Search

Muscular dystrophy (MD) patients can suffer from significant cardiac disease with resultant major morbidity and mortality. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) sought to better characterize our previously described outcomes associated with VAD therapy across multiple centers. We examined outcomes of patients with MD and dilated cardiomyopathy implanted with a durable VAD at participating centers from 9/2012 to 1/2023. A total of 48 VADs were implanted in 33 patients across 15 sites. While four patients received a VAD from 2012 to 2017, a further 29 received a VAD from 2018 to 2023. The most common MD was a dystrophinopathy (Becker, Duchenne, intermediate or affected carrier), followed by Emery-Dreifuss, Limb girdle and other MD. The median age at implant was 16.8 years (range 9.2-31.7). Seven (21%) patients were implanted as a bridge to transplant, 6 of whom survived to transplant. Of patients implanted as bridge to decision or destination therapy, 87% were alive at 1 year and 82% at 2 years. The overall frequencies of positive outcome (transplanted or alive on device) at 1 year and 2 years were 84% and 80%, respectively. Major complications included stroke (6%), sepsis (15%), tracheostomy (3%), and severe right heart failure requiring right-sided VAD (9%). Other common but not severe complications included other major infection (21%), bleeding (30%, although none required surgical intervention), and arrhythmias requiring cardioversion (15%). Longest follow-up in this cohort is now greater than 5 years on device. VADs are being increasingly utilized in the MD population and implantation can be successful, with similar complication rates to non-MD patients. Ongoing work in patient selection, assessing quality of life, and further surgical/medical optimization is needed. [ABSTRACT FROM AUTHOR]

Reports focused on adult heart transplant (HT) recipients with COVID-19 suggest an increased risk of severe disease. It is unclear if this holds true for pediatric HT patients, given the reported milder course of illness in children in general with COVID-19. We sought to rapidly implement a system for multi-center data collection on pediatric HT recipients and candidates, with the aim of describing the patient population and infection related outcomes. The Pediatric Heart Transplant Society (PHTS) is a multi-center collaboration whose main goal is to improve the outcomes of children who are listed and undergo HT. The society consists of pediatric HT centers in North America (n=53), UK (n=2), and Brazil (n=1). In response to the pandemic, PHTS developed a web-based platform to collect COVID-19 specific data in pediatric HT candidates and recipients. Non-PHTS centers were also invited to submit data. Data fields included pre-and post-HT patient characteristics, presumed vs. documented infection, need for hospitalization (including ICU and ventilator use), treatments administered, and 30-day outcome (death, resolution, sequelae, ongoing treatment). Data collection was initiated on 4/30/20. As of 9/28/20, there were 72 patients (7 pre-HT and 65 post-HT, median age 13 years) reported from 27 centers. Of these, 67 were PCR+ by nasal swab and 5 were presumed positive. Complete data with 30-day follow-up was available for 60 patients (7 pre and 53 post HTx). Hospitalization was common and occurred in 71% of the pre-HT and 32% of the post HTx patients. Of the pre-Tx patients, 43% required ICU and 14% were ventilated. In the post HTx group, 13% required ICU and 4% were ventilated. At 30 days a majority of pre-Tx had resolution of symptoms (n=6/7). Among post HTx patients, resolution occurred in 87%% (46/53) with 1 death at 30 days. The PHTS remains the most robust source of data on pediatric HT and this effort shows the adaptability of the registry. Although likely limited by reporting bias, these data represent the first known report of characteristics and early outcomes for pediatric HT candidates and recipients with COVID-19. As data collection continues, we aim to better understand the characteristics of patients with more severe disease in order to improve risk characterization and decrease the knowledge gap that currently exists in this unique population. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

