Children who stroke on VAD support: When is it safe to transplant and what are their outcomes?

OBJECTIVE: Ventricular assist devices (VADs) increase waitlist survival, yet the risk of stroke remains notable. The purpose of this study was to analyze how strokes on VAD support impact post-transplant (post-Tx) outcomes in children. METHODS: About 520 pediatric (<18 years) heart transplant candidates listed from January 2011 to April 2018 with a VAD implant date were matched between the United Network of Organ Sharing and Pediatric Health Information System databases. Patients were divided into pre-Tx Stroke and No Stroke cohorts. RESULTS: About 81% of the 520 patients were transplanted; 28% (n = 146) had a pre-Tx Stroke; and 59% (n = 89) of the Stroke patients were transplanted at a median of 57 (IQR 17-102) days from stroke. Significantly more No Stroke cohort (90%) were transplanted (p < 0.001). There was no difference in post-Tx survival between the Stroke and No Stroke cohorts (p = 0.440). Time between stroke and transplant for patients who died within 1 year of transplant was 32.0 days (median) compared to 60.5 days for those alive >1 year (p = 0.18). Regarding patients in whom time from stroke to transplant was more than 60 days, one-year survival of Stroke vs. No Stroke patients was 96% vs. 95% (p = 0.811), respectively. CONCLUSION: Patients with stroke during VAD support, once transplanted, enjoy similar survival compared to No Stroke patients. We hypothesize that allowing Stroke patients more time to recover could improve post-Tx outcomes. Unfortunately, the ideal duration of time between stroke and safe transplantation could not be determined and will require more detailed and larger studies in the future.

Right heart failure considerations in pediatric ventricular assist devices.

Right heart failure (RHF) is a vexing problem in children after left ventricular assist device (LVAD) implantation that can negatively impact transplant candidacy and survival. Anticipation, prevention, early identification and appropriate medical and device management of RHF are important to successful LVAD outcomes. However, there is limited pediatric evidence to guide practice. This pediatric-focused review summarizes the relevant literature and describes the harmonized approach to RHF from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION). This review seeks to improve RHF outcomes through the sharing of best practices and experience across the pediatric VAD community.

Recommendations for utilization of the paracorporeal lung assist device in neonates and young children with pulmonary hypertension.

The management of decompensating critically ill children with severe PH is extremely challenging and requires a multidisciplinary approach. Unfortunately, even with optimal care, these children might continue to deteriorate and develop inadequate systemic perfusion and at times cardiac arrest secondary to a pulmonary hypertensive crisis. Tools to support these children are limited, and at times, the team should proceed with offering extracorporeal support, especially in newly diagnosed patients who have not benefitted from medical therapy prior to their acute deterioration, in patients with severe pulmonary venous disease and in patients with alveolar capillary dysplasia. Currently, the only approved mode for extracorporeal support in pediatric patients with PH eligible for lung transplantation is ECMO. To decrease the risks associated with ECMO, and offer potential for increased duration of support, extubation, and rehabilitation, we transitioned four small children with refractory PH from ECMO to a device comprising an oxygenator interposed between the PA and LA. This work describes in great detail our experience with this mode of support with emphasis on exclusion criteria, the implantation procedure, and the post-implantation management.

ACTION-ARC Pediatric and Adult Congenital Heart Disease Ventricular Assist Device Adverse Event Definitions-2023.

Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD.

Taking ACTION: A Prognostic Tool for Pediatric Ventricular Assist Device Mortality.

We sought to develop a contemporary risk assessment tool for use in pediatric ventricular assist device (VAD) candidates to estimate risk for mortality on the device using readily available preimplantation clinical data. Training and testing datasets were created from Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry data on patients supported with a VAD from 2012 to 2021. Potential risk factors for mortality were assessed and incorporated into a simplified risk prediction model utilizing an open-source, gradient-boosted decision tree machine learning library, known as random forest. Predictive performance was assessed by the area under the receiver operating characteristic curve in the testing dataset. Nine significant risk factors were included in the final predictive model which demonstrated excellent discrimination with an area under the curve of 0.95. In addition to providing a framework for establishing pediatric-specific risk profiles, our model can help inform team expectations, guide optimal patient selection, and ultimately improve patient outcomes.

Initial multicenter experience with ventricular assist devices in children and young adults with muscular dystrophy: An ACTION registry analysis.

