverse events and outcomes were analyzed and compared.We identified 192 children and 247 young adult HeartWare patients. Baseline characteristics of children differed from young adults, with lower median weight of 51.5 kg (range, 13.1-162) vs 75.8 kg (range, 29.8-191; p ≤ 0.0001) and body surface area of 1.5 mSurvival in children supported with HeartWare is encouraging and comparable to young adults; however, adverse events are not uncommon in children. Ongoing evaluation of the HeartWare use in children is necessary to further decrease the rate of adverse events and understand obstacles to discharge.

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.

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.

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.

Purpose The use of bivalirudin has increased dramatically for primary thromboprophylaxis in pediatric paracorporeal ventricular assist device (VAD) support with limited data on optimal monitoring of effect. Partial thromboplastin time (aPTT) is commonly used for monitoring of bivalirudin, but can be impacted by line heparin, variability in assays and other patient factors. As such, we sought to examine the correlation of PTT to International Normalized Ratio (INR), as a possible monitoring tool for bivalirudin in in pediatric VAD patients. Methods Retrospective single center study of all children aged Results From 2015-2019, eleven patients (4 female), median age 5 months (range 0.5-40 months), weighing 7.8 kg (3.4-17.0kg) and body surface area of 0.4 m2 (range 0.2-0.7 m2) at time of implant were treated with bivalirudin for paracorporeal VAD thromboprophylaxis, of which 6 were on EXCOR devices, 4 were transitioned between continuous flow and EXCOR devices, and 1 patients was on CardioHelp extracorporeal membrane oxygenator connected to EXCOR cannula. A total of 900 days of paracorporeal VAD support generated 3,143 laboratory values for correlation. Correlations varied between aPTT assays, with highest median correlation coefficient for HA aPTT to INR of 0.72 (min 0.57 to max 0.81) in 4 patients with a total of 662 paired samples, as compared to correlation coefficient for aPTT to INR of 0.56 (min 0.32-0.91) in 10 patients with a total of 1,188 paired samples. Correlations varied between patients, with no association to age, device type or survival outcomes. The most important determinant for lack of correlation between aPTT to INR was concomitant administration of line heparin. Conclusion Patients treated with bivalirudin demonstrate individual correlations of their INR to PTT, with highest correlation to HA PTT by accounting for exogenous line heparin. This preliminary data provides foundation for ongoing study into the utility of INR for bivalirudin dosing and possible future application of point of care INR testing in this population.

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.

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

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.

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.

s S19 9-25 d. Hemorrhagic complication occurred in 15 (75%) at a median of 2 d (1-33 d) There were 6 (30%) deaths; 11 (55%) transplanted and 3 (15%) with recovery. Flow rate was not associated with death, hemorrhage or neurologic complications. When flow rates were < 3 L/min, 6/9 (67%) had thrombotic complications, as compared to 0 with flow rates ≥ 3 L/min (p = 0.014). Antiplatelet therapy was not associated with thrombosis or survival independent of flow rate. Conclusion: Pediatric patients on centrifugal VADs with flow rates < 3L/min have significantly more thrombotic complications, although with similar survival to those supported on higher flows. Antiplatelet therapy does not appear to ameliorate this risk. Further study into the optimal management of these patients is needed to minimize these morbidities.

Purpose As pediatric VAD use in the US has grown, wait-list mortality for children listed for heart transplant (HT) has decreased. It is unclear whether this decrease applies to children at highest risk of waitlist mortality, specifically children supported on ECMO or a ventilator at listing. Methods and Materials All patients Results Of 5,430 children listed for HT, 647 children were listed for HT while on ECMO. The number of patients (average 59 per year) and baseline characteristics of patient on ECMO at listing did not change appreciably over the 10-year period. For all patients, overall waitlist mortality declined 44% from 25% in 2001 to 14% (P figure 1 ] Conclusions While overall pediatric heart transplant waitlist mortality has improved significantly for US children in the past decade, waitlist mortality for the sickest children listed from ECMO or mechanical ventilation has not changed. Further research is needed to understand why the sickest patients do not appear to be benefiting from recent advances in circulatory support and refinements in organ allocation.

both left and right VAD applications, and cannula length and angle were determined for each application. Fitting was determined for pump placement in two configurations: (1) on the diaphragmatic surface of the heart; and (2) along the lateral ventricular wall. Intra-operative fitting studies were performed in 6 pediatric patients with a BSA range of 0.23 to 0.63 m 2 . Better fitting of the current pump prototype, for use as a left or right VAD, was possible when the model was placed on the diaphragm anterior to the ventricles. Intracorporeal implantation of the current pump prototype in the 3-month-old infants was hindered by the lack of retrosternal space for placement of the outflow graft with likely coronary and lung compression. Full intracorporeal implantation in Patient 4 (11 months of age, BSA 0.63 m 2 ) also seemed to create the potential for lung compression. Intracorporeal implantation appeared to be feasible in both 3-year-old patients (Figure 2). We have previously described the usefulness of 3-dimensional on-screen models in providing device-fitting information that could help overcome some limitations associated with animal and cadaver studies. 3 In the present study, intra-operative fitting provided additional in vivo information that augments data derived from other sources. Unlike imaging or cadaver studies, this in vivo approach allows direct visualization of possible positional interferences due to device placement during normal cardiac motion with full lung inflation. It also provides information regarding the lower limits of patient size for which an implantable system could be considered; for the present prototype, intracorporeal implantation in toddlers appears to be feasible. Based on these results, a next generation version of the PediPump that is considerably smaller is currently being developed and will undergo similar in vivo fitting studies to determine whether it can be adapted for use in infants.

Purpose Recent clinical experience suggests that heart transplant (HT) waiting times have increased for smaller children in the US. Limited data are available on actual trends in median waiting times for this population. We sought to describe median wait-times over the past 10 yrs for children between 10 and 25 kilograms at listing. Methods and Materials All children Results Of 5,427 children listed for transplant, 39% (2,112) were 25 kg at listing. For children between 10 and 25 kg at listing, overall median wait-times increased significantly from an average of 71 days over the first 3 years to 152 days over the last 3 years of the study period. [ figure 1 ] Median wait-times were relatively unchanged for infants 25 kg (10-year average 57 days). The total number of children listed annually in the 10-25 kg size group increased 18% (107 to 125 children/year) whereas overall waitlist mortality decreased 43% from 21% to 12%. Conclusions Waiting time has more than doubled for smaller children over the past decade while waiting time has remained largely unchanged for infants and older children. Longer waiting time in this size group may be explained in part by more children being listed for HT and fewer children dying while waiting, which may relate to significant growth in pediatric VAD utilization.