The presence of mechanical valves (MechV) introduces additional surgical and post-surgical complexity in patients supported with a ventricular assist device (VAD). There is limited data regarding the outcomes of VAD support in children with MechV. This study sought to assess clinical outcomes of children with MV at the time of VAD implant. All patients with a MechV at the time of VAD were identified in the ACTION database through 8/1/22. Patient implant characteristics and clinical outcomes were assessed. A total of 47 patients were identified (Table 1). The median age and weight were 5.5 years and 15.4 kg, respectively. The most common diagnosis was congenital heart disease (CHD) (40, 85%), including 18 patients (38%) with univentricular disease. Twenty-one (45%) were INTERMACS profile 2, 14 (30%) profile 1, and 13 (28%) supported on ECMO. A variety of VAD types were employed with the most common devices being paracorporeal continuous flow (21, 38%), paracorporeal pulsatile (17, 30%), and implantable continuous flow (15, 27%). Seventeen patients (36%) experienced major bleeding, 10 patients (21%) stroke, and 18 patients major infection (38%). To date, 27 (45%) patients have been transplanted (21, 35%) or recovered (6, 10%), while 12 died (20%). Seven patients (15%) remain on support and 1 transferred care. Patients with MechV who require VAD support constitute a complex, heterogeneous, and high risk population. Despite these challenges, successful VAD support is feasible. Balancing the risks of thrombosis and bleeding is a particular challenge and may be a target for anticoagulation harmonization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To evaluate for predictors of long-term renal function following repeat heart transplant (RT) in children and young adults. All RT at our center from 1995-2021 were reviewed. Estimated glomerular filtration rate (eGFR) was derived from CKiD U25 calculator using creatinine, measured at pre-RT, 1 week post-RT, 1-3 months, 6 months, and 12 months post-RT, and most recent follow-up. Associations between the following risk factors and development of chronic kidney disease, defined as stage 3b (CKD3b), were evaluated with linear regression: number of rejections prior to RT, pre-RT eGFR, 1-3 months post-RT eGFR, dialysis time, prior VAD/ECMO use, waitlist/bypass/ischemic time, time from RT, length of stay, and nephrotoxin use at RT. Receiving operating curves (ROC) were created to evaluate area under the curve (AUC) for development of CKD3b or higher. Time to event analysis was performed using Kaplan-Meier analysis and the log-rank test. RT was performed in 47 patients, with mean age of RT being 13 years old and half being male. Approximately 85% of patients identified as Caucasians. The reasons for RT were chronic rejection (40%) transplant vasculopathy (32%), graft failure (16%), acute rejection (6%), and other (6%). We found that eGFR 1-3 month post-transplant was statistically significant for the development of CKD3b (p = 0.013). Median follow up time was 2.5 years and the mean was 4 years. Figure 1a shows the survival based on an eGFR of 35mL/min/1.73m2 (p = 0.049). ROC analysis showed an area under the curve of 0.75 (Figure 1b). Sensitivity and specificity was 80% and 100%, respectively, for an eGFR of 35mL/min/1.73m2. Renal function at 1-3 months post-transplant is a long-term predictor of CKD3b in children, adolescence, and young adults undergoing RT. This finding suggests that early induction and maintenance immunosuppression may need to be modified. [ABSTRACT FROM AUTHOR]

The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) is a collaborative, multicenter learning health care system for children with heart failure receiving mechanical circulatory support. We studied the outcomes of patients enrolled in the ACTION network. Patients undergoing ventricular assist device (VAD) implantation and enrolled in the ACTION database between 4/1/18 and 7/31/22 were reviewed. Multivariable analysis studied the association of primary diagnosis, device type, INTERMACS profile, and implantation date with mortality. The cohort included 851 patients who received 1077 devices. Median age was 5.5 years (IQR 0.5-14.3), median weight 17.2 kg (IQR 6.8-53.8), and median BSA 0.73 m2 (IQR 0.35-1.6). Cardiomyopathy was the primary diagnosis in 524 (61%) patients, single ventricle congenital heart disease (CHD) in 206 (24%), and biventricular CHD in 107 (12%). Devices implanted included paracorporeal pulsatile (408/1077, 38%), implantable continuous (307/1077, 28%), paracorporeal continuous (282/1077, 26%), percutaneous pulsatile (75/1077, 7%), and total artificial heart (5/1077, 0.46%). At median follow-up time of 3 months, 525 (62%) patients underwent transplant, 80 (9%) underwent device explant for recovery, and 114 (13%) died on VAD. On multivariable analysis, biventricular (HR 2.4, 95% CI 1.4-41) and single ventricle CHD (HR 1.9, 95% CI 1.2-3.2, p=0.003), paracorporeal continuous device use (HR 3.1, 95%CI 1.9-5.1, p=0.001), and a more severe INTERMACS profile (HR 1.7, 95% CI 1.1-2.6, p=0.02) were associated with increased mortality. Adjusted mortality has decreased over time (Figure). Despite heterogeneity in diagnoses and device strategy, children can be supported with VAD with excellent outcomes, although patients with CHD remain at higher risk of mortality. Over time, there has been improvement in outcomes. Unique features of the learning network (collaboration, quality improvement, and education) are likely contributing factors. [ABSTRACT FROM AUTHOR]