PURPOSE: Cardiac disease results in significant morbidity and mortality in patients with muscular dystrophy (MD). Single centers have reported their ventricular assist device (VAD) experience in specific MDs and in limited numbers. This study sought to describe the outcomes associated with VAD therapy in an unselected population across multiple centers. METHODS: We examined outcomes of patients with MD and dilated cardiomyopathy implanted with a VAD at Advanced Cardiac Therapies Improving Outcomes Network (ACTION) centers from 9/2012 to 9/2020. RESULTS: A total of 19 VADs were implanted in 18 patients across 12 sites. The majority of patients had dystrophinopathy (66%) and the median age at implant was 17.2 years (range 11.7-29.5). Eleven patients were non-ambulatory (61%) and 6 (33%) were on respiratory support pre-VAD. Five (28%) patients were implanted as a bridge to transplant, 4 of whom survived to transplant. Of 13 patients implanted as bridge to decision or destination therapy, 77% were alive at 1 year and 69% at 2 years. The overall frequencies of positive outcome (transplanted or alive on device) at 1 year and 2 years were 84% and 78%, respectively. Two patients suffered a stroke, 2 developed sepsis, 1 required tracheostomy, and 1 experienced severe right heart failure requiring right-sided VAD. CONCLUSIONS: This study demonstrates the potential utility of VAD therapies in patients with muscular dystrophy. Further research is needed to further improve outcomes and better determine which patients may benefit most from VAD therapy in terms of survival and quality of life.

The Correlation of Endogenous Progesterone Concentration in Diestrus on Early Pregnancy Rate in Thoroughbred Mares.

The aim of this project was to test the hypothesis that progesterone concentration 5 days after ovulation did not differ between pregnant and nonpregnant Thoroughbred mares on stud farms located in the Waikato region of New Zealand. A prospective cohort study was performed involving five stud farms in the Waikato region of New Zealand during the 2018 breeding season. A total of 275 mares were enrolled in the study. Mares were served by 34 individual stallions. Blood samples were taken from each mare 5 days after ovulation (D0) and measured for progesterone concentration. Early pregnancy was confirmed at D14 by transrectal palpation and ultrasonography of the mares reproductive tract. Progesterone concentration at Day 5 post-ovulation was higher in mares determined to pregnant at Day 14 of gestation than in mares determined to be non-pregnant at Day 14 (6.4 ± 3.0 ng/ml vs. 5.5 ± 3.3 ng/ml respectively; P = .02). A negative association between increasing mare age and pregnancy rate was found but mare age had no effect on progesterone concentration at D5. In this study we found that although higher serum progesterone concentration at Day 5 post ovulation was associated with a higher pregnancy rate at Day 14, no predictive or definitive minimum required progesterone concentration could be identified. Additional studies are required to determine if a synthetic progestogens can serve to supplant natural progesterone to increase pregnancy rate in naturally bred mares.

Evolution of Ventricular Assist Device Support Strategy in Children With Univentricular Physiology.

BACKGROUND: Since 2012, we have supported 18 children with single ventricle (SV) physiology on ventricular assist devices (VADs) as a bridge to decision, transplantation, or recovery. We provide a detailed report of our cumulative surgical experience and lessons learned from these patients. METHODS: We reviewed all SV-VADs between March 2012 and April 2020. Implanted SV-VADs intended for short-term support were excluded. Demographic and clinical data included palliation stage at the time of VAD implantation, cannulation configuration, device type, duration of support, circuit and device interventions, postoperative support, anticoagulation strategy, complications, mortality, and 1-year survival postdischarge. RESULTS: Five SV newborns without prior surgical palliation, 8 infants post-Norwood/hybrid procedure, 4 infants post-Glenn, and 1 infant post-Fontan were initially supported with either continuous-flow (n = 13 of 18, 72%) or pulsatile-flow (n = 5 of 18, 28%) devices. Three (17%) of 18 transitioned to another device during support. Before VAD conversion, 9 (50%) of 18 were supported by extracorporeal membrane oxygenation. Outcomes included 7 (39%) of 18 who transplanted, 2 (11%) of 18 who recovered, and 9 (50%) of 18 who died before discharge. Of these deaths, 2 occurred after transplantation and 2 after explantation, and 5 had redirection of care while on support secondary to previously undiagnosed pulmonary venoocclusive disease (n = 2) or severe neurologic events (n = 3). Overall, 6 (33%) of 18 experienced neurologic injury. At last follow-up, 9 (50%) of 18 children were alive (median 1.2 [interquartile range, 0.8-4.3] years postexplantation/transplantation). CONCLUSIONS: Our experience shows that SV children, including newborns, can be successfully bridged to desired endpoints with proper patient selection and using specific cannulation strategies. Continuing utilization of this strategy is warranted for future children requiring VAD support.

Context-Responsive Anticoagulation Reduces Complications in Pediatric Extracorporeal Membrane Oxygenation.