Individuals born with defects resulting in a functionally univentricular heart Fontan-type palliation (FP) are prone to physiologic deterioration requiring advanced cardiac therapies. Given limitations to organ availability and long transplant waiting-list times, mechanical circulatory support (MCS) has become an important tool to permit individuals with a single ventricle circulation to either survive to transplant or may be used for destination therapy. The physiologic and clinical impact of MCS in FP patients are undefined. Centers participating in the ACTION Learning Network entered data on FP patients that received a VAD at their center, between 1/26/12 and 10/1/2019, in the ACTION Outcomes registry. Additional survey data on physiologic variables will be completed by Nov 2019. Thirty-nine FP patients were reported to the ACTION registry. Limited clinical variables can be found in table 1. MCS types included intracorporeal continuous flow support (25 patients), paracorporeal support (10), total artificial heart (2) and biventricular assist devices (1). Among supported patients, 23 % (9) died while on support, 10 % (4) are currently alive on support, and 67% (26) were transplanted and are alive while none died post-transplant. Major adverse events included major bleeding (17 episodes), driveline infection (n=1) and other neurologic dysfunction (n=1). There was no stroke or pump thrombosis (table 1). MCS implant improved NYHA functional class (12.5% versus 75% NYHA class 1/2) and decreased severe atrioventricular valve regurgitation (47% versus 30%). Complete clinical and hemodynamic data will be available and presented at the ISHLT meeting. This is the first multicenter report of FP outcomes post MCS. MCS results in improved functional status and decreased atrioventricular valve regurgitation in FP patients awaiting transplant without adverse post-transplant outcomes and with good on-device survival. MCS for Fontan patients as both destination and bridge to transplant is a reasonable option. [ABSTRACT FROM AUTHOR]

Patients with congenital heart disease (CHD) account for ∼40% of pediatric heart transplants (HT) performed in the United States. Our aim was to evaluate the overall trends for waitlist and post-transplant survival for children with CHD in the last three decades and identify risk factors for waitlist and post-transplant mortality in the current era. Children (age <18, n= 5741) listed for HT in the UNOS database from 1990-2017 were included. Patients were divided by time at initial listing into Era 1 (1/1/90-3/12/99), Era 2 (3/13/99-12/31/08) and Era 3 (1/1/09-12/31/17). Demographic and clinical characteristics at listing, including ventricular assist device (VAD) use, were compared across the 3 eras. Kaplan-Meier curves were generated to compare survival in the waitlist and post-transplant periods. We identified risk factors for increased waitlist and post-transplant mortality by bootstrap selection method. Compared to Era 1, CHD candidates in Eras 2 and 3 were older (mean age 3.5±5.4 vs 4.0±5.5 vs 4.2±5.5 years), more often of non-White race (26.7 vs 39.7 vs 41.6%), more likely on intravenous inotropes (31.1 vs 45.7 vs 46.6%) and on VAD support (1.1 vs 2.3 vs 3.2%). Compared to Era 2, those in Era 3 were less likely to have renal dysfunction (71.5 vs 54.0%) and pulmonary hypertension (27.8 vs 17.1%) or be on ECMO (14.8 vs 8.1%) or ventilator (29.8 vs 23.0%) pre-transplant. Compared to earlier Eras, children with CHD listed for HT in Era 3 had significantly improved 1-year waitlist (59.6 vs 58.4 vs 67.5%) and post-transplant survival (75.3 vs 80.6 vs 88.0%) (Figure) [p<0.05 for all]. Multivariable risk factors for waitlist and post-transplant mortality in Era 3 are shown in Table. Children with CHD listed for HT in the U.S. have had significant improvement in waitlist and post-transplant survival particularly in the last decade. Improved candidate selection and post-transplant care may have led to these advances. [ABSTRACT FROM AUTHOR]

Lack of both relevant clinical trials and real-world data (RWD) make it difficult to assess the effectiveness of any intervention in pediatric ventricular assist devices (VADs) population. Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry offers a means to capture RWD outside of traditional clinical trials. ACTION registry has introduced a standardized blinded adjudication process to provide VAD related adverse events (AEs) data with improved consistency and reliability. This study reviews the outcomes of the process at the end of its first year. The ACTION adjudication committee, comprised of experts in the field, reviews all critical adverse events, including neurological dysfunction (ND), device malfunctions (DM) and events that lead to death, on a quarterly basis. The committee also reviews a randomly selected subset (15%) of major bleeding (MB) and major infection (MI). Pre-adjudication reports are sent to the centers to upload source documents to a secure portal. Documents are de-identified by the Data Coordinating Center (DCC) and are shared with the chair and two assigned adjudication reviewers. Each AE is presented by the assigned reviewers at a virtual meeting followed by a period of discussion and final adjudication. Committee recommendations are sent as post-adjudication reports to make necessary changes to the AE data entered in registry. Total of 658 AEs were reported in the registry through June 2020. Thus far, 182 (28%) AEs were adjudicated (59 Neuro AE, 48 events leading to death, 37 DM, and 38 randomly selected from other AEs). Majority of AEs [150 (82%)] were adjudicated as classified, however, 25 (14%) were classified as non-AEs (DMs = 22, MB = 2, ND = 1). Eight (4.5%) reported events were reclassified in different categories (MI = 2, ND = 4, Events leading to cause of death = 2). As a result of this process, 34 additional events (Events leading to cause of death = 21; Stroke = 4; Other neurological events = 3; Bleeding = 4; Infection = 1; Device malfunction = 1) were identified by the committee that were not originally reported to the registry. ACTION adjudication process identified 18% misclassified and ∼5% unreported events, highlighting limitations of any registry data. However, an expert-led adjudication process with a follow-up DCC to site communications and training has the potential to improve the quality of RWD. [ABSTRACT FROM AUTHOR]

Social factors like race and insurance affect transplant outcomes. However, there is paucity of data and reasons remain unclear. We hypothesized that social factors affect clinical condition at listing and waitlist outcomes. Data from prospectively collected multi-center registry of the Pediatric Heart Transplant Society between January 1, 2000- December 31, 2019 were analyzed. Patients (pts) were divided by race as black, white, other (including those with multiple selections). Listing variables were analyzed using analysis of variance and chi-square test and waitlist outcomes by Kaplan Meier log rank test. Of 8284 pts listed for cardiac transplantation, 5565 were white, 1455 black and 1264 other. Compared to whites and others, black pts at listing were older (6.4yrs vs 5.6yrs vs 5.6yrs; p<0.001), more likely on US governmental insurance (69.8% vs 41.8% vs 50.2%; p<0.001) and had cardiomyopathy as the predominant diagnosis compared to congenital heart defect (CHD) (50.9% vs 44.3%). Black pts were more likely to be UNOS status 1A (73.7% vs 67.1% vs 64%), have higher priority status (82.7% vs 77.8% vs 75.2%), be in hospital (83% vs 75.2% vs 75.5%) and receive inotropes (66.3% vs 59% vs 58.3%) (p<0.001 for all factors). There were more ventricular assist devices in black pts compared to whites (8.6% vs 6.4%; p<0.001). Fewer black pts received a transplant for CHD (p=0.0005). Black pts had significantly higher waitlist mortality compared to whites and others (p=0.0038, figure), especially comparing US private health insurance (p =0.015), while outcomes were similar for US-governmental and single payer systems (UK, Canada). Black pts are sicker at listing and face higher waitlist mortality despite older age and a greater proportion of cardiomyopathy, typically associated with better outcomes. This suggests that the social construct of race negatively impacts consideration of, access or referral to pediatric cardiac transplantation, independent of access to private insurance coverage. [ABSTRACT FROM AUTHOR]