Purpose: We sought to determine the impact of a comprehensive, context-responsive anticoagulation and transfusion guideline on bleeding and thrombotic complication rates and blood product utilization during extracorporeal membrane oxygenation (ECMO). Design: Single-center, observational pre- and post-implementation cohort study. Setting: Academic pediatric hospital. Patients: Patients in the PICU, CICU, and NICU receiving ECMO support. Interventions: Program-wide implementation of a context-responsive anticoagulation and transfusion guideline. Measurements: Pre-implementation subjects consisted of all patients receiving ECMO between January 1 and December 31, 2012, and underwent retrospective chart review. Post-implementation subjects consisted of all ECMO patients between September 1, 2013, and December 31, 2014, and underwent prospective data collection. Data collection included standard demographic and admission data, ECMO technical specifications, non-ECMO therapies, coagulation parameters, and blood product administration. A novel grading scale was used to define hemorrhagic complications (major, intermediate, and minor) and major thromboembolic complications. Main Results: Seventy-six ECMO patients were identified: 31 during the pre-implementation period and 45 in the post-implementation period. The overall observed mortality was 33% with no difference between groups. Compared to pre-implementation, the post-implementation group experienced fewer major hemorrhagic and major thrombotic complications and less severe hemorrhagic complications and received less RBC transfusion volume per kg. Conclusions: Use of a context-responsive anticoagulation and transfusion guideline was associated with a reduction in hemorrhagic and thrombotic complications and reduced RBC transfusion requirements. Further evaluation of guideline content, compliance, performance, and sustainability is needed.

Berlin Heart EXCOR and ACTION post-approval surveillance study report.

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.

Right heart failure with left ventricular assist device implantation in children: An analysis of the Pedimacs registry database.

BACKGROUND: The use of ventricular assist device (VAD) in children has increased, but the decision of left VAD (LVAD) vs biventricular support remains a challenge. Children who undergo LVAD placement are at risk for right ventricular failure (RHF), but the incidence has not been described. METHODS: Analysis was performed for patients <18 years old who underwent durable LVAD placement within the Pedimacs registry (September 19, 2012-February 28, 2017), excluding single ventricle morphology and temporary devices. RHF was defined as the need for right ventriculalr assist device (RVAD) or prolonged inotrope use between 1 week to 1 month and 1 to 3 months. End-points included death, heart transplant (HT), and recovery. RESULTS: A total of 272 durable LVAD were placed of which 37 died on device over 24 month follow-up, primarily from multiorgan failure and neurologic dysfunction. RVAD occurred in 12 children at median 8.5 days, with 9 undergoing HT and 3 dying on device. In patients with only LVAD, RHF was present in 111/207 (55%) between 1 week to 1 month and 28/116 (25%) between 1 and 3 months. Younger age, smaller weight, Intermacs profile 1, chemical paralysis, and pulsatile flow VAD were associated with RHF. RHF was associated with increased risk of death on device at both >1 month (hazard ratio 3.2, 95% CI 1.4-7.7, p = 0.007) and >3 month (hazard ratio 6.9, 95% CI 2-23.1, p = 0.002). CONCLUSIONS: In children, RHF is common after durable LVAD implantation, but subsequent RVAD is relatively rare. RHF in children, as indicated by prolonged inotrope support, was associated with an increased risk of death on the device. Whether early RVAD support and higher waitlist status may improve the outcome remains unknown.

The Creation of a Pediatric Health Care Learning Network: The ACTION Quality Improvement Collaborative.

Improving the outcomes of pediatric patients with congenital heart disease with end-stage heart failure depends on the collaboration of all stakeholders; this includes providers, patients and families, and industry representatives. Because of the rarity of this condition and the heterogeneity of heart failure etiologies that occur at pediatric centers, learnings must be shared between institutions and all disciplines to move the field forward. To foster collaboration, excel discovery, and bring data to the bedside, a new, collaborative quality improvement science network-ACTION (Advanced Cardiac Therapies Improving Outcomes Network)-was developed to meet the needs of the field. Existing gaps in care and the methods of improvement that will be used are described, along with the mission and vision, utility of real-world data for regulatory purposes, and the organizational structure of ACTION is described.

Pediatric VAD Discharge and Outpatient Care.

The advancement of pediatric ventricular assist devices (VADs) has enabled pediatric centers to discharge VAD patients home and integrate them back into their communities. Creating standard work flow processes to ensure the educational needs of the patient, family, and community are met will enable programs to successfully manage VAD patients at home. Utilizing multidisciplinary teams to support these patients while hospitalized will greatly contribute to the patients and families readiness for discharge. Defining mutual goals and expectations for patients, families, and the VAD team will promote a superior discharge and outpatient experience.