Ventricular assist device (VAD) interrogations allow clinicians to establish and maintain optimal VAD settings through the support course. There is currently no data regarding standards for establishing and modifying pediatric VAD settings, despite a heterogeneous population with variable diagnoses, anatomy and physiology. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION), a 37-center North American learning network, was surveyed in July 2019 regarding current practices for establishing, monitoring and modifying pediatric VAD settings. A total of 25 (68%) centers responded to the survey. Criteria for establishing intraoperative device settings varied between solely surgeon determined (36%) versus global imaging, surgeon, and VAD team driven (60%). Post-operative inpatient and outpatient interrogations were performed predominantly (80%) by a VAD physician or advanced practice provider (APP), but frequency ranged from daily (64%) to weekly (24%) to even monthly (4%). There was consensus (100%) on including device trends and alarm assessment for VAD interrogation, but many centers (88%) include log file interpretation in each interrogation as well. Factors used for optimization of post-operative settings were mixed. Several centers (28%) rely only on device interrogation and clinical course while many (24%) utilize echocardiogram only. The majority (44%) of sites use a combination of echocardiogram and device interrogation to determine optimal support. Outpatient practices were similar amongst sites with the exception of device wean trials which had significant variation with regards to use of echocardiogram (16%), hemodynamic catheterization (8%) or a combination of both studies (76%). Billing practices for VAD interrogation were inconsistent amongst centers, particularly regarding billing frequency. VAD interrogation and optimization practices were highly variable amongst ACTION centers, most notably during inpatient hospitalizations. Given the majority of pediatric VAD patients remain hospitalized while on their device, a standardized approach to this process may minimize unnecessary variation. Furthermore, defining "standard" management approaches and device settings in varied pediatric populations may help define the optimal clinical approach to support. [ABSTRACT FROM AUTHOR]

Purpose Evidence in adult heart transplant (HT) patients (pt) shows that initiating sirolimus (SRL) slows progression of cardiac allograft vasculopathy (CAV) measured by intravascular ultrasound (IVUS). However, no data exist in children. We evaluated changes in maximal intimal thickness (MIT) using serial IVUS measurements in children who initiated SRL for increased MIT post-HT. Methods A single center retrospective review of all pt who underwent pediatric HT and initiated SRL after diagnosis (dx) of increased MIT. We included pt with at least one IVUS before and after starting SRL and excluded re-HT. Repeated measures were analyzed with a univariable linear mixed model with a breakpoint at the time of SRL initiation to account for differing numbers of IVUS studies between pt. The F test compared the difference in slopes before vs. after starting SRL. Results Twenty-eight pt met inclusion criteria and had HT between 1991 - 2007 with IVUS performed between 1995 - 2018. Mean age at HT was 4.1 ± 5.2 yr and 68% were male. Pre-HT dx was cardiomyopathy in 12 and congenital in 16. Mean number of rejection episodes was 1.9 ± 1.7 before SRL and 0.5 ± 0.9 after SRL (p<0.0001). There were a total of 217 IVUS evaluations, 128 before (4.6 ± 2.5 per pt) and 89 after (3.2 ± 2.0 per pt) initiation of SRL. Mean age at 1st IVUS evaluation was 9.5 ± 4.5 yrs. Mean time from HT to start of SRL was 12.2 ± 5 yr. Mean time from 1st IVUS to start of SRL was 6.8 ± 4.5 yr with a mean f/u time of 3.5 ± 2.6 yr after initiating SRL. Mean MIT at 1st IVUS was 0.16 ± 0.15 mm and increased significantly to 0.63 ± 0.48 mm prior to start of SRL (p = 0.001). Mean MIT did not change significantly from start of SRL to last follow-up (0.63 ± 0.48 vs 0.64 ± 0.38 mm; p = 0.47). The difference in the slopes of mean MIT before and after initiation of SRL is shown in Figure 1. Conclusion SRL initiation slowed the increase in MIT by IVUS in pediatric HT pt. This suggests that intimal thickening after pediatric HT may be mitigated by incorporating SRL into maintenance immunosuppression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]