Outcomes of children supported with devices labeled as "temporary" or short term: A report from the Pediatric Interagency Registry for Mechanical Circulatory Support.

BACKGROUND: Historically, the "temporary" or short-term ventricular assist device (VAD) was used only as a quick bridge to recovery for children with an acute process. In the current era, the devices that were originally used for temporary support are now being used to support children for longer durations and for a variety of indications. In this study we aimed to describe the overall use, patients' characteristics and outcomes of "temporary" VAD use in children. METHODS: The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Institutes of Health-supported national registry for United States Food and Drug Administration-approved VADs in patients <19 years of age at the time of VAD implantation (either durable or temporary VAD). Patients undergoing placement of a device classified as a temporary VAD between September 19, 2012 and June 30, 2016 were included. RESULTS: Temporary VADs were implanted in 63 patients at 20 centers, accounting for 19% of all pediatric VAD patients entered into PediMACS. The median age at implantation was 3.7 (range <1 day to 18) years. The underlying diseases were: congenital heart disease in 26 (41%), 20 of whom were classified as single ventricle; cardiomyopathy in 25 (40%); and myocarditis/rejection in 12 (19%). Patients were predominately Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1 (51%), and 10 patients (16%) had previously been supported with extracorporeal membrane oxygenation. Median duration of support was 15 (range <1 day to 227) days, with 41 patients (65%) being on support for ≥10 days. The most frequent adverse events were bleeding (29% of patients) and neurologic dysfunction (24% of patients). Overall, 71% (45) achieved a positive outcome (defined as bridge to recovery [30%], transplantation [17%], alive on device [2%] or transition to durable VAD [22%]). Eighty-eight percent (n = 22) of the cardiomyopathy patients and 60% (n = 12) of the single-ventricle patients achieved a favorable outcome. CONCLUSION: Devices historically classified as "temporary" pumps are being used not only as a short-term mechanical circulatory support strategy but also as a longer term support strategy. In this multi-institutional, high-acuity, complex patient cohort, the use of "temporary" VADs resulted in a positive outcome (bridge to transplant, recovery durable device or alive) in 71% of patients.

Simulation-Based Assessment of ECMO Clinical Specialists.

OBJECTIVE: The aims of the study were (1) to create multiple scenarios that simulate a range of urgent and emergent extracorporeal membrane oxygenation (ECMO) events and (2) to determine whether these scenarios can provide reliable and valid measures of a specialist's advanced skill in managing ECMO emergencies. DESIGN: Multiscenario simulation-based performance assessment was performed. SETTING: The study was conducted in the Saigh Pediatric Simulation Center at St. Louis Children's Hospital. SUBJECTS: ECMO clinical specialists participated in the study. MEASUREMENTS AND MAIN RESULTS: Twenty-five ECMO specialists completed 8 scenarios presenting acute events in simulated ECMO patients. Participants were evaluated by 2 separate reviewers for completion of key actions and for global performance. The scores were highest for the hemodilution scenario, whereas the air entrainment scenario had the lowest scores. Psychometric analysis demonstrated that ECMO specialists with more than 1 year of experience outperformed the specialists with less than 1 year of experience. Participants endorsed these sessions as important and representative of events that might be encountered in practice. CONCLUSIONS: The scenarios could serve as a component of an ECMO education curriculum and be used to assess clinical specialists' readiness to manage ECMO emergencies.

Continuous Flow Device Support in Children Using the HeartWare HVAD: 1,000 Days of Lessons Learned From a Single Center Experience.

The purpose of this study is to provide a single center experience with a continuous flow device in adolescents with end-stage heart failure. A retrospective single center analysis of patients aged 18 years or younger implanted with HVAD (HeartWare Inc, Framingham, MA) between October 2012 and March 2014 was performed. Demographics, preimplant and postimplant clinical data, survival, and adverse events (AEs) were recorded. A matched group of adults based on diagnosis, body surface area (BSA), and time period were used for outcome comparisons. Six adolescents with dilated cardiomyopathy were implanted with the HVAD. Median age and BSA were 13.4 years and 1.45 m2, respectively. All were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile-1 or profile-2. Median days on device were 108 with total patient-days on device of 1,017. Four adolescents were discharged home on device all in New York Heart Association 1. Five underwent transplantation with 100% survival. There were 18 AEs with one AE per 170 days on device. Compared with the adult cohort (n = 5), there was no difference in 1 year survival (p = 0.32). HVAD support in adolescents is highly successful as a bridge to transplantation. It provides early rehabilitation and improvement in quality of life. Morbidity is not negligible but appears comparable with that seen in adults.